4.4 Interim Analysis The interim analyses will be conducted according to the alpha spending function approach proposed by DeMets and Lan (1994) which provides flexibility about the time for interim analysis. The a1 spending function, which generates the approximate O’Brien-Fleming boundaries (O’Brien and Fleming, 1979), will be used for a conservation termination at the early stage of the study. In addition, the method of B-value developed by Lan and Wittes (1988), Li (1998) will be used to monitor the data and to compute the conditional probability of detecting either a positive or negative treatment effect at the scheduled end of the study given the present status. The primary efficacy endpoint for the interim analyses is the time to occurrence of second primary tumors. The toxicity will be monitored constantly throughout the study. The conduct of interim analyses and dissemination of the results of the interim analysis will follow the TCOG Data and Safety Monitoring guidelines for confidentiality. The TCOG Data and Safety Monitoring Committee will review the results of interim analyses for a possible early termination of the trial.