Optimizing Ovarian Function Preservation for Young Cervical Cancer Patients After Oophoropexy: A Dosimetric and Radiobiological Comparison of Three Radiotherapy Techniques (IMPT, TOMO, and VMAT)

Optimizing Ovarian Function Preservation for Young Cervical Cancer Patients After Oophoropexy: A Dosimetric and Radiobiological Comparison of Three Radiotherapy Techniques (IMPT, TOMO, and VMAT) | 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 Optimizing Ovarian Function Preservation for Young Cervical Cancer Patients After Oophoropexy: A Dosimetric and Radiobiological Comparison of Three Radiotherapy Techniques (IMPT, TOMO, and VMAT) Meiling Xu, Kailian Kang, Man Zhao, Suyan Bi, Jun Ma, Zhijian Chen, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8401559/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 10 You are reading this latest preprint version Abstract Purpose: To systematically compare the dosimetric performance and radiobiological outcomes of intensity-modulated proton therapy (IMPT), helical tomotherapy (TOMO), and volumetric modulated arc therapy (VMAT) for ovarian function preservation in young cervical cancer patients following radical hysterectomy with bilateral ovarian transposition. Methods: Ten premenopausal cervical cancer patients who received postoperative pelvic radiotherapy following bilateral ovarian transposition were retrospectively enrolled. Three treatment plans (IMPT, TOMO, VMAT) were designed for each patient with a uniform prescription of 45 Gy in 25 fractions. IMPT plans incorporated robust optimization accounting for setup uncertainty (5 mm) and range uncertainty (3.5%). Dosimetric parameters evaluated included target coverage (\((V_{100%})\)), homogeneity index (HI), ovarian mean dose (\((D_{mean})\)) and maximum dose (\((D_{max})\)), and dose-volume metrics for organs at risk (OARs: rectum, bladder, small intestine, sigmoid, femoral heads). Radiobiological analyses included equivalent uniform dose (EUD), normal tissue complication probability (NTCP), and excess absolute risk (EAR) of secondary malignancies using Schneider's mechanistic model. Results: All three techniques achieved clinically acceptable target coverage. IMPT demonstrated superior dose homogeneity (HI: \((0.02\pm0.01)\) vs. 0.04–0.06 for photon techniques, \((p<0.05)\)). For ovarian sparing, IMPT significantly reduced \((D_{mean})\) by approximately 95% compared to photon-based techniques (0.11–0.35 Gy vs. 4.44–5.24 Gy, \((p \le 0.002)\)) and substantially minimized low-dose exposure (\((V_{5Gy}<0.4)\) cc vs. 2.86–7.68 cc, \((p \le 0.018)\)). Both IMPT and TOMO achieved significantly lower maximum dose (\((D_{max})\)) to the rectum, bladder, and small intestine than VMAT (\((p<0.05)\)). IMPT reduced small intestine \((V_{35Gy})\) by approximately 30% and mean bladder dose by 35% compared to photon techniques. NTCP analysis demonstrated that IMPT significantly reduced the risk of late toxicity to the small intestine, rectum, and bladder compared to both TOMO and VMAT (\((p<0.05)\)), while comparable femoral head protection was observed between IMPT and VMAT, both significantly superior to TOMO (\((p<0.05)\)). EAR modeling revealed that IMPT minimized bladder cancer risk (\((p = 0.002)\)), whereas VMAT achieved the lowest rectal cancer risk (\((p \le 0.006)\). IMPT also reduced integral dose to normal tissue by 54% compared to photon modalities. VMAT exhibited the shortest beam-on time (\((2.20\pm0.05)\) min vs. TOMO \((8.18\pm0.99)\) min, \((p<0.001)\)). Conclusion: IMPT demonstrated unparalleled ovarian dose reduction and superior protection against radiation-induced secondary cancers for most pelvic OARs, establishing it as the optimal technique for ovarian function preservation when available. VMAT offers superior treatment efficiency but requires stringent ovarian dose constraints. TOMO provides comparable high-dose OAR protection to IMPT but is limited in minimizing low-dose ovarian exposure. Technique selection should be individualized based on available resources and patient priorities, with IMPT strongly recommended for young patients prioritizing long-term ovarian function. Cervical cancer Ovarian function preservation IMPT TOMO VMAT NTCP Secondary cancer risk EAR Full Text Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 08 Apr, 2026 Reviews received at journal 03 Apr, 2026 Reviewers agreed at journal 12 Mar, 2026 Reviews received at journal 25 Feb, 2026 Reviewers agreed at journal 25 Feb, 2026 Reviewers agreed at journal 26 Jan, 2026 Reviewers invited by journal 21 Jan, 2026 Editor assigned by journal 07 Jan, 2026 Submission checks completed at journal 07 Jan, 2026 First submitted to journal 06 Jan, 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-8401559","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":578803129,"identity":"f0461503-26c6-4df6-9510-ddee8505225b","order_by":0,"name":"Meiling Xu","email":"","orcid":"","institution":"National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital \u0026 Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical 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VMAT)","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":"radiation-oncology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"raon","sideBox":"Learn more about [Radiation Oncology](http://ro-journal.biomedcentral.com/)","snPcode":"13014","submissionUrl":"https://submission.nature.com/new-submission/13014/3","title":"Radiation Oncology","twitterHandle":"@OncoBioMed","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Cervical cancer, Ovarian function preservation, IMPT, TOMO, VMAT, NTCP, Secondary cancer risk, EAR","lastPublishedDoi":"10.21203/rs.3.rs-8401559/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8401559/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003ePurpose:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTo systematically compare the dosimetric performance and radiobiological outcomes of intensity-modulated proton therapy (IMPT), helical tomotherapy (TOMO), and volumetric modulated arc therapy (VMAT) for ovarian function preservation in young cervical cancer patients following radical hysterectomy with bilateral ovarian transposition.