Risk factors and outcome for children, adolescents and young adults with grossly resected (IRS group I/II) non-rhabdomyosarcoma soft tissue sarcomas

Background The role of adjuvant therapy after gross tumor (complete or microscopically incomplete) resection in children, adolescents and young adults with non-rhabdomyosarcoma soft tissue sarcomas (NRSTS) remains controversial. Patients and methods Clinical characteristics of patients aged 0-21 years with localized NRSTS who underwent microscopically complete (IRS group I) or incomplete (IRS group II) resection prospectively enrolled in European and North American cooperative group trials from 1991 to 2018 were analyzed. Results A total of 756 patients were enrolled in the ARST0332 ( n = 27), CWS-91, -96 and -2002P ( n = 266), MMT-95 ( n = 161) and NRSTS-2005 ( n = 302) studies. Median age at diagnosis was 12.6 years [interquartile range 8.7, 15.0]. Tumors were most commonly <5 cm ( n = 465; 64%), located in the extremity ( n = 464; 61%) and had T1 stage ( n = 579, 77%). Most common tumor histotypes were synovial sarcoma ( n = 249; 33%) and malignant peripheral nerve sheath tumor (MPNST, n = 107; 14%). Patients underwent IRS-I ( n = 434; 57%) or IRS-II ( n = 322; 43%) resection, followed by chemotherapy ( n = 302; 41%) and/or local radiotherapy ( n = 241; 33%). An additional resection was carried out in 17 IRS-II tumors, resulting in negative margins for all. Chemotherapy was more commonly added for IRS-II ( n = 193; 61%) than IRS-I tumors ( n = 109; 26%). Five-year overall survival was 88.8% (95% confidence interval, 86.5-91.2), and progression/relapse-free survival was 77.1% (74.1-80.3). Significant unfavorable prognostic factors were older age (>13 years), axial, T2 stage and large (>5 cm) tumors, MPNST histotype and high pathologic grade. Conclusion Outcome is favorable for patients with grossly resected NRSTS. Patients with unfavorable risk factors have a worse prognosis. The authors propose an algorithm to inform treatment decisions.