{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T04:29:59Z","timestamp":1784867399722,"version":"3.55.0"},"reference-count":40,"publisher":"Springer Science and Business Media LLC","issue":"9","license":[{"start":{"date-parts":[[2022,12,13]],"date-time":"2022-12-13T00:00:00Z","timestamp":1670889600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2022,12,13]],"date-time":"2022-12-13T00:00:00Z","timestamp":1670889600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Cancer Res Clin Oncol"],"published-print":{"date-parts":[[2023,8]]},"DOI":"10.1007\/s00432-022-04512-1","type":"journal-article","created":{"date-parts":[[2022,12,13]],"date-time":"2022-12-13T03:02:36Z","timestamp":1670900556000},"page":"5591-5602","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Clinical outcomes with atezolizumab plus bevacizumab or lenvatinib in patients with hepatocellular carcinoma: a multicenter real-world study"],"prefix":"10.1007","volume":"149","author":[{"given":"Mara","family":"Persano","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margherita","family":"Rimini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshifumi","family":"Tada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Goki","family":"Suda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigeo","family":"Shimose","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masatoshi","family":"Kudo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaekyung","family":"Cheon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabian","family":"Finkelmeier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ho Yeong","family":"Lim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenza","family":"Rimassa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9","family":"Presa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianluca","family":"Masi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changhoon","family":"Yoo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Lonardi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Tovoli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Kumada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoya","family":"Sakamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideki","family":"Iwamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoko","family":"Aoki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong Jae","family":"Chon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vera","family":"Himmelsbach","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiziana","family":"Pressiani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takumi","family":"Kawaguchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margarida","family":"Montes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caterina","family":"Vivaldi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caterina","family":"Sold\u00e0","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio","family":"Piscaglia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsushi","family":"Hiraoka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takuya","family":"Sho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Niizeki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoshi","family":"Nishida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Steup","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimo","family":"Iavarone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Di Costanzo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio","family":"Marra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Scartozzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emiliano","family":"Tamburini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Cabibbo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco Giuseppe","family":"Foschi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianna","family":"Silletta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masashi","family":"Hirooka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuya","family":"Kariyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joji","family":"Tani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masanori","family":"Atsukawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koichi","family":"Takaguchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ei","family":"Itobayashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinya","family":"Fukunishi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kunihiko","