Author: Angela Gathers, Christina Henson, Sakuntala Jagabattuni, Mark A. Newpower 👨🔬
Affiliation: University of Oklahoma HSC, Department of Otolaryngology, University of Oklahoma HSC, University of Oklahoma Health Sciences Center 🌍
Purpose: A previous departmental study showed an increase in ototoxicity (hearing loss) rates in head & neck cancer (HNC) patients treated with Intensity Modulated Proton Therapy (IMPT) vs. x-ray radiotherapy despite no statistically significant dose differences between the two modalities. The purpose of this study was to determine if enhanced variable relative biological effectiveness (vRBE) could account for ototoxicity, via audiometry examinations, in a small cohort of patients.
Methods: This study retrospectively assessed cochlear dose in a cohort of 20 HNC patients who received IMPT treatments. Audiometry exams before and after treatment were used to correlate hearing loss outcomes - determined by the Brock and Chang ototoxicity grading scales - with treatment planning metrics of mean dose and dose to 0.035 cc. A null hypothesis was tested for statistically significant dose differences between affected and unaffected patients assuming constant RBE = 1.1. Dose-averaged LET (LETd) was calculated in RayStation 12A and was used to compute vRBE according to several models from the literature. We also computed the product of dose and LETd. These metrics were used to determine statistically significant dose differences between patients with and without hearing loss. Administration of chemotherapy was also accounted for in the statistical analysis.
Results: Mann-Whitney U test p-values for mean dose and dose to 0.035 cc of the cochlea respectively - (a) null hypothesis (RBE=1.1): 0.25 and 0.28; with chemo: 0.40 and 0.40; no chemo: 0.46 and 0.63, (b) LETd x dose model: 0.28 and 0.26; with chemo: 0.23 and 0.20; no chemo: 0.27 and 0.27. The lowest MWU p-values resulted from using the Brock grading scale and LETd x dose model.
Conclusion: Dose differences between patients accounting for RBE=1.1, vRBE, and chemotherapy showed no statistical significance in explaining the variability in toxicity outcomes for this study’s cohort.