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U. Yılmaz



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    P1.03 - Poster Session with Presenters Present (ID 455)

    • Event: WCLC 2016
    • Type: Poster Presenters Present
    • Track: Radiology/Staging/Screening
    • Presentations: 1
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      P1.03-070 - The Impact of Advances in Systemic Staging on the Rate of Metachronous and Synchronous Metastases in Patients Lung Cancer (ID 4335)

      14:30 - 15:45  |  Author(s): U. Yılmaz

      • Abstract
      • Slides

      Background:
      To quantify the impact of advances in systemic staging (i.e. from CT-based to PET-based over the last ≈ 20 years) on the rate of distant metastases detected at their time of initial diagnosis (synchronous) and sometime after initial diagnosis (metachronous) in patients with lung cancer.

      Methods:
      The Surveillance, Epidemiology, and End Results (SEER) data base, representing 10 % of the US population was used to analyze lung cancers from 1988-2008. (a) The fraction of patients with overt synchronous metastases at diagnosis was noted. (b) Among patients without overt metastasis at diagnosis, their 5-year mortality rate was taken as an estimate of their rate of metachronous metastasis (as most deaths were due to distant metastases). (c) The overall rate of metastases (synchronous + metachronous) amongst all patients was computed. (d) The fraction of all metastases detectable at initial diagnosis (synchronous / [synchronous + metachronous]) was computed. Rates were computed for patient cohorts diagnosed in different time intervals from 1988-2008, to reflect the use of different systemic staging methods over the 20-year interval.

      Results:
      (a) The rate of synchronous metastatic disease slowly increased from ≈ 53% in the earlier years to ≈ 55% in 2008. (b) Among patients without overt metastasis at diagnosis, the rate of metachronous metastatic disease slowly decreased from ≈ 73% in the earlier years to ≈ 62% in 2008. (c) If one assumes that most of the metachronous metastatic lesions were present (but covert) at the time of the initial diagnosis of the primary disease, then one can estimate that ≈ 83-87% of patients have micro/macro metastatic disease at presentation (this rate is basically unchanged over time, but small changes over time may reflect the impact of systemic chemotherapy). (d) Among all patients with metastatic disease, ≈ 60.4% of metastatic lesions were detectable clinically or with CT at the time of diagnosis in the pre-PET era, vs. ≈ 66.6% of these lesions being detectable clinically or with CT and/or PET in the PET era.

      Conclusion:
      The addition of PET appears to have a small but measurable impact on the rates of synchronous and metachronous metastasis, resulting in stage migration from metachronous to synchronous (i.e. from covert to overt) metastases at the time of diagnosis. The addition of PET to the pre-treatment evaluation increases the ability to detect metastatic disease by ≈ 6% (from 60.4 to 66.6%).

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    P1.06 - Poster Session with Presenters Present (ID 458)

    • Event: WCLC 2016
    • Type: Poster Presenters Present
    • Track: Advanced NSCLC
    • Presentations: 1
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      P1.06-038 - Survival and Prognostic Factors of Oligometastatic Non-Small Cell Lung Carcinoma: A Single Center Experience (ID 5283)

      14:30 - 15:45  |  Author(s): U. Yılmaz

      • Abstract

      Background:
      In patients without targeted mutations platinum-based chemotherapy is still current treatment method with a median survival rates of 8-11 months. Patients with single side oligo-metastatic disease should be consider for curative aggressive therapies for both primary and metastatic sides for better survival (NCCN 2016).

      Methods:
      Totally 19 oligo-metastatic NSCLC patients was evaluated retrospectively by using hospital database. All patients had single metastatic side.

      Results:
      Among 19 eligible patents there was male predominance (n= 16, 84.2%). Eight patients had co-morbidities requiring regular medication. Histopathological, there were 13 (68.4%) adenocarcinoma and 6 (31.6%) non-adenocarcinoma. While brain was the most common site for metastasis 10 (52.6%), it was followed by bone (n=6, 31.6%). Treatments for primary tumour side were surgery (n=6, 31.7%), concurrent CRT (n=5, 26.3%) and sequential CRT (n=1, 5.3%). Median follow-up for whole cases were 59.1 weeks. Median overall survival (OS) and progression free survival (PFS) were 140 (±33.7) and 76 (±24.2) weeks respectively. Progressions were observed mostly in 45.4. week. Univariate cox regression analyses for OS and PFS is indicated in Table 1. Clinical T and N staging had significant relation with OS (p=0.02 and 0.03 respectively). There was no relation between bone or brain metastasis and histopathology, gender, clinical T and N staging. Median survival after first progression (SAFP) was 63 weeks (±SS 29.05). Among study parameters only clinical T staging had significant relation with SAFP (p=0.026). Median SFAP was better in patients with progression of primary tumour however median OS was better in patients with progression of distant metastasis (p>0.05).

