Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209–49. https://doi.org/10.3322/caac.21660.

Article  PubMed  Google Scholar 

Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008;359(4):378–90. https://doi.org/10.1056/NEJMoa0708857.

Article  CAS  PubMed  Google Scholar 

Cheng AL, Kang YK, Chen Z, Tsao CJ, Qin S, Kim JS, et al. Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial. Lancet Oncol. 2009;10(1):25–34. https://doi.org/10.1016/S1470-2045(08)70285-7.

Article  CAS  PubMed  Google Scholar 

Bruix J, Cheng AL, Meinhardt G, Nakajima K, De Sanctis Y, Llovet J. Prognostic factors and predictors of sorafenib benefit in patients with hepatocellular carcinoma: analysis of two phase III studies. J Hepatol. 2017;67:999–1008. https://doi.org/10.1016/j.jhep.2017.06.026.

Article  CAS  PubMed  Google Scholar 

Kudo M, Finn RS, Qin S, Han KH, Ikeda K, Piscaglia F, et al. Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial. Lancet. 2018;391(10126):1163–73. https://doi.org/10.1016/S0140-6736(18)30207-1.

Article  CAS  PubMed  Google Scholar 

Cheng AL, Qin S, Ikeda M, Galle PR, Ducreux M, Kim TY, et al. Updated efficacy and safety data from IMbrave150: atezolizumab plus bevacizumab vs. sorafenib for unresectable hepatocellular carcinoma. J Hepatol. 2022;76(4):862–73. https://doi.org/10.1016/j.jhep.2021.11.030.

Article  CAS  PubMed  Google Scholar 

Abou-Alfa GK, Lau G, Kudo M, Chan SL, Kelley RK, Furuse J, et al. Tremelimumab plus durvalumab in unresectable hepatocellular carcinoma. NEJM Evid. 2022. https://doi.org/10.1056/EVIDoa2100070.

Article  Google Scholar 

Bruix J, Qin S, Merle P, Granito A, Huang YH, Bodoky G, et al. Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2017;389(10064):56–66. https://doi.org/10.1016/S0140-6736(16)32453-9.

Article  CAS  PubMed  Google Scholar 

Abou-Alfa GK, Meyer T, Cheng AL, El-Khoueiry AB, Rimassa L, Ryoo BY, et al. Cabozantinib in patients with advanced and progressing hepatocellular carcinoma. N Engl J Med. 2018;379(1):54–63. https://doi.org/10.1056/NEJMoa1717002.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Zhu AX, Kang YK, Yen CJ, Finn RS, Galle PR, Llovet JM, et al. Ramucirumab after sorafenib in patients with advanced hepatocellular carcinoma and increased α-fetoprotein concentrations (REACH-2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2019;20(2):282–96. https://doi.org/10.1016/S1470-2045(18)30937-9.

Article  CAS  PubMed  Google Scholar 

Hutchins LF, Unger JM, Crowley JJ, Coltman CA Jr, Albain KS. Underrepresentation of patients 65 years of age or older in cancer-treatment trials. N Engl J Med. 1999;341(27):2061–7. https://doi.org/10.1056/NEJM199912303412706.

Article  CAS  PubMed  Google Scholar 

Tada T, Kumada T, Hiraoka A, Michitaka K, Atsukawa M, Hirooka M, et al. Safety and efficacy of lenvatinib in elderly patients with unresectable hepatocellular carcinoma: a multicenter analysis with propensity score matching. Hepatol Res. 2020;50(1):75–83. https://doi.org/10.1111/hepr.13427.

Article  CAS  PubMed  Google Scholar 

Freites-Martinez A, Santana N, Arias-Santiago S, Viera A. Using the Common Terminology Criteria for Adverse Events (CTCAE—Version 5.0) to evaluate the severity of adverse events of anticancer therapies. Actas Dermosifiliogr (Engl Ed). 2021;112(1):90–2.

Article  CAS  PubMed  Google Scholar 

Decoster L, van Puyvelde SK, Mohile U, Wedding U, Basso G, Colloca S, et al. Screening tools for multidimensional health problems warranting a geriatric assessment in older cancer patients: an update on SIOG recommendations. Ann Oncol. 2015;26:288–300. https://doi.org/10.1093/annonc/mdu210.

Article  CAS  PubMed  Google Scholar 

Hajiev S, Allara E, Motedayen Aval L, Arizumi T, Bettinger D, Pirisi M, et al. Impact of age on sorafenib outcomes in hepatocellular carcinoma: an international cohort study. Br J Cancer. 2021;124(2):407–13. https://doi.org/10.1038/s41416-020-01116-9.

Article  CAS  PubMed  Google Scholar 

Zhang D, Wang X, Zhang M, Yin Y, Guo J. Clinical efficacy of chemotherapy in colorectal cancer patients over 80 years old. Int J Colorectal Dis. 2022;37(8):1853–63. https://doi.org/10.1007/s00384-022-04222-7.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Owonikoko TK, Ragin CC, Belani CP, Oton AB, Gooding WE, Taioli E, et al. Lung cancer in elderly patients: an analysis of the surveillance, epidemiology, and end results database. J Clin Oncol. 2007;25(35):5570–7. https://doi.org/10.1200/JCO.2007.12.5435.

Article  PubMed  Google Scholar 

Shachar SS, Hurria A, Muss HB. Breast cancer in women older than 80 years. J Oncol Pract. 2016;12(2):123–32. https://doi.org/10.1200/JOP.2015.010207.

