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F. Popovic



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    P1.07 - Poster Session with Presenters Present (ID 459)

    • Event: WCLC 2016
    • Type: Poster Presenters Present
    • Track: SCLC/Neuroendocrine Tumors
    • Presentations: 2
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      P1.07-013 - Treatment Related Side Effects of Oral Topotecan in Small Cell Lung Cancer (ID 5000)

      14:30 - 14:30  |  Author(s): F. Popovic

      • Abstract

      Background:
      Lung cancer is the most common tumor in men and the second most common tumor in woman according to the latest data available from the Croatian National Cancer Registry. Approximately 20% of all lung cancers are categorized as small cell lung cancer (SCLC). Topotecan is recommended as second-line chemotherapy in treatment of SCLC. Topotecan can be administrated orally with the same effectiveness as parenteral.

      Methods:
      The aim of this study was to determine toxicity of oral topotecan in second line of chemotherapy and to establish the frequency of drug related admissions.

      Results:
      A total of 177 courses of therapy were administered to the 64 patients, 17 woman and 47 men, with SCLC patients ranging from 42 to 77 years with the mean age of 59.3. All the patients were treated in University Hospital Centre Zagreb from January 2012 to October 2015. Included patients had ECOG performance status of 0 or 1. Topotecan was administrated every 21 day, at the dose of 2.3 mg/m[2]/day, during 5 days. Average number of courses received was 2.8. Of all included patients 17 of them (26.5%) were admitted to hospital because of adverse events related to topotecan administration. The majority of patient hospitalizations (11 patients, 16.9%) was due to febrile neutropenia. Other reasons for hospitalization were severe diarrhea in 4 patients (6.2%), pneumonia in 1 patient (1.5%) and severe electrolyte imbalance in 1 patient (1.5%). Of 17 admissions to hospital 10 (58.9%) of them were after application of first chemotherapy cycle, 3 (17.6%) after second cycle and 4 (23.5%) after third cycle. Quantitative hematologic toxicities were assessed using the National Cancer Institute Common Toxicity Criteria. Anemia grade 3 or 4 occurred in 13 patients (20.3%). Grade 3 or 4 thrombocytpenia occurred in 7 patients (10.9%). Grade 3 or 4 neutropenia occurred in 16 patients (25%). Of other, non-hematologic adverse effects the most serious was grade 3 or 4 diarrhea that occurred in 5 patients (7.8%).

      Conclusion:
      although admission of oral topotecan is well tolerated it is related with high rate of hospitalizations due to myelotoxicity and gastrointestinal toxicity during therapy.

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      P1.07-051 - Incidence and Clinical Characteristics of Pulmonary Large-Cell Neuroendocrine Carcinoma: An Overview of Our Own Data (ID 6188)

      14:30 - 14:30  |  Author(s): F. Popovic

      • Abstract
      • Slides

      Background:
      Pulmonary neuroendocrine tumors are a heterogenous group of neoplasms. They are clasified into four histological types: typical carcinoid, atypical carcinoid, small-cell lung cancer (SCLC) and large-cell neuroendocrine carcinoma (LCNEC). They represent about 20% of all lung cancers. The most frequent one is small-cell lung cancer with incidence about 15%. In contrast, large-cell neuroendocrine carcinoma is an orphan disease with estimated incidence between 2.1% and 3.5%. Because of many diagnostic difficulties, LCNEC is considered to be of a higher frequency. It is lung neuroendocrine tumor, but it is also a type of non small-cell lung cancer (NSCLC). So its features overlap with both of these groups. However, the clinical behavior of LCNEC is very similar to SCLC and so new term high-grade neuroendocrine carcinoma (HGNEC) is in use.

      Methods:
      We retrospectively analysed patients diagnosed with cancer at our department between January 1, 2012 and December 31, 2014, with special focus on pulmonary neuroendocrine tumors. We examined incidence of different histologic types of pulmonary neuroendocrine tumors and sorted out patients with diagnosis of large-cell neuroendocrine carcinoma. We also analysed clinical characteristics of patients with LCNEC.

      Results:
      During the three-years period 1242 pulmonary patients were admitted to our department. Among them there were 726 newely diagnosed cancer patients. Various types of lung cancer were found in 652 patients. There were 104 patients with pulmonary neuroendocrine tumors, what makes about 16%. Thirteen of them (2%) were „pure“ LCNEC , 16 (2,5%) mixed LCNEC with small-cell component, 68 SCLC (10%), 4 atypical carcinoid, 2 typical carcinoid and 1 typical carcinoid in patient with adenocarcinoma. Generally in our patients high-grade neuroendocrine tumors make about 15%, and low-grade neuroendocrine tumors (carcinoides) make only 1% of all lung cancers. Most patients diagnosed with LCNEC were men over 50 years, heavy smokers, which is consistent with published data, but one patient was a 40-year-old woman.

      Conclusion:
      Pulmonary neuroendocrine tumors are group of neoplasms classified into four categories based on their patohistology. Three of them (carcinoides and LCNEC) are rare tumors. LCNEC is type of neuroendocrine tumor with most diagnostic and therapeutic difficulties. Clinical features of our patients are similar to previously published, while incidence is slightly lower.

