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30.09.2023 | Original Scientific Report

Machine-Based Learning Hierarchical Cluster Analysis: Sex-Based Differences in Prognosis Following Resection of Hepatocellular Carcinoma

verfasst von: Vivian Resende, Diamantis I. Tsilimigras, Yutaka Endo, Alfredo Guglielmi, Francesca Ratti, Luca Aldrighetti, Hugo P. Marques, Olivier Soubrane, Vincent Lam, George A. Poultsides, Irinel Popescu, Sorin Alexandrescu, Ana Gleisner, Guillaume Martel, Tom Hugh, Itaru Endo, Feng Shen, Timothy M. Pawlik

Erschienen in: World Journal of Surgery | Ausgabe 12/2023

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Abstract

Background

Patients with hepatocellular carcinoma (HCC) may have a heterogeneous presentation, as well as different long-term outcomes following surgical resection. We sought to use machine learning to cluster patients into different prognostic groups based on preoperative characteristics.

Methods

Patients who underwent curative-intent liver resection for HCC between 2000 and 2020 were identified from a large international multi-institutional database. A hierarchical cluster analysis was performed based on preoperative factors to characterize patterns of presentation and define disease-free survival (DFS).

Results

Among 966 with HCC, 3 distinct clusters were identified: Cluster 1 (n = 160, 16.5%), Cluster 2 (n = 537, 55.6%) and Cluster 3 (n = 269, 27.8%). Cluster 1 (n = 160, 16.5%) consisted of female patients (n = 160, 100%), low inflammation-based scores, intermediate tumor burden score (TBS) (median: 4.71) and high alpha-fetoprotein (AFP) levels (median 41.3 ng/mL); Cluster 2 consisted of male individuals (n = 537, 100%), mainly with a history of HBV infection (n = 429, 79.9%), low inflammation-based scores, intermediate AFP levels (median 26.0 ng/mL) and lower TBS (median 4.49); Cluster 3 was comprised of older patients (median age 68 years) predominantly male (n = 248, 92.2%) who had low incidence of HBV/HCV infection (7.1% and 8.2%, respectively), intermediate AFP levels (median 16.8 ng/mL), high inflammation-based scores and high TBS (median 6.58). Median DFS worsened incrementally among the three different clusters with Cluster 3 having the lowest DFS (Cluster 1: median not reached; Cluster 2: 34 months, 95% CI 23.0–48.0, Cluster 3: 19 months, 95% CI 15.0–29.0, p < 0.05).

Conclusion

Cluster analysis classified HCC patients into three distinct prognostic groups. Cluster assignment predicted DFS following resection of HCC with the female cluster having the most favorable prognosis following HCC resection.

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Veracruz N, Gish RG, Cheung R, Chitnis AS, Wong RJ (2022) Global incidence and mortality of hepatitis B and hepatitis C acute infections, cirrhosis and hepatocellular carcinoma from 2010 to 2019. J Viral Hepat 29(5):352–365. https://doi.org/10.1111/jvh.13663CrossRefPubMed

Llovet JM, Kelley RK, Villanueva A et al (2021) Hepatocellular carcinoma. Nat Rev Dis Primer 7(1):6. https://doi.org/10.1038/s41572-020-00240-3CrossRef

Pinna AD, Yang T, Mazzaferro V et al (2018) Liver transplantation and hepatic resection can achieve cure for hepatocellular carcinoma. Ann Surg 268(5):868–875. https://doi.org/10.1097/SLA.0000000000002889CrossRefPubMed

Tsilimigras DI, Bagante F, Moris D et al (2019) Defining the chance of cure after resection for hepatocellular carcinoma within and beyond the Barcelona clinic liver cancer guidelines: a multi-institutional analysis of 1010 patients. Surgery 166(6):967–974. https://doi.org/10.1016/j.surg.2019.08.010CrossRefPubMed

Tsilimigras DI, Mehta R, Guglielmi A et al (2020) Recurrence beyond the Milan criteria after curative-intent resection of hepatocellular carcinoma: a novel tumor-burden based prediction model. J Surg Oncol 122(5):955–963. https://doi.org/10.1002/jso.26091CrossRefPubMed

Beumer BR, Buettner S, Galjart B et al (2022) Systematic review and meta-analysis of validated prognostic models for resected hepatocellular carcinoma patients. Eur J Surg Oncol J Eur Soc Surg Oncol Br Assoc Surg Oncol 48(3):492–499. https://doi.org/10.1016/j.ejso.2021.09.012CrossRef

Calderon-Martinez E, Landazuri-Navas S, Vilchez E et al (2023) Prognostic scores and survival rates by etiology of hepatocellular carcinoma: a review. J Clin Med Res 15(4):200–207. https://doi.org/10.14740/jocmr4902CrossRefPubMedPubMedCentral

Nemes S, Jonasson JM, Genell A, Steineck G (2009) Bias in odds ratios by logistic regression modelling and sample size. BMC Med Res Methodol 9:56. https://doi.org/10.1186/1471-2288-9-56CrossRefPubMedPubMedCentral

Lash TL, Fox MP, MacLehose RF, Maldonado G, McCandless LC, Greenland S (2014) Good practices for quantitative bias analysis. Int J Epidemiol 43(6):1969–1985. https://doi.org/10.1093/ije/dyu149CrossRefPubMed

10.

