Real-world validation cohort
peritoneal disease
REGRESSION, PERITONEAL DISEASE, METASTASES, DISEASE
We selected eight variables for multivariate (adjusted) Cox proportional-hazards modeling of the real-world validation cohort. In this process, we aimed to harmonize the selection as much as possible to the variables used in the Cox regression modeling of the RECOURSE trial-based data (see below), with some alterations.The ECOG performance status (0–1 versus ≥2) was used as a stratification factor because this variable violated the proportional-hazards assumption when modeled as a covariate. Furthermore, we adjusted for seven additional covariates: time since diagnosis of first metastases (<18 versus ≥18 months); geographical region (UK versus Italy); age (<65 versus ≥65 years); sex; sidedness (left versus right); previous surgery (yes versus no); and peritoneal disease at the start of FTD/TPI treatment (yes versus no). Sidedness was used instead of primary site of the disease (colon versus rectum, as used in the RECOURSE trial-based analyses), because sidedness was most strongly associated with OS and only one of these two variables could be included due to high collinearity. Due to data unavailability for the real-world validation cohort, we were unable to factor in if the disease was refractory to fluoropyrimidine as part of the last previous regimen, previous use of regorafenib, the number of previous regimens and the number of metastatic sites in the analyses. In RECOURSE trial-based analyses, none of these factors were predictive and only the latter variable was prognostic for OS. Instead, based on significant (univariate) associations with OS in the real-world validation cohort, we decided to add the two variables ‘previous surgery’ and ‘peritoneal disease at the start of FTD/TPI treatment’ to our selection of covariates, although these data were unavailable for the RECOURSE trial dataset.