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R. Bowman

Moderator of

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    E07 - Staging in the Molecular Era (ID 7)

    • Event: WCLC 2013
    • Type: Educational Session
    • Track: Imaging, Staging & Screening
    • Presentations: 4
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      E07.1 - TNM Classification with Image Guided Interventions Such as EBUS / EUS (ID 403)

      14:00 - 15:30  |  Author(s): F.J. Herth

      • Abstract
      • Slides

      Abstract
      ENDOBRONCHIAL ULTRASOUND The integration of ultrasound technology and flexible fiberbronchoscopy enables imaging of lymph nodes, lesions and vessels located beyond the tracheobronchial mucosa. Developed in 2002, the EBUS-bronchoscope looks similar to a normal bronchovideoscope, but is 6.9mm wide and has a 2mm instrument channel and a 30 degree side viewing optic. Furthermore, a curved linear array ultrasonic transducer sits on the distal end and can be used either with direct contact to the mucosal surface or via an inflatable balloon which can be attached at the tip. This allows a conventional endoscopic picture side-by-side with the ultrasonic view. US scanning is performed at a frequency of 7.5-12 MHz with tissue penetration of 20 – 50mm. An ultrasound processor processes the US image. Procedure: The actual TBNA is performed by direct transducer contact with the wall of the trachea or bronchus. When a lesion is outlined, a needle of 21 gauge (NA-201SX-4022; Olympus Corporation, Tokyo, Japan) can be advanced through the working channel and lymph nodes can be punctured under real-time ultrasound visualisation. At the same time colour Doppler can be used to identify surrounding vascular structures. Once the target lymph node or mass has been clearly identified with EBUS, the needle is inserted under real-time US guidance. Suction is applied with a syringe, and the needle is moved back and forth inside the lesion. Lymph node stations that can be reached via EBUS are the highest mediastinal (station 1), the upper paratracheal (2L and 2R), lower paratracheal (4R and 4L), the subcarinal (station 7), the hilar (station 10) as well as the interlobar (station 11) and the lobar nodes (station 12). The highest staging N should be biopsied first otherwise the needle needs to be changed each time. Results: In recently published meta-analysis EBUS-TBNA has been shown to have a high-pooled sensitivity of 93% and specificity of 100% . Multiple publications have shown that even in patients with lymph nodes under 1cm (which had been termed N0 by CT criteria), with the use of EBUS-TBNA a large percentage could still be shown to have N2/N3 disease (some despite also being negative on PET-CT). Complications such as bleeding or infection are very rare and have only been reported as case reports. Endoesophageal ultrasound Gastroenterologists have been using this technique for many years in the investigation of oesophageal and pancreatic malignancies. Mediastinal EUS-FNAs were first used in the early 1990s and have subsequently become a popular method to diagnose a variety of intra-abdominal and intrathoracic masses, including mediastinal lesion. Procedure The linear EUS-Scope (has the same basic architecture as the EBUS and uses a scanner of between 5 and 10 MHz. The penetrating ultrasound depth can be up to 8cm. Needles used for biopsy are 19 or 