Tsilimigras DI, Hyer JM, Paredes AZ et al (2020) A novel classification of intrahepatic cholangiocarcinoma phenotypes using machine learning techniques: an international multi-institutional analysis. Ann Surg Oncol 27(13):5224–5232. https://doi.org/10.1245/s10434-020-08696-zCrossRefPubMed

11.

Tsilimigras DI, Mehta R, Moris D et al (2020) A machine-based approach to preoperatively identify patients with the most and least benefit associated with resection for intrahepatic cholangiocarcinoma: an international multi-institutional analysis of 1146 patients. Ann Surg Oncol 27(4):1110–1119. https://doi.org/10.1245/s10434-019-08067-3CrossRefPubMed

12.

Endo Y, Lima HA, Alaimo L et al (2023) Preoperative risk score (PreopScore) to predict overall survival after resection for hepatocellular carcinoma. HPB 25(3):353–362. https://doi.org/10.1016/j.hpb.2022.12.009CrossRefPubMed

13.

Johnson PJ, Berhane S, Kagebayashi C et al (2015) Assessment of liver function in patients with hepatocellular carcinoma: a new evidence-based approach-the ALBI grade. J Clin Oncol Off J Am Soc Clin Oncol 33(6):550–558. https://doi.org/10.1200/JCO.2014.57.9151CrossRef

14.

Lima HA, Endo Y, Alaimo L et al (2022) Tumor burden score and serum alpha-fetoprotein subclassify intermediate-stage hepatocellular Carcinoma. J Gastrointest Surg Off J Soc Surg Aliment Tract 26(12):2512–2521. https://doi.org/10.1007/s11605-022-05469-9CrossRef

15.

Tsilimigras DI, Hyer JM, Diaz A et al (2021) Impact of time-to-surgery on outcomes of patients undergoing curative-intent liver resection for BCLC-0, A and B hepatocellular carcinoma. J Surg Oncol 123(2):381–388. https://doi.org/10.1002/jso.26297CrossRefPubMed

16.

Kaiser HF (1958) The varimax criterion for analytic rotation in factor analysis. Psychometrika 23(3):187–200. https://doi.org/10.1007/BF02289233CrossRef

17.

Komaru Y, Yoshida T, Hamasaki Y, Nangaku M, Doi K (2020) Hierarchical clustering analysis for predicting 1-year mortality after starting hemodialysis. Kidney Int Rep 5(8):1188–1195. https://doi.org/10.1016/j.ekir.2020.05.007CrossRefPubMedPubMedCentral

18.

Ward JH (1963) Hierarchical grouping to optimize an objective function. J Am Stat Assoc 58(301):236–244. https://doi.org/10.1080/01621459.1963.10500845CrossRef

19.

Ogbuabor GFNU (2018) Clustering algorithm for a healthcare dataset using silhouette score value. Int J Comput Sci Inf Technol 10(2):27–37. https://doi.org/10.5121/ijcsit.2018.10203CrossRef

20.

Chidambaranathan-Reghupaty S, Fisher PB, Sarkar D (2021) Hepatocellular carcinoma (HCC): epidemiology, etiology and molecular classification. Adv Cancer Res 149:1–61. https://doi.org/10.1016/bs.acr.2020.10.001CrossRefPubMed

21.

Qiu ZC, Li C, Zhang Y et al (2023) Tumor burden score-AFP-albumin-bilirubin grade score predicts the survival of patients with hepatocellular carcinoma after liver resection. Langenbecks Arch Surg 408(1):250. https://doi.org/10.1007/s00423-023-02993-3CrossRefPubMed

22.

Tsilimigras DI, Bagante F, Moris D et al (2020) Recurrence patterns and outcomes after resection of hepatocellular carcinoma within and beyond the Barcelona clinic liver cancer criteria. Ann Surg Oncol 27(7):2321–2331. https://doi.org/10.1245/s10434-020-08452-3CrossRefPubMed

23.

Shakeel PM, Baskar S, Dhulipala VRS, Jaber MM (2018) Cloud based framework for diagnosis of diabetes mellitus using K-means clustering. Health Inf Sci Syst 6(1):16. https://doi.org/10.1007/s13755-018-0054-0CrossRefPubMedPubMedCentral

24.

Zhou Y, Varzaneh MG (2022) Efficient and scalable patients clustering based on medical big data in cloud platform. J Cloud Comput Heidelb Ger 11(1):49. https://doi.org/10.1186/s13677-022-00324-3CrossRef

25.

