MEDICAL REFERENCES




References for Radiation and Treatment 

16 MAY 2001 Wake Forest University Baptist Medical Center. 
Wake Forest first in world to perform new brain tumor treatment
WINSTON-SALEM, N.C. - Physicians at Wake Forest University Baptist Medical Center are the first in the world to treat a brain tumor patient with the newly FDA-approved GliaSite" Radiation Therapy System (RTS). The GliaSite RTS delivers site-specific, internal radiation to malignant brain tumors, treating the target area while minimizing exposure to healthy tissue.
Stephen B. Tatter, M.D., Ph.D., assistant professor of neurosurgery at Wake Forest University School of Medicine, performed the procedure on a 27 year-old patient with a glioblastoma multiforme. "GliaSite represents an important new treatment option for malignant brain tumors," said Tatter. "Until now, treatment for patients with recurrent brain tumors has been extremely limited. Radiation combined with surgery is the single most effective treatment, and the GliaSite RTS will enable these patients to receive additional radiation, while minimizing the risks associated with external beam radiation." The device is a balloon catheter that is inserted into the cavity created by surgical removal of the malignant brain tumor and filled with liquid radiation. Over a course of three to seven days, GliaSite delivers radiation directly to the tissue surrounding the cavity, where tumors are most likely to recur. ...
Traditionally, patients are first treated with external beam radiation therapy, in which the radiation travels from outside the body to the tumor site, passing through healthy brain tissue. While this treatment is proven to delay tumor regrowth, a second course of external beam radiation is rarely an option due to the high risk of damage to healthy tissue. 
"It's a significant advancement to be able to offer an improved therapy that delivers radiation directly to the site of the cancer, while maintaining the quality of life for patients by completing the treatment in just one week," said Tatter. In addition, study results suggest that the survival rate of these patients is favorable in comparison to the next best secondary treatment, which is surgery plus chemotherapy wafers.
Safety and performance of the device were demonstrated in a National Cancer Institute (NCI)-sponsored, multi-centered study. Tatter was the principal investigator for the national study, which involved patients with recurrent brain tumors. All of the patients had undergone previous surgery and radiation therapy, and more than half had received chemotherapy. The median survival rate of the patients is currently 14 months, with patients still being followed, a substantial improvement over the results historically seen with other treatments....




15 MAY 2001 University of Maryland Medical Center
UM physicians report promising results for TheraSphere, new treatment option for inoperable liver cancer
Cancer specialists from the University of Maryland Greenebaum Cancer Center report that early results of a new treatment for inoperable liver cancer, known as TheraSphere, are promising. They will report their findings at the 37th annual meeting of the American Society of Clinical Oncologists on May 15. ...Forty-five patients have undergone the procedure there since its introduction last fall, according to David Van Echo, M.D., professor of medicine at the University of Maryland School of Medicine and director of the New Drug Development Program at the Greenebaum Cancer Center. Most patients have shown a positive response, as marked by a reduction in tumor size or number of lesions, with minimal side effects,ö says Dr. Van Echo. 
TheraSphere is a unique new targeted therapy that spares healthy tissue while providing radiation directly to liver tumors, says Dr. Van Echo. Millions of microscopic glass beads containing the radioactive element, yttrium 90, are delivered via catheter into the femoral and hepatic arteries and transported directly to the liver. This mechanism allows a more concentrated dose precisely where it is needed most. Preliminary results have been very promising.
The most dramatic improvements have been noted in patients with gastrointestinal carcinoid tumors --those that develop in certain hormone-making cells û also called neuroendocrine cells -- of the digestive system. Extremely interesting is the fact that of three neuroendocrine patients treated with TheraSphere, all had tumors that completely disappeared,ö says Dr. Van Echo. Also showing favorable response to TheraSphere are patients with colorectal tumors. Of seven patients in this category, two have died of progressive cancer outside the liver, but the other five are doing well six months after treatment, says Dr. Van Echo. They had not been helped by conventional chemotherapy and the average length of survival with this particular diagnosis is three to six months. With TheraSphere treatment, they are all healthy, living longer and enjoying a higher quality of life.
TheraSphere was approved by the U.S. Food and Drug Administration (FDA) last March for the treatment of liver cancer that cannot be treated surgically. The FDA granted MDS Nordion, which makes TheraSphere, a Humanitarian Device Exemption. This exemption, which permits the FDA to approve devices based on proof of patient safety alone, encourages further research and development for diseases that affect few patients. 
...  Those less responsive to TheraSphere as a treatment option are patients who have larger liver tumors, for example. 
TheraSphere is a non-surgical outpatient procedure. Patients can return home the same day and treatment poses no safety threat to caregivers or family members. Side effects can include vomiting, mild fever, abdominal pain and gastric ulcers. Toxicities are evident in about 20 percent of patients treated. And though patients initially were treated with a single dose, the procedure is being evaluated as a two-part process in which the right lobe of the liver is treated and the left lobe is treated two to four weeks later. 
We are delivering the same amount of treatment using the sequential approach, says Dr. Van Echo. But by splitting the dose, we are exposing the surrounding tissue to less radiation and decreasing the chance of the patient developing gastrointestinal toxicities. 
The University of Maryland Greenebaum Cancer Center remains the only institution nationwide treating patients, other than those with primary liver cancer, with TheraSphere. Though fewer than 10,000 Americans are diagnosed with liver cancer each year, it is a rapidly fatal disease with few treatment options, says Dr.Van Echo. Surgery remains the preferred treatment, but fewer than 15 percent of patients qualify for that option due to the advanced progression of the disease. ...





Int J Radiat Oncol Biol Phys 1990 Mar;18(3):619-23 
Tolerance of the liver to the effects of Yttrium-90 radiation.
Gray BN, Burton MA, Kelleher D, Klemp P, Matz L. University Department of Surgery, Royal Perth Hospital, Western Australia. 
 "These data indicate that the human liver may tolerate relatively large radiation doses when delivered by Yttrium-90 microspheres embedded in the liver parenchyma as a number of discrete point sources." PMID: 2318695 
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2318695&dopt=Abstract



Int J Radiat Oncol Biol Phys 1994 Mar 30;28(5):1061-6 Comment in: Int J Radiat Oncol Biol Phys. 1994 Mar 30;28(5):1215-6 
Clinical results of long-surviving brain tumor patients who underwent boron neutron capture therapy. 
Hatanaka H, Nakagawa Y. Department of Neurosurgery, Teikyo University, Tokyo, Japan. 
PURPOSE: The present report is a review of long-term survivors in the patients with malignant brain tumors treated by boron neutron capture therapy. METHODS AND MATERIAL: One-hundred twenty patients with 119 intracranial tumors and one extracranial nerve-related tumor were treated by the current standard technique of boron-neutron capture therapy (BNCT) as of December 1992, using 10B-sodium-mercaptoundecahydrododecaborate. RESULTS: Out of 87 patients operated on before May 1987, 18 lived or have lived longer than 5 years. Nine of these 18 lived or have lived longer than 10 years out of 53 patients operated on before May 1982. Among more-than-10-year survivors, only two died at 17 and 12 years. All of the other are still alive.The two died of delayed radiation damage because BNCT was applied to glioblastomas which recurred after their conventional radiotherapy. They lacked evidence of tumors when they died. Out of these nine more-than-10-year survivors, three had been previously treated by conventional external radiotherapy and they developed radiation damage which brought all patients ultimately to an incapacitated condition. Two of the three died. All the other 6 who were free from previous radiation history are active in their jobs and have no evidence of tumors. CONCLUSION: It can be suggested that BNCT is a radiotherapy that can produce "cure" of both malignant and benign brain tumors while preserving a good quality of life if conducted without conventional radiotherapy.PMID: 8175390 http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8175390&dopt=Abstract 



No Shinkei Geka 1993 Dec;21(12):1089-95 
[Prospective dose-escalation study in stereotactic radiotherapy utilizing a linear accelerator: report from East Hokkaido Radiosurgery Study Group (EHRSSG)]. [Article in Japanese] 
Shirato H, Isu T, Shimizu Y, Nishioka T, Nonaka M, Abe S, Matsumura S, Shimizu T, Ichimura W, Suzuki K, et al. 
Department of Radiology, Obihiro Kousei Hospital. 
PMID: 8259218 




Radiother Oncol 1993 Apr;27(1):22-9 
Efficacy and toxicity of fractionated stereotactic radiotherapy in the treatment of recurrent gliomas (phase I/II study). 
Laing RW, Warrington AP, Graham J, Britton J, Hines F, Brada M. Neuro-oncology Unit, Institute of Cancer Research, Sutton, Surrey, UK. 
Twenty-two patients with recurrent glioma have been treated on a dose escalation protocol with fractionated stereotactic external beam radiotherapy (SRT). All had previously received radical radiotherapy (median dose 55 Gy) as part of the initial treatment. The dose of SRT was increased from 30 Gy in six fractions to 50 Gy in ten fractions. Median survival from the date of SRT was 9.8 months. There was no significant acute morbidity but five patients who received > or = 40 Gy developed steroid responsive neurological deterioration assumed to represent late radiation damage. The survival and toxicity in patients with recurrent glioma are comparable with interstitial therapy. Fractionated SRT is a noninvasive form of localised radiation which may be a suitable alternative to interstitial therapy in this group of patients. Publication Types: Clinical trial Clinical trial, phase i Clinical trial, phase ii PMID: 8327729 [PubMed - indexed for MEDLINE] 
J Neurooncol 1992 Nov;14(3):255-62


Epilepsia 1999 Nov;40(11):1551-6 
Gamma knife surgery for mesial temporal lobe epilepsy. Regis J, Bartolomei F, Rey M, Genton P, Dravet C, Semah F, Gastaut JL, Chauvel P, Peragut JC. Stereotactic and Functional Neurosurgery Department, Timone Hospital, Orsay, France. jregis@ap-hm.fr 
PURPOSE: Gamma knife radiosurgery (GK) allows precise and complete destruction of chosen target structures containing healthy and/or pathologic cells, without significant concomitant or late radiation damage to adjacent tissues. ... PMID: 10565582



Int J Radiat Oncol Biol Phys 1997 Jan 15;37(2):393-8 
Hypofractionated stereotactic radiotherapy in the management of recurrent glioma. 
Shepherd SF, Laing RW, Cosgrove VP, Warrington AP, Hines F, Ashley SE, Brada M. Neurooncology Unit, The Royal Marsden Hospital, Surrey, United Kingdom. 
.... Presumed radiation damage, defined as reversible steroid-dependent toxicity, was observed in 13 patients (36%) and required reoperation in 2 (6%). A total dose of >40 Gy was a major predictor of radiation damage (p < 0.005). ... Hypofractionated SRT is a noninvasive, well-tolerated, outpatient-based method of delivering palliative, high-dose, focal irradiation. PMID: 9069312


Multiple-fraction-per-day external beam radiotherapy for adults with supratentorial malignant gliomas. 
Halperin EC. 
CNS Cancer Consortium, Durham, N.C. 
The prognosis following therapy for adults with supratentorial malignant gliomas is poor. Standard therapy of 60 Gy of external beam radiotherapy with chemotherapy achieves a median survival time of 35 to 51 weeks following surgery. A variety of innovative therapies have been considered for therapy of malignant gliomas. Multiple-fraction-per-day (MFD) external beam radiotherapy has been evaluated by many investigators. The rationale for MFD teletherapy is based upon exploiting differences in the recovery capacity for radiation damage between slowly and rapidly proliferating tissues and/or shortening the overall treatment time. A large number of clinical trials have, for the most part, failed to show any survival benefit from MFD radiotherapy. These trials have utilized b.i.d. and t.i.d. radiotherapy with fraction sizes of 0.89 to 2 Gy to total doses of 30-81.6 Gy. The linear quadratic model of the radiation cell survival curve suggests that a biological effective tumoricidal dose > or = 10% higher than standard daily radiotherapy, with approximately isoeffective normal tissue damage, could be achieved at 1.2 Gy b.i.d. to a total dose of approximately 72 Gy. Trials of low dose per fraction MFD radiotherapy, to total doses less than 72 Gy, would be predicted to be inadequate to the task. 
PMID: 1460488 [PubMed - indexed for MEDLINE] 


Int J Radiat Oncol Biol Phys 1997 Jan 15;37(2):385-91 
Stereotactic irradiation without whole-brain irradiation for single brain metastasis. 
Shirato H, Takamura A, Tomita M, Suzuki K, Nishioka T, Isu T, Kato T, Sawamura Y, Miyamachi K, Abe H, Miyasaka K. Department of Radiology, Hokkaido University School of Medicine, Sapporo, Japan. 
... effectiveness of stereotactic irradiation (STI) alone without whole-brain irradiation (WBI) for a single metastatic brain tumor was analyzed retrospectively. ... The high response rate and short treatment period of STI alone are advantageous in the treatment of single brain metastasis in patients with active extracranial disease with WBI reserved for relapse. Because of the low complication rate, STI alone may be also useful in patients with good prognosis, without extracranial disease. PMID: 9069311 
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids= 9069311&dopt=Abstract


Int J Radiat Oncol Biol Phys 1985 Jul;11(7):1339-47 
Precision, high dose radiotherapy. II. Helium ion treatment of tumors adjacent to critical central nervous system structures. 
Saunders WM, Chen GT, Austin-Seymour M, Castro JR, Collier JM, Gauger G, Gutin P, Phillips TL, Pitluck S, Walton RE, et al. 
In this paper we present a technique for treating relatively small, low grade tumors located very close to critical, radiation sensitive central nervous system structures such as the spinal cord and the brain stem. A beam of helium ions is used to irradiate the tumor. The nearby normal tissues are protected by exploiting the superb dose localization properties of this beam, particularly its well defined and controllable range in tissue, the increased dose deposited near the end of this range (i.e., the Bragg peak), the sharp decrease in dose beyond the Bragg peak, and the sharp penumbra of the beam. To execute this type of treatment, extreme care must be taken in localization of the tumor and normal tissues, as well as in treatment planning and dosimetry, patient immobilization, and verification of treatment delivery. To illustrate the technique, we present a group of 19 patients treated for chordomas, meningiomas and low grade chondrosarcomas in the base of the skull or spinal column. We have been able to deliver high, uniform doses to the target volumes (doses equivalent to 60 to 80 Gy of cobalt-60) while keeping the doses to the nearby critical tissues below the threshold for radiation damage. Follow-up on this group of patients is short, averaging 22 months (2 to 75 months). Currently, 15 patients have local control of their tumor. Two major complications, a spinal cord transection and optic tract damage, are discussed in detail. Our treatment policies have been modified to minimize the risk of these complications in the future, and we are continuing to use this method to treat such patients. We are enthusiastic about this technique, since we believe there is no other potentially curative treatment for these patients. PMID: 4008290  





Int J Radiat Oncol Biol Phys 1999 Mar 1;43(4):763-75 
Figo IIIB squamous cell carcinoma of the cervix: an analysis of prognostic factors emphasizing the balance between external beam and intracavitary radiation therapy. 
Logsdon MD, Eifel PJ Division of Radiation Oncology, The University of Teaxs M. D. Anderson Cancer Center, Houston 77030, USA. [Record supplied by publisher] 
"Aggressive use of ICRT, carefully balanced with pelvic EBRT, is necessary to achieve the best ratio between tumor control and complications for patients with FIGO Stage IIIB carcinoma of the cervix. In our experience, the highest DSS rates and the lowest complication rates were achieved with a combination of 40-45 Gy of EBRT combined with ICRT." PMID: 10098431 http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10098431&dopt=Abstract




Cancer Radiother 1998 Jan-Feb;2(1):34-41 
[Low-dose postoperative vaginal brachytherapy of adenocarcinoma of the endometrium]. [Article in French] 
Charra-Brunaud C, Peiffert D, Hoffstetter S, Luporsi E, Guillemin F, Bey P Service de curietherapie, centre Alexis-Vautrin, Vandaeuvre-les-Nancy, France. [Record supplied by publisher] 

"Surgery is the primary treatment for endometrial carcinoma. Methods of complementary treatment are still debated, with the potential association of external radiotherapy and/or brachytherapy before or after surgery. This study was aimed at evaluating local control and complications rates in a series of patients treated by hysterectomy followed by postoperative vaginal low-dose rate brachytherapy (BT) combined with pelvic irradiation in case of poor prognosis factors". ..."Results obtained from this series are comparable with those of previous studies, particularly in regard to pre-operative BT. The complication rate is also satisfactory and depends on the irradiation precision and the definition of the target volume." PMID: 9749094 
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9749094&dopt=Abstract





Eur J Gynaecol Oncol 1998;19(4):350-1 
Brachytherapy in the presence of pyuria after pelvic irradiation for cervical cancer. 
Ampil FL, Bell MC Department of Radiology, Louisiana State University Medical Center, Shreveport 71130-3932, USA. 

Little is known about the effects of intracavitary brachytherapy (ICB) performed in the presence of pyuria resulting from external beam pelvic irradiation for cervical cancer (CC). A retrospective study of one decade of ICB for CC showed that brachytherapy was performed in the presence of pyuria in 26 women. Twelve women without pyuria during ICB served as a control group. Antibiotic therapy was routinely administered during intracavitary application. The crude survival rate at 5 years was 39% in patients with pyuria and 42% in women without pyuria; the corresponding local recurrence rates were 23% and 17%; the serious complication rates were 12% and 0% respectively. Intracavitary brachytherapy in the presence of pyuria may have a limited adverse effect on the outcome of women with cancer of the cervix. PMID: 9744724 
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9744724&dopt=Abstract





Bull Cancer 1997 Jun;84(6):625-9
[Uterine sarcoma treated by surgery and postoperative radiation therapy.Patterns of relapse, prognostic factors and role of radiation therapy].[Article in French]
Coquard R, Romestaing P, Ardiet JM, Mornex F, Sentenac I, Gerard JP. Service de radiotherapie-oncologie, Centre Hospitalier Lyon Sud, Pierre-Benite, France.

The objective was to evaluate the results of a combination of surgery and postoperative radiotherapy in patients with uterine sarcoma, to describe the patterns of relapse and to define prognostic factors. ... The survival in this study is higher than that described in series of patients treated with surgery alone. This study confirms the worse prognosis of uterine sarcoma in postmenopausal women. PMID: 9295866  [NB This is sarcoma, not leiomyosarcoma. Ed.]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9295866&dopt=Abstract



The use of electron beams in treating local recurrence of breast cancer in previously irradiated fields. 
Laramore GE, Griffin TW, Parker RG, Gerdes AJ. 
A retrospective study was performed to assess the efficacy of using electron beam therapy to treat locally recurrent breast cancer in previously-irradiated fields. In a group of patients who received postmastectomy nodal and chest wall megavoltage photon therapy to doses of 4000-5000 rads, an additional 4000-5000 rads were delivered to chest wall recurrences with 7-10 MeV electrons. Good tumor responses were obtained without unacceptable concomitant normal tissue damage. With a follow-up time of 9 months to 5 years, 62% (8 of 13) are alive and clinically free of disease in the irradiated volume. Two patients died at respective times of 5 and 6 months after retreatment, with only one showing evidence of chest wall recurrence. One patient showed no response to therapy and the remaining two patients recurred in the treated volume at 10 and 59 months. Morbidity was limited to dry and/or moist desquamation with no evidence of soft tissue necrosis. These results demonstrate that the first course of irradiation did not select for a subset of radioresistant tumor cells, and indicate that a second course of radiation therapy may have much to offer in controlling locally recurrent breast cancer. PMID: 638986 




Radiother Oncol 1996 Dec;41(3):233-6 
Clearance of parenchymal tumors following radiotherapy: analysis of hepatocellular carcinomas treated by proton beams. 
Ohara K, Okumura T, Tsuji H, Min M, Tatsuzaki H, Chiba T, Tsujii H, Akine Y, Itai Y. Department of Radiology, University Hospital, University of Tsukuba, Japan. PMID: 9027939 
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9027939&dopt=Abstract



Radiother Oncol 1996 Dec;41(3):209-14Related Articles, Books, LinkOut 
Soft tissue sarcoma of the extremity. Limb salvage after failure of combined conservative therapy. 
Catton C, Davis A, Bell R, O'Sullivan B, Fornasier V, Wunder J, McLean M. University Musculoskeletal Oncology Unit, Princess Margaret Hospital, Toronto, Canada. 
...Combined conservative surgery and re-irradiation provided superior local control to local re-excision alone and a functional outcome superior to amputation. Combined treatment with re-irradiation should be considered the primary salvage therapy for patients who fail combined therapy and who are suitable for conservative re-excision. Systemic relapse is a significant problem, and optimal therapy should minimize the risk of local relapse after the initial therapy. Eighteen patients (72%) had a history of intralesional excision as their initial intervention, and suggests that inappropriate initial management is a risk factor for relapse after combined conservative therapy. Improvements in therapy must include the appropriate education of the primary care physicians. PMID: 9027935 
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9027935&dopt=Abstract





Ann Acad Med Singapore 1996 May;25(3):352-8 
Kyoto University experience with intraoperative radiation therapy. 
Takahashi M, Shibamoto Y, Sasai K, Nishimura Y, Abe M. Department of Oncology, Kyoto University. 

To date, intraoperative radiotherapy has been performed at Kyoto University Hospital in a total of 480 patients with malignancies various sites. ... For patients with soft tissue sarcomas of the extremities, intraoperative radiotherapy was performed after the tumours were surgically removed to the greatest e* possible. Operation curability had a great impact on the local tumour control rate (82% for curative resection versus 18% for non-curati resection) and on the long-term survival rates (65% versus 8%, respectively). ... PMID: 8876900 http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8876900&dopt=Abstract





Br J Cancer 1995 Aug;72(2):287-92 
Reversal of radiation-induced cisplatin resistance in murine fibrosarcoma cells by selective modulation of the cyclic GMP-dependent transduction pathway. 
Eichholtz-Wirth H. GSF-Institut fur Strahlenbiologie, Neuherberg, Germany. 
Cisplatin resistance, induced in murine fibrosarcoma cells (SSK) in vitro or in vivo by low-dose irradiation, can be overcome by activation of the cyclic GMP(cGMP)-dependent transduction pathway. PMID: 7640207




Hematol Oncol Clin North Am 1995 Aug;9(4):817-23 
Preoperative therapy for soft tissue sarcoma. 
Eilber F, Eckardt J, Rosen G, Forscher C, Selch M, Fu YS. University of California at Los Angeles School of Medicine, USA. 
Soft tissue sarcomas appear to be an ideal tumor type for delivering preoperative therapy. The rationale for preoperative therapy is that it is delivered to undisturbed tissue planes with well-oxygenated tissue. This is of great benefit for radiation therapy, because with new computed tomography scan treatment planning it is possible to completely delineate the tumor without surgical clips or postoperative hematoma (or both) obscuring the tumor margin.  PMID: 7490243 




Hematol Oncol Clin North Am 1995 Aug;9(4):733-46 
Radiation as a therapeutic modality in sarcomas of the soft tissue. 
Suit H, Spiro I. Department of Radiation Oncology, Massachusetts General Hospital, Boston, USA. 
Management of the primary lesion in patients with soft tissue sarcomas is combined modality in the majority of instances. The modalities are surgery and irradiation. Radical surgery as currently practiced in major oncology centers does not achieve local control in an important proportion of patients. PMID: 7490238 





Cancer 1995 May 1;75(9):2299-306 
Preoperative regional therapy for extremity sarcoma. A tricenter update. 
Wanebo HJ, Temple WJ, Popp MB, Constable W, Aron B, Cunningham SL. Department of Surgery, Brown University, Providence, RI 02908, USA. 

Combined therapy for extremity sarcoma in a multicenter setting using preoperative radiation with sensitizing chemotherapy and adequate resection was associated with an excellent local control rate (98.5%) and reasonable long term tumor control, although distant metastases continued to be a major challenge PMID: 7712441 
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7712441&dopt=Abstract



Radiother Oncol 1993 Apr;27(1):46-54 
Selectivity of boron carriers for boron neutron capture therapy: pharmacological studies with borocaptate sodium, L-boronophenylalanine and boric acid in murine tumors. 
Gregoire V, Begg AC, Huiskamp R, Verrijk R, Bartelink H. Division of Experimental Therapy, The Netherlands Cancer Institute, Amsterdam. PMID: 8327732 http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8327732 &dopt=Abstract




Int J Radiat Oncol Biol Phys 1993 Dec 1;27(5):1159-63 
Reirradiation for rectal cancer and surgical resection after ultra high doses. 
Mohiuddin M, Lingareddy V, Rakinic J, Marks G Department of Radiation Oncology and Nuclear Medicine, Thomas Jefferson University Hospital, Philadelphia, PA 19107. [Record supplied by publisher] 

Local recurrence of rectal cancer following high-dose pelvic radiation presents a difficult management challenge. Conventional wisdom suggests that reirradiation should be avoided and radical pelvic surgery is hazardous after ultra high-dose radiation. ... Based on this experience, we believe that in selected patients radical surgical resection after cumulative ultra high doses (70-90 Gy) of radiation can be performed safely. A viable anastomosis is also possible in spite of these high doses. Planned reirradiation for palliative relief of symptoms can be effective without unusual risks of complication. Long-term effects of such ultra high dose radiation and surgery continue to be monitored. PMID: 8262842 http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8262842&dopt=Abstract





Surg Gynecol Obstet 1993 Mar;176(3):203-7 
Preoperative irradiation for unresectable carcinoma of the rectum. 
Whiting JF, Howes A, Osteen RT Department of Surgery, Brigham and Women's Hospital, Boston, Massachusetts. 

... Thirteen of the 20 patients were able to undergo resection with curative intent after radiotherapy. ...The incidence of complications in similar series is discussed and the need for better selection of patients is addressed. PMID: 8438190 
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8438190&dopt=Abstract





Gynecol Oncol 1993 Mar;48(3):328-32 
Intraoperative radiation therapy in gynecologic cancer: the Mayo Clinic experience. 
Garton GR, Gunderson LL, Webb MJ, Wilson TO, Martenson JA Jr, Cha SS, Podratz KC Division of Radiation Oncology,Mayo Clinic, Rochester, Minnesota 55905. 

... Patients with microscopic disease had significantly higher 5-year disease-free and overall survival (70 and 67%, respectively). In summary, IORT in combination with maximum debulking surgery with or without external beam therapy in patients with paraaortic or pelvic sidewall recurrences of gynecologic malignancies appeared to improve long-term local control and survival. The addition of hyperthermia or hypoxic sensitizers may be a consideration to further improve local control in patients with gross residual disease. .... IORT-related toxicity was acceptable. PMID: 8385058 
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8385058&dopt=Abstract





J Med Assoc Thai 1991 Sep;74(9):404-11 
Multidisciplinary "limb salvage" treatment of osteosarcoma. 
Pochanugool L, Nontasut S, Subhadharaphandou T, Hathirat P, Sirikulchayanonta V, Ratanatharathorn V, Yuktanonda P. Department of Radiology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand. 

Intraarterial plus systemic chemotherapy of cis-diamine dichloroplatinum-II and anthracycline together with preoperative radiation and "limb salvage" treatment have increased the chance of local control and facilitated the previous surgically nonresectable to be resectable. .... Late pulmonary metastases cause the need for future protocol for prophylactic lung therapy. PMID: 1791395 



Neurosurg Rev 1990;13(3):247-52 
Unusually long survival time after resection and irradiation of a brain metastasis from osteosarcoma. 
Niedeggen A, Weis J, Mertens R, Rother J, Brocheler J. Clinic of Neurosurgery, Rhenisch-Westphalian Technical University (RWTH) Aachen, West Germany. 

Cerebral metastases of osteosarcomas are rare. The cases published up to now have manifested only a short relapse-free period of survival. Intracranial filia generation must be anticipated if metastasis formation takes place in the lung. We report here on a young patient who underwent operation for an intraparenchymal cerebral metastasis 76 months after amputation of the left leg due to an osteosarcoma chondroblasticum, and who is, at present, healthy, 13 months after resection. This unusually long survival time is attributed to the good neurological status before craniotomy, early diagnosis, and the improvement of the cytostatic therapy (COSS-80-scheme). PMID: 1697937 





Strahlenther Onkol 1988 Jul;164(7):386-92 
[Results of whole lung irradiation and chemotherapy in comparison with partial lung irradiation in metastasizing, undifferentiated soft tissue sarcomas]. [Article in German] 
Zamboglou N, Furst G, Pape H, Bannach B, Molls M, Schmitt G. Klinik fur Strahlentherapie und Radiologische Onkologie, Universitat Dusseldorf. PMID: 3400046 http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3400046 &dopt=Abstract




Cancer 1987 Mar 1;59(5):908-15 
Clinical experience with intravenous radiosensitizers in unresectable sarcomas. 
Kinsella TJ, Glatstein E. 
Traditionally, adult bone and soft tissue sarcomas have been considered to be "radioresistant." ... Adult high-grade sarcomas can be controlled with high-dose radiotherapy and intravenous radiosensitizers, although the precise role of these agents is unclear. PMID: 3815269 
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3815269&dopt=Abstract




Intraarterial chemotherapy of head and neck tumors. 
Lee YY, Wallace S, Dimery I, Goepfert H. 
... Treatment with intraarterial chemotherapy using superselective catheterization before irradiation or surgery is beneficial in some patients. PMID: 3082167




Gan No Rinsho 1985 Jul;31(9 Suppl):1063-72 
[Multidisciplinary treatment of bone and soft tissue sarcomas]. [Article in Japanese] 
Furuya K, Wada N, Kawaguchi N, Amino K. 

