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Polymorphisms of the vascular endothelial growth factor gene and severe radiation pneumonitis in non-small cell lung cancer patients treated with definitive radiotherapy.

ABSTRACT: Vascular endothelial growth factor (VEGF) is a major mediator of angiogenesis and lung cancer progression. We hypothesized that VEGF polymorphisms may modulate the risk of radiation pneumonitis (RP) in non-small cell lung cancer (NSCLC) patients treated with definitive radiotherapy. We genotyped three potentially functional VEGF single nucleotide polymorphisms (-460 T > C [rs833061], -634 G > C [rs2010963] and +936 C > T [rs3025039]) and estimated the associations of their genotypes and haplotypes with severe radiation pneumonitis (RP ≥grade 3) in 195 NSCLC patients. We found that the VEGF genotypes of rs2010963 and rs3025039 single nucleotide polymorphisms as well as the -460C/-634G/+936C haplotype were predictors of RP development (adjusted hazard ratio [adjHR] = 2.33, 95% confidence interval [CI], 1.01-5.37, P = 0.047 for CC vs GG genotypes; adjHR = 28.13, 95% CI, 5.24-151.02, P < 0.001 for TT vs CC genotypes; and adjHR = 2.51, 95% CI, 1.27-4.98, P = 0.008 for T-C-T vs C-G-C haplotypes). In addition, there was a trend towards reduced RP risk in patients carrying an increased number of protective VEGF genotypes. Our data suggest that VEGF polymorphisms can modulate the risk of radiation pneumonitis in NSCLC patients treated with definitive radiotherapy. Large and independent studies are needed to confirm our findings.

SUBMITTER: Yin M

PROVIDER: S-EPMC3337362 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background:Radiation pneumonitis is a critical pulmonary toxicity after irradiation of the lung. Macrolides including clarithromycin (CAM) are antibiotics. They also have immunomodulatory properties and are used to treat respiratory inflammatory diseases. Radiation pneumonitis has similar pathology to them. Adverse reactions to macrolides are few and self-limited. We thus administered CAM to patients with high-risk factors for radiation pneumonitis, and retrospectively investigated whether CAM mitigated radiation pneumonitis following stereotactic body radiotherapy (SBRT). Methods:Among consecutive patients treated with SBRT, we retrospectively examined lung cancer patients treated with a total dose of 40-60 Gy in 5-10 fractions and followed ?6 months. Since January 2014, CAM has been administered in patients with pretreatment predictable radiation pneumonitis high-risk factors, including idiopathic interstitial pneumonias (IIPs), and elevated Krebs von den Lungen-6 (KL-6) and/or surfactant protein D (SP-D), and in patients developing early onset radiation pneumonitis. Results:Five hundred and eighty eligible patients were identified and divided into 445 patients during the non-CAM-administration era (non-CAM-era) (before December 2013) and 136 patients during the CAM-administration era (CAM-era) (after January 2014). Median follow-up durations were 38.0 and 13.9 months, respectively. The rates of radiation pneumonitis ? grade 2 and ? grade 3 were significantly lower in CAM-era (grade ?2, 16% vs. 9.6%, P=0.047; grade ?3, 3.8% vs. 0.73%, P=0.037). For patients with the pretreatment predictable high-risk factors, the rate of radiation pneumonitis ? grade 3 was significantly lower, and that of grade ?2 had a lower tendency (grade ?3, 7.2% vs. 0%, P=0.011; grade ?2, 21% vs. 9.6%, P=0.061). For patients developing early onset radiation pneumonitis, the rate of radiation pneumonitis ? grade 3 was also significantly lower (23% vs. 0%, P<0.05). Multivariate analysis revealed that dose-volumetric factor, the pretreatment predictable high-risk factors and non-CAM-administration era were significantly associated with or trended toward radiation pneumonitis ? grade 2 and ? grade 3. Conclusions:CAM mitigated radiation pneumonitis following SBRT. The efficacy of CAM should be con?rmed in prospective studies.

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Polymorphisms of the vascular endothelial growth factor gene and severe radiation pneumonitis in non-small cell lung cancer patients treated with definitive radiotherapy.

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