Development and Validation of a Nomogram for Predicting Overall and Cancer-Specific Survival in Elderly NSCLC Patients with Brain Metastases

Development and Validation of a Nomogram for Predicting Overall and Cancer-Specific Survival in Elderly NSCLC Patients with Brain Metastases | 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 Development and Validation of a Nomogram for Predicting Overall and Cancer-Specific Survival in Elderly NSCLC Patients with Brain Metastases Peiyang Fan, Yu Zhang, Zhiyuan Wang, Wencui Zhu, Fangfang Li, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8257867/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Brain metastases significantly compromise survival in elderly patients with non-small cell lung cancer; however, prognostic tools specifically designed for this vulnerable population are still lacking. Traditional TNM staging does not adequately address the intricate interplay of age, comorbidities, and metastasis patterns that are essential for guiding therapeutic decisions. Methods We analyzed 18,209 elderly patients (≥ 60 years) with non-small cell lung cancer and from the SEER database spanning the years 2000 to 2020. The X-tile software was employed to optimize the stratification of continuous variables, specifically age and tumor size. Independent predictors of overall survival and cancer-specific survival were identified using Cox regression and subsequently integrated into nomograms. The performance of the model was validated through the use of the C-index, area under the curve, calibration curves and decision curve analysis, with comparisons made to TNM staging. Results The cohort consisted of 9,514 patients with bone metastases. Multivariate analysis identified ten independent prognostic factors: age, race, grade, tumor size, N stage, surgical intervention, chemotherapy, and metastases to bone, brain, liver, and lung. Nomograms accurately predicted overall survival and cancer-specific survival at 6, 12, and 24 months. The area under the curve values ranged from 0.772 to 0.803, and decision curve analysis confirmed a superior discriminative ability and clinical net benefit compared to TNM staging (AUCs: 0.541–0.580). Surgical intervention and chemotherapy were associated with significantly improved survival outcomes, whereas radiotherapy demonstrated limited benefits in terms of overall survival. Conclusion This novel nomogram offers individualized survival predictions for elderly patients with non-small cell lung cancer and brain metastases, surpassing conventional staging methods. It improves surgical decision-making by incorporating metastasis burden and treatment modalities, thereby supporting personalized management in high-risk geriatric oncology. Non-small cell lung cancer Brain metastases Nomogram Overall survival Cancer-specific survival SEER program Prognosis Aged Full Text Additional Declarations No competing interests reported. Table 1 to 6 are available in the Supplementary Files section. Supplementary Files Table1.docx Table 1. Baseline characteristics of the NSCLS BM patients. Table2.docx Table 2. Baseline characteristics of the training and validation cohorts. Table3.docx Table 3. Univariate and multivariate Cox analyses of OS in the training cohort. Table4.docx Table 4. Univariate and multivariate Cox analyses of OS in the validation cohort. Table5.docx Table 5. NRI and IDI of the OS nomogram compared with TNM stage system. (IDI, integrated discrimination improvement; NRI, net reclassification index.) Table6.docx Table 6. NRI and IDI of the CSS nomogram compared with TNM stage system Cite Share Download PDF Status: Posted Version 1 posted 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. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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-8257867","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":556406898,"identity":"93e92949-0fad-47c5-a5d0-278fc441a7ab","order_by":0,"name":"Peiyang Fan","email":"","orcid":"","institution":"Department of Pathology, The First Affiliated Hospital of Kunming Medical University","correspondingAuthor":false,"prefix":"","firstName":"Peiyang","middleName":"","lastName":"Fan","suffix":""},{"id":556406899,"identity":"4ffbe6d9-3906-48dd-b3c2-a66442910b04","order_by":1,"name":"Yu Zhang","email":"","orcid":"","institution":"Department of 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12:13:14","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":31222,"visible":true,"origin":"","legend":"\u003cp\u003eTable 1.\u003cstrong\u003e \u003c/strong\u003eBaseline characteristics of the NSCLS BM patients.\u003c/p\u003e","description":"","filename":"Table1.docx","url":"https://assets-eu.researchsquare.com/files/rs-8257867/v1/06804785e60fe1b0510b1a40.docx"},{"id":97894172,"identity":"b730ca7a-1efc-4b8c-8596-2e930176a4e1","added_by":"auto","created_at":"2025-12-10 15:31:59","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":27384,"visible":true,"origin":"","legend":"\u003cp\u003eTable 2.\u003cstrong\u003e \u003c/strong\u003eBaseline characteristics of the training and validation cohorts.\u003c/p\u003e","description":"","filename":"Table2.docx","url":"https://assets-eu.researchsquare.com/files/rs-8257867/v1/701f875ac99da5f776ee2b41.docx"},{"id":97699955,"identity":"53337b90-0fa1-451a-8091-b47adddb95d0","added_by":"auto","created_at":"2025-12-08 12:13:14","extension":"docx","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":26925,"visible":true,"origin":"","legend":"\u003cp\u003eTable 3. Univariate and multivariate Cox analyses of OS in the training cohort.