Development of a multicomponent prediction model for acute esophagitis in lung cancer patients receiving chemoradiotherapy

Int J Radiat Oncol Biol Phys. 2011 Oct 1;81(2):537-44. doi: 10.1016/j.ijrobp.2011.03.012. Epub 2011 May 24.

Abstract

Purpose: To construct a model for the prediction of acute esophagitis in lung cancer patients receiving chemoradiotherapy by combining clinical data, treatment parameters, and genotyping profile.

Patients and methods: Data were available for 273 lung cancer patients treated with curative chemoradiotherapy. Clinical data included gender, age, World Health Organization performance score, nicotine use, diabetes, chronic disease, tumor type, tumor stage, lymph node stage, tumor location, and medical center. Treatment parameters included chemotherapy, surgery, radiotherapy technique, tumor dose, mean fractionation size, mean and maximal esophageal dose, and overall treatment time. A total of 332 genetic polymorphisms were considered in 112 candidate genes. The predicting model was achieved by lasso logistic regression for predictor selection, followed by classic logistic regression for unbiased estimation of the coefficients. Performance of the model was expressed as the area under the curve of the receiver operating characteristic and as the false-negative rate in the optimal point on the receiver operating characteristic curve.

Results: A total of 110 patients (40%) developed acute esophagitis Grade ≥2 (Common Terminology Criteria for Adverse Events v3.0). The final model contained chemotherapy treatment, lymph node stage, mean esophageal dose, gender, overall treatment time, radiotherapy technique, rs2302535 (EGFR), rs16930129 (ENG), rs1131877 (TRAF3), and rs2230528 (ITGB2). The area under the curve was 0.87, and the false-negative rate was 16%.

Conclusion: Prediction of acute esophagitis can be improved by combining clinical, treatment, and genetic factors. A multicomponent prediction model for acute esophagitis with a sensitivity of 84% was constructed with two clinical parameters, four treatment parameters, and four genetic polymorphisms.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Algorithms*
  • Antigens, CD / genetics
  • Area Under Curve
  • CD18 Antigens / genetics
  • Combined Modality Therapy / adverse effects
  • Combined Modality Therapy / methods
  • Endoglin
  • ErbB Receptors / genetics
  • Esophagitis / etiology*
  • Esophagus / drug effects
  • Esophagus / radiation effects
  • False Negative Reactions
  • Female
  • Genotype
  • Humans
  • Logistic Models
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics
  • Lung Neoplasms / radiotherapy*
  • Male
  • Middle Aged
  • Models, Biological*
  • Organs at Risk / radiation effects
  • Polymorphism, Genetic
  • ROC Curve
  • Radiotherapy Dosage
  • Receptors, Cell Surface / genetics
  • TNF Receptor-Associated Factor 3 / genetics

Substances

  • Antigens, CD
  • CD18 Antigens
  • ENG protein, human
  • Endoglin
  • Receptors, Cell Surface
  • TNF Receptor-Associated Factor 3
  • TRAF3 protein, human
  • EGFR protein, human
  • ErbB Receptors