Risk Group Stratification for Recurrence-Free Survival and Early Tumor Recurrence after Radiofrequency Ablation for Hepatocellular Carcinoma

Simple Summary Early detection and treatment of recurrence after radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) are important steps to improving patient survival. Although the prognosis after RFA for HCC may vary according to different risk levels, there is no standardized follow-up protocol according to each patient’s risk. This study aimed to stratify the patients according to their risk of recurrence-free survival (RFS) and early (≤2 years) tumor recurrence (ETR) based on predictive models and to evaluate whether the risk groups show differences in restricted mean survival times after RFA for HCC. Our predictive models were able to stratify patients into three groups according to their risk of RFS and ETR. The risk groups showed differences in RMSTs, which may be used to establish different follow-up protocols for the three risk groups. Abstract Purpose: Although the prognosis after radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) may vary according to different risk levels, there is no standardized follow-up protocol according to each patient’s risk. This study aimed to stratify patients according to their risk of recurrence-free survival (RFS) and early (≤2 years) tumor recurrence (ETR) after RFA for HCC based on predictive models and nomograms and to compare the survival times of the risk groups derived from the models. Methods: Patients who underwent RFA for a single HCC (≤3 cm) between January 2012 and March 2014 (n = 152) were retrospectively reviewed. Patients were classified into low-, intermediate-, and high-risk groups based on the total nomogram points for RFS and ETR, respectively, and compared for each outcome. Restricted mean survival times (RMSTs) in the three risk groups were evaluated for both RFS and ETR to quantitatively evaluate the difference in survival times. Results: Predictive models for RFS and ETR were constructed with c-indices of 0.704 and 0.730, respectively. The high- and intermediate-risk groups for RFS had an 8.5-fold and 2.9-fold higher risk of events than the low-risk group (both p < 0.001), respectively. The high- and intermediate-risk groups for ETR had a 17.7-fold and 7.0-fold higher risk than the low-risk group (both p < 0.001), respectively. The RMST in the high-risk group was significantly lower than that in the other two groups 9 months after RFA, and that in the intermediate-risk group became lower than that in the low-risk group after 21 months with RFS and 24 months with ETR. Conclusion: Our predictive models were able to stratify patients into three groups according to their risk of RFS and ETR after RFA for HCC. Differences in RMSTs may be used to establish different follow-up protocols for the three risk groups.

[1]  Kyunghwa Han,et al.  Restricted Mean Survival Time for Survival Analysis: A Quick Guide for Clinical Researchers , 2022, Korean journal of radiology.

[2]  Yong-Yuan Zhang,et al.  Preoperative Gadoxetic Acid-Enhanced MRI Based Nomogram Improves Prediction of Early HCC Recurrence After Ablation Therapy , 2021, Frontiers in Oncology.

[3]  M. Lee,et al.  Rim-arterial enhancing primary hepatic tumors with other targetoid appearance show early recurrence after radiofrequency ablation , 2021, European Radiology.

[4]  K. Carriere,et al.  Interobserver Variability and Diagnostic Performance of Gadoxetic Acid-enhanced MRI for Predicting Microvascular Invasion in Hepatocellular Carcinoma. , 2020, Radiology.

[5]  Young Kon Kim,et al.  Preoperative Prediction for Early Recurrence Can Be as Accurate as Postoperative Assessment in Single Hepatocellular Carcinoma Patients , 2020, Korean journal of radiology.

[6]  J. Han,et al.  Evaluation of a serum tumour marker‐based recurrence prediction model after radiofrequency ablation for hepatocellular carcinoma , 2020, Liver international : official journal of the International Association for the Study of the Liver.

[7]  Mohammad Ziaul Islam Chowdhury,et al.  Variable selection strategies and its importance in clinical prediction modelling , 2020, Family Medicine and Community Health Journal.

[8]  D. Lu,et al.  Updated 10-year outcomes of percutaneous radiofrequency ablation as first-line therapy for single hepatocellular carcinoma < 3 cm: emphasis on association of local tumor progression and overall survival , 2020, European Radiology.

[9]  J. I. Lee,et al.  Development and validation of a prognostic model for patients with hepatocellular carcinoma undergoing radiofrequency ablation , 2019, Cancer medicine.

[10]  D. Sinn,et al.  Effect of Microvascular Invasion Risk on Early Recurrence of Hepatocellular Carcinoma After Surgery and Radiofrequency Ablation , 2019, Annals of surgery.

