{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T22:14:09Z","timestamp":1789683249303,"version":"4.0.1"},"reference-count":67,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2024,11,7]],"date-time":"2024-11-07T00:00:00Z","timestamp":1730937600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,11,7]],"date-time":"2024-11-07T00:00:00Z","timestamp":1730937600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2025,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Optimizing the timing of radiotherapy and chemotherapy tailored to the body's biological clock (i.e., chronotherapy) might improve treatment efficacy and reduce side effects. This systematic review evaluated the effect of chrono\u2010radiotherapy and chrono\u2010chemotherapy on treatment efficacy, toxicity and adverse events in head and neck cancer (HNC) patients from prospective and retrospective studies published between the date of database inception until March 2024. The primary outcome measures for chrono\u2010radiotherapy were treatment efficacy and incidence of grade \u22653 oral mucositis, and the main outcome measures for chrono\u2010chemotherapy were objective response rate (ORR) and overall toxicity and adverse events. Of 7349 records identified, 22 studies with 3366 patients were included (chrono\u2010radiotherapy\u2009=\u20099 and chrono\u2010chemotherapy\u2009=\u200913). HNC patients who underwent chrono\u2010radiotherapy had 31% less risk of developing severe oral mucositis (grade \u22653) compared to evening radiotherapy (risk ratio: 0.69, 95% CI: 0.53\u20130.90,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.05). Further, HNC patients who underwent chrono\u2010chemotherapy using platinum\u2010based and antimetabolite agents had 73% less risk of lower ORR compared to nontime\u2010stipulated chemotherapy (risk ratio: 0.27, 95% CI: 0.09\u20130.84,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.05). In addition, HNC patients who underwent chrono\u2010chemotherapy had 41% less risk of lower overall toxicity and adverse events in comparison to nontime\u2010stipulated chemotherapy (risk ratio: 0.59, 95% CI: 0.47\u20130.72,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.05). In conclusion, chrono\u2010chemotherapy studies showed evidence of improved treatment efficacy, while in chrono\u2010radiotherapy it was maintained. Chrono\u2010radiotherapy and chrono\u2010chemotherapy studies provide evidence of reduced toxicity and adverse events. However, optimized circadian\u2010based multicentric clinical studies are needed to support chrono\u2010radiotherapy and chrono\u2010chemotherapy in managing HNC.\n                  <\/jats:p>","DOI":"10.1002\/ijc.35234","type":"journal-article","created":{"date-parts":[[2024,11,7]],"date-time":"2024-11-07T09:29:11Z","timestamp":1730971751000},"page":"1015-1032","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Chronotherapy in head and neck cancer: A systematic review and meta\u2010analysis"],"prefix":"10.1002","volume":"156","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0955-0055","authenticated-orcid":false,"given":"Mohammad","family":"Abusamak","sequence":"first","affiliation":[{"name":"Faculty of Dental Medicine and Oral Health Sciences McGill University  Montreal Quebec Canada"},{"name":"Faculty of Dentistry Dalhousie University  Halifax Nova Scotia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdel\u2010Azez","family":"Abu\u2010Samak","sequence":"additional","affiliation":[{"name":"Rutgers\u2010Trinitas Regional Medical Center  Elizabeth New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenji","family":"Cai","sequence":"additional","affiliation":[{"name":"Faculty of Dental Medicine and Oral Health Sciences McGill University  Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haider","family":"Al\u2010Waeli","sequence":"additional","affiliation":[{"name":"Faculty of Dentistry Dalhousie University  Halifax Nova Scotia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faez Saleh","family":"Al\u2010Hamed","sequence":"additional","affiliation":[{"name":"College of Dental Medicine, QU Health Qatar University  Doha Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad","family":"Al\u2010Tamimi","sequence":"additional","affiliation":[{"name":"Faculty of Dentistry University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malik","family":"Juweid","sequence":"additional","affiliation":[{"name":"Department of Radiology and Nuclear Medicine, School of Medicine University of Jordan  Amman Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akhilanand","family":"Chaurasia","sequence":"additional","affiliation":[{"name":"Department of Oral Medicine and Radiology King George's Medical University  Lucknow India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Belinda","family":"Nicolau","sequence":"additional","affiliation":[{"name":"Faculty of Dental Medicine and Oral Health Sciences McGill University  Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faleh","family":"Tamimi","sequence":"additional","affiliation":[{"name":"College of Dental Medicine, QU Health Qatar University  Doha Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,11,7]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21834"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.31937"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(21)01550\u20106"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1715715"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.6004\/jnccn.2020.0031"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coms.2018.06.001"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41416\u2010024\u201002655\u20101"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/978\u20103\u2010030\u201032316\u20105"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.31675"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1001\/archoto.2009.174"},{"issue":"11","key":"e_1_2_10_12_1","first-page":"6247","article-title":"Induction chemotherapy and sequential concomitant chemo\u2010radiation in locally advanced head and neck cancers: how induction\u2010phase intensity and treatment breaks May impact on clinical outcomes","volume":"35","author":"Franco P","year":"2015","journal-title":"Anticancer