Importance:Osteoradionecrosis (ORN) is a potentially debilitating late complication of radiotherapy (RT) for head and neck cancer. While proton therapy offers superior dose conformality, its impact on ORN risk remains uncertain, particularly in patients with oropharyngeal squamous cell carcinoma (OPSCC). Objective:To characterize the incidence, severity, and predictors of ORN in a large institutional cohort of patients with OPSCC treated with curative-intent RT, and to compare outcomes between proton therapy and intensity-modulated radiation therapy (IMRT). Design, Setting, and Participants:This retrospective cohort study included consecutive patients with OPSCC treated from January 2013 to December 2023 at a single high-volume academic institution. Patients received either IMRT or proton therapy (uniform scanning or pencil beam scanning). ORN diagnosis and grading were determined through standardized multidisciplinary review. The primary outcome was the 3-year rate of ORN. Cox regressions identified predictors of ORN. Data were analyzed from December 2024 to April 2025. Exposures:Radiotherapy modality (proton vs IMRT), patient demographic characteristics, smoking status, human papillomavirus status, tumor and/or node stage, chemotherapy, and radiation dosage. Results:The analysis included 1564 patients (mean [SD] age, 61.5 [9.6] years; 208 females [13.3%] and 1356 males [86.7%]) of whom 1389 patients (88.8%) had undergone IMRT, and 175 patients (11.2%) had undergone proton-based treatment. The 3-year incidence of any-grade ORN was 3.02% (95% CI, 2.22%-4.09%). ORN rates were significantly higher after proton therapy compared with IMRT (6.36% vs 2.69% at 3 years; hazard ratio [HR], 2.62; 95% CI, 1.39-4.93). Of 1344 definitive patients, 47 of 1210 patients in the IMRT group (3-year rate, 2.38%; 95% CI, 1.61-3.51%) developed ORN vs 11 of 134 patients in the proton group (3-year rate 7.47%; 95% CI, 3.40-16.02% [HR, 3.62; 95% CI, 1.85-7.09]). On multivariable analysis, proton therapy (HR, 2.92; 95% CI, 1.55-5.50), concurrent chemotherapy (HR, 3.29; 95% CI, 1.03-10.50), and smoking (HR, 2.33; 95% CI, 1.38-3.92) were independently associated with ORN. Grade 3 or greater ORN occurred in 0.67% of patients and did not appear to differ by RT modality. Conclusions and Relevance:In this large, relatively homogeneous cohort of patients with OPSCC, proton therapy was associated with a higher rate of ORN compared with IMRT, particularly in the definitive setting, although high-grade ORN remained uncommon across both modalities. These retrospective findings should be considered exploratory and underscore the need for future hypothesis-driven studies to refine dose constraints and optimize treatment planning to mitigate ORN risk among patients with OPSCC.
This cohort study evaluates the use of definitive rhinectomy and adjuvant radiotherapy with or without chemotherapy for patients who declined rhinectomy or had unresectable disease.
Stereotactic ablative radiotherapy (SABR) commonly is used for small liver metastases. Modern conformal radiotherapy techniques, including 3-dimensional conformal radiotherapy and intensity-modulated radiation therapy, enable the safe delivery of SABR to small liver volumes. For larger tumors, the safe delivery of SABR can be challenging due to a more limited volume of healthy normal liver parenchyma and the proximity of the tumor to radiosensitive organs, such as the stomach, duodenum, and large intestine. Controlling respiratory motion, the use of image guidance, and increasing the number of radiation fractions sometimes are necessary for the safe delivery of SABR in these situations.
Objective: To report the prevalence of osteoradionecrosis (ORN) in oral cavity (OC) cancer patients following intensity-modulation radiation therapy (IMRT) or proton therapy (PRT). Methods: A retrospective study was conducted on consecutive cohort of OC cancer patients treated with IMRT or PRT for squamous cell carcinoma (SCC). Patient information and treatment related variables were collected from medical records. Patients who developed ORN were uniformly graded using CTCAE v5. Cox proportional hazards model was used to compare risk factors between IMRT and PRT. Kaplan-Meier method was used to estimate the cumulative incidence (CI) of ORN. Results: A total of 479 OC SCC patients (426 treated with IMRT and 53 treated with PRT) were included in this study. The median follow-up time was 35 months (IQR, 17-68 months). The prevalence of ORN was similar between groups: 11% (47/426) in the IMRT group (21 Grade 1, 13 Grade 2, 13 Grade 3) and 11.3% (6/53) in the PRT group (2 Grade 1, 3 Grade 2, 1 Grade 3). The median time to ORN development was shorter following IMRT [13 months (IQR, 9-39)] compared to PRT [28 months (IQR, 4-42)].The 3-year CI of any grade ORN was 9.6 % and 11.4 % for IMRT and PRT (log-rank P-value = 0.550), respectively. On univariable analysis, smoking history (P = 0.072), tumor stage (P = 0.011), tumor with mandibular invasion (P = 0.007), and extent of mandibular intervention (P < 0.001) was associated with ORN development. On multivariable analysis, the extent of mandibular intervention remained a significant risk factor (P < 0.001). Conclusion: In this single-institution study, we found a similar prevalence of ORN following IMRT (11%) and PRT (11.3 %) in OC cancer patients.
The extreme light infrastructure (ELI) is emerging as a state-of-the-art facility providing international users with open access to ultrashort laser-driven particle bunches, ranging from a few femtoseconds to a few nanoseconds, for advanced radiobiology studies. ELI offers femtosecond-class laser pulses and ultrafast ionizing radiation characterized by extremely high instantaneous dose rates (107–1012 Gy/s). The versatility of ELI’s cutting-edge technologies enables the generation of high repetition rate (1 Hz–1 kHz) secondary sources (protons, ions, electrons, and neutrons) with energies from a few MeV to several hundred MeV, achieved over sub-millimetre to millimetre-scale acceleration lengths, along with fundamental research in the field of ultrahigh intensity laser-matter interaction based on the use of the highest peak power laser pulses available worldwide. Harnessing these laser-driven particle sources for radiobiology and medical research demands a coordinated international effort, with a strong focus on advancing scientific instrumentation and refining experimental methodologies to support progress in ultrafast laser-driven radiation biology. This roadmap underscores the need for systematically designed experiments across ELI facilities, supported by preparatory research at users’ home laboratories, alongside the ongoing development of instrumentation and infrastructure. These efforts are critical to rigorously assess and validate the therapeutic potential of these novel sources, paving the way for a transformative shift in radiation biology and medicine.
