{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T16:19:07Z","timestamp":1789834747153,"version":"4.0.1"},"reference-count":47,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2023,8,4]],"date-time":"2023-08-04T00:00:00Z","timestamp":1691107200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Importance<\/jats:title>\n<jats:p>The mechanisms underlying the association between chronic stress and higher mortality among individuals with cancer remain incompletely understood.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Objective<\/jats:title>\n<jats:p>To test the hypotheses that among individuals with active head and neck cancer, that higher stress-associated neural activity (ie. metabolic amygdalar activity [AmygA]) at cancer staging associates with survival.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Design<\/jats:title>\n<jats:p>Retrospective cohort study.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Setting<\/jats:title>\n<jats:p>Academic Medical Center (Massachusetts General Hospital, Boston).<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec005\">\n<jats:title>Participants<\/jats:title>\n<jats:p>240 patients with head and neck cancer (HNCA) who underwent <jats:sup>18<\/jats:sup>F-FDG-PET\/CT imaging as part of initial cancer staging.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec006\">\n<jats:title>Measurements<\/jats:title>\n<jats:p><jats:sup>18<\/jats:sup>F-FDG uptake in the amygdala was determined by placing circular regions of interest in the right and left amygdalae and measuring the mean tracer accumulation (i.e., standardized uptake value [SUV]) in each region of interest. Amygdalar uptake was corrected for background cerebral activity (mean temporal lobe SUV).<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec007\">\n<jats:title>Results<\/jats:title>\n<jats:p>Among individuals with HNCA (age 59\u00b113 years; 30% female), 67 died over a median follow-up period of 3 years (IQR: 1.7\u20135.1). AmygA associated with heightened bone marrow activity, leukocytosis, and C-reactive protein (P&lt;0.05 each). In adjusted and unadjusted analyses, AmygA associated with subsequent mortality (HR [95% CI]: 1.35, [1.07\u20131.70], P = 0.009); the association persisted in stratified subset analyses restricted to patients with advanced cancer stage (P&lt;0.001). Individuals within the highest tertile of AmygA experienced a 2-fold higher mortality rate compared to others (P = 0.01). The median progression-free survival was 25 months in patients with higher AmygA (upper tertile) as compared with 36.5 months in other individuals (HR for progression or death [95%CI], 1.83 [1.24\u20132.68], P = 0.001).<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec008\">\n<jats:title>Conclusions and relevance<\/jats:title>\n<jats:p>AmygA, quantified on routine <jats:sup>18<\/jats:sup>F-FDG-PET\/CT images obtained at cancer staging, independently and robustly predicts mortality and cancer progression among patients with HNCA. Future studies should test whether strategies that attenuate AmygA (or its downstream biological consequences) may improve cancer survival.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0279235","type":"journal-article","created":{"date-parts":[[2023,8,4]],"date-time":"2023-08-04T17:21:58Z","timestamp":1691169718000},"page":"e0279235","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":9,"title":["Amygdalar activity measured using FDG-PET\/CT at head and neck cancer staging independently predicts survival"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4871-4734","authenticated-orcid":true,"given":"Malek Z. 