External validation of an NTCP model for acute esophageal toxicity in locally advanced NSCLC patients treated with intensity-modulated (chemo-)radiotherapy

Frank J.W.M. Dankers*, Robin Wijsman, Esther G.C. Troost, Caroline J.A. Tissing-Tan, Margriet H. Kwint, José Belderbos, Dirk de Ruysscher, Lizza E. Hendriks, Lioe Fee de Geus-Oei, Laura Rodwell, Andre Dekker, René Monshouwer, Aswin L. Hoffmann, Johan Bussink

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

9 Citations (Scopus)


Background and purpose: We externally validated a previously established multivariable normal-tissue complication probability (NTCP) model for Grade ≥2 acute esophageal toxicity (AET) after intensity-modulated (chemo-)radiotherapy or volumetric-modulated arc therapy for locally advanced non-small cell lung cancer. Materials and methods: A total of 603 patients from five cohorts (A–E) within four different Dutch institutes were included. Using the NTCP model, containing predictors concurrent chemoradiotherapy, mean esophageal dose, gender and clinical tumor stage, the risk of Grade ≥2 AET was estimated per patient and model discrimination and (re)calibration performance were evaluated. Results: Four validation cohorts (A, B, D, E) experienced higher incidence of Grade ≥2 AET compared to the training cohort (49.3–70.2% vs 35.6%; borderline significant for one cohort, highly significant for three cohorts). Cohort C experienced lower Grade ≥2 AET incidence (21.7%, p < 0.001). For three cohorts (A–C), discriminative performance was similar to the training cohort (area under the curve (AUC) 0.81–0.89 vs 0.84). In the two remaining cohorts (D–E) the model showed poor discriminative power (AUC 0.64 and 0.63). Reasonable calibration performance was observed in two cohorts (A–B), and recalibration further improved performance in all three cohorts with good discrimination (A–C). Recalibration for the two poorly discriminating cohorts (D–E) did not improve performance. Conclusions: The NTCP model for AET prediction was successfully validated in three out of five patient cohorts (AUC ≥0.80). The model did not perform well in two cohorts, which included patients receiving substantially different treatment. Before applying the model in clinical practice, validation of discrimination and (re)calibration performance in a local cohort is recommended.

Original languageEnglish
Pages (from-to)249-256
Number of pages8
JournalRadiotherapy and oncology
Issue number2
Publication statusPublished - Nov 2018


  • Acute esophagitis
  • External validation
  • Intensity-modulated radiation therapy
  • Non-small cell lung cancer
  • Predictive modeling
  • n/a OA procedure


Dive into the research topics of 'External validation of an NTCP model for acute esophageal toxicity in locally advanced NSCLC patients treated with intensity-modulated (chemo-)radiotherapy'. Together they form a unique fingerprint.

Cite this