Liu Y, Chen PHC, Krause J, Peng L (2019) How to read articles that use machine learning: users’ guides to the medical literature. JAMA 322(18):1806–1816. https://doi.org/10.1001/jama.2019.16489CrossRefPubMed

26.

Trevor H, Tibshirani R, Friedman J (2009) Hierarchical clustering. The elements of statistical learning, 2nd edn. Springer, New York, pp 520–528

27.

Moore MM, Chua W, Charles KA, Clarke SJ (2010) Inflammation and cancer: causes and consequences. Clin Pharmacol Ther 87(4):504–508. https://doi.org/10.1038/clpt.2009.254CrossRefPubMed

28.

Esper DH, Harb WA (2005) The cancer cachexia syndrome: a review of metabolic and clinical manifestations. Nutr Clin Pract Off Publ Am Soc Parenter Enter Nutr 20(4):369–376. https://doi.org/10.1177/0115426505020004369CrossRef

29.

Fa A, Danos DM, Maniscalco L et al (2023) Is There really a difference in outcomes between men and women with hepatocellular cancer? Cancers 15(11):2892. https://doi.org/10.3390/cancers15112892CrossRefPubMedPubMedCentral

30.

Sempokuya T, Warner J, Azawi M, Nogimura A, Wong LL (2022) Current status of disparity in liver disease. World J Hepatol 14(11):1940–1952. https://doi.org/10.4254/wjh.v14.i11.1940CrossRefPubMedPubMedCentral

31.

Ruggieri A, Barbati C, Malorni W (2010) Cellular and molecular mechanisms involved in hepatocellular carcinoma gender disparity. Int J Cancer 127(3):499–504. https://doi.org/10.1002/ijc.25298CrossRefPubMed

32.

Li Y, Xu A, Jia S, Huang J (2019) Recent advances in the molecular mechanism of sex disparity in hepatocellular carcinoma. Oncol Lett 17(5):4222–4228. https://doi.org/10.3892/ol.2019.10127CrossRefPubMedPubMedCentral

33.

Zheng B, Zhu YJ, Wang HY, Chen L (2017) Gender disparity in hepatocellular carcinoma (HCC): multiple underlying mechanisms. Sci China Life Sci 60(6):575–584. https://doi.org/10.1007/s11427-016-9043-9CrossRefPubMed

34.

Ladenheim MR, Kim NG, Nguyen P et al (2016) Sex differences in disease presentation, treatment and clinical outcomes of patients with hepatocellular carcinoma: a single-centre cohort study. BMJ Open Gastroenterol 3(1):e000107. https://doi.org/10.1136/bmjgast-2016-000107CrossRefPubMedPubMedCentral

35.

Li T, Qin LX, Gong X et al (2014) Clinical characteristics, outcome, and risk factors for early and late intrahepatic recurrence of female patients after curative resection of hepatocellular carcinoma. Surgery 156(3):651–660. https://doi.org/10.1016/j.surg.2014.04.008CrossRefPubMed

36.

Lam CM, Yong JL, Chan AO et al (2005) Better survival in female patients with hepatocellular carcinoma: oral contraceptive pills related? J Clin Gastroenterol 39(6):533. https://doi.org/10.1097/01.mcg.0000165670.25272.46CrossRefPubMed

37.

Liang T, He Y, Mo S et al (2022) Gender disparity in hepatocellular carcinoma recurrence after curative hepatectomy. Ann Hepatol 27(3):100695. https://doi.org/10.1016/j.aohep.2022.100695CrossRefPubMed

38.

Tsilimigras DI, Hyer JM, Diaz A et al (2021) Synergistic impact of alpha-fetoprotein and tumor burden on long-term outcomes following curative-intent resection of hepatocellular Carcinoma. Cancers 13(4):747. https://doi.org/10.3390/cancers13040747CrossRefPubMedPubMedCentral

Titel: Machine-Based Learning Hierarchical Cluster Analysis: Sex-Based Differences in Prognosis Following Resection of Hepatocellular Carcinoma
verfasst von: Vivian Resende
Diamantis I. Tsilimigras
Yutaka Endo
Alfredo Guglielmi
Francesca Ratti
Luca Aldrighetti
Hugo P. Marques
Olivier Soubrane
Vincent Lam
George A. Poultsides
Irinel Popescu
Sorin Alexandrescu
Ana Gleisner
Guillaume Martel
Tom Hugh
Itaru Endo
Feng Shen
Timothy M. Pawlik
Publikationsdatum: 30.09.2023
Verlag: Springer International Publishing
Erschienen in: World Journal of Surgery / Ausgabe 12/2023
Print ISSN: 0364-2313
Elektronische ISSN: 1432-2323
DOI: https://doi.org/10.1007/s00268-023-07194-z

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Machine-Based Learning Hierarchical Cluster Analysis: Sex-Based Differences in Prognosis Following Resection of Hepatocellular Carcinoma