Fabio Bagante1,2, Katiuscha Merath1, Malcolm H Squires1, Matthew Weiss3, Sorin Alexandrescu4, Hugo P Marques5, Luca Aldrighetti6, Shishir K Maithel7, Carlo Pulitano8, Todd W Bauer9, Feng Shen10, George A Poultsides11, Olivier Soubrane12, Guillaume Martel13, B Groot Koerkamp14, Alfredo Guglielmi2, Endo Itaru15, Timothy M Pawlik16. 1. Department of Surgery, The Urban Meyer III and Shelley Meyer Chair in Cancer Research, The Ohio State University Wexner Medical Center, 395 W. 12th Ave., Suite 670, Columbus, OH, 43210, USA. 2. Department of Surgery, University of Verona, Verona, Italy. 3. Department of Surgery, Johns Hopkins Hospital, Baltimore, MD, USA. 4. Department of Surgery, Fundeni Clinical Institute, Bucharest, Romania. 5. Department of Surgery, Curry Cabral Hospital, Lisbon, Portugal. 6. Department of Surgery, Ospedale San Raffaele, Milan, Italy. 7. Department of Surgery, Emory University, Atlanta, GA, USA. 8. Department of Surgery, Royal Prince Alfred Hospital, University of Sydney, Sydney, Australia. 9. Department of Surgery, University of Virginia, Charlottesville, VA, USA. 10. Department of Surgery, Eastern Hepatobiliary Surgery Hospital, Shanghai, China. 11. Department of Surgery, Stanford University, Stanford, CA, USA. 12. Department of Hepatobiliopancreatic Surgery and Liver Transplantation, AP-HP, Beaujon Hospital, Clichy, France. 13. Division of General Surgery, Department of Surgery, University of Ottawa, Ottawa, ON, Canada. 14. Department of Surgery, Erasmus University Medical Centre, Rotterdam, Netherlands. 15. Gastroenterological Surgery Division, Yokohama City University School of Medicine, Yokohama, Japan. 16. Department of Surgery, The Urban Meyer III and Shelley Meyer Chair in Cancer Research, The Ohio State University Wexner Medical Center, 395 W. 12th Ave., Suite 670, Columbus, OH, 43210, USA. tim.pawlik@osumc.edu.
Abstract
BACKGROUND: The ability to provide accurate prognostic data after hepatectomy for intrahepatic cholangiocarcinoma (ICC) remains poor. We sought to develop and validate a nomogram to predict survival, as well as investigate the clinical implications of underestimating patients' risk of recurrence. METHODS: Patients undergoing curative-intent resection of ICC between 1990 and 2015 at 14 major hepatobiliary centers were included. Variables significant on multivariable analysis were used to construct a nomogram to predict disease-free survival (DFS). The nomogram assigned a score to each variable included in the model and calculated the risk of recurrence. RESULTS: Eight hundred ninety-seven patients are included in the analytic cohort. On multivariable Cox regression analysis, tumor size > 5 cm (HR 1.98, 95% CI 1.44-2.13; p < 0.001), multifocal ICC (HR 1.64, 95% CI 1.32-2.03; p < 0.001), lymph node metastasis (HR 1.63, 95% CI 1.25-2.11; p < 0.001), poorly differentiated tumor grade (HR 1.50, 95% CI 1.21-1.89; p < 0.001), and periductal infiltrating type (PI) morphology (HR 1.42, 95% CI 1.09-1.83; p = 0.008) were independent adverse risk factors associated with decreased DFS. The Harrell's c-index for the nomogram was 0.633 (with n = 5000 bootstrapping resamples) and the plot comparing predicted and actuarial DFS demonstrated a good calibration of the model. A subset of patients (n = 282) had a DFS worse than predicted (ΔPredicted DFS - Actuarial DFS > 6 months). Moreover, underestimation of a recurrence risk was more common among patients with clinicopathologic features traditionally considered "favorable." CONCLUSION: A nomogram based on standard clinicopathologic characteristics was suboptimal in its ability to predict accurately risk of recurrence among patients with ICC after curative-intent liver resection. Particularly, the risk of underestimating patient risk of recurrence was highest among patients with historically favorable characteristics. Over one third of patients recurred > 6 months earlier than the DFS predicted by the nomogram.
BACKGROUND: The ability to provide accurate prognostic data after hepatectomy for intrahepatic cholangiocarcinoma (ICC) remains poor. We sought to develop and validate a nomogram to predict survival, as well as investigate the clinical implications of underestimating patients' risk of recurrence. METHODS:Patients undergoing curative-intent resection of ICC between 1990 and 2015 at 14 major hepatobiliary centers were included. Variables significant on multivariable analysis were used to construct a nomogram to predict disease-free survival (DFS). The nomogram assigned a score to each variable included in the model and calculated the risk of recurrence. RESULTS: Eight hundred ninety-seven patients are included in the analytic cohort. On multivariable Cox regression analysis, tumor size > 5 cm (HR 1.98, 95% CI 1.44-2.13; p < 0.001), multifocal ICC (HR 1.64, 95% CI 1.32-2.03; p < 0.001), lymph node metastasis (HR 1.63, 95% CI 1.25-2.11; p < 0.001), poorly differentiated tumor grade (HR 1.50, 95% CI 1.21-1.89; p < 0.001), and periductal infiltrating type (PI) morphology (HR 1.42, 95% CI 1.09-1.83; p = 0.008) were independent adverse risk factors associated with decreased DFS. The Harrell's c-index for the nomogram was 0.633 (with n = 5000 bootstrapping resamples) and the plot comparing predicted and actuarial DFS demonstrated a good calibration of the model. A subset of patients (n = 282) had a DFS worse than predicted (ΔPredicted DFS - Actuarial DFS > 6 months). Moreover, underestimation of a recurrence risk was more common among patients with clinicopathologic features traditionally considered "favorable." CONCLUSION: A nomogram based on standard clinicopathologic characteristics was suboptimal in its ability to predict accurately risk of recurrence among patients with ICC after curative-intent liver resection. Particularly, the risk of underestimating patient risk of recurrence was highest among patients with historically favorable characteristics. Over one third of patients recurred > 6 months earlier than the DFS predicted by the nomogram.
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Keywords:
Drs. Bagante and Merath equally contributed to this manuscript.; ICC; Nomogram; Recurrence; Surgery; Survival
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