[11]  M. Abecassis,et al.  Diagnosis, Staging, and Management of Hepatocellular Carcinoma: 2018 Practice Guidance by the American Association for the Study of Liver Diseases , 2018, Hepatology.

[12]  P. Nahon,et al.  Percutaneous treatment of hepatocellular carcinoma: State of the art and innovations. , 2017, Journal of hepatology.

[13]  D. Sinn,et al.  Preoperative gadoxetic acid-enhanced MRI for predicting microvascular invasion in patients with single hepatocellular carcinoma. , 2017, Journal of hepatology.

[14]  C. Compton,et al.  The Eighth Edition AJCC Cancer Staging Manual: Continuing to build a bridge from a population‐based to a more “personalized” approach to cancer staging , 2017, CA: a cancer journal for clinicians.

[15]  J. Joh,et al.  Serum Tumor Markers Provide Refined Prognostication in Selecting Liver Transplantation Candidate for Hepatocellular Carcinoma Patients Beyond the Milan Criteria , 2016, Annals of surgery.

[16]  Y. Paik,et al.  Long-term Therapeutic Outcomes of Radiofrequency Ablation for Subcapsular versus Nonsubcapsular Hepatocellular Carcinoma: A Propensity Score Matched Study. , 2016, Radiology.

[17]  S. Behr,et al.  Rate of observation and inter-observer agreement for LI-RADS major features at CT and MRI in 184 pathology proven hepatocellular carcinomas , 2016, Abdominal Radiology.

[18]  B. Choi,et al.  Non-hypervascular hepatobiliary phase hypointense nodules on gadoxetic acid-enhanced MRI: risk of HCC recurrence after radiofrequency ablation. , 2015, Journal of hepatology.

[19]  Yong Eun Chung,et al.  Single Hepatocellular Carcinoma: Preoperative MR Imaging to Predict Early Recurrence after Curative Resection. , 2015, Radiology.

[20]  B. Sangro,et al.  Assessment of liver function in patients with hepatocellular carcinoma: a new evidence-based approach-the ALBI grade. , 2015, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[21]  Y. Paik,et al.  Small Hepatocellular Carcinoma: Radiofrequency Ablation versus Nonanatomic Resection--Propensity Score Analyses of Long-term Outcomes. , 2015, Radiology.

[22]  T. Vogl,et al.  Image-guided tumor ablation: standardization of terminology and reporting criteria--a 10-year update. , 2014, Radiology.

[23]  Y. Hao,et al.  Preoperative Aspartate Aminotransferase to Platelet Ratio is an Independent Prognostic Factor for Hepatitis B-Induced Hepatocellular Carcinoma After Hepatic Resection , 2014, Annals of Surgical Oncology.

[24]  Myeong-Jin Kim,et al.  Hyperintense HCC on hepatobiliary phase images of gadoxetic acid-enhanced MRI: correlation with clinical and pathological features. , 2012, European journal of radiology.

[25]  Ryosuke Tateishi,et al.  nature publishing group ORIGINAL CONTRIBUTIONS 569 CME Radiofrequency Ablation for Hepatocellular Carcinoma: 10-Year Outcome and Prognostic Factors LIVER , 2022 .

[26]  Sandro Rossi,et al.  Repeated radiofrequency ablation for management of patients with cirrhosis with small hepatocellular carcinomas: A long‐term cohort study , 2011, Hepatology.

[27]  James Sayre,et al.  Influence of large peritumoral vessels on outcome of radiofrequency ablation of liver tumors. , 2003, Journal of vascular and interventional radiology : JVIR.

[28]  M. Dumont,et al.  European Association for the Study of the Liver , 1971 .

[29]  Corrigendum to "EASL Clinical Practice Guidelines: Management of hepatocellular carcinoma" [J Hepatol 69 (2018) 182-236]. , 2019, Journal of hepatology.

[30]  M. Kudo,et al.  The ALBI grade provides objective hepatic reserve estimation across each BCLC stage of hepatocellular carcinoma. , 2017, Journal of hepatology.

[31]  M. Choi,et al.  Ten-year outcomes of percutaneous radiofrequency ablation as first-line therapy of early hepatocellular carcinoma: analysis of prognostic factors. , 2013, Journal of hepatology.

[32]  H. El‐Serag,et al.  Hepatocellular carcinoma. , 2011, The New England journal of medicine.

[33]  D. Woodfield Hepatocellular carcinoma. , 1986, The New Zealand medical journal.