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fear acquisition and extinction paradigm in women with childhood sexual-abuse-related post-traumatic stress disorder","volume":"35","author":"JD Bremner","year":"2005","journal-title":"Psychol Med"},{"key":"pone.0279235.ref019","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.psyneuen.2018.09.024","article-title":"Amygdalar activity predicts future incident diabetes independently of adiposity","volume":"100","author":"MT Osborne","year":"2019","journal-title":"Psychoneuroendocrinology"},{"issue":"9","key":"pone.0279235.ref020","doi-asserted-by":"crossref","DOI":"10.1161\/JAHA.117.006453","article-title":"Human Papillomavirus Status and the Risk of Cerebrovascular Events Following Radiation Therapy for Head and Neck Cancer","volume":"6","author":"D Addison","year":"2017","journal-title":"Journal of the American Heart 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axis in humans","volume":"8","author":"H Emami","year":"2015","journal-title":"JACC Cardiovascular imaging"},{"issue":"2","key":"pone.0279235.ref024","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/j.ejca.2008.10.026","article-title":"New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1)","volume":"45","author":"EA Eisenhauer","year":"2009","journal-title":"European journal of cancer (Oxford, England: 1990)"},{"issue":"4","key":"pone.0279235.ref025","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1002\/bimj.200410135","article-title":"Estimation of the Youden Index and its associated cutoff point","volume":"47","author":"R Fluss","year":"2005","journal-title":"Biom J"},{"issue":"1","key":"pone.0279235.ref026","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1002\/1097-0142(1950)3:1<32::AID-CNCR2820030106>3.0.CO;2-3","article-title":"Index for rating diagnostic tests","volume":"3","author":"WJ Youden","year":"1950","journal-title":"Cancer"},{"issue":"12","key":"pone.0279235.ref027","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1016\/j.biopsych.2010.04.027","article-title":"Amygdala Activity, Fear, and Anxiety: Modulation by Stress","volume":"67","author":"KJ Ressler","year":"2010","journal-title":"Biological psychiatry"},{"key":"pone.0279235.ref028","doi-asserted-by":"crossref","first-page":"176157","DOI":"10.1155\/2012\/176157","article-title":"Anatomy of the Temporal Lobe","volume":"2012","author":"JA Kiernan","year":"2012","journal-title":"Epilepsy Research and Treatment"},{"key":"pone.0279235.ref029","doi-asserted-by":"crossref","first-page":"24","DOI":"10.3389\/fncir.2016.00024","article-title":"Serotonin, Amygdala and Fear: Assembling the Puzzle","volume":"10","author":"M Bocchio","year":"2016","journal-title":"Frontiers in Neural Circuits"},{"key":"pone.0279235.ref030","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1186\/1756-6606-7-32","article-title":"Chronic stress impairs GABAergic control of amygdala through suppressing the tonic GABAA receptor currents","volume":"7","author":"Z-P Liu","year":"2014","journal-title":"Molecular Brain"},{"key":"pone.0279235.ref031","first-page":"165","article-title":"Anxiety disorders and GABA neurotransmission: a disturbance of modulation","volume":"11","author":"P. Nuss","year":"2015","journal-title":"Neuropsychiatric Disease and Treatment"},{"key":"pone.0279235.ref032","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1038\/nature19318","article-title":"Serotonin engages an anxiety and fear-promoting circuit in the extended amygdala","volume":"537","author":"CA Marcinkiewcz","year":"2016","journal-title":"Nature"},{"issue":"4","key":"pone.0279235.ref033","doi-asserted-by":"crossref","first-page":"1244","DOI":"10.1002\/hep.23441","article-title":"Serotonin promotes tumor growth in human hepatocellular cancer","volume":"51","author":"C Soll","year":"2010","journal-title":"Hepatology (Baltimore, Md)"},{"issue":"21","key":"pone.0279235.ref034","doi-asserted-by":"crossref","first-page":"2704","DOI":"10.3748\/wjg.v18.i21.2704","article-title":"GABA stimulates human hepatocellular carcinoma growth through overexpressed GABAA receptor theta subunit","volume":"18","author":"Y-H Li","year":"2012","journal-title":"World Journal of Gastroenterology: WJG"},{"key":"pone.0279235.ref035","first-page":"171","article-title":"GABA\u2019s Control of Stem and Cancer Cell Proliferation in Adult Neural and Peripheral Niches","volume":"24","author":"SZ Young","year":"2009","journal-title":"Physiology (Bethesda, Md)"},{"issue":"19","key":"pone.0279235.ref036","doi-asserted-by":"crossref","first-page":"1747","DOI":"10.1016\/j.jacc.2009.05.015","article-title":"The Sympathetic Nervous System in Heart Failure: Physiology, Pathophysiology, and Clinical Implications","volume":"54","author":"F Triposkiadis","year":"2009","journal-title":"Journal of the American College of