family":"Tsuji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toru","family":"Ishikawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuto","family":"Tajiri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hironori","family":"Ochi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Yasuda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hidenori","family":"Toyoda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chikara","family":"Ogawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Nishimura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Hatanaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoru","family":"Kakizaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noritomo","family":"Shimada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuhito","family":"Kawata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fujimasa","family":"Tada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideko","family":"Ohama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuhiro","family":"Nouso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asahiro","family":"Morishita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akemi","family":"Tsutsui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takuya","family":"Nagano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norio","family":"Itokawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomomi","family":"Okubo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taeang","family":"Arai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michitaka","family":"Imai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hisashi","family":"Kosaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsushi","family":"Naganuma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yohei","family":"Koizumi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinichiro","family":"Nakamura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaki","family":"Kaibori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroko","family":"Iijima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoichi","family":"Hiasa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonella","family":"Cammarota","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Burgio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Cascinu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Casadei-Gardini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,12,13]]},"reference":[{"key":"4512_CR1","doi-asserted-by":"publisher","first-page":"9379","DOI":"10.2147\/CMAR.S330195","volume":"13","author":"V Burgio","year":"2021","unstructured":"Burgio V, Iavarone M, Di Costanzo GG, Marra F, Lonardi S, Tamburini E et al (2021) Real-life clinical data of lenvatinib versus sorafenib for unresectable hepatocellular carcinoma in Italy. Cancer Manag Res 13:9379\u20139389","journal-title":"Cancer Manag Res"},{"key":"4512_CR2","first-page":"1","volume":"00","author":"A Casadei-Gardini","year":"2021","unstructured":"Casadei-Gardini A, Scartozzi M, Tada T, Yoo C, Shimose S, Masi G et al (2021) Lenvatinib versus sorafenib in first-line treatment of unresectable hepatocellular carcinoma: an inverse probability of treatment weighting analysis. Liver Int 00:1\u20139","journal-title":"Liver Int"},{"issue":"1","key":"4512_CR3","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/S1470-2045(08)70285-7","volume":"10","author":"AL Cheng","year":"2009","unstructured":"Cheng AL, Kang YK, Chen Z, Tsao CJ, Qin S, Kim JS et al (2009) 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 10(1):25\u201334","journal-title":"Lancet Oncol"},{"issue":"4","key":"4512_CR4","doi-asserted-by":"publisher","first-page":"862","DOI":"10.1016\/j.jhep.2021.11.030","volume":"76","author":"AL Cheng","year":"2022","unstructured":"Cheng AL, Qin S, Ikeda M, Galle PR, Ducreux M, Kim TY et al (2022) Updated efficacy and safety data from IMbrave150: Atezolizumab plus bevacizumab vs. sorafenib for unresectable hepatocellular carcinoma. J Hepatol 76(4):862\u2013873","journal-title":"J Hepatol"},{"issue":"15","key":"4512_CR5","doi-asserted-by":"publisher","first-page":"4071","DOI":"10.1200\/JCO.2021.39.15_suppl.4071","volume":"39","author":"M Ducreux","year":"2021","unstructured":"Ducreux M, Zhu AX, Cheng A-L et al (2021) IMbrave150: Exploratory analysis to examine the association between treatment response and overall survival (OS) in patients (pts) with unresectable hepatocellular carcinoma (HCC) treated with atezolizumab (atezo) + bevacizumab (bev) versus sorafenib (sor). J Clin Oncol 39(15):4071","journal-title":"J Clin Oncol"},{"issue":"15","key":"4512_CR6","doi-asserted-by":"publisher","first-page":"4596","DOI":"10.1200\/JCO.2020.38.15_suppl.4596","volume":"38","author":"RS Finn","year":"2020","unstructured":"Finn RS, Qin S, Ikeda M, Galle PR, Ducreux M, Kim T-Y et al (2020) Complete responses (CR) in patients receiving atezolizumab (atezo) + bevacizumab (bev) versus sorafenib (sor) in IMbrave150: a phase III clinical trial for unresectable hepatocellular carcinoma (HCC). J Clin Oncol 38(15):4596","journal-title":"J Clin Oncol"},{"key":"4512_CR7","doi-asserted-by":"crossref","unstructured":"Freites-Martinez A, Santana N, Arias-Santiago S, Viera A (2021) 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) 112(1):90\u201392.","DOI":"10.1016\/j.adengl.2019.05.021"},{"issue":"19","key":"4512_CR8","doi-asserted-by":"publisher","first-page":"2415","DOI":"10.3748\/wjg.v27.i19.2415","volume":"27","author":"Y Han","year":"2021","unstructured":"Han Y, Zhi WH, Xu F, Zhang CB, Huang XQ, Luo JF (2021) Selection of first-line systemic therapies for advanced hepatocellular carcinoma: a network meta-analysis of randomized controlled trials. World J Gastroenterol 27(19):2415\u20132433","journal-title":"World J Gastroenterol"},{"key":"4512_CR9","doi-asserted-by":"publisher","first-page":"382","DOI":"10.1111\/hepr.13460","volume":"50","author":"T Hatanaka","year":"2020","unstructured":"Hatanaka T, Kakizaki S, Nagashima T, Namikawa M, Tojima H, Shimada Y et al (2020) Analyses of objective response rate, progression-free survival, and adverse events in hepatocellular carcinoma patients treated with lenvatinib: a multicenter retrospective study. Hepatol Res 50:382\u2013395","journal-title":"Hepatol Res"},{"key":"4512_CR10","doi-asserted-by":"publisher","first-page":"3719","DOI":"10.1002\/cam4.2241","volume":"8","author":"A Hiraoka","year":"2019","unstructured":"Hiraoka A, Kumada T, Atsukawa M, Hirooka M, Tsuji K, Ishikawa T et al (2019) Prognostic factor of lenvatinib for unresectable hepatocellular carcinoma in real-world conditions-multicenter analysis. Cancer Med 8:3719\u20133728","journal-title":"Cancer Med"},{"key":"4512_CR11","doi-asserted-by":"publisher","first-page":"2786","DOI":"10.3390\/cancers13112786","volume":"13","author":"H Iwamoto","year":"2021","unstructured":"Iwamoto H, Shimose S, Noda Y, Shirono T, Niizeki T, Nakano M et al (2021) Initial experience of atezolizumab plus bevacizumab for unresectable hepatocellular carcinoma in real-world clinical practice. Cancers 13:2786","journal-title":"Cancers"},{"key":"4512_CR12","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s40425-019-0749-z","volume":"7","author":"BP Keenan","year":"2019","unstructured":"Keenan BP, Fong L, Kelley RK (2019) Immunotherapy in hepatocellular carcinoma: the complex interface between inflammation, fibrosis, and the immune response. J Immunother Cancer 7:1\u201313","journal-title":"J Immunother Cancer"},{"key":"4512_CR13","doi-asserted-by":"publisher","first-page":"1186","DOI":"10.1038\/bjc.2016.308","volume":"15","author":"L Khoja","year":"2016","unstructured":"Khoja L, Kibiro M, Metser U, Gedye C, Hogg D, Butler MO et al (2016) Patterns of response to anti-PD-1 treatment: an exploratory comparison of four radiological response criteria and associations with overall survival in metastatic melanoma patients. Br J Cancer 15:1186\u20131192","journal-title":"Br J Cancer"},{"key":"4512_CR14","doi-asserted-by":"publisher","first-page":"1747","DOI":"10.3390\/cancers14071747","volume":"14","author":"BK Kim","year":"2022","unstructured":"Kim BK, Cheon J, Kim H, Kang B, Ha Y, Kim DY et al (2022) Atezolizumab\/bevacizumab vs. lenvatinib as first-line therapy for unresectable hepatocellular carcinoma: a real-world, multi-center study. Cancers 14:1747","journal-title":"Cancers"},{"issue":"10126","key":"4512_CR15","doi-asserted-by":"publisher","first-page":"1163","DOI":"10.1016\/S0140-6736(18)30207-1","volume":"391","author":"M Kudo","year":"2018","unstructured":"Kudo M, Finn RS, Qin S, Han KH, Ikeda K, Piscaglia F et al (2018) Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial. Lancet 391(10126):1163\u20131173","journal-title":"Lancet"},{"issue":"4","key":"4512_CR16","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1200\/JCO.2019.37.4_suppl.186","volume":"37","author":"M Kudo","year":"2019","unstructured":"Kudo M, Finn RS, Qin S, Han K-H, Ikeda K, Cheng