21gauge, again equipped with a stylet. The procedure is usually performed on an outpatient basis and takes approx 30min. However, EUS-FNA has limited access as only lymph node stations 2L, 4L, 7, 8 and 9 are accessible through a transesophageal approach. Lymph node station 5 is not routinely accessible via EUS, and may require transvascular FNA.. Results. EUS is especially useful in staging of the posterior mediastinum. Multiple publications and a meta-analysis on EUS-FNA have shown a high sensitivity and specificity. Even in patients without mediastinal lymph node enlargement on CT, EUS-FNA has been able to demonstrate metastases in 25% of lung cancer patients. Also, the left adrenal can be reached and identified in 97% of cases. It has a so-called ‘seagull’ shape on ultrasound and is particularly well visualised in cases of metastatic enlargement. Furthermore, the left lobe of liver can also be reached. The hilar and pre-carinal lymph nodes cannot be reached. EUS is also more accurate and has a higher predictive value than either PET scan or CT for posterior mediastinal lymph nodes. The procedure carries only a very small risk of mediastinitis or bleeding. . For both techniques it´s important to remember, however, that with EBUS and EUS the negative predictive value is limited and therefore samples which do not contain tumour cells require follow up with a more definitive procedure such as mediastinoscopy or VATS. Combining EBUS and EUS For tissue sampling of mediastinal lymph nodes after conventional TBNA, the present authors prefer minimally invasive methods such as EBUS-TBNA and EUS-FNA to more invasive procedures such as mediastinoscopy and VATS. EUS-FNA and EBUS-TBNA have been shown to prevent mediastinoscopies to a large extent. EBUS-TBNA and EUS-FNA have a complementary reach in analysing mediastinal nodes whereby EBUS has access to the paratracheal, subcarinal and hilar regions and EUS to the lower mediastinum and aortopulmonary window. As shown above, EUS and EBUS provide access to different areas of the mediastinum. In combining techniques, most lymph node stations as well as the left adrenal gland can be reached (apart from stations 5 and 6). In six recent series the accuracy of EUS-FNA and EBUS-TBNA used in combination for the diagnosis of mediastinal cancer was 95% . Using the EBUS-Scope for both endobronchial as well as endoesophagel sampling, the sensitivity for cancer detection could be shown to be as high as 96% (EUS 89%, EBUS 91%), specificity 100% and negative predictive value of 96% (EUS 82%, EBUS 92%). CONCLUSION Overall, EBUS and EUS are safe and effective techniques for the staging of the mediastinum. They are minimally invasive and reduce the number of invasive staging procedures. Currently, the main limitation for EBUS and EUS are that they are predominantly performed at centres of excellence and hence only on selected patients. Training of physicians and surgeons remains the issue and performance of an adequate amount of procedures per year is required in order to maintain competency. Reimbursement remains an issue in some countries as well as the actual implementation into cancer guidelines within the hospitals. Increasingly both techniques are being used in hospitals across the world improving the diagnostic yield. Combined EBUS and EUS ought to be regarded as the “first techniques into the mediastinum”, called “complete endo-echo staging”.

