
<b>Preoperative Hyperthermia and Radiation

Neoadjuvant Preoperative Thermochemotherapy and Postoperative Chemoradiation

Preoperative Hyperthermia and Systemic Chemotherapy

Hyperthermic Intraoperative Intraperitoneal Chemotherapy / Hyperthermic Total Abdominal Perfusion


Preoperative Hyperthermia and Radiation</b>
Surgical resection was planned 4-6 weeks after the completion of radiation and hyperthermia in 97 patients with surgically resectable high grade STS, without metastases.  "Ten-year actuarial overall survival, cause-specific survival, and relapse-free survival are 50, 47, and 47% respectively. The predominant pattern of failure has been distant metastases with only 2 patients developing local failure alone. Ten-year actuarial local control for extremity tumors is 94%, 63% for the 19 patients with tumors at sites other than the extremity. ... For these aggressive high-grade soft tissue sarcomas, this treatment program of preoperative thermoradiotherapy provided excellent local regional control for extremity lesions (95%) and satisfactory local regional control (63%) of nonextremity sarcomas, but did not appear to influence the rate of distant metastases or survival. Complications were frequent but apart from the direct thermal burns, not too different from those reported for preoperative radiotherapy alone. More effective adjuvant systemic therapy is necessary to impact favorably on survival. [27]


<b>Neoadjuvant Preoperative Thermochemotherapy and Postoperative Chemoradiation</b>
"Patients with retroperitoneal or visceral (RP/V) soft-tissue sarcomas (STS) have a poor prognosis with a median survival of 20 months" 58 [21 primary, 18 recurrence, 19 inadequately resected] patients with RP/V STS were treated with 4 cycles of EIA [etoposide, ifosfamide, adriamycin] concurrently with regional hyperthermia, then surgery, then another 4 cycles of EIA and external beam radiation. "Median overall survival for the group was 31 months," for those with NED median survival was 76 months, for NON-NED 20 months.  "Patients responding to neoadjuvant thermochemotherapy associated significantly with NED... In conclusion, response to neoadjuvant thermochemotherapy is predictive for a better survival in patients with high-risk STS at unfavorable RP/V sites. Since local recurrence without distant metastasis often results in death for patients with RP/V tumors, local tumor control accomplished in part by neoadjuvant thermochemotherapy seems to improve survival. In order to prove the impact of RHT on the efficacy of neoadjuvant treatment, a randomized multicentric phase III trial (EORTC 62961/ ESHO RHT-95) has been initiated. [4*, also &&url]


<b>Preoperative Hyperthermia and Systemic Chemotherapy</b>
There is improvement of local control by regional hyperthermia combined with systemic chemotherapy (ifosfamide plus etoposide) in advanced sarcomas. [122]  Not only are the treatment results with regional hyperthermic perfusions excellent for both primary and locally recurrent sarcomas of the extremities, but limbs previously considered unsalvageable can be spared. [150]

"In this phase II study, activity and safety of neoadjuvant regional hyperthermia (RHT) combined with chemotherapy was investigated in 59 patients with primary advanced or recurrent high-risk soft-tissue sarcoma (STS). Patients received four EIA cycles consisting of etoposide, ifosfamide and doxorubicin combined with RHT followed by surgical resection and adjuvant treatment. The overall objective response (OR) rate was 17%, with one complete (2%) and eight partial (15%) responses. In addition, 13 minor responses (25%) were seen. At time of surgery, complete necrosis (pCR) occurred in 6 patients and >75% necrosis (favourable histological response (FHR)) in 12 patients. At the completion of protocol treatment, 36 patients were rendered disease-free which was significantly associated with the initial radiographic and/or pathological tumour response (P=0.004). Treatment-related toxicity was acceptable overall. At a medium follow-up of 82 months, local treatment failure occurred in 33 patients, median overall survival (OS) was 52 months, and the 5-year survival rate was 49% (95% confidence interval (CI): 36-61%). OS which did not differ for extremity versus non-extremity STS (P=0.21) was better for patients responding to EIA combined with RHT (P<0.01)." [4]  [Note: these were ADVANCED or recurrent sarcomas, not stage one, and the survival statistics reflect that. ] 

