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Baho Sidiqi



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    P2.17 - Treatment of Early Stage/Localized Disease (ID 189)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Treatment of Early Stage/Localized Disease
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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      P2.17-32 - Using Next-Generation Sequencing to Identify Genetic Predictors of Local Failure After Lung Stereotactic Body Radiation Therapy (Now Available) (ID 2708)

      10:15 - 18:15  |  Author(s): Baho Sidiqi

      • Abstract
      • Slides

      Background

      Lung stereotactic body radiation therapy (SBRT) is a well-established therapy for primary lung tumors or metastatic lung lesions from other primary sites. However, local failure after SBRT still occurs. We hypothesized that next-generation tumor sequencing may identify genetic characteristics that predict local failure.

      Method

      We conducted a retrospective analysis of all patients at our institution who received SBRT to the lung for either primary or metastatic tumors, and who underwent next-generation tumor sequencing utilizing an FDA-approved targeted panel of at least 341 genes. Patient and tumor characteristics, local failure, radiation dose, and all genetic alterations identified by the panel were collected. Univariate Cox proportional hazards analysis was performed. Because of the large number of genes in the panel, we limited analysis to genes with at least a 5% incidence of alteration in this cohort. To correct for multiple testing, we used a p-value of ≤ 0.001 as the significance threshold for genetic alterations.

      Result

      Between 2013 and 2018, 140 patients with 160 lung lesions (76 primary lung, 84 non-lung primary) were treated with SBRT to a median radiation biologically effective dose of 100 Gy (range 48-151 Gy). Median follow-up for local failure was 13.8 months. There were 39 local failures (24.4%) during the study period. On univariate analysis, colorectal histology (HR 2.2, p=0.037), BED<100 Gy (HR 2.1, p=0.019), and larger lesion size (HR 1.2, p=0.023) were associated with higher risk of local failure. 45 mutations occurred with greater than 5% frequency (≥8 times) in our cohort. Univariate analysis identified three genes for which alterations were significantly associated with local failure: APC (mutated 17 times, HR 3.5, p<0.001), ARID2 (n=8, HR 5.5, p<0.0005), and MGA (n=8, HR 5.2, p<0.001)

      Conclusion

      Next-generation tumor sequencing was able to identify genetic alterations associated with higher risk of local failure after lung SBRT. This hypothesis-generating study yielded three candidate genes significantly correlated with local failure. Further study is needed to validate the predictive value of these gene mutations, and their potential for selecting patients at higher risk for treatment failure after lung SBRT.

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