Journal article
Externally validated digital decision support tool for time-to-osteoradionecrosis risk-stratification using right-censored multi-institutional observational cohorts
Radiotherapy and oncology, Vol.207, 110890
06/2025
DOI: 10.1016/j.radonc.2025.110890
PMCID: PMC12085279
PMID: 40222595
Abstract
•Gender, pre-RT dental extractions and D25% are associated with faster onset of ORNJ.•Mandibular D25% is a significant factor for ORNJ development and accelerated onset.•Online time-to-ORNJ prediction tool facilitates clinical implementation.•Enhanced HNC survivorship care through time-to-ORNJ modeling.
Existing studies on osteoradionecrosis of the jaw (ORNJ) have primarily used cross-sectional data, assessing risk factors at a single time point. Determining the time-to-event profile of ORNJ has important implications to monitor oral health in head and neck cancer (HNC) long-term survivors.
Data were retrospectively obtained for a clinical observational cohort of 1129 patients (198 ORNJ cases) with HNC treated with radiotherapy (RT) at The University of Texas MD Anderson Cancer Center. A Weibull Accelerated Failure Time model was trained on previously identified dosimetric, clinical and demographic predictors. External validation was performed using an independent cohort of 265 patients (92 ORNJ cases) treated at Guy’s and St. Thomas’ Hospitals. To facilitate clinical implementation of the model, an online graphical user interface (GUI) was developed, including formal stakeholder usability testing.
Our model identified that gender (males), pre-RT dental extractions and D25% were associated with a 38 %, 27 % and 12 % faster onset of ORNJ, respectively, with adjusted time ratios of 0.62 (p = 0.11), 0.73 (p = 0.13) and 0.88 (p < 0.005). The model demonstrated strong internal calibration (integrated Brier score of 0.133, D-calibration p-value 0.998) and optimal discrimination at 72 months (Harrell’s C-index of 0.72).
This study is the first to demonstrate a direct relationship between radiation dose and the time to ORNJ onset, providing a novel characterization of the impact of delivered dose and patient-related factors not only on the probability of a late effect (ORNJ), but the conditional risk during survivorship.
Details
- Title: Subtitle
- Externally validated digital decision support tool for time-to-osteoradionecrosis risk-stratification using right-censored multi-institutional observational cohorts
- Creators
- Laia Humbert-Vidan - The University of Texas MD Anderson Cancer CenterSerageldin Kamel - The University of Texas MD Anderson Cancer CenterAndrew Wentzel - University of Illinois Urbana-ChampaignZaphanlene Kaffey - The University of Texas MD Anderson Cancer CenterMoamen Abdelaal - Emory and Henry CollegeKyle B. Spier - Paul L. Foster School of Medicine, El Paso, TX, USANatalie A. West - The University of Texas MD Anderson Cancer CenterG.Elisabeta Marai - University of Illinois Urbana-ChampaignGuadalupe Canahuate - University of IowaXinhua Zhang - University of Illinois Urbana-ChampaignMelissa M. Chen - The University of Texas MD Anderson Cancer CenterKareem A. Wahid - The University of Texas MD Anderson Cancer CenterJillian Rigert - The University of Texas MD Anderson Cancer CenterSeyedmohammadhossein Hosseinian - North Carolina State UniversityAndrew J. Schaefer - Rice UniversityKristy K. Brock - The University of Texas MD Anderson Cancer CenterMark Chambers - The University of Texas MD Anderson Cancer CenterAdegbenga O. Otun - The University of Texas MD Anderson Cancer CenterRuth Aponte-Wesson - The University of Texas MD Anderson Cancer CenterVinod Patel - Guy's and St Thomas' NHS Foundation TrustAndrew Hope - University of TorontoJack Phan - The University of Texas MD Anderson Cancer CenterAdam S. Garden - The University of Texas MD Anderson Cancer CenterSteven J. Frank - The University of Texas MD Anderson Cancer CenterWilliam H. Morrison - The University of Texas MD Anderson Cancer CenterMichael T. Spiotto - The University of Texas MD Anderson Cancer CenterDavid Rosenthal - The University of Texas MD Anderson Cancer CenterAnna Lee - The University of Texas MD Anderson Cancer CenterRenjie He - The University of Texas MD Anderson Cancer CenterMohamed A. Naser - The University of Texas MD Anderson Cancer CenterErin Watson - Princess Margaret Cancer CentreKatherine A. Hutcheson - The University of Texas MD Anderson Cancer CenterAbdallah S.R. Mohamed - The University of Texas MD Anderson Cancer CenterVlad C. Sandulache - Baylor College of MedicineLisanne V. van Dijk - University Medical Center GroningenAmy C Moreno - The University of Texas MD Anderson Cancer CenterTeresa Guerrero Urbano - Guy's and St Thomas' NHS Foundation TrustClifton D. Fuller - The University of Texas MD Anderson Cancer CenterStephen Y. Lai - The University of Texas MD Anderson Cancer Center
- Resource Type
- Journal article
- Publication Details
- Radiotherapy and oncology, Vol.207, 110890
- DOI
- 10.1016/j.radonc.2025.110890
- PMID
- 40222595
- PMCID
- PMC12085279
- NLM abbreviation
- Radiother Oncol
- ISSN
- 0167-8140
- eISSN
- 1879-0887
- Publisher
- Elsevier B.V; CLARE
- Grant note
- NIH/NIDCR: K12CA088084, R21DE031082, K01DE030524 NIH/NCI MD Anderson Cancer Center Core Support Grant (CCSG) Image-Driven Biologically-informed Therapy: P30CA016672-47 CCSG Head and Neck Program: P30CA016672-48 Radiation Research Unit at the Cancer Research UK City of London Centre Award: C7893/A28990 KWF Dutch Cancer Society: KWF-13529 NWO ZonMw through the VENI grant: NWO-09150162010173 Image Guided Cancer Therapy Research Program at The University of Texas MD Anderson Cancer Center - National Institutes of Health/NCI: P30CA016672 NIDCR Diversity Supplement Grant: 3R01DE028290-02S1, T32CA261856 NIH/NCINIH: UG3 TR004501 NSF: CNS-2320261 University of Illinois SystemNIDCR: U01DE032168, 1R01DE028290-01A1 NCI: R01 CA258827 HitachiNational Association of Proton Therapy
The authors would like to acknowledge the support from various funding sources that made this work possible. C.D.F. and S.Y.L. received related funding support from the NIH/NIDCR (U01DE032168/R01DE025248) . C.D.F. also receives infrastructure and salary support through the NIH/NCI MD Anderson Cancer Center Core Support Grant (CCSG) Image-Driven Biologically-informed Therapy (IDBT) program (P30CA016672-47) . S.Y.L. is supported through the CCSG Head and Neck Program (P30CA016672-48) . T.G.U. is supported by the Radiation Research Unit at the Cancer Research UK City of London Centre Award [C7893/A28990] . A.C.M. received funding from the NIH/NIDCR via grants K12CA088084, R21DE031082, and K01DE030524. L.V.V. received funding and salary support from KWF Dutch Cancer Society through a Young Investigator Grant (KWF-13529) and from NWO ZonMw through the VENI grant (NWO-09150162010173) . K.K.B. acknowledges support from the Image Guided Cancer Therapy Research Program at The University of Texas MD Anderson Cancer Center, which was partially funded by the National Institutes of Health/NCI under award number P30CA016672 and through a generous gift from the Apache Corporation. J.R. received salary support from the NIDCR Diversity Supplement Grant 3R01DE028290-02S1. K.A.W. was supported by the Image-Guided Cancer Therapy T32 Training Program Fellowship from T32CA261856. A.J.S. received funding from the NIH/NCI through grant R01CA257814-01. N.A.W. acknowledges funding support from 5R01DE028290-05. G.E.M. acknowledges funding support from NIH UG3 TR004501, NSF CNS-2320261, the University Scholar Award from the University of Illinois System, and NIH/NCI R01CA258827. A.S.R.M. received funding from NIDCR (U01DE032168, 1R01DE028290-01A1) and NCI (R01 CA258827) . S.J.F. received funding from Hitachi, NIH/NCI, the National Association of Proton Therapy, Affirmed Pharma and NASA/Baylor College of Medicine and honoraria from IBA.
- Language
- English
- Electronic publication date
- 04/11/2025
- Date published
- 06/2025
- Academic Unit
- Electrical and Computer Engineering
- Record Identifier
- 9984810950202771
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