A Failure Pattern Analyses in NSCLC Patients Received Immuno-Radiotherapy and a Dosimetric Feasibility Study of a Three-Ladder Radiotherapy Strategy.

[BACKGROUND] This study aimed to analyze failure patterns in stage III non-small cell lung cancer (NSCLC) patients treated with immuno-radiotherapy and to dosimetrically evaluate a novel three-ladder radiotherapy (3L-RT) strategy designed to address the observed local control deficit.

[METHODS] Clinical outcomes and failure patterns were retrospectively analyzed in 89 consecutive stage III NSCLC patients (2020-2023) treated with simultaneous integrated boost intensity modulated radiotherapy (SIB-IMRT) combined with immunotherapy. Separately, a dosimetric planning study was conducted to compare the feasibility of the proposed 3L-RT strategy (prescribing 74 Gy to GTV, 60 Gy to PTV-g, and 54 Gy to PTV-c) against conventional radiotherapy (PTV-c 60 Gy) on a distinct patient cohort, with and without 4D-CT simulation.

[RESULTS] Median follow-up was 23.2 months. Median progression-free survival (PFS) and overall survival (OS) were 19.4 and 41.1 months, respectively. Immuno-neoadj independently predicted superior PFS (HR: 0.32, p < 0.001) and OS (HR: 0.25, p = 0.013). Among 43 progression events (48.3%), local failure (53.5%) predominated, driven by primary tumor progression. Distant metastases occurred in 51.2% (pulmonary, osseous, and intracranial sites most frequent). In the dosimetric comparison, the 3L-RT strategy reduced cardiopulmonary exposure versus conventional plans: lung V20 decreased from 20.2% to 19.6%, cardiac V30 from 9.55% to 8.7%, and effective dose to immune cells (EDIC) from 3.9 Gy to 3.7 Gy (p < 0.001). Dose reductions persisted with 4D-CT integration.

[CONCLUSION] Within the studied clinical cohort, immunotherapy combined with SIB-IMRT correlates with favorable survival, yet local failure remains a predominant challenge. The proposed 3L-RT strategy is dosimetrically feasible, enabling targeted GTV dose escalation while sparing critical organs. These dosimetric findings support the rationale for future prospective clinical trials to evaluate whether this strategy can improve local control and survival outcomes.