Res"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.hoc.2008.08.014"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0360\u20103016(02)02756\u20106"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1177\/15330338241246653"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1080\/1120009X.2023.2300217"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2020.04.003"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002\u20109440(10)64135\u20101"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002\u20109440(10)65306\u20100"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978\u20100\u201012\u2010396971\u20102.00009\u20109"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14205071"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42003\u2010019\u20100607\u2010z"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2006.11.001"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pharmtox.48.113006.094626"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.13007"},{"issue":"5","key":"e_1_2_10_26_1","first-page":"1996","article-title":"Experimental chronotherapy of mouse mammary adenocarcinoma MA13\/C with docetaxel and doxorubicin as single agents and in Combination1","volume":"61","author":"Granda TG","year":"2001","journal-title":"Cancer Res"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470\u20102045(21)00639\u20102"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/ajco.12456"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11060\u2010019\u201003332\u20107"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.36522"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1080\/07420528.2023.2200495"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.n71"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1097\/XEB.0000000000000062"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/22.4.719"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.6028\/jres.087.022"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/sim.1482"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/sim.1186"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.2307\/3001616"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1136\/ebmental\u20102019\u2010300117"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.18637\/jss.v036.i03"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijrobp.2008.07.009"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1080\/09553000902883802"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.4103\/jrcr.jrcr_62_20"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.9734\/jcti\/2020\/v10i130118"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.21474\/IJAR01\/13127"},{"issue":"11","key":"e_1_2_10_46_1","first-page":"21","article-title":"Influence of circadian rhythm in radiation induced Mucositis in head and neck malignancies","volume":"6","author":"Kuriakose DVG","year":"2016","journal-title":"IOSR J Pharm"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1158\/1055\u20109965.EPI\u201019\u20100961"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.radonc.2021.02.039"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.radonc.2021.04.004"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11805\u2010006\u20100132\u2010y"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.3969\/j.issn.1000\u20108179.2012.06.010"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.5732\/cjc.013.10004"},{"key":"e_1_2_10_53_1","article-title":"Chronomodulated chemotherapy and concomitant radiotherapy, for the management of locally advanced, head and neck squamous cell carcinoma","author":"Verma Y","year":"2014","journal-title":"International Journal of Pharmacy & Life Sciences"},{"issue":"9","key":"e_1_2_10_54_1","first-page":"676","article-title":"Phase II clinical trial of two different modes of administration of the induction chemotherapy for locally advanced nasopharyngeal carcinoma","volume":"37","author":"Bi T","year":"2015","journal-title":"Zhonghua Zhong Liu Za Zhi"},{"key":"e_1_2_10_55_1","first-page":"709","article-title":"Clinical study of chrono\u2010chemotherapy in treating nasopharyngeal carcinoma patients with distant metastasis at preliminary diagnosis","author":"Mao Z","year":"2015","journal-title":"Chin J Clin Oncol"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.1080\/07420528.2017.1397684"},{"issue":"1","key":"e_1_2_10_57_1","first-page":"44","article-title":"Effect of administration time on toxicity induced by DCF in patients with Oral squamous cell carcinoma","volume":"8","author":"Li Y","year":"2018","journal-title":"Anti\u2010Tumor Pharm"},{"key":"e_1_2_10_58_1","doi-asserted-by":"publisher","DOI":"10.3760\/cma.j.issn.0253\u20103766.2020.02.009"},{"key":"e_1_2_10_59_1","doi-asserted-by":"publisher","DOI":"10.4103\/jcrt.JCRT_883_17"},{"key":"e_1_2_10_60_1","doi-asserted-by":"publisher","DOI":"10.1080\/07420528.2017.1392551"},{"key":"e_1_2_10_61_1","doi-asserted-by":"publisher","DOI":"10.2147\/OTT.S53098"},{"issue":"3","key":"e_1_2_10_62_1","first-page":"774","article-title":"Efficacy of induction chemotherapy combined with chrono\u2010chemotherapy and intensity\u2010modulated radiotherapy on locally advanced nasopharyngeal carcinoma","volume":"26","author":"Zhang S","year":"2021","journal-title":"J BUON"},{"key":"e_1_2_10_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yfrne.2013.11.003"},{"key":"e_1_2_10_64_1","doi-asserted-by":"publisher","DOI":"10.1200\/jco.2007.25.18_suppl.2507"},{"key":"e_1_2_10_65_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mds148"},{"key":"e_1_2_10_66_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12885\u2010023\u201011564\u20100"},{"key":"e_1_2_10_67_1","doi-asserted-by":"publisher","DOI":"10.3390\/ph15020255"},{"key":"e_1_2_10_68_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.m4087"}],"updated-by":[{"DOI":"10.1002\/ijc.35396","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2025,3,7]],"date-time":"2025-03-07T00:00:00Z","timestamp":1741305600000}}],"container-title":["International Journal of Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ijc.35234","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ijc.35234","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ijc.35234","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T15:36:15Z","timestamp":1788276975000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ijc.35234"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,7]]},"references-count":67,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2025,3,1]]}},"alternative-id":["10.1002\/ijc.35234"],"URL":"https:\/\/doi.org\/10.1002\/ijc.35234","archive":["Portico"],"relation":{},"ISSN":["0020-7136","1097-0215"],"issn-type":[{"value":"0020-7136","type":"print"},{"value":"1097-0215","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,7]]},"assertion":[{"value":"2024-07-31","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-10-09","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-11-07","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}