Cardiology"},{"issue":"4","key":"pone.0279235.ref037","doi-asserted-by":"crossref","first-page":"1380","DOI":"10.1172\/JCI33125","article-title":"Dopamine regulates endothelial progenitor cell mobilization from mouse bone marrow in tumor vascularization","volume":"118","author":"D Chakroborty","year":"2008","journal-title":"The Journal of clinical investigation"},{"issue":"7","key":"pone.0279235.ref038","first-page":"2517","article-title":"Different projections of the central amygdaloid nucleus mediate autonomic and behavioral correlates of conditioned fear. The Journal of neuroscience: the official journal of the","volume":"8","author":"JE LeDoux","year":"1988","journal-title":"Society for Neuroscience"},{"issue":"20","key":"pone.0279235.ref039","doi-asserted-by":"crossref","first-page":"1351","DOI":"10.1056\/NEJM199505183322008","article-title":"The hypothalamic-pituitary-adrenal axis and immune-mediated inflammation","volume":"332","author":"GP Chrousos","year":"1995","journal-title":"The New England journal of medicine"},{"issue":"24","key":"pone.0279235.ref040","doi-asserted-by":"crossref","first-page":"1719","DOI":"10.1056\/NEJMoa011871","article-title":"The Effect of Group Psychosocial Support on Survival in Metastatic Breast Cancer","volume":"345","author":"PJ Goodwin","year":"2001","journal-title":"New England Journal of Medicine"},{"issue":"6","key":"pone.0279235.ref041","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1002\/(SICI)1099-1611(199911\/12)8:6<474::AID-PON427>3.0.CO;2-A","article-title":"Effects of group CBT on the survival time of patients with metastatic breast cancer","volume":"8","author":"Sarah E","year":"1999","journal-title":"Psycho-Oncology"},{"key":"pone.0279235.ref042","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1038\/sj.bjc.6606073","article-title":"How traumatic is breast cancer? Post-traumatic stress symptoms (PTSS) and risk factors for severe PTSS at 3 and 15 months after surgery in a nationwide cohort of Danish women treated for primary breast cancer","volume":"104","author":"M O\u2019Connor","year":"2011","journal-title":"British Journal Of Cancer"},{"issue":"6","key":"pone.0279235.ref043","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1002\/(SICI)1099-1611(199811\/12)7:6<508::AID-PON376>3.0.CO;2-7","article-title":"A randomized controlled trial of the effects of group psychological therapy on survival in women with metastatic breast cancer","volume":"7","author":"AJ Cunningham","year":"1998","journal-title":"Psychooncology"},{"issue":"12","key":"pone.0279235.ref044","doi-asserted-by":"crossref","first-page":"3450","DOI":"10.1002\/cncr.23969","article-title":"Psychologic intervention improves survival for breast cancer patients","volume":"113","author":"BL Andersen","year":"2008","journal-title":"Cancer"},{"issue":"1","key":"pone.0279235.ref045","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.cellimm.2011.04.003","article-title":"Psychological stress is associated with altered levels of myeloid-derived suppressor cells in breast cancer patients","volume":"270","author":"BL Mundy-Bosse","year":"2011","journal-title":"Cellular immunology"},{"issue":"6","key":"pone.0279235.ref046","first-page":"Cd004253","article-title":"Psychological interventions for women with metastatic breast cancer","author":"M Mustafa","year":"2013","journal-title":"The Cochrane database of systematic reviews"},{"key":"pone.0279235.ref047","first-page":"A18768","article-title":"Increased Stress-related Neural Tissue Activity Potentiates Inflammation and Impedes the Anti-inflammatory Impact of Statins","volume":"136","author":"MTO Basma Hammad","journal-title":"Circulation"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0279235","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,4]],"date-time":"2023-08-04T17:22:35Z","timestamp":1691169755000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0279235"}},"subtitle":[],"editor":[{"given":"Tarik A.","family":"Rashid","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2023,8,4]]},"references-count":47,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2023,8,4]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0279235","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,8,4]]}}}