TOPLINE:

Overall, at 3 years, proton therapy was associated with higher rates of osteoradionecrosis than intensity‑modulated radiation therapy (IMRT) in patients with oropharyngeal squamous cell carcinoma (OPSCC), particularly in the definitive setting. However, the incidence of grade ≥ 3 osteoradionecrosis was rare in both groups.

METHODOLOGY:

• Osteoradionecrosis is a “potentially debilitating late complication” following radiotherapy for head and neck cancer, researchers explained. Although proton therapy offers improved dose conformality compared with IMRT, it’s unclear whether proton therapy can increase rates of osteoradionecrosis in patients with OPSCC.
• Researchers conducted a retrospective cohort study involving 1564 consecutive patients (mean age, 61.5 years) with OPSCC who underwent treatment from January 2013 to December 2023 at Memorial Sloan Kettering Cancer Center in New York City.
• Overall, 1389 patients (88.8%) received IMRT and 175 (11.2%) received proton-based therapy (either uniform scanning or pencil beam scanning).
• The median follow-up duration for the entire cohort was 56.6 months but was almost two times longer in the IMRT group (60.1 months vs 30.7 months for proton therapy).
• Researchers evaluated the rate of osteoradionecrosis at 3 years, and the associations between IMRT or proton therapy and osteoradionecrosis.

TAKEAWAY:

• At 3 years, the rate of osteoradionecrosis in the overall cohort was 3.0%. Proton therapy was associated with a significantly higher risk for osteoradionecrosis than IMRT at 3 years, ie, 6.4% vs 2.7% in the IMRT group (hazard ratio [HR], 2.62).
• Among patients who had definitive treatment (n = 1344), the rate of osteoradionecrosis at 3 years was higher among those who received proton therapy: 7.5% vs 2.4% for IMRT (HR, 3.62). However, among 220 patients treated postoperatively, the 3-year rate of osteoradionecrosis was numerically lower in the proton group — 3.0% (1 of 41 patients) vs 4.8% (9 of 179) in the IMRT group — though the difference was not statistically significant (HR, 0.55; 95% CI, 0.07-4.33 ).
• In a multivariable analysis, proton therapy (adjusted HR [aHR], 2.92), concurrent chemotherapy (aHR, 3.29), and smoking (aHR, 2.33) were independently associated with an increased risk for osteoradionecrosis.
• Severe osteoradionecrosis of grade 3 or higher was not common, reported in 10 patients overall at 3 years (0.67%) — 2 of 175 (1.14%) in the proton therapy group and 8 of 1389 (0.58%) in the IMRT group; however, the difference was not statistically significant (HR, 2.44; 95% CI,0.51-11.60).

IN PRACTICE:

“These retrospective findings should be considered exploratory,” according to the authors, who underscored the need for “prospective studies to better characterize risk factors and inform strategies to mitigate [osteoradionecrosis] while preserving the therapeutic advantages of advanced radiotherapy modalities.”

SOURCE:

The study, led by Fan Yang, MD, and Edward Christopher Dee, MD, Memorial Sloan Kettering Cancer Center, was published online in JAMA Otolaryngology-Head & Neck Surgery.

LIMITATIONS:

This single-institution retrospective study had several limitations including differences in the median follow-up time between the IMRT and proton therapy groups due to later adoption of proton therapy. While the patient cohort was large, the relatively small number of osteoradionecrosis cases resulted in wide confidence intervals for statistical estimates. Practice variations across different centers may have potentially altered osteoradionecrosis rates.

DISCLOSURES:

All authors were funded by the National Cancer Institute’s Cancer Center Support Grant. Several authors reported receiving consulting fees or speaking fees or having other ties with various sources. Full disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.