Fabio Bagante1, Gaya Spolverato2, Katiuscha Merath3, Matthew Weiss4, Sorin Alexandrescu5, Hugo P Marques6, Luca Aldrighetti7, Shishir K Maithel8, Carlo Pulitano9, Todd W Bauer10, Feng Shen11, George A Poultsides12, Olivier Soubrane13, Guillaume Martel14, B Groot Koerkamp15, Alfredo Guglielmi2, Itaru Endo16, Timothy M Pawlik17. 1. Department of Surgery, Ohio State University Wexner Medical Center, Columbus; Department of Surgery, University of Verona, Verona, Italy. 2. Department of Surgery, University of Verona, Verona, Italy. 3. Department of Surgery, Ohio State University Wexner Medical Center, Columbus. 4. Department of Surgery, Johns Hopkins University Hospital, Baltimore, MD. 5. Department of Surgery, Fundeni Clinical Institute, Bucharest, Romania. 6. Department of Surgery, Curry Cabral Hospital, Lisbon, Portugal. 7. Department of Surgery, Ospedale San Raffaele, Milan, Italy. 8. Department of Surgery, Emory University, Atlanta, GA. 9. Department of Surgery, Royal Prince Alfred Hospital, University of Sydney, Sydney, Australia. 10. Department of Surgery, University of Virginia, Charlottesville. 11. Department of Surgery, Eastern Hepatobiliary Surgery Hospital, Shanghai, China. 12. Department of Surgery, Stanford University, Stanford, CA. 13. Department of Hepatobiliopancreatic Surgery and Liver Transplantation, AP-HP, Beaujon Hospital, Clichy, France. 14. Division of General Surgery, Department of Surgery, University of Ottawa, Ottawa, ON, Canada. 15. Department of Surgery, Erasmus University Medical Centre, Rotterdam, Netherlands. 16. Gastroenterological Surgery Division, Yokohama City University School of Medicine, Yokohama, Japan. 17. Department of Surgery, Ohio State University Wexner Medical Center, Columbus. Electronic address: tim.pawlik@osumc.edu.
Abstract
BACKGROUND: Tumor burden is an important factor in defining prognosis among patients with primary and secondary liver cancers. Although the eighth edition of the American Joint Committee on Cancer staging system has changed the criteria for staging patients with intrahepatic cholangiocarcinoma to better define the effect of tumor burden on prognosis, the impact of intrahepatic cholangiocarcinoma tumor burden on overall survival has not been examined using a machine-learning tool. METHODS: Patients who underwent resection of intrahepatic cholangiocarcinoma at 1 of 14 participating international hospitals between 1990 and 2015 were identified. Classical survival models and the Classification and Regression Tree model were used to identify groups of patients with a homogeneous risk of death and investigate the hierarchical association between variables and overall survival. RESULTS: Among 1,116 patients included in the analysis, tumor size was ≤5 cm in 447 (40.1%) patients and >5 cm in 669 (59.9%) patients. Although 82.9% (n = 926) of patients had a single intrahepatic cholangiocarcinoma, 9.9% (n = 110) and 7.2% (n = 80) of patients had 2 and ≥3 tumors, respectively. Patients with intrahepatic cholangiocarcinoma tumors ≤5 cm and >5 cm had a 5-year overall survival of 51.7% and 32.6%, respectively (P < 0.001). Five-year overall survival decreased from 44.6% among patients with a single intrahepatic cholangiocarcinoma to 28.1% and 14.2% among patients with 2 and ≥3 intrahepatic cholangiocarcinomas, respectively (P < 0.001). Among the combinations of tumor size and intrahepatic cholangiocarcinoma tumor number used to estimate tumor burden, logarithmic transformation of tumor size (log tumor size) and intrahepatic cholangiocarcinoma tumor number had the highest concordance index. The Classification and Regression Tree model identified 8 classes of patients with a homogeneous risk of death, illustrating the hierarchical relationship between tumor burden (log tumor size and number of intrahepatic cholangiocarcinomas) and other factors associated with prognosis. CONCLUSION: Intrahepatic cholangiocarcinoma tumor size and number demonstrated a strong nonlinear association with survival after resection of intrahepatic cholangiocarcinoma. A log-model Classification and Regression Tree-derived tumor burden score may be a better tool to estimate prognosis of patients undergoing curative-intent resection of intrahepatic cholangiocarcinoma.