      Factor OS PFS
      Hazard Ratio p Hazard Ratio p
      Age (cut-off=65) 1.034 (0.18-5.1) 0.96 0.4 (0.1-2.2) 0.3
      Co-morbidity 2.3 (0.54-9.8) 0.24 3.4 (0.8-14) 0.07
      Brain Metastasis 0.88 (0.21-3.6) 0.86 1.5 (0.42-5.45) 0.52
      Histopathology (adeno vs non-adeno) 0.22 (0.03-1.4) 0.10 0.67 (0.16-2.8) 0.6
      Bone Metastasis 1.78 (0.43-7.31) 0.42 1.7 (0.47-6.6) 0.4
      pN Staging (n0 and N1-2) 0.12 (0-173) 0.21 0.94 (0.22-4.02) 0.94
      cT Staging 2.17 (1-4.7) 0.02 1.11 (0.73-1.81) 0.54
      cN Staging (n0 and N1-2) 2.3 (0.86-6.6) 0.03 1.77 (0.79-3.97) 0.1
      Non-surgical curative treatment 1.88 (0.41-8.52) 0.42 1.9 (0.50-7.38) 0.34
      Surgery 0.31 (0.06-1.65) 0.14 0.21 (0.02-1.78) 0.09


      Conclusion:
      Even oligo-metastatic NSCLC means stage 4 of disease, curative treatment approaches for both primary and metastasis sides can increase patients’ prognosis than other stage 4 cases. Similar to the existed retrospective studies we had OS more than 2 years and PFS more than 1 year.

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    P2.02 - Poster Session with Presenters Present (ID 462)

    • Event: WCLC 2016
    • Type: Poster Presenters Present
    • Track: Locally Advanced NSCLC
    • Presentations: 1
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      P2.02-005 - A Rare Clinical Presentation Of EGFR-Mutant Non-Small Cell Lung Cancer With Oligo-Acrometastasis (ID 5278)

      14:30 - 15:45  |  Author(s): U. Yılmaz

      • Abstract

      Background:
      44% of acrometastasis are originated from primary lung tumors and metastasis to digits is seen in 0.2% of patients with lung cancer. After clinical staging, amputation or radiotherapy are most often therapeutic options for pain palliation. We want to present an oligo-acrometastasis of fourth proximal phalanx of left hand from EGFR-mutant non-small cell lung cancer.

      Methods:
      A 58-year-old man was admitted with pain and swelling in fourth finger of his left hand (Figure 1A). Magnetic resonance imaging (MRI) of left upper extremity showed a destruction by a soft tissue measuring about 30x17 mm on the distal part of fourth proximal phalanx of left hand (Figure 1B-C). Three phase bone scan with technetium-99m methylene diphosphonate (MDP) revealed increased radiotracer uptake in the fourth finger. Diffuse increased uptake is seen at the left wrist secondary to the old fracture and trauma in both blood pool and metabolic phases and hypertrophic osteoartropathy in both tibia (Figure1E-F). Computed thorax tomography (CTT) revealed a 25x21 mm lobulated contour lesion in the posterior segment of right lower lobe (Figure 1H). CT-guided biopsy was performed and pathological examination showed non-small cell lung carcinoma-not otherwise specified (NSCLC-NOS). A 24x27x24 mm mass with SUV-max value 9.85 in the right lower lobe, right tracheobronchial and right hilar lymphadenopathies 13 mm in diameter was detected (SUV-max: 7.51) on PET-CT. Patient was staged as T1bN2M1b with oligoacrometastasis. Figure 1



      Results:
      His finger was amputated from metacarpophalangeal level and surgery margin was negative for tumour. Pathological diagnosis was metastatic NSCLC-NOS harbouring EGFR-21L858R mutation. After curative treatment of acrometastasis, concurrent chemo-radiotherapy was planned for primary lung cancer as a therapeutic approach. He is still under treatment.

      Conclusion:
      Oligometastatic disease by acral involvement in NSCLC is extremely rare. Curative treatment approach should be consider for both primary tumour and metastasis side.

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    P2.06 - Poster Session with Presenters Present (ID 467)

    • Event: WCLC 2016
    • Type: Poster Presenters Present
    • Track: Scientific Co-Operation/Research Groups (Clinical Trials in Progress should be submitted in this category)
    • Presentations: 1
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      P2.06-044 - Frequency of Mutations and Related Factors in Lung Adenocarcinoma Cases in Turkey (ID 5291)

      14:30 - 15:45  |  Author(s): U. Yılmaz

      • Abstract
      • Slides

      Background:
      Epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK) and c-ros oncogene 1 receptor tyrosine kinase (ROS1) gene mutations in lung adenocarcinoma (LA) cases give an opportunity to use some of targeted therapy agents. The aim of this study is to obtain EGFR, ALK and ROS1 gene mutation frequencies in Turkey and to examine the factors affecting these frequencies.

