Primary Tumor Failure After Definitive Chemoradiation in Locally Advanced Non-Small Cell Lung Cancer: A Brief Report on the Implications for NRG LU-008

This is the authors' abstract. We don't add key points for this paper.

Introduction:Locoregional failure (LRF) after definitive chemoradiation for locally advanced non-small cell cancer (LA-NSCLC) is suboptimal.LU-008 aims to improve local control through SBRT boost.We quantified first-failure patterns after modern chemoradiation and determined if patients with LRF had LU-008 eligibility.Methods: Consecutive adults treated with definitive chemoradiation (> 60 Gy, 1.8-2 Gy/fraction immunotherapy) from 2011-2021 at a single institution were reviewed.First progression was classified as isolated LRF, isolated DF, or synchronous LRF+DF; LRF was sub-classified as primary tumor failure (PTF), regional failure (RF), or PTF+RF.PTF was defined radiographically within the 90% isodose of the primary-tumor GTV.LU-008 eligibility (tumor < 7 cm, 1 node, primary > 2 cm from nodal CTV) was applied retrospectively.Cumulativeincidence functions used Fine-Gray models with death as a competing risk.Results: Among 786 patients (median follow-up 66.9 months), 484 first failures occurred: 109 isolated LRF, 122 synchronous LRF+DF, and 253 isolated DF.Isolated PTF occurred in 40 patients (5.1%); PTF+RF in 29 (3.7%).Five-year cumulative incidence was 52% for any DF, 42% for any LRF, 25% for any isolated LRF (DF-free), 17% for any PTF (PTF+RF, DF-free), and 10% for isolated PTF.Only 28 of 69 PTF-containing LRFs (41%) met LU-008 criteria.Failure patterns were similar for patients who received immunotherapy consolidation.Overall, 129 of 231 patients with any LRF (56 %) were LU-008-ineligible, commonly due to central or ultracentral primaries, and experienced earlier PTF (median 12.1 vs 22.4 mo, p = 0.002).PTF risk rose steeply with primary-tumor GTV up to ~200 cc. Conclusions:While DF is the most common site of failure, LRF remains a problem.Many PTFs after chemoradiation occur in patients who would be excluded from LU-008, mainly because of central tumor location.This high-risk subset of central primaries may require alternative escalation or combined-modality strategies beyond the proposed LU-008 paradigm.