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

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          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.

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          Most cited references32

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          Quantitative Analyses of Normal Tissue Effects in the Clinic (QUANTEC): an introduction to the scientific issues.

          Advances in dose-volume/outcome (or normal tissue complication probability, NTCP) modeling since the seminal Emami paper from 1991 are reviewed. There has been some progress with an increasing number of studies on large patient samples with three-dimensional dosimetry. Nevertheless, NTCP models are not ideal. Issues related to the grading of side effects, selection of appropriate statistical methods, testing of internal and external model validity, and quantification of predictive power and statistical uncertainty, all limit the usefulness of much of the published literature. Synthesis (meta-analysis) of data from multiple studies is often impossible because of suboptimal primary analysis, insufficient reporting and variations in the models and predictors analyzed. Clinical limitations to the current knowledge base include the need for more data on the effect of patient-related cofactors, interactions between dose distribution and cytotoxic or molecular targeted agents, and the effect of dose fractions and overall treatment time in relation to nonuniform dose distributions. Research priorities for the next 5-10 years are proposed. Copyright 2010 Elsevier Inc. All rights reserved.
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            External validity of risk models: Use of benchmark values to disentangle a case-mix effect from incorrect coefficients.

            Various performance measures related to calibration and discrimination are available for the assessment of risk models. When the validity of a risk model is assessed in a new population, estimates of the model's performance can be influenced in several ways. The regression coefficients can be incorrect, which indeed results in an invalid model. However, the distribution of patient characteristics (case mix) may also influence the performance of the model. Here the authors consider a number of typical situations that can be encountered in external validation studies. Theoretical relations between differences in development and validation samples and performance measures are studied by simulation. Benchmark values for the performance measures are proposed to disentangle a case-mix effect from incorrect regression coefficients, when interpreting the model's estimated performance in validation samples. The authors demonstrate the use of the benchmark values using data on traumatic brain injury obtained from the International Tirilazad Trial and the North American Tirilazad Trial (1991-1994).
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              Calculation of complication probability factors for non-uniform normal tissue irradiation: the effective volume method.

              An estimation of normal tissue complication probability factors is important, particularly for evaluating 3-dimensional treatment plans. A method has been developed to calculate complication probability factors for non-uniformly irradiated normal organs using dose volume histograms and complication probabilities for uniform partial organ irradiation. In the effective volume method each volume element of the histogram is considered independently and subject to a power law dose volume relationship. Thus, a non-uniform dose volume histogram is reduced to a uniform one with an effective volume, and a dose equal to the maximum dose to the organ. The complication probability is then obtained from known complication probabilities for uniform partial organ irradiation. The effective volume histogram transformation method is shown to obey various boundary conditions, and is illustrated by comparing probability calculations for alternative 3-dimensional treatment plans for the pelvis. In addition, the limitations of this histogram reduction method are discussed and compared to other calculational techniques. The use of probability factor calculations in treatment plan evaluation, and their role in numerical scoring is explored.
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                Author and article information

                Contributors
                tflee@kuas.edu.tw
                886-7-381-4526 , yeh5657@gmail.com , sayeh@outlook.com
                pjchao99@gmail.com
                cliyun2000@gmail.com
                clchiu@kuas.edu.tw
                hmting618@gmail.com
                hywang@cc.kuas.edu.tw
                yujie1115@gmail.com
                Journal
                Radiat Oncol
                Radiat Oncol
                Radiation Oncology (London, England)
                BioMed Central (London )
                1748-717X
                17 September 2015
                17 September 2015
                2015
                : 10
                : 194
                Affiliations
                [ ]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
                [ ]Institute of Clinical Medicine, Kaohsiung Medical University, Kaohsiung, 807 Taiwan ROC
                [ ]Department of Radiation Oncology, E-Da hospital, No.1, Yida Road, Jiaosu Village, Yanchao District, Kaohsiung City, 82445 Taiwan ROC
                [ ]Department of Medical Imaging and Radiological Sciences, I-Shou University, Kaohsiung, 840 Taiwan ROC
                [ ]Department of Radiation Oncology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, 83305 Taiwan ROC
                Article
                501
                10.1186/s13014-015-0501-x
                4574090
                26377924
                6edf93fa-7b1e-4ee3-bf25-b4b17de9c578
                © Lee et al. 2015

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 22 March 2015
                : 4 September 2015
                Categories
                Research
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                © The Author(s) 2015

                Oncology & Radiotherapy
                Oncology & Radiotherapy

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