Stereotactic MRI Guided Adaptive Radiotherapy: a pooled analysis of a master prospective trial

Abstract

Background Master clinical trial protocol structures offer administrative, procedural and statistical advantages but have not been applied in assessing new radiotherapy devices. Herein, we report on a pooled analysis from a first-of-kind master trial evaluating stereotactic MRI-guided adaptive radiotherapy (SMART). Methods Subjects were enrolled on a prospective master protocol evaluating SMART for multiple oncologic indications. CTCAE v5 toxicities, patient reported outcome measures (PROMs), and treatment efficiency metrics were assessed across the entire cohort and in anatomic subsets. Results 193 subjects were enrolled into 20 sub-protocols for different SMART indications. Data were analyzed from the first 161 subjects. The median time from subprotocol amendment submission to activation was 70.5 days (range 63-93). All completed phase I sub-protocols (n = 9) met the primary endpoints of safety and feasibility. The risk of grade 3+ toxicity was 1.9% (95%CI 0.4-5.3%), 7.1% (95%CI 0.9-23.5%), 1.8% (95%CI 0.05-9.6%) and 0% (95%CI 0.0-4.7%) in the overall cohort and thoracic, abdominal and pelvic subsets, respectively. PROMs (PROMIS-10) during and after SMART were unchanged from baseline in all subsets. SMART delivery efficiency improved over the study period (first vs final 3 months: 78.5 vs 48.2 minutes, p < .001). Adaptive planning performed for 771 fractions resulted in clinically significant plan improvements in 93.0% of fractions (52.7% for organ-at-risk sparing, 20.5% for target coverage and 19.8% for both). Conclusions SMART is feasible and safe for multiple thoracic, abdominal and pelvic radiotherapy indications. The master protocol platform offers an adaptable approach for assessment of new oncologic treatment technologies applicable to multiple indications. Clinical Trial NCT04115254