Radiotherapy quality assurance outcome and its correlation with survival in the SIOPEN High-Risk Neuroblastoma trial (HR-NBL1/SIOPEN). A report from the radiotherapy committee

Objectives Local control in high-risk neuroblastoma relies on effective multi-modality treatment, including radiotherapy. We evaluated the quality of radiotherapy delivered in the SIOPEN High-Risk Neuroblastoma trial (HR-NBL1/SIOPEN, EUDRACT 2006-001489-17) and investigated whether this correlated with survival. The protocol treatment was 21 Gy in 1.5 Gy fractions to the pre-operative primary tumour volume. Methods Radiotherapy data were submitted via the trial data centre website, SIOPEN-R-NET, or QUARTET platform. At least two members of the radiotherapy committee retrospectively performed a Radiotherapy Quality Assurance (RTQA) review which evaluated plan parameters including prescription and fractionation, delineations and dosimetry for target and normal tissue structures, as well as treatment technique and overall dosimetry against protocol requirements. Plans were rated as per protocol, justified, or unjustified deviation with no harm likely or potential for harm. Potential for harm indicates possible impact on local control or morbidity. A statistical analysis for correlation between the RTQA outcome and survival was performed. Results 2034 patients received radiotherapy, of which 236 (11.6%) had sufficient data for RTQA evaluation and statistical analysis. 112 (47%) cases were per protocol while 62 (26%) had justified and 62 (26%) had unjustified deviations. Cases scored with any potential for harm (n=63, 27%) fared significantly worse in terms of 5-year overall survival (OS) compared with per protocol cases; 0.34±0.08, 0.63±0.05 respectively (p=0.029). The RTQA cohort is representative of all patients who received radiotherapy. Conclusion Despite recommendations for RTQA review within the HR-NBL1/SIOPEN protocol, complete radiotherapy data submission rates were poor. Protocol deviations were demonstrated in the majority of cases. Cases with an RTQA outcome including potential for harm demonstrate significantly worse overall survival. Prospective RTQA is therefore recommended to improve both data completeness and protocol compliance and is being implemented in the SIOPEN High-risk Neuroblastoma Trial 2 using the QUARTET platform.