Abstract
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: ≥8 cm, intermediate/high grade (cohort A): >5 cm, low grade (cohort B). Cohort A: 3 cycles of neoadjuvant MAID, 2 cycles of interdigitated THAL (200 mg/day)/concurrent 22 Gy XRT, resection, 12 months of adjuvant THAL. Cohort B: neoadjuvant THAL/concurrent 50 Gy 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 12.8/10 cm. 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.
Highlights
Radiation Therapy Oncology Group (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
Due to the known thromboembolic risks and side effects associated with thalidomide, exclusion criteria for both cohorts included a known history of deep vein thrombosis or pulmonary embolus, a known hypercoagulable disorder, baseline Common Terminology Criteria for Adverse Events (CTCAE) v3.0 grade 2 or greater fatigue or other global neurocognitive symptomatology, taking sedating drugs, not agreeing to avoid sedating illegal “recreational” drugs or alcohol greater than one drink per day, or known acquired immune deficiency syndrome
Even excluding one event that occurred prior to initiating thalidomide and one catheterrelated event, the rate of venous thromboembolic (VTE) was still 27%. As this rate is comparable to the high rates of VTE seen with combination chemotherapy/thalidomide for other cancers, daily low-dose aspirin did not seem to effectively reduce the VTE risk
Summary
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. Cohort A: 3 cycles of neoadjuvant MAID, 2 cycles of interdigitated THAL (200 mg/day)/concurrent 22 Gy XRT, resection, 12 months of adjuvant THAL. Cohort B: neoadjuvant THAL/concurrent 50 Gy XRT, resection, 6 months of adjuvant THAL. In 1995, the Radiation Therapy Oncology Group (RTOG) initiated 9514, a phase II study of neoadjuvant MAID (Mesna, Adriamycin, Ifosfamide, Dacarbazine) chemoradiation for high-risk STS of the extremity and body wall. Patients with large (≥8 cm), high-grade STS were scheduled to receive 3 cycles of neoadjuvant MAID chemotherapy with interdigitated preoperative radiation therapy (44 Gy given in two 22 Gy courses) followed by surgical resection and additional cycles of adjuvant MAID chemotherapy. Grade 4 toxicity occurred in 81% of patients, 13% experienced significant wound complications, and there were 3 treatment-related deaths
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