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      E07.2 - Image Interpretation and New Adenocarcinoma-Classification (ID 404)

      14:00 - 15:30  |  Author(s): K. Garg

      • Abstract
      • Slides

      Abstract
      There is a widely divergent clinical, radiologic, molecular and pathologic spectrum within lung adenocarcinoma. Remarkable advances in understanding of the genetic mechanisms that underlie lung adenocarcinoma have altered the diagnostic criteria that determine subsequent treatment. The use of the term bronchioloalveolar carcinoma (BAC) encompassed a broad spectrum of tumors ranging from solitary small peripheral lung tumors with a 100% 5-year survival to widespread advanced disease with a 10% 3-5 year survivals, with widely varying use of terminology even after publication of the 2004 WHO Classification. There are also clinical, radiologic, immunohistochemical, and molecular differences that are distinguishable among the subsets of mucinous and non-mucinous types of adenocarcinoma. In 2011, a new Classification of Lung Adenocarcinoma was therefore proposed by the International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society. The 2011 classification addressed three important weaknesses in the previous classification. First, it eliminated the term BAC. Second, it added new terminologies of carcinoma-in-situ, and minimally invasive adenocarcinoma to recognize that minimal invasion (< 5mm). Third, it replaced the terminology of mixed adenocarcinoma. The widespread availability of MDCT and abundance of new information obtained especially from low-dose CT lung cancer screening programs, have increased our understanding of the types and management of small peripheral lung nodules encountered in daily clinical practice, in particular, the importance and prevalence of subsolid pulmonary nodules (atypical adenomatous hyperplasia (AAH), ground glass nodules (GGN) and part-solid nodules). Thin section CT has emerged as a new biomarker for lung adenocarcinoma subtypes. The staging system is based solely on the anatomic extent of the disease. Other factors, such as clinical symptoms or molecular biological characterization of the tumor or attenuation of nodules on CT are not factored in the new TNM classification. Increasing T status reflects tumors that are larger or invasive. In lung cancer nodal staging depends on the location of involved nodes (as opposed to the number of nodes). The M descriptor defines the presence or absence of distant metastatic disease. In 2007, The International Association for the Study of Lung Cancer (IASLC) revised the lung cancer stage groupings based on newer survival data. In the 7[th] edition of TNM classification of lung cancer, following modifications were made: (a) Size cut points, in addition to the 3 cm cut point that traditionally separated T1 and T2 tumors, was introduced at 2, 5, and 7 cm. T1 tumors were now subdivided into T1a and T1b around the 2 cm cut point. T2 tumors were subdivided into T2a and T2b around the 5 cm cut point, and tumors larger than 7 cm. were classified as T3. (b) Cases in which additional tumor nodules are found were reclassified. Those in the same lobe as the primary tumor are now classified as T3, those in the other ipsilateral lobes are T4 and those in the opposite lung are now M1a. (c) Cases associated with pleural or pericardial nodules or effusions were reclassified from T4 to M1a. M1 disease due to distant metastasis was reclassified as M1b. A new IASLC nodal chart, with precise definitions was also agreed, reconciling the previous differences between the Japanese and Mountain-Dresler charts. The concept of nodal zones was introduced to make such classification relevant to those dealing with bulky nodal deposits that transgress the boundaries of individual nodal stations. Further improvements in stage discrimination and management of lung cancer could be expected in the future, as more robust data related to genetic make-up and biological behavior affecting survival of tumors becomes available.

