Treatment-Related Pain in Refractory Cancer Pain: Prevalence, Mechanisms, and Clinical Implications in a Tertiary Referral Cohort

Treatment-Related Pain in Refractory Cancer Pain: Prevalence, Mechanisms, and Clinical Implications in a Tertiary Referral Cohort | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Treatment-Related Pain in Refractory Cancer Pain: Prevalence, Mechanisms, and Clinical Implications in a Tertiary Referral Cohort Rotem Agur, Barak Cohen, Mulham Sabbah, Silviu Brill, Maor Staierman, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9172163/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 6 You are reading this latest preprint version Abstract Background: The long-term effects of cancer treatment are increasingly driving persistent pain in cancer survivors; however, the contribution and clinical profile of cancer treatment–related pain (CTRP) in refractory pain populations remain poorly defined. Methods: We conducted a retrospective cohort study of consecutive patients (N = 622) referred to a tertiary multidisciplinary cancer pain clinic for initial evaluation of refractory pain (January 2021-June 2025). Pain etiology was classified using ICD-11 criteria as treatment-related pain (TRP; MG30.11), tumor-related pain (MG30.10), or non–cancer-related pain. The multivariate logistic regression analysis identified factors associated with TRP attribution. Results: TRP was identified in 42.1% of patients (n = 262). Patients with TRP were younger than those with tumor-related pain (mean 58.1 ± 14.8 vs 64.2 ± 12.8 years, p < 0.001). Peripheral neuropathy was strongly associated with TRP attribution (adjusted odds ratio 9.18; 95% CI 2.56–32.83). Neuropathic (46.2%) and mixed (35.9%) mechanisms predominated in TRP, whereas nociceptive mechanisms were more common in tumor-related pain. Conclusions: Treatment-related pain constitutes a major component of refractory cancer pain and demonstrates a distinct clinical and mechanistic profiles. Its predominance among younger survivors supports its characterization as a survivorship-associated morbidity rather than an end-of-life phenomenon. These findings support the earlier recognition and integration of mechanism-informed, multidisciplinary supportive care strategies to improve outcomes in patients with persistent treatment-related pain. Cancer survivorship Treatment-related pain Refractory cancer pain Neuropathic pain Multidisciplinary pain management Full Text Additional Declarations No competing interests reported. Supplementary Files eAppendixDefinitionsandCoding.docx S1TableandCaption.docx SupplementaryTableS1B.docx S2TableCaption.docx S2Table.xlsx SupplementaryTableS3A3SB.docx SupplementaryTableS3A.xlsx SupplementaryTableS3B.xlsx TableS4.docx TableS5.docx Cite Share Download PDF Status: Under Review Version 1 posted Reviews received at journal 23 Apr, 2026 Reviewers agreed at journal 18 Apr, 2026 Reviewers invited by journal 16 Apr, 2026 Editor assigned by journal 15 Apr, 2026 Submission checks completed at journal 26 Mar, 2026 First submitted to journal 19 Mar, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-9172163","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":626143333,"identity":"548f01c5-92e9-419a-ba17-64f42f288b31","order_by":0,"name":"Rotem Agur","email":"","orcid":"","institution":"Tel Aviv Sourasky Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Rotem","middleName":"","lastName":"Agur","suffix":""},{"id":626143339,"identity":"648833eb-eae0-481f-b68f-4c1a8ea4fa4d","order_by":1,"name":"Barak Cohen","email":"","orcid":"","institution":"Tel Aviv Sourasky Medical 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Cohort","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"supportive-care-in-cancer","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"jscc","sideBox":"Learn more about [Supportive Care in Cancer](https://www.springer.com/journal/520)","snPcode":"520","submissionUrl":"https://submission.nature.com/new-submission/520/3","title":"Supportive Care in Cancer","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Cancer survivorship, Treatment-related pain, Refractory cancer pain, Neuropathic pain, Multidisciplinary pain management","lastPublishedDoi":"10.21203/rs.3.rs-9172163/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9172163/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e The long-term effects of cancer treatment are increasingly driving persistent pain in cancer survivors; however, the contribution and clinical profile of cancer treatment–related pain (CTRP) in refractory pain populations remain poorly defined.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e We conducted a retrospective cohort study of consecutive patients (N = 622) referred to a tertiary multidisciplinary cancer pain clinic for initial evaluation of refractory pain (January 2021-June 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Pain etiology was classified using ICD-11 criteria as treatment-related pain (TRP; MG30.11), tumor-related pain (MG30.10), or non–cancer-related pain. The multivariate logistic regression analysis identified factors associated with TRP attribution.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e TRP was identified in 42.1% of patients (n = 262). Patients with TRP were younger than those with tumor-related pain (mean 58.1 ± 14.8 vs 64.2 ± 12.8 years, p \u0026lt; 0.001). Peripheral neuropathy was strongly associated with TRP attribution (adjusted odds ratio 9.18; 95% CI 2.56–32.83). Neuropathic (46.2%) and mixed (35.9%) mechanisms predominated in TRP, whereas nociceptive mechanisms were more common in tumor-related pain.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions:\u003c/strong\u003e Treatment-related pain constitutes a major component of refractory cancer pain and demonstrates a distinct clinical and mechanistic profiles. Its predominance among younger survivors supports its characterization as a survivorship-associated morbidity rather than an end-of-life phenomenon. These findings support the earlier recognition and integration of mechanism-informed, multidisciplinary supportive care strategies to improve outcomes in patients with persistent treatment-related pain.\u003c/p\u003e","manuscriptTitle":"Treatment-Related Pain in Refractory Cancer Pain: Prevalence, Mechanisms, and Clinical Implications in a Tertiary Referral Cohort","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-04-24 00:57:16","doi":"10.21203/rs.3.rs-9172163/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2026-04-23T12:33:34+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"217247011308541512521213024152608792190","date":"2026-04-18T09:47:27+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-04-16T08:59:05+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-04-15T16:28:18+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-03-26T05:22:30+00:00","index":"","fulltext":""},{"type":"submitted","content":"Supportive Care in Cancer","date":"2026-03-19T17:44:14+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"supportive-care-in-cancer","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"jscc","sideBox":"Learn more about [Supportive Care in Cancer](https://www.springer.com/journal/520)","snPcode":"520","submissionUrl":"https://submission.nature.com/new-submission/520/3","title":"Supportive Care in Cancer","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"c591e4eb-686c-4911-8351-4f3a140c8fb0","owner":[],"postedDate":"April 24th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-04-24T00:57:16+00:00","versionOfRecord":[],"versionCreatedAt":"2026-04-24 00:57:16","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9172163","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9172163","identity":"rs-9172163","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}