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTen premenopausal cervical cancer patients who received postoperative pelvic radiotherapy following bilateral ovarian transposition were retrospectively enrolled. Three treatment plans (IMPT, TOMO, VMAT) were designed for each patient with a uniform prescription of 45 Gy in 25 fractions. IMPT plans incorporated robust optimization accounting for setup uncertainty (5 mm) and range uncertainty (3.5%). Dosimetric parameters evaluated included target coverage (\\((V_{100%})\\)), homogeneity index (HI), ovarian mean dose (\\((D_{mean})\\)) and maximum dose (\\((D_{max})\\)), and dose-volume metrics for organs at risk (OARs: rectum, bladder, small intestine, sigmoid, femoral heads). Radiobiological analyses included equivalent uniform dose (EUD), normal tissue complication probability (NTCP), and excess absolute risk (EAR) of secondary malignancies using Schneider's mechanistic model.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll three techniques achieved clinically acceptable target coverage. IMPT demonstrated superior dose homogeneity (HI: \\((0.02\\pm0.01)\\) vs. 0.04–0.06 for photon techniques, \\((p\u0026lt;0.05)\\)). For ovarian sparing, IMPT significantly reduced \\((D_{mean})\\) by approximately 95% compared to photon-based techniques (0.11–0.35 Gy vs. 4.44–5.24 Gy, \\((p \\le 0.002)\\)) and substantially minimized low-dose exposure (\\((V_{5Gy}\u0026lt;0.4)\\) cc vs. 2.86–7.68 cc, \\((p \\le 0.018)\\)). Both IMPT and TOMO achieved significantly lower maximum dose (\\((D_{max})\\)) to the rectum, bladder, and small intestine than VMAT (\\((p\u0026lt;0.05)\\)). IMPT reduced small intestine \\((V_{35Gy})\\) by approximately 30% and mean bladder dose by 35% compared to photon techniques. NTCP analysis demonstrated that IMPT significantly reduced the risk of late toxicity to the small intestine, rectum, and bladder compared to both TOMO and VMAT (\\((p\u0026lt;0.05)\\)), while comparable femoral head protection was observed between IMPT and VMAT, both significantly superior to TOMO (\\((p\u0026lt;0.05)\\)). EAR modeling revealed that IMPT minimized bladder cancer risk (\\((p = 0.002)\\)), whereas VMAT achieved the lowest rectal cancer risk (\\((p \\le 0.006)\\). IMPT also reduced integral dose to normal tissue by 54% compared to photon modalities. VMAT exhibited the shortest beam-on time (\\((2.20\\pm0.05)\\) min vs. TOMO \\((8.18\\pm0.99)\\) min, \\((p\u0026lt;0.001)\\)).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIMPT demonstrated unparalleled ovarian dose reduction and superior protection against radiation-induced secondary cancers for most pelvic OARs, establishing it as the optimal technique for ovarian function preservation when available. VMAT offers superior treatment efficiency but requires stringent ovarian dose constraints. TOMO provides comparable high-dose OAR protection to IMPT but is limited in minimizing low-dose ovarian exposure. Technique selection should be individualized based on available resources and patient priorities, with IMPT strongly recommended for young patients prioritizing long-term ovarian function.\u003c/p\u003e","manuscriptTitle":"Optimizing Ovarian Function Preservation for Young Cervical Cancer Patients After Oophoropexy: A Dosimetric and Radiobiological Comparison of Three Radiotherapy Techniques (IMPT, TOMO, and VMAT)","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-01-26 13:07:24","doi":"10.21203/rs.3.rs-8401559/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-04-08T07:37:51+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-03T21:20:47+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"67305121052779070107141818703448171246","date":"2026-03-12T19:28:12+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-02-26T04:27:32+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"258711904992858474544075625281834615589","date":"2026-02-26T00:05:53+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"205460012129779449730019985082296436468","date":"2026-01-27T03:03:40+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-01-22T03:00:26+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-01-07T22:41:23+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-01-07T09:37:56+00:00","index":"","fulltext":""},{"type":"submitted","content":"Radiation Oncology","date":"2026-01-07T00:25:22+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"radiation-oncology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"raon","sideBox":"Learn more about [Radiation Oncology](http://ro-journal.biomedcentral.com/)","snPcode":"13014","submissionUrl":"https://submission.nature.com/new-submission/13014/3","title":"Radiation Oncology","twitterHandle":"@OncoBioMed","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"bd21b3ca-7e54-4505-8215-14095ac00375","owner":[],"postedDate":"January 26th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-05-13T14:38:02+00:00","versionOfRecord":[],"versionCreatedAt":"2026-01-26 13:07:24","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8401559","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8401559","identity":"rs-8401559","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}