Retrospective Analysis of Radiofrequency Ablation in Patients with Small Solitary Hepatocellular Carcinoma: Survival Outcomes and Development of a Machine Learning Prognostic Model

Abstract

Background and Objective

The effectiveness of radiofrequency ablation (RFA) in improving long-term survival outcomes for patients with a solitary hepatocellular carcinoma (HCC) measuring 5 cm or less remains uncertain. This study was designed to elucidate the impact of RFA therapy on the survival outcomes of these patients and to construct a prognostic model for patients following RFA.

Methods

This study was performed using the Surveillance, Epidemiology, and End Results (SEER) database from 2004 to 2017, focusing on patients diagnosed with a solitary HCC lesion ≤5 cm in size. We compared the overall survival (OS) and cancer-specific survival (CSS) rates of these patients with those of patients who received hepatectomy, radiotherapy, or chemotherapy or who were part of a blank control group. To enhance the reliability of our findings, we employed stabilized inverse probability treatment weighting (sIPTW) and stratified analyses. Additionally, we conducted a Cox regression analysis to identify prognostic factors. XGBoost models were developed to predict 1-, 3-, and 5-year CSS. The XGBoost models were evaluated via receiver operating characteristic (ROC) curves, calibration plots, decision curve analysis (DCA) curves and so on.

Results

Regardless of whether the data were unadjusted or adjusted for the use of sIPTWs, the 5-year OS (46.7%) and CSS (58.9%) rates were greater in the RFA group than in the radiotherapy (27.1%/35.8%), chemotherapy (32.9%/43.7%), and blank control (18.6%/30.7%) groups, but these rates were lower than those in the hepatectomy group (69.4%/78.9%). Stratified analysis based on age and cirrhosis status revealed that RFA and hepatectomy yielded similar OS and CSS outcomes for patients with cirrhosis aged over 65 years. Age, race, marital status, grade, cirrhosis status, tumor size, and AFP level were selected to construct the XGBoost models based on the training cohort. The areas under the curve (AUCs) for 1, 3, and 5 years in the validation cohort were 0.88, 0.81, and 0.79, respectively. Calibration plots further demonstrated the consistency between the predicted and actual values in both the training and validation cohorts.

Conclusion

RFA can improve the survival of patients diagnosed with a solitary HCC lesion ≤5 cm. In certain clinical scenarios, RFA achieves survival outcomes comparable to those of hepatectomy. The XGBoost models developed in this study performed admirably in predicting the CSS of patients with solitary HCC tumors smaller than 5 cm following RFA.

References

[1] Ahn KS, Kang KJ. Appropriate treatment modality for solitary small hepatocellular carcinoma: Radiofrequency ablation vs. resection vs. transplantation?. Clin Mol Hepatol, 2019, 25(4): 354-359.

[2] Chen MS, Li JQ, Zheng Y, et al. . A prospective randomized trial comparing percutaneous local ablative therapy and partial hepatectomy for small hepatocellular carcinoma. Ann Surg, 2006, 243(3): 321-328.

[3] Feng K, Yan J, Li X, et al. . A randomized controlled trial of radiofrequency ablation and surgical resection in the treatment of small hepatocellular carcinoma. J Hepatol, 2012, 57(4): 794-802.

[4] N’Kontchou G, Mahamoudi A, Aout M, et al. . Radiofrequency ablation of hepatocellular carcinoma: long-term results and prognostic factors in 235 Western patients with cirrhosis. Hepatology, 2009, 50(5): 1475-1483.

[5] Yang W, Yan K, Goldberg SN, et al. . Ten-year survival of hepatocellular carcinoma patients undergoing radiofrequency ablation as a first-line treatment. World J Gastroenterol, 2016, 22(10): 2993-3005.

[6] Xu Q, Kobayashi S, Ye X, et al. . Comparison of hepatic resection and radiofrequency ablation for small hepatocellular carcinoma: a meta-analysis of 16,103 patients. Sci Rep, 2014, 4: 7252.

[7] Huang G, Chen X, Lau WY, et al. . Quality of life after surgical resection compared with radiofrequency ablation for small hepatocellular carcinomas. Br J Surg, 2014, 101(8): 1006-1015.

[8] Huang J, Yan L, Cheng Z, et al. . A randomized trial comparing radiofrequency ablation and surgical resection for HCC conforming to the Milan criteria. Ann Surg, 2010, 252(6): 903-912.

[9] Kuo Y, Huang T, Yen H, et al. . Nomogram to Predict the Long-Term Overall Survival of Early-Stage Hepatocellular Carcinoma after Radiofrequency Ablation. Cancers (Basel), 2023, 15(12): 3156.

[10] Takuma Y, Shota I, Miyatake H, et al. . Nomograms to Predict the Disease-free Survival and Overall Survival after Radiofrequency Ablation for Hepatocellular Carcinoma. Intern Med, 2018, 57(4): 457-468.

[11] Tran KA, Kondrashova O, Bradley A, et al. . Deep learning in cancer diagnosis, prognosis and treatment selection. Genome Med, 2021, 13: 152.

[12] Jiang J, Pan H, Li M, et al. . Predictive model for the 5-year survival status of osteosarcoma patients based on the SEER database and XGBoost algorithm. Sci Rep, 2021, 11(1): 5542.

[13] Li C, Liu M, Li J, et al. . Machine learning predicts the prognosis of breast cancer patients with initial bone metastases. Front Public Health, 2022, 10: 1003976.

