
<b>&&url
This excellent section of the virtual trials website attempts to explain the latest brain tumor treatments that are in general use in plain English, with a brief overview of each, then details on the treatments and where to find them. Unlike the rest of the "Clinical Trials & Noteworthy Treatments For Brain Tumors" site, this section is only the author's OPINIONS of the material. Use it for general information, to get ideas of what is available out there, but then discuss it with your own doctors. </b>


<b>Radiation URLs


Staten Island, NY University Hospital &&url

Oncolink Article &&url

Fermi National Accelerator Laboratory &&url
 
Massachusetts General Hospital, Harvard Medical School &&url  

Loma Linda, CA, University Medical Center &&url

Gamma Knife Radiosurgery

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Brain Anatomy</b>

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<b>Annotated References for this section:</b>


1. Surg Neurol 2000 Aug;54(2):160-4 
<b>Brain metastasis in patients with sarcoma: an analysis of histological subtypes, clinical characteristics, and outcomes. </b>
Yoshida S, Morii K, Watanabe M, Saito T. Department of Neurosurgery, Niigata Cancer Center Hospital, Niigata, Japan. 

"... Brain metastasis was found in 27 (5.6%) of 480 patients with systemic sarcoma (7.2% soft part sarcoma, 3.5% bone sarcoma, 15.1% distant metastasis). Of these 27 sarcoma patients with brain metastases, lung metastasis occurred in 16 patients (59.3%). <b>Out of 10 patients surgically treated, 8 patients survived more than 16 months. Median survival period after craniotomy was 25.4 months."</b> 
"...We recommend aggressive treatment for those patients with brain metastases whose performance scores are over 70." 
&&url PMID: 11077098 


2. Neurochirurgie 1999 Dec;45(5):382-92 
<b>[Cerebral metastases: radiotherapy and chemotherapy]. [Article in French] </b>
Helfre S, Pierga J. Institut Curie, 26, rue d'Ulm, 75005 Paris, France. 

"Brain metastases are common events in adult patients with solid tumors. The choice of the optimal therapy is still challenging and controversial. Whole brain radiotherapy (WBRT) is a standard practice in most patients with an excellent palliative effect. <b>Boost to gross disease has also been advocated without a clear benefit. Moreover following extended irradiation, a substantial proportion of the long term survivors (>6 months), will present documented cognitive impairments. Patients with favorable prognostic factors can benefit from more aggressive therapy: local resection, mono or multifractionated irradiation with or without radiosensitizing agents, stereotactic radiotherapy, brachytherapy. </b>Although brain metastases of solid tumors occur in the presence of progressive widespread disease, chemotherapy has played a limited role in their treatment. Poor drug penetration across the normal blood-brain barrier of chemotherapy agents is not a limiting factor because of the neovascularization in the tumor. [?] The few prospective studies that have addressed this issue, especially in lung and breast tumors, are reviewed." 
&&url PMID: 10717587 


3.  Neuro-oncol 2001 Jan;3(1):46-54  
<b>Importance of dose intensity in neuro-oncology clinical trials: summary report of the Sixth Meeting of the Blood-Brain Barrier Disruption Consortium.</b>
Doolittle ND, Anderson CP, Bleyer WA, Cairncross JG, Cloughesy T, Eck 
SL, Guastadisegni P, Hall WA, Muldoon LL, Patel SJ, Peereboom D, Siegal 
T, Neuwelt EA.
Dept of Neurology, Oregon Health Sciences University, Portland  97201-3098, USA.

 " Therapeutic options for the treatment of malignant brain tumors have been limited, in part, because of the presence of the blood-brain barrier. For this reason, the Sixth Annual Meeting of the Blood-Brain 
Barrier Disruption Consortium, the focus of which was the "Importance of Dose Intensity in Neuro-Oncology Clinical Trials," was convened ...This meeting...brought together clinicians and basic scientists from across the U.S. to discuss the role of dose intensity and enhanced chemotherapy delivery in the treatment of malignant brain tumors and to design multicenter clinical trials. "
"Optimizing chemotherapy delivery to the CNS is crucial, particularly in view of recent progress identifying certain brain tumors as chemosensitive. The discovery that specific constellations of genetic alterations can predict which tumors are chemoresponsive, and can therefore more accurately predict prognosis, has important implications for delivery of intensive, effective chemotherapy regimens with acceptable toxicities. This report summarizes the discussions, future directions, and key questions regarding dose-intensive treatment of ... metastatic cancer of the brain. The promising role of cytoenhancers and chemoprotectants as part of dose-intensive regimens for chemosensitive brain tumors and development of improved gene therapies ... are discussed."   
Publication Types: Congresses  
&&url PMID: 11305417 


4.  Curr Oncol Rep 2000 Sep;2(5):445-53 
<b>Cytotoxic chemotherapy: advances in delivery, pharmacology, and testing.</b>
Ciordia R, Supko J, Gatineau M, Batchelor T.
Brain Tumor Center, Massachusetts General Hospital Cancer Center, Harvard Medical School, Cox 315, 100 Blossom Street, Boston, MA 02114, USA.

