Outcomes of Children With Orbital Rhabdomyosarcoma, 1991-2016: A Report From the International Soft Tissue Sarcoma Consortium (INSTRuCT).

BACKGROUND: Patients with orbital rhabdomyosarcoma (ORMS) historically have 10-year overall survival (OS) rates > 85% with multimodal therapy. We aimed to determine if favorable outcomes were preserved on contemporary international cooperative group trials in the context of shifting treatment approaches, including chemotherapy reduction and changes in the indications for radiation therapy (RT) and RT dose. METHODS: We identified patients with newly diagnosed ORMS (orbit and eyelid sites) from 11 North American and European cooperative group trials from 1991 to 2016. Demographic and clinical characteristics were collected. Event-free survival (EFS) and OS were calculated from the time of trial enrollment except post-relapse OS, which was calculated from the time of recurrence. RESULTS: Of 679 patients with ORMS, the 10-year EFS and OS were 74.6% (71.0%-77.8%) and 92.9% (90.6%-94.8%). In patients with Group III, non-alveolar ORMS (n = 425, 62.6%), the 10-year EFS and OS were 78% (74%-82%) and 95% (92%-97%), respectively. Anaplasia was associated with inferior 10-year EFS (79.8% vs. 84.2%, p = 0.03), and the 10-year post-recurrence OS was 78% (67%-86%). Patients with localized alveolar ORMS (n = 81; PAX::FOXO1 fusion positive in 13/33 patients with known fusion status) had a 10-year EFS of 71% (60%-80%) and OS of 88% (79%-94%). Infants < 1 year (n = 22) had a 5-year EFS of 31% (12%-52%) and OS of 61% (37%-78%). Metastatic ORMS (age ≥1) was rare (n = 5; 4/5 alveolar histology), and no patients survived more than 4 years. CONCLUSION: Favorable survival in patients with ORMS was preserved despite shifts in treatment strategies. Patients with localized alveolar ARMS and recurrent ORMS had favorable survival. Infants < 1 year and those ≥ 1 with metastatic disease had poor prognosis and require new therapeutic approaches.