Tao Wei1,2, Xu-Feng Zhang1,3, Feng Xue1, Fabio Bagante3,4, Francesca Ratti5, Hugo P Marques6, Silvia Silva6, Olivier Soubrane7, Vincent Lam8, George A Poultsides9, Irinel Popescu10, Razvan Grigorie10, Sorin Alexandrescu10, Guillaume Martel11, Aklile Workneh11, Alfredo Guglielmi4, Tom Hugh12, Luca Aldrighetti5, Itaru Endo13, Timothy M Pawlik14. 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. 2. Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. 3. Division of Surgical Oncology, Department of Surgery, Medical Center and James Comprehensive Cancer Center, The Ohio State University Wexner, Columbus, OH, USA. 4. Department of Surgery, University of Verona, Verona, Italy. 5. Department of Surgery, Ospedale San Raffaele, Milano, Italy. 6. Department of Surgery, Curry Cabral Hospital, Lisbon, Portugal. 7. Department of Hepatobiliopancreatic Surgery, APHP, Beaujon Hospital, Clichy, France. 8. Department of Surgery, Westmead Hospital, Sydney, NSW, Australia. 9. Department of Surgery, Stanford University, Stanford, CA, USA. 10. Department of Surgery, Fundeni Clinical Institute, Bucharest, Romania. 11. Department of Surgery, University of Ottawa, Ottawa, ON, Canada. 12. Department of Surgery, School of Medicine, The University of Sydney, Sydney, NSW, Australia. 13. Yokohama City University School of Medicine, Yokohama, Japan. 14. Division of Surgical Oncology, Department of Surgery, Medical Center and James Comprehensive Cancer Center, The Ohio State University Wexner, Columbus, OH, USA. Tim.Pawlik@osumc.edu.
Abstract
BACKGROUNDS: Extrahepatic recurrence of hepatocellular carcinoma (HCC) after surgical resection is associated with unfavorable prognosis. The objectives of the current study were to identify the risk factors and develop a nomogram for the prediction of extrahepatic recurrence after initial curative surgery. METHODS: A total of 635 patients who underwent curative-intent resection for HCC between 2000 and 2017 were identified from an international multi-institutional database. The clinicopathological characteristics, risk factors, and long-term survival of patients with extrahepatic recurrence were analyzed. A nomogram for the prediction of extrahepatic recurrence was established and validated in 144 patients from an external cohort. RESULTS: Among the 635 patients in the derivative cohort, 283 (44.6%) experienced recurrence. Among patients who recurred, 80 (28.3%) patients had extrahepatic ± intrahepatic recurrence, whereas 203 (71.7%) had intrahepatic recurrence only. Extrahepatic recurrence was associated with more advanced initial tumor characteristics, early recurrence, and worse prognosis versus non-extrahepatic recurrence. A nomogram for the prediction of extrahepatic recurrence was developed using the β-coefficients from the identified risk factors, including neutrophil-to-lymphocyte ratio, multiple lesions, tumor size, and microvascular invasion. The nomogram demonstrated good ability to predict extrahepatic recurrence (c-index: training cohort 0.786; validation cohort: 0.845). The calibration plots demonstrated good agreement between estimated and observed extrahepatic recurrence (p = 0.658). CONCLUSIONS: An externally validated nomogram was developed with good accuracy to predict extrahepatic recurrence following curative-intent resection of HCC. This nomogram may help identify patients at high risk of extrahepatic recurrence and guide surveillance protocols as well as adjuvant treatments.
BACKGROUNDS: Extrahepatic recurrence of hepatocellular carcinoma (HCC) after surgical resection is associated with unfavorable prognosis. The objectives of the current study were to identify the risk factors and develop a nomogram for the prediction of extrahepatic recurrence after initial curative surgery. METHODS: A total of 635 patients who underwent curative-intent resection for HCC between 2000 and 2017 were identified from an international multi-institutional database. The clinicopathological characteristics, risk factors, and long-term survival of patients with extrahepatic recurrence were analyzed. A nomogram for the prediction of extrahepatic recurrence was established and validated in 144 patients from an external cohort. RESULTS: Among the 635 patients in the derivative cohort, 283 (44.6%) experienced recurrence. Among patients who recurred, 80 (28.3%) patients had extrahepatic ± intrahepatic recurrence, whereas 203 (71.7%) had intrahepatic recurrence only. Extrahepatic recurrence was associated with more advanced initial tumor characteristics, early recurrence, and worse prognosis versus non-extrahepatic recurrence. A nomogram for the prediction of extrahepatic recurrence was developed using the β-coefficients from the identified risk factors, including neutrophil-to-lymphocyte ratio, multiple lesions, tumor size, and microvascular invasion. The nomogram demonstrated good ability to predict extrahepatic recurrence (c-index: training cohort 0.786; validation cohort: 0.845). The calibration plots demonstrated good agreement between estimated and observed extrahepatic recurrence (p = 0.658). CONCLUSIONS: An externally validated nomogram was developed with good accuracy to predict extrahepatic recurrence following curative-intent resection of HCC. This nomogram may help identify patients at high risk of extrahepatic recurrence and guide surveillance protocols as well as adjuvant treatments.