A-L et al (2019a) Analysis of survival and objective response (OR) in patients with hepatocellular carcinoma in a phase III study of lenvatinib (REFLECT). J Clin Oncol 37(4):186","journal-title":"J Clin Oncol"},{"issue":"8","key":"4512_CR17","doi-asserted-by":"publisher","first-page":"1084","DOI":"10.3390\/cancers11081084","volume":"11","author":"M Kudo","year":"2019","unstructured":"Kudo M, Ueshima K, Chan S, Minami T, Chishina H, Aoki T et al (2019b) Lenvatinib as an initial treatment in patients with intermediate-stage hepatocellular carcinoma beyond up-to-seven criteria and child\u2013pugh A liver function: a proof-of-concept study. Cancers (basel) 11(8):1084","journal-title":"Cancers (basel)"},{"key":"4512_CR18","doi-asserted-by":"publisher","first-page":"571","DOI":"10.1002\/cam4.4468","volume":"11","author":"JKH Liu","year":"2022","unstructured":"Liu JKH, Irvine AF, Jones RL, Samson A (2022) Immunotherapies for Hepatocellular Carcinoma. Cancer Med 11:571\u2013591","journal-title":"Cancer Med"},{"key":"4512_CR19","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1055\/s-2007-1007122","volume":"19","author":"JM Llovet","year":"1999","unstructured":"Llovet JM, Bru C, Bruix J (1999) Prognosis of hepatocellular carcinoma: the BCLC staging classification. Semin Liver Dis 19:329\u2013338","journal-title":"Semin Liver Dis"},{"issue":"4","key":"4512_CR20","doi-asserted-by":"publisher","first-page":"378","DOI":"10.1056\/NEJMoa0708857","volume":"359","author":"JM Llovet","year":"2008","unstructured":"Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF et al (2008) Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 359(4):378\u2013390","journal-title":"N Engl J Med"},{"issue":"1","key":"4512_CR21","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1038\/s41572-020-00240-3","volume":"7","author":"JM Llovet","year":"2021","unstructured":"Llovet JM, Kelley RK, Villanueva A, Singal AG, Pikarsky E, Roayaie S et al (2021) Hepatocellular Carcinoma. Nat Rev Dis Primers 7(1):6","journal-title":"Nat Rev Dis Primers"},{"key":"4512_CR22","doi-asserted-by":"publisher","first-page":"382","DOI":"10.1159\/000507022","volume":"9","author":"S Maruta","year":"2020","unstructured":"Maruta S, Ogasawara S, Ooka Y, Obu M, Inoue M, Itokawa N et al (2020) Potential of lenvatinib for an expanded indication from the REFLECT trial in patients with advanced hepatocellular carcinoma. Liver Cancer 9:382\u2013396","journal-title":"Liver Cancer"},{"key":"4512_CR23","doi-asserted-by":"publisher","first-page":"385","DOI":"10.2147\/CEG.S256691","volume":"13","author":"K Ogushi","year":"2020","unstructured":"Ogushi K, Chuma M, Uojima H, Hidaka H, Numata K, Kobayashi S et al (2020) Safety and efficacy of lenvatinib treatment in Child-Pugh A and B patients with unresectable hepatocellular carcinoma in clinical practice: a multicenter analysis. Clin Exp Gastroenterol 13:385\u2013396","journal-title":"Clin Exp Gastroenterol"},{"key":"4512_CR24","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1007\/s40801-020-00179-7","volume":"7","author":"T Ohki","year":"2020","unstructured":"Ohki T, Sato K, Kondo M, Goto E, Sato T, Kondo Y et al (2020) Impact of adverse events on the progression-free survival of patients with advanced hepatocellular carcinoma treated with lenvatinib: a multicenter retrospective study. Drugs Real World Outcomes 7:141\u2013149","journal-title":"Drugs Real World Outcomes"},{"key":"4512_CR25","doi-asserted-by":"publisher","first-page":"681","DOI":"10.1038\/nrgastro.2015.173","volume":"12","author":"J Prieto","year":"2015","unstructured":"Prieto J, Melero I, Sangro B (2015) Immunological landscape and immunotherapy of hepatocellular carcinoma. Nat Rev Gastroenterol Hepatol 12:681\u2013700","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"4512_CR26","doi-asserted-by":"publisher","first-page":"213","DOI":"10.3390\/cancers13020213","volume":"13","author":"IG Rapposelli","year":"2021","unstructured":"Rapposelli IG, De Matteis S, Lanuti P, Valgiusti M, Bartolini G, Ulivi P et al (2021a) Heterogeneity of response and immune system activity during treatment with nivolumab in hepatocellular carcinoma: results from a single-institution retrospective analysis. Cancers 13:213","journal-title":"Cancers"},{"issue":"12","key":"4512_CR27","doi-asserted-by":"publisher","first-page":"2997","DOI":"10.1111\/liv.15014","volume":"41","author":"IG Rapposelli","year":"2021","unstructured":"Rapposelli IG, Tada T, Shimose S, Burgio