Thromboembolic events associated with thalidomide and multimodality therapy for soft tissue sarcomas: Results of RTOG 0330

Introduction. RTOG 0330 was developed to address the toxicity of RTOG 9514 and to add thalidomide (THAL) to MAID chemoradiation for intermediate/high grade soft tissue sarcomas (STSs) and to preoperative radiation (XRT) for low-grade STS. Methods. Primary/locally recurrent extremity/trunk STS: ≥8cm, intermediate/high grade (cohort A): 5cm, low grade (cohort B). Cohort A: 3 cycles of neoadjuvant MAID, 2 cycles of interdigitated THAL (200mg/day)/ concurrent 22 Gy XRT, resection, 12 months of adjuvant THAL. Cohort B: neoadjuvant THAL/concurrent 50Gy XRT, resection, 6 months of adjuvant THAL. Planned accrual 44 patients. Results. 22 primary STS patients (cohort A/B 15/7). Cohort A/B: median age of 49/47 years; median tumor size 12.8/10cm. 100 preoperative THAL/XRT and surgical resection. Three cycles of MAID were delivered in 93 cohort A. Positive margins: 27 cohort A/29 cohort B. Adjuvant THAL: 60 cohort A/57 cohort B. Grade 3/4 venous thromboembolic (VTE) events: 40 cohort A (1 catheter thrombus and 5 DVT or PE) versus 0 cohort B. RTOG 0330 closed early due to cohort A VTE risk and cohort B poor accrual. Conclusion. Neoadjuvant MAID with THAL/XRT was associated with increased VTE events not seen with THAL/XRT alone or in RTOG 9514 with neoadjuvant MAID/XRT.