Abstract

BackgroundTo evaluate factors associated with osteoradionecrosis of the jaw (ORNJ) in patients with head and neck squamous cell carcinoma (HNSCC), focusing on jaw-related dose–volume histogram (DVH) parameters.MethodsWe retrospectively reviewed the medical records of 616 patients with HNSCC treated with curative-intent or postoperative radiation therapy (RT) during 2008–2018. Patient-related (age, sex, history of smoking or alcohol use, diabetes mellitus, performance status, pre-RT dental evaluation, pre- or post-RT tooth extraction), tumor-related (primary tumor site, T-stage, nodal status), and treatment-related (pre-RT surgery, pre-RT mandible surgery, induction or concurrent chemotherapy, RT technique) variables and DVH parameters (relative volumes of the jaw exposed to doses of 10 Gy–70 Gy [V10–70]) were investigated and compared between patients with and without ORNJ. The Mann–Whitney U test was used to compare RT dose parameters. Univariate and multivariate Cox regression analyses were used to assess factors associated with ORNJ development. Kaplan–Meier analyses were performed for cumulative ORNJ incidence estimation.ResultsForty-six patients (7.5%) developed ORNJ. The median follow-up duration was 40 (range 3–145) months. The median time to ORNJ development was 27 (range 2–127) months. DVH analysis revealed that V30–V70 values were significantly higher in patients with than in those without ORNJ. In univariate analyses, primary tumor site, pre-RT mandible surgery, post-RT tooth extraction, and V60 > 14% were identified as important factors. In multivariate analyses, V60 > 14% (p = 0.0065) and primary tumor site (p = 0.0059) remained significant. The 3-year cumulative ORNJ incidence rates were 2.5% and 8.6% in patients with V60 ≤ 14% and > 14%, respectively (p < 0.0001), and 9.3% and 1.4% in patients with oropharyngeal or oral cancer and other cancers, respectively (p < 0.0001).ConclusionsV60 > 14% and oropharyngeal or oral cancer were found to be independent risk factors for ORNJ. These findings might be useful to minimize ORNJ incidence in HNSCC treated with curative RT.

Highlights

  • To evaluate factors associated with osteoradionecrosis of the jaw (ORNJ) in patients with head and neck squamous cell carcinoma (HNSCC), focusing on jaw-related dose–volume histogram (DVH) parameters

  • Cut-off points for DVH parameters were selected based on the Akaike information criterion (AIC) for the Patient‐ and treatment‐related characteristics Among the 616 patients included in the study, the median follow-up time was 40 months

  • 83% of 47 Osteoradionecrosis of the jaw (ORNJ) sites were located in the body of the jaw, 43% were located in the angle or ramus, and 11% were identified in the symphyseal or parasymphyseal area; ORNJ was not observed in the condylar process/ head or coronoid

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Summary

Introduction

To evaluate factors associated with osteoradionecrosis of the jaw (ORNJ) in patients with head and neck squamous cell carcinoma (HNSCC), focusing on jaw-related dose–volume histogram (DVH) parameters. Osteoradionecrosis of the jaw (ORNJ) is among the most serious late complications observed in patients with head and neck squamous cell carcinoma (HNSCC) treated with radiation therapy (RT). The incidence of ORNJ has decreased in recent times, from approximately 20% several decades ago to 4–8% in the modern era [8, 13, 14, 17,18,19] This tendency might be attributed to improvements in RT techniques, such as the intensity-modulated RT (IMRT), currently used. Few studies have reported the RT dose–volume correlation of the irradiated jaw [14,15,16], and the dose–volumetric threshold of ORNJ has not been clearly determined

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