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      E07.3 - IASLC Staging Projects Update (ID 405)

      14:00 - 15:30  |  Author(s): R. Rami-Porta

      • Abstract
      • Slides

      Abstract
      Background The origin of the International Association for the Study of Lung Cancer (IASLC) Lung Cancer Staging Project took place during an international workshop on intrathoracic staging organized at the Royal Brompton Hospital, London, UK, in 1996. (1) At that time, the 6[th] edition of the tumour, node and metastasis (TNM) classification was in press, but its limitations and weaknesses were discussed in an international and multidisciplinary forum. The main conclusion was the need for a large international database that could be used to refine and update the TNM classification of lung cancer. Two years later, the IASLC Board approved the creation of an International Staging Committee (ISC), whose first co-chairs were Mr. Peter Goldstraw and the late Dr. Robert Ginsberg. An international call was made to promote participation and data sharing, and potential participants were summoned to subsequent meetings and workshops. Data on lung cancer patients diagnosed from 1990 to 2000 were collected from 46 different sources in 20 countries around the world. Data were stored, managed and analysed at Cancer Research And Biostatistics (CRAB), a biostatistics agency based in Seattle, WA, USA. By the end of 2005, 100,869 cases had been registered and 81,495 were analyzable: 68,463 non-small cell lung cancers (NSCLC) and 13,032 small cell lung cancers (SCLC). (2) The analyses of these cases allowed the IASLC to issue recommendations for changes to the 6[th] edition of the TNM classification. The recommendations were accepted by the Union for International Cancer Control (UICC) and by the American Joint Committee on Cancer (AJCC), and were introduced in the 7[th] edition of the TNM classification. (3, 4, 5) With the revision undertaken for the 7[th] edition, a new period of data-based revisions started, with the IASLC leading the revision process and informing the UICC and the AJCC of the potential changes in the classification based on the analyses of its growing international databases. The analyses of the retrospective IASLC database showed that a more detailed database, containing specific information on T, N and M descriptors, would be necessary to continue the revision process. Therefore, in 2009, a call was made for international participation in the prospective collection of data to inform the 8[th] edition of the TNM classification of lung cancer, due to be published in 2016. (6) The IASLC Prospective Phase of the Lung Cancer Staging Project This prospective phase of the project included a new retrospective collection of data from 1999 to 2010. 94,684 patients were collected: 78,640 analyzable cases of NSCLC and 5,912 analyzable cases of SCLC. These cases will be used to inform the 8[th] edition of the TNM classification and are now being analysed at CRAB. Expansion to Other Thoracic Malignancies The ISC incorporated mesothelioma in 2008 and thymic malignancies and oesophageal cancer in 2009. The structure of the ISC was modified to accommodate more tumours and members. Four domains were created: lung cancer domain (chaired by this writer), mesothelioma domain (chaired by Dr. Valerie Rusch), thymic malignancies domain (chaired by Dr. Frank Detterbeck) and oesophageal cancer domain (chaired by Dr. Tom Rice). To increase the participation of more specialists without increasing the number of ISC members and the budget, advisory boards for mesothelioma, thymic malignancies and oesophageal cancer were created. The retrospective database of mesothelioma contains 3,101 surgically treated patients, and its first analysis has been already published. (7) The International Mesothelioma Interest Group (IMIG) and the Mesothelioma Applied Research Foundation (MARF) collaborate with the IASLC Mesothelioma Staging Project. The prospective collection of cases is now ongoing, includes surgically and non-surgically treated patients, and is intended to inform the 8[th] edition of the TNM classification. A side-project on volumetric computerized tomography for clinical staging is also underway. The retrospective database of thymic malignancies has data on more than 10,000 cases, and the prospective collection of data is ongoing. The ISC works closely with the International Thymic Malignancies Interest Group (ITMIG) (8) and with thymic working groups of scientific societies, such as the European Society of Thoracic Surgeons, the European Association for Cardiothoracic Surgery, etc. The main objective is to device a data-driven, internationally acceptable TNM classification for thymic malignancies, both thymomas and thymic carinomas. The retrospective database of the oesophageal cancer is kept at the Cleveland Clinic, Cleveland, OH, USA, and contains data on more than 10,000 patients. Cases are provided by members of the Worldwide Esophageal Cancer Collaboration (WECC). (9) The revised 7[th] edition of the TNM classification of oesophageal cancer was based on the analyses of the surgically treated patients of this database. (10) Expansion to Prognostic Factors Given the importance of more precise prognostication, besides that provided by the TNM classification and staging system, the IASLC Board decided to expand the activities of the Committee to prognostic factors. To make this activity more patent, the name of the Committee was changed to Staging and Prognostic Factors Committee in February 2013. References 1. Goldstraw P. Report on the international workshop on intrathoracic staging, London, October 1996. Lung Cancer 1997;18:107-111. 2. Goldstraw P, Crowley JJ . The International Association for the Study of Lung Cancer international staging project on lung cancer. J Thorac Oncol 2006;1:281-286 3. Goldstraw P, ed. Staging manual in thoracic oncology. Orange Park, FL: Editorial Rx Press; 2009. 4. Sobin L, et al., eds. TNM classification of malignant tumours. 7[th] edition. Oxford: Wiley-Blackwell; 2009;138-146. 5. Edge SB et al., eds. Cancer staging manual. 7[th] edition. New York: Springer; 2010;253-270. 6. Giroux DJ et al. The IASLC lung cancer staging project. Data elements for the prospective project. J Thorac Oncol 2009;4:679-683. 7. Rusch VW et al. Initial analysis of the International Association for the Study of Lung Cancer mesothelioma database. J Thorac Oncol 2012;7:1631-1639. 8. Detterbeck FC, Huang J. Overview. J Thorac Oncol 2011;6(Suppl 3):s1689-1690. 9. Rice TW et al. Worldwide esophageal cancer collaboration. Dis Esophagus 2009;22:1-8. 10. Rice TW et al. 7[th] edition of the AJCC Cancer Staging Manual: esophageal and esophagogastric junction. Ann Surg Oncol 2010;17:1721-1724.

