HIGH GRADE SOFT TlSSUE SARCOMAS OF THE EXTREMITIES TREATED WITHOUT RADITATION. RESULTS FOLLOWING INDUCTION CHEMOTHERAPY AND SURGICAL RESECTION

Robert M. Henshaw, MD (Washington Cancer Inst., 110 Irving St NW, Washington DC 20010)

Induction chemotherapy for soft tissue sarcomas, based upon experience gained with bone sarcomas, can produce dramatic tumor necrosis, raising the question of whether radiation is necessary for these patients. Purpose: To review the clinical results of patients with high-grade extremity soft tissue sarcomas treated with induction chemotherapy and surgical resection.

Methods: A single institution interdisciplinary team specializing in sarcomas treated all patients included in this study. Core needle biopsies and routine staging studies were performed to confirm diagnosis. Only patients with non-metastatic high-grade STS of the pelvis and extremities were eligible. Pts were offered conventional surgery and radiation only if an amputation could be safely avoided. Chemotherapy: 2 protocols were used during the period of this study. Both included 2 cycles of intra-arterial cis-platinum and continuous IV adriamycin prior to surgical resection. The second protocol also included a cycle of adriamycin and ifosfamide. Pts received additional cycles postoperatively for a total of 6 cycles in both groups. Surgery: Following chemo and restaging, all pts were offered a limb sparing resection when appropriate. Standard principles of resection were followed. Detailed histologic evaluation of chemotherapy effect and surgical margins was performed on all specimens. Radiation: Pts judged to be at high risk of local recurrence because of either prior attempted surgical resection before referral, low percentage of tumor necrosis, or close surgical margins were offered radiation. Only pts that did not receive radiation are included in this study.

Results: 46 pts between 1985 and 1998 were treated with induction chemotherapy. 13 pts who received adjuvant radiation and 1 pt who died prior to surgical resection were excluded. The most common tumor was MFH or liposarcoma. The most common location was the proximal thigh. All tumors were Enneking stage IIB with the exception of a IIA MFH of the hand. 30/32 pts underwent a successful limb sparing procedure. Median time from surgical resection is 4.5 yrs. 4/32 pts developed metastatic disease, of whom 3 have died. 2/32 pts developed local recurrence; both were treated with wide re-resection and adjuvant radiation. Of these pts, 1 is alive free of disease at 4 yrs and 1 died of metastatic disease 10 yrs post op. 1 pt has been diagnosed with pancreatic CA as a second primary, but remains alive and free of sarcoma. Disease free survival was 77% and overall survival was 86% at 5 years by Kaplan Meier analysis.

Conclusions: 1. Intensive induction chemotherapy with adriamycin, ifosfamide and cis-platinum can be extremely effective for high-grade STS, permitting limb sparing surgery in many pts that might otherwise require amputation 2. Radiation is not necessary for those pts who have a good response to chemotherapy and negative wide margins following surgical resection. 3. All pts with large, deep, high-grade STS of the extremities should be considered candidates for induction chemotherapy.