Article  PubMed  Google Scholar 

Tada T, Kumada T, Hiraoka A, Hirooka M, Kariyama K, Tani J, Real-life Practice Experts for HCC (RELPEC) Study Group and the Hepatocellular Carcinoma Experts from 48 clinics in Japan (HCC 48) Group, et al. Safety and efficacy of atezolizumab plus bevacizumab in elderly patients with hepatocellular carcinoma: a multicenter analysis. Cancer Med. 2022;11(20):3796–808. https://doi.org/10.1002/cam4.4763.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Vithayathil M, D’Alessio A, Fulgenzi CAM, Nishida N, Schönlein M, von Felden J, et al. Impact of older age in patients receiving atezolizumab and bevacizumab for hepatocellular carcinoma. Liver Int. 2022;42(11):2538–47. https://doi.org/10.1111/liv.15405.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Rimini M, Rimassa L, Ueshima K, Burgio V, Shigeo S, Tada T, et al. Atezolizumab plus bevacizumab versus lenvatinib or sorafenib in non-viral unresectable hepatocellular carcinoma: an international propensity score matching analysis. ESMO Open. 2022;7(6): 100591. https://doi.org/10.1016/j.esmoop.2022.100591.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Casadei-Gardini A, Rimini M, Tada T, Suda G, Shimose S, Kudo M, et al. Atezolizumab plus bevacizumab versus lenvatinib for unresectable hepatocellular carcinoma: a large real-life worldwide population. Eur J Cancer. 2023;180:9–20. https://doi.org/10.1016/j.ejca.2022.11.017.

Article  CAS  PubMed  Google Scholar 

Wildiers H, Heeren P, Puts M, Topinkova E, Janssen-Heijnen ML, Extermann M, et al. International Society of Geriatric Oncology consensus on geriatric assessment in older patients with cancer. J Clin Oncol. 2014;32(24):2595–603. https://doi.org/10.1200/JCO.2013.54.8347.

Article  PubMed  PubMed Central  Google Scholar 

Mohile SG, Dale W, Somerfield MR, Hurria A. Practical assessment and management of vulnerabilities in older patients receiving chemotherapy: ASCO Guideline for Geriatric Oncology Summary. J Oncol Pract. 2018;14(7):442–6. https://doi.org/10.1200/JOP.18.00180.

Article  PubMed  Google Scholar 

Dotan E, Walter LC, Browner IS, Clifton K, Cohen HJ, Extermann M, et al. NCCN Guidelines® insights: older adult oncology, version 1.2021. J Natl Compr Cancer Netw. 2021;19(9):1006–19. https://doi.org/10.6004/jnccn.2021.0043.

Article  Google Scholar 

Alexander K, Korc-Grodzicki B. Comprehensive geriatric assessment (CGA) for cancer patients. In: Extermann M, editor. Geriatric oncology. Cham: Springer International Publishing; 2018. p. 1–14.

Google Scholar 

Bruijnen CP, Heijmer A, van Harten-Krouwel DG, van den Bos F, de Bree R, Witteveen PO, et al. Validation of the G8 screening tool in older patients with cancer considered for surgical treatment. J Geriatr Oncol. 2021;12(5):793–8. https://doi.org/10.1016/j.jgo.2020.10.017.

Article  CAS  PubMed  Google Scholar 

Socha K, Sołtysik BK, Cieślak-Skubel A, Piechocka-Wochniak E, Błaszczak R, Kostka T. Validation of the Vulnerable Elders Survey-13 (VES-13) in hospitalized older patients. Eur Geriatr Med. 2016;7(5):449–53. https://doi.org/10.1016/j.eurger.2016.03.008.

Article  Google Scholar 

Yang CJ, Brown AB, Deng JZ, Lui NS, Backhus LM, Shrager JB, et al. The oldest old: a national analysis of outcomes for patients 90 years or older with lung cancer. Ann Thorac Surg. 2020;109(2):350–7. https://doi.org/10.1016/j.athoracsur.2019.09.027.

Article  PubMed  Google Scholar 

Nakayama Y, Kawamura H, Honda M, Takano Y, Takiguchi K, Kamiga T, et al. Benefit of intensive chemotherapy for elderly patients aged 80 years or older with metastatic colorectal cancer: a state-wide multicenter cohort study. Int J Clin Oncol. 2021;26(7):1248–56. https://doi.org/10.1007/s10147-021-01909-9.

Article  CAS  PubMed  Google Scholar 

Takahashi A, Moriguchi M, Seko Y, Ishikawa H, Yo T, Kimura H, et al. Impact of relative dose intensity of early-phase lenvatinib treatment on therapeutic response in hepatocellular carcinoma. Anticancer Res. 2019;39(9):5149–56. https://doi.org/10.21873/anticanres.13710.

Article  CAS  PubMed  Google Scholar 

Chan LL, Mo FKF, Law ALY, Shum TCY, Tai AYP, Lee A-S, et al. Impact of dose adjustment on clinical outcomes of lenvatinib-treated patients with advanced hepatocellular carcinoma (HCC). Poster presented at: 16th Annual International Liver Cancer Association Conference, September 1–4, 2022, Madrid. Accessed September 7, 2022.

Welland S, Leyh C, Finkelmeier F, Jefremow A, Shmanko K, Gonzalez-Carmona MA, et al. Real-world data for lenvatinib in hepatocellular carcinoma (ELEVATOR): a retrospective multicenter study. Liver Cancer. 2022;11(3):219–32. https://doi.org/10.1159/000521746.

Article  CAS  PubMed  PubMed Central