{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T09:00:00Z","timestamp":1766998800019,"version":"3.48.0"},"reference-count":48,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,27]],"date-time":"2025-12-27T00:00:00Z","timestamp":1766793600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Soonchunhyang University Research Fund"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: Globally, the incidence rate of hepatocellular carcinoma (HCC) has increased among elderly patients. Elderly patients often present with multiple comorbidities that affect treatment tolerance and outcomes, and the optimal management strategy for this population has not yet been established. Therefore, we assessed comorbidities in elderly patients and investigated the treatment outcomes of radiotherapy (RT) to liver-confined HCC. Methods: We retrospectively reviewed 40 elderly patients aged \u226570 years with liver-confined HCC, who were treated with RT between 2015 and 2023. Comorbidity was assessed by using the Charlson Comorbidity Index (CCI). Survival outcomes were analyzed using the Kaplan\u2013Meier method. Results: The median age was 75 years (range, 70\u201387 years). The Barcelona Clinic Liver Cancer stage was 0 in 7 patients, A in 10 patients, B in 9 patients, and C in 14 patients. Most patients (85%) had Child\u2013Pugh class A hepatic function before RT. The CCI scores ranged from 2 to 9 (median, 5). Various RT techniques were applied according to patients\u2019 condition, tumor burden, and treatment aim: three-dimensional conformal radiotherapy in four patients, intensity-modulated radiotherapy in 20 patients; and stereotactic body radiotherapy in 16 patients. RT was delivered with radical intent in 30 patients and with palliative intent in 10 patients. The median biological effective dose calculated with an \u03b1\/\u03b2 ratio of 10 was 53.7 Gy10 (range, 39\u2013134.4 Gy10). The median follow-up period after RT was 18 months. The 1-year local progression-free survival and overall survival (OS) rates were 74% and 81%, respectively, and the 3-year rates were 44% and 52%, respectively. Patients with CCI &lt; 5 had more favorable OS than those with CCI \u2265 5, but the difference was not statistically significant. Conclusions: RT for liver-confined HCC appears to be a feasible treatment option for elderly patients with multiple comorbidities.<\/jats:p>","DOI":"10.3390\/cancers18010091","type":"journal-article","created":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T08:47:27Z","timestamp":1766998047000},"page":"91","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Radiotherapy for Liver-Confined Hepatocellular Carcinoma in Elderly Patients with Comorbidity"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0637-4110","authenticated-orcid":false,"given":"Sun Hyun","family":"Bae","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology, Soonchunhyang University College of Medicine, Bucheon 14584, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7113-3623","authenticated-orcid":false,"given":"Young Seok","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine, Soonchunhyang University College of Medicine, Bucheon 14584, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8694-777X","authenticated-orcid":false,"given":"Sang Gyune","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine, Soonchunhyang University College of Medicine, Bucheon 14584, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeong-Ju","family":"Yoo","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine, Soonchunhyang University College of Medicine, Bucheon 14584, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jae Myeong","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Radiology, Soonchunhyang University College of Medicine, Bucheon 14584, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sanghyeok","family":"Lim","sequence":"additional","affiliation":[{"name":"Department of Radiology, Soonchunhyang University College of Medicine, Bucheon 14584, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jae Hong","family":"Jung","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Soonchunhyang University College of Medicine, Bucheon 14584, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1517-9950","authenticated-orcid":false,"given":"Chan Kyu","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Hematology-Oncology, Soonchunhyang University College of Medicine, Bucheon 14584, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,27]]},"reference":[{"key":"ref_1","first-page":"229","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1357","DOI":"10.1002\/cam4.4530","article-title":"The burden of primary liver cancer caused by specific etiologies from 1990 to 2019 at the global, regional, and national levels","volume":"11","author":"Yang","year":"2022","journal-title":"Cancer Med."