Sample Size and Randomization
Cancer
DISEASE, EVENT, CANCER
In this study, we used a superiority trial design. The probability of the outcome event in the test population was approximately 35%. It was expected to take 4 years to enroll all participants, with a follow-up period of 1 year after the last patient randomization. As such, a minimum of 134 patients was required for each group to achieve 80% power at the 5% level to detect a 10% increment in 1-year OS. Based on a 10% dropout rate, a final sample size of 150 for each group was required. Eligible patients were randomized 1:1 to receive S-1–based definitive SIB-RT followed by consolidated chemotherapy (CRTCT group) or SIB-RT alone (RT group) by a central randomization center (National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Beijing, China). Sequential assignment of patients was performed with R software using random block sizes of 4 with stratification of disease stage (IIa vs IIb vs III vs IVa vs IVb) and participating center. A random assignment number was allocated to each patient and provided to the respective investigators via telephone.According to our protocol, when 80% of the patients (240 patients) enrolled in the study by February 19, 2019, 34 of 127 patients (26.8%) assigned to the CRTCT group were unable to complete concurrent chemotherapy and only 20 patients (15.7%) stopped treatment owing to treatment-related toxic effects. We subsequently enlarged the sample size by retaining the sample size of RT group according to the initial plan (150 patients) and changed the randomization proportion from 1:1 to 4:3 (CRTCT group:RT group) to enroll more patients into the CRTCT group. Consequently, the number of patients who completed RT in the RT group was similar to those who completed concurrent chemoradiotherapy in CRTCT group (133 patients vs 134 patients).