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

• Published in: Radiotherapy and oncology 2015-10, Vol.117 (1), p.49-54
• Main Authors: Wijsman, Robin, Dankers, Frank, Troost, Esther G.C, Hoffmann, Aswin L, van der Heijden, Erik H.F.M, de Geus-Oei, Lioe-Fee, Bussink, Johan
• Format: Article
• Language: English
• Subjects: Adult; Aged; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - pathology; Carcinoma, Non-Small-Cell Lung - radiotherapy; Chemoradiotherapy; Cohort Studies; Esophageal Diseases - etiology; Esophagitis; Esophagus - radiation effects; Female; Hematology, Oncology and Palliative Medicine; Humans; Intensity-modulated radiation therapy; Lung Neoplasms - drug therapy; Lung Neoplasms - pathology; Lung Neoplasms - radiotherapy; Male; Middle Aged; Models, Statistical; Multivariate Analysis; Non-small cell lung cancer; Predictive models; Radiation Injuries - etiology; Radiometry; Radiotherapy Dosage; Radiotherapy, Intensity-Modulated - adverse effects; Radiotherapy, Intensity-Modulated - methods; Retrospective Studies
• ISSN: 0167-8140; 1879-0887
• DOI: 10.1016/j.radonc.2015.08.010

Abstract 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.