Top Line: Conjecture about increased risk of osteoradionecrosis with proton therapy for head and neck cancer are alive and well.
The Study: Here we have the most robust series to date confirming an association between osteoradionecrosis and proton therapy. It retrospectively analyzes 1,564 patients patients receiving radiation (89% photon / 11% proton) for oropharyngeal squamous cell carcinoma at MSKCC from 2013-2023. The rate of osteoradionecrosis was only 3% across the board, but there was a notable modality split: 6.4% after protons versus 2.7% after photons. In the definitive cohort, the gap widened to 7.5% versus 2.4%, respectively. Fortunately, grade 3+ osteoradionecrosis remained rare (1.1% versus 0.6%), and median time to necrosis was approximately 2 years after either modality. On multivariable analysis, proton therapy (HR 2.9), smoking (HR 2.3), and concurrent chemotherapy (HR 3.3) independently predicted osteoradionecrosis. “We also note that in our study there was a lower proportion of patients with concurrent chemotherapy, lower proportion of N2 and N3 disease, and higher proportion of never smokers in the proton cohort, which could bias ORN rates downward for proton therapy.” Why the difference? The leading hypothesis is that the relative biological effectiveness of protons in the mandible is higher than the classically used factor of 1.1.
TBL: Proton therapy for head and neck cancers likely carries a higher risk of osteoradionecrosis, particularly in the definitive setting, meaning aggressively limiting mandibular proton hot spots via online/offline adaptive replanning or otherwise as well as prioritizing pre-treatment dental clearance is paramount. | Yang, JAMA Otolaryngol Head Neck Surg 2025
The Study: Here we have the most robust series to date confirming an association between osteoradionecrosis and proton therapy. It retrospectively analyzes 1,564 patients patients receiving radiation (89% photon / 11% proton) for oropharyngeal squamous cell carcinoma at MSKCC from 2013-2023. The rate of osteoradionecrosis was only 3% across the board, but there was a notable modality split: 6.4% after protons versus 2.7% after photons. In the definitive cohort, the gap widened to 7.5% versus 2.4%, respectively. Fortunately, grade 3+ osteoradionecrosis remained rare (1.1% versus 0.6%), and median time to necrosis was approximately 2 years after either modality. On multivariable analysis, proton therapy (HR 2.9), smoking (HR 2.3), and concurrent chemotherapy (HR 3.3) independently predicted osteoradionecrosis. “We also note that in our study there was a lower proportion of patients with concurrent chemotherapy, lower proportion of N2 and N3 disease, and higher proportion of never smokers in the proton cohort, which could bias ORN rates downward for proton therapy.” Why the difference? The leading hypothesis is that the relative biological effectiveness of protons in the mandible is higher than the classically used factor of 1.1.
TBL: Proton therapy for head and neck cancers likely carries a higher risk of osteoradionecrosis, particularly in the definitive setting, meaning aggressively limiting mandibular proton hot spots via online/offline adaptive replanning or otherwise as well as prioritizing pre-treatment dental clearance is paramount. | Yang, JAMA Otolaryngol Head Neck Surg 2025