Abstract

BackgroundThe vascular endothelial cells are important targets of radiotherapy, which may be involved in the pathogenesis of radiation pneumonitis (RP). This study investigated the variations of circulating endothelial progenitor cells (EPCs) and transforming growth factor-beta-1 (TGF-β1) during three-dimensional conformal radiation therapy (3D-CRT) in patients with non–small-cell lung cancer (NSCLC) and analyzed the correlation between these variations with the occurrence of RP.Patients and methodsFrom November 2008 to November 2009, eighty-four consecutive patients receiving 3D-CRT for stage III disease were evaluated prospectively. Circulating EPCs and TGF-β1 levels were measured at baseline, every 2 weeks during, and at the end of treatment. RP was evaluated prospectively at 6 weeks after 3D-CRT.ResultsThirty-eight patients (47.5%) experienced score 1 or more of RP. The baseline levels of EPCs and TGF-β1 were analyzed, no difference was found between patients with and without RP during and after 3D-CRT. By serial measurement of TGF-β1 and EPCs levels, we found that the mean levels of EPCs in the whole population remained stable during radiotherapy, but the mean levels of TGF-β1 increased slowly during radiotherapy. TGF-β1 and EPCs levels were all significantly higher at week 2, week 4 and week 6 in patients with RP than that in patients without RP, respectively. During the period of radiation treatment, TGF-β1 levels began to increase in the first 2 weeks and became significantly higher at week 6 (P < 0.01). EPCs levels also began to increase in the first 2 weeks and reached a peak at week 4. Using an ANOVA model for repeated-measures, we found significant associations between the levels of TGF-β1 and EPCs during the course of 3D-CRT and the risk of developing RP (P < 0.01). Most of the dosimetric factors showed a significant association with RP.ConclusionEarly variations of TGF-β1 and EPCs levels during 3D-CRT are significantly associated with the risk of RP. Variations of circulating TGF-β1 and EPCs levels during 3D-CRT may serve as independent predictive factors for RP.Trial registrationTrials registration number: 20070618

Highlights

  • The vascular endothelial cells are important targets of radiotherapy, which may be involved in the pathogenesis of radiation pneumonitis (RP)

  • By serial measurement of TGF-β1 and endothelial progenitor cells (EPCs) levels, we found that the mean levels of EPCs in the whole population remained stable during radiotherapy, but the mean levels of TGF-β1 increased slowly during radiotherapy

  • Using an ANOVA model for repeated-measures, we found significant associations between the levels of TGF-β1 and EPCs during the course of 3D-CRT and the risk of developing RP (P < 0.01)

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Summary

Introduction

The vascular endothelial cells are important targets of radiotherapy, which may be involved in the pathogenesis of radiation pneumonitis (RP). This study investigated the variations of circulating endothelial progenitor cells (EPCs) and transforming growth factor-beta-1 (TGF-β1) during three-dimensional conformal radiation therapy (3D-CRT) in patients with non–small-cell lung cancer (NSCLC) and analyzed the correlation between these variations with the occurrence of RP. Non–small-cell lung cancer (NSCLC) is the most common cancer in developed countries. Among the patients received thoracic radiotherapy, 8% to 13% developed severe toxicity, and approximately 1.6% died from RP [1]. Several biological factors need to be considered for understanding the molecular events in developing radiation-induced complications in normal tissues [2,3,4,5]

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