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A. Sukari



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    P1.08 - Poster Session 1 - Radiotherapy (ID 195)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Radiation Oncology + Radiotherapy
    • Presentations: 1
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      P1.08-011 - Dosimetric Predictors of Esophageal Toxicity in Patients with Non-small Cell Lung Cancer Receiving Chemotherapy and Radiotherapy (ID 1507)

      09:30 - 09:30  |  Author(s): A. Sukari

      • Abstract

      Background
      Esophageal toxicity can be a dose-limiting event in patients with non-small cell lung cancer receiving chemotherapy and radiotherapy necessitating treatment breaks with potential to cause adverse treatment related factors. The objective of this study was to investigate those factors, both clinical and dosimetric, which predict for esophageal toxicity.

      Methods
      Patients (pts) with non-small cell lung cancer prospectively enrolled into an IRB approved database were retrospectively reviewed. Pts with biopsy-proven non-small cell lung cancer treated with radiotherapy alone, sequential or concurrent chemoradiotherapy had maximal esophageal toxicity scored per CTCAE 4.0 criteria. V5, V10, V20, V30, V40, V50, V60, V70, esophageal hot spot, and dose per fraction were the dosimetric variables and age, sex, race, chemotherapy, and stage were the clinical variables investigated. Data were analyzed using SAS (SAS INC, Cary, NC) Version 9.2 software package. Ordinal maximum reported esophageal toxicity was evaluated using logistic regression. A multivariable regression model was fit using important univariate predictors along with a backwards elimination stepwise regression. Probability of esophageal toxicity as a function of absorbed dose in a partial volume was modeled by the method of Lyman, by converting the dose volume histograms into an equivalent fractional volume receiving the maximum dose in the DVH, using the effective volume method of Kutcher and Burman. The parameters in this model (D50, slope m and volume exponent n) were determined by maximum likelihood estimation.

      Results
      A total of 100 pts were enrolled between 7/10 and 12/12 into a prospective database and eligible for analysis. Pts were excluded without a complete dose volume histogram data or were stage I disease leaving 71 eligible for analysis, 43 females and 28 males with a median age of 61 (range: 39-85). 14 pts were treated with radiotherapy alone while 23 received sequential treatment and 34 concurrent treatment. The median delivered dose was 66.6 Gy (range: 27.5-66.6) in a median of 1.8 Gy (range: 1.8-3.0) per fraction. Maximal esophageal toxicity was rated as 0: 12pts, 1: 21 pts, 2: 33 pts, and 3: 5pts. Univariate predictors of > grade 2 esophageal toxicity included, V5-V60 and use of concurrent chemotherapy. The maximum likelihood fit of the Lyman model parameters to patients with ≥ 2 esophageal symptoms were n=0.26 m=0.32, TD50=39.1 Gy when the α/β ratio was assumed to be 10 Gy. The maximal likelihood fit of the Lyman model parameters to patients when the α/β ratio was not set were n=0.26, m=0.32 and TD50 39.3 with the α/β calculated at 7.6 Gy. Patients not having chemotherapy had a higher TD50, 46.4 Gy as compared to patients having chemotherapy, TD50=37.1 Gy, p=0.09.

      Conclusion
      We have shown the TD50 for > grade 2 esophageal toxicity is lower for patients receiving chemotherapy and radiotherapy compared to patients receiving radiotherapy alone. This is first report to show the α/β ratio for esophageal toxicity may be lower than 10. Confirmations of these data are needed in an independent data set.

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    P1.18 - Poster Session 1 - Pathology (ID 175)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Pathology
    • Presentations: 1
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      P1.18-007 - Multiplex testing of driver mutations in Non-Small Cell Lung Cancer (NSCLCs) of African-American (AA) patients (ID 1312)

      09:30 - 09:30  |  Author(s): A. Sukari

      • Abstract

      Background
      Recently driver genetic alterations have been identified in NSCLC that can be targeted for therapeutic interventions. Previous reports have suggested that rates of certain mutations may vary according to ethnic background. We conducted multiplex testing of NSCLCs of AA and white patients to assess variability in the mutation rates by race.

      Methods
      We identified tumor tissues of 139 AA and 340 white NSCLC patients collected as part of three different institutional review board approved studies. Using the Sequenom MassArray system and a multiplexed panel, we analyzed tumor DNA for 214 oncogenic mutations in 26 genes previously identified in NSCLC. Estimated risk (Odds Ratios (OR)) of any mutation and specific gene mutations among AA patients compared to white patients were calculated after adjusting for age, sex, smoking status and histology (adenocarcinoma versus non-adenocarcinoma). Information on smoking status was unavailable on 45 patients and was not included in calculations of ORs for some genes (OR[b]).

      Results
      The median age at diagnosis was 60 vs 66 years in AA vs white patients; 42% of AA patients and 65% of white patients were males; 67% of AA patients and 49% of white patients had adenocarcinoma; 67% of AA patients and 85% of white patients had stage I/II NSCLC and 10% of AA patients and 6% of white patients were never smokers. 43% of the AA patients and 46% of white patients had at least one mutation detected (OR=0.8; 0.5-1.2). 19% of AA patients and 8% of white patients had more than 1 mutation detected (OR 2.1; 1.1-4.1) (Table 1). AA patients were more likely to harbor mutations in STK11 (LKB1) (OR=7.5; 3.1-18.2) and NOTCH1 (OR[b]=8.4; 2.2-31.7), and they were less likely to have MET mutations (OR[b]=0.2; 0.1-1.1) then white patients. While not statistically significant, AA had lower prevalence of Kras mutations (OR[b]=0.5, 0.2-1.0) and p53 mutations (OR= 0.7; 0.4-1.4). Table 1

      Outcome OR for African American Race 95% CI P
      Any driver mutation[a] 0.8 0.5-1.2 0.203
      >1 driver mutation[a] 2.1 1.1-4.1 0.036
      STK11 Mutation[a] 7.5 3.1-18.2 <.001
      P53 Mutation[a] 0.7 0.4-1.4 0.359
      Kras Mutation[b] 0.5 0.2-1.0 0.041
      NOTCH1 Mutation[b] 8.4 2.2-31.7 0.002
      MET mutation[b] 0.2 0.1-1.1 0.065
      [a]Adjusted for age, sex, ever/never smoking and adeno/non-adeno
      [b]Adjusted for age, sex, and adeno/non-adeno

      Conclusion
      Our analysis of NSCLCs shows that AAs were more likely to have multiple genetic mutations than whites and the mutation profile differs by race.