Definition of an Normal Tissue Complication Probability Model for the Inner Ear in Definitive Radiochemotherapy of Nasopharynx Carcinoma

Background: Definitive radiochemotherapy is the treatment of choice for locally advanced nasopharyngeal carcinoma. Due to the vicinity of the nasopharynx to the inner ear and the use of ototoxic platinum-based chemotherapy, there is a risk for irreversible damage to the auditory system. To avoid or minimize these critical side effects, radiation exposure to each inner ear must be balanced between target volume coverage and toxicity. However, normal tissue complication probability (NTCP) models of the inner ear validated by clinical data are rare. Patients and Methods: This retrospective study investigates the inner ear toxicity of 46 patients who received radio(chemo-)therapy for nasopharyngeal carcinoma at our institution from 2004 to 2021 according to CTCAE $5.0$ criteria. For each inner ear, the mean $\left(Dmean\right)$ and maximum $\left(Dmax\right)$ dose in Gray $\left(Gy\right)$ was evaluated and correlated with clinical toxicity data. Based on the data, an NTCP model and a cutoff dose logistic regression model (CDLR) were created. Results: In 11 patients ($23.9\%$) hearing impairment and/or tinnitus was observed as a possible therapy-associated toxicity. $Dmean$ was between 15–$60$ Gy, whereas $Dmax$ was between 30–$75$ Gy. There was a dose-dependent, sigmoidal relation between inner ear dose and toxicity. A $Dmean$ of $44$ Gy and $65$ Gy was associated with inner ear damage in $25\%$ and $50\%$ of patients, respectively. The maximum curve slope (m) was found at $50\%$ and is $m=0.013$. The Dmax values showed a $25\%$ and $50\%$ complication probability at $58$ Gy and $69$ Gy, respectively, and a maximum slope of the sigmoid curve at $50\%$ with $m=0.025$. Conclusion: There is a sigmoidal relation between radiation dose and incidence of inner ear toxicities. Dose constraints for the inner ear of $<44$ Gy $\left(Dmean\right)$ or $<58$ Gy $\left(Dmax\right)$ are suggested to limit the probability of inner ear toxicity $<25\%$.