      Methods:
      EGFR, ALK, ROS1 mutation analyses were examined in a total of 971 LA cases; 745 men (76.7%), and 226 women (23.3%) diagnosed in 12 hospitals from different districts of Turkey were enrolled in the study. The demographic characteristics, smoking status, asbestos exposure history, radiological findings associated with asbestos exposure (AE) were investigated with relation to the frequencies of EGFR, ALK and ROS1 gene mutations. In the univariate analysis of the study data chi-square and t-tests were used. To determine the independent factors associated with gene mutations, multivariate logistic regression model was created with the variables that give p <0.10 level of significance in univariate analysis.

      Results:
      The mean age of 971 patients was 60.8±9.8 years (range:23-91). Smoking rate was 92.6% in men, 42.5% in women (p<0.001). The number of patients with AE history was 279 (28.7%) and the number of patients with radiologic findings associated with AE was 114 (11.7%). The frequencies of EGFR, ALK and ROS1 mutations were 15.9% (152/956), 3.3% (26/768) and 1.6% (6/379), respectively. Female patients were more likely to have EGFR mutations compared with male patients (37.8% versus 9.3%; p<0,001). Never-smokers had higher incidence of EGFR mutations than smokers (39.6% versus 10.3%; p<0.001). The patients with radiological findings of AE had a 24.6% rate of EGFR mutations compared with a 14.7% rate of patients with no radiological findings (p=0.007). ALK rearrengement was detected in patients with younger age, having history of AE or radiological findings associated with AE (11.1%; p<0.001, 5.9%; p=0.014, 6.7%; p=0.044, respectively). No associated factor was found with ROS1 fusion frequency.

      Conclusion:
      To have a relationship between radiographic findings associated with AE or AE history and EGFR and ALK mutation frequencies is an original finding. The obtained results will be useful in the discussion of standards of treatment with the new agents and pathogenesis. *This study was carried out through the project named as “Network cooperation for the management of environmental and occupational exposure to mineral fibers induced pulmonary pathologies” which was supported by General Directorate of Health Researches, Republic of Turkey, Ministry of Health.

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    P3.03 - Poster Session with Presenters Present (ID 473)

    • Event: WCLC 2016
    • Type: Poster Presenters Present
    • Track: Mesothelioma/Thymic Malignancies/Esophageal Cancer/Other Thoracic Malignancies
    • Presentations: 1
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      P3.03-052 - Diagnostic Utility of Mesothelin, Osteopontin and Megakaryocyte Potentiation Factor in Turkish Patients with Malignant Mesothelioma (ID 4864)

      14:30 - 15:45  |  Author(s): U. Yılmaz

      • Abstract
      • Slides

      Background:
      Malignant mesothelioma (MM) is an agressive tumor with poor prognosis, thus early assessment is important. We investigated the presence of mesothelin, osteopontin and megakaryocyte potentiation factor (MPF) levels in both sera and pleural effusions of MM patients and compared to the lung cancer, other malignancy, exudative and transudative effusions.

      Methods:
      Patients were enrolled into 5 study groups as demonstrated in table 1. Serum and pleural mesothelin, osteopontin and MPF levels of study groups were measured with enzyme-linked immunosorbent assay and compared with using convenient statistical methods.

      Results:
      Figure 1 Figure 2 Mesothelin and osteopontin levels in both sera and pleural effusions were found to be statistically different among groups (Table 1). Pleural mesothelin and osteopontin levels were significant parameters to differentiate MM from the other groups (p=0.0001; p=0.002 respectively). When cut off value of pleural mesothelin level was set at 169.6ng/mL, sensitivity was 71.4 % and specificity was 88% for MM. When cut off value of pleural osteopontin level was set at 521.25ng/mL, sensitivity was 64.3% and specificity was 80% for MM (Figure 1). Pleural but not sera MPF level of MM patients was significantly higher than patients with lung cancer (p=0.021).





      Conclusion:
      Mesothelin, osteopontin and MPF levels can be used as diagnostic bio-markers to detect MM.

