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


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.
Department of Radiation Oncology, Radboud University Medical Center, Nijmegen, The Netherlands. Electronic address: robin.wijsman@radboudumc.nl.
Robin
R
Wijsman
Department of Radiation Oncology, Radboud University Medical Center, Nijmegen, The Netherlands.
Frank
F
Dankers
Institute of Radiooncology, Helmholtz-Zentrum Dresden-Rossendorf, Germany; Department of Radiotherapy and Radiooncology, University Hospital Carl Gustav Carus at the Technische Universität Dresden, Germany; OncoRay, National Center for Radiation Research in Oncology, Dresden, Germany.
Esther G C
EG
Troost
Institute of Radiooncology, Helmholtz-Zentrum Dresden-Rossendorf, Germany; Department of Radiotherapy and Radiooncology, University Hospital Carl Gustav Carus at the Technische Universität Dresden, Germany.
Aswin L
AL
Hoffmann
Department of Pulmonary Diseases, Radboud University Medical Center, Nijmegen, The Netherlands.
Erik H F M
EH
van der Heijden
Department of Radiology, Leiden University Medical Center, The Netherlands; Biomedical Photonic Imaging Group, MIRA Institute, University of Twente, Enschede, The Netherlands.
Lioe-Fee
LF
de Geus-Oei
Department of Radiation Oncology, Radboud University Medical Center, Nijmegen, The Netherlands.
Johan
J
Bussink
D000328:Adult; D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D059248:Chemoradiotherapy; D015331:Cohort Studies; D004935:Esophageal Diseases / Q000209:etiology*; D004947:Esophagus / Q000528:radiation effects*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D015999:Multivariate Analysis; D011832:Radiation Injuries / Q000209:etiology*; D011874:Radiometry; D011879:Radiotherapy Dosage; D050397:Radiotherapy, Intensity-Modulated / Q000009:adverse effects / Q000379:methods; D012189:Retrospective Studies
Esophagitis; Intensity-modulated radiation therapy; Non-small cell lung cancer; Predictive models