{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T17:33:44Z","timestamp":1789061624868,"version":"build-2803163510"},"reference-count":23,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T00:00:00Z","timestamp":1741651200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Head &amp; Neck"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Purpose<\/jats:title><jats:p>Hypercalcemia is the most common metabolic disorder in cancer, affecting 10%\u201320% of patients with advanced malignancies, including squamous cell carcinoma of the head and neck (HNSCC), though its prognostic significance remains poorly studied. This study aimed to evaluate the prognostic impact of hypercalcemia at diagnosis in patients with locally advanced or metastatic HNSCC and to explore underlying mechanisms and treatment options.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We conducted a bicentric, retrospective analysis of patients diagnosed between 2015 and 2021, including those with locally advanced or metastatic HNSCC undergoing chemotherapy. Hypercalcemia at diagnosis was defined as an albumin\u2010corrected serum calcium level\u2009&gt;\u20092.6\u2009mmol\/L, equivalent to 10.4\u2009mg\/dL. The primary outcome was overall survival (OS), compared between hypercalcemic and non\u2010hypercalcemic patients using multivariate analysis. Progression\u2010free survival (PFS), along with clinical, biological, and therapeutic characteristics were also evaluated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The study included 286 HNSCC patients, 225 (78.7%) of whom were male. Hypercalcemia incidence was 17.8%. The median OS for the cohort was 7.9\u2009months (95% CI\u2009=\u20096.8\u201310.6). Hypercalcemic patients had a median OS of 5.9\u2009months (95% CI\u2009=\u20093.8\u20137.9), compared to 9.1\u2009months (95% CI\u2009=\u20097.3\u201311.7) in non\u2010hypercalcemic patients (<jats:italic>p<\/jats:italic>\u2009=\u20090.002). In multivariate analysis, hypercalcemia was associated with worse OS (HR\u2009=\u20091.73, 95% CI\u2009=\u20091.17\u20132.56, <jats:italic>p<\/jats:italic>\u2009=\u20090.006). Median PFS was 4.3\u2009months (95% CI\u2009=\u20093.6\u20135.5) for all patients. Hypercalcemic patients had a significantly shorter PFS of 2.4\u2009months (95% CI\u2009=\u20091.9\u20134.8) compared to 4.7\u2009months (95% CI\u2009=\u20093.8\u20135.9) in non\u2010hypercalcemic patients (<jats:italic>p<\/jats:italic>\u2009=\u20090.0025). Multivariate analysis identified hypercalcemia and oral cavity tumors as negative prognostic factors, with HRs of 1.76 and 1.86, respectively. Bone metastasis rates were similar (17.6% vs. 16.2%), but local osteolysis was significantly higher in hypercalcemic patients (54.1% vs. 27.2%, <jats:italic>p<\/jats:italic>\u2009=\u20090.003). Bisphosphonates were administered to 38% of hypercalcemic patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>In this study, hypercalcemia was an independent negative prognostic factor of survival and rapid progression in patients with locally advanced or metastatic HNSCC.<\/jats:p><\/jats:sec>","DOI":"10.1002\/hed.28126","type":"journal-article","created":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T20:18:22Z","timestamp":1741724302000},"page":"2174-2182","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Prognosis and Phenotypes of Advanced Head and Neck Carcinoma Associated With Hypercalcemia"],"prefix":"10.1002","volume":"47","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4818-3363","authenticated-orcid":false,"given":"Elodie","family":"Mamou","sequence":"first","affiliation":[{"name":"Department of Medical Oncology, Sorbonne Universit\u00e9, Assistance Publique\u2010H\u00f4pitaux de Paris (AP\u2010HP), Piti\u00e9 Salp\u00eatri\u00e8re Hospital  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Gougis","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Sorbonne Universit\u00e9, Assistance Publique\u2010H\u00f4pitaux de Paris (AP\u2010HP), Piti\u00e9 Salp\u00eatri\u00e8re Hospital  Paris France"},{"name":"Department of Pharmacology, Sorbonne Universit\u00e9, Institut National de la sant\u00e9 et de la Recherche m\u00e9dicale (INSERM), Assistance Publique\u2013H\u00f4pitaux de Paris (AP\u2010HP), Clinical Investigation Center (CIC\u20101901), Piti\u00e9\u2010Salp\u00eatri\u00e8re Hospital  Paris France"},{"name":"Residual Tumor &amp; Response to Treatment Laboratory, RT2Lab, INSERM, U932 Immunity and Cancer, Institut Curie, Universit\u00e9 Paris Cit\u00e9  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baptiste","family":"Abbar","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Sorbonne Universit\u00e9, Assistance Publique\u2010H\u00f4pitaux de Paris (AP\u2010HP), Piti\u00e9 Salp\u00eatri\u00e8re Hospital  Paris France"},{"name":"Centre d'Immunologie et Des Maladies Infectieuses (CIMI\u2010Paris), Sorbonne Universit\u00e9  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean\u2010philippe","family":"Spano","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Sorbonne Universit\u00e9, Assistance Publique\u2010H\u00f4pitaux de Paris (AP\u2010HP), Piti\u00e9 Salp\u00eatri\u00e8re Hospital  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laetitia","family":"Morardet","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Sorbonne Universit\u00e9, Assistance Publique\u2010H\u00f4pitaux de Paris (AP\u2010HP), Piti\u00e9 Salp\u00eatri\u00e8re Hospital  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aurore","family":"Vozy","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Sorbonne Universit\u00e9, Assistance Publique\u2010H\u00f4pitaux de Paris (AP\u2010HP), Piti\u00e9 Salp\u00eatri\u00e8re Hospital  Paris France"},{"name":"Centre d'Immunologie et Des Maladies Infectieuses (CIMI\u2010Paris), Sorbonne Universit\u00e9  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,3,11]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcte.2018.05.004"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.7861\/clinmedicine.17-3-270"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMcp042806"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1677\/erc.1.00543"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1055\/a-1049-0647"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMcp2113128"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.3810\/pgm.2004.04.1486"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells13121051"},{"key":"e_1_2_8_10_1","unstructured":"\u201cEpidemiologic Trends in Head and Neck Cancer and Aids in Diagnosis \u2010 Oral and Maxillofacial Surgery Clinics\u201dDisponible sur 2023 https:\/\/www.oralmaxsurgery.theclinics.com\/article\/S1042\u20103699(14)00002\u20108\/fulltext."},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(19831215)52:12<2261::AID-CNCR2820521217>3.0.CO;2-K"},{"issue":"5","key":"e_1_2_8_12_1","first-page":"154","article-title":"Hypercalcemia in Advanced Head and Neck Squamous Cell Carcinoma: Prevalence and Potential Impact on Palliative Care","volume":"7","author":"Alsirafy S. A.","year":"2009","journal-title":"Journal of Supportive Oncology"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.oraloncology.2005.04.013"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.1711710310"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1177\/43.1.7822764"},{"issue":"7","key":"e_1_2_8_16_1","first-page":"2755","article-title":"PTHrP Regulates Angiogenesis and Bone Resorption via VEGF Expression","volume":"30","author":"Isowa S.","year":"2010","journal-title":"Anticancer Research"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2014-4250"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12957-024-03522-2"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0140\u20106736(19)32591\u20107"},{"key":"e_1_2_8_20_1","first-page":"517","article-title":"Paraneoplastic Humorally Mediated Hypercalcemia Induced by Parathyroid Hormone\u2010Related Protein in Gynecologic Malignancies: A Systematic Review","volume":"32","author":"Savvari P.","year":"2009","journal-title":"Oncology Research and Treatment"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.endinu.2022.06.006"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13613-019-0606-8"},{"key":"e_1_2_8_23_1","first-page":"1779","article-title":"Hypercalcemia of Malignancy and New Treatment Options","volume":"11","author":"Sternlicht H.","year":"2015","journal-title":"Therapeutics and Clinical Risk Management"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.14740\/wjon953w"}],"container-title":["Head &amp; Neck"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/hed.28126","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,17]],"date-time":"2025-07-17T02:33:13Z","timestamp":1752719593000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/hed.28126"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,11]]},"references-count":23,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2025,8]]}},"alternative-id":["10.1002\/hed.28126"],"URL":"https:\/\/doi.org\/10.1002\/hed.28126","archive":["Portico"],"relation":{},"ISSN":["1043-3074","1097-0347"],"issn-type":[{"value":"1043-3074","type":"print"},{"value":"1097-0347","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,11]]},"assertion":[{"value":"2024-12-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-02-10","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-03-11","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}