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Abraham J Wu



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    MA02 - Miscellaneous Topics in the Management of Early Stage Lung Cancer (ID 116)

    • Event: WCLC 2019
    • Type: Mini Oral Session
    • Track: Treatment of Early Stage/Localized Disease
    • Presentations: 1
    • Now Available
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      MA02.06 - Dose-Volume Factors Predicting Airway Stenosis After SBRT for Ultra-Central Lung Tumors (Now Available) (ID 1454)

      10:30 - 12:00  |  Author(s): Abraham J Wu

      • Abstract
      • Presentation
      • Slides

      Background

      The safety of SBRT is uncertain for ultra-central tumors (near the proximal airways or esophagus). One potential toxic effect of ultra-central SBRT is stenosis of the proximal airways, which can lead to airway obstruction and lung collapse. Predictors of such toxicity in this population are urgently needed. We therefore studied dose-volume correlates of airway stenosis after ultra-central SBRT.

      Method

      88 patients with tumors abutting the proximal bronchial tree (PBT) or PTVs overlapping esophagus (n = 76 and 23; 11 met both criteria) were included. 53 (60%) had primary/locally recurrent lung cancer, and 35 had lung metastases. All had 5, 8 or 15 fractions of image-guided radiotherapy with BED ≥84Gy (α/β=10). The lobar bronchi (LB) were contoured from the takeoff from the main bronchus to the bifurcation into segmental bronchi. The primary endpoint was grade 2 or higher lobar bronchial stenosis (LBS), defined as radiographic evidence of narrowing or complete obstruction of at least one lobar bronchus (CTCAE v4). Dose-volume histograms (DVHs) using linear-quadratic equivalent doses in 2 Gy fractions were calculated for the LB with α/β = 3 Gy. Mean equivalent doses (MEDs) to the LB were tested for correlation with LBS using a Cox proportional hazards model, and the log rank test with patient data split at the median value of the MEDs to the LB. Statistical significance was defined as p < 0.05.

      Result

      Median follow up was 14.3 months. There were 24 cases of LBS (27%). Median time to onset of LBS2+ was 8.6 months after end of treatment (range 2-19 months). LBS was significantly correlated with MED to the LB (p = 0.02). Incidence of LBS was significantly different in patients with MED to the LB < or > the median value of 35.4 Gy (p = 0.004 log-rank test), with actuarial rates of 19% and 55% respectively at 14 months, and 19% and 70% respectively at 24 months; and with raw rates of 15.9% and 38.6% respectively.

      Conclusion

      We observed a high rate of lobar stenosis after ultra-central SBRT. Incidence of lobar stenosis was significantly correlated with dose to the lobar bronchi. In particular, mean equivalent dose to the lobar bronchi was significantly correlated with LBS. Our analysis suggests that limiting the mean equivalent dose to the lobar bronchi to < 35.4 Gy results in a two year actuarial incidence of LBS of <19%, and a raw incidence <16%.

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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): Abraham J Wu

      • 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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