{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T13:27:25Z","timestamp":1786541245295,"version":"build-2736575974"},"reference-count":35,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T00:00:00Z","timestamp":1765152000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100011693","name":"Department for Business, Energy and Industrial Strategy, UK Government","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100011693","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014653","name":"Manchester Biomedical Research Centre","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100014653","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000769","name":"University of Oxford","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000769","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000361","name":"Diabetes UK","doi-asserted-by":"publisher","award":["SBF008\/1156"],"award-info":[{"award-number":["SBF008\/1156"]}],"id":[{"id":"10.13039\/501100000361","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013342","name":"NIHR Imperial Biomedical Research Centre","doi-asserted-by":"publisher","award":["NIHR203308"],"award-info":[{"award-number":["NIHR203308"]}],"id":[{"id":"10.13039\/501100013342","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000272","name":"National Institute for Health and Care Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000691","name":"Academy of Medical Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014013","name":"UK Research and Innovation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100014013","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["RRCOER-Jun24\/100004"],"award-info":[{"award-number":["RRCOER-Jun24\/100004"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["RRNPSF-Jan23\/100001"],"award-info":[{"award-number":["RRNPSF-Jan23\/100001"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["CTRQQR-2021\\\\100002"],"award-info":[{"award-number":["CTRQQR-2021\\\\100002"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000780","name":"European Commission","doi-asserted-by":"publisher","award":["101 136 835"],"award-info":[{"award-number":["101 136 835"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","thegreenjournal.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Radiotherapy and Oncology"],"published-print":{"date-parts":[[2026,1]]},"DOI":"10.1016\/j.radonc.2025.111324","type":"journal-article","created":{"date-parts":[[2025,12,7]],"date-time":"2025-12-07T23:02:32Z","timestamp":1765148552000},"page":"111324","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"special_numbering":"C","title":["Systemic complement protein levels as biomarkers of chemoradiotherapy response in anal squamous cell carcinoma"],"prefix":"10.1016","volume":"214","author":[{"given":"D.","family":"Majorova","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9625-2111","authenticated-orcid":false,"given":"R.","family":"Samuel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Muirhead","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0815-9203","authenticated-orcid":false,"given":"A.","family":"Hasson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4932-2839","authenticated-orcid":false,"given":"DJ.","family":"MacLean","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-2171-5523","authenticated-orcid":false,"given":"F.","family":"Ismail","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"EJ.","family":"Cheadle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Jacobs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-1616-8533","authenticated-orcid":false,"given":"D.","family":"Halliday","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Saunders","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"BD.","family":"Nicholson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.","family":"O\u2019Neill","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Sebag-Montefiore","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3081-7850","authenticated-orcid":false,"given":"A.","family":"Samson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9580-2169","authenticated-orcid":false,"given":"MM.","family":"Olcina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.radonc.2025.111324_b0005","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1016\/S1470-2045(13)70086-X","article-title":"Mitomycin