BACKGROUND:Tumor burden is an important factor in defining prognosis among patients with primary and secondary liver cancers. Although the eighth edition of the American Joint Committee on Cancer staging system has changed the criteria for staging patients with intrahepatic cholangiocarcinoma to better define the effect of tumor burden on prognosis, the impact of intrahepatic cholangiocarcinoma tumor burden on overall survival has not been examined using a machine-learning tool. METHODS:Patients who underwent resection of intrahepatic cholangiocarcinoma at 1 of 14 participating international hospitals between 1990 and 2015 were identified. Classical survival models and the Classification and Regression Tree model were used to identify groups of patients with a homogeneous risk of death and investigate the hierarchical association between variables and overall survival. RESULTS: Among 1,116 patients included in the analysis, tumor size was ≤5 cm in 447 (40.1%) patients and >5 cm in 669 (59.9%) patients. Although 82.9% (n = 926) of patients had a single intrahepatic cholangiocarcinoma, 9.9% (n = 110) and 7.2% (n = 80) of patients had 2 and ≥3 tumors, respectively. Patients with intrahepatic cholangiocarcinoma tumors ≤5 cm and >5 cm had a 5-year overall survival of 51.7% and 32.6%, respectively (P < 0.001). Five-year overall survival decreased from 44.6% among patients with a single intrahepatic cholangiocarcinoma to 28.1% and 14.2% among patients with 2 and ≥3 intrahepatic cholangiocarcinomas, respectively (P < 0.001). Among the combinations of tumor size and intrahepatic cholangiocarcinoma tumor number used to estimate tumor burden, logarithmic transformation of tumor size (log tumor size) and intrahepatic cholangiocarcinoma tumor number had the highest concordance index. The Classification and Regression Tree model identified 8 classes of patients with a homogeneous risk of death, illustrating the hierarchical relationship between tumor burden (log tumor size and number of intrahepatic cholangiocarcinomas) and other factors associated with prognosis. CONCLUSION:Intrahepatic cholangiocarcinoma tumor size and number demonstrated a strong nonlinear association with survival after resection of intrahepatic cholangiocarcinoma. A log-model Classification and Regression Tree-derived tumor burden score may be a better tool to estimate prognosis of patients undergoing curative-intent resection of intrahepatic cholangiocarcinoma.
Authors: Joshua S Jolissaint; Tiegong Wang; Kevin C Soares; Joanne F Chou; Mithat Gönen; Linda M Pak; Thomas Boerner; Richard K G Do; Vinod P Balachandran; Michael I D'Angelica; Jeffrey A Drebin; T P Kingham; Alice C Wei; William R Jarnagin; Jayasree Chakraborty Journal: HPB (Oxford) Date: 2022-02-17 Impact factor: 3.842
Authors: Diamantis I Tsilimigras; Kota Sahara; Lu Wu; Dimitrios Moris; Fabio Bagante; Alfredo Guglielmi; Luca Aldrighetti; Matthew Weiss; Todd W Bauer; Sorin Alexandrescu; George A Poultsides; Shishir K Maithel; Hugo P Marques; Guillaume Martel; Carlo Pulitano; Feng Shen; Olivier Soubrane; B Groot Koerkamp; Amika Moro; Kazunari Sasaki; Federico Aucejo; Xu-Feng Zhang; Ryusei Matsuyama; Itaru Endo; Timothy M Pawlik Journal: JAMA Surg Date: 2020-09-01 Impact factor: 14.766
Authors: Lukas Müller; Aline Mähringer-Kunz; Simon Johannes Gairing; Friedrich Foerster; Arndt Weinmann; Fabian Bartsch; Lisa-Katharina Heuft; Janine Baumgart; Christoph Düber; Felix Hahn; Roman Kloeckner Journal: J Clin Med Date: 2021-05-12 Impact factor: 4.241