Single Nucleotide Polymorphisms Of Inflammation-Related Genes As Predictive Risk Factors Of Radiation Pneumonitis After Stereotactic Body Radiation Therapy For Stage I Non-Small Cell Lung Cancer

Severe radiation pneumonitis (RP) after stereotactic body radiation therapy (SBRT) for the patients with early stage primary lung cancer is generally rare toxicity but sometimes gets to be severe adverse effect. It is important but has not been achieved to predict patients who are at high risk of developing severe RP and its monitoring techniques. Although human diversity to a certain amount is explained by clinical and dosimetric factors, the presence of specific genetic variants also influences the occurrence of radiation-induced damage. So, the purpose of the study was to search reliable biologic markers to predict the risk of RP after SBRT, we investigated the association between single nucleotide polymorphisms (SNPs) in inflammation-related genes and risk of radiation pneumonitis (RP) in the patients with stage I non-small-cell lung cancer (NSCLC) treated by SBRT. Using genomic DNA samples from totally 223 patients with stage I NSCLC treated by SBRT were acquired and genotyped 21 SNPs of inflammation-related genes by mainly MassARRAY system (Sequenom) to detect the difference in the mass of nucleotides. We used logistic regression analyses to evaluate the effect of genotypes in other factors of patients characteristics, variety of laboratory data or CT findings before SBRT, and SBRT dose distribution in the normal lung volume on the risk of RP, in particular as a worse status, grade (CTCAE version 3.0) > or = 2 RP combined with simultaneous inflammatory shadow outside of the irradiated volume on the CT images. There were 139 men and 84 women in the study, with median age of 81 years. SBRT dose was from12.5 to 66.7 Gy in from 4 to 10 fractions. Mean of the ration of normal lung volume irradiated 20 Gy or more to the total normal lung volume (V20) and the mean normal lung dose was 6.5 % (range: 1.2-16.9 %), and 4.3 Gy (range: 0.20-9.9 Gy), respectively. Grade > or = 2 RP and inflammatory shadow outside of the irradiated volume were observed in 36 (16.1%) and 34 (15.2%), respectively. Multivariate analysis found a history of heart failure or steroid administration, the ratio of volume irradiated 10Gy or more in the total normal lung volume (V10), and genotypes of EGFR (rs11543848) to be significantly higher risk factors of grade > or = 2 RP combined with inflammatory shadow outside of the irradiated volume. When excluding six cases with a history of steroid administration, only genotype of EGFR (rs11543848) was a significantly higher risk factor of grade > or = 2 RP combined with inflammatory shadow outside of the irradiated volume. Our results showed that the SNP with genotypes of EGFR might be a higher risk of severe RP in patients with NSCLC treated with SBRT. Replication studies with more patients are required to validate these results.