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

Abstract

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 (Dmean) and maximum (Dmax) dose in Gray (Gy) 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 (Dmean) or <58 Gy (Dmax) are suggested to limit the probability of inner ear toxicity <25%.

Cancer and Non-Cancer Effects Following Ionizing Irradiation

“…Thariat et al [ 20 ] reviewed the current knowledge on normal tissue complications in the eye and orbit (e.g., the lacrimal gland, eyelashes, eyelids, cornea, lens, macula/retina, optic nerves and chiasma) following radiotherapy. Peuker et al [ 21 ] found a sigmoidal relationship between radiation dose and the incidence of inner ear toxicity following radiotherapy for nasopharyngeal carcinoma, and proposed dose constraints to reduce inner ear toxicity.…”

“…Therefore, this Special Issue ( ) aims to serve as a forum to gather the latest developments and discuss future prospects in the field of normal tissue responses to radiation exposure. The Special Issue consists of 18 articles [ 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 ] outlining the cancer and non-cancer effects of radiation occurring in various tissues (e.g., those in the circulatory, sensory, nervous, respiratory, and reproductive systems), including studies on mitigation strategies and biomarkers, as outlined below.…”