B. Id Said1, A. V. Louie2, S. N. Badiyan3, A. Bang4, A. Bezjak5, K. L. M. Chua6, C. Faivre-Finn7, Y. Geng8, F. M. Kong9, D. Przybysz Jr10, P. M. Putora11, P. M. Schuffenegger12, S. Siva13, M. X. Welliver14, F. McDonald15, and S. G. Chun16; 1Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, ON, Canada, 2Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada, 3Department of Radiation Oncology, UT Southwestern Medical Center, Dallas, TX, 4BC Cancer - Vancouver, Vancouver, BC, Canada, 5Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada, 6National Cancer Centre Singapore, Singapore, Singapore, 7The University of Machester and The Christie NHS Foundation Trust, Manchester, United Kingdom, 8Research Medical Library, The University of Texas MD Anderson Cancer Center, Houston, TX, 9The University of Hong Kong, Hong Kong, China, 10Washington University School of Medicine, St. Louis, MO, 11Kantonsspital St. Gallen, St. Gallen, Switzerland, 12Pontificia Universidad Catolica de Chile, Santiago, Chile, 13Peter MacCallum Cancer Centre, Melbourne, VIC, Australia, 14Department of Radiation Oncology, Comprehensive Cancer Center, The Ohio State University, Columbus, OH, 15The Institute of Cancer Research, London, United Kingdom, 16Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
Purpose/Objective(s): Hypofractionated radiotherapy (hypo-RT) offers potential advantages over conventional RT in locally advanced non-small cell lung cancer (LA-NSCLC), including shorter treatment times and potentially enhanced biological effectiveness. However, systematic appraisals of its efficacy and safety are lacking. Materials/
Methods: A systematic search was conducted on Ovid MEDLINE, Ovid Embase, Wiley Cochrane Library, and ClinicalTrials.gov for English publications from 2010 to January 26, 2023. Prospective studies and clinical trials investigating hypo-RT in LA-NSCLC (> 2 Gy per fraction) delivered alone or in combination with concurrent chemotherapy were included. Outcomes of interest included overall survival (OS), progression free survival (PFS) as well as treatment-related esophageal and pulmonary toxicity. Results: We analyzed 30 studies with 1290 patients, including one randomized controlled trial. The majority of evaluable patients had stage III disease (79%), with most studies utilizing 3D-CRT (n=11), IMRT (n=9), or a combination of both techniques (n=3), while a smaller subset utilized protons (n=4), carbon-ions (n=2), and tomotherapy (n=1). The median RT prescription dose, fraction size and biologically effective dose BED(10) was 60 Gy (range 23-85.5), 3 Gy per fraction (2.2-8.5), and 82 Gy (41-118). The median OS for hypo-RT alone (reported by 10 studies) was 13.6 months (6-46), while the 1-, 2-, and 3-year OS was 77.2% (38-98), 50.9% (38-85), and 32.1% (29-61%), respectively. The median OS in patients treated with concurrent chemotherapy (in 12 studies) was 25.85 months (13-38), with 1-, 2-, and 3-year OS rates reported as 74.75% (50-89), 56.15% (38-68), and 50% (49-61%). The rate of severe (grade 3+) esophageal and pulmonary toxicity in patients receiving chemotherapy ranged from 0% to 17% for both, while for patients treated with hypo-RT alone, the rates were 0% to 9% and 0% to 6%, respectively. Conclusion: Hypo-RT for LA-NSCLC is a safe and viable treatment option in carefully selected patients unable to undergo standard treatment with conventionally fractionated chemoradiation. However, its application requires careful patient selection, specialized technical expertise and stringent dose constraints, especially when combined with chemotherapy. The integration of hypo-RT with emerging treatments, including immunotherapy and particle therapy, presents a promising area for future research, although optimal protocols remain to be established.