V, Kumada T, Iwamoto H et al (2021b) Adverse events as potential predictive factors of activity in patients with advanced hepatocellular carcinoma treated with lenvatinib. Liver Int 41(12):2997\u20133008","journal-title":"Liver Int"},{"issue":"3","key":"4512_CR28","doi-asserted-by":"publisher","first-page":"681","DOI":"10.1016\/j.jhep.2021.11.018","volume":"76","author":"M Reig","year":"2022","unstructured":"Reig M, Forner A, Rimola J, Ferrer-F\u00e0brega J, Burrel M, Garcia-Criado \u00c1 et al (2022) BCLC strategy for prognosis prediction and treatment recommendation: the 2022 update. J Hepatol 76(3):681\u2013693","journal-title":"J Hepatol"},{"issue":"12","key":"4512_CR29","doi-asserted-by":"publisher","first-page":"1229","DOI":"10.1111\/hepr.13718","volume":"51","author":"M Rimini","year":"2021","unstructured":"Rimini M, Shimose S, Lonardi S, Tada T, Masi G, Iwamoto H et al (2021) Lenvatinib versus Sorafenib as first-line treatment in hepatocellular carcinoma: a multi-institutional matched case-control study. Hepatol Res 51(12):1229\u20131241","journal-title":"Hepatol Res"},{"issue":"5","key":"4512_CR30","doi-asserted-by":"publisher","first-page":"483","DOI":"10.1080\/13543784.2022.2053108","volume":"31","author":"M Rimini","year":"2022","unstructured":"Rimini M, Liscia N, Burgio V, Casadei-Gardini A (2022) Why does survival of hepatocellular carcinoma patients remain so low? Key stumbling blocks and questions in preclinical and clinical development. Expert Opin Investig Drugs 31(5):483\u2013494","journal-title":"Expert Opin Investig Drugs"},{"key":"4512_CR31","doi-asserted-by":"publisher","first-page":"1769","DOI":"10.3390\/cancers11111769","volume":"11","author":"R Sasaki","year":"2019","unstructured":"Sasaki R, Fukushima M, Haraguchi M, Miuma S, Miyaaki H, Hidaka M et al (2019) Response to lenvatinib is associated with optimal relative dose intensity in hepatocellular carcinoma: experience in clinical settings. Cancers 11:1769","journal-title":"Cancers"},{"issue":"3","key":"4512_CR32","doi-asserted-by":"publisher","first-page":"2257","DOI":"10.3892\/ol.2020.11758","volume":"20","author":"S Shimose","year":"2020","unstructured":"Shimose S, Kawaguchi T, Tanaka M, Iwamoto H, Miyazaki K, Moriyama E et al (2020) Lenvatinib prolongs the progression-free survival time of patients with intermediate-stage hepatocellular carcinoma refractory to transarterial chemoembolization: a multicenter cohort study using data mining analysis. Oncol Lett 20(3):2257\u20132265","journal-title":"Oncol Lett"},{"key":"4512_CR33","doi-asserted-by":"publisher","first-page":"160","DOI":"10.3390\/cancers13010160","volume":"13","author":"S Shimose","year":"2021","unstructured":"Shimose S, Iwamoto H, Tanaka M, Niizeki T, Shirono T, Noda Y et al (2021) Alternating lenvatinib and trans-arterial therapy prolongs overall survival in patients with intermediate stage hepatocellular carcinoma: a propensity score matching study. Cancers 13:160","journal-title":"Cancers"},{"key":"4512_CR34","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1111\/hepr.13511","volume":"50","author":"T Sho","year":"2020","unstructured":"Sho T, Suda G, Ogawa K, Shigesawa T, Suzuki K, Nakamura A et al (2020) Lenvatinib in patients with unresectable hepatocellular carcinoma who do not meet the REFLECT trial eligibility criteria. Hepatol Res 50:966\u2013977","journal-title":"Hepatol Res"},{"issue":"12","key":"4512_CR35","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2020.4930","volume":"6","author":"MB Sonbol","year":"2020","unstructured":"Sonbol MB, Riaz IB, Naqvi SAA (2020) Systemic therapy and sequencing options in advanced hepatocellular carcinoma: a systematic review and network meta-analysis. JAMA Oncol 6(12):e204930","journal-title":"JAMA Oncol"},{"issue":"11","key":"4512_CR36","doi-asserted-by":"publisher","first-page":"1069","DOI":"10.1080\/14737140.2018.1524297","volume":"18","author":"A Spallanzani","year":"2018","unstructured":"Spallanzani A, Orsi G, Andrikou K, Gelsomino F, Rimini M, Riggi L et al (2018) Lenvatinib as a therapy for unresectable hepatocellular carcinoma. Expert Rev Anticancer Ther 18(11):1069\u20131076","journal-title":"Expert Rev Anticancer Ther"},{"key":"4512_CR37","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1016\/j.ejca.2017.10.017","volume":"88","author":"M Tazdait","year":"2018","unstructured":"Tazdait M, Mezquita L, Lahmar J, Ferrara R, Bidault F, Ammari S et al (2018) Patterns of responses in metastatic NSCLC during