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K. Vandecasteele



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    P2.06 - Poster Session 2 - Prognostic and Predictive Biomarkers (ID 165)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Biology
    • Presentations: 1
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      P2.06-030 - Radiation-induced lung damage quantification with CT scans: Correlation with single nucleotide polymorphisms (ID 2420)

      09:30 - 09:30  |  Author(s): K. Vandecasteele

      • Abstract

      Background
      Radiation-induced lung damage (RILD) is a dose-limiting toxicity of lung radiotherapy. Individual sensitivity can be measured by changes in Hounsfield Units over time (delta HU) on CT scans (De Ruysscher et al. Acta Oncol 2013). This endpoint is specific for lung damage and does not correlate with dyspnoea, which is multi-factorial. In this study, we investigated the association between density changes over time and SNPs aiming at finding individual sensitivity for RILD.

      Methods
      Delta HU/Gy and delta HU/Gy x MLD (Mean Lung Dose), the latter to take into account a volume factor for RILD, were correlated with 314 SNPs related to fibrosis and inflammation. The outcome variables were square root transformed because both were not normally distributed. Univariate ANOVA analyses were performed for comparisons of means. P-values of less than 0.01 were considered to be significant.

      Results
      Eighty-nine lung cancer patients were studied, 63 men and 26 females. Twenty patients were treated with radiotherapy alone, 31 with sequential chemo-RT and 38 with concurrent chemo-RT. Twenty percent of the patients developed grade 2 or more clinical dyspnoea after treatment. Three SNPs were significantly correlated with delta HU/Gy: rs2252070 (p=0.006, MMP13), rs2230588 (p=0.009, JAK1) and rs12901071 (p=0.009, SMAD3) [Table 1A]. For delta HU/Gy x MLD, significant associations were found for rs3819122 (p=0.008, SMAD4), rs2230529 (p=0.009, ITGB2) and rs2230588 (p=0.009, JAK1) [Table 1B]. Figure 1

      Conclusion
      Quantification of CT density changes due to radiotherapy, measured as HU changes over time as a specific and quantitative endpoint for RILD correlates with specific SNPs in genes involved in signal transduction of cytokines (SMAD3/4, JAK1), in the extracellular matrix (MMP13) and in cell adhesion (ITGB2). External validation will follow.