Prospective Feasibility and Phase 1/2 Trial of Preoperative Proton Beam Therapy With Concurrent Chemotherapy for Resectable Stage IIIA or Superior Sulcus Non-Small Cell Lung Cancer

For patients with locally advanced non-small cell lung cancer (LA-NSCLC), a recognized management paradigm is trimodality therapy; this refers to neoadjuvant chemoradiation therapy (CRT) followed by resection. 1 Albain KS Swann RS Rusch VW et al. Radiotherapy plus chemotherapy with or without surgical resection for stage III non-small-cell lung cancer: A phase III randomised controlled trial. Lancet. 2009; 374: 379-386 Abstract Full Text Full Text PDF PubMed Scopus (1217) Google Scholar ,2 Albain KS Rusch VW Crowley JJ et al. Concurrent cisplatin/etoposide plus chest radiotherapy followed by surgery for stages IIIA (N2) and IIIB non-small-cell lung cancer: Mature results of Southwest Oncology Group phase II study 8805. J Clin Oncol. 1995; 13: 1880-1892 Crossref PubMed Scopus (825) Google Scholar Trimodality management may be challenging in older patients with significant comorbidities, suboptimal performance statuses, and extensive smoking histories. Proton beam therapy (PBT) is an attractive option for potentially reducing toxicities of neoadjuvant CRT. 3 Lazarev S Rosenzweig K Samstein R et al. Where are we with proton beam therapy for thoracic malignancies? Current status and future perspectives. Lung Cancer. 2021; 152: 157-164 Abstract Full Text Full Text PDF PubMed Scopus (5) Google Scholar A randomized trial in esophageal cancer found reduced total toxicity burden with neoadjuvant PBT versus intensity modulated radiation therapy (IMRT). 4 Lin SH Hobbs BP Verma V et al. Randomized phase IIB trial of proton beam therapy versus intensity-modulated radiation therapy for locally advanced esophageal cancer. J Clin Oncol. 2020; 38: 1569-1579 Crossref PubMed Scopus (147) Google Scholar Akin to the benefits of PBT in the neoadjuvant setting for esophageal cancer, neoadjuvant PBT for LA-NSCLC could allow safe delivery of the desired prescription dose while maintaining low doses to organs at risk, which may influence postoperative outcomes, functional status, and/or quality of life. 5 Verma V Simone 2nd, CB Mishra MV. Quality of life and patient-reported outcomes following proton radiation therapy: A systematic review. J Natl Cancer Inst. 2018; 110: 341-353 Crossref Scopus (74) Google Scholar