Time to broaden the eligibility criteria in pediatric oncology trials? An analysis of patients with rhabdomyosarcoma non-eligible to the EpSSG RMS2005 trial

Purpose Clinical trials include a series of eligibility and exclusion criteria that define the study population to reduce inter-patient heterogeneity and increase safety. Little is known about children with oncological diseases excluded from trials because they do not satisfy these criteria. We analysed the eligibility criteria adopted in the European paediatric Soft tissue sarcoma Study Group RMS2005 study and the survival of non-eligible patients. Patients and Methods RMS2005 run from 10/2005 to 12/2016. Eligibility criteria were age ≤25 years; pathologically proven diagnosis of rhabdomyosarcoma (RMS); no evidence of metastases; no pre-treatment; no pre-existing conditions preventing treatment; no previous malignant tumours and an interval between diagnostic surgery and the start of treatment ≤8 weeks. Clinical characteristics, 5-year progression-free survival (PFS), and overall survival (OS) were analysed for eligible and non-eligible patients. Results The 79 non-eligible patients (4.3% of registered patients) were older than eligible patients (p<0.0001), with RMS arising in favourable sites (p=0.004) and completely resected at diagnosis (p<0.0001). PFS for non-eligible vs. eligible patients was 67.1% (95%CI 55.3-76.5) vs. 71.5% Journal Pre-proof (95%CI 69.3-73.6) (p=0.23) and OS 77.1% (95%CI 65.7-85.1) vs. 80.4% (95%CI 78.4-82.3) (p=0.12), respectively. Patients with a delayed start of treatment or pre-treated had significantly better PFS than those with a pre-existing condition (p=0.0004). Conclusion: non-eligible patients data should be systematically collected. This will be important to confirm that trial eligibility criteria for patients with RMS could be modified without jeopardizing results and increasing study enrolment and generalizability of results.