Risk of Osteoradionecrosis in Patients With Oral Cavity Cancer Undergoing Radiation Therapy

Key Clinical Summary: 

• Design/Population: A retrospective cohort study evaluated 479 patients with oral cavity squamous cell carcinoma who underwent intensity-modulated radiation therapy or proton therapy between 2013 and 2023. 
• Key Outcomes: At a median follow-up of 35 months, osteoradionecrosis developed in 11% of IMRT-treated patients and 11.3% of proton-treated patients with 3-year cumulative incidences of 9.6% and 11.4%, respectively. Median time to osteoradionecrosis was 13 months after IMRT vs 28 months after proton therapy. On multivariable analysis, the extent of mandibular surgery was the strongest predictor of osteoradionecrosis, and higher mandibular radiation dose and irradiated bone volume were associated with increased risk.
• Clinical Relevance: In postoperative oral cavity cancer, modern radiation modalities show comparable osteoradionecrosis risk, emphasizing the importance of treatment planning, mandibular dose minimization, and multidisciplinary prevention strategies, including dental evaluation and oral care, to reduce long-term toxicity and preserve quality of life.

Annu Singh, MD, Memorial Sloan Kettering Cancer Center, New York, New York, discusses results from a retrospective cohort study comparing incidence of late-term osteoradionecrosis among patients with oral cavity cancer undergoing intensity-modulated and proton radiation therapy. 

Results demonstrated that osteoradionecrosis rates were similar however the median time to onset was longer with proton therapy. The study also identified mandibular surgery extent and radiation dose to the mandible as key predictors of osteoradionecrosis. 

Transcript:

Good afternoon, all. My name is Annu Singh, and I'm the assistant attending in the dental service, department of surgery, and I'm one of the co-first authors of this multidisciplinary team project that we worked on with Dr Tree, who is a visiting radiation oncology fellow from Thailand, along with Dr Christie, and under the valuable mentorship of Dr Cherry Estilo and Dr Nancy Lee.

We published a study in 2025 in the Journal of Oral Oncology where we examined [osteoradionecrosis] as a potential late complication following modern radiation treatment for oral cavity cancer patients. One of the biggest challenges in treating head and neck cancers is not only curing the cancer, but also preventing serious long-term complications from the cancer treatment. 

As Dr Christie mentioned, one serious condition is osteoradionecrosis of the jaw. It's a condition in which the irradiated bone, commonly the mandible, becomes affected after head and neck radiation therapy and this can clinically present as exposed bone with chronic pain, infection, and in advanced cases there can be a need for additional surgery. It is relatively uncommon, but it can significantly impact patients' quality of life, affecting speech, swallowing, and mastication after the entire cancer treatment is completed. Although modern radiation techniques have reduced toxicity levels, [osteoradionecrosis] still remains one of the most feared long-term complications in head and neck cancer. 

Patients with oral cavity cancer are often treated with surgery followed by radiation therapy to reduce the risk of recurrence and today, as Dr Christie mentioned, we have 2 advanced radiation technologies that are commonly used in this therapy: which are intensity-modulated radiation therapy (IMRT) and proton therapy. Both these technologies allow physicians to target tumors more precisely and spare the surrounding healthy tissues– that means reduced toxicities. However, the jawbones, especially the mandible, still receive radiation during the treatment. The tongue, the buccal mucosa, and the gingival subsites are considered very high-risk regions because of their proximity to the mandible and that can increase the risk of [osteoradionecrosis]. Similarly, advanced tumor disease often necessitates larger tumor volumes and higher mandibular involvement.

The important clinical question clinicians have been asking is does the type of radiation therapy affect the risk of this complication in patients with oral cavity cancer. To the best of our knowledge, our study is the first to directly compare the osteoradionecrosis rates between IMRT and proton therapy, specifically in patients with oral cavity cancer receiving postoperative radiation therapy.

In this study, we analyzed a consecutive cohort of 479 patients with squamous cell carcinoma of the oral cavity who underwent surgery followed by radiation therapy. This was the patient cohort after the inclusion and exclusion criteria we applied. Among that, 426 patients received IMRT and 53 patients, a very small portion of patients, received proton therapy, and were followed up for a median follow-up time of about 35 months.

What we found was even interesting– our findings showed that osteoradionecrosis remains a clinically important complication, 11% of the patients treated with IMRT developed osteoradionecrosis—that is 47 out of the 426 patients—whereas 11.3% of patients treated with proton therapy—that is six out of the 53 patients—developed [osteoradionecrosis] . When we looked at the longer-term outcomes, the 3-year cumulative incidence of [osteoradionecrosis] was about 9.6% for IMRT and 11.4%, higher for proton therapy, showing similar rates between the two treatment modalities. Another interesting finding was related to the time to development of [osteoradionecrosis] . So the median time to develop [osteoradionecrosis] was about 13 months after IMRT compared to about 28 months after proton therapy.

We also examined factors associated with the complication. On a univariable analysis, smoking history, tumor stage, tumor with mandibular invasion, and the extent of mandibular intervention—that is, patients who received any mandibular resection versus no mandibular resection—were associated with  [osteoradionecrosis] development. However, on the multivariable modeling, the extent of mandibular surgery or intervention emerged as a significant predictor of osteoradionecrosis, emphasizing the importance of coordinated care between surgeons, radiation oncologists, and dental specialists.

Importantly, the dosimetric analysis demonstrated a clear association with mandibular dose-response parameters and [osteoradionecrosis] development. Higher maximum mandibular doses, as well as larger irradiated mandibular volumes were correlated with increased risk. There was a significantly greater overlap volume between the planning target volume and mandible in the [osteoradionecrosis]  risk group, especially with IMRT.

Now overall, the study provides important real-world data showing that modern radiation techniques—both IMRT and proton therapy—have comparable rates of [osteoradionecrosis] in patients with oral cavity cancer.

Based on these findings, we need future collaborative research using larger cohorts, prospective data collection, standardized dosimetric measures, and rigorous statistical methods that will help determine whether proton therapy provides significant benefits in reducing [osteoradionecrosis] risk compared with IMRT in oral cavity cancers. 

The important takeaway from our work, including Dr Tree's research in the oropharynx group, is the value of careful treatment planning and preventive strategies, which include pre-radiation dental evaluation, removal of teeth with poor prognosis prior to initiation of radiation therapy, maintenance of oral hygiene instructions when appropriate, and ongoing patient surveillance. As treatments become more effective and patients live longer, understanding the dose-response relationship and the comparative effects of radiation modalities will allow us to individualize treatment, minimize toxicity, and ultimately improve quality of life and functional outcomes.

Source:

Treechairusame T, Singh A, Dee EC, et al. Osteoradionecrosis as a complication following post-operative intensity-modulated radiation therapy or proton therapy for oral cavity cancer. Oral Oncol. Published online August 8, 2025. doi:10.1016/j.oraloncology.2025.107581

Yang F, Dee EC, Singh A, et al. Osteoradionecrosis after intensity-modulated radiation therapy or proton therapy in oropharyngeal carcinoma. JAMA Otolaryngol Head Neck Surg. Published online November 26, 2025. doi:10.1001/jamaoto.2025.4179