A combined Cox and logistic model provides accurate predictive performance in estimation of time-dependent probabilities for recurrence of intrahepatic cholangiocarcinoma after resection

Seogsong Jeong; Guijuan Luo; Qiang Gao; Jing Chen; Xiaolong Liu; Liangqing Dong; Yongjie Zhang; Feng Shen; Qingbao Cheng; Chengjun Sui; Jingfeng Liu; Hongyang Wang; Qiang Xia; Lei Chen

doi:10.21037/hbsn.2020.01.07

A combined Cox and logistic model provides accurate predictive performance in estimation of time-dependent probabilities for recurrence of intrahepatic cholangiocarcinoma after resection

Hepatobiliary Surg Nutr. 2021 Aug;10(4):464-475. doi: 10.21037/hbsn.2020.01.07.

Authors

Seogsong Jeong^{1

2}, Guijuan Luo^{2

3}, Qiang Gao⁴, Jing Chen^{2

3}, Xiaolong Liu⁵, Liangqing Dong⁴, Yongjie Zhang⁶, Feng Shen⁷, Qingbao Cheng⁸, Chengjun Sui⁹, Jingfeng Liu⁵, Hongyang Wang^{2

3}, Qiang Xia¹, Lei Chen^{2

10}

Affiliations

¹ Department of Liver Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
² International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, Second Military Medical University, Shanghai, China.
³ National Center for Liver Cancer, Shanghai, China.
⁴ Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, Shanghai, China.
⁵ Mengchao Hepatobiliary Hospital, Fujian Medical University, Fuzhou, China.
⁶ Biliary Tract Department II, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
⁷ Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
⁸ Biliary Tract Department I, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
⁹ Department of Special Medical Care & Liver Transplantation, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
¹⁰ Shanghai Cancer Center, Shanghai Medical College, Fudan University; Shanghai, China.

Abstract

Background: Intrahepatic cholangiocarcinoma has heterogeneous outcomes after resection. There remains a need for broadly applicable recurrence-specific tool offering precise evaluation on curativeness of resection.

Methods: A four hospital-based clinical cohort involving 1,655 patients with intrahepatic cholangiocarcinoma who received surgical resection were studied. Cox and logistic models were networked into one system containing risk categories with distinctive probabilities of recurrence. Prediction of time-to-recurrence was performed by formulizing time-dependent risk probabilities. The model was validated in three clinical cohorts (n=332).

Results: From the training cohort, 10 and 11 covariates, including diabetes, cholelithiasis, albumin, platelet count, alpha fetoprotein, carbohydrate antigen 19-9, carcinoembryonic antigen, hepatitis B virus infection, tumor size and number, resection type, and lymph node metastasis, from Cox and logistic models were identified significant for recurrence-free survival (RFS). The combined Cox & logistic ranking system (CCLRS)-adjusted time-dependent probabilities were categorized into seven ranks (5-yr RFS for lowest and highest ranks were 75% vs. 0%; hazard ratio 18.5, 95% CI: 14.7-24.9, P<0.0001). The CCLRS was validated with a minimum area under curve value of 0.8086. Prediction of time-to-recurrence was validated to be excellent (Pearson r, 0.8204; P<0.0001).

Conclusions: The CCLRS allows precise estimation on risk of recurrence for intrahepatic cholangiocarcinoma after resection. It could be applicative when estimating time-dependent disease status and stratifying individuals who sole resection of the tumor would not be curative.

Keywords: Primary liver cancer; biliary malignancy; hepatectomy; nomogram; regression model; resection; surgery.