or cisplatin chemoradiation with or without maintenance chemotherapy for treatment of squamous-cell carcinoma of the anus (ACT II): a randomised, phase 3, open-label, 2\u00d72 factorial trial","volume":"14","author":"James","year":"2013","journal-title":"Lancet Oncol"},{"key":"10.1016\/j.radonc.2025.111324_b0010","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1016\/j.ijrobp.2013.07.035","article-title":"Anal Carcinoma: Impact of TN Category of Disease on Survival, Disease Relapse, and Colostomy failure in US Gastrointestinal Intergroup RTOG 98-11 phase 3 Trial","volume":"87","author":"Gunderson","year":"2013","journal-title":"Int J Radiat Oncol"},{"key":"10.1016\/j.radonc.2025.111324_b0015","article-title":"Advances in anal cancer treatment: current standards, the role of immunotherapy and emerging strategies","volume":"100180","author":"Ntellas","year":"2025","journal-title":"ESMO Gastrointest Oncol"},{"key":"10.1016\/j.radonc.2025.111324_b0020","doi-asserted-by":"crossref","DOI":"10.1016\/j.smim.2024.101921","article-title":"The complement system in clinical oncology: applications, limitations and challenges","volume":"77","author":"Ajona","year":"2025","journal-title":"Semin Immunol"},{"key":"10.1016\/j.radonc.2025.111324_b0025","doi-asserted-by":"crossref","DOI":"10.1080\/2162402X.2024.2328433","article-title":"Humoral complementomics \u2013 exploration of noninvasive complement biomarkers as predictors of renal cancer progression","volume":"13","author":"Revel","year":"2024","journal-title":"Oncoimmunology"},{"key":"10.1016\/j.radonc.2025.111324_b0030","doi-asserted-by":"crossref","DOI":"10.1016\/j.smim.2025.101963","article-title":"Harnessing complement biomarkers for precision cancer care","volume":"78","author":"Hamidi","year":"2025","journal-title":"Semin Immunol"},{"key":"10.1016\/j.radonc.2025.111324_b0035","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1016\/S0140-6736(23)01524-6","article-title":"Complement in human disease: approved and up-and-coming therapeutics","volume":"403","author":"West","year":"2024","journal-title":"Lancet"},{"key":"10.1016\/j.radonc.2025.111324_b0040","article-title":"The future of complement therapeutics","volume":"577\u2013615","author":"Kolev","year":"2024","journal-title":"Explor Immunol"},{"key":"10.1016\/j.radonc.2025.111324_b0045","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.smim.2013.04.009","article-title":"Anaphylatoxins coordinate innate and adaptive immune responses in allergic asthma","volume":"25","author":"Schmudde","year":"2013","journal-title":"Semin Immunol"},{"key":"10.1016\/j.radonc.2025.111324_b0050","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1111\/imr.12472","article-title":"The \u201cins and outs\u201d of complement-driven immune responses","volume":"274","author":"Freeley","year":"2016","journal-title":"Immunol Rev"},{"key":"10.1016\/j.radonc.2025.111324_b0055","article-title":"The Complement Receptors C3aR and C5aR are a New Class of Immune Checkpoint Receptor in Cancer Immunotherapy","author":"Wang","year":"2019","journal-title":"Front Immunol"},{"key":"10.1016\/j.radonc.2025.111324_b0060","doi-asserted-by":"crossref","DOI":"10.1136\/jitc-2022-004717","article-title":"Complement downregulation promotes an inflammatory signature that renders colorectal cancer susceptible to immunotherapy","volume":"10","author":"Krieg","year":"2022","journal-title":"J Immunother Cancer"},{"key":"10.1016\/j.radonc.2025.111324_b0065","doi-asserted-by":"crossref","DOI":"10.1016\/j.smim.2024.101927","article-title":"The role of the complement system in the response to cytotoxic therapy","volume":"77","author":"Lee","year":"2025","journal-title":"Semin