... 1975 was the year when Adriamycin was introduced... The data of the group study of soft tissue sarcoma sponsored by Ministry of Health and Welfare show that in 318 cases of soft tissue sarcomas of extremities, the recurrence rate during the period between 1962 and 1976 is 52%, metastasis rate 69%, and overall survival at 5 years 42%. From 1972 to 1983, in 414 cases treated by the orthopaedic clinics of the same group the recurrence rate become as low as 23% metastasis rate 45% and overall survival at 5 years 56%. In our clinics, 89 patients with soft tissue sarcomas were treated by the curative wide resection and the recurrence rate is 12%, metastasis rate 25%, and overall survival at 5 years 78%. In this series, in 80% of cases limb salvage is succeeded. PMID: 4057570 





Int J Radiat Oncol Biol Phys 1985 Jan;11(1):123-8 
Intra-arterial infusion of radiosensitizer (BUdR) combined with hypofractionated irradiation and chemotherapy for primary treatment of osteogenic sarcoma. 
Martinez A, Goffinet DR, Donaldson SS, Bagshaw MA, Kaplan HS. 

Combined modality treatment was given in nine patients of osteogenic sarcoma wherein the tumor was unresectable because of location or amputation was refused. This alternative to massive surgery comprised hypofractionated irradiation, intra-arterial infusion of the radiosensitizer 5'-bromodeoxyuridine (BUdR) and adjuvant systemic chemotherapy. .... On the basis of our experience, we believe that new approaches using modifications of external beam irradiation with different fractionation schedules or better radiosensitizing compounds may hold promise for patients with non-resectable osteosarcoma. PMID: 3855408 http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3855408&dopt=Abstract




Recent Results Cancer Res 1983;86:204-8 
Intra-arterial infusion of bromodeoxyuridine and radiotherapy in osteosarcoma and other bone malignancies. 
Lejeune FJ, Regnier R, Nogaret JM, Jabri M. 

In order to avoid amputation, which does not seem to improve survival in osteosarcoma, we have initiated a limb-preservation program using intra-arterial radiosensitization.. PMID: 6580684 
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6580684&dopt=Abstract





J Maxillofac Surg 1978 May;6(2):98-103 
The effects of "BAR" therapy on oral malignant tumors. 
Nagai T, Sakaizumi K, Asanami S, Lian SL, Tomita O, Hirayama T. 

"BAR" therapy is a combined therapy with BUdR (Radiosensitizer), Antimetabolites (5-FU, FT-207 etc.) and Radiation for malignant tumours. How radiation can be reduced as far as possible and how the effects of treatment can be increased as much as possible are the objectives of this study of combining radiation and BUdR therapy. PMID: 353211 





Can J Surg 1977 Nov;20(6):530-6 
Radiation treatment of Ewing's sarcoma and osteogenic sarcoma.
Jenkin RD. 
... When the primary site makes resection impracticable, the response to irradiation and chemotherapy is encouraging. PMID: 271036 





Rev Interam Radiol 1977 Jul;2(3):123-33 
Recent advances in radiotherapy. 
Munzenrider JE. 
Significant recent achievement in radiotherapy are presented, with brief discussions of brachytherapy, clinical dose-rate effects, ultrafractionation, and total and half-body irradiation. Reports on radiation modifiers, including hyperbaric oxygen, chemical radiosensitizers, and normal tissue protective agents are briefly summarized, while the potential of local and systemic hyperthermia is discussed in greater detail. Recent reports of local tumor control in so-called "radioresistant tumors," such as salivary gland tumors, adenocarcinomas of the breast, prostate and pancreas, malignant melanoma and malignant carcinoid, are summarized. Current status of heavy particle radiotherapy is discussed in detail. Results of initial clinical trials of neutron beam therapy are summarized, and a brief review of proton beam clinical trials and pion beam facilities is included. Recent reports defining the role of combined irradiation and surgery in rectal and breast cancer, and in soft tissue sarcomas, are discussed. Reports of enhanced radiation toxicity seen with concomitant or sequential chemotherapy and radiotherapy are detailed, including CNS toxicity seen with methotrexate and cytosine arabinoside, cardiotoxicity with adriamycin, and pulmonary toxicity with bleomycin. New or improved diagnostic techniques with special relevance to radiotherapy treatment planning, including CT scanning, histerography, internal mammary lymphoscintigraphy, and upper extremity lymphangiography are described. PMID: 408898





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Mechanisms of Radiation Damage & Radiosensitivity [How It Works]
Medical Journal References
These are some interesting and perhaps relevant publications related to topics discussed earlier, as well as serving as references for the material presented.



Radiat Res 2001 Feb;155(2):360-8 
Effects of radiation on tumor intravascular oxygenation, vascular configuration, development of hypoxia, and clonogenic survival. 
Lord E, Paoni S. Department of Radiation Oncology, University of Rochester School of Medicine, New York, USA. 
The underlying physiological mechanisms leading to tumor reoxygenation after irradiation have elicited considerable interest, but they remain somewhat unclear. The current study was undertaken to determine the effects of a single dose of 10 Gy gamma radiation on both tumor pathophysiology and radiobiologically hypoxic fraction. .... At 24 h postirradiation, ... results demonstrate that tumor hypoxia develops at an increased distance from perfused blood vessels after irradiation,...By 72 h postirradiation, all physiological parameters had returned to the levels in volume-matched, nonirradiated controls. ... Although such direct measurements have previously proven valuable in predicting tumor response to therapy or oxygen manipulation, a combination of parameters is required to adequately describe the mechanisms underlying these changes after irradiation. PMID: 11175672

Hyperbaric oxygen corrects sacral plexopathy due to osteoradionecrosis appearing 15 years after pelvic irradiation.
Videtic GM, Venkatesan VM Department of Radiation Oncology, London Regional Cancer Centre, Ontario,Canada. [Record supplied by publisher]
In 1982, a 55-year-old woman was treated by total cystectomy and adjuvant radiotherapy/chemotherapy for a leiomyosarcoma of the bladder. Fifteen years later she presented with symptoms and signs of sacral plexopathy. Investigations revealed osteoradionecrosis of the sacrum. Hyperbaric oxygen therapy (HBO2) was instituted and progressive resolution of the neurological complaints followed. HBO2 should be considered when managing late-onset sequelae in previously irradiated patients. PMID: 10465478
Int J Radiat Oncol Biol Phys 1996 Apr 1;35(1):103-11
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10465478&dopt=Abstract 




Toxicology 2000 Nov 30;155(1-3):73-82 
Oxidative damage to mitochondria in normal and cancer tissues, and its modulation. 
Kamat JP, Devasagayam TP. Cell Biology Division, Bhabha Atomic Research Centre, Mumbai, India. 
Cellular damage induced by reactive oxygen species (ROS) in normal tissues has been implicated in the etiology of several human ailments. Among the subcellular organelles, damage to mitochondria is considered crucial and can lead to cytotoxicity and cell death.... Our study shows that ROS can induce significant oxidative damage in mitochondria from both normal and tumor tissues and this can be inhibited by natural antioxidants like tocotrienols, nicotinamide and caffeine. Damage, on the other hand, can be enhanced by deuteration of the buffer and oxygenation. Our results hence demonstrated that mitochondria were sensitive to damage by ROS and its modulation may have potential uses in prevention of the disease in normal tissues; if damage can be selectively induced in tumor, it can lead to its regression. PMID: 11154799 http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11154799&dopt=Abstract



Radiother Oncol 2000 Mar;54(3):261-71 
Variation in sensitizing effect of caffeine in human tumour cell lines after gamma-irradiation. 
Valenzuela MT, Mateos S, Ruiz de Almodovar JM, McMillan TJ. Laboratoio de Investigaciones Medicas y Biologia Tumoral, Departamento de Radiologia y Medicina Fisica, Facultad de Medicina, Universidad de Granada, 18071, Granada, Spain. 
... The data presented confirm that p53 status can be a significant determinant of the efficacy of caffeine as radiosensitizer in these tumour cell lines, and document the importance of the G2 checkpoint in this effect. PMID: 10738085 
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10738085 &dopt=Abstract



Radiation-recall enteritis after actinomycin-D and adriamycin therapy. 
Stein RS. 
A 22-year-old man developed four episodes of bowel obstruction after radiation therapy for a testicular tumor metastatic to retroperitoneal nodes. Each episode followed a course of chemotherapy with actinomycin-D or adriamycin. On one occasion bowel resection was required and revealed vascular changes compatible with radiation injury. The case appears to be an example of radiation recall injury involving the small bowel. The decision to use actinomycin-D or adriamycin must be weighed against the risk of tissue injury when a predisposition to radiation damage is present. PMID: 684478 


Br J Radiol 2000 Oct;73(874):1100-4 
Gas exchange parameters in radiotherapy patients during breathing of 2%, 3.5% and 5% carbogen gas mixtures. 
Baddeley H, Brodrick PM, Taylor NJ, Abdelatti MO, Jordan LC, Vasudevan AS, Phillips H, Saunders MI, Hoskin PJ. Paul Strickland Scanner Centre, Mount Vernon Hospital, Rickmansworth Road, Northwood, Middlesex HA6 2RN, UK. 

The gas mixture carbogen may be breathed by patients to enhance the oxygenation level and therefore the radiosensitivity of tumours. However, owing to the high CO2 content, its inhalation is associated with patient intolerance. Our aim was to determine a suitable carbon dioxide and oxygen gas mixture with similar enhancement of arterial oxygenation to 5% carbogen and with improved patient tolerance. ... The results suggest that 2% CO2 in O2 enhances arterial oxygen levels to a similar extent as 3.5% and 5% CO2 and that it is well tolerated. PMID: 11271904


Gan To Kagaku Ryoho 2000 Oct;27(12):1816-8 
[Chemoradiotherapy with low-dose cisplatin and 5-FU for advanced esophageal cancer]. [Article in Japanese] 
Tajima M, Ichikawa W, Takagi Y, Uetake Y, Kojima K, Osanai T, Takenaka S, Nihei Z, Sugihara K. Dept. of Surgery II, Tokyo Medical and Dental University. 
We evaluated the efficacy of chemoradiotherapy (CRT) for advanced esophageal cancer, from the view point of response. The relationship between chemo-radiosensitivity and dihydropyridine dehydrogenase (DPD), thymidylate synthase (TS), and p53 was investigated immunohistochemically. ... PMID: 11086419 

 


Radiother Oncol 2000 Oct;57(1):91-6 
Multivariate analysis of pulmonary fibrosis after electron beam irradiation for postmastectomy chest wall and regional lymphatics: evidence for non-dosimetric factors. 
Huang EY, Wang CJ, Chen HC, Sun LM, Fang FM, Yeh SA, Hsu HC, Hsiung CY, Wu JM. Department of Radiation Oncology, Chang Gung Memorial Hospital, 123 Ta-Pei Road, Niao-Sung Hsiang, Kaohsiung Hsien, Taiwan. 

To evaluate the factors associated with pulmonary fibrosis after postmastectomy electron beam irradiation of chest wall and regional lymphatics in patients with breast cancer. ... Only Grade 1 radiation-induced late pulmonary toxicity was noted in 33 patients (29%). Twenty-six patients (24%) developed pulmonary fibrosis under unbolused chest wall. Lung fibrosis under bolused chest wall was noted in 11 patients (10%). Statistical difference (P<0.01) was noted between the incidence of fibrosis in these two sites. In multivariate analysis of lung fibrosis under unbolus-covered chest wall, the independent prognostic factors are low body mass index (BMI) (P<0.01), tamoxifen taking (P=0.03), and no treatment interruption (P=0.03). No independent factor was associated with lung fibrosis under bolus-covered chest wall in multivariate analysis. ... In the analysis of pulmonary fibrosis induced by unbolused electron beam, BMI rather than body weight and body height is a strong prognostic factor. Tamoxifen and short overall time can predispose the development of lung fibrosis. Publication Types: Clinical trial PMID: 11033193  



Int J Radiat Oncol Biol Phys 2000 Sep 1;48(2):339-45 
Blood hemoglobin level may affect radiosensitivity-preliminary results on acutely reacting normal tissues. 
Henke M, Bechtold C, Momm F, Dorr W, Guttenberger R. Abteilung Strahlentherapie, Radiologische Universitatsklinik, Freiburg, Germany. henke@uni-freiburg.de 
...A decreased blood hemoglobin concentration may-perhaps by an impaired tissue oxygenation-reduce the radiosensitivity of normal tissue such as skin and mucosa. However, the data is preliminary and needs further confirmation. PMID: 10974446 http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10974446&dopt=Abstract


Cancer 1996 Jun 1;77(11):2407-12
Hyperbaric oxygen therapy for the treatment of radiation-induced sequelae in children. The University of Pennsylvania experience.
Ashamalla HL, Thom SR, Goldwein JW Department of Radiation Oncology, New York Methodist Hospital, Brooklyn 11215, USA. [Record supplied by publisher]
... The role of hyperbaric oxygen (HBO) therapy in the treatment of radiation-related sequelae in adults is well known... Except for two patients who had initial anxiety, nausea, and vomiting, the HBO treatments were well tolerated. In all but one patient, the outcome was excellent. In the six patients who had prophylactic HBO, all continued to demonstrate complete healing of their orthodontal scars at last follow-up. In the four patients who received HBO as a therapeutic modality, all 4 had documented disappearance of signs and symptoms of radionecrosis and two patients demonstrated new bone growth on follow-up computed tomography scan. One patient with vasculitis and seventh cranial nerve palsy had transient improvement of hearing; however, subsequent audiograms returned to baseline. .... The use of hyperbaric oxygen for children with radiation-induced bone and soft tissue complications is safe and results in few significant adverse effects. It is a potentially valuable tool both in the prevention and treatment of radiation-related complications. PMID: 8635114
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8635114&dopt=Abstract


Clin Oncol (R Coll Radiol) 1999;11(3):198-9
Improving cancer radiotherapy with 2-deoxy-D-glucose: phase I/II clinical trials on human cerebral gliomas. 
Mohanti BK, Rath GK, Anantha N, Kannan V, Das BS, Chandramouli BA, Banerjee AK, Das S, Jena A, Ravichandran R, Sahi UP, Kumar R, Kapoor N, Kalia VK, Dwarakanath BS, Jain V. Kidwai Memorial Institute of Oncology, Bangalore, India. 
PURPOSE: Evaluation of tolerance, toxicity, and feasibility of combining large fraction (5 Gy) radiotherapy with 2-deoxy-D-glucose (2DG), an inhibitor of glucose transport and glycolysis, which has been shown to differentially inhibit repair of radiation damage in cancer cells.METHODS AND MATERIALS: Twenty patients with supratentorial glioma (Grade 3/4), following surgery were treated with four weekly fractions of oral 2DG (200 mg/kg body weight) followed by whole brain irradiation (5 Gy). Two weeks later, supplement focal radiation to the tumor (14 Gy/7 fractions) was given. Routine clinical evaluation, x-ray computerized tomography (CT), and magnetic resonance (MR) imaging were carried out to study the acute and late radiation effects. RESULTS: All the 20 patients completed the treatment without any interruption. The vital parameters were within normal limits during the treatment. None reported headache during the treatment. Mild to moderate nausea and vomiting were observed during the days of combined therapy (2DG + RT) in 10 patients. No significant deterioration of the neurological status was observed during the treatment period. Seven patients were alive at 63, 43, 36, 28, 27, 19, and 18 months of follow-up. In these patients, the clinical and MR imaging studies did not reveal any late radiation effects. CONCLUSIONS: Feasibility of administering the treatment (2DG + 5 Gy) is demonstrated by the excellent tolerance observed in all 20 patients. Further, the clinical and MR studies also show the absence of any brain parenchymal damage. Publication Types: Clinical trial Clinical trial, phase i PMID: 8641905 




Radiother Oncol 1999 Dec;53(3):233-45 
Acute and late toxicity, tumour control and intrinsic radiosensitivity of primary fibroblasts in vitro of patients with advanced head and neck cancer after concomitant boost radiochemotherapy. 
Rudat V, Dietz A, Nollert J, Conradt C, Weber KJ, Flentje M, Wannenmacher M. Department of Radiation Oncology, University of Heidelberg, Germany. 

The existence of hereditary factors influencing the cellular response to ionising radiation has led to the hypothesis that the inter-patient variability of clinical radiation reactions may, at least in part, be attributable to an individual, or intrinsic, radiosensitivity. Considerable effort has been spent in the development of test systems that would determine individual radiosensitivity before or early during radiotherapy to possibly predict treatment outcome, but the results are still conflicting. The present explorative study was therefore aimed at the detection of associations between acute and late radiation effects, tumour control and in vitro radiosensitivity of primary normal tissue fibroblasts. ...
 In our study of patients with advanced cancer of the head and neck, neither the normal fibroblast SF2 nor the severity of acute radiation effects were able to predict late radiation effects or locoregional tumour control. PMID: 10660204  http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10660204&dopt=Abstract


Clin Cancer Res 2000 Aug;6(8):3159-65 
Potential role of microvessel density in predicting radiosensitivity of T1 and T2 stage laryngeal squamous cell carcinoma treated with radiotherapy. 
Kamijo T, Yokose T, Hasebe T, Yonou H, Sasaki S, Hayashi R, Ebihara S, Miyahara H, Hosoi H, Ochiai A. Pathology, Division, National Cancer Center Research Institute East, Chiba, Japan. 

Curative radiotherapy is the first choice of therapy for T1 and T2 stage laryngeal squamous cell carcinoma (LSCC) patients to preserve their phonation. Patients with recurrent tumors who undergo salvage surgery require prolonged nasal feeding. Therefore, clinical interest has been focused on elucidating a predictive factor indicating which tumors are likely to be radiosensitive before radiotherapy. We analyzed the relations between radiosensitivity and ... epidermal growth factor receptor overexpression) and microvessel density ... in biopsy specimens from 31 LSCC patients given radiotherapy ... ...These results indicate that MVD is a potentially useful clinical factor predicting radiosensitivity for patients with early stage LSCCs before treatment. PMID: 10955798

Radiother Oncol 1998 Feb;46(2):185-91 
In vitro radiation-induced apoptosis and early response to low-dose radiotherapy in non-Hodgkin's lymphomas. 
Dubray B, Breton C, Delic J, Klijanienko J, Maciorowski Z, Vielh P, Fourquet A, Dumont J, Magdelenat H, Cosset JM. Departement d'Oncologie Radiotherapie, Institut Curie, Paris, France. 
PURPOSE: Prospective investigation of spontaneous and in vitro radiation-induced apoptosis to predict early response to palliative radiotherapy in patients with non-Hodgkin's lymphomas. ... Spontaneous and in vitro radiation-induced apoptosis can be easily and quickly assessed on cells obtained by fine-needle sampling of non-Hodgkin's lymphoma lesions. The present results suggest that in vitro radiation-induced apoptosis could be used as a predictive assay of early response to low-dose in vivo irradiation in patients with non-Hodgkin's lymphomas. PMID: 9510046 
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9510046&dopt=Abstract




Radiother Oncol 1998 Mar;46(3):239-48 Comment in: Radiother Oncol. 1998 Mar;46(3):225-7 
Age has no impact on acute and late toxicity of curative thoracic radiotherapy. 
Pignon T, Gregor A, Schaake Koning C, Roussel A, Van Glabbeke M, Scalliet P. Department of Radiotherapy-Oncology, Hopital de la Timone, Marseille, France. 

Radiotherapy is a treatment method frequently employed in the management of thoracic tumours. Although the highest incidence of these tumours is found in elderly people, tolerance to radiotherapy is not well documented in older age groups. Many physicians are tempted to alter the radiotherapy planning in a population with a supposed lower life expectancy in order to prevent acute reactions whereas late reactions are often ignored. The current study aimed to determine the influence of age on the frequency and severity of acute and late side effects and also whether the prognosis of tumours sufficiently differed between ages to justify different attitudes towards their management. 
... The absence of toxicity observed in the current study regardless of age reinforces the conviction that age per se is not a sufficient reason to exclude patients in good general condition with thoracic tumour from curative radiotherapy when medically indicated. PMID: 9572616 http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9572616&dopt=Abstract

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Zhongguo Zhong Xi Yi Jie He Za Zhi 1997 Aug;17(8):465-6 
[Clinical study of combined Chinese herbal medicine with move stripe field radiation in treating primary hepatocellular carcinoma]. [Article in Chinese] 
Han JQ, Chen SD, Zhai LM. Shandong Institute of Tumor Prevention and Treatment, Jinan. 

To find a more effective treatment of primary hepatocellular carcinoma by using combined therapy of Chinese herbal medicine with radiotherapy. ... Prospective study was conducted with double-blind method on prognosis of patients treated with combined therapy of Xuefu Zhuyu decoction and move stripe field radiation on entire liver. A control group was established and treated with placebo and radiotherapy. ... The 1-, 3- and 5-year survival rates of the test group were higher than those of the control group by 20.0%, 23.4% and 16.6% respectively. The remote metastatic rate of the two groups were not different significantly. ... Xuefu Zhuyu decoction showed coordinative effect with radiotherapy on antitumor, it could enhance the radiosensitivity of liver cancer cells, increase the radiation tolerance of normal hepatocytes and reduce the side effect of radiotherapy. PMID: 10322831
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10322831&dopt=Abstract



[The morphological characteristics of sarcoma M1 cells before and after irradiation]. [Article in Russian] 
Abrosimov AI, Skoropad VI. 
Morphology of the death of rat sarcoma M1, cells before and in varying time after irradiation at doses of 10 and 20 Gy with and without metronidazole (as a radiosensitizer) was investigated at the light optic and electron microscopic levels. Two types of death: necrosis and apoptosis with the prevalence of the former were revealed. Irradiation and the use of metronidazole did not influence the type of death of sarcoma M1 cells. PMID: 1943570 http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1943570&dopt=Abstract



Int J Radiat Oncol Biol Phys 1989 Jan;16(1):139-42 
Tumor bed effect-induced reduction of tumor radiocurability through the increase in hypoxic cell fraction. 
Milas L, Hunter N, Peters LJ. University of Texas M.D. Anderson Hospital and Tumor Institute, Houston 77030. 
... TBE causes the reduction in tumor radiocurability through the increase in hypoxic fraction of tumor cells. PMID: 2912935  



Radiobiologiia 1986 Mar-Apr;26(2):227-31 
[Radiosensitizing effect of interferon synthesis inducers]. [Article in Russian] 
Leonidze DL, Afanas'ev GG, Poverennyi AM, Pelevina II. 
The preinjection of inductors of leukocytic interferon synthesis of rapid (poly I.poly C, dextransulfate) and slow (tyloron) types to mice bearing inoculated solid sarcoma 37 considerably increases the efficiency of X-irradiation of tumors: the coefficient of tumor growth inhibition (kappa *) exceeds 1.0, and the number of animals with the completely regressed tumors increases. The effectiveness of the procedure depends on the time of the injection of the preparations and modes of irradiation. PMID: 2422676




Clin Exp Metastasis 1985 Jan-Mar;3(1):21-7 
Increase in radiosensitivity of lung micrometastases by hyperbaric oxygen. 
Milas L, Hunter NM, Ito H, Brock WA, Peters LJ. 
Four-day-old artificial pulmonary micrometastases of two murine fibrosarcomas, designated FSA and NFSA, showed increased sensitivity to ionizing radiation by a factor of 1.13 when animals were exposed to hyperbaric oxygen breathing before and during irradiation, implying the presence of hypoxia in the micrometastases. At the time of irradiation the diameter of FSA and NFSA metastases was smaller than 200 and 100 microns, respectively, which, on the basis of oxygen diffusion, could not be responsible for hypoxia. It is assumed that hypoxia of micrometastases is passive, reflecting the radiobiological hypoxia of lung tissue that could exist under normal breathing conditions. PMID: 4042454 

 


 
Int J Radiat Oncol Biol Phys 1984 Sep;10(9):1623-6 
Enhanced tumor responses through therapies combining CCNU, MISO and radiation. 
Siemann DW, Hill SA. 
Studies were performed to determine whether the radiation sensitizer misonidazole (MISO) could enhance the tumor control probability in a treatment strategy combining radiation and the nitrosourea 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU)...  [In Mice]  PMID: 6480451 

 

Int J Radiat Oncol Biol Phys 1984 Sep;10(9):1545-9 
Tumor sensitization and protection: influence of stromal injury on estimates of dose modification. 
Williams MV, Rojas A, Denekamp J. 
Tumor regrowth delay is an assay which reflects tumor cell kill but can be modified by growth rate changes resulting from damage to the stroma (tumor bed effects). If the stromal damage is modified by radiosensitizers and radioprotectors to a different degree from the tumor cells, the overall measurement of dose modifying factors may be influenced by the choice of a regrowth size for the growth delay analysis...[In mice]  It appears that stromal damage may be the cause of the radioprotection observed in the carcinoma, whereas direct tumor cell radioprotection is indicated in the fibrosarcoma. Both direct tumor cell killing and cell death secondary to stromal damage will play an important role in determining the local control of irradiated tumors. PMID: 6090359 

 


Int J Radiat Oncol Biol Phys 1984 Aug;10(8):1203-5 
Hypoxic cell sensitizers and heavy charged particle beams may play complementary roles in killing hypoxic tumor cells. 
Curtis SB, Tenforde TS, Afzal SM. 
[In Mice]  . PMID: 6432747  

Br J Cancer 1980 Dec;42(6):861-70 
In vivo interaction of anti-cancer drugs with misonidazole or metronidazole: methotrexate, 5-fluorouracil and adriamycin. 
Tannock IF. 
I have studied the effects on growth of two tumours in mice and on host toxicity, of combining Misonidazole (MISO) or Metronidazole (METRO) with ... METRO and MISO increase the anti-tumour effects of some anti-cancer drugs, but may also increase host toxicity. Nitroimidazoles should be used with caution in combination with chemotherapy. PMID: 7459220 



Br J Cancer 1980 Jan;41(1):1-9 
Is tumour radiosensitization by misonidazole a general phenomenon? 
Denekamp J, Hirst DG, Stewart FA, Terry NH. 
PMID: 7362769 
 


Vopr Onkol 1977;23(8):17-27 
[Hyperbaric oxygenation in the preoperative radiotherapy of soft tissue sarcomas]. [Article in Russian] 
Sergeev SI, Dar'ialova SL, Lavnikova GA. 
Based on the study of clinical and morphological criteria for estimation of the efficacy of distance gammatherapy under hyperbaric oxygenation in the combined treatment of patients with soft tissue sarcomas, it was concluded that hyperbaric oxygenation employed in radiotherapy contributed to the increased rate of neoplasms damage. The latter resulted in a decreased percentage of the recurrence. The attenuation of local radiation and less number of postoperative complications indicate that healthy tissues surrounding the tumor are preserved. No rise in the percentage of distant metastases was noted in irradiation under hyperbaric oxygenation. Publication Types: Clinical trial PMID: 333747
Vopr Onkol 1975;21(5):63-73 



[Universal approaches to the control of tissue radiosensitivity during radiation therapy of malignant tumors].[Article in Russian] 
Iarmonenko SP. 
Approaches to the problem of the control over tissue radiosusceptibility, united by the common purpose--a need for selective increase of the intact tissues tolerance to overcome tumor hypoxia, are discussed. Such universal approaches include an application of radiation characterized by high linear wastes of radiation energy, methods of increased oxygenation of tumors, the use of electron sink compounds, and irradiation under conditions of hypoxia--hypoxiradiotherapy. .... PMID: 1210147

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RadioSensitizers and RadioChemoTherapy

Medical Journal References


Am J Clin Oncol 2001 Apr;24(2):107-12 
Improved overall survival among responders to preoperative chemoradiation for locally advanced rectal cancer. 
Janjan NA, Crane C, Feig BW, Cleary K, Dubrow R, Curley S, Vauthey JN, Lynch P, Ellis LM, Wolff R, Lenzi R, Abbruzzese J, Pazdur R, Hoff PM, Allen P, Brown T, Skibber J. Departments of Radiation Oncology, The University of Texas, M.D. Anderson Cancer Center, Houston 77030, USA. PMID: 11319280



Int J Radiat Oncol Biol Phys 2001 May 1;50(1):1-12 
Preoperative hyperfractionated radiotherapy with concurrent chemotherapy in resectable esophageal cancer. 
Kim JH, Choi EK, Kim SB, Park SI, Kim DK, Song HY, Jung HY, Min YI. Department of Radiation Oncology, Esophageal Disease Study Group, Asan Medical Center, University of Ulsan Medical College, 388-1 Poongnap-Dong, Songpa-Ku, Seoul 138-736, South Korea. jhkim2@www.amc.seoul.kr 
... Preoperative chemoradiotherapy in this trial showed improved clinical and pathologic tumor response and survival when compared to historical results. Patients who underwent esophagectomy following chemoradiation showed decreased local recurrence and improved survival and disease-free survival rates ... PMID: 11316540 



Hepatogastroenterology 2000 Jul-Aug;47(34):1142-6 
Intraoperative and conformal external-beam radiation therapy in patients with locally advanced pancreatic carcinoma; results from a feasibility phase II study. 
Furuse J, Ogino T, Ryu M, Kinoshita T, Konishi M, Kawano N, Ishikura S, Shimizu W, Sekiguchi R, Moriyama N, Iwasaki M, Yoshino M. Department of Internal Medicine, National Cancer Center Hospital East, Chiba, Japan. jfuruse@east.ncc.go.jp 
... Chemoradiation therapy is widely indicated to patients with locally advanced pancreatic carcinoma, though the capability of radiotherapy alone is not assessed enough. The purpose of this study is to clarify the efficacy and safety of a more intensive radiotherapy for those patients. ...: The above radiotherapy is considered to be active for the locally advanced pancreatic cancer with acceptable toxicity, when the gastrointestinal tract is excluded from the radiation field. This should be further assessed in late phase II studies involving a large number of patients. PMID: 11020899 http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11020899&dopt=Abstract



Am J Surg 2000 Jun;179(6):508-13 
The role of multimodality therapy for resectable esophageal cancer. 
Meneu-Diaz JC, Blazquez LA, Vicente E, Nuno J, Quijano Y, Lopez-Hervas P, Devesa M, Fresneda V. Departamento de Cirugia General y del Aparato Digestivo, Hospital Universitario Ramon y Cajal, Universidad de Alcala de Henares, Madrid, Spain. 
BACKGROUND: There is an increasing interest in the role of combined therapy to achieve long-term survival for patients with resectable esophageal neoplasms. Surgery provides excellent palliation with relatively low morbidity and mortality rates, but cure remains elusive. ...% (12) remained alive. Actuarial survival rates at 12, 23, and 37 months were 56.2%, 36.9%, and 21.9%, respectively. CONCLUSIONS: .... Surgery alone remains the standard therapy for esophageal cancer. PMID: 11004342 



Aggressive angiomyxoma: irradiation for recurrent disease. 
Rhomberg W, Jasarevic Z, Alton R, Kompatscher P, Beer G, Breitfellner G. Abteilung fur Radioonkologie, Landeskrankenhaus Feldkirch, Austria. 