[14] Mathew G, Agha R, Albrecht J, et al. . STROCSS 2021: Strengthening the reporting of cohort, cross-sectional and case-control studies in surgery. Int J Surg, 2021, 96: 106165.

[15] Jia W, Shi W, Yao Q, et al. . Identifying immune infiltration by deep learning to assess the prognosis of patients with hepatocellular carcinoma. J Cancer Res Clin Oncol, 2023, 149(14): 12621-12635.

[16] Putot A, Bouiller K, Laborde C, et al. . Association Between Early Antibiotic Therapy and In-Hospital Mortality Among Older Patients With SARS-CoV-2 Pneumonia. J Gerontol A Biol Sci Med Sci, 2022, 77(4): e115-e123.

[17] Yu W, Lu Y, Shou H, et al. . A 5-year survival status prognosis of nonmetastatic cervical cancer patients through machine learning algorithms. Cancer Med, 2023, 12(6): 6867-6876.

[18] Ye Q, Chai X, Jiang D, et al. . Identification of active molecules against Mycobacterium tuberculosis through machine learning. Brief Bioinform, 2021, 22(5): bbab068.

[19] Yu Y, Tran H. An XGBoost-Based Fitted Q Iteration for Finding the Optimal STI Strategies for HIV Patients. IEEE Trans Neural Netw Learn Syst, 2024, 35(1): 648-656.

[20] Li C, Liu M, Zhang Y, et al. . Novel models by machine learning to predict prognosis of breast cancer brain metastases. J Transl Med, 2023, 21(1): 404.

[21] Bray F, Ferlay J, Soerjomataram I, et al. . Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2018, 68(6): 394-424.

[22] European Association For The Study Of The Liver European Organization For Research and Treatment Of Cancer. EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol, 2012, 56(4): 908-943.

[23] Stefanini B, Ielasi L, Chen R, et al. . TKIs in combination with immunotherapy for hepatocellular carcinoma. Expert Rev Anticancer Ther, 2023, 23(3): 279-291.

[24] Forner A, Reig M, Bruix J. Hepatocellular carcinoma. Lancet, 2018, 391(10127): 1301-1314.

[25] Sidali S, Trepo E, Sutter O, et al. . New concepts in the treatment of hepatocellular carcinoma. United European Gastroenterol J, 2022, 10(7): 765-774.

[26] Takayama T, Hasegawa K, Izumi N, et al. . Surgery versus Radiofrequency Ablation for Small Hepatocellular Carcinoma: A Randomized Controlled Trial (SURF Trial). Liver Cancer, 2022, 11(3): 209-218.

[27] Fang Y, Chen W, Liang X, et al. . Comparison of long-term effectiveness and complications of radiofrequency ablation with hepatectomy for small hepatocellular carcinoma. J Gastroenterol Hepatol, 2014, 29(1): 193-200.

[28] Dong SC, Bai DS, Wang FA, et al. . Radiofrequency ablation is an inferior option to liver resection for solitary hepatocellular carcinoma ≤5 cm without cirrhosis: A population-based study with stratification by tumor size. Hepatobiliary Pancreat Dis Int, 2023, 22(6): 605-614.

[29] Kim G, Lee HW. Development and validation of a prognostic model for patients with hepatocellular carcinoma undergoing radiofrequency ablation. Cancer Med, 2019, 8(11): 5023-5032.

[30] Ding M, Zhao X, Zhao M, et al. . Prognostic Nomogram for Patients with Hepatocellular Carcinoma After Thermal Ablation. Cardiovasc Intervent Radiol, 2020, 43(11): 1621-1630.

[31] Kao Y, Chiou Y, Hung H, et al. . Younger hepatocellular carcinoma patients have better prognosis after percutaneous radiofrequency ablation therapy. J Clin Gastroenterol, 2012, 46(1): 62-70.

[32] Waki K, Aikata H, Katamura Y, et al. . Chayama, K. Percutaneous radiofrequency ablation as first-line treatment for small hepatocellular carcinoma: results and prognostic factors on long-term follow up. J Gastroenterol Hepatol, 2010, 25(3): 597-604.

[33] Bai M, Cui M, Yang W, et al. . The 10-year Survival Analysis of Radiofrequency Ablation for Solitary Hepatocellular Carcinoma 5 cm or Smaller: Primary versus Recurrent HCC. Radiology, 2021, 300(2): 458-469.

[34] Krajc K, Mirosevic S, Sajovic J, et al. . Marital status and survival in cancer patients: A systematic review and meta-analysis. Cancer Med, 2023, 12(2): 1685-1708.

[35] Kao Y, Chiou Y, Hung H, et al. . Serum alpha-fetoprotein response can predict prognosis in hepatocellular carcinoma patients undergoing radiofrequency ablation therapy. Clin Radiol, 2012, 67(5): 429-436.

[36] Jia B, Zhang D, Ludwig M, et al. . Radiofrequency ablation versus resection for hepatocellular carcinoma in patients with Child-Pugh A liver cirrhosis: a meta-analysis. Clin Radiol, 2017, 72(12): 1066-1075.

[37] D’Avola D, Granito A, Torre-Alaez M, et al. . The importance of liver functional reserve in the nonsurgical treatment of hepatocellular carcinoma. J Hepatol, 2022, 76(5): 1185-1198.