Multivariable normal-tissue complication modeling of acute esophageal toxicity in advanced stage non-small cell lung cancer patients treated with intensity-modulated (chemo-)radiotherapy

Robin Wijsman, Frank Dankers, Esther G.C. Troost, Aswin L. Hoffmann, Erik H.F.M. Van Der Heijden, Lioe-Fee De Geus-Oei, Johan Bussink

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Background and purpose The majority of normal-tissue complication probability (NTCP) models for acute esophageal toxicity (AET) in advanced stage non-small cell lung cancer (AS-NSCLC) patients treated with (chemo-)radiotherapy are based on three-dimensional conformal radiotherapy (3D-CRT). Due to distinct dosimetric characteristics of intensity-modulated radiation therapy (IMRT), 3D-CRT based models need revision. We established a multivariable NTCP model for AET in 149 AS-NSCLC patients undergoing IMRT. Materials and methods An established model selection procedure was used to develop an NTCP model for Grade ≥2 AET (53 patients) including clinical and esophageal dose-volume histogram parameters. Results The NTCP model predicted an increased risk of Grade ≥2 AET in case of: concurrent chemoradiotherapy (CCR) [adjusted odds ratio (OR) 14.08, 95% confidence interval (CI) 4.70-42.19; p <0.001], increasing mean esophageal dose [Dmean; OR 1.12 per Gy increase, 95% CI 1.06-1.19; p <0.001], female patients (OR 3.33, 95% CI 1.36-8.17; p = 0.008), and ≥cT3 (OR 2.7, 95% CI 1.12-6.50; p = 0.026). The AUC was 0.82 and the model showed good calibration. Conclusions A multivariable NTCP model including CCR, Dmean, clinical tumor stage and gender predicts Grade ≥2 AET after IMRT for AS-NSCLC. Prior to clinical introduction, the model needs validation in an independent patient cohort.
Original languageEnglish
Pages (from-to)49-54
Number of pages6
JournalRadiotherapy and Oncology
Issue number1
Publication statusPublished - 1-Oct-2015
Externally publishedYes


  • Esophagitis
  • Intensity-modulated radiation therapy
  • Non-small cell lung cancer
  • Predictive models
  • cisplatin
  • etoposide
  • gemcitabine
  • adult
  • advanced cancer
  • aged
  • area under the curve
  • article
  • cancer grading
  • cancer radiotherapy
  • cancer staging
  • chemoradiotherapy
  • esophagitis
  • female
  • histogram
  • human
  • intensity modulated radiation therapy
  • major clinical study
  • male
  • non small cell lung cancer
  • priority journal
  • radiation injury
  • risk assessment

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