Multi-institutional Development and External Validation of a Nomogram Predicting Recurrence After Curative Liver Resecti

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ORIGINAL ARTICLE – HEPATOBILIARY TUMORS

Multi-institutional Development and External Validation of a Nomogram Predicting Recurrence After Curative Liver Resection for Neuroendocrine Liver Metastasis Jun-Xi Xiang, MD1, Xu-Feng Zhang, MD, PhD1,2, Matthew Weiss, MD3, Luca Aldrighetti, MD4, George A. Poultsides, MD5, Todd W. Bauer, MD6, Ryan C. Fields, MD7, Shishir Kumar Maithel, MD8, Hugo P. Marques, MD9, and Timothy M. Pawlik, MD, MPH, PhD, FACS, FRACS (Hon.)2 1

Department of Hepatobiliary Surgery and Institute of Advanced Surgical Technology and Engineering, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China; 2Department of Surgery, The Urban Meyer III and Shelley Meyer Chair for Cancer Research, Health Services Management and Policy, The Ohio State University Wexner Medical Center, Columbus, OH; 3Department of Surgery, Johns Hopkins Hospital, Baltimore, MD; 4Department of Surgery, Scientific Institute San Raffaele, Vita-Salute San Raffaele University, Milan, Italy; 5Department of Surgery, Stanford University, Stanford, CA; 6Department of Surgery, University of Virginia, Charlottesville, VA; 7Department of Surgery, School of Medicine, Washington University, St. Louis, MO; 8Department of Surgery, Emory University, Atlanta, GA; 9 Department of Surgery, Curry Cabral Hospital, Lisbon, Portugal

ABSTRACT Objectives. To establish and externally validate a novel nomogram to predict recurrence of patients undergoing curative liver resection for neuroendocrine liver metastasis (NELM). Methods. A total of 279 patients who underwent curative liver resection for NELM identified from an international multicenter database were utilized to develop a nomogram to predict recurrence; 98 cases from two different institutions were used to externally validate the nomogram. Results. Among 279 patients in the development cohort, median age was 57 years, and 50.5% were male. On multivariate analysis, primary tumor location (pancreatic vs nonpancreatic, HR 2.1, p = 0.004), tumor grade (Ref. well, moderate HR 1.9, p = 0.022; poor HR 1.6, p = 0.238), lymph node metastasis (positive vs negative, HR 2.6, p = 0.002), and extent of resection (major vs

parenchymal-sparing resection, HR 0.3, p = 0.001) were independently associated with recurrence-free survival. The beta coefficients from the final multivariable model were utilized to develop a nomogram. The nomogram demonstrated good ability to predict risk of recurrence (training cohort, C-index 0.754; validation cohort, C-index 0.748). The calibrated nomogram predicted recurrence-free survival that closely corresponded to actual recurrence. Decision curve analysis demonstrated that the nomogram had a good net benefit for most of the threshold probabilities, especially between 20 and 60%, in both development and validation cohorts. Conclusions. The externally validated novel nomogram predicted 3- and 5-year recurrence-free survival among patients with NELM. Prediction of individual recurrence risk may help guide personalized estimates of prognosis, as well as surveillance

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