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    SC23 - The Importance of Co-Operative Groups (ID 347)

    • Event: WCLC 2016
    • Type: Science Session
    • Track: Scientific Co-Operation/Research Groups (Clinical Trials in Progress should be submitted in this category)
    • Presentations: 1
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      SC23.03 - How Could High-Volume Centers in Developing Countries Access Cooperative Group Trials? (ID 6696)

      16:00 - 17:30  |  Author(s): U. Yılmaz

      • Abstract
      • Presentation
      • Slides

      Abstract:
      Lung cancer has the second highest absolute incidence globally as well as in developing countries and ranks fourth in developed countries. It is the most common cause of cancer death by absolute cases globally as well as in developing and developed regions. The economic burden of lung cancer care is highest relative to other cancers in the European Union. Research is at the core of achieving improved outcomes from cancer, be it in defining country-specific epidemiology of the disease, understanding the pathogenesis of disease, identifying new targets for therapeutic agents, or directing policy to achieve affordable and equitable outcomes. Cancer researchs are one of the most globally active domains of science, with more than $14 billion per annum. A critical part of the health research portfolio is the testing of interventions through randomized controlled trials. Trials can range from highly controlled explanatory trials through to pragmatic trials of new health technologies and models of service delivery. Recruitment problems also have practical and financial impacts, as they can delay completion of research or reduce its timely impact on patient health and wellbeing. Achieving appropriate levels of patient and professional participation has been a significant obstacle to evidence-based practice. Published data show that the minority of trials recruit successfully, either in terms of reaching their planned sample size, or delivering the planned sample in the expected recruitment window Despite all the diffuculties, clinical trials have become increasingly globalized due to the inclusion of more non-traditional locations, especially those in central and eastern Europe, Latin America, and Asia. The increased globalization of clinical research has arisen for several reasons, but primarily due to the need for faster and more economically efficient studies. Moves towards standardizing and harmonizing clinical research practices have facilitated the rise of globalized clinical research. However, the expansion of multinational clinical research peaked in 2009, which could reflect that the large-scale expansion of multinational clinical research effort has reached its global capacity. When the distribution of multinational clinical trials is examined after being stratified according to the condition or disease, lung cancer is not among the five most frequently studied conditions apart from Asia. The results of a bibliometric analysis of global research on lung cancer between 2004-2013 in the 24 leading countries in cancer research showed that despite a doubling of the volume of lung cancer research worldwide between 2004 and 2013, it still only accounts for a small proportion of the overall oncology research publication output (5.6%). In fact, the relative commitment (RC) to lung cancer research compared with that to total oncology research output has fallen in most countries during this period, including in the 23 countries with exception of the China. Turkey, Poland, Canada, Greece, and the United States, despite having the highest country-specific burden of lung cancer, have all seen a decrease in their RC to lung cancer research. Research from Norway, Austria, Switzerland, Belgium, and Sweden had the highest proportion of international contributors . By comparison, relative to their research output, the East Asian countries (Taiwan, India, the Republic of Korea, and Japan) and Turkey had the least amount of international collaboration. With regard to multinational studies, only 1.2% of articles had collaborators from five or more countries and 0.3% from 10 or more countries. The aim of co-operative groups in oncology is to perform multi-center clinical trials for cancer research. Research results are often conveyed to the worldwide medical community through scientific publications. In order to complete the trials within the period specified, it is obvious the need of the qualified and high-volume cancer centers. The barriers to participation of high-volume hospitals in the cooperative group trials should be determined and eliminated. Since the 1970s, centers for thoracic diseases that emerged from former tuberculosis hospitals, particularly in Europe, have focused on the diagnosis and treatment of patients with lung cancer. Traditionally, these centers were staffed by pulmonologists and thoracic surgeons, but now include an extended range of health care workers including the disciplines of radiation oncology, medical oncology, palliative care and rehabilitation medicine. These high-volume centers treat all aspects of problems affecting patients with lung cancer. In 2010, the hospitals with a median 400 new patients per year were in Albania, Belarus, Bulgaria, the Czech Republic, Poland, Romania and Slovenia. The hospitals with more than 1000 new patients with lung cancer per year were in Poland, Bulgaria, Croatia, Turkey. We have to foster the cooperative study groups in lung cancer to provide collaboration between study group and these hospitals. High-volume hospitals should be identified and hospital-based representatives should be determined. Supreme organisations as European Thoracic Oncology Platform providing collaboration among study groups and hospitals, should be able to invite the high-volume hospitals with site evaluation. These high-volume centers have to review whether adequately equipped and set up or not for participation in research projects and clinical trials. References 1- Gaga M. An Official American Thoracic Society/European Respiratory Society Statement: The role of the pulmonologist in the diagnosis and management of lung cancer. Am J Respir Crit Care Med 2013; 188(4): 503-7. 2- Blum T. G. The European initiative for quality management in lung cancer care. Eur Respir J. 2014; 43: 1254-77 3- Loddenkemper R, 100 years DGP-100 years of pneumology in Germany. Pneumologie 2010; 64:7-17. 4- Richter TA. Clinical research: A globalized network. PLoS ONE 2014; 9(12): 1-12 5- Aggarwal A. The state of lung cancer research: A global analysis. J Thorac Oncol 2016; 11(7): 1040-50

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