Statistical analysis
PD, SD
REGRESSION, EVENTS, EVENT
The aim of this study was to determine if patients who responded to NET should choose ET alone or CT+ET as adjuvant therapy, in terms of DFS. To prepare for this analysis, all centers scheduled to participate in this study (Based on these survey results, the HR thresholds for choosing between the two treatments under conditions A and B were set at 0.9 and 0.6, respectively. A total of about 200 events were needed to provide a statistical power of 90% with these thresholds. Assuming that the 5-year DFS in the entire population was 88% and that 90% of the subjects would show CR, PR, or SD to NET, about 1,460 patients were needed to observe an occurrence of about 200 events during the planned follow-up of up to 8 years (a 3-year enrollment period plus a 5-year follow-up period). Accounting for an expected withdrawal of about 10% of the subjects, 1,700 patients were planned to be enrolled.Patient enrollment did not proceed on schedule and the Study Steering Committee proposed postponing the enrollment period from 3 to 5 years and the total study period from 8 to 10 years in March 2011, which was approved by the Independent Data Monitoring Committee. We set the selection probability as 90%, but it was judged that it was possible to almost achieve the purpose of this study at about 80%–85%, in which case, about 170 events were required for both groups. In addition, assuming that the 5-year DFS for the overall population was 88%, the durations of the accrual and follow-up periods were 5 and 10 years (15 years for the longest follow-up period), respectively. A total sample size of 630 patients was required. Assuming that about a quarter of the preoperative patients were not registered in the second (postoperative) stage, the total sample size required was about 850 patients. Kaplan–Meier curves for DFS, DDFS, and OS were estimated for each response group. Median 8-year DFS/OS/DDFS with confidence intervals (CIs) were calculated based on the Greenwood’s formulae. A Cox’s proportional hazard model was used to investigate the relationships between clinical response to ET (CR, PR, or SD versus PD), DFS, DDFS, and OS. HRs with 95% CIs were obtained for DFS, DDFS, and OS. Logistic regression was used to investigate the relationships between predictive variables (age, body mass index, histological grade, Ki67, PgR, T, and HER2) and clinical responses. Given that this analysis was not performed at the pre-planned time and because further extension of the observation period would not achieve the planned event, we consulted with a biostatistician and decided to perform the analysis, even though the primary endpoint could not be proven with statistical certainty.