... This is a case report on a 27-year-old man who underwent 4 surgical procedures of the left lower extremity because of a recurrent soft tissue neoplasm, .... A palliative resection with macroscopic residuals left was performed in February 1998, followed by a radiation therapy with 56 Gy total dose and a concomitant administration of the radiosensitizer razoxane per os. The single radiation doses were 200 cGy 5 times a week. ... Radiation therapy combined with the sensitizer razoxane is able to control a recurrent AAM for an unknown time. It remains open whether a radiation treatment alone would have had a similar effect. PMID: 10962999 




Anticancer Res 2000 May-Jun;20(3B):2137-43 
Caffeine-potentiated radiochemotherapy and function-saving surgery for high-grade soft tissue sarcoma. 
Tsuchiya H, Yamamoto N, Asada N, Terasaki T, Kanazawa Y, Takanaka T, Nishijima H, Tomita K. Department of Orthopedic Surgery, School of Medicine, Kanazawa University, Japan. 
Caffeine, which has a DNA-repair inhibiting effect, enhances the cytocidal effects of anticancer drugs and radiation.We present a preliminary report on the results of a new treatment, "radiochemotherapy combined with caffeine" (K3 protocol), for high-grade soft tissue sarcomas. .... Preoperatively, three to five courses of intra-arterial chemotherapy using cisplatin, caffeine and doxorubicin after radiation therapy were administered. Following the preoperative therapy, function-saving surgery was performed for all cases. Complete response was observed in six patients, partial response in six and no change in five. The effectiveness rate of caffeine-potentiated radiochemotherapy was therefore 71%. The histological response for radiochemotherapy was better than that for chemotherapy alone.... Complications resulting from the preoperative radiation comprised of serious inflammation in three patients and skin necrosis in another three. Twelve patients have remained free of disease, two patients are alive with disease and three have died of metastatic disease with a mean follow-up period of 36 months. There was no local tumor recurrence. These preliminary findings suggest that caffeine-potentiated radiochemotherapy contributed to a satisfactory local response and the success of function-saving surgery for high-grade soft tissue sarcomas. PMID: 10928167 
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10928167&dopt=Abstract


Radiother Oncol 2000 Mar;54(3):261-71 
Variation in sensitizing effect of caffeine in human tumour cell lines after gamma-irradiation. 
Valenzuela MT, Mateos S, Ruiz de Almodovar JM, McMillan TJ. Laboratoio de Investigaciones Medicas y Biologia Tumoral, Departamento de Radiologia y Medicina Fisica, Facultad de Medicina, Universidad de Granada, 18071, Granada, Spain. 
... The data presented confirm that p53 status can be a significant determinant of the efficacy of caffeine as radiosensitizer in these tumour cell lines, and document the importance of the G2 checkpoint in this effect. PMID: 10738085
 http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10738085&dopt=Abstract



Cancer Res 2000 Mar 1;60(5):1326-31 
Preferential enhancement of tumor radioresponse by a cyclooxygenase-2 inhibitor. 
Kishi K, Petersen S, Petersen C, Hunter N, Mason K, Masferrer JL, Tofilon PJ, Milas L. Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston 77030-4095, USA. 
Cyclooxygenase-2 (COX-2), an inducible isoform of cyclooxygenase, is overexpressed in many types of malignant tumors, where it mediates production of prostaglandins (PGs), which in turn may stimulate tumor growth and protect against damage by cytotoxic agents. 

This study investigated whether SC-'236, a selective inhibitor of COX-2, potentiates antitumor efficacy of radiation without increasing radiation injury to normal tissue. Mice bearing the sarcoma FSA ... Overall, our findings demonstrated that treatment with a selective inhibitor of COX-2 greatly enhanced tumor radioresponse without markedly affecting normal tissue radioresponse. Thus, COX-2 inhibitors have a high potential for increasing the therapeutic ratio of radiotherapy. PMID: 10728694 
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10728694&dopt=Abstract



Int J Radiat Oncol Biol Phys 2000 May 1;47(2):435-42 
Local radiotherapy with or without transcatheter arterial chemoembolization for patients with unresectable hepatocellular carcinoma. 
Cheng JC, Chuang VP, Cheng SH, Huang AT, Lin YM, Cheng TI, Yang PS, You DL, Jian JJ, Tsai SY, Sung JL, Horng CF. 
Departments of Department ofRadiation Oncology, Koo Foundation Sun Yat-Sen Cancer Center, Taipei, Taiwan. jasoncheng@mail.kfcc.org.tw 
PURPOSE: To evaluate the treatment outcome, patterns of failure, and prognostic factors for patients with unresectable hepatocellular carcinoma (HCC) treated with local radiotherapy alone or as an adjunct to transcatheter arterial chemoembolization (TACE). ... Radiotherapy is effective in the treatment of patients with unresectable HCC. Its effect appeared to be more prominent within the site to which radiation was given. The combination of TACE and radiation was associated with better control of HCC than radiation given alone, probably due to the selection of patients with favorable prognosis for the combined treatment. ... PMID: 10802371


Int J Radiat Oncol Biol Phys 1999 Jul 15;44(5):1125-35 
Maximizing therapeutic gain with gemcitabine and fractionated radiation. 
Mason KA, Milas L, Hunter NR, Elshaikh M, Buchmiller L, Kishi K, Hittelman K, Ang KK. Department of Experimental Radiation Oncology, The Unversity of Texas M.D. Anderson Cancer Center, Houston, USA. mason@notes.mdacc.tmc.edu 
PURPOSE/OBJECTIVE: The nucleoside analogue gemcitabine inhibits cellular repair and repopulation, induces apoptosis, causes tumor growth delay, and enhances radiation-induced growth delay. After single doses of drug and radiation, maximum enhancement of tumor response was obtained when gemcitabine preceded radiation by at least 24 h. Conversely, the cellular radioresponse of the normal gastrointestinal epithelium was slightly protected when gemcitabine and radiation were separated by 24 h. This differential response created a time frame within which therapeutic gain could be maximized. In our present investigation, we sought to define the most therapeutically beneficial scheme of gemcitabine administration when combined with fractionated radiotherapy. 
... All 3 schedules of drug administration produced therapeutic gain; however, when gemcitabine was given more than once in a 5-fraction radiation treatment schedule, normal tissue toxicity increased. The highest therapeutic gain (1.4) was achieved by giving a single dose of gemcitabine (25 mg/kg) 24 h before the start of fractionated radiotherapy. PMID: 10421547
 http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10421547&dopt=Abstract





Ann Surg Oncol 1998 Mar;5(2):106-12 
Preoperative idoxuridine and radiation for large soft tissue sarcomas: clinical results with five-year follow-up. 
Sondak VK, Robertson JM, Sussman JJ, Saran PA, Chang AE, Lawrence TS. 
Department of Surgery, University of Michigan Medical Center, Ann Arbor 48109-0932, USA. 

... Local control remains an important issue in the management of large soft tissue sarcomas. Radiation is the main adjuvant to surgery for local therapy of sarcomas, but it requires relatively high doses, hitherto considered prohibitive in areas such as the retroperitoneum. We developed a preoperative treatment approach to large soft tissue sarcomas that would deliver a high total dose of radiation administered in conjunction with the halogenated pyrimidine radiosensitizer idoxuridine (IdUrd).
... Using the dose and schedule we employed, resection of large soft tissue sarcomas was possible after high-dose radiation delivered in conjunction with IdUrd. Although local control was acceptable, the high rate of distant failure represents a limitation of any local approach to the treatment of large soft tissue sarcomas and suggests the need for integration of this approach with an effective systemic therapy. PMID: 9527262 http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9527262&dopt=Abstract



Radiother Oncol 1997 Nov;45(2):167-74 
Nicotinamide as a radiosensitizer in tumours and normal tissues: the importance of drug dose and timing. 
Horsman MR, Siemann DW, Chaplin DJ, Overgaard J. Department of Experimental Clinical Oncology, Danish Cancer Society, Aarhus University Hospital, Aarhus C. 
Nicotinamide is a radiation sensitizer currently undergoing clinical testing. This was an experimental study to determine the importance of drug dose and time interval between drug administration and irradiation for radiosensitization. ... Clinically achievable doses of nicotinamide will enhance tumour radiation damage while having minimal effects in normal tissues, but for the best tumour effect radiation should be given at the time of peak plasma drug concentrations. PMID: 9424008
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9424008&dopt=Abstract



Hinyokika Kiyo 1997 Aug;43(8):589-92 
[Retrovesical leiomyosarcoma responsive to preoperative chemoradiotherapy: a case report]. [Article in Japanese] 
Namiki S, Hoshi S, Suzuki K, Orikasa S. Department of Urology, Tohoku University School of Medicine. 
A 70-year-old man with dysuria was referred to our hospital. Computed tomography scan and magnetic resonance imaging demonstrated a large solid tumor in the retrovesical space. Transurethral needle biopsy revealed leiomyosarcoma. Since the size of the tumor decreased markedly by intraarterial chemotherapy with cisplatin, methotrexate and pirarubicin, in combination with radiotherapy (40 Gy), surgical extirpation of the tumor was performed. Neither infiltration to the adjacent organs or lymph node metastasis was recognized. The patient had been free of recurrence for 12 months after operation. PMID: 9310784 




Acta Oncol 1997;36(3):323-30 
Neutral metoclopramide induces tumor cytotoxicity and sensitizes ionizing radiation of a human lung adenocarcinoma and virus induced sarcoma in mice. 
Olsson AR, Hua J, Sheng Y, Pero RW. Department of Cell and Molecular Biology, University of Lund, Sweden. Anders.Olsson@wblab.lu.se 
PMID: 9208905 



Int J Radiat Oncol Biol Phys 1996 Dec 1;36(5):1077-84 
Radiotherapy vs. radiotherapy and razoxane in the treatment of soft tissue sarcomas: final results of a randomized study. 
Rhomberg W, Hassenstein EO, Gefeller D. Department of Radiooncology, Landesklinikum, Feldkirch, Austria. 
PURPOSE: The effect of the sensitizer razoxane on soft tissue sarcomas (STS) was prospectively evaluated in a randomized, controlled trial. The main purpose of the study was to determine the response rates and local control under the combined treatment compared to irradiation alone. ...Radiotherapy combined with razoxane seems to improve the local control in inoperable, residual, or recurrent STS compared to radiotherapy alone. The combined treatment is a fairly well tolerated procedure at low costs. It can be recommended for inoperable primary STS or gross disease after incomplete resection, conditions which are still associated with limited local control and a grave prognosis. Publication Types: Clinical trial Randomized controlled trial PMID: 8985029 http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8985029&dopt=Abstract


 
Gan To Kagaku Ryoho 1996 Aug;23(9):1209-12 
[Successful treatment of recurrent endometrial stromal sarcoma by radiotherapy and intra-arterial chemotherapy with CDDP and ADM]. [Article in Japanese] 
Kakimoto K, Ando Y. Dept. of Obstetrics and Gynecology, Osaka Prefectural Habikino Hospital. 
PMID: 8751813 



J Clin Oncol 1999 Jan;17(1):31-40 
Bromodeoxyuridine alternating with radiation for advanced uterine cervix cancer: a phase I and drug incorporation study. 
Eisbruch A, Robertson JM, Johnston CM, Tworek J, Reynolds KR, Roberts JA, Lawrence TS Department of Radiation Oncology, University of Michigan, Ann Arbor, USA. eisbruch@umich.edu [Record supplied by publisher] 
... In this schedule, 1,000 mg/m2/d is the maximum-tolerated dose of BUdR. BUdR incorporation levels in tumors were consistent with clinically significant radiosensitization. ...PMID: 10458215 



Carcinogenesis 1995 May;16(5):1029-35 
In vivo tumor measurement of DNA damage, DNA repair and NAD pools as indicators of radiosensitization by metoclopramide. 
Olsson A, Sheng Y, Kjellen E, Pero RW. Department of Molecular Ecogenetics, University of Lund, Sweden. 
PMID: 7767961 



Lung Cancer 1994 Mar;10 Suppl 1:S263-70 
Radiosensitization by cytotoxic drugs. The EORTC experience by the Radiotherapy and Lung Cancer Cooperative Groups. 
Schaake-Koning C, van den Bogaert W, Dalesio O, Festen J, Hoogenhout J, van Houtte P, Kirkpatrick A, Koolen M, Maat B, Nijs A, et al. Netherlands Cancer Institute, Amsterdam. 
A three-arm randomized trial was performed to assess the acute and late toxicity and the impact on survival of the combination high-dose, split-course radiotherapy with 30 mg/m2 cisplatin (cDDP) weekly, with 6 mg/m2 cisplatin daily compared to radiotherapy alone in patients with non-small cell lung cancer (NSCLC). The study started in May 1984 and was closed in May 1989 after 331 patients were randomised. The analysis was performed after a minimum follow-up period of 22 months. Radiotherapy (RT) consisted of 30 Gy, 10 fractions, five fractions a week; then a 3-week split followed by 25 Gy in 10 fractions. Nausea and vomiting were increased for a majority of the patients in the combined treatment arms during treatment. There was no addition of bone marrow suppression, renal dysfunction or esophagitis. Increase of late radiation damage was not observed. Local control (= absence of local progression) was improved for patients treated according to the daily cisplatin arm. This has lead to an improvement in overall survival. There was no effect in time to distant metastasis due to the combined modality. The treatment influence was confirmed in the multivariate analysis. Conclusion: local control and survival can be improved by combining radiotherapy with daily low-dose cisplatin in patients with inoperable NSCLC. PMID: 8087519 


Anticancer Res 1993 Nov-Dec;13(6A):2101-6 
Response of the FSaII fibrosarcoma to antiangiogenic modulators plus cytotoxic agents. 
Teicher BA, Holden SA, Ara G, Northey D. Dana-Farber Cancer Institute, Boston, MA 02115. 
... Thus, antiangiogenic therapies can potentiate the efficacy of standard anticancer therapies. PMID: 7507654 http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7507654 &dopt=Abstract



Cancer 1977 Feb;39(2 Suppl):987-98 
Chemical modification of radiation effects
Phillips TL.
A number of powerful chemical compounds that modify radiation effects have been discovered and tested both in the laboratory and clinically over the past 25 years. There are four major classes of compounds: aminothiol radio-protectors which act on well vascularized euoxic cells and concentrate in tissues such as skin, gut and marrow; nitromidazole radiosensitizers which act on hypoxic tumor cells; pyrimidine analogues which are incorporated into the DNA of cycling cells and cause radiosensitization; and cancer themotherapy agents which, in addition to their ability to kill tumor cells directly, also may sensitize tumor and normal cells to radiation. The mechanism of action, experimental activity, and clinical results or the potential for each of these agents are reviewed.  PMID: 319901



S Afr Med J 1979 Sep 22;56(13):528-31 
Photosensitizers and radiosensitizers in dermatology and oncology.
Bruckner V.
Two therapeutic modalities are currently of great interest, namely photo- and radiosensitization. Whereas photosensitizers only function in combination with ultraviolet (UV) light, radiosensitizers act only in combination with ionizing radiation. Because of the small UV penetration, up to a maximum of 0,5 mm, photosensitization can take place only at the surface of the body, ie. the skin. Photosensitizers are applied in dermatology in order to optimize and improve the UV therapy of certain diseases (mainly psoriasis, mycosis fungoides and vitiligo). Radiosensitizers lead to an increase in sensitivity of the hypoxic and therefore radioresistant parts of tumours against X- and gamma-radiation. With sufficient concentration within the tumour, they can act where the radiation can reach, even in the deeper parts of the body. They represent a modern and useful aid to radiation oncology. Because of neurotoxic effects, however, their practical use is limited. A short review of the history, mechanisms of action, application and side-effects of these photo- and radiosensitizers is presented.
PMID: 550390 



Pediatr Hematol Oncol 1991 Apr-Jun;8(2):187-92 
Dactinomycin potentiation of radiation pneumonitis: a forgotten interaction. 
Cohen IJ, Loven D, Schoenfeld T, Sandbank J, Kaplinsky C, Yaniv Y, Jaber L, Zaizov R. Sambur Center for Pediatric Hematology/Oncology, Beilinson Medical Center, Petah Tiqva, Israel. 
No mention of dactinomycin potentiation of pulmonary radiation was found in a review of the literature of the past 12 years. Before that, this complication was well described and investigators had calculated that dactinomycin increased the toxic effect of lung radiation by a factor of 1.3 and reduced the radiation tolerance of the lung by at least 20%. An example of such a toxic effect is described in the treatment of a 7-year-old girl with lung metastases from Ewing's sarcoma. The chemotherapy protocol followed contained cyclophosphamide, vincristine, dactinomycin, adriamycin, cisplatinum, VP16, and radiotherapy. The treatment was associated with fatal pulmonary fibrosis following the reintroduction of dactinomycin after radiotherapy. Our experience suggests that there is clinical significance to this complication in sarcoma therapy when dactinomycin-containing protocols are used with radiation in the treatment of pulmonary metastases. PMID: 1863544 



Br J Cancer 1991 Jan;63(1):109-13 
Nicotinamide, Fluosol DA and Carbogen: a strategy to reoxygenate acutely and chronically hypoxic cells in vivo. Chaplin DJ, Horsman MR, Aoki DS. Medical Biophysics Unit, B.C. Cancer Research Centre, Vancouver, Canada. 
. PMID: 1846549 

Free Radic Res Commun 1991;12-13 Pt 2:595-9 
Time modulation effect of diethyldithiocarbamate (DDC) on radiosensitization by superoxide dismutase (SOD) inhibition. 
Kent C, Blekkenhorst G. Research Institute for Medical Biophysics, Medical Research Council, Tygerberg, South Africa. 
Superoxide dismutase (SOD) is known to protect cells from the lethal effects of ionizing radiation by the dismutation of oxygen radicals. Diethyldithiocarbamate (DDC) is known inhibitor of SOD and may therefore be useful as a radiosensitizer. DDC however, is also a thiol radioprotector due to its ability to scavenge radiation induced free radicals. We have shown that DDC, if administered to tumours 1 hour prior to x-irradiation exerts a protective effect, whereas if administered 4 hours prior to irradiation, it radiosensitizes. This time modulation effect is not apparent after neutron irradiation where DDC protects in both situations. We have also examined the effect of DDC on the LD50/30 in mice after total body irradiation. PMID: 1648012 



 
Int J Cancer 1988 Jul 15;42(1):129-34 
Anti-tumor effects of tumor necrosis factor alone or combined with radiotherapy. 
Sersa G, Willingham V, Milas L. Department of Experimental Radiotherapy, University of Texas, M.D. Anderson Hospital and Tumor Institute, Houston 77030. 
Recombinant human tumor necrosis factor (rHuTNF) was investigated for its ability to increase the response of murine tumors to ionizing radiation. Both multiple i.v. administrations of rHuTNF and local tumor irradiation caused a significant delay in tumor growth. The effect of treatment with both agents combined was greater than the additive effect of the individual treatments. Furthermore, rHuTNF significantly increased tumor radiocurability, as assessed by the TCD50 assay. rHuTNF was not cytotoxic to tumor cells, nor did it affect their radiosensitivity. The in vivo anti-tumor effect of rHuTNF and its augmentation of tumor radioresponse were mediated through indirect mechanisms, either immunological or non-immunological. rHuTNF was also effective in reducing the damaging effect of ionizing radiation on bone-marrow progenitor cells, which could increase the therapeutic advantage of the rHuTNF-radiotherapy combination. These experiments suggest that rHuTNF is potentially beneficial in combination with radiotherapy. PMID: 3391701




Int J Radiat Oncol Biol Phys 1985 Nov;11(11):1941-6 
A phase I study of intravenous iododeoxyuridine as a clinical radiosensitizer. 
Kinsella TJ, Russo A, Mitchell JB, Collins JM, Rowland J, Wright D, Glatstein E. 
. PMID: 2997090 




Int J Radiat Oncol Biol Phys 1986 Aug;12(8):1537-40 
Enhancement of radiation effects by acyclovir. 
Sougawa M, Akagi K, Murata T, Kawasaki S, Sawada S, Yoshii G, Tanaka Y. 
Acyclovir (ACV), a new antiviral drug, was used to investigate its effect of radiosensitivity in tumors in vivo. ...ACV is already clinically used as an antiviral drug. Its ability to radiosensitize tumors could therefore have clinical potential when combined with radiotherapy. PMID: 3759578 




J Maxillofac Surg 1978 May;6(2):98-103 
The effects of "BAR" therapy on oral malignant tumors. 
Nagai T, Sakaizumi K, Asanami S, Lian SL, Tomita O, Hirayama T. 
"BAR" therapy is a combined therapy with BUdR (Radiosensitizer), Antimetabolites (5-FU, FT-207 etc.) and Radiation for malignant tumours. How radiation can be reduced as far as possible and how the effects of treatment can be increased as much as possible are the objectives of this study of combining radiation and BUdR therapy. PMID: 353211 




Rev Interam Radiol 1977 Jul;2(3):123-33 
Recent advances in radiotherapy. 
Munzenrider JE. 
Significant recent achievement in radiotherapy are presented, with brief discussions of brachytherapy, clinical dose-rate effects, ultrafractionation, and total and half-body irradiation. Reports on radiation modifiers, including hyperbaric oxygen, chemical radiosensitizers, and normal tissue protective agents are briefly summarized, while the potential of local and systemic hyperthermia is discussed in greater detail. Recent reports of local tumor control in so-called "radioresistant tumors," such as salivary gland tumors, adenocarcinomas of the breast, prostate and pancreas, malignant melanoma and malignant carcinoid, are summarized. Current status of heavy particle radiotherapy is discussed in detail. Results of initial clinical trials of neutron beam therapy are summarized, and a brief review of proton beam clinical trials and pion beam facilities is included. Recent reports defining the role of combined irradiation and surgery in rectal and breast cancer, and in soft tissue sarcomas, are discussed. Reports of enhanced radiation toxicity seen with concomitant or sequential chemotherapy and radiotherapy are detailed, including CNS toxicity seen with methotrexate and cytosine arabinoside, cardiotoxicity with adriamycin, and pulmonary toxicity with bleomycin. New or improved diagnostic techniques with special relevance to radiotherapy treatment planning, including CT scanning, histerography, internal mammary lymphoscintigraphy, and upper extremity lymphangiography are described. Publication Types: Review PMID: 408898

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ABDOMEN & PELVIS
Radiation Damage
References from medical journals 


Radiother Oncol 1999 Oct;53(1):37-44 
Therapeutic outcome and relation of acute and late side effects in the adjuvant radiotherapy of endometrial carcinoma stage I and II. 
Weiss E, Hirnle P, Arnold-Bofinger H, Hess CF, Bamberg M Department of Radiation Oncology, University of Goettinigen, Germany. [Record supplied by publisher] 

...159 consecutive patients with stage I and II endometrial carcinoma were treated with external radiotherapy and vaginal brachytherapy after hysterectomy [and BSO] ... [radiation] side effects were evaluated, in particular with regard to the relation of acute and late toxicity. ... Acute toxicity was seen in 65.4% of patients, all grade 1 or 2, late toxicity grade 1 or 2 in 18.8%, grade 3 or 4 complications in 1.8%. The estimated 5-year freedom from late toxicity was 76.8%. Seventy-seven percent of all patients with treatment interruptions or premature end of therapy experienced late injury. In ten of 33 patients with late sequelae there was no free interval between early and late toxicity. No relation of radiation technique/fractionation and the rate of side effects was noticed. ... Adjuvant radiotherapy leads to excellent pelvic control, with few serious complications. Major acute toxicity shows significant correlation with the incidence of severe late injury, which we suggest to classify in part as consequential late effects. PMID: 10624851 
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10624851&dopt=Abstract




Ginecol Obstet Mex 1999 Jul;67:341-5 
[The treatment of rectorrhagia secondary to postradiation proctitis with 4% formalin]. [Article in Spanish] 
Coyoli-Garcia O, Alvarado-Cerna R, Corona Bautista A, Pacheco Perez M Servicio de Coloproctologia, Hospital Regional Lic. Adolfo Lopez Mateos, ISSSTE Mex., D.F. [Record supplied by publisher] 
Radiation proctitis is a common complication of radiotherapy for pelvic malignancies. In the chronic form it might lead to intractable or massive hemorrhage unresponsive to conventional therapy. In these cases surgery is associated with a high morbidity. Seven female patients previously treated with external beam radiation for carcinoma of the uterus and cervix were included. They had required multiple blood transfusions (median 2), and still had low hemoglobin rates and active hemorrhagic radiation proctitis... The formalin therapy is an effective, safe, simple and inexpensive treatment for rectal bleeding caused by radiation proctitis. PMID: 10496056 




Rev Esp Med Nucl 1999 Aug;18(4):292-7 
[Bone metastasis versus insufficiency fractures due to pelvic radiotherapy for gynecologic neoplasm]. [Article in Spanish] 
Martinez Caballero A, Moreno Yubero A, Caballero Carpena O, Serrano Vicente J, Verdu Rico J, Navarro Navarro M, Anton Leal M, Crespo Martinez C, Clemente Quiles J Servicio de Medicina Nuclear, Hospital Clinico Universitario San Juan, Alicante, Valencia, 03550, Espana. [Record supplied by publisher] 
Five cases of patients with gynecological neoplasm ... who underwent pelvic external radiotherapy and intracavitary brachytherapy in whom pathologic pelvic uptake was found in the bone scan are presented. The diagnosis was pelvic insufficiency fractures due to radiotherapy adverse effects on the skeletal system ... Both bone metastases and insufficiency fractures must be considered in the differential diagnosis of bone pain in irradiated pelvises. ... PMID: 10481113



Int J Radiat Oncol Biol Phys 1998 Jul 1;41(4):835-41 Comment in: Int J Radiat Oncol Biol Phys. 1999 Jul 1;44(4):968-9 
Sensory and motor dysfunction assessed by anorectal manometry in uterine cervical carcinoma patients with radiation-induced late rectal complication. 
Kim GE, Lim JJ, Park W, Park HC, Chung EJ, Seong J, Suh CO, Lee YC, Park HJ. Department of Radiation Oncology, Yonsei Cancer Center, Seoul, Korea. 

 the effects of radiation on anorectal function in patients with carcinoma of the uterine cervix. ... Physiologic changes of the anorectum in patients with late radiation proctitis seem to be caused by a variety of sensory and/or motor dysfunctions in which many different mechanisms are working together. The reduced rectal reservoir capacity and impaired sensory functions were crucial factors for functional disorder in such patients. In addition, radiation damage to the external anal sphincter muscle was considered to be an important cause of motor dysfunction.PMID: 9652846 




Gynecol Oncol 1999 Jan;72(1):10-5 
Postoperative radiotherapy in early stage carcinoma of the uterine cervix: treatment results and prognostic factors. 
Yeh SA, Wan Leung S, Wang CJ, Chen HC Department of Radiation Oncology, Chang Gung Memorial Hospital-Kaohsiung, Taiwan. [Record supplied by publisher] 
Comparing 179 women [group 1] who had radical hysterectomy & postop irradiation, with 159 women [group2] who had radical hysterectomy & intracavitary brachytherapy: " The overall 5-year intestinal and urinary complication-free rate was 66 and 82%, respectively. The overall incidence of grade 3 or above late rectal and urinary sequelae was 10%. For patients sustaining leg lymphedema after radiotherapy, there was higher incidence of severe leg cellulitis which warranted antibiotics treatment." Copyright 1999 Academic Press. [abstract rewritten and heavily edited.] PMID: 9889023 
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9889023&dopt=Abstract




J Surg Oncol 1997 Feb;64(2):109-14 
Advances in prevention of radiation damage to visceral and solid organs in patients requiring radiation therapy of the trunk. 
Ritter EF, Lee CG, Tyler D, Ferraro F, Whiddon C, Rudner AM, Scully S. Duke University Medical Center, Durham, North Carolina 27710, USA. 
... We detail our use of saline breast implants placed in polyglycolic acid mesh sheets to displace visceral and solid organs away from the radiation field. RESULTS: Analysis of CT scans and dose volume histograms reveal that this technique successfully displaces uninvolved organs away from the radiation fields, thereby minimizing the radiation dose to such organs and tissues. CONCLUSION: We believe this is a safe and efficacious method to prevent radiation damage to visceral and solid organs adjacent to trunk tumor sites. PMID: 9047246 
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9047246&dopt=Abstract



Gynecol Oncol 1996 Oct;63(1):40-6
Arterial occlusion complicating treatment of gynecologic cancer: a case series.
Levenback C, Burke TW, Rubin SC, Curtin JP, Wharton JT Department of Gynecologic Oncology, The University of Texas M.D. Anderson Cancer Center, Houston 77030, USA. [Record supplied by publisher]
.... Three patients underwent amputation of a lower extremity when they developed chronic arterial insufficiency after pelvic radiotherapy. The patients were irradiated at the ages of 28, 30, and 35 years for cervix cancer in two patients and a low-grade retroperitoneal sarcoma in one patient. Two received neutron beam therapy and one received conventional photon beam therapy. All three had extensive late radiation morbidity to the bladder and rectum and had multiple prior surgeries. The amputations occurred at the ages of 48, 48, and 55 due to accelerated arteriosclerosis. Two patients died as a result of this complication. Acute and chronic arterial occlusions are rare yet dramatic complications of therapy for gynecologic cancer. PMID: 8898166
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8898166&dopt=Abstract




Am J Gastroenterol 1996 Jul;91(7):1309-11
Radiation proctitis: a review.
Babb RR Gastroenterology Division, Palo Alto Medical Clinic, California 94301, USA.[Record supplied by publisher]
Radiation therapy of cancers in the pelvic region may lead to radiation proctitis. Radiation injury to the rectal wall eventually causes connective tissue fibrosis and obliterative endarteritis with subsequent local tissue ischemia. Patients with radiation proctitis may be minimally ill and heal spontaneously. However, symptoms of proctitis may persist, and the disease progresses to chronic bleeding and/or stricture and fistula formation. Medical therapy is often unsuccessful, and surgery is eventually required. Because of numerous postoperative complications and no guarantee of success, surgery should only be done as a last resort. PMID: 8677984




Radiographics 1996 Nov;16(6):1251-70; 
Gastrointestinal tract involvement by gynecologic diseases.
Szucs RA, Turner MA Department of Radiology, Medical College of Virginia Hospitals, Richmond 23298-0615, USA.[Record supplied by publisher]
Involvement of the gastrointestinal tract by gynecologic disease processes-endometriosis, gynecologic neoplasms, inflammatory processes, and complications from radiation therapy or surgery for gynecologic tumors-may mimic primary gastrointestinal carcinoma on radiologic images. .... Radiation colitis causes narrowing of the rectum with intact mucosa and can be differentiated from recurrent tumor, unlike radiation-induced injury of the small bowel, which may be difficult to distinguish. ...Familiarity with the varied patterns of gastrointestinal tract involvement is important for accurate interpretation of imaging studies. PMID: 8946534



Am J Surg 1996 Oct;172(4):335-40 
The ileocecal reservoir for rectal replacement in complicated radiation proctitis. 
von Flue MO, Degen LP, Beglinger C, Harder FH. 
Department of Surgery, Kantonsspital, Basel University, Switzerland. 

