Design and pre-trial dose planning quality assurance of the Nordic trial of inhomogeneous dose escalated radiotherapy for patients with limited disease small cell lung cancer: NIELS.

Abstract

The NIELS trial will examine if inhomogeneous dose-escalated radiotherapy up to a mean dose of 80 Gy in 40 fractions (fx), twice-daily delivered (BID), for patients with limited disease small cell lung cancer can improve overall survival. Because of the inherent risks of dose-escalation, pre-trial QA is particularly important. This study aims to examine the feasibility of the NIELS trial planning approach in a multicenter setting. The NIELS trial will randomize patients between standard dose radiotherapy (60 Gy/40fx BID) and inhomogeneous dose-escalated radiotherapy (up to 80 Gy/40fx BID). Five representative patient cases were distributed to seven Nordic centers for pre-trial QA planning of a standard and an escalated dose plan. Targets for escalation were primary tumor (GTVp) and involved lymph nodes (GTVn). We evaluated inter-center variation in achievable dose-escalation and doses to organs at risk (OAR). All targets could be escalated beyond the standard dose, with a median mean dose of 79.6 Gy [76.9-81.0] and 75.8 Gy [68.3-81.1] for GTVp and GTVn. Some targets could not be fully escalated due to OAR proximity. Three separate breaches of mandatory OAR constraints were observed in 35 escalated dose plans. There was a statistical difference in mean lung dose between standard and escalated plans, though clinically small, with a median inter-patient difference of 0.3 Gy. There were no differences in mean doses to the heart and esophagus. Inhomogeneous dose-escalation as planned in the NIELS trial is feasible, and the dose-escalation can be performed respecting the OAR constraints in a multi-center setting.