Colorectal liver metastases: Surgery versus thermal ablation (COLLISION) - a phase III single-blind prospective randomized controlled trial

Background: Radiofrequency ablation (RFA) and microwave ablation (MWA) are widely accepted techniques to eliminate small unresectable colorectal liver metastases (CRLM). Although previous studies labelled thermal ablation inferior to surgical resection, the apparent selection bias when comparing patients with unresectable disease to surgical candidates, the superior safety profile, and the competitive overall survival results for the more recent reports mandate the setup of a randomized controlled trial. The objective of the COLLISION trial is to prove non-inferiority of thermal ablation compared to hepatic resection in patients with at least one resectable and ablatable CRLM and no extrahepatic disease. Methods: In this two-arm, single-blind multi-center phase-III clinical trial, six hundred and eighteen patients with at least one CRLM (≤3cm) will be included to undergo either surgical resection or thermal ablation of appointed target lesion(s) (≤3cm). Primary endpoint is OS (overall survival, intention-to-treat analysis). Main secondary endpoints are overall disease-free survival (DFS), time to progression (TTP), time to local progression (TTLP), primary and assisted technique efficacy (PTE, ATE), procedural morbidity and mortality, length of hospital stay, assessment of pain and quality of life (QoL), cost-effectiveness ratio (ICER) and quality-adjusted life years (QALY). Discussion: If thermal ablation proves to be non-inferior in treating lesions ≤3cm, a switch in treatment-method may lead to a reduction of the post-procedural morbidity and mortality, length of hospital stay and incremental costs without compromising oncological outcome for patients with CRLM. Trial registration:NCT03088150 , January 11th 2017

Incorporating circulation statistics in bias correction of GCM ensembles: hydrological application for the Rhine basin

An adapted statistical bias correction method is introduced to incorporate circulation-dependence of the model precipitation bias, and its influence on estimated discharges for the Rhine basin is analyzed for a historical period. The bias correction method is tailored to time scales relevant to flooding events in the basin. Large-scale circulation patterns (CPs) are obtained through Maximum Covariance Analysis using reanalysis sea level pressure and high-resolution precipitation observations. A bias correction using these CPs is applied to winter and summer separately, acknowledging the seasonal variability of the circulation regimes in North Europe and their correlation with regional precipitation rates over the Rhine basin. Two different climate model ensemble outputs are explored: ESSENCE and CMIP5. The results of the CP-method are then compared to observations and uncorrected model outputs. Results from a simple bias correction based on a delta factor (NoCP-method) are also used for comparison. For both summer and winter, the CP-method offers a statistically significant improvement of precipitation statistics for subsets of data dominated by particular circulation regimes, demonstrating the circulation-dependence of the precipitation bias. Uncorrected, CP and NoCP corrected model outputs were used as forcing to a hydrological model to simulate river discharges. The CP-method leads to a larger improvement in simulated discharge in the Alpine area in winter than in summer due to a stronger dependence of Rhine precipitation on atmospheric circulation in winter. However, the NoCP-method, in comparison to the CP-method, improves the discharge estimations over the entire Rhine basin