Total rectal resection is the radical treatment method for radiation proctitis complications. Park's straight colo-anal reconstruction to replace the rectum often impairs anal continence, increases stool frequency, and causes imperative urgency. We developed and assessed a colo-anal reconstruction (ileocecal reservoir) after resection of radiation-damaged rectum. ... This rectal replacement technique permits good defecation quality and excellent anorectal function. PMID: 8873525 



Urology 1996 Mar;47(3):387-94
Effect of pelvic radiotherapy for prostate cancer on bowel, bladder, and sexual function: the patient's perspective.
Crook J, Esche B, Futter N Department of Radiation Oncology, Ottawa Regional Cancer Centre, Canada. [Record supplied by publisher]

... A confidential questionnaire was distributed to 202 prostate cancer patients. ... The sequelae of pelvic radiotherapy as viewed from the patient's perspective reveal a major alteration in bowel function in 11%, significant bladder symptoms in 4%, and loss of potency in 35%. PMID: 8633407



Br J Radiol 1996 Jun;69(822):548-54
Incidence and possible aetiological factors in the development of pelvic insufficiency fractures following radical radiotherapy.
Bliss P, Parsons CA, Blake PR Pelvic Unit, Royal Marsden Hospital, London. [Record supplied by publisher]
Five patients out of a total of 183 treated with radical radiotherapy for carcinoma of cervix at The Royal Marsden Hospital from 1991 to 1994 inclusive have developed severe pelvic fractures. ... We suggest that the presence of a connective tissue disorder in a patient with other risk factors such as steroid use, old age and osteopenia should alert the clinician to the risk of radionecrosis following radical irradiation. PMID: 8757658



Radiol Med (Torino) 1995 May;89(5):643-6 
[Ileal obstruction following radiosurgical treatment for rectosigmoid neoplasm]. [Article in Italian] 
Cerrotta A, Gardani G, Lozza L, Kenda R, Tana S, Valvo F, Zucali R Divisione di Radioterapia A, Istituto Nazionale per lo Studio e la Cura dei Tumori di Milano. [Record supplied by publisher] 

A series of 191 patients submitted to adjuvant radiotherapy after surgery for rectal and rectosigmoid carcinoma from January, 1975, to December, 1990, has been analyzed to evaluate the incidence of high grade small bowel late toxicity ....Fourteen patients (7.3%) developed sequelae grades III/IV: three of them died of toxicity. Average free interval between radiation and complication was 23 months (range: 4-87). The following risk factors were investigated: sex, age, type of surgery on primary rectosigmoid cancer, previous abdominal or pelvic surgery, radiation technique, treated volume, administered radiation dose. .... The only factors significantly related to late intestinal complications were the beam arrangement and, consequently, the treated volume. Detailed analysis showed that radiation sequelae developed in 12/106 (11.3%) patients treated with the two sagittal fields technique, while small bowel toxicity was observed in only 2/85 (2.3%) patients treated with the three--or four--fields technique. The difference is statistically significant (p < 0.05). Another significant correlation was the ratio between treated volume and late complications incidence observed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID: 7617904 
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7617904&dopt=Abstract



Clin Oncol (R Coll Radiol) 1995;7(2):123-6 
Hip complications following chemoradiotherapy. 
Jenkins PJ, Montefiore DJ, Arnott SJ. St Bartholomew's Hospital, London, UK. 
Chemoradiotherapy protocols are a recent development in the management of tumours where preservation of organ function is important. It is now recognized that such combined treatment may produce adverse effects below the accepted dose thresholds for either modality. This enhancement of toxicity is generally thought to reflect depletion of stem cells within the tissue concerned. We report four patients who have developed avascular necrosis or fractures of the hip following chemoradiotherapy for carcinoma of the vulva or anus. These complications developed after a radiation dose of 4500 cGy in 20 fractions. The possible role of cytotoxic agents in sensitizing bone to radiation damage is discussed, and a novel mechanism is proposed to account for this phenomenon. PMID: 7619762 




Dis Colon Rectum 1994 Dec;37(12):1245-9 
Clinicopathologic characteristics of large bowel cancer developing after radiotherapy for uterine cervical cancer. 
Shirouzu K, Isomoto H, Morodomi T, Ogata Y, Araki Y, Kakegawa T. First Department of Surgery, Kurume University School of Medicine, Japan. 

... [A retrospective chart review was performed] to clarify the characteristics of large bowel cancer developing after radiotherapy for uterine cervical cancer. ..:. 
The latent period was a mean of 20.5 years. The most common site was in the rectum (16/32). Mucin-producing carcinoma was observed in 53.1 percent, with an especially high rate of 75 percent in the rectum. Histologic radiation damage was also demonstrated at a high rate of 64.3 percent. C
 It was difficult to judge from clinicopathologic findings whether large bowel cancer developed with relation to radiation effect. We emphasize, however, that the characteristics are different from ordinary large bowel cancer. Particular consideration should be given to the high incidence of mucin-producing carcinoma. PMID: 7995152 



 
Abdom Imaging 1994 Nov-Dec;19(6):556-8 
"Segmental" prolonged cortical nephrogram as a result of radiation damage to the kidneys.
Older RA, Gay SB, Friday JM. Department of Radiology, University of Virginia Health Sciences Center, Charlottesville 22908. 
We present two cases showing bilateral segmental delayed nephrograms secondary to radiation injury which occurred during radiation therapy for retroperitoneal adenopathy... PMID: 7820034




Jpn J Clin Oncol 1994 Oct;24(5):294-8 
A case of radiation-induced rectal cancer developing after a long-term follow-up. 
Shirouzu K, Isomoto H, Morodomi T, Ogata Y, Araki Y, Kakegawa T. First Department of Surgery, Kurume University School of Medicine, Fukuoka. 
... The time interval between the radiotherapy and the development of the rectal cancer was 19 years. .... Other radiation damage was additionally found including colitis, endarteritis and intestinal wall fibrosis.. PMID: 7967109 



Strahlenther Onkol 1994 Aug;170(8):437-40 
Radiation enteropathy. 
Farthmann EH, Imdahl A, Eggstein S. Chirurgische Universitatsklinik Freiburg. 
PURPOSE: Radiation enteropathy presents a complex clinical picture which varies from case to case. Diagnosis and treatment require a thorough knowledge of the natural history of the condition and of the complications which are to be expected. ...: Haemorrhage, vomiting, diarrhoea and, occasionally, perforation are the signs of acute radiation enteropathy, which appears weeks or months after radiotherapy. Except for perforations, these can usually be treated conservatively. Chronic radiation enteropathy does not manifest itself until years after irradiation, with diarrhoea, obstruction and the development of fistulae. ..., many cases require operative intervention. This usually consists of resection, the establishment of a bypass anastomosis or enterostomy. In 44% of the patients postoperative complications followed, with a mortality of 22%. The cause of the high complication rate is partly the poor general condition of the patient, and partly the radiation induced impairment in wound healing, which may lead to insufficiency of the anastomosis and the development of fistulae. ...The treatment of radiation enteropathy is a demanding task. Because of the high complication rate, it is generally wise to choose the least risky procedure. PMID: 8085209 
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8085209&dopt=Abstract


 
Cancer 1995 Feb 1;75(3):836-43 
Ureteral stricture as a late complication of radiotherapy for stage IB carcinoma of the uterine cervix. 
McIntyre JF, Eifel PJ, Levenback C, Oswald MJ Division of Radiotherapy, University of Texas, M. D. Anderson Cancer Center, Houston 77030. [Record supplied by publisher] 

...Ureteral stricture is a rare late complication of curative radiotherapy for carcinoma of the cervix. A retrospective study was performed to determine the incidence and latency of radiation-induced ureteral stricture, to investigate possible contributing factors, and to compare the time course and presenting characteristics of ureteral compromise caused by late radiation injury or tumor recurrence. .... The overall incidences of severe ureteral stenosis were 1.0, 1.2, 2.2, and 2.5% at 5, 10, 15, and 20 years, respectively, reflecting a continuous actuarial risk increase of approximately 0.15% per year. .... Patients who were treated with centrally blocked external fields or who received more than two transvaginal radiation treatments were at increased risk for developing ureteral stenosis. The risk was similar for patients treated with radiation alone or followed by extrafascial hysterectomy. 
...During the first 5 years after treatment, tumor recurrence is the most common cause of ureteral stricture in patients treated with radiotherapy for carcinoma of the cervix. However, radiation injury to the ureter, although rare, may not become apparent for many years, necessitating continued vigilance throughout the lives of these patients. PMID: 7828135
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7828135&dopt=Abstract


Acta Chir Belg 1995;95(4 Suppl):190-4 
Survival of patients with radiation enteritis of the small and the large intestine. 
Libotte F, Autier P, Delmelle M, Gozy M, Pector JC, Van Houtte P, Gerard A Service of Oncologic Surgery, Institut Jules Bordet, Brussels, Belgiumx [Record supplied by publisher] 
We reviewed the clinical and survival data of 108 consecutive patients who presented with radiation enteritis between 1965 and 1981. One hundred and two (94%) had been irradiated for carcinoma of the cervix uteri. The median follow-up was of 11 years. The median time of occurrence of severe radiation-induced lesions (obstruction, perforation) after radiotherapy was of 18 months, against 10.5 months for mild symptoms (e.g., tenesmus) and 9 months for rectal bleeding (p < 0.001). Cox survival analysis taking into account the stage of the cancer and the age at diagnosis showed that rectal bleeding is a factor with a prognosis significantly poorer than the mild symptoms (p = 0.05), equivalent to that of the severe complications. We conclude that in the evaluation of patients who underwent radiotherapy for abdominal or pelvic tumours, rectal bleeding should be considered as a sign of serious radiation-induced complication. PMID: 8779298 
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8779298&dopt=Abstract




Strahlenther Onkol 1994 Nov;170(11):675-6 
[Vitamin B12 malabsorption following pelvic irradiation]. [Article in German] 
Dunst J [Record supplied by publisher] PMID: 7974186 



Gynecol Oncol 1994 Apr;53(1):114-20 
Small bowel obstruction following radical hysterectomy: risk factors, incidence, and operative findings. 
Montz FJ, Holschneider CH, Solh S, Schuricht LC, Monk BJ Department of Obstetrics and Gynecology, UCLA Center for the Health Sciences 90024. [Record supplied by publisher] 

Three groups:  hysterectomy with: No radiation, preop radiation or postop radiation. 
... We concluded that small bowel obstructions due to intraperitoneal adhesions are frequent sequelae of radical hysterectomy, being more common if concomitant radiotherapy is given. PMID: 8175009 




Rev Med Chil 1994 Jan;122(1):53-8 
[Experience with the use of stomach in bladder reconstruction]. [Article in Spanish] 
Castillo O, Van Cauwelaert R, Azocar G, Aguirre C, Wholer C. Unidad de Urologia, Clinica Santa Maria, Santiago de Chile. 
Bladder reconstruction with a gastric portion, as an alternative to other intestinal segments, has gained popularity lately. We have used a vascularized gastric segment for bladder replacement in 20 patients aged 3 to 77 years old, between 1990 and 1993. The surgical indication was due to a severe radiation cystitis in 11 cases, ...PMID: 8066345 



Gynecol Oncol 1993 Mar;48(3):328-32 
Intraoperative radiation therapy in gynecologic cancer: the Mayo Clinic experience. 
Garton GR, Gunderson LL, Webb MJ, Wilson TO, Martenson JA Jr, Cha SS, Podratz KC Division of Radiation Oncology, Mayo Clinic, Rochester, Minnesota 55905. [Record supplied by publisher] 

Nineteen patients with recurrent and two patients with locally advanced gynecologic malignancies received intraoperative radiation therapy (IORT) with electrons at the Mayo Clinic..., IORT in combination with maximum debulking surgery with or without external beam therapy in patients with paraaortic or pelvic sidewall recurrences of gynecologic malignancies appeared to improve long-term local control and survival. The addition of hyperthermia or hypoxic sensitizers may be a consideration to further improve local control in patients with gross residual disease. The high incidence of distant metastasis warrants the search for effective systemic chemotherapy. IORT-related toxicity was acceptable. PMID: 8385058 
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8385058&dopt=Abstract



Anticancer Res 1993 Sep-Oct;13(5C):1877-81 
Vitamin B12 malabsorption after irradiation for gynaecological tumours. 
Snijders-Keilholz A, Griffioen G, Davelaar J, Trimbos JB, Leer JW. Department of Clinical Oncology, Leiden University Medical Centre, The Netherlands. 
... Ten patients (23%) were found to have decreased levels of serum vitamin B12, of which six (14%) were assumed to be caused by malabsorption due to radiation damage to the terminal ileum .... Neither the radiation dose or volume nor the manifestation of acute or late radiation side effects appeared to be correlated with the finding of decreased levels of vitamin B12. It is concluded that even in asymptomatic patients who received pelvic irradiation, serum vitamin B12 levels can serve as a marker for radiation enteropathy. It is advocated to check vitamin B12 levels prior to the radiation treatment as well as during the follow-up of these patients. PMID: 8267396


Eur J Surg Oncol 1993 Aug;19(4):336-41 
Surgical intervention for complications caused by late radiation damage of the small bowel: a retrospective analysis. 
van Halteren HK, Gortzak E, Taal BG, Helmerhorst TJ, Aleman BM, Hart AA, Zoetmulder FA. Department of Surgery, Netherlands Cancer Institute, Amsterdam. 
We studied the records of 46 patients who had been operated on between 1974 and 1990 in The Netherlands Cancer Institute because of complications due to late radiation damage of the small bowel. ... The following factors led to an increase in complication-risk: hypoalbuminemia, more than one laparotomy prior to irradiation and a short interval (< 12 months) between irradiation and surgical intervention. The following factors related to a poorer survival: incomplete resection of the primary tumor and a short interval (< 12 months) between irradiation and surgical intervention. ... PMID: 8359282 
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8359282&dopt=Abstract




Zentralbl Chir 1992;117(11):595-8 
[Reversible fixation of the small intestine for minimizing radiation damage with polyglycolic acid mesh--initial experiences]. [Article in German] 
Arndt M, Pelster FW, Potter R. Abteilung Allgemein- und Gefasschirurgie, Chirurgischen Universitatsklinik Munster. 
.... No severe disturbance of bowel motility was seen. By sonographic and barium controls it could demonstrated that it was possible to keep the small intestine above the radiation fields as long as it was necessary for radiation treatment. After 3-4 months it could be demonstrated that the small bowel had descended into the pelvis again. PMID: 1335198 




Radiat Res 1990 Sep;123(3):331-44 Erratum in: Radiat Res 1991 Dec;128(3):326 
Cancer mortality following radium treatment for uterine bleeding. 
Inskip PD, Monson RR, Wagoner JK, Stovall M, Davis FG, Kleinerman RA, Boice JD Jr. Department of Epidemiology, Harvard University School of Public Health, Boston, Massachusetts 02115. 

Cancer mortality in relation to radiation dose was evaluated among 4153 women treated with intrauterine radium (226Ra) capsules for benign gynecologic bleeding disorders between 1925 and 1965. Average follow up was 26.5 years (.... Overall, 2763 deaths were observed versus 2687 expected based on U.S. mortality rates [standardized mortality ratio (SMR) = 1.03]. Deaths due to cancer, however, were increased (SMR = 1.30), especially cancers of organs close to the radiation source. For organs receiving greater than 5 Gy, excess mortality of 100 to 110% was noted for cancers of the uterus and bladder 10 or more years following irradiation, while a deficit was seen for cancer of the cervix, one of the few malignancies not previously shown to be caused by ionizing radiation. Part of the excess of uterine cancer, however, may have been due to the underlying gynecologic disorders being treated. Among cancers of organs receiving average or local doses of 1 to 4 Gy, excesses of 30 to 100% were found for leukemia and cancers of the colon and genital organs other than uterus; no excess was seen for rectal or bone cancer. Among organs typically receiving 0.1 to 0.3 Gy, a deficit was recorded for cancers of the liver, gall bladder, and bile ducts combined, death due to stomach cancer occurred at close to the expected rate, a 30% excess was noted for kidney cancer (based on eight deaths), and there was a 60% excess of pancreatic cancer among 10-year survivors, but little evidence of dose-response. Estimates of the excess relative risk per Gray were 0.006 for uterus, 0.4 for other genital organs, 0.5 for colon, 0.2 for bladder, and 1.9 for leukemia. Contrary to findings for other populations treated by pelvic irradiation, a deficit of breast cancer was not observed (SMR = 1.0). Dose to the ovaries (median, 2.3 Gy) may have been insufficient to protect against breast cancer. For organs receiving greater than 1 Gy, cancer mortality remained elevated for more than 30 years, supporting the notion that radiation damage persists for many years after exposure. PMID: 2217730 http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2217730&dopt=Abstract




Gynecol Oncol 1990 Jun;37(3):367-73 
Randomized study of whole-abdomen irradiation versus pelvic irradiation plus cyclophosphamide in treatment of early ovarian cancer. 
Sell A, Bertelsen K, Andersen JE, Stroyer I, Panduro J. Department of Oncology, Arhus University Hospital, Denmark. 

...118 patients ... ovarian cancer were randomized to abdominal irradiation or pelvic irradiation + cyclophosphamide. ... Twenty-five percent of the patients treated with pelvic irradiation + cyclophosphamide had hemorrhagic cystitis, probably caused by radiation damage and cyclophosphamide cystitis. Eight percent had late gastrointestinal symptoms requiring surgery. PMID: 2351321 


Radiology 1990 Jun;175(3):805-13 
Postirradiation changes in the pelvis: assessment with MR imaging. 
Sugimura K, Carrington BM, Quivey JM, Hricak H. 
Department of Radiology, University of California, San Francisco 94143.   2343132 http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2343132&dopt=Abstract




Clin Radiol 1990 Mar;41(3):165-9 
Radiological changes in the gastrointestinal and genitourinary tract following radiotherapy for carcinoma of the cervix. 
Taylor PM, Johnson RJ, Eddleston B, Hunter RD. Department of Diagnostic Radiology, Christie Hospital and Holt Radium Institute, Withington, Manchester. PMID: 2323163 http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2323163&dopt=Abstract




Strahlenther Onkol 1990 Apr;166(4):271-4Related Articles, Books, LinkOut 
[Treatment of radiogenic colitis with a rectal foam containing cortisol. Clinical and pharmacologic data]. [Article in German] 
Szepesi S, Jacobi V, Vecsei P, Bottcher HD. Zentrum der Radiologie, Pharmakologisches Institut der Ruprecht-Karls-Universitat Heidelberg. 
the local therapy of Colifoam can be considered an additional treatment of radiation-induced colitis (proctitis). PMID: 2330541 






J Clin Oncol 1989 Jun;7(6):718-24 
Long-term follow-up of testicular function following radiation therapy for early-stage Hodgkin's disease. 
Kinsella TJ, Trivette G, Rowland J, Sorace R, Miller R, Fraass B, Steinberg SM, Glatstein E, Sherins RJ. Department of Human Oncology, University of Wisconsin Clinical Cancer Center, Madison 53792. 
Seventeen male patients with pathological staged I-IIIA1 Hodgkin's disease were followed prospectively for radiation damage to the testes from low-dose scattered irradiation.... Radiation treatment techniques to shield the testes are discussed. PMID: 2497228 

 
Patients with distant metastases were not given radiation. First results point to IORT providing lasting improvement of pancreatic pain. It is too early to know whether survival time is favourably influenced.  PMID: 2423312

Eur J Gynaecol Oncol 1989;10(5):302-7 
Results of radiotherapy of cervix cancer stage IB depending on the techniques of intracavitary gamma-therapy. 
Vishnevskaya EE. Scientific Research Inst. of Oncology and Medical Radiology of the BSSR Health Ministry, USSR. 

.... The frequency of radiation damage was found by investigation to depend on the variant of gamma-therapy used. Radiation reactions in the course of treatment and after its completion were most frequent in patients irradiated by traditional intracavitary technique.. PMID: 2806316 




Gynecol Oncol 1988 May;30(1):15-20 Erratum in: Gynecol Oncol 1988 Oct;31(2):369 
Salvage radiotherapy for carcinoma of the ovary following chemotherapy. 
Cheung AY. Department of Radiation Oncology, University of Western Ontario, London, Canada. PMID: 3366392
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3366392&dopt=Abstract




Dis Colon Rectum 1987 Dec;30(12):953-8 
Colon and anorectal cancer after pelvic irradiation. 
Jao SW, Beart RW Jr, Reiman HM, Gunderson LL, Ilstrup DM. Section of Colon and Rectal Surgery, Mayo Clinic, Rochester, Minnesota. 
Seventy-six cases of colon or anorectal cancer after pelvic irradiation for other malignant or benign lesions were reviewed. ... percent had received irradiation for gynecologic malignancy. The cancer developed at a mean of 15.2 years after irradiation (peak frequency between five and ten years); 85 percent of the patients had a mild to prominent radiation reaction around the cancer. ... only 17 percent of patients presented with symptoms of radiation proctitis, and the mean radiation dosages were not high. High radiation dosage and severe radiation damage may not be essential for radiation-associated colorectal cancer. The overall five-year survival rate was 48 percent. Close surveillance of the colon and anorectal regions of these high-risk patients at five years after irradiation is indicated. PMID: 3691269 





Eur J Surg Oncol 1987 Feb;13(1):21-5 
Rectal carcinoma: a new technique to allow safer postoperative irradiation of the pelvis. 
Allen PI, Fielding JW, Middleton MD, Priestman TJ. 
... This paper describes a simple and quick method of excluding the small bowel from the pelvis which, combined with more sophisticated radiation field planning, could dramatically reduce the incidence of enteric effects. PMID: 3545905 [



 
Dtsch Med Wochenschr 1986 Jun 6;111(23):892-6 
[Intraoperative radiation treatment of carcinoma of the pancreas. Initial clinical results].[Article in German] 
Bodner E, Glaser K, Aufschnaiter M, Kohle W, Url M, Frommhold H. 
Intraoperative radiotherapy (IORT) was administered to 13 patients with carcinoma of the pancreas, using high-velocity electrons of a LINAC accelerator in a single dose of maximally 25 Gy applied directly to the tumour or tumour bed with the abdomen open. There were no disorders of wound healing or other serious early complications which could be ascribed to the radiation. Stomach and intestines were excluded from the radiation field to avoid late radiation damage, such as stenoses or ulcers. The method is particularly indicated for locally non-resectable, non-metastasized pancreatic carcinoma, possibly also as tumour-bed radiation during radical surgery.

J Surg Oncol 1987 Oct;36(2):93-7 
Surgical treatment of intestinal radiation injury. 
Makela J, Nevasaari K, Kairaluoma MI. Department of Surgery, Oulu University Central Hospital, Finland. 

...The overall operative mortality was 14%; morbidity, 47%; ... Colostomy (N = 20) carried the lowest risk of mortality, 0%, as compared with resection (N = 17) and bypass procedure (N = 6), which were accompanied by the mortalities of 24% and 33%, respectively. During the follow-up (3-13 years) 12 patients (28%) died of recurrent cancer and 9 patients (21%) of persistent radiation injury, which yielded an overall mortality of 65% after resection and 50% and 65% after bypass and colostomy procedures, respectively. Continuing radiation damage led to 15 late reoperations. Ten of these were performed after colostomy, four after resection, and one after bypass. We conclude that colostomy cannot be regarded as a preferred operative method, because it does not prevent the progression of radiation injury and because it is, for this reason, associated with a higher late-complication rate. A more radical surgery is recommended but with the limitation that the operative method must be adapted to the operative finding. PMID: 3657181 
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3657181&dopt=Abstract



 
The endoscopic spectrum of late radiation damage of the rectosigmoid colon. 
den Hartog Jager FC, van Haastert M, Batterman JJ, Tytgat GN. 
The endoscopic spectrum of late radiation damage to the rectosigmoid colon in 90 patients seen over a 10 year period (1973-1983) is presented. The main endoscopic findings were abnormalities of the mucosa with characteristic telangiectasis, luminal narrowing, superficial or deep solitary ulcers or more extensive diffuse ulceration and fistulae. A knowledge of the pathognomonic features may lead to early detection and treatment.PMID: 4065051 



Histopathology 1985 May;9(5):517-34 
Vascular changes in radiation bowel disease. 
Hasleton PS, Carr N, Schofield PF. 

