Statistical analysis
tumor, CMT
RECURRENCES, REGRESSION, TUMOR, SECONDARY
The HD16 trial had two independent co-primary objectives. The first question addressed whether RT could be omitted from standard CMT after a negative PET-2 without a clinically relevant loss of tumor control. Non-inferiority of ABVD alone over standard CMT would be established if the upper limit of the 2-sided 95% CI for the hazard ratio (HR) for PFS was below the predefined non-inferiority margin of 3.01 in a per-protocol analysis of the PET-2-negative patient population. Second, the HD16 trial aimed to assess whether a positive PET-2 represented a risk factor for PFS among patients assigned to receive CMT by demonstrating superiority of patients with a negative PET-2 result from the standard CMT group over those with a positive PET-2 from both treatment groups. Details on statistical methods and sample size calculation have been published previously [OS as well as in-field and out-field recurrences, were analyzed as secondary endpoints for the before mentioned RT and PET objectives. SPM were analyzed in the PET-2-negative population to complement the primary non-inferiority objective. Cardiac function was analyzed in the entire study population by assigned treatment group separately for male and female patients in a complete-case analysis. Fertility outcomes were analyzed by assigned treatment groups in pre-defined subgroups of male patients aged 18–60 years at enrollment and female patients aged 18–40 years at enrollment.We analyzed PFS and OS using the Kaplan-Meier method, including HRs and 95% CIs obtained from Cox regression models and log-rank tests where applicable. To assess the prognostic impact of PET-2 independently from baseline factors, this analysis was performed by multivariate Cox regression including all stratification factors (except for recruiting site). SPM, in-field and out-field recurrences and childbirth after therapy were analyzed using cumulative incidence functions, with sub-distribution HRs and p values obtained from univariate Fine-Gray models. Other secondary endpoints were analyzed by means of descriptive statistics. Analysis sets remained unchanged from the primary analysis [