PD-1 or PDL-1 inhibitor therapy: comparison of RECIST 1.1, irRECIST and iRECIST criteria. Eur J Cancer 88:38\u201347","journal-title":"Eur J Cancer"},{"key":"4512_CR38","doi-asserted-by":"publisher","first-page":"952","DOI":"10.3390\/cancers11070952","volume":"11","author":"K Ueshima","year":"2019","unstructured":"Ueshima K, Nishida N, Hagiwara S, Aoki T, Minami T, Chishina H et al (2019) Impact of baseline ALBI grade on the outcomes of hepatocellular carcinoma patients treated with lenvatinib: a multicenter study. Cancers 11:952","journal-title":"Cancers"},{"key":"4512_CR39","doi-asserted-by":"publisher","first-page":"492","DOI":"10.1038\/ni.2035","volume":"12","author":"EJ Wherry","year":"2011","unstructured":"Wherry EJ (2011) T cell exhaustion. Nat Immunol 12:492\u2013499","journal-title":"Nat Immunol"},{"key":"4512_CR40","doi-asserted-by":"publisher","DOI":"10.1016\/j.ctrv.2021.102239","volume":"99","author":"F Zambrana","year":"2021","unstructured":"Zambrana F, Carril-Ajuria L, G\u00f3mez de Lia\u00f1o A, Martinez Chanza N, Manneh R, Castellano D et al (2021) Complete response and renal cell carcinoma in the immunotherapy era: the paradox of good news. Cancer Treat Rev 99:102239","journal-title":"Cancer Treat Rev"}],"container-title":["Journal of Cancer Research and Clinical Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00432-022-04512-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00432-022-04512-1\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00432-022-04512-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,12,2]],"date-time":"2023-12-02T21:37:44Z","timestamp":1701553064000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00432-022-04512-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,13]]},"references-count":40,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2023,8]]}},"alternative-id":["4512"],"URL":"https:\/\/doi.org\/10.1007\/s00432-022-04512-1","relation":{},"ISSN":["0171-5216","1432-1335"],"issn-type":[{"value":"0171-5216","type":"print"},{"value":"1432-1335","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,13]]},"assertion":[{"value":"10 October 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 December 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 December 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"M.K. has received grants from Taiho Pharmaceuticals, Chugai Pharmaceuticals, Otsuka, Takeda, Sumitomo Dainippon-Sumitomo, Daiichi Sankyo, AbbVie, Astellas Pharma, and Bristol-Myers Squibb; has received grants and personal fees from MSD, Eisai, and Bayer, and is an adviser for MSD, Eisai, Bayer, Bristol-Myers Squibb, Eli Lilly and ONO Pharmaceutical. L.R. has received consulting fees from Amgen, ArQule, AstraZeneca, Basilea, Bayer, BMS, Celgene, Eisai, Exelixis, Genenta, Hengrui, Incyte, Ipsen, IQVIA, Lilly, MSD, Nerviano Medical Sciences, Roche, Sanofi, Servier, Taiho Oncology, Zymeworks; lecture fees from AbbVie, Amgen, Bayer, Eisai, Gilead, Incyte, Ipsen, Lilly, Merck Serono, Roche, Sanofi; travel expenses from AstraZeneca; and institutional research funding from Agios, ARMO BioSciences, AstraZeneca, BeiGene, Eisai, Exelixis, Fibrogen, Incyte, Ipsen, Lilly, MSD, Nerviano Medical Sciences, Roche, Zymeworks. F.P. has received consulting or lecture fees from Consulting or lecture fees in the last two years from: Astrazeneca, Bayer, Bracco, EISAI, ESAOTE, Exact Sciences, IPSEN; MSD; Roche, Samsung, Tiziana Life Sciences. M.S. is an advisor for MSD, Eisai, MERCK, SERVIER, and AMGEN. A.C-G. has received grants and personal fees from MSD, Eisai, Bayer, and is an advisor for MSD, Eisai, Bayer, Bristol-Myers Squibb, AstraZeneca and GSK. The other authors have no relevant financial or non-financial interests to disclose.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"Study was approved by Ethics Committee at each center (number of approval code 113\/INT\/2021 by the IRCCS San Raffaele Hospital Ethic Committee), complied with the provisions of the Good Clinical Practice guidelines and the Declaration of Helsinki and local laws, and fulfilled the Regulation (EU) 2016\/679 of the European Parliament and of the Council of 27 April 2016 on the protection of natural persons with regard to the processing of personal data.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics statement"}},{"value":"Informed consent was obtained from all individual participants included in the study.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}}]}}