"The efficacy of thermochemotherapy in adult patients with primary, recurrent or inadequately resected non-metastatic high-risk soft-tissue sarcomas (STS) was assessed. 54 patients were prospectively treated with four cycles of etoposide, ifosfamide and doxorubicin (EIA) combined with regional hyperthermia (RHT) followed by surgery, another four cycles of EIA without RHT and external beam radiation. The objective response rate was 16% and at a median follow-up time of 57 months, the 4-year estimated rates of local failure-free survival (LFFS), distant metastasis-free survival (DMFS), event-free survival (EFS) and overall survival (OS) were 59% ... 59% ... 26% ... and 40% ...respectively. OS was in favour of patients responding to neoadjuvant treatment .... In comparison to a preceding ... study including pre- and postsurgical thermochemotherapy (RHT-91), at a 4-year follow-up the RHT-95 study cohort showed an inferior LFFS rate (P=0.027), but this did not affect DMFS (P=0.558) or OS (P=0.126). Hence, postsurgical thermochemotherapy seems critical for local tumour control without affecting survival."  [5]


<b>Hyperthermic Intraoperative Intraperitoneal Chemotherapy / Hyperthermic Total Abdominal Perfusion</b>
Hyperthermic intraoperative intraperitoneal chemotherapy for peritoneal sarcomatosis involves treating the patient regionally with hyperthermia, while also bathing the abdominal cavity and its contents in a solution of chemotherapy agents, during an operation.  [17]

Hyperthermic intraperitoneal intraoperative chemotherapy using doxorubicin and cisplatin, combined with cytoreductive surgery was investigated as a new multimodal treatment for peritoneal [abdominal] ... sarcomatosis. Thirty-one patients were enrolled in a phase I trial.  During an operation, tumor bulk was removed leaving only nodules of 3mm or less. They concluded: "Cytoreductive surgery combined with HIIC is an expensive but feasible therapeutic approach for locally advanced abdominal tumors. Because our preliminary findings for local disease control are encouraging," they will consider further investigation.  [1]  
 
"Surgery remains the principal modality of therapy in the management of primary and recurrent retroperitoneal STS."  33 patients [with retroperitoneal STS] underwent complete resections.  Eleven of them received locoregional chemotherapy by HTAP. "The overall cumulative 5-year survival rates in patients with stage IIA and advanced disease were 82% and 22%, respectively ... tumor stage, use of HTAP and type of operation were found to have significant influence on overall survival (P<0.05)." Results showed "complete resection along with HTAP chemotherapy may improve survival in patients with retroperitoneal STS. These phase II data could be used to support the initiation of a phase III trial to test HTAP in patients submitted to complete resection of retroperitoneal STS." [36]

Leila of the LMS List, in Brasil, underwent this procedure because of continuous recurrence of her Uterine LMS.  &&url

She states: Hi Doreen,

     I am so glad you wrote me! I have high grade LMS that has caused me eight surgeries in the last two years. The recurrences were happening in interval of four months each. I almost had lost hopes for treatment and was expecting for the worst. In 31st October of 2001, I had a major surgery performed with hyperthermic and intraoperative chemotherapy. Since then I am clear. That is, for me, a paradise. Now, on the 14th of June, I will do new CT scans and I hope to still be clear.

What really makes me happy is the fact that you are paying attention to hyperthermia as an instrument for controlling sarcomatosis. You have asked about the temperature. Well, they heated my abdominal cavity at 43 deg centigrade.  The surgery lasted 16 hours and the entire tumor between bladder and sigmoid was removed. For one hour and half the hyperthermic chemo was done with the drug Mitomicin at 43 deg C. They put four catheters intra-abdominally for the postoperative chemo at room temperature. Afterwards, the abdomen was closed and I went to a Intensive Care Unity, where I stayed for five days, two of them receiving chemo intra-abdominal with the drug Cisplatin in room temperature.  Doctor Sugarbaker from Washington developed this technique.  &&url 

I have side effects after the surgery with hyperthermic and intraoperative chemo. I stayed for two months with problems in my hands (peripheral neuropathy) and in February I stayed for eight days in the hospital with intestinal blockage. But now I am very well, and especially: I am clear! I pray every day to continue clear.  In my case, the hyperthermia was a miracle.
