Prospective clinical implementation of the robust optimization planning technique in long-course photon radiotherapy treatment for lung cancer.

Abstract

Optimizing photon radiotherapy techniques is crucial in the integrated treatment of lung cancer. We prospectively evaluated the clinical implementation of the robust optimization (RO) technique in comparison with the conventional planning target volume (PTV) optimization (PTVO) technique. Unresectable stage III non-small cell lung cancer (NSCLC) or limited small cell lung cancer patients undergoing definitive radiotherapy were eligible. For each patient, 2 planning approaches were compared: (1) internal target volume (ITV)-based RO, with 0.5 cm setup uncertainties in cardinal directions around ITV and (2) PTVO, with PTV = ITV+0.5 cm isotropic expansion. Comparison included nominal and robust target coverage (TC), healthy tissue sparing, and, for NSCLC patients, estimated dose to immune cells (EDIC) and normal tissue complication probability (NTCP) values for pulmonary, esophageal toxicity, and 24-month mortality. Robustness evaluation (RE) acceptance criteria were ITV V95% ≥ 95% and spinal cord maximum dose < 45 Gy in all perturbed scenarios. Each enrolled patient was actually treated with the plan (RO or standard PTVO) that was judged superior in terms of TC and organs at risk (OAR) sparing. The Wilcoxon test was used for data analysis. p < 0.05 was considered statistically significant. Between June 2024 and June 2025, 24 patients were prospectively enrolled. Nominal TC metrics were comparable between RO and PTVO. Lungs, heart, and esophagus doses were significantly reduced with RO. RO significantly reduced EDIC (p = 0.002), pulmonary (p = 0.0015), and esophageal (p = 0.003) NTCP values. TC and cord maximum dose acceptance criteria at RE were fulfilled in 99.4%/99.4% and in 100%/91% of the perturbed scenarios for RO and PTVO, respectively. At planning comparison, the RO was selected for the actual clinical treatment and delivery in 21 (87%) patients. The first clinical implementation of RO for lung cancer radiotherapy was feasible and promising; RO represents a valid alternative to PTVO in this setting.