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.