Virtual Library

Start Your Search

F. Detterbeck

Author of

  • +

    IA05 - The Practical Use of the TNM Classifications for Thoracic Cancers (ID 291)

    • Event: WCLC 2016
    • Type: Interactive Session
    • Track: Radiology/Staging/Screening
    • Presentations: 1
    • +

      IA05.03 - Thymic Carcinoma Cases (ID 6526)

      11:00 - 12:30  |  Author(s): F. Detterbeck

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

  • +

    P1.05 - Poster Session with Presenters Present (ID 457)

    • Event: WCLC 2016
    • Type: Poster Presenters Present
    • Track: Early Stage NSCLC
    • Presentations: 1
    • +

      P1.05-017 - The Prognostic Impact of EGFR, KRAS and TP53 Somatic Mutations in Curatively Resected Early-Stage Lung Adenocarcinomas (ID 4527)

      14:30 - 15:45  |  Author(s): F. Detterbeck

      • Abstract

      As the 5-year survival among individuals undergoing curative-intent resection for early-stage lung cancer approaches 50%, identification of prognostic biomarkers useful for risk stratification is a priority. While somatic mutation profiling drives treatment choice in advanced disease, its usefulness among early-stage patients is not well-established.

      From May 2011 through December 2014, The Yale Lung Cancer Biorepository enrolled 192 individuals who underwent curative-intent complete resection for Stage IA-IIIA adenocarcinoma. Demographics and lifestyle choices were ascertained by interview using validated questionnaires. Pathologic characterization of index tumors, including CLIA Laboratory-assayed EGFR/KRAS status, was extracted from the medical record. A custom targeted resequencing panel covering all coding exons from 93 lung adenocarcinoma-related genes was designed. Buffy coat-derived germline DNA and tumor DNA, extracted from the FFPE surgical specimen, were sequenced on the Ion Torrent platform with >90% of the assayed amplicons achieving >30x coverage in both tumor and germline from each case. Somatic nonsynonymous tumor variants were identified using the Torrent Variant Caller. Bivariate associations were evaluated by Chi-square or ANOVA. Survival analyses were conducted using Cox modeling.

      181/192 (94.3%) participants underwent EGFR/KRAS somatic mutation profiling with 43 EGFR mutations and 71 KRAS mutations detected. EGFR mutations were more common among well- and moderately-differentiated lesions (p=0.06) and among never or former light smokers (p=0.0007). Seventy-two percent of EGFR and 81.7% of KRAS mutations were found among female patients (p=0.0008). The joint distribution between smoking and gender favored EGFR mutations among female never/former smokers, KRAS mutations among female ever-smokers and EGFR/KRAS wild-type status among male ever-smokers (p=0.0002). After adjustment for AJCC 7[th] edition Tstage, Nstage and presence of lymphovascular invasion, KRAS mutations (HR=2.14; 95% CI:1.04-4.43; p=0.04) but not EGFR mutations (p=0.63) were prognostic for poorer disease-free survival. Targeted resequencing data is available on 148 cases. The nonsynonymous mutation burden ranged from 0-7 with 84% of cases having ≤3. In addition to KRAS and EGFR, frequent mutations were noted in p53 (n=40; 27.0%), STK11 (n=10; 6.8%) and PIK3CA (n=7; 4.7%) with 4 genes mutated in 6 cases. TP53 mutations were associated with high nonsynonymous mutation burden (p<0.0001) and the joint distribution with EGFR/KRAS status revealed the highest burden among KRAS[mut]/TP53[mut] (3.94±1.57) followed by EGFR[mut]/TP53[mut] (3.07±1.61) and EGFR_KRAS[wt]/TP53[mut] (2.20±1.40; p<0.0001).

      KRAS[mut], like EGFR[mut], is associated with female gender but only KRAS[mut] is prognostic following curative-intent resection. Elevated mutation burden observed among KRAS[mut]/TP53[mut] may offer novel therapeutic options following recurrence.