Immunol"},{"key":"10.1016\/j.radonc.2025.111324_b0070","doi-asserted-by":"crossref","first-page":"5510","DOI":"10.1073\/pnas.92.12.5510","article-title":"Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension","volume":"92","author":"Wang","year":"1995","journal-title":"PNAS"},{"key":"10.1016\/j.radonc.2025.111324_b0075","doi-asserted-by":"crossref","first-page":"2735","DOI":"10.15252\/embj.201591881","article-title":"Complement activation, regulation, and molecular basis for complement\u2010related diseases","volume":"34","author":"Bajic","year":"2015","journal-title":"EMBO J"},{"key":"10.1016\/j.radonc.2025.111324_b0080","doi-asserted-by":"crossref","first-page":"856","DOI":"10.1084\/jem.154.3.856","article-title":"Formation of the initial C3 convertase of the alternative complement pathway. Acquisition of C3b-like activities by spontaneous hydrolysis of the putative thioester in native C3","volume":"154","author":"Pangburn","year":"1981","journal-title":"J Exp Med"},{"key":"10.1016\/j.radonc.2025.111324_b0085","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1111\/j.1749-6632.1983.tb18116.x","article-title":"Initiation of the alternative complement pathway due to spontaneous hydrolysis of the thioester of C3 a","volume":"421","author":"Pangburn","year":"1983","journal-title":"Ann N Y Acad Sci"},{"key":"10.1016\/j.radonc.2025.111324_b0090","doi-asserted-by":"crossref","first-page":"1498","DOI":"10.1084\/jem.148.6.1498","article-title":"Mechanism of action of factor D of the alternative complement pathway","volume":"148","author":"Lesavre","year":"1978","journal-title":"J Exp Med"},{"key":"10.1016\/j.radonc.2025.111324_b0095","doi-asserted-by":"crossref","first-page":"3721","DOI":"10.1016\/j.celrep.2018.11.093","article-title":"Mutations in an Innate Immunity Pathway are Associated with Poor overall Survival Outcomes and Hypoxic Signaling in Cancer","volume":"25","author":"Olcina","year":"2018","journal-title":"Cell Rep"},{"key":"10.1016\/j.radonc.2025.111324_b0100","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1002\/cam4.241","article-title":"Complement anaphylatoxins as immune regulators in cancer","volume":"3","author":"Sayegh","year":"2014","journal-title":"Cancer Med"},{"key":"10.1016\/j.radonc.2025.111324_b0105","doi-asserted-by":"crossref","DOI":"10.1038\/nrneph.2016.70","article-title":"Complement in disease: a defence system turning offensive","author":"Ricklin","year":"2016","journal-title":"Nat Rev Nephrol"},{"key":"10.1016\/j.radonc.2025.111324_b0110","doi-asserted-by":"crossref","DOI":"10.1038\/s41568-019-0210-0","article-title":"Context-dependent roles of complement in cancer","author":"Roumenina","year":"2019","journal-title":"Nat Rev Cancer"},{"key":"10.1016\/j.radonc.2025.111324_b0115","doi-asserted-by":"crossref","DOI":"10.1172\/JCI168277","article-title":"Improving radiotherapy in immunosuppressive microenvironments by targeting complement receptor C5aR1","volume":"133","author":"Beach","year":"2023","journal-title":"J Clin Invest"},{"key":"10.1016\/j.radonc.2025.111324_b0120","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1016\/j.immuni.2015.03.009","article-title":"Complement is a Central Mediator of Radiotherapy-Induced Tumor-specific Immunity and Clinical Response","volume":"42","author":"Surace","year":"2015","journal-title":"Immunity"},{"key":"10.1016\/j.radonc.2025.111324_b0125","doi-asserted-by":"crossref","first-page":"818","DOI":"10.1016\/j.celrep.2014.06.051","article-title":"Complement-dependent modulation of antitumor immunity following radiation therapy","volume":"8","author":"Elvington","year":"2014","journal-title":"Cell Rep"},{"key":"10.1016\/j.radonc.2025.111324_b0130","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1186\/s12885-022-09729-4","article-title":"Prognostic factors for patients with anal cancer treated with conformal radiotherapy\u2014a systematic review","volume":"22","author":"Theophanous","year":"2022","journal-title":"BMC Cancer"},{"key":"10.1016\/j.radonc.2025.111324_b0135","doi-asserted-by":"crossref","first-page":"2144","DOI":"10.1016\/S0140-6736(25)00631-2","article-title":"Retifanlimab with carboplatin and paclitaxel for locally recurrent or metastatic squamous cell carcinoma of the anal canal (POD1UM-303\/InterAACT-2): a