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    P2.03b - Poster Session with Presenters Present (ID 465)

    • Event: WCLC 2016
    • Type: Poster Presenters Present
    • Track: Advanced NSCLC
    • Presentations: 1
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      P2.03b-009 - Brain Metastasis and Epidermal Growth Factor Receptor Mutations in Croatian Caucasians with Lung Adenocarcinoma (ID 5182)

      14:30 - 14:30  |  Author(s): F. Popovic

      • Abstract
      • Slides

      Background:
      The brain is a common site of metastasis in non-small cell lung cancer (NSCLC). The aim of this study was two-fold: 1) to determine the incidence of brain metastasis (BM) in Caucasian lung adenocarcinoma patients with epidermal growth factor receptor (EGFR) mutations and 2) to evaluate the frequencies and potential relationship of the different EGFR mutations with BM.

      Methods:
      A retrospective cohort study was conducted at a Croatian tertiary hospital (Clinic for Respiratory Diseases “Jordanovac”) using data collected from medical records. Caucasian patients with primary NSCLC who were tested for EGFR mutation status between January 2014 and October 2015 were included.

      Results:
      Of 1040 NSCLC samples tested, 122 (11.7%) patients with lung adenocarcinoma harboured EGFR mutations; six EGFR positive (+) patients (four with BM) had repeat EGFR testing. The majority of EGFR mutants were females (n= 90, 77.6%), non-smokers (including never-smokers and former-smokers; n= 95, 92.2%), diagnosed with advanced disease (stage IIIB/IV) at first presentation (n= 75, 68.8%), and median age at initial diagnosis of primary lung cancer was 65 years (35 - 90). Twenty-three (19.8%) of 116 EGFR+ patients were diagnosed with BM; for six EGFR+ patients, data about BM was missing. Most were 64 years of age or younger (n= 15, 65.2%) at diagnosis of BM (median age: 62 years, 48 - 72). Synchronous BM disease at initial diagnosis of lung cancer was found in 43.5% of EGFR+ patients with BM (n= 10). There were more EGFR+ women with BM (n= 20, 87%) than men. Single exon 19 deletion and exon 21 L858R mutations were the most common subtypes in both EGFR+ patients without BM (n= 44, 47.3% and n= 27, 27.8%, respectively) and with BM (n= 13, 56.5% and n= 5, 21.7%, respectively). One BM patient (4.3%) had a double mutation (exon 19 and 21), while six non-BM patients (6.2%) had simultaneous pairings, most commonly between exon 19 and 20 (n=3, 3.1%). Although exon 18 mutations were seen in six patients without BM (6.2%), none were found in BM+EGFR+ patients. Exon 20 T790M mutation occurred in 17.4% of BM patients (n= 4) versus 15.3% of non-BM patients (n= 15). Rare EGFR double mutations (exon 18 and 20) were found in two non-BM patients (2.2%).

      Conclusion:
      Larger long-term prospective studies to explore and confirm these results in BM+EGFR+ patients are warranted. In the era of precision oncology, molecular testing of EGFR mutations may further clarify the pathogenesis of lung cancer-associated BM.

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    P3.02c - Poster Session with Presenters Present (ID 472)

    • Event: WCLC 2016
    • Type: Poster Presenters Present
    • Track: Advanced NSCLC
    • Presentations: 1
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      P3.02c-019 - The Use of Metformin and the Incidence of Metastases at the Time of Diagnosis in Patients with Lung Cancer and Type 2 Diabetes (ID 6116)

      14:30 - 14:30  |  Author(s): F. Popovic

      • Abstract

      Background:
      Lung cancer is often insidious disease. It usually produces only a few symptoms until the disease is advanced. At initial diagnosis 20% of patients have localized disease, 25% of patients have regional metastasis and 55% of patients have distant spread of disease. Metastasis is a process by which a small number of cancer cells undergo numerous alterations, which enables them to form secondary tumors at another and often multiple sites in the host. Recently, studies have suggested that cancer stem cells are the originators of metastasis. Cancer stem cells are small populations of slowly dividing, tretment – resistant , undifferentiated cancer cells that are being discovered in a different cancers. Metformin has proved to be effective in the treatment of glioblastomas and neuroblastomas, in vitro, by targeting their cancer stem cell population. Recently, studies have shown that metformin use is not associated with a decreased risk of lung cancer in patients with type 2 diabetes, but it has been suggested that metformin use is associated with improved survival among patients with stage IV NSCLC patients.

      Methods:
      The aim of our study was to compare incidence of metastasis in lung cancer patients (NSCLC and SCLC) that were treated with metformin and patients with lung cancer that were not treated with metformin. It is a retrospective analysis of lung cancer patients diagnosed at our department between January 1, 2012 and December 31 2013. and data were collected from our computerized base.

      Results:
      During the two-year period in our department there were 335 newly diagnosed lung cancer patients. Among them there were 25 (7%) patients with diabetes mellitus that were on therapy with metformin prior to lung cancer diagnosis for at least six months. We have proved significant difference between two groups in the incidence of patients with distant spread of disease (stage IV) at the time of diagnosis. Metformin group had a lower inicidence of stage IV at the time of diagnosis ( 44% vs 64%; x2 =4.14; p=0.041). The results did neither revealed a significant difference in total number of patients with distant spread nor in the type of metastasis.

      Conclusion:
      We have shown that patients that were treated with metformin had lower incidenece of distant metastases at the time of diagnosis. Further research should evaluate biologic mechanisms and test the effect of metformin on inhibiting the cancer spread in prospective clinical trials.