Main Session
Sep 30
SS 37 - Head and Neck 4: Refining Radiation: What Clinical Trials Can Tell Us

314 - Osteoradionecrosis as a Complication Following Intensity-Modulated Radiation Therapy or Proton Therapy in the Treatment of Oropharyngeal Carcinoma

01:05pm - 01:15pm PT
Room 314

Presenter(s)

Edward Dee, MD Headshot
Edward Dee, MD - Memorial Sloan Kettering Cancer Center, Middletown Township, NJ

E. C. Dee1, F. Yang1, A. Singh2, Y. Wu1, J. Suggitt3, T. Treechairusame1,4, E. S. Polanco5, A. Honawar5, Z. Zhang5,6, D. Mah7, K. Sine8, A. Shim9, H. Lin9, J. J. Kang1,10, C. J. Tsai11, S. McBride1, N. Riaz1, D. Gelblum1, K. Zakeri1, L. Chen5, A. Shamseddine1, Y. Yu1, J. Huryn2, S. Yom2, J. Cracchiolo2, I. Ganly2, M. Cohen2, E. Sherman12, A. Ho12, R. J. Wong2, C. Estilo2, and N. Y. Lee1; 1Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, 2Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, 3Michigan State University, East Lansing, MI, 4Division of Radiation Oncology, Department of Radiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand, 5Memorial Sloan Kettering Cancer Center, New York, NY, 6Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, 7ProCure Proton Therapy Center - New Jersey, Somerset, NJ, 8ProCure Proton Therapy Center, Somerset, NJ, 9New York Proton Center, New York, NY, 10Yale University Department of Radiation Oncology, New Haven, CT, 11Princess Margaret Cancer Centre, Toronto, ON, Canada, 12Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY

Purpose/Objective(s):

Osteoradionecrosis (ORN) is a late complication of head and neck radiotherapy (RT) that negatively impacts survivorship. Although there is an abundance of literature reporting on ORN for photon-based RT, few studies have investigated ORN trends with proton therapy. Additionally, most ORN literature incorporates a broad mix of head and neck subsites. Therefore, we report our 10-year institutional experience with ORN in a homogenous and consecutive cohort of oropharyngeal squamous cell carcinoma (OPSCC) patients treated with curative-intent radiotherapy, representing the largest available institutional series.

Materials/Methods:

A consecutive cohort of 1564 OPSCC patients (1344 definitive, 220 post-operative) treated with at least 50Gy at our institution between 2013 and 2023 were included. Patients received either intensity modulated radiation therapy (IMRT, n=1389) or proton beam therapy (PBT, n=175). ORN was diagnosed on imaging or on clinical exam during surveillance by surgery, radiation oncology, or dentistry. CTCAE version 5 was used for ORN grading.

Results:

Median follow-up was 60.1 months for the IMRT cohort and 30.7 months for the proton cohort. The overall rate of any grade of ORN was 4.35%. Of these, 8 (11.76%) had CTCAE grade 1 ORN, 50 (73.53%) had grade 2 ORN, and 10 (14.71%) had grade 3 ORN.

Among IMRT patients, 56 (4.03%) developed ORN compared to 12 (6.86%) proton therapy patients (hazard ratio [HR] 2.62, 95%CI 1.39—4.93, P=0.003). Median times to ORN were comparable: 25 months (range 2-91) IMRT vs. 23.5 months (range 2-45) PBT.

Post-operative versus definitive treatment setting was not associated with ORN (univariate Cox HR 1.00, 95% CI 0.51—1.95, P=0.99). On subset analysis of the 1344 definitive RT patients, 47/1210 (3.88%) of IMRT patients developed ORN as compared to 11/134 (8.21%) of PBT patients (HR 3.62, 95% CI 1.85—7.09, P<0.001).

On multivariable analysis including treatment modality and use of chemotherapy, PBT was associated with increased hazard of ORN (HR 2.75, 95%CI 1.46—5.19, P=0.002). Concurrent chemotherapy was also independently associated with increased hazard of ORN (HR 3.34, 95%CI 1.05—10.65, P=0.041).

Only 10 of 1564 (0.64%) patients developed CTCAE grade 3 ORN. Grade 3 ORN rates were 2/175 (1.14%) with PBT versus 8/1389 (0.58%) with IMRT (HR 2.44, 95%CI 0.51—11.60, P=0.26).

Conclusion:

The overall prevalence of ORN was 4.35% (0.64% >grade 3) in this consecutive cohort of OPSCC patients treated with either IMRT or PBT. Any grade ORN was statistically higher for protons versus IMRT, a difference that may have been driven by definitive PBT. Given uncertainties with relative biological effectiveness calculations in proton therapy, avoidance of hot-spots, frequent replanning, and use of empirical proton-specific normal tissue constraints may help to reduce rates of ORN. Future work should explore combining proton and photon therapies, especially in the definitive setting.