A series of 20 cases of radiation bowel disease (RBD) was studied qualitatively and the arterial changes were studied quantitatively. A control series of 45 cases was studied. In the control cases there were positive correlations between the medial thickness of all vessels studied and the diastolic blood pressure as well as the incidence of intimal fibrosis in both intramural and extramural arteries. The medial thickness in all the arteries in cases of RBD was significantly higher than in the controls. This was probably due to the large number of fibrin thrombi which increased the vascular resistance. The degree of intimal fibrosis of the intramural arteries and arterioles was significantly greater than in the controls. Similarly the incidence of intimal fibrosis in all arterioles and intramural arteries was greater than the control group. The degree of intimal fibrosis was related to the dose of radiation received. The effect of radiation was an on-going process since the percentage of arterioles with intimal fibrosis increased with the time after radiotherapy. Blood pressure and age played no part in these correlations in RBD. The most consistently observed qualitative changes in RBD were in the arteries, arterioles and to a lesser extent the veins. These showed fibrin thrombi, fibrinoid necrosis, subendothelial oedema and fibrin. Various stages of healing were seen in the vessels. We believe that the blood vessels are the main site of injury in RBD and that the endothelial cell is the initial target for radiation damage. PMID: 4007790 




Int J Radiat Oncol Biol Phys 1983 Oct;9(10):1445-50Related Articles, Books, LinkOut 
The relationship between early and late gastrointestinal complications of radiation therapy for carcinoma of the cervix. 
Bourne RG, Kearsley JH, Grove WD, Roberts SJ. 
In a retrospective analysis of 1,390 consecutive patients with carcinoma of the cervix treated by high dose radiation therapy alone at the Queensland Radium Institute, we report a quantitative relationship between the early and late gastrointestinal complications arising from such treatment. Of these 1,390 patients, 157 (11.3%) experienced early, serious complications. For geographic reasons, it was only possible to evaluate 784 patients for late post-irradiation complications. Twenty-eight (3.6%) developed one or more late bowel complications, which included adhesions, fistulae, strictures, perforation, colitis and vascular occlusion. Factors affecting the relative risk of developing either an early or late complication were analyzed and are discussed. There was an 8.2% incidence of late complications developing in those patients who had experienced early complications, compared with a 3.0% incidence of late complications developing in patients without early complications. Thus, the risk of developing a late complication was greater by a factor of 2.7 in those patients developing an early one (p less than 0.05). However, of the 28 patients developing late complications, 21 (75%) did not experience a severe acute one. PMID: 6415005 [PubMed - indexed for MEDLINE] 




Br J Surg 1981 Jul;68(7):488-92 
The surgical treatment of the radiation-damaged rectum. 
Cooke SA, de Moor NG. 
Details are given of 37 consecutive patients with radiation damage to the rectum. Twenty-eight presented with rectovaginal fistulas, 3 with haemorrhage from ulcerative proctitis, 3 with low rectal strictures, 2 with a painful rectal ulcer and 1 with a rectal carcinoma. Thirty-five of the 37 had been treated for carcinoma of the cervix, and of these, 30 were Black South African women in whom this disease forms approximately 70 per cent of all malignancies. Associated pathology in these patients included urinary fistulas, small bowel fistulas or stenoses and a variable degree of fibrosis of the pelvic cellular tissue. Treatment involved subtotal rectal resection with restoration of continuity by means of a peranal sleeve anastomosis between healthy colon and the rectal stump denuded of its mucosa. Technical success was achieved in 35 of the 37 patients, with no mortality. The functional results were assessed both subjectively and objectively in 31 patients followed up for more than 6 months. Full continence was achieved in 54 per cent initially, improving to 75 per cent (21 of 28) at 1 year postoperatively. At 1 year, variable degrees of incontinence for a liquid stool persisted in 7 of 9 patients who had low fistulas with a low anastomosis at dentate line level. Where anastomosis was possible at a higher level, all 19 patients cured of fistula, ulcer, stenosis or haemorrhagic proctitis were fully continent at 1 year. PMID: 7248720



Eur Urol 1981;7(2):115-7 
Kidney damage by ionizing radiation. 
Kosters S, Birzele H, Hienz HA, Baumbusch F. 
The report describes a case of radiation damage to a kidney due to radiotherapy of a sarcoma of the muscles of the back. The characteristic clinical, pathological and histological findings and the results of X-ray investigation are presented in detail. PMID: 7461003 [PubMed - indexed for MEDLINE] 
Br J Surg 1981 Jan;68(1):25-8 



Chylous ascites and obstructive lymphoedema of the small bowel following abdominal radiotherapy. 
Hurst PA, Edwards JM. 
The case history of a patient who developed chylous ascites following abdominal irradiation for recurrent carcinoma of the colon is presented. Laparotomy revealed generalized radiation damage of the small bowel with a particularly severely affected segment of jejunum, from the serosal surface of which chyle was seen to be leaking. Mesenteric lymphangiography revealed an obstruction to lymphatic drainage in the mesentery. Resection of the worst affected segment of bowel prevented further development of chylous ascites. PMID: 519163 

 


Radiology 1979 Aug;132(2):479-82 
Factors predisposing to radiation-related small-bowel damage. 
Potish RA, Jones TK Jr, Levitt SH. 
From 1970 through 1977, 92 patients with ovarian cancer received 20 Gy (2,000 rad) to the abdomen, followed by 30 Gy (3,000 rad) to the pelvis. Small-bowel obstruction developed in 7 (7.6%). The number of previous laparotomies, thin physique, and hypertension were significantly associated with complications. Two patients receiving isoniazid and 2 receiving Premarin had enteric complications. Pre-existing vascular damage may potentiate radiation damage to the small bowel. PMID: 461811 [PubMed

 

South Med J 1978 Aug;71(8):960-1 
Radiation-recall enteritis after actinomycin-D and adriamycin therapy. 
Stein RS. 
A 22-year-old man developed four episodes of bowel obstruction after radiation therapy for a testicular tumor metastatic to retroperitoneal nodes. Each episode followed a course of chemotherapy with actinomycin-D or adriamycin. On one occasion bowel resection was required and revealed vascular changes compatible with radiation injury. The case appears to be an example of radiation recall injury involving the small bowel. The decision to use actinomycin-D or adriamycin must be weighed against the risk of tissue injury when a predisposition to radiation damage is present. PMID: 684478  



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Radiation Damage
Medical Journal References


Histopathology 1985 May;9(5):517-34 
Vascular changes in radiation bowel disease. 
Hasleton PS, Carr N, Schofield PF. 

A series of 20 cases of radiation bowel disease (RBD) was studied qualitatively and the arterial changes were studied quantitatively. A control series of 45 cases was studied. In the control cases there were positive correlations between the medial thickness of all vessels studied and the diastolic blood pressure as well as the incidence of intimal fibrosis in both intramural and extramural arteries. The medial thickness in all the arteries in cases of RBD was significantly higher than in the controls. This was probably due to the large number of fibrin thrombi which increased the vascular resistance. The degree of intimal fibrosis of the intramural arteries and arterioles was significantly greater than in the controls. Similarly the incidence of intimal fibrosis in all arterioles and intramural arteries was greater than the control group. The degree of intimal fibrosis was related to the dose of radiation received. The effect of radiation was an on-going process since the percentage of arterioles with intimal fibrosis increased with the time after radiotherapy. Blood pressure and age played no part in these correlations in RBD. The most consistently observed qualitative changes in RBD were in the arteries, arterioles and to a lesser extent the veins. These showed fibrin thrombi, fibrinoid necrosis, subendothelial oedema and fibrin. Various stages of healing were seen in the vessels. We believe that the blood vessels are the main site of injury in RBD and that the endothelial cell is the initial target for radiation damage. PMID: 4007790  



Can J Surg 1983 Jan;26(1):88-91 
Radiation damage to large arteries. 
Kalman PG, Lipton IH, Provan JL, Walker PM, Miles JT, Yeung HP. 
Little is known about late changes in large arteries after radiotherapy. Much more is known about damage to other organs and tissues. The arterial changes resemble chronic, progressive atherosclerosis which may be due to a combination of periarterial fibrosis, direct damage to the arterial wall, occlusion of vasa vasorum and acceleration of naturally occurring atherosclerosis. Factors that may predispose to arterial occlusion that relate to radiotherapy include maximum tissue dose, beam energy and field size. The authors present four patients with axillary artery occlusion that occurred 10 to 27 years after mastectomy and irradiation. The axillary artery is seldom affected by segmental atherosclerotic occlusive disease. Hence, the cause of the occlusion was most likely the irradiation. All patients did well after bypass grafting. PMID: 6821774



Br J Radiol 1998 Aug;71(848):872-5 
Carotid artery stenosis in patients who have undergone radiation therapy for head and neck malignancy. 
Dubec JJ, Munk PL, Tsang V, Lee MJ, Janzen DL, Buckley J, Seal M, Taylor D. 
Department of Radiology, Vancouver Hospital, BC, Canada. 
Although it is established that small and medium sized arteries undergo extensive radiation damage, the effect on large vessels such as the carotid arteries is less well understood. ...Carotid artery stenosis appears to be increased in patients who have previously undergone treatment with radiotherapy to the head and neck regions compared with controls (p < 0.001). These findings suggest that radiation has an adverse effect on large vessels. ...PMID: 9828801 



Radiat Res 1996 Sep;146(3):313-20 
Boron neutron capture irradiation of the rat spinal cord: histopathological evidence of a vascular-mediated pathogenesis. 
Morris GM, Coderre JA, Bywaters A, Whitehouse E, Hopewell JW. The Research Institute, Churchill Hospital, Oxford, United Kingdom. 
A histopathological study was carried out on the spinal cord of rats after boron neutron capture (BNC) irradiation.... This points to the vascular endothelium as being the critical target cell population, damage to which results in the development of the lesions seen in the spinal cord after BNC irradiation and, by inference, after irradiation with more conventional modalities. PMID: 8752310  
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8752310&dopt=Abstract




Neuroradiology 1994 Nov;36(8):611-3 
Bilateral aneurysms of the cavernous internal carotid arteries following yttrium-90 implantation. 
McConachie NS, Jacobson I. Department of Radiology, Dundee Royal Infirmary, UK. 
We present a case of bilateral aneurysms of the cavernous internal carotid arteries probably caused by radiation damage due to yttrium-90 implantation for a pituitary adenoma. Other possible aetiological factors are discussed. PMID: 7862276 [PubMed - indexed for MEDLINE] 




Clin Radiol 1994 Sep;49(9):630-3 
Percutaneous intervention for radiation damage to axillary arteries. 
McBride KD, Beard JD, Gaines PA. Department of Radiology, Royal Hallamshire Hospital, Sheffield. 
Radiation injury to subclavian and axillary arteries is a rare and late complication of radiotherapy. ... PMID: 7955891  




Strahlenther Onkol 1995 Aug;171(8):427-36
[Radiation sequelae in the large arteries. A review of clinical and experimental data]. [Article in German] 
Schultz-Hector S, Kallfass E, Sund M. GSF-Institut fur Strahlenbiologie, Neuherberg. 

...: In the course of radiation therapy of malignant tumors, inclusion of major arteries into the radiation field is often inevitable. ...clinical case reports and studies were compiled and analyzed with respect to the effect of irradiation on the risk of arteriosclerotic changes within the radiation field.
 ... a consistent 3- to 4-fold increase in carotid stenoses is observed following radiation therapy of head and neck tumors. The majority of clinically symptomatic stenoses, however, is not observed earlier than 8 years post irradiation. ... Following mediastinal or thoracic wall irradiation, the risk of coronary artery disease is significantly increased after follow-up times of > or = 10 years. Radiation related arterial injury is sharply limited to arterial segments included in the treatment field and is often observed in unusual locations. ... Irradiation of large blood vessels in the course of tumor therapy represents a long-term local risk factor for development of arteriosclerosis. PMID: 7652665


J Interv Cardiol 1995 Aug;8(4):355-8Related Articles, Books, LinkOut 
Directional coronary atherectomy for the diagnosis and treatment of radiation-induced coronary artery stenosis. 
Joseph A, Dunker D, Talley JD, Seeger J, Ackerman D. Department of Pathology, University of Louisville School of Medicine, USA. 
While radiation therapy has been known to cause myocardial and pericardial damage, its role in accentuating coronary artery disease in the absence of traditional cardiovascular risk factors has been controversial. As younger patients with treatable cancers are being treated with mediastinal radiation, coronary artery disease as a cause for severe chest pain should be entertained as a possible diagnosis. ... PMID: 10172446 

 

Rofo Fortschr Geb Rontgenstr Neuen Bildgeb Verfahr 1991 Jan;154(1):39-43 
[Arterial lesions following radiotherapy]. [Article in German] 
Paes E, Treitschke F, Suhr P, Friedrich JM, Mickley V, Vollmar JF. 
Abteilung fur Gefass-, Thorax- und Herzchirurgie, Klinikum der Universitat Ulm. 
... The time interval between radiotherapy because of malignancy and onset of symptoms due to radiation-induced atherosclerosis was on an average 7 years (1 month-29 years). A typical morphological finding at angiography was the well-localised vascular lesion in the previous radiation area, its localisation clearly distinguishable from typical atherosclerotic lesions. ... PMID: 1846691  


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BONE
Radiation Damage
Medical Journal References


Clin Oncol (R Coll Radiol) 1995;7(2):123-6 
Hip complications following chemoradiotherapy. 
Jenkins PJ, Montefiore DJ, Arnott SJ. St Bartholomew's Hospital, London, UK. 
PMID: 7619762 
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7619762&dopt=Abstract

J Periodontol 1993 Dec;64(12):1253-8 
Severe progressive periodontal destruction due to radiation tissue injury. 
Yusof ZW, Bakri MM. Department of Oral Pathology, Oral Medicine, and Periodontology, Dental Faculty, University of Malaya, Malaysia. 
.... Radiation bone injury is a long-term manifestation which could progress to osteoradionecrosis. ... The possible pathogenesis of these events is described as they relate to the sequential radiographic changes observed over a period of 6 years until the involved teeth were exfoliated. .... PMID: 8106955  
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8106955&dopt=Abstract

Radiat Med 1989 Jan-Feb;7(1):32-5 
Thoracic vertebral photopenia may predict fatty changes of the corresponding bone marrow following irradiation. 
Shih WJ, Li CY, Coffey CW, Maruyama Y. Nuclear Medicine Division, Veterans Administration Medical Center, Lexington, Kentucky. 
.... At autopsy a section of the corresponding bone marrow showed extensive fatty changes with very few residual blood vessels. Radiation damage of the vascular networks may significantly reduce the blood supply, when integrity of the blood supply is essential for delivery of a normal bone image by the bone-imaging agent. Interruption of blood supply may cause photopenia, and this interruption plus irradiation to marrow elements may also affect the hematopoietic activity of the corresponding bone marrow. ... PMID: 2762587

Acta Oncol 1988;27(2):117-22 
Spontaneous radiation-induced rib fractures in breast cancer patients treated with postmastectomy irradiation. A clinical radiobiological analysis of the influence of fraction size and dose-response relationships on late bone damage.
Overgaard M. Department of Oncology and Radiotherapy, Radiumstationen, Aarhus, Denmark. 

...Patients treated with a large dose per fraction had significantly higher incidence of late bone damage (19%) than patients treated with a standard dose per fraction (6%) ...PMID: 3390342


 
Gan No Rinsho 1987 Aug;33(10):1131-3
[Rib fracture after postoperative tangential irradiation in breast cancer]. [Article in Japanese] 
Shimamura Y, Jingu K, Hayabuchi N, Miyoshi M, Masuda K. Dept. of Radiotherapy, National Kyushu Cancer Center. 
Incidence of rib fracture was analyzed for 118 postoperated breast cancer patients who were tangentially irradiated at the Department of Radiology, Kyushu University, from 1961 to 1976 and followed more than 5 years. Rib fracture was observed in 5% and 50% of cases treated with total radiation doses of 32.5 Gy and 52.5 Gy respectively. PMID: 3669304 





Oral Surg Oral Med Oral Pathol 1983 Jun;55(6):580-8 
Actinomyces israelii in osteoradionecrosis of the jaws. Histopathologic and immunocytochemical study of five cases. 
Happonen RP, Viander M, Pelliniemi L, Aitasalo K. 
Infections and operation as the precipitant/s of osteo radio necrosis of the jaw.
.PMID: 6348637 
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6348637&dopt=Abstract 




Am J Anat 1978 Feb;151(2):295-305 
Effects of therapeutic radiation on microstructure of the human mandible. 
Savostin-Asling I, Silverman S Jr. 
Mandibular bone from eight patients who had received therapeutic radiation (6,000-7,200 rads) for intra-oral cancer was obtained at surgery (1 month to 9 years after radiation) and compared histologically with non-irradiated mandibular bone from five subjects. Measurements made on the internal remodeling process of cortical bone included the extent of internal surface and the fraction indicating resorption, and the proportions of osteones which were incomplete (less than 3/4 filled with matrix), complete, and plugged. Appreciable differences were observed in all parameters except plugged osteones. The findings suggested early cessation of osteogenesis, and somewhat later cessation of resopriton, without subsequent resumption of either process. The histologic appearance of the osteoblasts, osteoclasts, and osteones was in accord. Microfractures found in the irradiated bone were not seen to have healed. Radiation damage to the osteoprogenitor cells is postulated. PMID: 626157 



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Bone Marrow Damage
Medical Journal References





Int J Radiat Biol 1989 Dec;56(6):963-73 
Nuclear lysate sedimentation measurements of peripheral blood lymphocytes from radiotherapy patients. 
Deeley JO, Moore JL. South Wales Radiotherapy and Oncology Service, Velindre Hospital, Cardiff, U.K. 
When isolated nuclei of human lymphocytes are challenged with 2 M NaCl a histone-free-DNA-protein (HF-DNA) complex is released. In a linear sucrose gradient (pH 8.0) the sedimentation distance of HF-DNA is reduced when immediately isolated from cells irradiated in vitro. At low doses, if irradiated cells are incubated at 37 degrees C the sedimentation behaviour approaches that of unirradiated cells (i.e. repair). In the present study such repair was usually complete within 1 h. The radiation damage to lymphocytes from a healthy donor group and three patient groups consisting of new patients (before radiotherapy), well patients (2 to 6 years post-radiotherapy) and patients with complications attributed to radiotherapy was similar. The lymphocytes from most healthy donors and new patients demonstrated complete repair of radiation damage following an incubation of 1 h at 37 degrees C. However, 2/29 (6.9 per cent) healthy donors and 2/25 (8 per cent) new patients demonstrated poor repair. Of those patients now attending with 'bowel complications' attributed to radiotherapy 7/16 (44 per cent) demonstrated poor repair. In contrast, all those (11/11) described as 'well and complication-free' showed good repair. PMID: 2574224 



Med Klin 1975 Feb 28;70(9):385-91
[Radiation late damage of the thoracic marrow after irradiation in the thoracic region (author's transl)]. [Article in German] 
Busse O, Wieland C, Egge M. 
A report is given about radiation late damage on the thoracic marrow, ... in irradiation of the mediastinal region, the exposure of the spinal marrow should be reduced, although the dose alone is not decisive for the development of a radiation myelopathy. PMID: 1124051 
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1124051&dopt=Abstract


Indian J Exp Biol 1989 Nov;27(11):1005-7 
Radiat Med 1989 Jan-Feb;7(1):32-5 
Thoracic vertebral photopenia may predict fatty changes of the corresponding bone marrow following irradiation. 
Shih WJ, Li CY, Coffey CW, Maruyama Y. Nuclear Medicine Division, Veterans Administration Medical Center, Lexington, Kentucky.

 ... At autopsy a section of the corresponding bone marrow showed extensive fatty changes with very few residual blood vessels. Radiation damage of the vascular networks may significantly reduce the blood supply, when integrity of the blood supply is essential for delivery of a normal bone image by the bone-imaging agent. Interruption of blood supply may cause photopenia, and this interruption plus irradiation to marrow elements may also affect the hematopoietic activity of the corresponding bone marrow. The occurrence of radiation-induced photopenia on a bone-imaging study may indicate fatty changes of the corresponding marrow. PMID: 2762587 





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Radiation Induced Brain Damage
Medical Journal References





Neurol Med Chir (Tokyo) 1996 Dec;36(12):870-5; discussion 876 
Long-term evaluation of radiation-induced brain damage by serial magnetic resonance imaging. 
Kato T, Sawamura Y, Tada M, Abe H, Shirato H. 
Department of Neurosurgery, University of Hokkaido School of Medicine, Sapporo. 
PMID: 9002715 
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=X9002715dopt=Abstract




Strahlenther Onkol 1996 Oct;172(10):559-66 
[Blood volume changes after the radiotherapy of the central nervous system]. [Article in German] 
Wenz F, Fuss M, Scholdei R, Essig M, Lohr F, Rempp K, Brix G, Knopp MV, Engenhart R, Wannenmacher M. Radiologische Universitatsklinik Heidelberg. 
BACKGROUND: The pathogenesis of late delayed radiation damage in normal brain tissue is most likely due to damage to the vascular endothelium. The mitotic activity of gliomas was shown to correlate with the tumor induced angiogenesis. Dynamic susceptibility contrast MR imaging (DSC MRI) allows the measurement of the cerebral hemodynamics based on the indicator dilution theory. We describe theory and technique of the method and present our experience with blood volume measurements after irradiation of the CNS.
PMID: 8966673 
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8966673&dopt=Abstract





Int J Radiat Oncol Biol Phys 1994 Oct 15;30(3):557-65 
Radiation therapy for pituitary adenoma: treatment outcome and prognostic factors. 
Tsang RW, Brierley JD, Panzarella T, Gospodarowicz MK, Sutcliffe SB, Simpson WJ. Department of Radiation Oncology, Princess Margaret Hospital, Toronto, Ontario, Canada. 
...Radiation was the contributing cause of the hypopituitarism in only 23%, 16%, and 13%, respectively. There were no cases of brain necrosis or radiation damage to the optic pathways. Two patients developed a fatal in-field glioma of the brain stem at 10 and 15 years following radiation. CONCLUSION: Postoperative external beam radiation therapy is highly effective in preventing recurrence of hormonally inactive pituitary adenomas. Hypopituitarism is commonly observed, but radiation can only be incriminated as the contributing cause in approximately one-fifth of the cases. Treatment of patients at the time of recurrence gave comparable local control rates to those irradiated initially. Favorable patients (age < or = 50, with small tumors removed totally) probably can be safely observed postoperatively with radiation reserved for recurrence. PMID: 7928486 http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7928486&dopt=Abstract



J Endocrinol Invest 1994 Sep;17(8):615-23 
A prospective study of hypothalamus pituitary function after cranial irradiation with or without radiosensitizing chemotherapy. 
Huang TS, Huang SC, Hsu MM. Department of Medicine, National Taiwan University Hospital, Taipei, Republic of China. 
Hypopituitarism can occur after cranial irradiation.... In conclusion, cranial irradiation caused a progressive impairment of the hypothalamus-pituitary-endocrine axes. Combined CT may mask the radiation damage to GnRH neuron by inducing primary hypogonadism. There may be hippocampal damage in addition to hypothalamo-pituitary damage after cranial irradiation. Publication Types: Clinical trial Randomized controlled trial PMID: 7868799 


J Neurosurg 1990 Oct;73(4):502-12 Comment in: J Neurosurg. 1991 Jun;74(6):1026-7 
The long-term side effects of radiation therapy for benign brain tumors in adults. 
al-Mefty O, Kersh JE, Routh A, Smith RR. Department of Neurosurgery, University of Mississippi Medical Center, Jackson. 
...Findings related to tumor recurrence or surgery were excluded. Twenty-two patients had complications considered to be delayed side effects of radiotherapy. Two patients had visual deterioration developing 3 and 6 years after treatment; six had pituitary dysfunction; and 17 had varying degrees of parenchymal changes of the brain, occurring mostly in the temporal lobes and relating to the frequent presentation of pituitary tumors (two of these also had pituitary dysfunction). One clival tumor with the radiographic appearance of a meningioma, developed 30 years post-irradiation for acromegaly. This study unveils considerable delayed sequelae of radiotherapy in a series of adult patients receiving what is considered "safe" treatment for benign brain tumors. PMID: 2204689




Neurol Med Chir (Tokyo) 1990 Jan;30(1):36-42Related Articles, Books, LinkOut 
Radiation-induced brain damage in children--histological analysis of sequential tissue changes in 34 autopsy cases. 
Oi S, Kokunai T, Ijichi A, Matsumoto S, Raimondi AJ. Department of Neurosurgery, Kobe University School of Medicine. 
.... The histological features of irradiated brains were compared with those of non-irradiated brains. Microscopic findings included demyelination (seven cases), focal necrosis (six cases), cortical atrophy (four cases), endothelial proliferation (four cases), and telangiectatic vascular proliferation with vascular thickening and oozing of a thick fluid (one case). Such findings were rare in non-irradiated patients. Demyelination was observed earliest in a patient who died 5 months after radiation therapy and was more common after 9 months. Focal necrosis was first observed 9 months post-irradiation but was more advanced and extensive after 1 year. Calcified foci were found only after 60 months. Various vascular changes such as vascular thickening and thrombosis suggested ischemic insult to the brain as a late effect of radiation injury. ... the manifestations of radiation-induced injury depend on the time elapsed after irradiation. PMID: 1694271 


Acta Neurochir (Wien) 1989;99(3-4):104-8 
Incidence of late radiation necrosis with transient mass effect after interstitial low dose rate radiotherapy for cerebral gliomas. 
Wowra B, Schmitt HP, Sturm V. Clinic of Neurosurgery, University of Heidelberg, Federal Republic of Germany. 
Late radiation necroses constitute a hazard in low dose rate interstitial irradiation for inoperable gliomas. An incidence of 40% (8/20 patients) was found after permanent implantation of Iodine-125 seeds. This finding may even underestimate the real frequency...The occurrence of radiation necrosis was correlated with total radiation dose, amount of implanted radioactivity, and with velocity of tumour shrinkage. A mechanism underlying the development of radiation necrosis is proposed: A rapid shrinkage of tumour after interstitial Iodine-125 implantation may cause a significant irradiation of surrounding brain tissue, which was initially lying outside the target volume... the risk of radiation damage should be minimized. This could probably be achieved either by reduction of irradiation dose, or by using temporary implants of Iodine-125. PMID: 2549766 


Gen Hosp Psychiatry 1986 Nov;8(6):437-41 
Radiation damage to the brain: neuropsychiatric aspects. 
McMahon T, Vahora S. 
Although radiation necrosis of the brain is a recognized complication of irradiation of the central nervous system, the psychiatric aspects of this phenomenon are less well defined. Two cases of radiation necrosis in which psychiatric symptoms were a prominent part of the clinical picture are presented. Factors that determine the evolution and clinical presentation of radiation necrosis are reviewed. In particular, the role of the consultation psychiatrist in the diagnosis and management of such patients is discussed. PMID: 3792834 


J Neurosurg 1986 Oct;65(4):490-4 
Hypothalamic dysfunction following whole-brain irradiation. 
Mechanick JI, Hochberg FH, LaRocque A. 
The authors describe 15 cases with evidence of hypothalamic dysfunction 2 to 9 years following megavoltage whole-brain x-irradiation .... Fourteen patients displayed symptoms reflecting disturbances of personality, libido, thirst, appetite, or sleep. .... Seven patients developed cognitive abnormalities. .... Cortical atrophy was present in 50% of cases and third ventricular dilatation in 58%. Hypothalamic dysfunction, heralded by endocrine, behavioral, and cognitive impairment, represents a common, subtle form of radiation damage. PMID: 3760958 



Surg Neurol 1984 Jan;21(1):35-41 
Multifocal brain radionecrosis masquerading as tumor dissemination. 
Safdari H, Boluix B, Gros C. 
The authors report on an autopsy-proven case of multifocal widespread radionecrosis involving both cerebral hemispheres and masquerading as tumor dissemination on a CT scan done 13 months after complete resection of an oligodendroglioma followed by radiation therapy. This case demonstrates that radiation damage may be present in a CT scan as a multifocal, disseminated lesion. Since the survival of brain-tumor patients who have undergone radiation therapy is prolonged by aggressive therapy, the incidence and variability of radiation-induced complications in such cases is likely to increase. For similar reasons, the radionecrosis in such cases should be taken into consideration. A short review of the CT scan findings and diagnostic and therapeutic considerations in a case of widespread radionecrosis is presented. The need for appropriate diagnosis and subsequent life-saving management is emphasized. PMID: 6689807 


Q J Med 1982 Summer;51(203):279-91 
Cerebral embolism in cancer patients. 
Kearsley JH, Tattersall MH. 
Sudden neurological deterioration suggesting embolism in a patient with a history of cancer should alert the physician to the possibility of a non-metastatic, and therefore potentially reversible, cause of cerebral embolism before cerebral metastasis is implicated. During a four year period, we have observed eight cases of acute cerebral embolism among 3000 cancer patients seen in a department of medical oncology. Five patients had features post mortem of non-bacterial thrombotic endocarditis, and in one, the diagnosis had been made antemortem, but treatment with heparin did not prevent further emboli. Two patients had radiation related carotid vascular disease, and one patient post lymphangiographic embolism. The literature reporting these uncommon causes of cerebral embolism is reviewed. Post-lymphangiographic embolism carries a uniformly good prognosis. In selected cases of post-irradiation cerebral embolism, surgical intervention may prevent a neurological catastrophe. Non-bacterial thrombotic endocarditis and mucin embolism are of uncertain aetiology and natural history; long-term survival is uncommon, and treatment does not appear to influence the clinical course or outcome. PMID: 7146312 



Neurosurgery 1981 Mar;8(3):329-33 
Radiation necrosis after treatment of solitary intracranial metastases. 
Sundaresan N, Galicich JH, Deck MD, Tomita T. 
During the period from July 1977 to June 1980, 75 patients underwent the surgical excision of solitary brain metastases, and 61 of these patients received whole brain radiation. Three patients developed chronic radiation necrosis. In the 3 patients with necrosis, computed tomography suggested recurrent tumor; the histological diagnosis of necrosis only was obtained at operation in 2 of these patients and by autopsy in the third. Radiation damage resulted in the death of 1 patient, a chronic vegetative state in another, and severe neurological deficit in the third. An additional 4 patients had neurological complications probably related to radiation therapy. As the survival of such patients is prolonged by aggressive treatment, the incidence of radiation-induced complications is likely to increase. The optimal dose of radiation necessary to destroy microscopic foci of tumor after the surgical resection of a single brain metastasis is unknown. Because of the significant incidence of damage after radiation as currently delivered, studies using graded, lower doses are indicated. PMID: 7242882 





Morphol Igazsagugyi Orv Sz 1980 Apr;20(2):130-4 
[Post-irradiation brain necrosis causing apoplexy and death 33 years after irradiation].[Article in Hungarian] 
Frohlich A. 
A case of post-irradiation brain-necrosis resulting in apoplexia of the cerebellum after 33 years of irradiation (19 984 r.) of a presumptive cerebellar tumour in childhood is reported. The pathohistologic study revealed symptoms of the "late" damage and vascular changes appeared to be the most prominent. Thickening of the vessel walls, hyperplasia of collagen fibres and deposition of calcium in the media, were the most characteristic lesions revealed. In some of the small vessels isolated calcification of the media was observed. It seems most probable, that in the development of apoplexia vascular alterations could play an important part. In the available literature author has not found report on a similarly long interval elapsing between the irradiation and death. PMID: 7266501 




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CHEST
Radiation Damage
Medical Journal References



Radiother Oncol 2001 Mar;58(3):295-301 
Circulating atrial natriuretic peptide plasma levels as a marker for cardiac damage after radiotherapy. 
Wondergem J, Strootman EG, Frolich M, Leer JW, Noordijk EM. Department of Clinical Chemistry, Leiden University Medical Centre, Leiden, The Netherlands. 
PMID: 11230891 


Radiother Oncol 2001 Mar;58(3):287-94
Left sided vocal cord paralysis: a newly recognized late complication of mediastinal irradiation. 
Johansson S, Lofroth PO, Denekamp J. Department of Radiation Sciences, Translational Research Group, Umea University Hospital, Umea, S-901 85, Sweden. 
...: A left-sided vocal cord paralysis of patients treated with mediastinal radiotherapy might not indicate only tumour recurrence but also mediastinal fibrosis. Small differences in patient positioning cannot be excluded as the cause of the difference in the two series. We postulate that other more subtle damage to the vagus nerve may occur without being recognized as late radiation injury. PMID: 11230890 
 

