Normal tissue complication probability modeling for cochlea constraints to avoid causing tinnitus after head-and-neck intensity-modulated radiation therapy

Tsair-Fwu Lee, Shyh-An Yeh, Pei-Ju Chao, Liyun Chang, Chien-Liang Chiu, Hui-Min Ting, Hung-Yu Wang, Yu-Jie Huang

Radiation-induced tinnitus is a side effect of radiotherapy in the inner ear for cancers of the head and neck. Effective dose constraints for protecting the cochlea are under-reported. The aim of this study is to determine the cochlea dose limitation to avoid causing tinnitus after head-and-neck cancer (HNC) intensity-modulated radiation therapy (IMRT). In total 211 patients with HNC were included; the side effects of radiotherapy were investigated for 422 inner ears in the cohort. Forty-nine of the four hundred and twenty-two samples (11.6 %) developed grade 2+ tinnitus symptoms after IMRT, as diagnosed by a clinician. The Late Effects of Normal Tissues-Subjective, Objective, Management, Analytic (LENT-SOMA) criteria were used for tinnitus evaluation. The logistic and Lyman-Kutcher-Burman (LKB) normal tissue complication probability (NTCP) models were used for the analyses. The NTCP-fitted parameters were TD 50  = 46.31 Gy (95 % CI, 41.46-52.50), γ 50  = 1.27 (95 % CI, 1.02-1.55), and TD 50  = 46.52 Gy (95 % CI, 41.91-53.43), m = 0.35 (95 % CI, 0.30-0.42) for the logistic and LKB models, respectively. The suggested guideline TD 20 for the tolerance dose to produce a 20 % complication rate within a specific period of time was TD 20  = 33.62 Gy (95 % CI, 30.15-38.27) (logistic) and TD 20  = 32.82 Gy (95 % CI, 29.58-37.69) (LKB). To maintain the incidence of grade 2+ tinnitus toxicity <20 % in IMRT, we suggest that the mean dose to the cochlea should be <32 Gy. However, models should not be extrapolated to other patient populations without further verification and should first be confirmed before clinical implementation.