American Radium Society Appropriate Use Criteria: Accelerated hypofractionated radiotherapy in the multidisciplinary management of locally-advanced non-small cell lung cancer ineligible for concurrent chemotherapy.

INTRODUCTION: While accelerated hypofractionated radiotherapy has increasingly been adopted in the multidisciplinary management of locally-advanced non-small cell lung cancer (NSCLC) ineligible for concurrent chemotherapy, there is a paucity of randomized prospective evidence guiding utilization. Given the marked heterogeneity in the presentations of locally-advanced NSCLC, the American Radium Society (ARS) Thoracic Appropriate Use Criteria (AUC) Panel evaluated the appropriateness of accelerated hypofractionation in the context of multidisciplinary management.

METHODS: Five clinical variants representing manifestations of locally-advanced NSCLC were developed by the 15-member multidisciplinary ARS Thoracic AUC panel. The English-language medical literature was formally reviewed from 2010-2025 and scrutinized for prospective clinical trials utilizing accelerated hypofractionation for concurrent chemotherapy ineligible patients. All case variants were evaluated with respect to use of radiation technique, radiation fractionation, and utilization of programmed death-ligand 1 (PD-L1) immunotherapy with Modified Delphi methodology. Consensus recommendations were reviewed and approved by the ARS Executive Committee and subject to public comment.

RESULTS: The literature review identified 228 articles, of which there were 14 prospective trials/registries including nine Phase I-II trials, four prospective registries, and one randomized Phase III trial. There was consensus that it is appropriate to utilize intensity modulated radiation therapy and proton therapy across presentations of locally-advanced NSCLC, with the aim of constraining the lung V20Gy<30% and heart V40Gy<20% with accelerated hypofractionation. When utilizing 15-fraction accelerated hypofractionation for disease abutting the esophagus or brachial plexus, there was consensus that it is inappropriate to exceed doses of 45-55 Gy. With respect to PD-L1 immunotherapy, there was consensus that consolidative immunotherapy after definitive radiation therapy is appropriate, but that concurrent immunotherapy is inappropriate. There was panel consensus that it may be appropriate to utilize induction PD-L1 immunotherapy prior to radiation therapy in cases of bulky or N3 disease to test disease biology. Across variants, there was consensus that conventionally fractionated radiotherapy to 60 Gy in 30 fractions remains appropriate.

CONCLUSIONS: The ARS Thoracic AUC Panel has provided consensus case-based guidelines on the multidisciplinary management of locally-advanced NSCLC ineligible for concurrent chemotherapy reflecting the heterogeneity of disease presentation in this population. In absence of randomized prospective data demonstrating superiority of accelerated hypofractionation, conventionally fractionated radiotherapy remains an appropriate option.