{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T20:50:50Z","timestamp":1789678250050,"version":"4.0.1"},"reference-count":39,"publisher":"Elsevier BV","issue":"1","license":[{"start":{"date-parts":[[2023,2,1]],"date-time":"2023-02-01T00:00:00Z","timestamp":1675209600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2023,2,1]],"date-time":"2023-02-01T00:00:00Z","timestamp":1675209600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2022,12,9]],"date-time":"2022-12-09T00:00:00Z","timestamp":1670544000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["jacc.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["JACC: CardioOncology"],"published-print":{"date-parts":[[2023,2]]},"DOI":"10.1016\/j.jaccao.2022.09.006","type":"journal-article","created":{"date-parts":[[2023,1,17]],"date-time":"2023-01-17T14:27:01Z","timestamp":1673965621000},"page":"102-113","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":27,"title":["Cardiac Toxicity of Alectinib in Patients\u00a0With ALK+ Lung Cancer"],"prefix":"10.1016","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4361-0020","authenticated-orcid":false,"given":"Melinda A.","family":"Pruis","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.D. Marijn","family":"Veerman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H. Carlijne","family":"Hassing","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daan A.C.","family":"Lanser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marthe S.","family":"Paats","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ron H.N.","family":"van Schaik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ron H.J.","family":"Mathijssen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Manintveld","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne-Marie C.","family":"Dingemans","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.jaccao.2022.09.006_bib1","series-title":"Cancer Stat Facts: Lung and Bronchus Cancer","year":"2022"},{"key":"10.1016\/j.jaccao.2022.09.006_bib2","doi-asserted-by":"crossref","DOI":"10.1016\/j.critrevonc.2020.103194","article-title":"Molecular testing and targeted therapy for non-small cell lung cancer: current status and perspectives","volume":"157","author":"Imyanitov","year":"2021","journal-title":"Crit Rev Oncol Hematol"},{"key":"10.1016\/j.jaccao.2022.09.006_bib3","doi-asserted-by":"crossref","first-page":"423","DOI":"10.2147\/CLEP.S69718","article-title":"Prevalence and natural history of ALK positive non-small-cell lung cancer and the clinical impact of targeted therapy with ALK inhibitors","volume":"6","author":"Chia","year":"2014","journal-title":"Clin Epidemiol"},{"key":"10.1016\/j.jaccao.2022.09.006_bib4","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.lungcan.2013.07.025","article-title":"Genetic alterations defining NSCLC subtypes and their therapeutic implications","volume":"82","author":"Pikor","year":"2013","journal-title":"Lung Cancer"},{"key":"10.1016\/j.jaccao.2022.09.006_bib5","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1056\/NEJMoa1704795","article-title":"Alectinib versus crizotinib in untreated alk-positive non-small-cell lung cancer","volume":"377","author":"Peters","year":"2017","journal-title":"N\u00a0Engl J Med"},{"key":"10.1016\/j.jaccao.2022.09.006_bib6","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.1016\/j.jtho.2019.03.007","article-title":"Updated efficacy and safety data and impact of the EML4-ALK fusion variant on the efficacy of alectinib in untreated ALK-positive advanced non-small cell lung cancer in the global phase III ALEX study","volume":"14","author":"Camidge","year":"2019","journal-title":"J\u00a0Thorac Oncol"},{"key":"10.1016\/j.jaccao.2022.09.006_bib7","doi-asserted-by":"crossref","first-page":"3043","DOI":"10.1111\/bcp.14752","article-title":"Drug-induced