Late recurrence of hepatocellular carcinoma after radiofrequency ablation: a multicenter study of risk factors, patterns

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Late recurrence of hepatocellular carcinoma after radiofrequency ablation: a multicenter study of risk factors, patterns, and survival Yi Yang 1 & Yi Chen 1,2 & Feng Ye 3 & Xiaojing Cao 1,4 & Yujing Xin 1 & Yanan Wang 1 & Yong Lei 5 & Xiao Li 1 & Duiping Feng 2 & Xiang Zhou 1 & Qingsheng Fan 5 Received: 17 April 2020 / Revised: 9 October 2020 / Accepted: 3 November 2020 # European Society of Radiology 2020

Abstract Objective This study aims to determine the risk factors, patterns, and long-term survival outcomes of late recurrence after radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) within the Milan criteria and develop a nomogram to predict the recurrence-free survival (RFS). Materials and methods This retrospective study included patients with HCC within the Milan criteria, who received RFA at three hospitals in China from January 2011 to December 2016. The clinical variables were assessed by univariate and multivariate Cox regression analyses. Results A total of 398 patients were included. The median follow-up was 58.7 months (range: 24.1–96.0). Ninety-eight patients had late recurrence. Furthermore, 14 patients (14.29%) had local tumor progression (LTP) alone, 43 patients (43.88%) had intrahepatic distant recurrence (IDR) alone, 15 patients (15.31%) had extrahepatic recurrence (ER) alone, three patients (3.06%) had both LTP and IDR, six patients (6.12%) had both LTP and ER, and 17 patients (17.35%) had both IDR and ER. Patients without late recurrence had better long-term overall survival (OS) compared to those with late recurrence (p < 0.001). Male gender, multiple tumors, and cirrhosis were the independent risk factors of late recurrence. A well-discriminated and calibrated nomogram was constructed to predict the probability of RFS. Conclusion Male gender, multiple tumors, and cirrhosis are the independent risk factors of late recurrence after RFA for HCC within the Milan criteria. Late recurrence might mainly occur from de novo HCC under the background of cirrhosis. An individualized surveillance and prevention strategy for HCC patients after RFA should be developed. Key Points • In the present retrospective study of 398 patients, male gender, multiple tumors, and cirrhosis were the independent risk factors of late recurrence (> 2 years) of HCC after RFA. • The most common pattern of late recurrence was intrahepatic distant recurrence alone (n = 43, 43.88%). Late recurrence might mainly occur from de novo HCC under the background of cirrhosis. • A prognostic nomogram was built to predict the individualized recurrence-free survival after RFA, which achieved good calibration and discriminatory ability with a concordance index of 0.763.

Yi Yang and Yi Chen contributed equally to this work. * Xiang Zhou [email protected]

3

Department of Diagnostic Radiology, National Cancer Center/ National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China

4

Department of Interventional Ultraso