Statistical Analysis
SECONDARY
The investigators and the ethics committee agreed upon an a priori determined sample size of 80 patients for the phase II trial as a sufficient number to assess the feasibility and safety of perioperative systemic therapy.For the primary study aim (i.e., comparison of five predefined PROs between both arms), all patients who completed questionnaires at two or more comparative timepoints (i.e., baseline and 3 and 6 months postoperatively) were included. In these patients, differential effects in scores over time and scores at each timepoint were compared between both arms using linear mixed modeling (LMM) with the use of maximum likelihood estimation and an unstructured covariance matrix with a two-level structure [i.e., repeated timepoints (lower level), patients (higher level)]. If there were no statistically significant differences in differential effects in scores over time and in scores at each timepoint, scores of both arms were merged to longitudinally compare baseline scores with scores at subsequent timepoints using LMM. To account for multiple testing in primary comparative analyses, For the secondary study aim (i.e., longitudinal exploration of all PROs of patients receiving perioperative systemic therapy in the experimental arm), all patients who completed questionnaires at baseline and after neoadjuvant treatment were included. In these patients, baseline scores were compared with scores measured after neoadjuvant treatment using LMM. All PROs with a statistically significant difference in scores between these timepoints were further analyzed and (graphically) presented. To account for multiple testing in secondary explorative analyses, statistical significance was pragmatically set at For each statistically significant difference, a Cohen’s 