Improving Outcomes in NSCLC: Optimum Dose Fractionation in Radical Radiotherapy Matters.

Introduction: We analyzed a comprehensive national radiotherapy data set to compare outcomes of the most frequently used moderate hypofractionation regimen (55 Gy in 20 fractions) and conventional fractionation regimen (60-66 Gy in 30-33 fractions).

Methods: A total of 169,863 cases of NSCLC registered in England from January 2012 to December 2016 obtained from the Public Health England were divided into cohort 1 (training set) diagnosed in 2012 to 2013 and cohort 2 (validation set) diagnosed in 2014 to 2016. Radiotherapy data were obtained from the National Radiotherapy Dataset and linked by National Health Service number to survival data from the Office of National Statistics and Hospital Episode Statistics, from which surgical data and Charlson comorbidity index were obtained. Of 73,186 patients with stages I to III NSCLC, 12,898 received radical fractionated radiotherapy (cohort 1-4894; cohort 2-8004). The proportional hazards model was used to investigate overall survival from time of diagnosis. Survival was adjusted for the prognostic factors of age, sex, stage of disease, comorbidity, other radical treatments, and adjuvant chemotherapy, and the difference between the treatment schedules was summarized by hazard ratio (HR) and 95% confidence interval. The significance of any difference was evaluated by the log likelihood test.

Results: Of patients with stages I to III NSCLC, 17% to 18% received radical fractionated radiotherapy. After adjustment for independent prognostic factors of age, stage, comorbidity, and other radical and adjuvant treatments, patients in cohort 1 treated with the 2.75 Gy per fraction regimen had a median survival of 25 months compared with 29 months for patients treated with the 2 Gy per fraction regimen (HR = 1.16, p = 0.001). Similarly, in cohort 2, the respective median survival values were 25 and 28 months (HR = 1.10, p = 0.02).

Conclusions: Big data analysis of a comprehensive national cohort of patients with NSCLC treated in England suggests that compared with a 4-week regimen of 55 Gy in 20 fractions, a 6-week regimen of conventional daily fractionation to a dose of 60 to 66 Gy at 2 Gy per fraction is associated with a survival benefit. Within the limitations of the retrospective big data analysis with potential selection bias and in the absence of randomized trials, the results suggest that conventional fractionation regimens should remain the standard of care.