Association between radiotherapy protocol variations and outcome in the CONVERT trial

Background: Radiotherapy quality assurance (QA) is integral to radiotherapy delivery. Here we report comprehensive contouring, dosimetry, and treatment delivery QA, describe protocol compliance, and detail the impact of protocol variations on acute grade >= 3 toxicity, progression free survival (PFS), and overall survival (OS) in the phase III CONVERT trial.Materials/Methods: Radiotherapy planning data from one hundred randomly selected patients were requested. Members of the CONVERT Trial Management Group (TMG) recontoured the heart, lung, and spinal cord organs at risk (OAR) according to the trial guideline. The existing radiotherapy plan were re-applied to the new structures and the new dosimetric data were recollected. Compliance with radiotherapy QA components were recorded and radiotherapy QA components were pooled into protocol variations: acceptable, acceptable variation, and unacceptable variation. Univariable analysis with a Cox proportional hazards model established the relationship between protocol variations and patient outcome.Results: Ninety-three cases were submitted for retrospective radiotherapy QA review. Demographics of the radiotherapy QA cohort (n=93) matched the non-QA (n=450) cohort. 97.8% of gross tumour volume (GTV) contours were protocol compliant. OAR contours were non-compliant in 79.6% instances of the heart, 37.6% lung, and 75.3% spinal cord. Of the non-compliant heart contours, 86.5% and 2.7% had contours caudal and cranial to the protocol-defined heart borders. 10.8% did not include the pericardial sac and 2.7% did not include the anterior aspect of the pericardium. Eleven (11.8%) submissions exceeded protocol-defined dosimetric heart constraints; six of which were only noted on the application of protocol-compliant contours. Unacceptable variations were not associated with an increase in grade 3 toxicity (p=0.808), PFS (p=0.232), or OS (p=0.743).Conclusion: Non-protocol compliant heart contours were associated with increased dose delivered to the heart OAR, with 11.8 % of submitted heart structures exceeding protocol-defined constraints. In this QA cohort of patients with small cell lung cancer, unacceptable variations were not associated with acute grade >= 3 toxicity, PFS, or OS. Radiotherapy QA remains the cornerstone of high-quality radiotherapy delivery and should be embedded into clinical trial and non-clinical trial practice; clinical trials should report standardised radiotherapy QA parameters alongside trial outcomes.