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      E07.4 - PET/CT/MRI for diagnosis and staging of non-small cell lung cancer (ID 406)

      14:00 - 15:30  |  Author(s): Y. Ichikawa

      • Abstract
      • Slides

      Abstract
      Tumor diagnosis, tumor staging, and patient treatment in clinical oncology depend on morphological and molecular imaging procedures, such as magnetic resonance imaging (MRI), computed tomography (CT), and positron emission tomography (PET). Radiological and functional imaging studies, however, have well-known, inherent limitations that limit their diagnostic accuracy in assessing tumor stage and therapeutic response. Both CT and MRI provide mainly morphological information on the tumor and potential metastasis. However, the lack of functional information frequently limits the value of these studies when assessing lymph nodes metastasis. Accurate staging of patients with non-small cell lung cancer (NSCLC) is of paramount importance because stage significantly affects both treatment options and prognosis. The management of NSCLC often requires a multimodality approach for accurate diagnosis and staging and for patient treatment. Some of the most important advances in the treatment of lung cancer have been the development and implementation of accurate and functional imaging. In numerous studies the diagnostic capability of whole-body MRI, PET and PET/CT for cancer staging has been evaluated and compared. In the primary evaluation of pulmonary lesions, fluorodeoxyglucose (FDG)-PET scans are useful for distinguishing benign from malignant etiologies. Several studies investigating the accuracy of FDG-PET in diagnosing malignant pulmonary lesions have estimated its sensitivity and specificity to be 96.8% and 77.8%, respectively. In the same analysis, FDG-PET was found to be superior to CT for evaluating nodal and distant metastases and changed therapeutic management in 18% of the cases studied. However, PET has been shown to be less sensitive for characterizing smaller lung lesions. The positive predictive value (PPV) of FDG-PET is significantly lower for lesions smaller than 1 cm than for larger lesions (0.36 vs 0.90, p=0.015). The lower PPV for smaller lesions reflects a higher rate of false-positive FDG-PET scans. A comparison of the characteristics of PET-negative and PET-positive tumors has shown significant differences in lesion size (p < 0.001), histopathological type (p < 0.001), and pathological stage (p = 0.028). Both lesion size (p < 0.001) and histopathological tumor type (p < 0.001) were significant factors for determining whether PET results were negative or positive. This study established that negative PET findings were likely for lesions 2 cm or smaller and for adenocarcinomas (i.e., adenocarcinoma in situ and well-differentiated adenocarcinomas). A meta-analysis of 59 studies has shown that PET/CT is useful for detecting lymph node metastasis and extrathoracic metastasis. PET/CT is significantly more sensitive and specific than conventional CT alone and more sensitive than PET alone for staging NSCLC. Furthermore, PET/CT demonstrates excellent sensitivity (0.91) and specificity (0.98) for bone metastasis. However, PET/CT has high specificity but low sensitivity for detecting brain metastasis. The question of bone metastasis was most thoroughly answered by a recent meta-analysis of 17 studies comparing FDG-PET/CT, FDG-PET, MRI, and bone scintigraphy. The pooled sensitivity of each of the modalities in the detection of metastasis was 92%, 87%, 77%, and 86%, respectively, and the specificity was 98%, 94%, 92%, and 88%, respectively. When compared with other imaging modalities, FDG-PET appears to offer no additional information regarding the presence of metastatic disease in the brain. The current standard of care is to evaluate the brain metastasis with MRI in all patients, except those with clinical stage IA disease. A recent study of 1122 patients with PET-CT–determined stage I (T1-2N0) NSCLC suggests that invasive staging is not indicated for such patients, especially if a PET scan of the mediastinum is negative. Several studies have assessed the prognostic implications of mediastinal PET findings in patients undergoing curative resection of NSCLC. The rates of locoregional and distant recurrence are higher in patients with positive mediastinal PET findings than in patients with negative findings for the N0/N1 subset. The higher rate of locoregional failure in patients with positive preoperative PET findings in the mediastinum might lead to postoperative radiation therapy. Although chemotherapy is recommended for most patients with N1 disease, chemotherapy is generally not recommended for patients with N0 disease. The higher rate of distant failure in patients with positive preoperative mediastinal PET findings might lead to chemotherapy being recommended. On the other hand, pathologic confirmation with invasive mediastinal staging, either by mediastinoscopy alone or by mediastinoscopy combined with thoracotomy, is recommended if mediastinal lymph node abnormalities are detected with PET-CT. Several recent studies have shown that diffusion-weighted magnetic resonance imaging (DWI) has a higher specificity for N staging of NSCLC than does FDG PET/CT and has the potential to be a reliable alternative noninvasive imaging method for the preoperative staging of mediastinal and hilar lymph nodes in patients with NSCLC. Short inversion time inversion-recovery (STIR) turbo spin-echo (SE) MRI may be useful for distinguishing metastatic lymph nodes from nonmetastatic lymph nodes in patients with NSCLC. This imaging method might be more sensitive and accurate than CT, conventional T1-weighted MRI, FDG PET, or FDG PET/CT. We can prospectively compare the diagnostic capabilities of STIR turbo SE imaging, DWI, and FDG PET/CT for N staging in patients with NSCLC. In patients with NSCLC, quantitative and qualitative assessments of N staging obtained with STIR turbo SE MR imaging are more sensitive and more accurate than those obtained with DWI or FDG PET/CT. A new technology, PET-MRI, is now being established. To guarantee the clinically valuable, time- and cost-efficient use of PET/MRI, it is essential that appropriate indications be chosen, that cross-modality training be performed, that the acquisition protocols be optimized, and that the images be carefully reviewed, taking into account potential artifacts. Additional studies are needed to determine how PET/MRI might best be used clinically and to prospectively verify its clinical abilities. The increased use of FDG-PET will help clinicians to select the most appropriate treatments for each patient and thereby improve outcomes and avoid toxic therapies that are unlikely to be beneficial.

