C-reactive protein is superior to white blood cell count for early detection of complications after pancreatoduodenectomy: a retrospective multicenter cohort study

Background: Early detection of major complications after pancreatoduodenectomy could improve patient management and decrease the “failure-to-rescue” rate. In this retrospective cohort study, we aimed to compare the value of C-reactive protein (CRP) and white blood cell count (WBC) in the early detection of complications after pancreatoduodenectomy. Methods: We assessed pancreatoduodenectomies between January 2012 and December 2017. Major complications were defined as grade III or higher according to the Clavien-Dindo classification. Postoperative pancreatic fistula (POPF) was a secondary endpoint. ROC-curve and logistic regression analysis were performed for CRP and WBC. Results were validated in an external cohort. Results: In the development cohort (n = 285), 103 (36.1%) patients experienced a major complication. CRP was superior to WBC in detecting major complications on postoperative day (POD) 3 (AUC:0.74 vs. 0.54, P < 0.001) and POD 5 (AUC:0.77 vs. 0.68, P = 0.031), however not on POD 7 (AUC:0.77 vs. 0.76, P = 0.773). These results were confirmed in multivariable analysis and in the validation cohort (n = 202). CRP was also superior to WBC in detecting POPF on POD 3 (AUC: 0.78 vs. 0.54, P < 0.001) and POD 5 (AUC: 0.83 vs. 0.71, P < 0.001). Conclusion: CRP appears to be superior to WBC in the early detection of major complications and POPF after pancreatoduodenectomy

Predicting clinical benefit from everolimus in patients with advanced solid tumors, the CPCT-03 study

Background: In this study, our aim was to identify molecular aberrations predictive for response to everolimus, an mTOR inhibitor, regardless of tumor type. Methods: To generate hypotheses about potential markers for sensitivity to mTOR inhibition, drug sensitivity and genomic profiles of 835 cell lines were analyzed. Subsequently, a multicenter study was conducted. Patients with advanced solid tumors lacking standard of care treatment options were included and underwent a pre-treatment tumor biopsy to enable DNA sequencing of 1,977 genes, derive copy number profiles and determine activation status of pS6 and pERK. Treatment benefit was determined according to TTP ratio and RECIST. We tested for associations between treatment benefit and single molecular aberrations, clusters of aberrations and pathway perturbation. Results: Cell line screens indicated several genes, such as PTEN (P = 0.016; Wald test), to be associated with sensitivity to mTOR inhibition. Subsequently 73 patients were included, of which 59 started treatment with everolimus. Response and molecular data were available from 43 patients. PTEN aberrations, i.e. copy number loss or mutation, were associated with treatment benefit (P = 0.046; Fisher's exact test). Conclusion: Loss-of-function aberrations in PTEN potentially represent a tumor type agnostic biomarker for benefit from everolimus and warrants further confirmation in subsequent studies