"... A major factor in the failure of iv chemotherapy [for treatment of brain tumors] is the blood-brain barrier (BBB), a physiologic impediment to the delivery of cytotoxic chemotherapeutic drugs to the central nervous system (CNS). Intra-arterial and intrathecal infusion, blood-brain barrier disruption, high-dose chemotherapy, intratumoral administration, and convection-enhanced delivery are methods developed to overcome the BBB. Although some of these methods may increase the local concentration-time profile, improvement in clinical outcomes has yet to be definitively established. New methods for assessment of drug delivery to the brain tumor will assume increasing importance in the study of new cytotoxic chemotherapeutic drugs for these types of cancer. Pharmacokinetic studies are critical components of these clinical trials and allow         assessment of drug delivery to the CNS and brain tumor. Additionally, pharmacokinetic studies will remain an important component of early clinical trials, particularly for identifying significant drug interactions involving the various supporting medications that are typically used in this patient population."  
&&url PMID: 11122877 



5.  Neurosurgery 2000 Jul;47(1):199-207         
<b>Unexpected neurotoxicity of etoposide phosphate administered in combination with other chemotherapeutic agents after blood-brain barrier modification to enhance delivery, using propofol for general anesthesia, in a rat model.</b>
Fortin D, McCormick CI, Remsen LG, Nixon R, Neuwelt EA.
Dept of Neurology, Oregon Health Sciences University, and Veterans Administration Medical Center, Portland, USA.

"... Osmotic blood-brain barrier disruption (BBBD) increases brain and brain tumor delivery of chemotherapeutic agents, which results in increased efficacy against brain tumors. We previously noted that the use of propofol anesthesia for BBBD increased the percentage of successful disruptions, resulting in delivery of increased amounts of chemotherapeutic drugs. This study evaluated the neurotoxicity of combination chemotherapeutic administration with this enhanced delivery system."...
"Neurotoxicity was significantly increased for etoposide phosphate combination groups, particularly when both drugs were administered IA after BBBD. This increase in neurotoxicity may reflect on increase in         drug delivery observed with propofol anesthesia. ..." 
&&url PMID: 10917363 


6. Clin Pharmacol Ther 2000 Jun;67(6):631-41 
<b>Pharmacokinetics of methotrexate in cerebrospinal fluid and serum after osmotic blood-brain barrier disruption in patients with brain lymphoma.</b>
Zylber-Katz E, Gomori JM, Schwartz A, Lossos A, Bokstein F, Siegal T.
Division of Medicine, the Neuro-Oncology Center, Hadassah University Hospital, Jerusalem, Israel. esterzk@hadassah.org.il

"... Enhanced methotrexate delivery to the central nervous system can be attained by intra-arterial administration combined with osmotic disruption of the blood-brain barrier compared with simple intra-arterial or intravenous administration." 
&&url PMID: 10872645 


7. Cancer 1988 Feb 1;61(3):593-601 
<b>Sarcoma metastatic to the brain.</b>
Lewis AJ.
Department of Pathology, University of Toronto, Ontario, Canada.

"...Reportedly, most types of sarcomas are able to metastasize to the brain, and are represented in these 94 patients.  ... There may be a group of tumors, including ...perhaps leiomyosarcoma ... in which the incidence of brain metastases has increased with improved sarcoma chemotherapy ... In this group particularly... the presence of lung metastases may increase the probability of brain metastasis occurring subsequently. 
&&url PMID: 3276383 


8. Med Pediatr Oncol 1985;13(5):280-92 
<b>Sarcoma metastatic to the central nervous system parenchyma: a review of the literature.</b>
Sarno JB, Wiener L, Waxman M, Kwee J.

<b>Sarcoma metastatic to cerebral parenchyma, although rare, occurs more frequently than generally recognized. With increased duration of survival due to multi-modal therapy, more CNS metastases are being 
found. A literature search occasioned by a patient with metastatic sarcoma has produced some interesting results.</b>  
&&url PMID: 3897818 


9. Cancer <b>1975</b> Nov;36(5):1843-51 
<b>Increased incidence of cerebral metastases in sarcoma patients with         prolonged survival from chemotherapy. Report of cases of leiomyosarcoma         and chondrosarcoma.</b>
Gercovich FG, Luna MA, Gottlieb JA.

<b>Soft tissue and bony sarcomas rarely metastasize to the central nervous system, particularly to the cerebral hemispheres. In 456 patients with metastatic sarcoma, only 6 (1.3%) had cerebral metastases documented by brain scan at the time of referral for chemotherapy. Adriamycin-containing combination chemotherapeutic regimens have led to a significant increase in the median survival of patients from the start of chemotherapy (18 + months for responders compared, to 7 months in nonresponders). </b>Of 14 patients relapsing after a response or stabilization of disease of 6 months or greater, the cause of relapse was the development of cerebral metastases in 5 (36%). Two of these cases, one a patient with leiomyosarcoma and one with chondrosarcoma, were documented by autopsy and are reported in detail because of their rarity in the medical literature. Although the numbers are small, <b>the increased incidence of cerebral metastases in the group relapsing after a lengthy response suggests that improved chemotherapy for sarcomas resulting in improved survival may be changing the pattern of metastatic disease, and may require new therapeutic approaches.</b> 
&&url PMID: 1192369 