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Author of

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    MO11 - Screening and Epidemiology (ID 131)

    • Event: WCLC 2013
    • Type: Mini Oral Abstract Session
    • Track: Imaging, Staging & Screening
    • Presentations: 2
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      MO11.02 - Validation of electronic nose exhaled breath VOC profile in discriminating between subjects with early stage lung cancer and healthy ever smokers. (ID 2574)

      16:15 - 17:45  |  Author(s): R. Bowman

      • Abstract
      • Presentation
      • Slides

      Background
      Early diagnosis of lung cancer is associated with a better survival. The measurement of volatile organic compounds (VOCs) in exhaled breath using an electronic nose may prove to be a novel, effective and simple technique for screening and diagnosing lung cancer. The aim was to test the validity of the VOC profile in discriminating subjects with early stage lung cancer (I and II) (ESLC) from healthy ever smokers (HS).

      Methods
      243 subjects: 54 ESLC and 189 HS provided a breath sample after tidally breathing through an inspiratory port filter for 5 minutes. It was analysed using a 32 sensor Cyranose 320 (Smiths Detection). Subjects were divided into training (n=159) and independent test set (n=84) groups. Canonical discrimination analyses were performed to determine significance of difference between subject groups and calculate cross validated accuracy (CVV) of the groups using leave one out classification method. Area under the curve (AUC) of Receiver Operating Characteristic Curves were also determined (SPSS V17.0).

      Results
      Validation of the training VOC profile model using an independent test group showed 79% accuracy (p=0.001) in distinguishing ESLC (n=20) from HS (n=64). (AUC 0.933). There was no significant difference in age, lung function and smoking history between the training and test groups.

      Conclusion
      Exhaled breath VOC profile model to discriminate between ESLC subjects and HS was validated in an independent group with a high accuracy. A clinically high sensitivity of the VOC profile model to discriminate between ESLC and HS can be achieved by selecting an appropriate cut point. The cyranose has potential to be a clinically useful diagnostic and screening tool for early stage lung cancer.

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      MO11.10 - DISCUSSANT (ID 3994)

      16:15 - 17:45  |  Author(s): R. Bowman

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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    P1.14 - Poster Session 1 - Mesothelioma (ID 194)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Mesothelioma
    • Presentations: 1
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      P1.14-011 - Changes in expression of cancer drug resistance genes in mesothelioma cells exposed to carboplatin (ID 2610)

      09:30 - 16:30  |  Author(s): R. Bowman

      • Abstract

      Background
      Background A proportion of patients with mesothelioma respond to chemotherapy consisting of pemetrexed and platinum, but tumour responsiveness most often becomes blunted after several cycles. To discover the mechanism of loss of sensitivity to chemotherapeutic agents, we compared expression of cancer drug resistance genes between platinum sensitive and resistant mesothelioma cells.

      Methods
      Mesothelioma cells generated from three chemo-naïve patients propagated in cell culture were exposed to increasing concentrations of carboplatin until in vitro resistance of at least one log10 concentration difference in IC50 was achieved in dose response cytotoxicity assays. For each individual, cells resistant to carboplatin at 8µg/ml and at 20µg/ml were generated. Control cells from each line were passaged in parallel in medium only. Cells were in log phase growth and culture medium was free of platinum for at least two weeks prior to extraction of RNA using Qiagen RNAeasy Mini kits. High quality RNA (assessed by denaturing gel electrophoresis) was then DNase treated and reverse transcribed using Qiagen RT² Profiler PCR Array reagents. Gene expression in control and platinum resistant cells was determined from the Cancer Drug Resistance PCR Array of (Catalogue Array PAHS-004Z) according to manufacturer’s instructions.

      Results
      SULT1E1 was overexpressed in one mesothelioma line resistant to carboplatin at 8µg/ml, and in two of three resistant to 20µg/ml carboplatin, in comparison with parallel passaged controls. One of three cell lines resistant to carboplatin at both the 8µg/ml and 20µg/ml level overexpressed ERBB3, and another resistant at 20µg/ml overexpressed PPARγ. Drug resistance genes displayed more aberrant expression in cells resistant to higher concentrations of carboplatin.

      Conclusion
      The increase in expression of these three genes in mesothelioma resistant to carboplatin suggests that they may be useful targets for circumvention of resistance, but their mechanistic role in development of platinum resistance requires demonstration. In particular, since PPARγ ligands (e.g. roglitazone) have been shown to sensitise cancer cells to chemotherapeutic agents, and are proposed as anticancer agents, it is possible that the functional effect of PPARγ upregulation is moderating rather than causal. Supported by Cancer Australia.