peripheral oedema: An aetiology-based review","volume":"87","author":"Largeau","year":"2021","journal-title":"Br J Clin Pharmacol"},{"key":"10.1016\/j.jaccao.2022.09.006_bib8","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1016\/j.jtho.2021.01.1605","article-title":"A\u00a0phase 2 study of capmatinib in patients with MET-altered lung cancer previously treated with a MET inhibitor","volume":"16","author":"Dagogo-Jack","year":"2021","journal-title":"J\u00a0Thorac Oncol"},{"key":"10.1016\/j.jaccao.2022.09.006_bib9","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1016\/j.ccr.2011.04.004","article-title":"CH5424802, a selective ALK inhibitor capable of blocking the resistant gatekeeper mutant","volume":"19","author":"Sakamoto","year":"2011","journal-title":"Cancer Cell"},{"key":"10.1016\/j.jaccao.2022.09.006_bib10","doi-asserted-by":"crossref","first-page":"22137","DOI":"10.18632\/oncotarget.25154","article-title":"Systematic review and meta-analysis of selected toxicities of approved ALK inhibitors in metastatic non-small cell lung cancer","volume":"9","author":"Costa","year":"2018","journal-title":"Oncotarget"},{"key":"10.1016\/j.jaccao.2022.09.006_bib11","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1161\/CIRCRESAHA.109.206920","article-title":"Molecular mechanisms of cardiovascular toxicity of targeted cancer therapeutics","volume":"106","author":"Cheng","year":"2010","journal-title":"Circ Res"},{"key":"10.1016\/j.jaccao.2022.09.006_bib12","first-page":"172","article-title":"Osimertinib-induced cardiotoxicity","volume":"1","author":"Kartik","year":"2019","journal-title":"J\u00a0Am Coll Cardiol CardioOnc"},{"key":"10.1016\/j.jaccao.2022.09.006_bib13","series-title":"Alecensa: EPAR - Product Information","year":"2021"},{"key":"10.1016\/j.jaccao.2022.09.006_bib14","doi-asserted-by":"crossref","first-page":"1387","DOI":"10.1200\/JCO.2016.70.0229","article-title":"Cardiac toxicity after radiotherapy for stage III non-small-cell lung cancer: pooled analysis of dose-escalation trials delivering 70 to 90 Gy","volume":"35","author":"Wang","year":"2017","journal-title":"J\u00a0Clin Oncol"},{"key":"10.1016\/j.jaccao.2022.09.006_bib15","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1016\/j.jtho.2020.11.002","article-title":"Cardiac toxicity of thoracic radiotherapy: existing evidence and future directions","volume":"16","author":"Banfill","year":"2021","journal-title":"J\u00a0Thorac Oncol"},{"key":"10.1016\/j.jaccao.2022.09.006_bib16","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1002\/cpt.1989","article-title":"Exposure-response analyses of anaplastic lymphoma kinase inhibitors crizotinib and alectinib in non-small cell lung cancer patients","volume":"109","author":"Groenland","year":"2021","journal-title":"Clin Pharmacol Ther"},{"key":"10.1016\/j.jaccao.2022.09.006_bib17","series-title":"Common Terminology Criteria for Adverse Events (CTCAE)","year":"2021"},{"key":"10.1016\/j.jaccao.2022.09.006_bib18","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.jchromb.2019.03.011","article-title":"Quantification of afatinib, alectinib, crizotinib and\u00a0osimertinib in human plasma by liquid chromatography\/triple-quadrupole mass spectrometry; focusing on the stability of osimertinib","volume":"1113","author":"Veerman","year":"2019","journal-title":"J\u00a0Chromatogr B Analyt Technol Biomed Life Sci"},{"key":"10.1016\/j.jaccao.2022.09.006_bib19","doi-asserted-by":"crossref","first-page":"1010","DOI":"10.1161\/CIRCULATIONAHA.110.940577","article-title":"Chronotropic incompetence","volume":"123","author":"Peter","year":"2011","journal-title":"Circulation"},{"issue":"12","key":"10.1016\/j.jaccao.2022.09.006_bib20","doi-asserted-by":"crossref","first-page":"2029","DOI":"10.1016\/j.jtho.2021.07.030","article-title":"Pharmacovigilance