Catheter Cardiovasc Interv 2001 Feb;52(2):242-8
Post mediastinal radiation coronary artery disease and its effects on arterial conduits. 
Khan MH, Ettinger SM. Section of Cardiology, Penn State University-Milton S. Hershey Medical Center, Hershey, Pennsylvania 17033, USA. 
Therapeutic mediastinal radiation predisposes patients to an increased risk of developing premature coronary artery disease. Other structures surrounding the heart within the radiation field are also susceptible to injury. This case report highlights the importance of recognizing concurrent damage to the internal mammary artery that, in this particular group of patients, may not be the ideal arterial conduit for coronary artery bypass surgery. PMID: 11170340


Minerva Cardioangiol 2000 Mar;48(3):79-87
Cardiac damage following therapeutic chest irradiation. Importance, evaluation and treatment. 
Vallebona A. ASL n. 4 Chiavarese, Ospedale di Rapallo, Genova. 
. ... Pericardial disease is the most well known expression of radiation induced heart disease, although the whole cardiac structure is compromised because of the structural and consequently functional impairment. Myocardial damage can lead to a congestive heart failure, typically due to a restrictive cardiomyopathy. Coronary artery obstructive disease frequently involves ostial coronary segments and the left main, for this reason it does appear particularly harmful. All patients undergoing chest irradiation require serial cardiological evaluation. Important risk factors of radiation induced heart disease are previous chemotherapy, radiation exposition exceeding 4000 Rad, administration next to the heart and on the left side of the chest must be taken into particular consideration. The cardiac damage limitation basically is founded on prevention. Significant results have been obtained with fractional exposition, high energy utilization and "split" zone covering. The radiotherapeutic technical improvement with the comprehensive individual patient risk evaluation will provide a substantial benefit for the future. The consultant cardiologist should cooperate with the oncologist and the radiotherapist, providing specific competence and continuative care. PMID: 10838837 



Radiographics 2000 Jan-Feb;20(1):67-81 
Unusual radiologic findings in the thorax after radiation therapy. 
Mesurolle B, Qanadli SD, Merad M, Mignon F, Baldeyrou P, Tardivon A, Lacombe P, Vanel D. 
Department of Radiology, Institut Gustave-Roussy, Villejuif, France. 
... Radiation therapy produces dramatic effects in the lung. Pulmonary necrosis is an uncommon, severe, late complication of adjuvant postoperative radiation therapy. Bronchiolitis obliterans with organizing pneumonia is a distinct clinicopathologic entity characterized by patchy, migratory, peripheral air-space infiltrates. Radiation therapy can also cause spontaneous pneumothorax, mesothelioma, and lung cancer. In the mediastinum, radiation therapy may cause thymic cysts, calcified lymph nodes, and esophageal injuries. Cardiovascular complications of radiation therapy are often delayed and insidious. Premature coronary artery stenosis occurs after radiation therapy to the mediastinum. Radiation therapy may also give rise to calcifications of the ascending aorta, pericardial disease, valvular injuries, and conduction abnormalities. Women who undergo thoracic irradiation before the age of 30 years have a high risk of developing a second breast cancer. Radiation-induced sarcomas are an infrequent but well-recognized complication of radiation therapy. Other chest wall injuries due to radiation therapy are osteochondroma and rib or clavicle fractures. Knowledge of the imaging features of injuries caused by radiation therapy can prevent misinterpretation as recurrent tumor and may facilitate further treatment. PMID: 10682772 


Radiographics 2000 Jan-Feb;20(1):83-98 
Radiation-induced lung disease and the impact of radiation methods on imaging features. 
Park KJ, Chung JY, Chun MS, Suh JH. Department of Radiology, Ajou University Medical Center, Paldal, Suwon, South Korea. 
... Irradiation with oblique beam angles results in unusual distribution of radiation-induced lung disease. ... use of tangential beam portals may induce radiation pneumonitis or fibrosis at the peripheral ... portals may produce lesions in the lung apex that appear similar to pulmonary tuberculosis...s. CT is more sensitive to radiation-induced lung disease than chest radiography and demonstrates related changes earlier. Furthermore, it more clearly depicts the precise distribution and pattern of disease. Familiarity with the imaging findings in radiation-induced lung disease produced by different radiation methods will help radiologists interpret abnormalities seen at chest radiography and CT in affected patients. Publication Types: Review Review, tutorial PMID: 10682774 


Dig Surg 1998;15(3):224-6 
Salvage esophagectomy after unsuccessful curative chemoradiotherapy for squamous cell cancer of the esophagus. 
Meunier B, Raoul J, Le Prise E, Lakehal M, Launois B. Department of Digestive Surgery and Transplantation, Centre Hospitalier Universitaire Rennes, France. 
Surgery was performed on 6 patients after unsuccessful chemoradiotherapy for squamous cell cancer of the esophagus. The operation was very difficult due to post-irradiation sequelae in 5.... PMID: 9845589 
 


Nihon Kokyuki Gakkai Zasshi 1999 Feb;37(2):97-101
[Quantitative analysis of pulmonary functional damage due to heavy ion particle irradiation therapy for lung cancer]. [Article in Japanese] 
Homma T, Ohtsu I, Tomioka S, Inoue M, Hasegawa S, Miyamoto T. Division of Respiratory Disease, University of Tsukuba, Ibaraki, Japan. 
Seventeen patients with clinical stage I lung cancer were given irradiation therapy with heavy ion radioactive rays at 73.1 +/- 11.2 GyE. Lung injury due to irradiation was evaluated by measuring routing parameters of pulmonary function. No statistically significant changes in these parameters were observed after irradiation, even in patients followed up for a period of 1 year. Chest X-ray examinations, including CT scan images, disclosed the development of nonsegmental consolidations in the irradiated areas, changing into minor fibrosis 1 year later. We concluded that heavy ion particle irradiation has minimal impact on pulmonary function, and is of therapeutic valve to elderly patients and patients with complications. PMID: 10214036 



Respiration 1996;63(3):187-90Related 
Bilateral diaphragmatic paralysis after mediastinal radiotherapy. 
De Vito EL, Quadrelli SA, Montiel GC, Roncoroni AJ. Instituto de Investigaciones Medicas Alfredo Lanari, Universidad de Buenos Aires, Argentina. 
... Radiation-induced neuropathy is well documented in other nerves as the brachial plexus. The timing, the applied dose and the location of the nerve within the radiation field are suggestive of radiation-induced phrenic nerve damage. Partial recovery was achieved after 4 years' follow-up. PMID: 8739491  



G Chir 1996 Jan-Feb;17(1-2):37-42 
[Late radiation-induced injuries: breast carcinoma in post-actinic ulceration of the thoracic-breast region with infected osteoradionecrosis. A case report]. [Article in Italian] Sironi I, Crespi AM, Magnoni E, Mattioli M, Rossi R, Vai S, Russo A. Prima Divisione Chirurgia Generale Pizzamiglio, Ospedale Niguarda Ca' Granda, Milano. 

Severe skin reactions are commonly observed after breast irradiation. Chronic ulcerations, soft tissue damage and osteonecrosis are well-known though relatively rare long-term radiation-induced injuries. The ever-present possibility of recurrence or persistence of the primary malignant neoplasm within the irradiated tissue must be always suspected and adequately established by multiple biopsies before planning an eventual resective and or reconstructive strategy. In the present report a neoplastic recurrence arised from an extensive radiation-induced ulceration along the parasternal area with chest wall osteonecrosis complicated by infection ... PMID: 8679412 



Gastrointest Endosc 1995 Feb;41(2):109-14 
Assessment of sucralfate coating by sequential scintigraphic imaging in radiation-induced esophageal lesions. 
Taal BG, Vales Olmos RA, Boot H, Hoefnagel CA. Department of Gastro-enterology and Nuclear Medicine, The Netherlands Cancer Institute/Antoni van Leeuwenhoekhuis, Amsterdam. 
The value of mucosal protection with sucralfate in cases of gastric ulceration is well documented.Although sucralfate is advocated as treatment of esophageal lesions, we found it to be of limited value in the management of radiation-induced esophagitis; .. These findings suggest that the inability of sucralfate to alleviate irradiation-induced odynophagia may be related to insufficient duration of adherence of this compound to damaged esophageal mucosa. PMID: 7720996 
 


Vopr Kurortol Fizioter Lech Fiz Kult 1995 Jan-Feb;(1):27-9
[The rehabilitation of patients with secondary (radiation) injuries to the brachial plexus].[Article in Russian] 
Bardychev MS, Pasov VV. 
A close control is needed over large nerve trunks and plexuses in the course of their area radiation in cancer patients to prevent radiation damage to peripheral nervous system. Rehabilitation of patients with radiation-induced plexitis and neuritis urges early diagnosis and treatment as essential conditions for adequate recovery of the limb function. Diagnosis of radiation damage to peripheral nervous system should rest on clinical electrophysiological findings defining the degree of the nerve fiber injury and predict treatment outcomes. PMID: 7785217 




G Ital Cardiol 1994 Jul;24(7):817-23
[Radiation-induced constrictive pericarditis. Associated cardiac lesions, therapy and follow-up]. [Article in Italian] 
Orzan F, Brusca A. Istituto di Medicina e Chirurgia Cardiovascolare, Universita di Torino. 
... Radiation therapy of the chest and mediastinum can damage all cardiac structures, the pericardium being the most frequently involved one. It is little appreciated, however, that radiation-induced constrictive pericarditis can be associated with significant involvement of coronary arteries, myocardium and valves. ... Retrospective evaluation of ... 8 patients, who had received 30-50 Gy to the chest ...7-23 years before the diagnosis of constrictive pericarditis. 
Six patients had symptoms related to the pericardial disease, one had angina and syncope, one was in congestive heart failure. ... All patients had mitral regurgitation, 5 had also tricuspid insufficiency and 5 had aortic regurgitation. The degree of the valvular regurgitation was > or = 3+ in four instances. Critical coronary arterial stenoses were discovered in 3 cases. The coronary ostia were involved in 5 cases (2 critical, 3 non critical). A diagnosis of restrictive cardiomyopathy was arrived at in 4 instances, always after pericardiectomy. Seven patients were operated on.... One patient died at surgery, two died 16 and 72 months thereafter. The remaining 5 have mild symptoms 11-60 months (mean 29) after the discharge from the hospital.
Radiation-induced pericardial constriction is frequently associated with coronary artery disease, mostly silent, with valvular insufficiency, and with myocardial disease. Thorough cardiac evaluation in such patients is mandatory. Surgical treatment frequently uncovers an underlying restrictive myopathy that presents a serious diagnostic and therapeutic challenge. PMID: 7926379  http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7926379&dopt=Abstract



Dig Dis Sci 1994 Mar;39(3):655-60 
Morphology and pathology of radiation-induced esophagitis. Double-blind study of naproxen vs placebo for prevention of radiation injury. 
Soffer EE, Mitros F, Doornbos JF, Friedland J, Launspach J, Summers RW. Department of Medicine, University of Iowa Hospitals, Iowa City 52242. 
...We conclude that acute radiation injury to the esophagus is observed in approximately half the patients receiving radiation therapy and can result in substantial morbidity.  PMID: 8131705 
 


Cardiologia 1993 Mar;38(3):163-72 
[Cardiopathy due to therapeutic irradiation of the thorax. The diagnostic criteria]. [Article in Italian] 
Brusca A, Orzan F, Figliomeni MC. Istituto di Medicina e Chirurgia Cardiovascolare, Universita degli Studi, Torino. 
.... ... was established that radiation therapy was the cause of the cardiac problems in 19 cases: 4 with ischaemic symptoms, 8 with pericardial disease, 4 with complete atrioventricular block, and 3 with valvular disease and congestive heart failure. Coronary ostial lesions were found in all patients with angina, and in 8 of the 14 patients without angina (in 1 the coronary arteries were not investigated), and were critical in 4. .. PMID: 8339305 


Br Heart J 1993 Jun;69(6):496-500
Severe coronary artery disease after radiation therapy of the chest and mediastinum: clinical presentation and treatment. 
Orzan F, Brusca A, Conte MR, Presbitero P, Figliomeni MC. Istituto di Medicina e Chirurgia Cardiovascolare, Universita degli Studi di Torino, Italy. 
...Coronary arterial disease can be reasonably ascribed to the effects of chest irradiation when the patients are young and free from risk factors, especially if the obstructions are ostial and there is important damage to other cardiac structures. In patients with damage to other cardiac structures angina and infarction are often absent and coronary angiography seems to be mandatory. Patients often require surgical treatment and postoperative complications are common. PMID: 8343315 


Postgrad Med 1992 Feb 1;91(2):211-5
Heart disease after mediastinal radiotherapy. 
Arsenian MA. Cape Ann Medical Center, Gloucester, Massachusetts. 
The greatest risk for most cancer patients is inadequate treatment of their disease. Although mediastinal radiotherapy is a safer procedure than it was 20 years ago, it still may damage the thoracic viscera, including the heart. Cardiovascular problems tend to present subtly years later, when the patient may not recall the prior radiation or may not deem it significant. An awareness of this long latency period and of the wide spectrum of heart disease that may result from radiotherapy is essential for management of these patients. PMID: 1738741 


Int J Radiat Oncol Biol Phys 1992;22(5):887-96 Comment in: Int J Radiat Oncol Biol Phys. 1992;22(5):1157-8 
Cardiovascular mortality in a randomized trial of adjuvant radiation therapy versus surgery alone in primary breast cancer. Rutqvist LE, Lax I, Fornander T, Johansson H. Radiumhemmet, Karolinska Hospital, Stockholm, Sweden. 
One concern with adjuvant radiation therapy for early breast cancer is the potential risk of increasing intercurrent mortality due to radiation-induced damage of the myocardium. The paper presents an analysis of long-term survival among 960 patients with primary breast cancer included in a randomized trial of pre- or postoperative radiation therapy (45 Gy/5 weeks) versus surgery alone. All patients were treated with a modified radical mastectomy. The mean follow-up was 16 years (range: 13-19 years). During the entire follow-up period there was an overall survival difference in favor of the irradiated patients that was of borderline significance (p = 0.09). There was no increase in intercurrent mortality due to any cause.However, when the results were analyzed according to estimated doses of radiation to the myocardium, the subset of patients who received the highest doses, that is, those treated with tangential 60Co fields for left-sided tumors, were found to have a significantly increased risk of death due to ischemic heart disease compared to the surgical controls (relative hazard: 3.2, p less than 0.05). No such increase was observed among the patients who received less radiation to the myocardium, that is, whose chest wall and internal mammary nodes were treated with electrons or those with right-sided tumors, irrespective of the treatment technique. It is concluded that cardiovascular mortality associated with radiation therapy for early breast cancer is correlated with the biological dose of radiation to the heart and the irradiated volume. All of the following factors are thus important: laterality of the tumor, portal arrangements, radiation energy, fractionation, and total dose. The study illustrates that an increased cardiovascular mortality can be avoided by the use of appropriate techniques and avoidance of excessive treatment. Publication Types: Clinical trial Randomized controlled trial PMID: 1555981   http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1555981&dopt=Abstract


Ann Chir 1992;46(8):725-31Related Articles, Books, LinkOut
[Radiation-induced sternal tumors: value of myocutaneous flap of the latissimus dorsi].[Article in French] 
Riquet M, Bellamy J, Houel R, de Gramont A, Zittoun R, Debesse B. Service de Chirurgie Thoracique, Hopital Laennec, Paris. 
Two patients treated by radiotherapy, one 13 years previously for Hodgkin's thymoma and the other 10 years previously for breast cancer, presented with a radiation-induced sternal tumour. ... These tumours are rare, but the radiation-induced skin damage requires wide excision.... PMID: 1285612 


Pediatr Hematol Oncol 1991 Apr-Jun;8(2):187-92 
Dactinomycin potentiation of radiation pneumonitis: a forgotten interaction. 
Cohen IJ, Loven D, Schoenfeld T, Sandbank J, Kaplinsky C, Yaniv Y, Jaber L, Zaizov R. Sambur Center for Pediatric Hematology/Oncology, Beilinson Medical Center, Petah Tiqva, Israel. 
No mention of dactinomycin potentiation of pulmonary radiation was found in a review of the literature of the past 12 years. Before that, this complication was well described and investigators had calculated that dactinomycin increased the toxic effect of lung radiation by a factor of 1.3 and reduced the radiation tolerance of the lung by at least 20%. An example of such a toxic effect is described in the treatment of a 7-year-old girl with lung metastases from Ewing's sarcoma. The chemotherapy protocol followed contained cyclophosphamide, vincristine, dactinomycin, adriamycin, cisplatinum, VP16, and radiotherapy. The treatment was associated with fatal pulmonary fibrosis following the reintroduction of dactinomycin after radiotherapy. Our experience suggests that there is clinical significance to this complication in sarcoma therapy when dactinomycin-containing protocols are used with radiation in the treatment of pulmonary metastases. PMID: 1863544


Ned Tijdschr Geneeskd 1991 Jul 27;135(30):1363-6 
[Radiation injury presenting as tumor recurrence following irradiation for non-small-cell bronchus carcinoma].[Article in Dutch] 
van der Planken HJ, Njo KH, Karim AB. Academisch Ziekenhuis Vrije Universiteit, afd. Radiotherapie, Amsterdam. 
Case records of two irradiated patients, each with an inoperable non-small cell carcinoma of the bronchus, are presented. After an initial period of 1.3 and 2.3 years, respectively, of regression of the tumour ...[there occurred] severe pain due to multiple rib fractures in one and a superior vena cava syndrome in the other, suggestive of tumour regrowth. Careful comparison of results of all radiographic images and radiotherapy data suggested osteoradionecrosis as the cause of the rib fractures in one patient. The long time interval and the stabilization of the symptoms in the other made tumour regrowth unlikely. The so-called late tissue reaction after radiotherapy as a possible cause of symptoms in both patients is discussed. PMID: 1650923  


Eur J Surg Oncol 1990 Oct;16(5):430-5 
Radiation therapy for locally advanced breast cancer: prognostic factors and complication rate. 
Weshler Z, Brufman G, Sulkes A, Warner-Efraty E, Ben-Baruch N, Biran S, Fuks Z. Department of Radiation and Clinical Oncology, Hadassah University Hospital, Jerusalem, Israel. 
A retrospective analysis was carried out in 100 patients with locally advanced breast cancer without distant metastases treated by radiotherapy between 1960 and 1979. The primary tumor was irradiated to a total dose of 60 Gy in 76 patients and to doses ranging between 60 and 80 Gy in 24 patients. The regional lymphatics were treated with doses between 50 and 60 Gy. Following radiotherapy, chemotherapy was administered to 58 patients and hormonal therapy to 29, while 13 patients received no further therapy. Locoregional recurrences were documented in 29% and distant metastases in 49% of patients. The actuarial survival was 56% at 5 years, 21% at 10 years and 14% at 15 years. At 10 years 90% of the surviving patients had some degree of radiation damage. PMID: 2209839 
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2209839&dopt=Abstract



Rofo Fortschr Geb Rontgenstr Neuen Bildgeb Verfahr 1990 Jun;152(6):662-6 
[Plexus neuropathy: tumor infiltration or radiation damage]. [Article in German] 
Ebner I, Anderl H, Mikuz G, Frommhold H. Universitatsklinik fur Strahlentherapie, Innsbruck. 
Plexus neuropathies often occur in patients with breast cancer after varying periods following surgery and postoperative radiotherapy. In most cases this has been ascribed to radiation fibrosis. The attempt to arrive at a clinical diagnosis fails because of the similarity of symptoms in both cases namely pain and the absence of motoric and sensory reflexes. But a clear diagnosis is of fundamental importance for further treatment. Only a surgical intervention can verify the diagnosis. In this study, the results of operative findings are presented and compared with a second group of patients who had died of breast cancer having undergone surgery and radiotherapy. The findings brought a surprising fact to light: a considerably high percentage of all patients suffered from large scale tumour infiltration in the plexus. The morphology and histopathology of these lesions are described. Possible explanations are given for the difference in lesion patterns, so that a clinical diagnosis might be derived therefrom. PMID: 2163070 


Rev Pneumol Clin 1989;45(2):86-9
[Aspergillosis and radiation-induced pneumonia. What relationship? Apropos of 2 cases].[Article in French] 
Bellamy J, Broquie G, Leroy-Terquem E, Verdoux P. Centre chirurgical Val d'Or-Saint-Cloud. 
The authors report the cases of 2 patients who underwent lobectomy followed by irradiation for lung cancer and subsequently developed an aspergillus-infected cavity in the irradiated lung parenchyma. It is far from certain that aspergillosis must always develop in a pre-existing cavity. In cases where it developed on post-radiotherapy lung lesions, our 2 patients and a review of the literature encline us to believe that the fungus itself is responsible for the formation of cavities in lesions of radiation pneumonia. Treatment of such disease can only be surgical, and in spite of post-irradiation and post-surgery sclerosis, elective excision of the lesions is the best solution. PMID: 2799225


Can Assoc Radiol J 1987 Mar;38(1):27-31
Pulmonary complications of multimodality therapy for esophageal carcinoma. 
Duprat G Jr, Chalaoui J, Sylvestre J, Robidoux A, Duranceau A.   PMID: 2438284 http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2438284&dopt=Abstract


Int J Radiat Oncol Biol Phys 1987 Feb;13(2):179-88
Acute radiation-induced pulmonary damage: a clinical study on the response to fractionated radiation therapy. 
Mah K, Van Dyk J, Keane T, Poon PY. 
Acute radiation-induced pulmonary damage can be a significant cause of morbidity in radiation therapy of the thorax. A prospective, clinical study was conducted to obtain dose-response data on acute pulmonary damage caused by fractionated radiation therapy. ... Over the linear portion of the dose-response curve, a 5% increase in ED (or total dose if N and T remain constant), predicts a 12% increase in the incidence of acute radiation-induced pulmonary damage. PMID: 3818385 
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3818385&dopt=Abstract


Int J Tissue React 1987;9(6):509-13
Proposed evaluation scale for damage to healthy tissues as a result of radiotherapy of chest, head and neck cancers. 
Stucchi F, Bertoni F, Bignardi M, Ciottoli GB, Bardelli D. Department of Radiotherapy, Regional Hospital, Varese, Italy. 
The authors present, as a criterion of side-effect damage, an evaluation scheme based on the qualitative grading of the acute, intermediate and late effects of the therapeutic irradiation of chest, head and neck cancers. The choice of individual qualitative clinical criteria is complex and arbitrary, although the parameters used are currently found in the literature on radiotherapy. Nevertheless the classifications they have proposed, applied clinically in cases of head and neck cancers, have proved useful in assessing the risk factors of acute and late radiation effects according to the doses delivered. The gradings here described constitute a useful tool for the preliminary assessment of radiation damage and will facilitate the comparative analysis of different case series. PMID: 3448028 



J Comput Assist Tomogr 1986 Sep-Oct;10(5):736-43 
Assessment of acute radiation-induced pulmonary changes using computed tomography. 
Mah K, Poon PY, Van Dyk J, Keane T, Majesky IF, Rideout DF. 
... CT scans of 54 patients were performed before and at preselected times during the 6 months following fractionated radiation therapy of the thorax. ... 36 patients were scored as having postirradiation pulmonary findings. ... All 36 patients demonstrated lung opacities in an irregular, homogeneous, or nonhomogeneous pattern within the radiation beam boundaries. In addition, the following characteristics were observed at various frequencies in these 36 patients: extension of the changes across anatomic tissue boundaries (50%), air bronchograms (25%), loss of lung volume (15%), and pleural thickening (15%). Confinement of the findings within the irradiated volume was the only specific characteristic of postirradiation changes. ... PMID: 3745541 
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3745541&dopt=Abstract



Int J Radiat Oncol Biol Phys 1985 Jun;11(6):1127-36
Influence of thorax irradiation on the survival of mice with spontaneous or artificial lung metastases from a transplantable mammary adenocarcinoma. 
Wondergem J, Haveman J, van der Schueren E. 
The effect of thorax irradiation on lung metastases...was studied. Increasing the interval between the moment at which lung metastases are supposed to originate and the thorax irradiation resulted in a rapid decrease of the effectiveness of this treatment in preventing the development of lung metastases. Early treatment of the mice not only resulted in a considerable number of animals that were cured, but also in a significant decrease in the number of tumor localizations in the lung of those animals still developing metastases. Thorax irradiation performed later was much less effective; at autopsy the lung showed a large number of small metastases. Increasing the radiation dose led to an increased number of cures; however, an increased number of mice dying of lethal lung damage was also observed. ... PMID: 3997595   http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3997595&dopt=Abstract



Gan No Rinsho 1984 Jul;30(9 Suppl):1225-30
[Complication of radiation therapy]. [Article in Japanese] 
Imajo Y, Suematsu T, Narabayashi I, Gose K, Takimoto S, Kimura S, Matsuura S. 
The radiation pneumonitis is a major complication for patients receiving thoracic irradiation. This report describe the radiographic recognition, pathological change and impaired pulmonary functions of radiation pneumonitis. The 57 patients with lung cancer treated with radiation are analyzed on the pneumonitis by chest X-P. Among these, 50 patients (88%) develop radiation pneumonitis. Repeated CT scans give more detailed information than conventional radiograms as to exudative changes. The pathological analysis are made on the 35 patients of which affected lungs are resected after pre-operative irradiation. Three phases are recognized in the evolution of pneumonitis, the congestive, the degenerative, and the fibrotic. Adding to the morphological damage, pulmonary functions also deteriorate both in ventilation and perfusion scans. PMID: 6471424 


Cancer 1984 Dec 1;54(11):2319-23
Late effects of adjuvant radiotherapy for breast cancer. 
Ferguson DJ, Sutton HG Jr, Dawson PJ. 
Complications requiring in-hospital treatment were observed in 24 of 221 consecutively treated patients (11%) who were followed from 8 to 42 years after postmastectomy irradiation. There were four sarcomas of the treated chest wall, three squamous carcinomas (two in the esophagus), two angiosarcomas of the swollen homolateral arm, nine chronic ulcers, five respiratory insufficiencies, six pathologic fractures of the radiated shoulder or ribs, two fatal cardiomyopathies, one persisting leukopenia with fatal brain abscess, and one severe neurovascular impairment of the arm. In a comparable group of 394 consecutive postmastectomy patients who were not irradiated, one similar event, a myxosarcoma of an unswollen arm, was observed. Only long-term follow-up can determine the ultimate risks of radiotherapy. PMID: 6498728 
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6498728&dopt=Abstract



Ann Cardiol Angeiol (Paris) 1983 Nov;32(7):465-72 
[Cardiac complications of radiotherapy]. [Article in French] 
Vacheron A, Heulin A, Metzger JP, Baubion N, Le Pailleur C, Delage F, Gilles R, Laugier A, Schlienger M, Delaby F. 
...
 radiotherapy also carries a risk of severe cardiac complications. ... Ionizing radiation can damage the three layers of the heart and the coronary arteries. Pericardial involvement is the most frequent, occurring in 10 to 12 per cent of cases. It generally occurs 6 to 18 months after the radiotherapy and may present either acutely (35 per cent of cases) or chronically (65 per cent of cases). It is often latent, only detected on X-rays or on ultrasound. Constrictive forms can occur, which require pericardiectomy. Myocardial fibrosis, which is anatomically common, may present as disturbances of repolarization, arrhythmia or disturbances of conduction, or even cardiac failure. Rarely, radiation damage of the coronary arteries can cause angina or myocardial infarction. These cases can benefit from coronary artery by-pass grafts. All of these lesions have a common anatomical denominator: fibrosis, which develops progressively following the radiotherapy. It has now been demonstrated that the incidence of cardiac radiation lesions can be reduced by homogeneous distribution of the dose of radiation administered to the mediastinum, by treating each side alternately, by fractionating the radiation and staggering the sessions and by reducing the cardiac mass which is irradiated. PMID: 6660823

Radiology 1983 Jul;148(1):257-8 
Pacemaker failure resulting from radiation damage. 
Quertermous T, Megahy MS, Das Gupta DS, Griem ML. 
The authors present a case of radiation-induced pacemaker failure. After 2,000 rad (20 Gy) of photon irradiation for metastatic bronchogenic carcinoma, the pulse generator circuitry failed, producing a "runaway" rhythm. This suggests that present pacemaker circuitry may be more susceptible to irradiation than previously believed, and that even modest radiation doses can induce life-threatening arrhythmias. PMID: 6856846 



Klin Monatsbl Augenheilkd 1983 Jun;182(6):560-4 
Cancer Treat Rep 1983 Dec;67(12):1099-103
Heart size and function after radiation therapy to the mediastinum in patients with Hodgkin's disease. 
Gomez GA, Park JJ, Panahon AM, Parthasarathy KL, Pearce J, Reese P, Bakshi S, Henderson ES. 

