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W. Olszewski



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    P1.02 - Poster Session 1 - Novel Cancer Genes and Pathways (ID 144)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Biology
    • Presentations: 1
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      P1.02-016 - Non-small cell lung cancer and EGFR mutation in Poland - preliminary results from single institution study (ID 3239)

      09:30 - 16:30  |  Author(s): W. Olszewski

      • Abstract

      Background
      Lung cancer is the first cause of death among all cancers in the world and every year more than 1.6 million patients die from lung cancer. In Polish population morbidity and mortality from lung cancer persist in the first location and amount respectively 21.4% and 31.2% of all cancers. Over the last 30 years the development of targeted therapy significantly influenced the routine practice in pathology. The treatment based on identification of the type of tumor is still crucial information however the importance of predictive or prognostic molecular markers has become significant step in the choice of treatment. Identification of mutations in the EGFR gene in non-small cell lung cancer (NSCLC) fully illustrates the impact of molecular biology in treatment decisions. The use of one of the small molecule tyrosine kinase inhibitors, gefitinib or erlotinib depends on confirmation presence of activating somatic EGFR mutation.

      Methods
      The aim of the study was to evaluate the EGFR mutations in two types of material cytological and histological. 189 histological, paraffin-embedded materials as well as 12 fresh and 72 fixed cytology specimens obtained by trans-thoracic, computed tomography supported biopsy or during bronchofiberoscopy were included. Material and methods. 273 patients with confirmed NSCLC were entered into the study. Each specimen contained at least 50% of tumor cells. The macrodissecion was performed on histological specimens to maximize tumor cells content. DNA was extracted from both types of material and the EGFR mutation was analyzed in exons 18, 19 20 and 21 using the direct sequencing method

      Results
      The mean age of patients was 61.5 years (range 25 – 84 years) with males predominance (151 males vs. 122 females). The histological types included: adenocarcinoma 186 (69%), squamous cell carcinoma 44 (16%), NSCLC, not-otherwise specified 30 (11%), large cell carcinoma 9 (3%) and adenosquamous carcinoma 4 (1%). Both types of material were equally sufficient to evaluate EGFR mutations. The ratio of molecularly non-diagnostic material due to DNA degradation or too scant DNA probe was respectively for cytological and histological material 1.2% vs. 4.75% (p<0.01). The percentage of EGFR somatic mutations were 10.62%. Females suffered more frequently from adenocarcinoma (females 70.49% vs. males 66.23%, p <0.01) and had significantly higher rate of EGFR mutations (females 17.21% vs. males 3.97%, p<0.01). Mutations in exons 21 and 19 together accounted for 87% of all types of mutations of the EGFR gene. Apart from these, two patients had co-existence of activating/inhibiting mutations: L858R (exon 21) with T790M (exon 20) and G719C (exon 18) with S768I (exon 20).

      Conclusion
      This study allows for the first time to estimate an EGFR mutation frequency in Polish population. Moreover the results have strengthened the importance of reusing cytological material in molecular evaluation. Cytological material recovered from fixed preparations and stained with hematoxylin and eosin showed comparable DNA quality to fresh tumor cells. The cytology especially fine needle aspirates as well as small biopsy material provide molecular biological information which is a key issue for the targeted treatment options.

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    P2.11 - Poster Session 2 - NSCLC Novel Therapies (ID 209)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Medical Oncology
    • Presentations: 1
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      P2.11-018 - EGFR mutations in NSCLC patients in Central Europe: the INSIGHT observational study (ID 1635)

      09:30 - 16:30  |  Author(s): W. Olszewski

      • Abstract

      Background
      Central European countries are among those with the highest incidence rates of lung cancer and most of these cancers are smoking-related. The INSIGHT observational study aimed at assessing prevalence and treatment of patients with EGFR mutations in clinical practice in Central Europe. Here we report on the overall findings of this study.

      Methods
      Patients with NSCLC and tested for EGFR mutations between 15 November 2011 and 31 March 2013 in 14 centers from 6 Central European countries (Austria, Czech Republic, Hungary, Poland, Slovakia, Slovenia) were enrolled. EGFR mutations were determined by sequencing, PCR or other techniques.

      Results
      Here we report data on 1009 NSCLC patients who had been enrolled into the INSIGHT study. The patients had the following characteristics: median age 64 (range 29-93), 62% male, 38% female, 99.9% Caucasians, ECOG performance status 0-1, 2 and 3-4 in 79%, 17% and 4%; 19% never-smokers, 46% former smokers, 35% current smokers; 79% adenocarcinomas, 2% adenosquamous carcinomas, 7% squamous cell carcinomas, 9% NSCLC NOS and 3% others; tumor stages I-II, III and IV in 15.5%, 24% and 60.5% of the patients. EGFR mutations were found in 163 (16%) patients. Patients with mutations had the following characteristics: age median 66 (range 34-89) years, 46% male, 54% female, 47% never-smokers, 38% former smokers, 15% current smokers; performance status was recorded in 153 patients and was 0, 1, 2 and 3 in 30%, 50%, 14% and 6% of the patients. The mutation-positive tumors had the following characteristics: 85% adenocarcinomas, 4% adenosquamous carcinomas, 4% squamous cell carcinomas, 2% NSCLC NOS, and 5% others. Among patients with mutations, exon 18 mutations were seen in 7% of the patients, exon 19 mutations in 50% of the patients including deletions in 39%, exon 20 mutations in 12%, exon 21 mutations in 39% including L858R in 28% of the patients. Detailed data on systemic treatment were available for 122 patients with advanced EGFR mutation-positive NSCLC and most of these patients received EGFR-directed tyrosine kinase inhibitors during the course of their disease.

      Conclusion
      The INSIGHT observational study demonstrated that EGFR mutation testing has been established in the participating centres in Central Europe. The mutation rate of 16% is on the upper limit of the range seen in Western European countries but a potential selection bias for testing of patients with higher likelihood of harboring EGFR mutations cannot be excluded. Systemic treatment in patients with EGFR mutations is similar to treatment patterns observed in other countries. This study was supported by Boehringer Ingelheim Regional Center Vienna.