analysis of cardiac toxicities associated with targeted therapies for metastatic NSCLC","volume":"16","author":"Waliany","year":"2021","journal-title":"J\u00a0Thorac Oncol"},{"key":"10.1016\/j.jaccao.2022.09.006_bib21","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/S0140-6736(17)30565-2","article-title":"Alectinib versus crizotinib in patients with ALK-positive non-small-cell lung cancer (J-ALEX): an open-label, randomised phase 3 trial","volume":"390","author":"Hida","year":"2017","journal-title":"Lancet"},{"key":"10.1016\/j.jaccao.2022.09.006_bib22","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1007\/s00280-017-3253-5","article-title":"Effect of alectinib on cardiac electrophysiology: results from intensive electrocardiogram monitoring from the pivotal phase II NP28761 and NP28673 studies","volume":"79","author":"Morcos","year":"2017","journal-title":"Cancer Chemother Pharmacol"},{"key":"10.1016\/j.jaccao.2022.09.006_bib23","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1016\/S2213-2600(19)30053-0","article-title":"Alectinib versus crizotinib in untreated Asian patients with anaplastic lymphoma kinase-positive non-small-cell lung cancer (ALESIA): a randomised phase 3 study","volume":"7","author":"Zhou","year":"2019","journal-title":"Lancet Respir Med"},{"key":"10.1016\/j.jaccao.2022.09.006_bib24","doi-asserted-by":"crossref","first-page":"e6","DOI":"10.1016\/j.jacc.2012.11.007","volume":"61","author":"Tracy","year":"2013","journal-title":"J\u00a0Am Coll Cardiol"},{"key":"10.1016\/j.jaccao.2022.09.006_bib25","first-page":"1","article-title":"Crizotinib inhibits hyperpolarization-activated cyclic nucleotide-gated channel 4 activity","volume":"3","author":"Zhang","year":"2017","journal-title":"Cardiooncology"},{"key":"10.1016\/j.jaccao.2022.09.006_bib26","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.lungcan.2021.08.014","article-title":"ALK inhibitor-induced bradycardia: a systematic-review and meta-analysis","volume":"161","author":"Cirne","year":"2021","journal-title":"Lung Cancer"},{"key":"10.1016\/j.jaccao.2022.09.006_bib27","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1159\/000499086","article-title":"Efficacy and safety of ALK tyrosine kinase inhibitors in elderly patients with advanced ALK-positive non-small cell lung cancer: findings from the real-life cohort","volume":"42","author":"Bedas","year":"2019","journal-title":"Oncol Res Treat"},{"key":"10.1016\/j.jaccao.2022.09.006_bib28","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1007\/s00280-013-2234-6","article-title":"Phase I, dose-escalation study of AZD7762 alone and in combination with gemcitabine in Japanese patients with advanced solid tumours","volume":"72","author":"Seto","year":"2013","journal-title":"Cancer Chemother Pharmacol"},{"key":"10.1016\/j.jaccao.2022.09.006_bib29","doi-asserted-by":"crossref","first-page":"5903","DOI":"10.1002\/cncr.27575","article-title":"Phase 1 dose-escalation trial evaluating the combination of the selective MET (mesenchymal-epithelial transition factor) inhibitor tivantinib (ARQ 197) plus erlotinib","volume":"118","author":"Goldman","year":"2012","journal-title":"Cancer"},{"issue":"suppl 1","key":"10.1016\/j.jaccao.2022.09.006_bib30","doi-asserted-by":"crossref","first-page":"S33","DOI":"10.1007\/BF00171982","article-title":"Phase I study of tiazofurin (2-beta-D-ribofuranosylthiazole-4-carboxamide, NSC 286193)","volume":"8","author":"Maroun","year":"1990","journal-title":"Invest New Drugs"},{"key":"10.1016\/j.jaccao.2022.09.006_bib31","first-page":"161","article-title":"Cardiotoxicity and oncological treatments","volume":"111","author":"Schlitt","year":"2014","journal-title":"Dtsch Arztebl Int"},{"key":"10.1016\/j.jaccao.2022.09.006_bib32","doi-asserted-by":"crossref","first-page":"2018","DOI":"10.1056\/NEJMoa2027187","article-title":"first-line