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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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      P1.24-003 - A comparison of the Lung Cancer journey - Metropolitan and Non-Metropolitan (ID 674)

      09:30 - 16:30  |  Author(s): R. Bowman

      • Abstract

      Background
      Referrals and diagnostic pathways for people with symptoms of suspected lung cancer vary by where a person lives and ease of accessing services. Lung cancer diagnostic specialist and treatment services are mostly located in major cities, which can make access for people living in regional/rural and remote areas more difficult compared to major cities. Studies have shown that remoteness of residence is associated with an increase of lung cancer incidence and mortality. Hypothesis: The time required for the evaluation of suspected lung cancer is longer for people from regional/rural and remote areas compared to people living in metropolitan Queensland. The aim of the research study is to describe and compare the journey from referral to diagnosis for people with suspected lung cancer from regional/rural and remote areas referred to The Prince Charles Hospital , a tertiary referral center, compared to metropolitan residents.

      Methods
      A retrospective study of consecutive people with suspected lung cancer referred to The Prince Charles Hospital from December 2010 onwards will be reviewed. Data on patient demographics and referral patterns will be collected from medical records and relevant Queensland Health patient information systems. Information systems include Queensland Oncology Online, Queensland Oncology Analysis System (OASys), The Viewer, Hospital Based Corporate Information System (HBCIS), Practix, Outpatient Services Information Management (OSIM), Picture Archive and Communication System (PACS) and Auscare. The following times will be compared between regional/rural/remote (defined as >50km from TPCH) and metropolitan (<50km from TPCH) patients: (A) from receipt of referral to first specialist appointment (FSA), (B) FSA to first pathological (cytology or histology) diagnosis (FPD), (C) FPD to first multidisiciplinary team discussion (MDT) and (D) MDT to first definitive treatment (FDT). .

      Results
      Preliminary results show that there are clear differences in times to first specialist appointments, diagnosis and definitive treatment experienced by patients living in more regional and remote areas compared to patients from the metropolitan area. Patients from more regional and remote areas on average waited longer for their first specialist appointments e.g. Non Metro: N= 103 60% of patients seen within 30 days of a written referral and 28% were seen within 7 days. Metro: N= 60 78% patients seen within 30 days of a written referral and 50% were seen within 7 days There was also a pattern of admitting patients from remote areas to have all diagnostic workup and commence treatment as an inpatient. Admitting patients from remote areas for diagnostic workup appears to have decreased time to treatment for this cohort of patients although the cost effectivenss to the health service is unknown.

      Conclusion
      Lung cancer is a devastating disease and has a poor prognosis. Lung cancer diagnostic and treatment pathways should be developed for patients living in more regional and remote areas of Queensland to ensure times to diagnosis and treatment are optimised. Potentially this will decrease emotional and financial strain suffered by patients and their families as well as being cost effective to health services.

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    P2.24 - Poster Session 2 - Supportive Care (ID 157)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Supportive Care
    • Presentations: 1
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      P2.24-001 - Lung cancer in rural and remote Aboriginal and Torres Strait Islander communities in Queensland (ID 212)

      09:30 - 16:30  |  Author(s): R. Bowman

      • Abstract

      Background
      The status of lung cancer in rural and remote Aboriginal and Torres Strait Islander ( from this point referred to as Indigenous) communities in Queensland is unclear. It is not known how much of a problem lung cancer is in these communities nor how much awareness exists regarding lung cancer risk factors and early symptoms. Several factors contribute to the uncertainty of lung cancer status in rural and remote communities. Factors include the quality of reporting Indigenous status and cancer registration, cultural influences affecting treatment decisions, access to health services and availability of culturally appropriate lung cancer information resources . Research on lung cancer in rural and remote Indigenous communities in Queensland is needed to improve lung cancer diagnostic and referral pathways and develop culturally appropriate and effective lung cancer information resources. Study Aims: 1. Describe the local and regional health care facilities for Indigenous people who may be referred for suspected lung cancer across the state of Queensland. 2. Interview Indigenous people and health workers in 3 population sample groups from six rural and remote Indigenous communities in Queensland to identify if there are variations in patient flow relative to predicted utilisation of local and regional health care facilities.

