American Radium Society™ Appropriate Use Criteria Systematic Review and Guidelines on Reirradiation for Non-small Cell Lung Cancer Executive Summary

Definitive thoracic reirradiation can improve outcomes for select patients with non-small cell lung cancer (NSCLC) with locoregional recurrences. To date, there is a lack of systematic reviews on safety or efficacy of NSCLC reirradiation and dedicated guidelines. This American Radium Society Appropriate Use Criteria Systematic Review and Guidelines provide practical guidance on thoracic reirradiation safety and efficacy and recommends consensus of strategy, techniques, and composite dose constraints to minimize risks of high-grade/fatal toxicities. Preferred Reporting Items for Systematic Reviews and Meta-Analyses systematic review assessed all studies published through May 2020 evaluating toxicities, local control and/or survival for NSCLC thoracic reirradiation. Of 251 articles, 52 remained after exclusions (3 prospective) and formed the basis for recommendations on the role of concurrent chemotherapy, factors associated with toxicities, and optimal reirradiation modalities and dose-fractionation schemas. Stereotactic body radiation therapy improves conformality/dose escalation and is optimal for primary-alone failures, but caution is needed for central lesions. Concurrent chemotherapy with definitive reirradiation improves outcomes in nodal recurrences but adds toxicity and should be individualized. Hyperfractionated reirradiation may reduce long-term toxicities, although data are limited. Intensity modulated reirradiation is recommended over 3D conformal reirradiation. Particle therapy may further reduce toxicities and enable safer dose escalation. Acute esophagitis/pneumonitis and late pulmonary/cardiac/esophageal/brachial plexus toxicities are dose limiting for reirradiation. Recommended reirradiation composite dose constraints (2 Gy equivalents): esophagus V60 <40%, maximum point dose (Dmax) < 100 Gy; lung V20 <40%; heart V40 <50%; aorta/great vessels Dmax < 120 Gy; trachea/proximal bronchial tree Dmax < 110 Gy; spinal cord Dmax < 57 Gy; brachial plexus Dmax < 85 Gy. Personalized thoracic reirradiation approaches and consensus dose constraints for thoracic reirradiation are recommended and serve as the basis for ongoing Reirradiation Collaborative Group and NRG Oncology initiatives. As very few prospective and small retrospective studies formed the basis for generating the dose constraint recommended in this report, further prospective studies are needed to strengthen and improve these guidelines.