Purpose: Osteoradionecrosis of the jaw (ORNJ) is a severe iatrogenic disease characterized by bone death after radiation therapy (RT) to the head and neck. With over 9 published definitions and at least 16 diagnostic/staging systems, the true incidence and severity of ORNJ are obscured by lack of a standard for disease definition and severity assessment, leading to inaccurate estimation of incidence, reporting ambiguity, and likely under-diagnosis worldwide. This study aimed to achieve consensus on an explicit definition and phenotype of ORNJ and related precursor states through data standardization to facilitate effective diagnosis, monitoring, and multidisciplinary management of ORNJ. Methods: The ORAL Consortium comprised 69 international experts, including representatives from medical, surgical, radiation oncology, and oral/dental disciplines. Using a web-based modified Delphi technique, panelists classified descriptive cases using existing staging systems, reviewed systems for feature extraction and specification, and iteratively classified cases based on clinical/imaging feature combinations. Results: The Consortium ORNJ definition was developed in alignment with SNOMED-CT terminology and recent ISOO-MASCC-ASCO guideline recommendations. Case review using existing ORNJ staging systems showed high rates of inability to classify (up to 76%). Ten consensus statements and nine minimum data elements (MDEs) were outlined for prospective collection and classification of precursor/ORNJ stages. Conclusion: This study provides an international, consensus-based definition and MDE foundation for standardized ORNJ reporting in cancer survivors treated with RT. Head and neck surgeons, radiation, surgical, medical oncologists, and dental specialists should adopt MDEs to enable scalable health information exchange and analytics. Work is underway to develop both a human- and machine-readable knowledge representation for ORNJ (i.e., ontology) and multidisciplinary resources for dissemination to improve ORNJ reporting in academic and community practice settings.

The individual collaborators/authors declare the following competing interests: National Institutes of Health (grants, travel, honoraria); Padagis (honoraria); NPi (honoraria); Castle Biosciences (consulting); Galera Therapeutics (consulting, grants); EMD Serono (advisory board, in-kind support, consulting, grants); UpToDate Inc (royalties); Cardinal Health (grants, consulting); Guy's and St Thomas' NHS Foundation Trust (grants); King's College London (grants); Canadian Institutes of Health Research (grants); Canadian Foundation for Innovation (grants);Cancer Research Society (grants); Merck (advisory service, consulting, honoraria, travel, grants); Pfizer (stock, consulting, honoraria). Moderna (stock); Healthcare Services Group (stock); Dr. Reddy's Laboratories (stock); CVS Health (stock). Organon (stock); Myomo (stock); Rewalk Robotics (stock); Elekta AB (grants, in-kind support, honoraria, travel); Philips Medical System (honoraria, travel); Varian/Siemens Healthineers (honoraria, travel). Kallsio, Inc. (royalties, licenses);Nanobiotix (consulting); LEO SAB (consulting, stock options);Shanghai JoAnn Medical Company(consulting); Yingming (consulting); Sanofi-Regeneron (honoraria); Merck Sharp & Dohme (honoraria); Glaxo Smith Kline (honoraria); Merus (honoraria); Sun Pharma (honoraria); Angelini (honoraria, consulting); MeiraGtx (grants);PCCA (grants); Mureva (grants); K pharmaceuticals (honoraria, consulting); Lipella Pharmaceuticals (honoraria, consulting); Amgen (honoraria, consulting); Bristol Myers Squibb (grants); Debiopharm (grants);ACI Clinical (consulting);Genentech (consulting); Astellas (consulting); Immunitas (consulting, stock);SIRPant (consulting); LEK (consulting); Burns and White (expert testimony); Doximity (stock).

This work was supported directly or in part by funding/resources from the National Institutes of Health (NIH) National Institute for Dental and Craniofacial Research (K01DE030524, U01DE032168, R21DE031082, R56/R01DE025248, R01DE028290); NIH National Cancer Institute (K12CA088084, P30CA016672); the NIH National Institute of Biomedical Imaging and Bioengineering (R25EB025787); the University of Texas MD Anderson Cancer Center via the Charles and Daneen Stiefel Center for Head and Neck Cancer Oropharyngeal Cancer Research Program; and the MD Anderson Image-guided Cancer Therapy Program.

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

IRB of the University of Texas MD Anderson Cancer Center gave ethical approval for this work.

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

Data availability statement: The data that support the findings of this study are openly available in an NIH-supported generalist scientific data repository [figshare] at http://doi.org/10.6084/m9.figshare.25546723; though embargoed pending peer-review, data is available upon request in the interim.

http://doi.org/10.6084/m9.figshare.25546723