Note that patients who undergo sequential tumor bed boost will have their post radiotherapy assessment postponed till boost is completed. This would mean at the 2nd week in patients receiving 1 week RT and the 4th week in patients undergoing 3 week RT.
In each study visit a clinical assessment including a history and examination will be undertaken. Adverse events related to radiotherapy will be recorded in a case record form. Quality of life questionnaires will be administered on the visits as indicated. During the follow up period patients will undergo mammogram of intact breast(s) at 12 - 18 month intervals or as per the institutional policy.

Sample Size {14}

Non-inferiority margin and justification for the same

Assuming that the locoregional recurrence rate in the control arm is 5%, a non-inferiority boundary of 3% is clinically acceptable and corresponds to a hazard rate of 1.63. The choice of the non-inferiority boundary is arbitrary to a significant extent and we base it on the guidance that it should not be larger than the expected benefit from adjuvant radiotherapy. A large volume of data is available regarding the benefit of adjuvant radiotherapy in breast cancer patients. In the setting of breast conservation surgery, the EBCTCG meta-analysis demonstrated that use of adjuvant radiotherapy reduced the 5-year local recurrences by 17 % after breast conservation surgery(2), while in the postmastectomy setting the 5-year local recurrence was reduced by 14.7% for N+ patients(3). The START trials were designed to show a difference of 5% as the non-inferiority boundary(33). This is approximately 33% of the benefit that can be expected from RT vs no RT. Since the START trials have demonstrated that the 40 Gy is non-inferior to 50 Gy we can thus consider a non-inferiority boundary of 3% as appropriate for this study.

Sample size

The sample is calculated based on the assumption that the 5 year local recurrence rate in the control arm is 5% with an exponential distribution. We hypothesize that the use of 1 week course of adjuvant radiotherapy will not increase the locoregional recurrence beyond 8% (absolute difference of 3%), corresponding to a hazard ratio of 1.63. We further assume that patients will be accrued over 5 years with an initial ramp up in the first year and that 2% of the patients will be lost to follow-up each year of the trial. The total trial duration is expected to be 10 years to ensure a minimum follow up of 5 years for the last patient. For a fixed sample size design to achieve the required number of events to achieve a one sided Type I error of 0.025 and a power of 80% the total number of events required is 140. The total planned sample size is 2100 patients.

Recruitment {15}

Patients will be recruited from the outpatient departments of the disease management group at each institute. No advertising is permitted for recruitment and no inducements will be given for recruitment of patients in the study. Central randomization will be done at Tata Medical Center using permuted block randomization.