Early Imaging Identification of Osteoradionecrosis and Classification Using the Novel ClinRad System: Results from A Retrospective Observational Cohort

Objective Osteoradionecrosis of the jaw (ORNJ) is a chronic radiation-associated toxicity that lacks standardized classification criteria and treatment guidelines. Understanding early signs of tissue injury could help us better predict, prevent, and conservatively manage ORN. Our primary aims were to identify initial clinically-detected signs of ORN, determine the frequency of imaging-detected ORNJ, and validate the ability to classify cases using the novel system, ClinRad. Study Design A retrospective electronic health record review of 91 patients treated for head and neck cancer at The University of Texas MD Anderson Cancer Center with suspected ORN was performed by an Oral Medicine specialist to identify initial signs of ORN. Patients who received reirradiation to the head and neck or did not have enough evidence of ORN were excluded. A descriptive analysis was performed.

51 patients met the inclusion criteria. Half (53%) presented with imaging findings and exposed bone. Imaging findings in the absence of bone exposure were identified in 37%, of which disease progression was observed in 26%. All cases were classifiable using ClinRad.

Subclinical signs of bony changes consistent with ORN may be evident on imaging without exposed bone, supporting the use of imaging surveillance. ClinRad provided a mechanism to classify all cases at early onset. Data availability statement Anonymized data for the reported analyses is made publicly available on figshare at 10.6084/m9.figshare.28292186. Reporting guideline compliance statement In accordance with the EQUATOR Network (Enhancing the QUAlity and Transparency Of health Research) guidance, we have utilized the RECORD checklist, a guideline for the “REporting of studies Conducted using Observational Routinely-collected health data” (Benchimool El at al., 2015) The RECORD checklist is provided as a Supplementary file and available via 10.6084/m9.figshare.28292219. Data was anonymized in accordance with the EQUATOR guideline “Preparing raw clinical data for publication: guidance for journal editors, authors, and peer reviewers” (Hrynaszkiewicz I et al., 2010). Competing Interest Statement C.D. Fuller received unrelated honoraria, travel, meals, in-kind, and research grants from Elekta AB; honoraria, travel, and meals from Varian Medical Systems/Siemens Healthineers; honoraria and travel from Philips Medical Systems, and receives patent licensing/royalties from Kallisio, Inc. through the University of Texas. V.C. Sandulache is a consultant for and equity holder in Femtovox Inc and serves on the Data Monitoring Committee for an unrelated PDS Biotechnology clinical trial. M. Chambers serves as Executive IRB Chair (MD Anderson) and NIDCR as Chair of a Data Safety Monitoring Committee (NIDCR). Funding Statement Direct infrastructure support was provided by the multidisciplinary Stiefel Oropharyngeal Research Fund of the University of Texas MD Anderson Cancer Center. Support was also received from the Charles and Daneen Stiefel Center for Head and Neck Cancer and the National Institutes of Health (NIH). ZYKs time was supported by a doctoral fellowship from the Cancer Prevention Research Institute of Texas (grant #RP210042). A.C. Moreno received salary support from the NIDCR Mentored Career Development Award (K01DE030524). S.Y. Lai, V.C. Sandulache, and C.D. Fuller received support from NIDCR (R56/R01DE025248, U01DE032168, R01DE028290). C.D. Fuller also receives funding from the NCI (R01CA258827, R01CA257814). J. Rigert receives salary support from the NIDCR Diversity Supplement (3R01DE028290-02S1). A.C. Moreno and L. Humbert Vidan receive salary support from NIDCR (R21DE031082). C. Dem receives salary support from NIH grant (R01CA257814-01). Author Declarations 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: Waiver of consent was contained under the University of Texas MD Anderson Cancer Center institutional review board under IRB Protocol RCR 03-0800 which allows secondary analysis of annonymized deidentified image data for listed research purpose. Ethical approval was given for the study. 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