lorlatinib or crizotinib in advanced ALK-positive lung cancer","volume":"383","author":"Shaw","year":"2020","journal-title":"N\u00a0Engl J Med"},{"key":"10.1016\/j.jaccao.2022.09.006_bib33","doi-asserted-by":"crossref","DOI":"10.1093\/eurheartj\/ehab724.2848","article-title":"Bradycardia associated with ALK inhibitors in the treatment of non-small cell lung cancers: a systematic review and meta-analysis","volume":"42","author":"Zhou","year":"2021","journal-title":"Eur Heart J"},{"key":"10.1016\/j.jaccao.2022.09.006_bib34","doi-asserted-by":"crossref","first-page":"1552","DOI":"10.1016\/j.jtho.2017.06.070","article-title":"Pooled systemic efficacy and safety data from the pivotal phase II studies (NP28673 and NP28761) of alectinib in ALK-positive non-small cell lung cancer","volume":"12","author":"Yang","year":"2017","journal-title":"J\u00a0Thorac Oncol"},{"key":"10.1016\/j.jaccao.2022.09.006_bib35","doi-asserted-by":"crossref","first-page":"e265","DOI":"10.1016\/S1470-2045(20)30069-3","article-title":"Clinical implications of food-drug interactions with small-molecule kinase inhibitors","volume":"21","author":"Veerman","year":"2020","journal-title":"Lancet Oncol"},{"key":"10.1016\/j.jaccao.2022.09.006_bib36","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1007\/s10549-018-5058-6","article-title":"A\u00a0real-world study of cardiac events in > 3700 patients with HER2-positive early breast cancer treated with trastuzumab: final analysis of the OHERA study","volume":"174","author":"Lidbrink","year":"2019","journal-title":"Breast Cancer Res Treat"},{"key":"10.1016\/j.jaccao.2022.09.006_bib37","doi-asserted-by":"crossref","first-page":"4107","DOI":"10.1200\/JCO.2005.04.9551","article-title":"Long-term cardiac tolerability of trastuzumab in metastatic breast cancer: the M.D. Anderson Cancer Center experience","volume":"24","author":"Valentina","year":"2006","journal-title":"J\u00a0Clin Oncol"},{"key":"10.1016\/j.jaccao.2022.09.006_bib38","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1186\/s40959-020-00079-3","article-title":"J.\u00a0Early- and late anthracycline-induced cardiac dysfunction: echocardiographic characterization and response to heart failure therapy","volume":"6","author":"Kamphuis","year":"2020","journal-title":"Cardio-Oncology"},{"key":"10.1016\/j.jaccao.2022.09.006_bib39","doi-asserted-by":"crossref","first-page":"1721","DOI":"10.1002\/ejhf.1292","article-title":"Activity and outcomes of a cardio-oncology service in the United Kingdom-a five-year experience","volume":"20","author":"Pareek","year":"2018","journal-title":"Eur J Heart Fail"}],"container-title":["JACC: CardioOncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2666087322005129?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2666087322005129?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T18:56:58Z","timestamp":1762973818000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2666087322005129"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2]]},"references-count":39,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2023,2]]}},"alternative-id":["S2666087322005129"],"URL":"https:\/\/doi.org\/10.1016\/j.jaccao.2022.09.006","relation":{},"ISSN":["2666-0873"],"issn-type":[{"value":"2666-0873","type":"print"}],"subject":[],"published":{"date-parts":[[2023,2]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Cardiac Toxicity of Alectinib in Patients\u00a0With ALK+ Lung Cancer","name":"articletitle","label":"Article Title"},{"value":"JACC: CardioOncology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.jaccao.2022.09.006","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2022 Published by Elsevier on behalf of the American College of Cardiology Foundation.","name":"copyright","label":"Copyright"}]}}