Risk-based treatment for nonrhabdomyosarcoma soft tissue sarcomas (NRSTS) in patients under 30 years of age: Children’s Oncology Group study ARST0332.

Abstract

10008 Background: NRSTS comprise ~4% of childhood cancer but only 3 prospective clinical trials have been performed in the U.S. in the past 40 years. Tumor grade, size, resection potential, and extent of disease influence outcome. ARST0332 evaluated a risk-based treatment strategy for young NRSTS patients designed to limit therapy for low-risk disease and to test a combined chemoradiotherapy approach for unresected higher risk disease. Methods: Newly diagnosed NRSTS patients < 30 years old were assigned to 4 treatment arms based on risk: A (surgery only): grossly excised low-grade and ≤ 5 cm widely excised high-grade tumor; B (55.8 Gy radiotherapy [RT]): ≤ 5 cm marginally resected high-grade tumor; C (ifosfamide/doxorubicin chemotherapy + 55.8 Gy RT): > 5 cm grossly resected tumor ± metastases; D (neoadjuvant ifosfamide/doxorubicin chemotherapy and 45 Gy RT, then surgery and an RT boost based on margins): > 5cm unresected tumor ± metastases. Results: 551 eligible patients were enrolled on Arm A (212), B (19), C (120), and D (200). Most common subtypes were synovial sarcoma (149), malignant peripheral nerve sheath tumor (60), and undifferentiated sarcoma (48). Tumors were 53% extremity, 72% high grade, 76% > 5 cm, and 14% metastatic. There were no toxic deaths; 2% had unexpected grade 4 adverse events. By treatment arm, at a median follow-up of 2.6 years, estimated 3-year event-free survival was: A 91%, B 79%, C 68%, D 52% and overall survival was: A 99%, B 100%, C 81%, D 66%. Conclusions: This novel risk-based treatment strategy segregated patients into clinically meaningful risk groups and produced outcomes similar to or slightly better than historical controls while using RT less frequently and at lower doses. This study defines the new standard of care for pediatric NRSTS against which future interventions should be compared. Clinical trial information: NCT00346164.