title: Normal tissue complication probability modeling for cochlea constraints to avoid causing tinnitus after head-and-neck intensity-modulated radiation therapy.
abstract: BACKGROUND
  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).
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Medical Physics and Informatics Laboratory of Electronics Engineering, National Kaohsiung University of Applied Sciences, 415, Chien Kung Road, San-Min District, Kaohsiung, 80778, Taiwan, ROC. tflee@kuas.edu.tw.|Institute of Clinical Medicine, Kaohsiung Medical University, Kaohsiung, 807, Taiwan, ROC. tflee@kuas.edu.tw.
authors.forename: Tsair-Fwu
authors.initials: TF
authors.lastname: Lee
authors.affiliation: Medical Physics and Informatics Laboratory of Electronics Engineering, National Kaohsiung University of Applied Sciences, 415, Chien Kung Road, San-Min District, Kaohsiung, 80778, Taiwan, ROC. yeh5657@gmail.com.|Department of Radiation Oncology, E-Da hospital, No.1, Yida Road, Jiaosu Village, Yanchao District, Kaohsiung City, 82445, Taiwan, ROC. yeh5657@gmail.com.|Department of Medical Imaging and Radiological Sciences, I-Shou University, Kaohsiung, 840, Taiwan, ROC. yeh5657@gmail.com.
authors.forename: Shyh-An
authors.initials: SA
authors.lastname: Yeh
authors.affiliation: Medical Physics and Informatics Laboratory of Electronics Engineering, National Kaohsiung University of Applied Sciences, 415, Chien Kung Road, San-Min District, Kaohsiung, 80778, Taiwan, ROC. pjchao99@gmail.com.|Department of Radiation Oncology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, 83305, Taiwan, ROC. pjchao99@gmail.com.
authors.forename: Pei-Ju
authors.initials: PJ
authors.lastname: Chao
authors.affiliation: Department of Medical Imaging and Radiological Sciences, I-Shou University, Kaohsiung, 840, Taiwan, ROC. cliyun2000@gmail.com.
authors.forename: Liyun
authors.initials: L
authors.lastname: Chang
authors.affiliation: Medical Physics and Informatics Laboratory of Electronics Engineering, National Kaohsiung University of Applied Sciences, 415, Chien Kung Road, San-Min District, Kaohsiung, 80778, Taiwan, ROC. clchiu@kuas.edu.tw.|Institute of Clinical Medicine, Kaohsiung Medical University, Kaohsiung, 807, Taiwan, ROC. clchiu@kuas.edu.tw.
authors.forename: Chien-Liang
authors.initials: CL
authors.lastname: Chiu
authors.affiliation: Medical Physics and Informatics Laboratory of Electronics Engineering, National Kaohsiung University of Applied Sciences, 415, Chien Kung Road, San-Min District, Kaohsiung, 80778, Taiwan, ROC. hmting618@gmail.com.|Department of Radiation Oncology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, 83305, Taiwan, ROC. hmting618@gmail.com.
authors.forename: Hui-Min
authors.initials: HM
authors.lastname: Ting
authors.affiliation: Medical Physics and Informatics Laboratory of Electronics Engineering, National Kaohsiung University of Applied Sciences, 415, Chien Kung Road, San-Min District, Kaohsiung, 80778, Taiwan, ROC. hywang@cc.kuas.edu.tw.|Institute of Clinical Medicine, Kaohsiung Medical University, Kaohsiung, 807, Taiwan, ROC. hywang@cc.kuas.edu.tw.
authors.forename: Hung-Yu
authors.initials: HY
authors.lastname: Wang
authors.affiliation: Department of Radiation Oncology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, 83305, Taiwan, ROC. yujie1115@gmail.com.
authors.forename: Yu-Jie
authors.initials: YJ
authors.lastname: Huang
mesh_terms: D000328:Adult; D000368:Aged; D003051:Cochlea / Q000528:radiation effects*; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006258:Head and Neck Neoplasms / Q000532:radiotherapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008962:Models, Theoretical; D011832:Radiation Injuries / Q000209:etiology; D011879:Radiotherapy Dosage; D011880:Radiotherapy Planning, Computer-Assisted; D050397:Radiotherapy, Intensity-Modulated / Q000009:adverse effects*; D014012:Tinnitus / Q000209:etiology*