Connective Tissue Oncology Society

2001 CTOS Annual Meeting Posters— Medical Oncology

RTOG 95-14: A PHASE II STUDY OF NEOADJUVANT CHEMOTHERAPY (CT) AND RADIATION THERAPY (RT) IN THE MANAGEMENT OF HIGH RISK, HIGH GRADE, SOFT TISSUE SARCOMAS (STS) OF THE EXTREMITIES AND BODY WALL: A PRELIMINARY REPORT.
W G Kraybill¹, I J Spiro¹, J Harris¹, D S Ettinger¹, A Trotti¹, D R Lucas¹, R Blum², B R Eisenberg¹
¹Radiation Therapy Oncology Group, ²Eastern Cooperative Oncology Group

OBJECTIVE: Introduction and Objectives: Previous reports have demonstrated improved disease- free survival in patients with large high risk STS given neoadjuvant chemotherapy, radiation therapy and post resection chemotherapy when compared with matched controls not given chemotherapy. To evaluate this in the multi-institutional setting, the Radiation Therapy Oncology Group (RTOG) instituted a Intergroup Phase II trial of multi-agent CT and preoperative RT combined with resection in patients with high-grade, high-risk STS of the extremities and body wall. Other objectives were to develop a sarcoma working group for future Phase II and Phase III clinical trials and to develop a tissue repository for future studies.

METHODS: Methods: To assess toxicity, response rates, local control, distant recurrence, survival and complications, 66 patients with primary high grade (II or III of III) STS > 8 cm in maximum diameter were treated with high-dose neoadjuvant CT (Modified MAID) plus G-CSF and preoperative RT and 3 cycles of postoperative CT plus G-CSF. RT 44GY was given in split courses of 22GY between cycles of CT.

RESULTS: Results: The first 45 patients had potentially 1-year follow-up and were eligible for analysis. Of which, forty-two Mo patients were analyzed. Median tumor diameter was 13 cm (Range 8 – 55). Thirty-four (81%)were Grade 3 tumors and 8 (19%) were Grade 2 on a 3 grade system. Median follow-up was 2.35 years (0.23-3.53). Thirty-five patients had clear surgical margins. Seven patients had persistent disease with 4 having involved margins at the time of resection, 1 patient having unresectable tumor due to progression, and 2 patients requiring amputation secondary to disease. Two patients have relapsed locally, 3 patients have relapsed in the lungs, 1 patient developed metastases in the right shoulder and 2 patients developed a second primary. Six patients have died, 3 due to recurrent sarcoma, 2 due to a second primary, and 1 for reasons pending clarification. The observed toxicities were 76% (32) Grade 4 hematologic toxicity and 24% (10) Grade 4 non-Hematologic toxicity. Twenty-nine patients (69%) experienced Grade 4 neutropenia and 12 (29%) Grade 4 thrombocytopenia. Grade 4 skin toxicity in 5 patients (12%) was the most common non-hematologic toxicity. While these expected toxicities are significant, 85% of patients completed preoperative CT, 93% of patients completed preoperative RT and 75% completed postoperative chemotherapy. Delayed wound healing was reported in only 10 patients (26%). Estimated 2-year survival in these high-risk tumors was 95%. There were 42 patients in the survival analysis and only 40 patients in other analysis. There is only survival data on 2 patients. Of the 21 patients excluded from the analysis because they were entered after April 1999, 16 (76%) have experienced grade IV toxicity. Three of 21 (14%) have died, all of causes related to the cancer under study.

CONCLUSION: Conclusions: While this is a preliminary report, the estimated 2-year survival in these very high-risk patients is encouraging with tolerable toxicity.