title: Normal tissue complication probability model parameter estimation for xerostomia in head and neck cancer patients based on scintigraphy and quality of life assessments.
abstract: BACKGROUND
  With advances in modern radiotherapy (RT), many patients with head and neck (HN) cancer can be effectively cured. However, xerostomia is a common complication in patients after RT for HN cancer. The purpose of this study was to use the Lyman-Kutcher-Burman (LKB) model to derive parameters for the normal tissue complication probability (NTCP) for xerostomia based on scintigraphy assessments and quality of life (QoL) questionnaires. We performed validation tests of the Quantitative Analysis of Normal Tissue Effects in the Clinic (QUANTEC) guidelines against prospectively collected QoL and salivary scintigraphic data.
  
  
  METHODS
  Thirty-one patients with HN cancer were enrolled. Salivary excretion factors (SEFs) measured by scintigraphy and QoL data from self-reported questionnaires were used for NTCP modeling to describe the incidence of grade 3+ xerostomia. The NTCP parameters estimated from the QoL and SEF datasets were compared. Model performance was assessed using Pearson's chi-squared test, Nagelkerke's R2, the area under the receiver operating characteristic curve, and the Hosmer-Lemeshow test. The negative predictive value (NPV) was checked for the rate of correctly predicting the lack of incidence. Pearson's chi-squared test was used to test the goodness of fit and association.
  
  
  RESULTS
  Using the LKB NTCP model and assuming n=1, the dose for uniform irradiation of the whole or partial volume of the parotid gland that results in 50% probability of a complication (TD50) and the slope of the dose-response curve (m) were determined from the QoL and SEF datasets, respectively. The NTCP-fitted parameters for local disease were TD50=43.6 Gy and m=0.18 with the SEF data, and TD50=44.1 Gy and m=0.11 with the QoL data. The rate of grade 3+ xerostomia for treatment plans meeting the QUANTEC guidelines was specifically predicted, with a NPV of 100%, using either the QoL or SEF dataset.
  
  
  CONCLUSIONS
  Our study shows the agreement between the NTCP parameter modeling based on SEF and QoL data, which gave a NPV of 100% with each dataset, and the QUANTEC guidelines, thus validating the cut-off values of 20 and 25 Gy. Based on these results, we believe that the QUANTEC 25/20-Gy spared-gland mean-dose guidelines are clinically useful for avoiding xerostomia in the HN cohort.
authors.affiliation: Medical Physics and Informatics Laboratory, Department of Electronics Engineering, National Kaohsiung University of Applied Sciences, Kaohsiung, Taiwan, ROC. tflee@kuas.edu.tw
authors.forename: Tsair-Fwu
authors.initials: TF
authors.lastname: Lee
authors.forename: Pei-Ju
authors.initials: PJ
authors.lastname: Chao
authors.forename: Hung-Yu
authors.initials: HY
authors.lastname: Wang
authors.forename: Hsuan-Chih
authors.initials: HC
authors.lastname: Hsu
authors.forename: PaoShu
authors.initials: P
authors.lastname: Chang
authors.forename: Wen-Cheng
authors.initials: WC
authors.lastname: Chen
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D006258:Head and Neck Neoplasms / Q000150:complications* / Q000473:pathology / Q000532:radiotherapy; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D008962:Models, Theoretical; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D011336:Probability; D011788:Quality of Life; D011877:Radionuclide Imaging; D011878:Radiotherapy / Q000009:adverse effects*; D014987:Xerostomia / Q000453:epidemiology* / Q000209:etiology*