},{"key":"ref_3","unstructured":"GBD 2019 Demographics Collaborators (2020). Global age-sex-specific fertility, mortality, healthy life expectancy (HALE), and population estimates in 204 countries and territories, 1950\u20132019: A comprehensive demographic analysis for the Global Burden of Disease Study 2019. Lancet, 396, 1160\u20131203."},{"key":"ref_4","first-page":"10","article-title":"Cancer statistics, 2025","volume":"75","author":"Siegel","year":"2025","journal-title":"CA Cancer J. Clin."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1521","DOI":"10.4254\/wjh.v7.i11.1521","article-title":"Management of hepatocellular carcinoma in the elderly","volume":"7","author":"Borzio","year":"2015","journal-title":"World J. Hepatol."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Ma, T., Weng, Z., Zhou, S., Feng, L., Qin, Z., and Ma, D. (2025). Global burden and regional inequalities of cancer in older adults from 1990 to 2021 and its projection until 2050. BMC Public Health, 25.","DOI":"10.1186\/s12889-025-24910-7"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1111\/hepr.12279","article-title":"Long-term outcome of elderly patients (75 years or older) with hepatocellular carcinoma","volume":"44","author":"Hori","year":"2014","journal-title":"Hepatol. Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"48","DOI":"10.3748\/wjg.v12.i1.48","article-title":"Hepatocellular carcinoma in extremely elderly patients: An analysis of clinical characteristics, prognosis and patient survival","volume":"12","author":"Tsukioka","year":"2006","journal-title":"World J. Gastroenterol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"140","DOI":"10.17998\/jlc.2025.08.05","article-title":"Surgical treatment of hepatocellular carcinoma: An expert consensus-based practical recommendation from the Korean Liver Cancer Association","volume":"25","author":"Park","year":"2025","journal-title":"J. Liver Cancer"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"145","DOI":"10.21873\/invivo.11451","article-title":"Characteristics and Outcomes of Extreme Elderly Patients With Hepatocellular Carcinoma in South Korea","volume":"33","author":"Seo","year":"2019","journal-title":"In Vivo"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2595","DOI":"10.1200\/JCO.2013.54.8347","article-title":"International Society of Geriatric Oncology consensus on geriatric assessment in older patients with cancer","volume":"32","author":"Wildiers","year":"2014","journal-title":"J. Clin. Oncol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1016\/j.jamcollsurg.2013.07.007","article-title":"Referral patterns and treatment choices for patients with hepatocellular carcinoma: A United States population-based study","volume":"217","author":"Hyder","year":"2013","journal-title":"J. Am. Coll. Surg."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"9","DOI":"10.2147\/JHC.S101448","article-title":"Hepatocellular carcinoma in elderly patients: Challenges and solutions","volume":"3","author":"Brunot","year":"2016","journal-title":"J. Hepatocell. Carcinoma"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/0021-9681(87)90171-8","article-title":"A new method of classifying prognostic comorbidity in longitudinal studies: Development and validation","volume":"40","author":"Charlson","year":"1987","journal-title":"J. Chronic Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1159\/000521288","article-title":"Charlson Comorbidity Index: A Critical Review of Clinimetric Properties","volume":"91","author":"Charlson","year":"2022","journal-title":"Psychother. Psychosom."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3901","DOI":"10.1007\/s00268-020-05686-w","article-title":"Predictive Value of the Age-Adjusted Charlson Comorbidity Index for Outcomes After Hepatic Resection of Hepatocellular Carcinoma","volume":"44","author":"Shinkawa","year":"2020","journal-title":"World J. Surg."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1683","DOI":"10.2147\/CMAR.S361495","article-title":"The Age-Adjusted Charlson Comorbidity Index Predicts Prognosis in Elderly Cancer Patients","volume":"14","author":"Zhou","year":"2022","journal-title":"Cancer Manag. Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1806","DOI":"10.1200\/JCO.21.02656","article-title":"Radiation Therapy in Older Adults With Cancer: A Critical Modality in Geriatric Oncology","volume":"40","author":"Amini","year":"2022","journal-title":"J. Clin. Oncol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.prro.2021.09.004","article-title":"External Beam Radiation Therapy for Primary Liver Cancers: An ASTRO Clinical Practice Guideline","volume":"12","author":"Apisarnthanarax","year":"2022","journal-title":"Pract. Radiat. Oncol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Jang, W.I., Jo, S., Moon, J.E., Bae, S.H., and Park, H.C. (2023). The Current Evidence of Intensity-Modulated Radiotherapy for Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis. Cancers, 15.","DOI":"10.3390\/cancers15204914"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/j.ijrobp.2023.08.015","article-title":"Stereotactic Body Radiation Therapy for Hepatocellular Carcinoma: Meta-Analysis and International Stereotactic Radiosurgery Society Practice Guidelines","volume":"118","author":"Bae","year":"2024","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"286","DOI":"10.17998\/jlc.2024.06.26","article-title":"Recent update of proton beam therapy for hepatocellular carcinoma: A systematic review and meta-analysis","volume":"24","author":"Bae","year":"2024","journal-title":"J. Liver Cancer"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Reig, M., Sanduzzi-Zamparelli, M., Forner, A., Rimola, J., Ferrer-Fabrega, J., Burrel, M., Garcia-Criado, A., Diaz, A., Llarch, N., and Iserte, G. (J. Hepatol., 2025). BCLC strategy for prognosis prediction and treatment recommendations: The 2025 update, J. Hepatol., in press.","DOI":"10.1016\/j.jhep.2025.10.020"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"98","DOI":"10.3857\/roj.2023.00353","article-title":"Radiotherapy trend in elderly hepatocellular carcinoma: Retrospective analysis of patients diagnosed between 2005 and 2017","volume":"41","author":"Bae","year":"2023","journal-title":"Radiat. Oncol. J."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"13715","DOI":"10.1038\/s41598-020-70624-8","article-title":"Recalibration and validation of the Charlson Comorbidity Index in an Asian population: The National Health Insurance Service-National Sample Cohort study","volume":"10","author":"Choi","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1080\/00365521.2025.2487539","article-title":"Non-liver comorbidity in patients with hepatocellular carcinoma and curative treatments\u2014A Swedish national registry study","volume":"60","author":"Helmersson","year":"2025","journal-title":"Scand. J. Gastroenterol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1420","DOI":"10.21037\/tcr-20-2912","article-title":"Treatment outcomes of helical tomotherapy for hepatocellular carcinoma in terms of intermediate-dose spillage","volume":"10","author":"Bae","year":"2021","journal-title":"Transl. Cancer Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3964","DOI":"10.21037\/tcr-22-1565","article-title":"Stereotactic body radiotherapy using helical tomotherapy for hepatocellular carcinoma: Clinical outcome and dosimetric comparison of Hi-ART vs. Radixact","volume":"11","author":"Bae","year":"2022","journal-title":"Transl. Cancer Res."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Guo, H., Wu, T., Lu, Q., Dong, J., Ren, Y.F., Nan, K.J., Lv, Y., and Zhang, X.F. (2017). Hepatocellular carcinoma in elderly: Clinical characteristics, treatments and outcomes compared with younger adults. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0184160"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"362","DOI":"10.17998\/jlc.2023.08.03","article-title":"The efficacy of treatment for hepatocellular carcinoma in elderly patients","volume":"23","author":"Lee","year":"2023","journal-title":"J. Liver Cancer"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1411","DOI":"10.21873\/invivo.11618","article-title":"A Review of Hepatocellular Carcinoma in Elderly Patients Focused on Management and Outcomes","volume":"33","author":"Cho","year":"2019","journal-title":"In Vivo"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.1002\/hep.1840360609","article-title":"NAFLD may be a common underlying liver disease in patients with hepatocellular carcinoma in the United States","volume":"36","author":"Marrero","year":"2002","journal-title":"Hepatology"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"274","DOI":"10.17998\/jlc.2024.08.13","article-title":"Evolving trends in treatment patterns for hepatocellular carcinoma in Korea from 2008 to 2022: A nationwide population-based study","volume":"24","author":"Han","year":"2024","journal-title":"J. Liver Cancer"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1206","DOI":"10.1093\/jnci\/djp239","article-title":"Association of a cancer diagnosis with vulnerability and frailty in older Medicare beneficiaries","volume":"101","author":"Mohile","year":"2009","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1016\/j.ijrobp.2007.04.016","article-title":"Proton