... A significantly higher proportion of patients who had received RT to the mediastinum had a decrease in transverse heart diameter and cardiothoracic ratio. ...t our findings indicate a subclinical cardiomyopathy in more than one-half of the patients who received RT to the mediastinum, suggesting that the incidence of heart damage after mediastinal RT might be higher than expected. Prospective studies are necessary to elucidate the incidence and implications of this potentially serious complication. PMID: 6652627 http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6652627&dopt=Abstract



Invest Radiol 1977 May-Jun;12(3):224-37
Regional and total lung function in patients following pulmonary irradiation. 
Prato FS, Kurdyak R, Saibil EA, Rider WD, Aspin N. 
Regional and total lung function measurements and chest radiographs were obtained from 18 patients with cancer of the breast from 3 months to 6.7 years after the start of treatment. A control group of 20 patients was studied before radiotherapy but after mastectomy. The functional parameter most affected by radiation was blood flow. In some cases in which the radiographic changes were mild the functional measurements indicated severe vascular damage. The radiation appears to reduce the number and efficiency of functioning lung units within the irradiated region. PMID: 863626 



Med Klin 1975 Feb 28;70(9):385-91
[Radiation late damage of the thoracic marrow after irradiation in the thoracic region (author's transl)]. [Article in German] 
Busse O, Wieland C, Egge M. 
A report is given about radiation late damage on the thoracic marrow, basing on the case histories of 100 patients irradiated in the mediastinal region with telegamma from a 60 Cobalt or 137 Caesium source between 1959, January 1st and 1972, december 31st. 77 patients were followed up during 18 months after the radiotherapy was ended; in 3 of them (equal to 4 p.c.) a radiation-induced myelopathy was found. These 3 cases were suffering from Hodgkin's disease, whereas in none of the patients with bronchial carcinoma--in spite of markedly higher radiation doses--any late damage was observed. Therefore, in irradiation of the mediastinal region, the exposure of the spinal marrow should be reduced, although the dose alone is not decisive for the development of a radiation myelopathy. PMID: 1124051 



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HEAD and NECK 
Radiation Damage
Medical Journal References



Clin Oncol (R Coll Radiol) 2000;12(6):403-8 
Late radiation side-effects in three patients undergoing parotid irradiation for benign disease. Armour A, Ghanna P, O'Rielly B, Habeshaw T, Symonds P. Beatson Oncology Centre, Western Infirmary, Glasgow, UK. 
We report three patients in whom standard radiation therapy was given and serious late radiation damage was seen. The first patient suffered recurrent parotiditis and a parotid fistula. He was treated initially with 20 Gy in ten fractions via a 300 kV field. Further irradiation was required 1 year later and 40 Gy was given in 2 Gy fractions by an oblique anterior and posterior wedged photon pair. Ten years later he developed localized temporal bone necrosis. The second patient, with pleomorphic salivary adenoma, developed localized temporal bone necrosis 6 years after 60 Gy had been given using standard fractionation and technique. The third patient received 55 Gy in 25 fractions for a pleomorphic salivary adenoma and after 3 years developed temporal bone necrosis. Sixteen years later the same patient developed cerebellar and brainstem necrosis. All patients developed chronic persistent infection during or shortly after the radiation therapy, which increased local tissue sensitivity to late radiation damage. As a result, severe bone, cerebellar and brainstem necrosis was observed at doses that are normally considered safe. We therefore strongly recommend that any infection in a proposed irradiated area should be treated aggressively, with surgical debridement if necessary, before radiotherapy is administered, or that infection developing during or after irradiation is treated promptly.PMID: 11202094 



Int J Radiat Oncol Biol Phys 2000 Dec 1;48(5):1311-22 
Final report of a randomized trial on altered-fractionated radiotherapy in nasopharyngeal carcinoma prematurely terminated by significant increase in neurologic complications. 
Teo PM, Leung SF, Chan AT, Leung TW, Choi PH, Kwan WH, Lee WY, Chau RM, Yu PK, Johnson PJ. Department of Clinical Oncology, Prince of Wales Hospital, Shatin, Hong Kong, People's Republic of China. teoml@ha.org.hk 
PURPOSE: The aim of the present study was to compare the survival, local control and complications of conventional/accelerated-hyperfractionated radiotherapy and conventional radiotherapy in nonmetastatic nasopharyngeal carcinoma (NPC). ... Accelerated hyperfractionation when used in conjunction with a two-dimensional radiotherapy planning technique, in this case the Ho's technique, resulted in increased radiation damage to the central nervous system without significant improvement in efficacy. PMID: 11121628 
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11121628&dopt=Abstract




Int J Oral Maxillofac Surg 1999 Feb;28(1):50-2 Comment in: Int J Oral Maxillofac Surg. 2000 Apr;29(2):155 
Cerebral radionecrosis following the treatment of parotid tumours: a case report and review of the literature. 
Coghlan KM, Magennis P. Oral and Maxillofacial Unit, The Royal London Hospital, England. 
Radiotherapy is an accepted part of the treatment of malignant tumours of the parotid gland. ... Radiotherapy to the parotid bed is not without morbidity. Complications may arise as a result of radiation damage to neighbouring structures and there is also potential to induce malignant disease. A patient, whose postoperative radiotherapy following resection of a pleomorphic salivary gland adenoma was complicated by cerebral necrosis, is discussed. The literature pertaining to morbidity of radiotherapy for parotid tumours is reviewed.  PMID: 10065650 


Ups J Med Sci 1998;103(3):203-11 
Proton irradiation of malignant uveal melanoma. A five year follow-up of patients treated in Uppsala, Sweden. 
Naeser P, Blomquist E, Montelius A, Thoumas KA. Department of Ophthalmology, Uppsala University, Sweden. 
PMID: 10052109 



J Nucl Med 1998 Sep;39(9):1551-4 
Intermediate and long-term side effects of high-dose radioiodine therapy for thyroid carcinoma. 
Alexander C, Bader JB, Schaefer A, Finke C, Kirsch CM. Department of Nuclear Medicine, Saarland University Medical Center, Homburg/Saar, Germany. 

... Severe long-term side effects are rare after high-dose radioiodine treatment. Moderate side effects are common. The side effects are commonly the result of radiation damage to the salivary glands. The frequency of such complaints advocates regular protection of the salivary glands. PMID: 9744341 http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9744341&dopt=Abstract



Neurology 1997 Apr;48(4):1107-9
Post-irradiation neuromyotonia in bilateral facial and trigeminal nerve distribution. 
Marti-Fabregas J, Montero J, Lopez-Villegas D, Quer M. 
Department of Neurology, Hospital de la Santa Creu i Sant Pau, Universitat Autonoma de Barcelona, Spain. 
We describe a patient with episodic involuntary contraction in the lower facial and masseter muscles, in whom we recorded neuromyotonic discharges. The neuromyotonia was a delayed effect of radiation therapy and responded to carbamazepine therapy. PMID: 9109911 


Ear Nose Throat J 1995 Jan;74(1):39-42, 45-8 
Dysphagia in patients with three different etiologies of salivary gland dysfunction. 
Rhodus NL, Moller K, Colby S, Bereuter J. Division of Oral Medicine, Oral Diagnosis & Radiology, School of Dentistry, University of Minnesota, Minneapolis 55455. 
PMID: 7867530 


J Periodontol 1993 Dec;64(12):1253-8 
Severe progressive periodontal destruction due to radiation tissue injury. 
Yusof ZW, Bakri MM. Department of Oral Pathology, Oral Medicine, and Periodontology, Dental Faculty, University of Malaya, Malaysia. 
... Radiation bone injury is a long-term manifestation which could progress to osteoradionecrosis. A case of radiation tissue injury to the periodontium is presented. The possible pathogenesis of these events is described as they relate to the sequential radiographic changes observed over a period of 6 years until the involved teeth were exfoliated. The post-irradiation management of the teeth with advancing periodontal disease in the path of irradiation was by conservative means, including good personal oral hygiene care, scaling and root planing, periodic chlorhexidine irrigation, and topical fluoride application. PMID: 8106955 
Gaoxiong Yi Xue Ke Xue Za Zhi 1993 Jul;9(7):401-9

The effects of radiation therapy on salivary function in patients with head and neck cancer.
Kuo WR, Wu CC, Lian SL, Ching FY, Lee KW, Juan KH. Department of Otolaryngology, Kaohsiung Medical College, Taiwan, Republic of China. 
. It is important that the radiation therapist should preserve salivary function whenever possible. PMID: 8366544 
 


Nippon Naibunpi Gakkai Zasshi 1993 Nov 20;69(10):1035-43
[Thyroid and radiation]. [Article in Japanese] 
Yamashita S, Namba H, Nagataki S. Department of Cell Physiology, Nagasaki University School of Medicine. 
.... The thyroid is an organ that is usually susceptible to exposure to ionizing radiation, both by virtue of its ability to concentrate radioiodine (internal radiation) and by routine medical examination: Chest X-ray, Dental X-ray, X-irradiation of cervical lymphnodes etc. (external radiation). Iodine-131 is widely used for the therapy of Graves' disease and thyroid cancers, of which the disadvantage is radiation-induced hypothyroidism but not complications of thyroid tumor. The thyroid gland is comparatively radioresistant, however, the data obtained from Hiroshima, Nagasaki and Marshall islands indicates a high incidence of external radiation-induced thyroid tumors as well as hypothyroidism. The different biological effects of internal and external radiation remains to be further clarified. Interestingly, recent reports demonstrate the increased number of thyroid cancer in children around Chernobyl in Belarus. In this review, we would like to introduce the effect of radiation on the thyroid gland at the molecular, cellular and tissue levels. Furthermore the clinical usefulness of iodine-131, including the safety-control for radiation exposure will be discussed. PMID: 8282128 


Int J Radiat Oncol Biol Phys 1992;24(2):359-67
A survey of prevention and treatment regimens for oral sequelae resulting from head and neck radiotherapy used in Dutch radiotherapy institutes. 
Jansma J, Vissink A, Bouma J, Vermey A, Panders AK, Gravenmade EJ. Department of Oral and Maxillofacial Surgery, University Hospital Groningen, The Netherlands. 
Radiation treatment plays an important role in the management of head and neck cancer. Unfortunately several radiation-induced side effects may occur including mucositis, hyposalivation, radiation caries, trismus and osteoradionecrosis. It is generally accepted that most side effects can be prevented or reduced in severity. ... and the observation that a rather large number of patients were not referred, or not timely referred to the dental team. There seems to be a need for the development of a general protocol for the prevention of oral complications applicable in all centers. PMID: 1526875 
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1526875&dopt=Abstract


J Am Optom Assoc 1989 Sep;60(9):664-7 
Retinopathy secondary to radiation therapy for squamous cell carcinoma. 
Groomer AE, Gutwein DE. Eye Clinic, VA Medical Center, Huntington, WV 25704. 
This report discusses a case of radiotherapy-induced retinopathy following treatment of squamous cell carcinoma. Treatment of the carcinoma with external beam radiotherapy to the supraorbital region and base of the skull was followed by the onset of retinopathy. The sensory retina, as well as other central nervous system tissues, is highly resistant to radiation damage; however, the retinal vasculature is extremely sensitive to radiation damage, producing a retinopathy that is characteristic of other vascular occlusive diseases. Management is discussed. PMID: 2794336 


Med Radiol (Mosk) 1988 Oct;33(10):30-5 
[Local radiation reactions and injuries in neutron and combined therapy of tumors using the U-120 cyclotron]. [Article in Russian] 
Musabaeva LI, Lavrenkov KA, Demochko VB, Podoplekin MV, Novikov VA. 
Early local radiation reactions and radiation damage during fast neutron therapy of head and neck tumors were studied. The frequency of moist epidermitis in a radical course of neutron therapy was 33%, that in combined neutron and photon irradiation was 21%. Mucosal reactions were observed in 30-35% of the patients with tumors of the oral mucosa. The most frequent radiation damage in a long-term period were fibrotic changes of the skin and subcutaneous connective tissue. PMID: 3185187 


Int J Tissue React 1987;9(6):509-13
Proposed evaluation scale for damage to healthy tissues as a result of radiotherapy of chest, head and neck cancers. 
Stucchi F, Bertoni F, Bignardi M, Ciottoli GB, Bardelli D. Department of Radiotherapy, Regional Hospital, Varese, Italy. 
PMID: 3448028 


Retina 1987 Fall;7(3):142-7 
Retinopathy following radiation therapy of paranasal sinus and nasopharyngeal carcinoma. 
Midena E, Segato T, Piermarocchi S, Corti L, Zorat PL, Moro F.Institute of Ophthalmology, University of Padova, Italy. 
Radiation retinopathy is a complication of the therapeutic irradiation of orbital and periorbital structures. ... This study demonstrates that radiation retinopathy occurs in a significant number of cases when the eye is not totally involved in the irradiation field and shows at least two different clinical aspects in relation to the radiation treatment. It also suggests that portal design and choroidal circulation damage may represent important factors in the development of radiation retinopathy. PMID: 3423429 


Clin Endocrinol (Oxf) 1986 Jun;24(6):643-51 
Hypothalamic hypopituitarism following cranial irradiation for nasopharyngeal carcinoma.
Lam KS, Wang C, Yeung RT, Ma JT, Ho JH, Tse VK, Ling N. 
... These data suggest that post-irradiation hypopituitarism in these patients results from radiation damage to the hypothalamus leading to varying degrees of deficiency of the hypothalamic releasing or inhibitory factors. PMID: 3098456


Int J Radiat Oncol Biol Phys 1986 Mar;12(3):401-5 
Oral side effects of head and neck irradiation: correlation between clinical manifestations and laboratory data. 
Kuten A, Ben-Aryeh H, Berdicevsky I, Ore L, Szargel R, Gutman D, Robinson E. 
... We found that most of the parotids have to be outside of the treated volume, when the rest of the major salivary glands are irradiated, to prevent severe dryness phenomena. PMID: 3957738 


Int J Radiat Oncol Biol Phys 1985 Jul;11(7):1339-47 
Precision, high dose radiotherapy. II. Helium ion treatment of tumors adjacent to critical central nervous system structures. 
Saunders WM, Chen GT, Austin-Seymour M, Castro JR, Collier JM, Gauger G, Gutin P, Phillips TL, Pitluck S, Walton RE, et al. 
In this paper we present a technique for treating relatively small, low grade tumors located very close to critical, radiation sensitive central nervous system structures such as the spinal cord and the brain stem. A beam of helium ions is used to irradiate the tumor. The nearby normal tissues are protected by exploiting the superb dose localization properties of this beam, particularly its well defined and controllable range in tissue, the increased dose deposited near the end of this range (i.e., the Bragg peak), the sharp decrease in dose beyond the Bragg peak, and the sharp penumbra of the beam. To execute this type of treatment, extreme care must be taken in localization of the tumor and normal tissues, as well as in treatment planning and dosimetry, patient immobilization, and verification of treatment delivery. To illustrate the technique, we present a group of 19 patients treated for chordomas, meningiomas and low grade chondrosarcomas in the base of the skull or spinal column. We have been able to deliver high, uniform doses to the target volumes (doses equivalent to 60 to 80 Gy of cobalt-60) while keeping the doses to the nearby critical tissues below the threshold for radiation damage. Follow-up on this group of patients is short, averaging 22 months (2 to 75 months). Currently, 15 patients have local control of their tumor. Two major complications, a spinal cord transection and optic tract damage, are discussed in detail. Our treatment policies have been modified to minimize the risk of these complications in the future, and we are continuing to use this method to treat such patients. We are enthusiastic about this technique, since we believe there is no other potentially curative treatment for these patients. PMID: 4008290 


Cancer 1985 Mar 15;55(6):1190-4 
Thyroid dysfunction and neoplasia in children receiving neck irradiation for cancer. 
Fleming ID, Black TL, Thompson EI, Pratt C, Rao B, Hustu O. 
The reported relationship of radiation exposure and thyroid carcinoma stimulated this retrospective study of 298 patients treated at St. Jude Children's Hospital with radiation therapy to the neck for childhood cancer to identify patients who developed subsequent thyroid abnormalities. ... Inclusion in the study required 5 years of disease-free survival following therapy for their original tumor, which included thyroid irradiation. Follow-up has been 100%. Most patients also received chemotherapy. Seventeen patients were found to have decreased thyroid reserve with normal levels of free triiodothyroxine (T3) or free thyroxin, (T4) and an elevated level of thyroid-stimulating hormone (TSH). In nine patients hypothyroidism developed, with decreased T3 or T4 levels and an elevated level of TSH. One hyperthyroid patient was identified. Two patients had thyroiditis, and seven had thyroid neoplasms: (carcinoma in two, adenoma in two, colloid nodule in one, and undiagnosed nodules in two). This survey has demonstrated an increased incidence of thyroid dysfunction and thyroid neoplasia when compared to the general population. The importance of long-term follow-up for thyroid disease is emphasized in patients who have received thyroid irradiation. The possible role of subclinical hypothyroidism with TSH elevation coupled with radiation damage to the thyroid gland as a model for the development of neoplastic disease is discussed. PMID: 3855682 



Br J Oral Maxillofac Surg 1984 Apr;22(2):77-86 
A pilot study of the clinical effects of irradiation on the oral tissues. 
Al-Tikriti U, Martin MV, Bramley PA. 
PMID: 6585226 


Ophthalmology 1982 Dec;89(12):1494-501 
Radiation retinopathy. 
Brown GC, Shields JA, Sanborn G, Augsburger JJ, Savino PJ, Schatz NJ. 
The wide spectrum of radiation retinopathic manifestations from local or external beam irradiation is described in 36 eyes. The most commonly encountered ophthalmoscopic signs of retinopathy include retinal hard exudates, hemorrhages, microaneurysms, cotton-wool spots, and telangiectases. The fluorescein angiographic hallmark of radiation-induced retinopathy is retinal capillary nonperfusion, supporting the concept that vascular decompensation is the primary mechanism in the production of radiation damage to the posterior segment. PMID: 7162794 



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LIMB
Radiation Damage
Medical Journal References




Skeletal Radiol 1996 Aug;25(6):537-43 
MR characterization of post-irradiation soft tissue edema. 
Richardson ML, Zink-Brody GC, Patten RM, Koh WJ, Conrad EU. Department of Radiology SB-05, University of Washington, Seattle 98195, USA. 

...Radiation therapy is often used to treat bone und soft tissue neoplasms, and commonly results in soft tissue edema in the radiation field. However, the time course, distribution and degree of this edema have not been well characterized. .... Muscle, on the other hand, showed a decrease in size following treatment. This was mild for the photon-treated group and more marked for the neutron-treated group. ...There is a relatively wide variation in the duration and degree of post-irradiation edema in soft tissues. This edema seems to persist longer in the intramuscular septa than in fat or muscle. Although the duration of follow-up was limited, our study suggests that this edema resolves in roughly half the photon-treated patients within 2-3 years post-treatment and in less than 20% of neutron-treated patients by 3-4 years post-treatment. Muscle atrophy was seen in both photon- and neutron-treated patients, but was more severe in the neutron-treated group. PMID: 8865487 
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8865487&dopt=Abstract 



Cancer 1982 Apr 15;49(8):1597-604 
The growth rate of bone sarcomas and survival after radiotherapy with tourniquet-induced hypoxia: a clinical study. 
Balmukhanov SB, Turdugulov I, Karibjanova Z, Revesz L. 
... Radiation therapy was given with three--four doses of 20--25 Gy to the tumors that, together with the surrounding normal tissues, had been made hypoxic by the application of a tourniquet. Amputations were not performed unless required eventually by some serious late radiation damage, such as grave functional deficiency, and/or painful fibrosis and ankyloses. In no case did microscopic examination of the amputated tissues reveal the persistence of any viable, neoplastic cells. The five-year survival of a total of 69 patients was 26%. Survival expectancy was found to be closely related to the volume doubling time of the tumors, as was the incidence of the metastases. The data stress the importance of volume doubling time as a predictive factor and indicate, furthermore, that treatment with a few massive radiation doses in combination with tourniquet-induced hypoxia is effective in the local control of bone sarcomas. The several late reaction of the normal tissues to the treatment will, however, require amputations in most of the five-year survivors. PMID: 7066865 



Vestn Khir Im I I Grek 1980 Jul;125(7):53-9 
[Secondary (radiation) edemas of the extremities]. [Article in Russian] 
Tsyb AF, Bardychev MS, Guseva LI. 
The results of clinical examinations and treatment of 96 patients with secondary (radiation) edemas of the extremities developing in late terms after radiation therapy of malignant tumors are discussed. The edema genesis is associated both with immediate radiation damage of lymph and blood vessels (veins), and with fibrous alterations of tissues in the radiation zone. PMID: 7414894] 




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NEW CANCERS
Radiation Damage
Medical Journal References


Bone Marrow Transplant 2000 May;25(9):1011-3 
Radiation-induced bone sarcoma following total body irradiation: role of additional radiation on localized areas. 
Kirova YM, Rafi H, Voisin MC, Rieux C, Kuentz M, Mouel SL, Levy E, Cordonnier C Oncology Department, Henri Mondor University Hospital, Creteil, France. [Record supplied by publisher] . PMID: 10800073 
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10800073&dopt=Abstract



Pediatr Neurosurg 1998 Feb;28(2):63-6 
Radiation exposure in the myelomeningocele population. 
Gaskill SJ, Marlin AE. Pediatric Neurosurgery of South Texas, P.A., San Antonio, USA.
Radiation-induced carcinoma is known to occur with lower doses of radiation exposure than previously recognized. The myelomeningocele population, because of its complex medical problems, is exposed to relatively high doses of radiation from diagnostic radiographs performed throughout their lives...These data suggest that the radiation burden from diagnostic radiographs in the myelomeningocele population may ultimately contribute to carcinogenesis, mutagenesis and other radiation damage. Specific strategies for reducing the lifetime radiographic exposure in these patients are discussed in detail. PMID: 9693333 
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9693333&dopt=Abstract



Environ Health Perspect 1997 Dec;105 Suppl 6:1497-8 
Thyroid-stimulating hormone levels in children from Chernobyl.
Quastel MR, Goldsmith JR, Mirkin L, Poljak S, Barki Y, Levy J, Gorodischer R. Soroka Medical Center, Beer Sheva, Israel. maay100@bgumail.bgu.ac.il 
This study assesses parameters of thyroid function in persons who resided in Ukraine, Belarus, and southern Russia and exposed at 0 to 16 years of age to radioiodine contamination from the Chernobyl accident.... A working hypothesis is proposed by which the shift in TSH levels in girls from high radiocontamination areas was associated with subclinical radiation damage from environmental radioiodine at the time of the accident. PMID: 9467071 


Stem Cells 1997;15 Suppl 2:207-10 
Overview of 1993 research activities in Belarus related to the Chernobyl accident. 
Krissenko N. Belarus Ministry of Health, Minsk, Belarus. 
This overview describes the medical and biological consequences of the Chernobyl nuclear power plant accident that had been assessed by Belarus scientists as of 1993. In particular, childhood thyroid cancer has increased in both frequency and severity. Other malignant tumors may have also increased, as may have childhood diseases that result from impaired immune function. It is unknown whether these increases in human disease (other than thyroid cancer) are due to improved methods of reporting or to exposure to ionizing radiation. In addition to the medical consequences of radiation damage, there are also significant psychological problems endured by the population living in contaminated areas. The Republic of Belarus has participated in several international programs for the study and management of widespread radiation exposure, and will continue to do so. Programs to address issues of radiation protection and population safety are being implemented wherever possible. PMID: 9368306 


Med Pediatr Oncol 1997 Dec;29(6):568-72 
Treatment of childhood post-irradiation sarcoma of bone in cancer survivors. 
Cefalo G, Ferrari A, Tesoro-Tess JD, Gianni MC, Fossati-Bellani F, Lombardi F, Massimino M. Division of Pediatric Oncology, Istituto Nazionale Tumori, Milano, Italy. 

... This is a retrospective review of five children with post-irradiation bone sarcoma (PIS). ... Chemotherapy alone, using an intensive regimen effective for primary osteogenic sarcoma, may be an adequate therapy for childhood post-irradiation sarcoma. PMID: 9324346

Radiat Res 1997 May;147(5):579-84 
Unexpected rates of chromosomal instabilities and alterations of hormone levels in Namibian uranium miners. 
Zaire R, Notter M, Riedel W, Thiel E. Department of Hematology and Oncology, University Medical Centre, Benjamin Franklin, Free University Berlin, Germany. 
A common problem in determining the health consequences of radiation exposure is factoring out other carcinogenic influences. The conditions in Namibia provide a test case for distinguishing the effects of long-term low-dose exposure to uranium from the other environmental factors because of good air quality and the lack of other industries with negative health effects. Present records indicate a much higher prevalence of cancer among male workers in the open-pit uranium mine in Namibia compared with the general population. The objective of the present study was to determine whether long-term exposure to low doses of uranium increases the risk of a biological radiation damage which would lead to malignant diseases .... A representative cohort of 75 non-smoking, HIV-negative miners was compared to a control group of 31 individuals with no occupational history in mining. A sixfold increase in uranium excretion among the miners compared to the controls was recorded (P < 0.001). Furthermore, we determined a significant reduction in testosterone levels (P < 0.008) and neutrophil count (P < 0.004) in miners compared to the unexposed controls. A threefold increase in chromosome aberrations in the miners compared to the nonexposed controls was recorded (P < 0.0001). Most remarkably, cells with multiple aberrations such as "rogue" cells were observed for the first time in miners; these cells had previously been found only after short-term high-dose radiation exposure, e.g. from the Hiroshima atomic bomb or the Chernobyl accident. We conclude that the miners exposed to uranium are at an increased risk to acquire various degrees of genetic damage, and that the damage may be associated with an increased risk for malignant transformation. As expected, the chronic radiation injury of the hematopoietic system resulted in low neutrophil counts. Also, low hormone levels probably reflect damage to the gonadal endocrine system. PMID: 9146703 
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9146703&dopt=Abstract


Pediatr Hematol Oncol 1995 Mar-Apr;12(2):185-8 Comment in: Pediatr Hematol Oncol. 1995 Mar-Apr;12(2):111-3 
Acute lymphoblastic leukemia in a girl treated for osteosarcoma. 
Miniero R, Barisone E, Vivenza C, Brach del Prever A, Besenzon L, Cordero di Montezemolo L, Madon E. Department of Pediatrics, University of Turin, Italy. 
PMID: 7626388 



J Natl Cancer Inst 1994 Jun 1;86(11):842-9 
Cancer following radiotherapy for peptic ulcer. 
Griem ML, Kleinerman RA, Boice JD Jr, Stovall M, Shefner D, Lubin JH. Department of Radiation Oncology, University of Chicago, Ill 60637. 
BACKGROUND: Radiotherapy for peptic ulcer was used between 1937 and 1965 to control excessive gastric acid secretions (mean dose, 14.8 Gy). Patients with this benign condition live many years after treatment and are at risk for late effects. PURPOSE: Our purpose was to investigate the risk of death from cancer following radiotherapy for peptic ulcer. METHODS: A mortality study was conducted of 3609 patients with peptic ulcer; 1831 were treated with radiation and 1778 were treated by other means. Extensive methods were used to trace patients. Radiation doses to specific organs were reconstructed from the original radiotherapy records. RESULTS: Nearly 70% of patients were found to have died. The average period of observation was 21.5 years (maximum 51 years). Compared with the general population, patients treated with or without radiation were at significantly increased risk of dying of cancer and non-malignant diseases of the digestive system. Risk of death due to heart disease was slightly higher following radiotherapy. Cancers of the stomach, pancreas, lung, and prostate were increased in both irradiated and nonirradiated patients. Radiotherapy was linked to significantly high relative risks (RRs) for all cancers combined (RR = 1.53; 95% confidence interval [CI] = 1.3-1.8), for cancers of the stomach (RR = 2.77; 95% CI = 1.6-4.8), pancreas (RR = 1.87; 95% CI = 1.0-3.4), and lung (RR = 1.70; 95% CI = 1.2-2.4), and for leukemia (RR = 3.28; 95% CI = 1.0-10.6). Radiation combined with surgery, or given to treat gastric ulcer, appeared to increase the risk of stomach cancer 10-fold, which was greater than the sum of individual effects. Patients with gastric ulcers were at higher risk for stomach cancer than patients with duodenal ulcers.  CONCLUSIONS: Patients with peptic ulcer are at increased risk of dying of cancer, related in part to lifestyle factors and treatment. Radiotherapy and surgery together appear to induce carcinogenic processes that greatly enhance the development of stomach cancer. The risk of radiation-induced stomach cancer was 0.25 extra deaths per 10,000 persons per year per Gy, somewhat lower than reported in other studies. High-dose radiation may have increased the risk of pancreatic cancer, a condition rarely found elevated in irradiated populations, but misclassified death notices may have contributed to the excess. Cancer mortality remained high for up to 50 years, indicating that radiation damage may persist to the end of life.  PMID: 8182765 
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8182765&dopt=Abstract

Eur J Surg Oncol 1994 Feb;20(1):53-6
Post irradiation sarcoma of soft tissue and bone. 
Pitcher ME, Davidson TI, Fisher C, Thomas JM. Sarcoma Unit, Royal Marsden Hospital, London, UK. 
Thirty-eight patients with sarcomas of soft tissue and bone which followed previous radiotherapy have been treated at the Royal Marsden Hospital between 1951 and 1992. The ... median time to development of sarcoma was 11 years. The only long term survivors were those who had complete surgical excision. Seven patients required forequarter amputation (30% of the extremity sarcomas) which reflects their frequent situation in the shoulder girdle and upper arm and the close proximity to the brachial plexus and vascular bundle. The overall prognosis was poor (5-year survival 30%) and probably reflects the poor prognostic factors (size, grade and tumour site) present at the time of diagnosis. PMID: 8131870 


J Submicrosc Cytol 1987 Apr;19(2):365-9
Post-irradiation leiomyosarcoma. Case report with immunohistochemical studies. 
Korbi S, Meyer D, Skalli O, Gabbiani G, Kapanci Y. 
We report here one case of post-irradiation leiomyosarcoma. The diagnosis of this was confirmed using anti-intermediate filament antibodies: tumor cells were positive for anti-vimentin and anti-desmin but negative for anti-prekeratin and anti-epithelial membrane antigen. The positive staining with anti-desmin clearly indicates a muscular origin although the tumor cells were not stained by two anti-actin antibodies, one directed against alpha-smooth muscle actin and the other against alpha-striated muscle actin. Irradiation was motivated by a wrong diagnosis of breast carcinoma when the patient was 13 year-old. The laps of time separating irradiation and the occurrence of the leiomyosarcoma was 13 years. The total dose was 6,000 rads. This is the ninth case of post-irradiation leiomyosarcomas reported in the literature. PMID: 2439703 


J Dermatol Surg Oncol 1984 Mar;10(3):200-3 
Radiation-induced basal-cell carcinoma. 
Allison JR Jr. 
Four patients developed 129 basal-cell carcinoma (BCC) in areas of prior radiation without evidence of radiation damage. The time lag between radiation and appearance of the cancers was 20 years. It is proposed that we are dealing with a subset of the population not previously recognized. These patients were not related to other groups, such as the nevoid basal-cell carcinoma syndrome. PMID: 6699258 


Ann Acad Med Singapore 1981 Jul;10(3):267-76 
Radiation induced cancer: a report of 10 cases. 
Tan BC, Chia KB. 
Ionizing radiations have been shown to be carcinogenic to man as well as experimental animals. Malignancies following therapeutic radiation occur rarely. Over the past 10 years the authors recorded 10 cases of tumours in irradiated tissues. ... The clinical features of these cases are discussed and other cases reported in the literature are reviewed. PMID: 6277226 


Cancer 1979 Nov;44(5):1601-5
Breast carcinoma and basal cell epithelioma after x-ray therapy for hirsutism. 
Schwartz RA, Burgess GH, Milgrom H. 

