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A. Izadifar



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    P1.03 - Poster Session 1 - Technology and Novel Development (ID 150)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Biology
    • Presentations: 1
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      P1.03-005 - High throughput array and sensitive mass spectrometry technology applied to Transbronchial Needle Aspiration allow the (detection of hundreds molecular targets) tumor profiling for routine care personalized medicine (ID 2432)

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

      • Abstract

      Background
      The personalized therapies against specific genetic targets in tumoral cells like EGFR mutations or EML-ALK translocation, or the development of minimized invasive procedures for diagnosis and cancer staging have dramatically improved the outcome of patients with lung cancer. The combination of the wide use of Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration (EBUS-TBNA) and genetic testing to individually tailor chemotherapy should become the standard of care. However, the rapid evolution of personalized medicine is toward the routine testing of high number of biomarkers per patient. Therefore, we have tested whether the recently developed DNA arrays and multiplex technologies could increase the suitability of very small size biopsies performed by EBUS-TBNA for the high-throughput molecular diagnosis

      Methods
      Fourty consecutive EBUS TBNAs with histologically diagnosed lung adenocarcinoma were tested using the high throughput array and sensitive mass spectrometry technology (Massarray, Sequenom) for the detection of 216 mutations in 26 cancer genes (Lungcarta).Each of the 40 DNAs extracted from only one 19- to 22-gauge needle aspiration spread on a glass slide per patient has been successfully amplified and analyzed within one-day experiment for all of the 238 mutations

      Results
      Five patients (12.5 %) exhibited EGFR mutations and received either gefitinib or erlotinib, 1 of them exhibiting the T790M resistance mutation. One patient had the BRAFV600E mutation confirmed 1-y later on a skin metastasis and thus entered a phase II trial to receive anti-BRAF therapy. There were EBUS-TBNA exhibiting mutations in KRAS (n=7), PI3K (n=1) and cMET (n=1), and insertion in HER2 (n=2).

      Conclusion
      In conclusion, only one 19-22 gauge needle aspiration is suitable in routine care for the detection of at least 238 mutations, to guide treatment decisions and offer patients to benefit from current and future individually targeted drugs

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    P1.24 - Poster Session 1 - Clinical Care (ID 146)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Supportive Care
    • Presentations: 1
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      P1.24-046 - How are treated French patients with metastatic lung adenocarcinoma with "uncommon" EGFR mutations? How could we do better? (ID 3109)

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

      • Abstract

      Background
      The progression-free survival and response rate of patients with EGFR-mutant tumors treated with an EGFR TKI has been reported to be superior to standard chemotherapeutic regimens. These mutations, concentrated in the exons 18 to 21 encoding the tyrosine kinase domain of the receptor. However, TKI sensitivity depends upon the nature and location of the mutations. Eighty to 90% of all lung adenocarcinoma-associated EGFR mutations are short, in-frame deletions in exon 19 and the exon 21 point mutation L858R; 70% of tumors with the latter mutations respond to treatment with the EGFR TKIs. The remaining 10 to 20 % of EGFR mutations include several additional point mutations that can be considered as "uncommon mutations". Their identification is problematic for therapeutic decision. Indeed, it remains unclear whether these mutations have benefit upon progression-free or overall survival. Therefore a comprehensive strategy is required to prioritize treatment decisions by physicians in the routine clinical practice.

      Methods
      By retrospectively analyzing mutational data of 3,200 consecutive patients with metastatic lung adenocarcinomas diagnosed for EGFR mutational status, we have identified those whose tumors had uncommon mutations (mutations that were neither base pair deletion in exon 19 nor the L858R in exon 21). We have contacted the physicians in charge of these patients and asked them the individual therapeutic decision. We have also questioned them about the level of their knowledge on the sensitivity of uncommon mutations to TKIs and how to improve this knowledge.

      Results
      Out of 3,200 metastatic lung adenocarcinomas, 351 tumors (11%) exhibited abnormalities in the exons 18 to 21. Of these 351 EGFR mutated tumors, 171 (48.7%) were base pair deletions in the exon 19: and 129 (36.7%) were the L868R in the exon 21. The 14.5 % remaining tumors showed "uncommon" mutations. There were G719 to A, C, or S mutations in 18 patients (5%), the L861Q mutation in 14 patients (3%) and only 1 Ins 18 pb in the exon 19. In exon 20, the T790M mutations were found in 4 tumors and in-frame insertions of varying lengths that confer resistance to TKI in 2 patients. Ten additional mutations, most of them being double mutations, were observed in 12 patients (3.4%). Of the 51 patients with uncommon mutations, 15 (29%) have received gefitinib or erlotinib whereas at least 32 patients should have received anti-EGFR therapies. Reasons for this difference were 1) the lack of knowledge of the sensitivity of rare mutations, and mostly double mutations, 2) the difficulty of finding the answer, either on the record or in the scientific literature, 3) the possibility of introducing a platinum-based chemotherapy, 4) the lack of experience of the theranostic which includes many gene mutations.

      Conclusion
      Opportunities for improvement could be: 1) better information on the medical report when there is scientific evidence suggesting sensitivity or resistance of the rare mutation. 2) in parallel, a more accurate information on the lack of knowledge on the sensitivity or resistance, 3) a website for quick access to this type of information and changes along with the knowledge evolution.