      Methods
      1. Using publically available information, identify relevant health care facilities including those with diagnostic bronchoscopy (with or without endobronchial ultrasound (EBUS) services across Queensland to predict expected referral pathways for suspected lung cancer. 2. Using quantitative and qualitative approaches to learn preferred referral pathways from 3 target population groups including patients referred for medical treatment with symptoms suspicious of lung cancer or confirmed lung cancer, Indigenous health workers, Indigenous community members aged 18 years and older. Frequency distributions in terms of the following will be analysed: demographics, current health status, social situation, access to health services, social and financial impact of treatment and information resources. Frequency distributions will be cross tabulated with age, education attainment, socio-economic characteristics, cultural influences, lung cancer awareness and knowledge. The responses to narrative questions will be analysed to identify main themes. These themes will be categorised by issues relating to lung cancer knowledge, cultural influences and beliefs, the patient experience and access to lung cancer medical and support services.

      Results
      We identified a spectrum of health care services across Queensland where patients may be referred for lung cancer management, ranging from public to private facilities. There are seventeen discrete Indigenous communities in Queensland. Compared to the nearest health care facility which offer diagnostic bronchosopy, 5 discrete Indigenous communities are situated > 200km away, 9 > 500km away and 2> 1000km away. Only one is situated 50km away.

      Conclusion
      The research findings will provide a clear understanding of the affect of lung cancer in rural and remote Indigenous communities in Queensland. Knowledge gained from research will enable better health service planning and help reduce any health disparities experienced by Indigenous people; particularly those who live in less advantaged areas compared to other Australians when facing a diagnosis of possible or confirmed lung cancer.

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    P3.01 - Poster Session 3 - Cancer Biology (ID 147)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Biology
    • Presentations: 1
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      P3.01-011 - Heterogeneity in tumour content and necrosis in primary lung cancers: Implications for molecular analysis (ID 3326)

      09:30 - 16:30  |  Author(s): R. Bowman

      • Abstract

      Background
      Lung adenocarcinoma (AC) and squamous cell carcinoma (SCC) tumours have a large variance in tumour cell content. This heterogeneity is a concern for genomic studies, as it is difficult to distinguish mutational differences between tumour and non-tumour if low percentage tumour is used for analysis. In addition to this, tumour samples are affected by the amount of necrosis present, as the overall number of viable cells is decreased. We assessed tumour and necrotic content in lung tumour specimens from AC and SCC patients and aimed to identify possible implications for the suitability of these samples in molecular characterisation studies using next generation sequencing technology.

      Methods
      Lung tissue specimens were collected during the period of 1990 to 2013 from patients at The Prince Charles Hospital who consented to donate their surgically resected lung tissues for research. Tissues were macroscopically dissected, snap frozen in liquid nitrogen and stored at -80°C. A tissue section was taken and stained with haematoxylin and eosin (H&E) for two pathologists to independently assess tumour cell and necrotic content. Tumour cell content (TC) in each specimen was scored as percentage of viable cells as seen on the H&E slide, where necrotic content (NC) was recorded as a percentage of the whole slide section. Statistics were calculated using SPSS v21 software. Tumour specimens screened for eligibility to The Cancer Genome Atlas sequencing project are presented here.

      Results
      Tumours from 62 AC and 104 SCC subjects were scored (specimen characteristics in Table 1). Scoring between the two pathologists was highly correlated, with a high intraclass reliability (0.94 and 0.96 for TC and NC respectively).

      Table 1: Clinical and Pathological Characteristics of Specimens
      AC SCC
      Number of Specimens 384 609
      Number of Males/Females 36/26 84/20
      Median Specimens per Subject 4 4
      Range of Specimens per Subject 1-25 1-27
      Median TC 35% 30%
      Range of TC 0-88% 0-90%
      Median NC 0% 6%
      Range of NC 0-90% 0-100%
      Median Age 62 yrs 68 yrs
      Range of Age 45-85 yrs 46-91 yrs
      Median Smoking Pack Years 40 56
      Range of Smoking Pack Years 0-115 0-158
      TC varied from 0-~90% for both subtypes. Comparing AC and SCC, the median TC was higher in AC than SCC (35% vs 30% respectively, p<0.05). NC varied from 0-~100%, but was generally low. The median NC was statistically significantly different between AC and SCC (0% and 6% respectively, p<0.001). TC was weakly correlated with NC (Spearman Rank r = 0.32, p<0.01). There were no clinically important correlations between smoking pack years, gender or age with TC and NC of specimens.

      Conclusion
      Lung AC and SCC specimens are heterogeneous in terms of TC and NC. Therefore, only a small proportion of resected lung cancer specimens meet the criteria required for massively parallel sequencing projects that require high quality tumour DNA and RNA (ie low NC) and relatively low stromal contamination (ie high TC).