beam therapy for aged patients with hepatocellular carcinoma","volume":"69","author":"Hata","year":"2007","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Shiba, S., Abe, T., Shibuya, K., Katoh, H., Koyama, Y., Shimada, H., Kakizaki, S., Shirabe, K., Kuwano, H., and Ohno, T. (2017). Carbon ion radiotherapy for 80 years or older patients with hepatocellular carcinoma. BMC Cancer, 17.","DOI":"10.1186\/s12885-017-3724-4"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1111\/hepr.12916","article-title":"Clinical outcomes of stereotactic body radiotherapy for elderly patients with hepatocellular carcinoma","volume":"48","author":"Teraoka","year":"2018","journal-title":"Hepatol. Res."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Iwata, H., Ogino, H., Hattori, Y., Nakajima, K., Nomura, K., Hayashi, K., Toshito, T., Sasaki, S., Hashimoto, S., and Mizoe, J.E. (2021). Image-Guided Proton Therapy for Elderly Patients with Hepatocellular Carcinoma: High Local Control and Quality of Life Preservation. Cancers, 13.","DOI":"10.3390\/cancers13020219"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1100","DOI":"10.1016\/j.jgo.2021.01.001","article-title":"Charlson comorbidity index and G8 in older old adult (\u226580 years) hepatocellular carcinoma patients treated with stereotactic body radiotherapy","volume":"12","author":"Loi","year":"2021","journal-title":"J. Geriatr. Oncol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"136","DOI":"10.17998\/jlc.2022.08.18","article-title":"Stereotactic body radiation therapy for elderly patients with small hepatocellular carcinoma: A retrospective observational study","volume":"22","author":"Jang","year":"2022","journal-title":"J. Liver Cancer"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"137","DOI":"10.4103\/jcrt.jcrt_1118_24","article-title":"Efficacy and safety of stereotactic body radiation therapy in elderly patients with cirrhosis and large advanced hepatocellular carcinoma","volume":"21","author":"Sharma","year":"2025","journal-title":"J. Cancer Res. Ther."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"15330338231206335","DOI":"10.1177\/15330338231206335","article-title":"Proton Beam Therapy and Photon-Based Magnetic Resonance Image-Guided Radiation Therapy: The Next Frontiers of Radiation Therapy for Hepatocellular Carcinoma","volume":"22","author":"Zaki","year":"2023","journal-title":"Technol. Cancer Res. Treat."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1929","DOI":"10.1007\/s11605-013-2324-0","article-title":"Surgical outcomes and clinical characteristics of elderly patients undergoing curative hepatectomy for hepatocellular carcinoma","volume":"17","author":"Hirokawa","year":"2013","journal-title":"J. Gastrointest. Surg."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Wang, C.M., Chen, Z.X., Ma, P.C., Chen, J.M., Jiang, D., Hu, X.Y., Ma, F.X., Hou, H., Ma, J.L., and Geng, X.P. (2023). Oncological prognosis and morbidity of hepatectomy in elderly patients with hepatocellular carcinoma: A propensity score matching and multicentre study. BMC Surg., 23.","DOI":"10.1186\/s12893-023-02230-0"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.prro.2023.08.016","article-title":"Defining Minimum Treatment Parameters of Ablative Radiation Therapy in Patients With Hepatocellular Carcinoma: An Expert Consensus","volume":"14","author":"Yanagihara","year":"2024","journal-title":"Pract. Radiat. Oncol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"3874","DOI":"10.1118\/1.2349696","article-title":"The management of respiratory motion in radiation oncology report of AAPM Task Group 76","volume":"33","author":"Keall","year":"2006","journal-title":"Med. Phys."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2166","DOI":"10.1093\/annonc\/mdr587","article-title":"Screening older cancer patients: First evaluation of the G-8 geriatric screening tool","volume":"23","author":"Bellera","year":"2012","journal-title":"Ann. Oncol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1016\/S0959-8049(99)00319-6","article-title":"Measuring comorbidity in older cancer patients","volume":"36","author":"Extermann","year":"2000","journal-title":"Eur. J. Cancer"}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/1\/91\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T08:56:54Z","timestamp":1766998614000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/1\/91"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,27]]},"references-count":48,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,1]]}},"alternative-id":["cancers18010091"],"URL":"https:\/\/doi.org\/10.3390\/cancers18010091","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,27]]}}}