Neoadjuvant Concurrent Chemoradiation for High-Risk Adult Soft Tissue Sarcoma - 19 Years of a Single Institution Experience

Resumo

Introduction: Although Surgery and Radiation therapy (RT) represent standard therapy in High-Risk Soft Tissue Sarcomas (HRSTS), its sequence remains controversial. Neoadjuvant chemoradiation improves survival in patients with HRSTS. Tumor size, surgical margins, and pathologic complete response (pCR) are prognostic factors with unknown significance.
Material and Methods: Retrospective analysis of 25 patients with stage III HRSTS, who underwent neoadjuvant treatment (2002-2020), with 16 receiving preoperative chemoradiation (Adriamycin 90mg/m2 + Dacarbazine 900mg/m2 + Ifosfamide 10mg/m2 ± Vincristin 2mg bolus; 4500-5400cGy/25-30fr) and surgery. Clinical and pathologic data and treatment-related toxicities were assessed. Survival and univariate analyses were performed using Kaplan-Meier Method and Cox regression (a=0.05).
Results: Sixteen patients were included: 68.8% male, median age 44 [18-78] years. Median tumor size was 12 [5-25] cm and 68.8% were extremity sarcomas. Four (25%) patients had pleomorphic liposarcoma and 25% spindle cell sarcomas. Most patients (87.5%) had high grade (G3) tumors. No patient interrupted RT. Median of 7 [5-10] chemotherapy cycles, with cycle postponement in 18.8% patients. Surgery (75% wide excision) occurred on a median of 2 [1-9] months after RT and was uncomplicated in 68.8% (25% wound dehiscence, 12.5% wound necrosis and 6.3% osteitis). Fourteen (87.5%) patients presented negative surgical margins (R0) and 25% pathologic complete response (pCR), with 60% of resected specimens showing ≥90% pathologic necrosis. Eight (50%) patients had hematological toxicity G3-4: 18.8% anemia; 50% leukopenia; 25% thrombocytopenia. Eleven (68.8%) patients presented radiation-induced dermatitis (62.5%, G1-2). For a median follow-up time of 6.3 years [8 months – 18 years], 3 and 5-year survival rates were: Overall Survival and Disease-Free Survival were equivalent (62.5% and 56.3%); Local Recurrence-Free Survival (LRFS) of 92.9%; Distant Disease-Free Survival of 68.8% and 61.9%; Disease-Specific Survival of 75% and 67.5%, respectively. Microscopic positive margins influenced LRFS (50% vs 100%; p=0.014). DSS was non-significantly influenced by pCR (p=0.161) and largest tumor dimension≤10cm (p=0.332).
Conclusion: Neoadjuvant chemoradiation is an acceptable strategy in HRSTS, with comparable survivals to reported data and manageable acute toxicity. Complete resection rates were high and associated with improved LRFS. Smaller tumors (≤10cm) and achieving pCR appears to be favorable prognostic factors.