global, phase 3 randomised controlled trial","volume":"405","author":"Rao","year":"2025","journal-title":"Lancet"},{"key":"10.1016\/j.radonc.2025.111324_b0140","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1016\/j.clon.2023.09.003","article-title":"Improving Outcomes with Chemoradiotherapy in the Mucosal Squamous Cell Carcinomas \u2013 Immune Checkpoint Inhibition and Broken promises","volume":"35","author":"Samuel","year":"2023","journal-title":"Clin Oncol"},{"key":"10.1016\/j.radonc.2025.111324_b0145","doi-asserted-by":"crossref","first-page":"1334","DOI":"10.1016\/S1470-2045(23)00479-5","article-title":"Durvalumab versus placebo with chemoradiotherapy for locally advanced cervical cancer (CALLA): a randomised, double-blind, phase 3 trial","volume":"24","author":"Monk","year":"2023","journal-title":"Lancet Oncol"},{"key":"10.1016\/j.radonc.2025.111324_b0150","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.1016\/S0140-6736(24)00317-9","article-title":"Pembrolizumab or placebo with chemoradiotherapy followed by pembrolizumab or placebo for newly diagnosed, high-risk, locally advanced cervical cancer (ENGOT-cx11\/GOG-3047\/KEYNOTE-A18): a randomised, double-blind, phase 3 clinical trial","volume":"403","author":"Lorusso","year":"2024","journal-title":"Lancet"},{"key":"10.1016\/j.radonc.2025.111324_b0155","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1038\/bjc.2015.448","article-title":"Tumour-infiltrating lymphocyte scores effectively stratify outcomes over and above p16 post chemo-radiotherapy in anal cancer","volume":"114","author":"Gilbert","year":"2016","journal-title":"Br J Cancer"},{"key":"10.1016\/j.radonc.2025.111324_b0160","doi-asserted-by":"crossref","first-page":"874","DOI":"10.1016\/j.clon.2020.09.003","article-title":"A prospective Study of Diffusion-weighted magnetic Resonance Imaging as an Early Prognostic Biomarker in Chemoradiotherapy in Squamous Cell Carcinomas of the Anus","volume":"32","author":"Muirhead","year":"2020","journal-title":"Clin Oncol"},{"key":"10.1016\/j.radonc.2025.111324_b0165","doi-asserted-by":"crossref","first-page":"5767","DOI":"10.1158\/1078-0432.CCR-18-0922","article-title":"Prognostic Impact of Residual HPV ctDNA Detection after Chemoradiotherapy for Anal Squamous Cell Carcinoma","volume":"24","author":"Cabel","year":"2018","journal-title":"Clin Cancer Res"},{"key":"10.1016\/j.radonc.2025.111324_b0170","doi-asserted-by":"crossref","first-page":"2451","DOI":"10.3390\/cancers13102451","article-title":"The Clinical Value of measuring Circulating HPV DNA during Chemo-Radiotherapy in Squamous Cell Carcinoma of the Anus","volume":"13","author":"Lef\u00e8vre","year":"2021","journal-title":"Cancers (Basel)"},{"key":"10.1016\/j.radonc.2025.111324_b0175","doi-asserted-by":"crossref","DOI":"10.1016\/j.ebiom.2023.104691","article-title":"Low-grade intestinal inflammation two decades after pelvic radiotherapy","volume":"94","author":"Devarakonda","year":"2023","journal-title":"EBioMedicine"}],"container-title":["Radiotherapy and Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0167814025053289?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0167814025053289?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T12:28:40Z","timestamp":1786537720000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0167814025053289"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1]]},"references-count":35,"alternative-id":["S0167814025053289"],"URL":"https:\/\/doi.org\/10.1016\/j.radonc.2025.111324","relation":{},"ISSN":["0167-8140"],"issn-type":[{"value":"0167-8140","type":"print"}],"subject":[],"published":{"date-parts":[[2026,1]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Systemic complement protein levels as biomarkers of chemoradiotherapy response in anal squamous cell carcinoma","name":"articletitle","label":"Article Title"},{"value":"Radiotherapy and Oncology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.radonc.2025.111324","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 The Authors. Published by Elsevier B.V.","name":"copyright","label":"Copyright"}],"article-number":"111324"}}