\u003c/p\u003e","description":"","filename":"Table3.docx","url":"https://assets-eu.researchsquare.com/files/rs-8257867/v1/08b92c7f644b756cdccb00b6.docx"},{"id":97894284,"identity":"a635f764-93ff-4754-9eac-17898c0cd94b","added_by":"auto","created_at":"2025-12-10 15:32:13","extension":"docx","order_by":4,"title":"","display":"","copyAsset":false,"role":"supplement","size":23087,"visible":true,"origin":"","legend":"\u003cp\u003eTable 4. Univariate and multivariate Cox analyses of OS in the validation cohort.\u003c/p\u003e","description":"","filename":"Table4.docx","url":"https://assets-eu.researchsquare.com/files/rs-8257867/v1/9428c0470cf9fdd895f558f8.docx"},{"id":97893501,"identity":"407c1fa2-75eb-430a-a516-d43bbb9b3e0f","added_by":"auto","created_at":"2025-12-10 15:30:36","extension":"docx","order_by":5,"title":"","display":"","copyAsset":false,"role":"supplement","size":20675,"visible":true,"origin":"","legend":"\u003cp\u003eTable 5. NRI and IDI of the OS nomogram compared with TNM stage system. (IDI, integrated discrimination improvement; NRI, net reclassification index.)\u003c/p\u003e","description":"","filename":"Table5.docx","url":"https://assets-eu.researchsquare.com/files/rs-8257867/v1/232865f5b9e2f5d189ec6dbf.docx"},{"id":97699957,"identity":"9c93a48d-7b47-4295-a757-5e4b1715c242","added_by":"auto","created_at":"2025-12-08 12:13:14","extension":"docx","order_by":6,"title":"","display":"","copyAsset":false,"role":"supplement","size":20489,"visible":true,"origin":"","legend":"\u003cp\u003eTable 6. NRI and IDI of the CSS nomogram compared with TNM stage system\u003c/p\u003e","description":"","filename":"Table6.docx","url":"https://assets-eu.researchsquare.com/files/rs-8257867/v1/c39e4745a7a396ba9fb04f61.docx"}],"financialInterests":"\u003cp\u003eNo competing interests reported.\u003c/p\u003e\n\u003cp\u003eTable 1 to 6 are available in the Supplementary Files section.\u003c/p\u003e","formattedTitle":"Development and Validation of a Nomogram for Predicting Overall and Cancer-Specific Survival in Elderly NSCLC Patients with Brain Metastases","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"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":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Non-small cell lung cancer, Brain metastases, Nomogram, Overall survival, Cancer-specific survival, SEER program, Prognosis, Aged","lastPublishedDoi":"10.21203/rs.3.rs-8257867/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8257867/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e\u003cp\u003eBrain metastases significantly compromise survival in elderly patients with non-small cell lung cancer; however, prognostic tools specifically designed for this vulnerable population are still lacking. Traditional TNM staging does not adequately address the intricate interplay of age, comorbidities, and metastasis patterns that are essential for guiding therapeutic decisions.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eWe analyzed 18,209 elderly patients (\u0026ge;\u0026thinsp;60 years) with non-small cell lung cancer and from the SEER database spanning the years 2000 to 2020. The X-tile software was employed to optimize the stratification of continuous variables, specifically age and tumor size. Independent predictors of overall survival and cancer-specific survival were identified using Cox regression and subsequently integrated into nomograms. The performance of the model was validated through the use of the C-index, area under the curve, calibration curves and decision curve analysis, with comparisons made to TNM staging.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eThe cohort consisted of 9,514 patients with bone metastases. Multivariate analysis identified ten independent prognostic factors: age, race, grade, tumor size, N stage, surgical intervention, chemotherapy, and metastases to bone, brain, liver, and lung. Nomograms accurately predicted overall survival and cancer-specific survival at 6, 12, and 24 months. The area under the curve values ranged from 0.772 to 0.803, and decision curve analysis confirmed a superior discriminative ability and clinical net benefit compared to TNM staging (AUCs: 0.541\u0026ndash;0.580). Surgical intervention and chemotherapy were associated with significantly improved survival outcomes, whereas radiotherapy demonstrated limited benefits in terms of overall survival.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e\u003cp\u003eThis novel nomogram offers individualized survival predictions for elderly patients with non-small cell lung cancer and brain metastases, surpassing conventional staging methods. It improves surgical decision-making by incorporating metastasis burden and treatment modalities, thereby supporting personalized management in high-risk geriatric oncology.\u003c/p\u003e","manuscriptTitle":"Development and Validation of a Nomogram for Predicting Overall and Cancer-Specific Survival in Elderly NSCLC Patients with Brain Metastases","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-12-08 12:13:09","doi":"10.21203/rs.3.rs-8257867/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"60241925-5c78-4a2a-a95a-68316b81eaa0","owner":[],"postedDate":"December 8th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-12-08T12:13:12+00:00","versionOfRecord":[],"versionCreatedAt":"2025-12-08 12:13:09","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8257867","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8257867","identity":"rs-8257867","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}