ABSTRACT
INTRODUCTION: There is no standard treatment after resection of colorectal liver metastases and the role of systemic therapy remains controversial. To avoid over- or undertreatment, proper risk stratification with regard to postoperative treatment strategy is highly needed. We recently demonstrated the prognostic relevance of EMT-related (epithelial-mesenchymal transition) genes in stage II/III CRC. As EMT is a major step in CRC progression, we now aimed to analyse the prognostic relevance of EMT-related genes in stage IV CRC using the study cohort of the FIRE-3 trial, an open-label multi-centre randomised controlled phase III trial of patients with metastatic CRC. METHODS: Overall and progression free survival were considered as endpoints (n = 350). To investigate the prognostic relevance of EMT-related genes on either endpoint, we compared predictive performance of different models using clinical data only to models using gene data in addition to clinical data, expecting better predictive performance if EMT-related genes have prognostic value. In addition to baseline models (Kaplan Meier (KM), (regularised) Cox), Random Survival Forest (RSF), and gradient boosted trees (GBT) were fit to the data. Repeated, nested five-fold cross-validation was used for hyperparameter optimisation and performance evaluation. Predictive performance was measured by the integrated Brier score (IBS). RESULTS: The baseline KM model showed the best performance (OS: 0.250, PFS: 0.251). None of the other models were able to outperform the KM when using clinical data only according to the IBS scores (OS: 0.253 (Cox), 0.256 (RSF), 0.284 (GBT); PFS: 0.254 (Cox), 0.256 (RSF), 0.276 (GBT)). When adding gene data, performance of GBT improved slightly (OS: 0.262 vs. 0.284; PFS: 0.268 vs. 0.276), however, none of the models performed better than the KM baseline. CONCLUSION: Overall, the results suggest that the prognostic relevance of EMT-related genes may be stage-dependent and that EMT-related genes have no prognostic relevance in stage IV CRC.
ABSTRACT
BACKGROUND: Textbook outcome (TO) is a multidimensional measure reflecting the ideal outcome after surgery. As a benchmarking tool, it provides an objective overview of quality of care. Uniform definitions of TO in hepato-pancreato-biliary (HPB) surgery are missing. This study aimed to provide a definition of TO in HPB surgery and identify obstacles and predictors for achieving it. METHODS: A systematic literature search was conducted using PubMed, Embase, and Cochrane Database according to PRISMA guidelines. Studies published between 1993 and 2021 were retrieved. After selection, two independent reviewers extracted descriptive statistics and derived summary estimates of the occurrence of TO criteria and obstacles for achieving TO using co-occurrence maps. RESULTS: Overall, 30 studies were included. TO rates ranged between 16-69 per cent. Commonly chosen co-occurring criteria to define TO included 'no prolonged length of stay (LOS)', 'no complications', 'no readmission', and 'no deaths'. Major obstacles for achieving TO in HPB surgery were prolonged LOS, complications, and readmission. On multivariable analysis, TO predicted better overall and disease-free survival in patients with cancer. Achievement of TO was more likely in dedicated centres and associated with procedural and structural indicators, including high case-mix index and surgical volume. CONCLUSION: TO is a useful quality measure to benchmark surgical outcome. Future definitions of TO in HPB surgery should include 'no prolonged LOS', 'no complications', 'no readmission', and 'no deaths'.