We report a 60-year-old woman with a history of x-ray therapy for generalized hirsutism at 20 years of age who at the age of 37 years developed the first of numerous basal cell epitheliomas on her trunk, including chest, on a background of radiation damaged skin. At the age of 51 years one of the basal cell epitheliomas was biopsied and an incidental histologic finding was a breast carcinoma. The basal cell epithelioma is clearly linked with x-ray exposure; breast cancer is less so although there is impressive epidemiologic evidence supporting an association between human breast cancer and radiation exposure. In view of an association between thyroid cancer and dermatologic x-ray therapy, further investigation of such an association with breast cancer should be considered. It may be wise to evaluate patients who received dermatologic x-ray exposure to their breasts for possible breast cancer and to consider radiation induced skin damage on or near the skin overlying the thyroid or breasts as a cutaneous marker of internal malignancy or potential internal malignancy. PMID: 498032 


CRC Crit Rev Clin Radiol Nucl Med 1975 Jul;6(3):425-39
A survey of the benefits and risks in the practice of radiology. 
Payne JT, Loken MK. 
The findings from both animal and human studies on the radiation risk at low doses and low dose rates are far from conclusive, primarily due to statistical limitations. However, to arrive at some estimate of radiation risk, a conservative approach has been taken, and a linear extrapolation of radiation effects from high doses to low doses has been made. Thus, it is assumed that any exposure to radiation carries some risk of somatic or genetic damage and that there is no threshold or safe dose. In medical practice, diagnostic radiological procedures should be performed only if useful clinical information will be derived. In addition, this information should be obtained at the least possible risk to the patient. For mass chest X-rays, mammography, and lung scans, a quantitative determination of benefit to risk is developed. This approach, though possible desirable, is exceedingly difficult to establish for most diagnostic radiological procedures. Thus, good clinical judgement should be employed in radiological practice, just as it should be employed in all aspects of medical practice. PMID: 1097189 


Minerva Ginecol 1997 Jul-Aug;49(7-8):345-54 
[Radiotherapy of cancer of the uterine cervix and successive appearance of new malignant growth in the irradiated field]. [Article in Italian] 
Russo F, Spina C, Coscarella G, Sileri PP, Arturi A, Stolfi VM Dipartimento di Chirurgia, Universita degli Studi di Roma Tor Vergata. [Record supplied by publisher] 
Among the late complications of high-dosage pelvic radiotherapy for cervical cancer, anorectal and bladder malignancies are sporadically reported in the literature. In this study the possible relationships of previous radiotherapy with late appearance of neoplasms are analyzed and in particular post-radiotherapy interval, dosage and type or irradiation to the cervical area. The mechanisms or neoplastic transformation or irradiated tissues are also studied. ..., the possible cause-effect relationships between previous radiotherapy and subsequent appearance of neoplasms are analyzed as well as the potential therapeutical consequences or considering these women high-risk subjects. The usefulness or recruiting women with history or previous radiotherapy for cervical cancer in a strict follow-up program (ultrasonography, cytology and endoscopy) is suggested in order to make an early diagnosis of the new pelvic malignancy with a better possibility for treatment. Review, tutorial PMID: 9380297 



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SKIN
Radiation Damage
Medical Journal References


Khirurgiia (Mosk) 1999;(10):60-2 
[Clinical features, diagnosis and treatment for trophic, late radiation ulcers and ulcers undergone malignant transformation]. [Article in Russian] 
Tostykh PI, Stranadko EF, Koraboev UM, Duvanskii VA, Kalinin MR, Vatlin KI. 
Clinical and histological examinations of 1562 patients with trophic and advanced radiation ulcers were carried out during 30 years. Malignant transformation of the ulcers has been revealed in 14 of them: sarcoma--in 1, and cancer--in 13. From all the patients with advanced radiation ulcers, malignant transformation was detected in 7.07%, and in cases of ulcers of the other genesis--in 0.81% of cases. Malignant transformation of ulcers of non-radiation genesis occurs on the average after 19 years, and of radiation one--after 3.8 years. Early diagnosis of skin cancer, at the site of the ulcer is rather difficult and depends thoroughly on oncological alert and timely morphological examination of various skin areas. A new, rather perspective and relatively simple method of treatment for ulcerative forms of cancer of the skin is photodynamic therapy (PhDT). This method showed to be effective even in those patients who failed conventional methods of treatment (relapses), or had contraindications. PhDT has broaden the armory of the oncologists and oncodermatologists for treatment of complicated forms of cancer of the skin. PMID: 10540557 


Klin Monatsbl Augenheilkd 1999 Dec;215(6):355-60 
[Long-term radiation damage to the skin and eye after combined beta- and gamma- radiation exposure during the reactor accident in Chernobyl]. [Article in German]  Junk AK, Egner P, Gottloeber P, Peter RU, Stefani FH, Kellerer AM. Ludwig-Maximilians-Universitat Munchen, Augenklinik. akj19@columbia.edu 
PMID: 10637800  
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10637800&dopt=Abstract



Biol Trace Elem Res 1998 Jul;63(1):11-8 
Structural and trace element changes in scalp hair of radiographers. 
Man AC, Zheng YH, Mak PK. Department of Applied Physics, The Hong Kong Polytechnic University, Hung Hom, Kowloon. 



...The structural damage to the hair follicles of the radiographers was quite obvious, and this may be a good qualitative indicator of radiation damage at low doses. The concentrations of aluminum (Al), potassium (K), and vanadium (V) in hair of the radiographers were significantly higher, whereas those of antimony (Sb) and magnesium (Mg) were significantly lower than those of nonradiographers. Some of our findings were quite consistent with those of others in determining the changes in trace element concentrations in irradiated tissue. PMID: 9764566 




Radiother Oncol 1996 Jul;40(1):23-30 Comment in: Radiother Oncol. 1996 Jul;40(1):1-3 Radiother Oncol. 1997 Jun;43(3):324-5 
Underprediction of human skin erythema at low doses per fraction by the linear quadratic model. 
Hamilton CS, Denham JW, O'Brien M, Ostwald P, Kron T, Wright S, Drr W. Radiation Oncology Department, Newcastle Mater Misericordiae Hospital, NSW, Australia. 
PMID: 8844884 



Hautarzt 1995 May;46(5):319-24 
[In vitro and in vivo studies of local disinfection and wound healing]. [Article in German] 
Hagedorn M, Hauptmann S, Essinger U, Kaden P, Mittermayer C. Hautklinik der Stadtischen Kliniken, Darmstadt. 
Wound healing represents a dynamic process of increasing scientific interest, ...Additionally it was shown, using cultures of fibroblasts, that chiniofon-containing antiseptic does not inhibit the growth of fibroblasts, whereas PVP-iodine solution, a widely used antiseptic, clearly reduces the growth of fibroblasts. The good clinical results in the treatment of acute and chronic radiation damage indicate that chiniofon-containing antiseptic may have antiflammatory activity. PMID: 7607895


Plast Reconstr Surg 1993 Aug;92(2):294-300 
Surgical treatment of radiation injuries of the hand.
Milanov NO, Shilov BL, Tjulenev AV. Department of Microsurgery, National Research Center of Surgery, Academy of Medical Sciences, Moscow, Russia. 
This paper describes the wound management and treatment of 12 consecutive patients with severe radiation damage to the hands. Three of these were secondary to therapeutic radiation ...and nine were healthy professional people exposed to radiation in the work-place. All lesions were characteristic radiation burns with ulcerative necrotic changes of the skin and subcutaneous tissues...We conclude that management of radiation-induced injuries to the hand should be done with aggressive debridement and immediate coverage with well-vascularized flaps, either regional or free-tissue transfers. This will result in adequate wound healing and the most rapid, effective return of function with rapid institution of therapeutic modalities. PMID: 8337280 



J Am Acad Dermatol 1984 Jul;11(1):53-7 
Drug eruptions presenting at sites of prior radiation damage (sunlight and electron beam). 
Shelley WB, Shelley ED, Campbell AC, Weigensberg IJ. 
Two patients are described in whom sunburn and electron beam radiodermatitis, respectively, were critical determinants in localizing the initial presentation of drug eruptions. In the first instance, a severe sunburn of the back and thighs was followed 7 months later by the appearance of a toxic epidermal necrolysis drug reaction to trimethoprim-sulfamethoxazole in the exact sites of the previous bullous sunburn reaction. In the second patient, a radiodermatitis of the left upper arm due to electron beam therapy for metastatic breast cancer was followed 7 weeks later by a codeine drug reaction confined to the area of the radiodermatitis. In both instances, oral rechallenge with the offending drug reproduced the eruption. PMID: 6234333



J Dermatol Surg Oncol 1984 Mar;10(3):200-3 
Radiation-induced basal-cell carcinoma. 
Allison JR Jr. 
Four patients developed 129 basal-cell carcinoma (BCC) in areas of prior radiation without evidence of radiation damage. The time lag between radiation and appearance of the cancers was 20 years. It is proposed that we are dealing with a subset of the population not previously recognized. These patients were not related to other groups, such as the nevoid basal-cell carcinoma syndrome. PMID: 6699258 



Ann Dermatol Venereol 1979 Nov;106(11):875-82 
[On five new cases of association of basal cell carcinoma and multiple Pinkus fibroepithelial tumors on the spine following radiation damage to the skin (author's transl)]. [Article in French] Colomb D, Brechard JL, Gho A, Caux Y. 
The authors report five new cases associating basal cell epithelioma and multiple Pinkus fibro-epithelial tumors on the spine after radiation damage to the skin. One of them had previously published three similar observations: so his experience refers to eight cases. The authors recall similar cases of the literature, they discuss the relations between basal cell epitheliomas and Pinkus premalignant fibro-epithelial tumors of the skin. Histologically they saw several aspects of transition between the two types of tumors. They study the patterns of cancers found after radiation therapy, influence of type of radiations, dose, age, and intervals since X-rays. As regards such cases, the necessity of systematically searching for previous radiations by X-rays in the affected zone is emphasized.PMID: 539699 



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Spinal Cord
Radiation Damage
Medical Journal References


Brain 1996 Oct;119 ( Pt 5):1429-39 
The post-irradiation lower motor neuron syndrome neuronopathy or radiculopathy? 
Bowen J, Gregory R, Squier M, Donaghy M. Department of Clinical Neurology, Radcliffe Infirmary, Oxford, UK. 
It is not known whether the post-irradiation lower motor neuron syndrome results from radiation damage to motor neuron cell bodies or from damage to the nerve roots of the cauda equina. ... The first reported neuropathological study... was performed in one patient who died. This showed a radiation-induced vasculopathy of the proximal spinal roots, with preservation of motor neuronal cell bodies and spinal cord architecture. These clinical, radiological, neurophysiological and pathological findings all point to a predominantly, but not exclusively, motor radiculopathy affecting the irradiated portion of the cauda equina proximal to the dorsal root ganglia. Radiation exposure exceeded 40 Gy both in our series and in previous reports. The natural history of this disorder is one of relentless deterioration occasionally punctuated by 1-2-year periods of stability. Post-irradiation lumbosacral radiculopathy is a more accurate name for this condition. PMID: 8931568 
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8931568&dopt=Abstract



Int J Radiat Oncol Biol Phys 1994 Oct 15;30(3):575-81 Comment in: Int J Radiat Oncol Biol Phys. 1995 May 15;32(2):554 
Radiation myelopathy following single courses of radiotherapy and retreatment. 
Wong CS, Van Dyk J, Milosevic M, Laperriere NJ. Department of Radiation Oncology, Princess Margaret Hospital/Ontario Cancer Institute, Toronto, Canada. 

...To assess the latent time, survival and dose-fractionation factors associated with permanent radiation myelopathy following single and multiple courses of radiotherapy to the spinal cord. ...: A retrospective analysis was undertaken .... Twenty-four patients developed permanent myelopathy after one course of radiation therapy and 11 patients following retreatment. Seven patients had histological confirmation of radiation myelopathy at autopsy. ... The actuarial survival was 14% at 5 years (median: 8.3 months) from the date of diagnosis of radiation myelopathy. Latent times for myelopathy following a single course of treatment (mean: 18.5 months, 7-57 months), were significantly longer than those after reirradiation (mean: 11.4 months, 4-25 months), p = 0.03. There was not a single incident of myelopathy in patients who received fractionated radiotherapy given once daily to an extrapolated response dose (ERD) of < or = 100 Gy2 (equivalent to 50 Gy in 25 daily fractions). Four patients who developed myelopathy after an ERD of < 100 Gy2 were all treated on accelerated fractionation protocols with multiple fractions given per day. Patients who were reirradiated received significantly higher doses (mean ERD of 148 Gy2) than those who had a single course of treatment (mean ERD of 121 Gy2), p = 0.001. ... We conclude that the risk of radiation myelopathy following conventionally fractionated radiotherapy to the spinal cord is extremely small; giving multiple fractions per day reduces the spinal cord tolerance; latent time to myelopathy decreases following retreatment; and there is possible long-term recovery of radiation damage in the human spinal cord. PMID: 7928488 
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7928488&dopt=Abstract



Strahlenther Onkol 1993 Sep;169(9):543-4 
[Radiation-induced myelitis following accelerated radiotherapy]. [Article in German] 
Dunst J, Dunst U, Wittmoser W. Strahlentherapeutische Klinik, Universitat Erlangen-Nurnberg. 
We report a case of suspected radiation-induced myelitis after twice-daily irradiation with a cord dose of 45.8 Gy. The 48-year old patient had been irradiated with two daily fractions of 1.8 Gy up to 70.2 Gy for oropharyngeal cancer T4 N2 G3 M0 and achieved a complete remission. The spinal cord received 42 Gy by open fields plus 3.8 Gy scatter irradiation after field reduction. Six months after radiotherapy clinical signs of tetraparesis occurred with two lesions in the cervical cord on MR-images. A complete neurological diagnostic procedure revealed no other causes than suspected radiation damage. This is the only case of radiation myelitis among 90 patients treated twice daily and over 2000 patients irradiated with conventional fractionation in the same technique and doses. PMID: 8211674 



Cancer 1991 Nov 15;68(10):2138-41 
Incidence of radiation myelitis of the cervical spinal cord at doses of 5500 cGy or greater. 
Jeremic B, Djuric L, Mijatovic L. Department of Oncology, University Hospital of Kragujevac, Yugoslavia. 
The incidence of permanent damage to the spinal cord as a complication of radiation therapy generally correlates positively with total radiation dose. .... The results of this study suggest that radiation damage to the cervical spinal cord correlates not only with total radiation dose, but also with fraction size. Low fraction sizes appear to decrease the incidence of such damage. PMID: 1913452 
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1913452&dopt=Abstract



Radiother Oncol 1990 Mar;17(3):209-18 
Neurological damage in patients irradiated twice on the spinal cord: a morphologic and electrophysiological study. 
Magrini SM, Biti GP, de Scisciolo G, Bartelli M, Pinto F, Caramella D, Villari N. Hospital Department of Radiotherapy, University Department of Radiotherapy, Florence, Italy. 
We reviewed the files of 950 patients treated for Hodgkin's disease since 1966 and were able to find five patients treated with radiochemotherapy and irradiated twice on volumes including a cord segment, at various time intervals, and surviving until now. Seven patients with comparable clinical and therapeutic features, but not reirradiated on the cord, were chosen as a control group and were examined with the same diagnostic procedures. The cumulative cord dose in the reirradiated patients was recalculated and ranged from 50 to 70 Gy. All these patients and the control cases were followed up for more than 10 years and presented no or only minor neurological symptoms. We compare the results of both magnetic resonance imaging (MRI) and electrophysiological studies (spinal and scalp recorded somatosensory evoked potentials--SEPs) in an attempt to define the characteristics of the subclinical damage present in these patients. While no cord abnormality was demonstrated with MRI, electrophysiological studies evidenced a clear difference between cases and controls, as far as the D10-P1 conduction time and SEPs average amplitude are concerned. Advantages and drawbacks of a wider use of electrophysiological methods in research work on cord radiation damage are presented, along with the possible implications of the results obtained for the understanding of the pathogenesis and of the dose dependence of radiation myelitis (RM). PMID: 2320750 



Clin Neuropathol 1988 May-Jun;7(3):134-8 
Late nervous system disorders in cured malignant lymphoma: a clinical and neuropathological study. 
Vesterby A, Reske-Nielsen E, Kristensen IB, Jastrup B, Thorling K. Department of Neuropathology, Aarhus Kommunehospital, University of Aarhus, Denmark. 
A 53-year-old woman was treated for and cured of low grade malignant lymphoma, localized to the neck, by irradiation and chemotherapy. One year later she developed signs of damage to the spinal cord with slight paraparesis of the lower extremities, which remained stationary for seven years. Then, new and rapidly progressive central and peripheral neurological symptoms developed. About one year later the patient died. At autopsy a malignant glioma of the right temporal lobe and radiation damage to the spinal cord were found. Lymphocytic infiltrations in the peripheral nerves and muscles of the lower extremities were also seen. A severe neurogenic atrophy was present but no relapse of malignant lymphoma was found. Depressed immune defense is suggested to be the cause of the pathological changes of the nervous system in this case. The inflammation of the peripheral nerves might be due to activation of a latent virus infection. PMID: 3203483 



Cancer 1981 Oct 1;48(7):1680-3 
Intramedullary tumor metastasis simulating radiation myelitis: report of a case. 
Margolis L, Smith ME, Fortuin FD, Chin FK, Liebel SA, Hill DR.
A case of suspected radiation myelitis based on clinical history, previous irradiation, neurologic deficit in the irradiated volume, and normal myelogram is reported. At autopsy, intramedullary metastatic disease was found, but not radiation damage. All radiation details must be considered before making the diagnosis of radiation myelitis with confidence. It is important not to exclude other potentially helpful treatment, such as surgery or chemotherapy, by the presumptive diagnosis of radiation myelitis. PMID: 7284968 



Psychiatr Neurol Med Psychol (Leipz) 1980 Nov;32(11):663-8 
[Radiation myelopathy following radiotherapy of larynx cancer]. [Article in German] 
Buchholz A, Dahn I. 
On the basis of a case of radiation myelopathy after irradiation of a larynx carcinoma, the morphological characteristics and the clinical phenomena are demonstrated. In spite of constant improvement of the radiation therapy, the occurrence of a radiation damage of the central nervous system must be expected and included in the differential-diagnostic considerations. PMID: 7208709 



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Prevention of Radiation Damage
Medical Journal References


Br J Dermatol 1996 Jan;134(1):77-84 
UVA-induced immune suppression in human skin: protective effect of vitamin E in human epidermal cells in vitro. 
Clement-Lacroix P, Michel L, Moysan A, Morliere P, Dubertret L. Laboratoire de Dermatologie, INSERM U312, Hopital Saint-Louis, Paris, France. 
UVA (320-400 nm) radiation damage to membranes, proteins, DNA and other cellular targets is predominantly related to oxidative processes. In the present study, we demonstrated that cutaneous UVA-induced immunosuppression can be related, at least in part, to the appearance of these oxidative processes. The UVA-induced oxidative processes in freshly isolated epidermal cells were monitored by measuring the thiobarbituric acid reactive substances (TBARS) as an index of peroxidation. The in vitro immunosuppressive effects of UVA were demonstrated by measuring the allogeneic lymphocyte proliferation induced by epidermal cells or purified Langerhans cells in the mixed epidermal cell-lymphocyte reaction (MECLR). In addition, the effects of a potent antioxidant (vitamin E) on these two UVA-induced processes were analysed. Our results showed that the antigen-presenting function of Langerhans cells measured in the MECLR is dose-dependently decreased by UVA radiation (up to 20J/cm2).Overnight incubation of epidermal cells with vitamin E (400 mumol/l) before irradiation partially protected epidermal cells from the immunosuppressive effects of UVA radiation,and decreased TBARS release into the supernatant (a decrease of 35% compared with a control without vitamin E). Our results suggest that UVA radiation may alter cell-presenting antigen function partly via the generation of reactive oxygen species which trigger peroxidative processes, and these data contribute to the understanding of the role of oxidative mechanisms in immune suppression induced by UVA radiation. Our in vitro model can be used to quantify UV-mediated epidermal cell damage and the degree of immune photoprotection provided by various agents. PMID: 8745890 


Radiat Res 1983 Apr;94(1):10-40 
Radiation biology: the conceptual and practical impact on radiation therapy. 
Suit HD. 
Radiation biology has had an important impact on clinical radiation therapy by providing a rationale for implementation of new treatment strategies and for clinical concepts or practices thereby increasing their acceptance. The observed rather narrow range of D0 and n values for mammalian cells contributed to successful trials of radiation treatment of several "radiation-resistant" tumors, e.g., carcinoma of prostate, color-rectum, and sarcoma of soft tissue. Attention of clinicians was forcibly directed to assessment of local results (local failure, treatment complications) and not merely survival at 5 years by the extensive literature of cell survival curves (in vivo and in vitro) and dose-response assays on normal and tumor tissues. Upon these same laboratory results a scientific rationale was developed for use of shrinking field technique, low dose for subclinical disease, and the combination of moderate dose radiation therapy and conservative surgery. The entire area of clinical research into altered dose fractionation schedules is based upon research on cell proliferation kinetics and repair of radiation damage. The understanding that the time for complete regression of tumor depends not only upon cell kill but also on the pattern of cell proliferation of the progeny of lethally irradiated cells and the abundance of stroma provided a basis for accepting patients with slowly responding tumors for treatment. There remains a wide field of need in research in this area as even today a large proportion of patients who die of cancer die with their cancer uncontrolled at the primary site. Publication Types: Historical article PMID: 6344129 
Cancer 1978 Mar;41(3):991-5

Am J Roentgenol 1976 Dec;127(6):1027-32 
Inherent cellular radiosensitivity of human tumors of varying clinical curability. 
Weichselbaum RR, Epstein J, Little JB, Kornblith P. 
It is well known that radiation therapy can be successfully used to cure or control some types of human tumors, while consistently failing in others. This has been ascribed to several factors including differences in the intrinsic sensitivity of the tumor cells and in their ability to recover from radiation damage. In this study, human tumor cells from an osteogenic sarcoma, a glioblastoma, and two medulloblastomas, as well as cells from human skin, were established in tissue culture, and the in vitro x-ray survival and DNA repair parameters determined. No significant differences in either clonogenic survival or DNA strand rejoining ability could be detected among these human tumors or skin cells, despite the wide variability in their radiocurability in vivo. In addition, skin cell strains derived from patients exhibiting markedly sensitive or resistant skin reactions during fractionated radiotherapy showed no differences in survival characteristics from normal controls. It is therefore suggested that the wide range of radiocurabilities seen among various human tumors cannot be explained on the basis of inherent cellular factors responsible for the survival of tumor cells after x-irradiation. PMID: 1069484 


Indian J Exp Biol 1989 Nov;27(11):1005-7
2-Deoxy-D-glucose induced modification of chromosomal damage in UV-irradiated peripheral human leukocytes. 
Kalia VK, Jain VK. 
UV-irradiation (0.6 J/m2) of peripheral human leukocytes 27 hr after PHA-stimulation induced a considerable mitotic delay in the cultures. Approximately two thirds of the chromosomal aberrations induced by UV were gaps of the chromatid and isochromatid types. Treatment with glucose antimetabolite 2-deoxy-D-glucose (2-DG) alone did not induce any chromosomal damage. Presence of 2-DG (5 mM, equimolar with glucose) for 2 hr after UV-irradiation resulted in a significant reduction in the frequency of cells with aberrations. Decrease in the total aberrations per cell was also observed. The data are consistent with earlier observations that 2-DG reduces the manifestation of radiation damage in normal proliferating cells. PMID: 2620927 


Int J Radiat Biol 1989 Dec;56(6):963-73 
Nuclear lysate sedimentation measurements of peripheral blood lymphocytes from radiotherapy patients. 
Deeley JO, Moore JL. South Wales Radiotherapy and Oncology Service, Velindre Hospital, Cardiff, U.K. 
When isolated nuclei of human lymphocytes are challenged with 2 M NaCl a histone-free-DNA-protein (HF-DNA) complex is released. In a linear sucrose gradient (pH 8.0) the sedimentation distance of HF-DNA is reduced when immediately isolated from cells irradiated in vitro. At low doses, if irradiated cells are incubated at 37 degrees C the sedimentation behaviour approaches that of unirradiated cells (i.e. repair). In the present study such repair was usually complete within 1 h. The radiation damage to lymphocytes from a healthy donor group and three patient groups consisting of new patients (before radiotherapy), well patients (2 to 6 years post-radiotherapy) and patients with complications attributed to radiotherapy was similar. The lymphocytes from most healthy donors and new patients demonstrated complete repair of radiation damage following an incubation of 1 h at 37 degrees C. However, 2/29 (6.9 per cent) healthy donors and 2/25 (8 per cent) new patients demonstrated poor repair. Of those patients now attending with 'bowel complications' attributed to radiotherapy 7/16 (44 per cent) demonstrated poor repair. In contrast, all those (11/11) described as 'well and complication-free' showed good repair. PMID: 2574224

Hautarzt 1990 Aug;41(8):448-50
[Exacerbation of progressive scleroderma following roentgen therapy]. [Article in German] 
Haustein UF. Klinik und Poliklinik fur Hautkrankheiten des Bereichs Medizin, Karl-Marx-Universitat Leipzig. 
In a 38-year-old female patient suffering from progressive scleroderma and breast carcinoma the clinical features were exacerbated and became generalized after radiotherapy, and unfortunately regressed only transiently during aggressive polychemotherapy. Links between progressive scleroderma and carcinoma and the immune system are discussed. The risk of post-irradiation worsening of progressive scleroderma is pointed out. PMID: 2177048 


Cancer 1977 Feb;39(2 Suppl):987-98 
Chemical modification of radiation effects
Phillips TL.
A number of powerful chemical compounds that modify radiation effects have been discovered and tested both in the laboratory and clinically over the past 25 years. There are four major classes of compounds: aminothiol radio-protectors which act on well vascularized euoxic cells and concentrate in tissues such as skin, gut and marrow; nitromidazole radiosensitizers which act on hypoxic tumor cells; pyrimidine analogues which are incorporated into the DNA of cycling cells and cause radiosensitization; and cancer themotherapy agents which, in addition to their ability to kill tumor cells directly, also may sensitize tumor and normal cells to radiation. The mechanism of action, experimental activity, and clinical results or the potential for each of these agents are reviewed. PMID: 319901


CRC Crit Rev Clin Radiol Nucl Med 1975 Jul;6(3):425-39
A survey of the benefits and risks in the practice of radiology. 
Payne JT, Loken MK. 
The findings from both animal and human studies on the radiation risk at low doses and low dose rates are far from conclusive, primarily due to statistical limitations. However, to arrive at some estimate of radiation risk, a conservative approach has been taken, and a linear extrapolation of radiation effects from high doses to low doses has been made. Thus, it is assumed that any exposure to radiation carries some risk of somatic or genetic damage and that there is no threshold or safe dose. In medical practice, diagnostic radiological procedures should be performed only if useful clinical information will be derived. In addition, this information should be obtained at the least possible risk to the patient. For mass chest X-rays, mammography, and lung scans, a quantitative determination of benefit to risk is developed. This approach, though possible desirable, is exceedingly difficult to establish for most diagnostic radiological procedures. Thus, good clinical judgement should be employed in radiological practice, just as it should be employed in all aspects of medical practice. PMID: 1097189 


Radiat Res 2000 Sep;154(3):342-6 
Identification of potential mRNA biomarkers in peripheral blood lymphocytes for human exposure to ionizing radiation. 
Amundson SA, Do KT, Shahab S, Bittner M, Meltzer P, Trent J, Fornace AJ Jr. National Institutes of Health, National Cancer Institute, Bethesda, MD 20892, USA. 
Since early in the Atomic Age, biological indicators of radiation exposure have been sought, but currently available methods are not entirely satisfactory. Using cDNA microarray hybridization to discover new potential biomarkers, we have identified genes expressed at increased levels in human peripheral blood lymphocytes after ex vivo irradiation. We recently used this technique to identify a large set of ionizing radiation-responsive genes in a human cell line (Oncogene 18, 3666-3672, 1999). The present set of radiation markers in peripheral blood lymphocytes was identified 24 h after treatment, and while the magnitude of mRNA induction generally decreased over time, many markers were still significantly elevated up to 72 h after irradiation. In all donors, the most highly responsive gene identified was DDB2, which codes for the p48 subunit of XPE, a protein known to play a crucial role in repair of ultraviolet (UV) radiation damage in DNA. Induction of DDB2, CDKN1A (also known at C1P1/WAF1) and XPC showed a lineardose-response relationship between 0.2 and 2 Gy at 24 and 48 h after irradiation, with less linearity at earlier or later times. These results suggest that relative levels of gene expressions in peripheral blood cells may provide estimated of environmental radiation exposures. PMID: 11012342 

