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P. Goldstraw

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    G01 - Progress in Lung Cancer: Celebrating 40 Years of IASLC and Research Progress (ID 14)

    • Event: WCLC 2013
    • Type: Other Sessions
    • Track: Other Topics
    • Presentations: 4
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      G01.1 - Surgery and Staging (ID 436)

      H. Asamura

      • Abstract
      • Slides

      Abstract
      Staging is an objective measurement of the extent of cancer to allow logical grouping of patients with similar prognosis and pathobiological characteristics. Actually, the stage is expressed as combination of three factors: the size and invasion of the primary tumor (T), metastasis to the locoregional lymph nodes (N), and distant disease (M). Nowadays, any planning of the treatment is not possible without accurate staging. Moutain, who took the great leadership in the revision of TNM staging system, described staging as “assigning a simple coded designation to be a patient in accordance with an established set of rules”. Traditionally, UICC and AJCC have taken an initiative for the revision of the classification rules of TNM system. Since 7[th] edition which was published in 2009, IASLC was principally involved in the creation of proposals for revision to UICC and AJCC based upon the world-wide database. This process was known as “IASLC Lung Cancer Staging Project” lead by Goldstraw, and it is still underway for 8[th] edition. Although TNM staging system covers the malignant tumors of most organs, such aggressive intervention of international academic societies has been rarely seen except IASLC. The advent of mediastinoscopy, PET, and EBUS technique contrubuted to better staging. The IASLC Staging Project is now extended to cover not only lung cancer but also mesothelioma, thymic tumors, and esophageal cancer. As of 2013, surgery is still playing a principal role in the treatment of lung cancer especially for the relatively early stages of the disease with curative intent. Surgery is respected as the integration of two different parts: "art (surgical skill)" and "science". Therefore, we should realize that the evolution of lung cancer surgery has been achieved by the refinement of surgeons’ skills and advent of new technique (technology) as well as the accumulation of novel scientific evidence given by the well planned clinical trials. Surgery for lung cancer began as pneumonectomy as early as in 1930. However, the present-day gold standard surgery for lung cancer is defined as at least lobectomy and lymph node sampling/dissection. Series of clinical trials in 1980’s, mainly focusing upon the prognostic evaluation of adjuvant chemotherapy, were performed by Lung Cancer Study Group. The technically challenging surgery, such as those for superior sulcus tumor, has been also improved greatly. Even tumors located at the difficult potion of the thoracic inlet could be resected by refined method as shown by Grunenwald. How to manage the metastasis to the locoregional lymph nodes is also an important issue. Owing to the lymph node map originally drawn by Naruke and colleagues in 1970’s, the precise location of the metastatic nodes could be documented, and further analyses and comparison of the resected lung cancer with node metastasis became possible. The prognostic impact of the lymph node dissection was evaluated by the recent ACOSG study. In 1990’s, the minimally invasive technique (video-assisted thoracic surgery) was introduced in the surgery for lung cancer, and the comparison between open and VATS procedures were being performed. The trend toward the minimally invasive surgery is now generalized in the thoracic surgical community. The future directions in lung cancer surgery include the development of less invasive technique such as robotics, the improvement of the adjuvant treatment with new active drugs, the definition of the role of surgery in the multimodality treatment for advanced lung cancer, and the comparison between surgery and other local modalities (SBRT, ablation) as the treatment for pathologically early lung cancer. References 1970’s Pearson FG et al. The role of mediastinoscopy in the selection of treatment for bronchial carcinoma with involvement of superior mediastinal lymph nodes. J Thorac Cardiovasc Surg 1972;64:382-90. Naruke T et al. Lymph node mapping and curability at various levels of metastasis in resected lung cancer. J Thorac Cardiovasc Surg 1978;76:832-9. 1980’s Holmes EC, et al. THE LUNG CANCER STUDY GROUP. A randomized comparison of the effects of adjuvant therapy on resected stages II and III non-small cell carcinoma of the lung. Ann Surg 1985;202:335-41 Mountain CF. A new international staging system for lung cancer. Chest 1986;89:225S-33S 1990-1995 Valk PE, et al. Staging of non-small-cell lung cancer by whole-body positron emission tomographic imaging. Ann Thorac Surg 1995;60:1573-82. Lung Cancer Study Group. Randomized trial of lobectomy versus limited resection for T12 N0 non-small cell lung cancer. Ann Thorac Surg 1995;60:615-23. 1995-2000 TNM Classification of Malignant Tumours. 5[th] Ed. Lung. International Union Against Cancer. Wiley-Liss, New York, pp93-97, 1997. Grunenwald D et al. Transmanubrial osteomuscular sparing approach for apical chest tumors. Ann Thorac Surg 1997;63:563-6. 2001-2005 Goya T et al. Prognosis of 6,644 resected non-small cell lung cancers in Japan: a Japanese lung cancer registry study. Lung Cancer 2005;50:227-34. Mateu-Navarro M et al. Remediastinoscopy after induction chemotherapy in non-small cell lung cancer. Ann Thorac Surg 2000;70:391-395. Van Schil PE et al. Remediastinoscopy after neoadjuvant therapy for non-small cell lung cancer. Lung Cancer 2002;37:281-285. Stamatis G et al. Repeat mediastinoscopy as a restaging procedure. Pneumologie 2005;59:862-866. De Leyn P et al. Prospective comparative study of integrated PET-CT scan versus re-mediastinoscopy in the assessment of residual mediastinal lymph node disease after induction chemotherapy for mediastinoscopy proven IIIA-N2 non-small cell lung cancer. A Leuven Lung Cancer Group study. J Clin Oncol 2006;24:3333-9. 2005-2010 The IASLC Staging Manual in Thoracic Oncology, Editorial Rx, Florida, 2009. Falcoz et al. The Thoracic Surgery Scoring System (Thoracoscore): Risk model for in-hospital death in 15,183 patients requiring thoracic surgery., J Thorac Cardiovasc Surg 2007;133:325-32. 2010- Yasufuku K et al. A prospective controlled trial of endobronchial ultrasound-guided transbronchial needle aspiration compared with mediastinoscopy for mediatinal lymph node staging of lung cancer. J Thorac Cardiovasc Surg 2011;142:1393-400. Darling GE et al. Randomized trial of mediastinal lymph node sampling versus complete lymphadenectomy during pulmonary resection in the patient with N0 or N1 (less than hilar) non-small cell carcinoma: Results of the American College of Surgery Oncology Group Z0030 Trial. J Thorac Cardiovasc Surg 2011;141:662-70. Swanson SJ et al. Video-Assisted Thoracoscopic Lobectomy Is Less Costly and Morbid Than Open Lobectomy: A Retrospective Multiinstitutional Database Analysis., Ann Thorac Surg 2012;93:1027-32

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      G01.2 - Early Detection, Etiology, Epidemiology, Pulmonology and Radiology (ID 437)

      P.E. Postmus

      • Abstract
      • Slides

      Abstract
      Etiology and epidemiology Awareness that lung cancer is for many patients a self-inflicted disease has become common knowledge and its incidence can only be reduced by an active fight against smoking . The IASLC has always considered this as very important (1). The last decade much attention was given the non-smokers who developed lung cancer. These patients have specific characteristics, of which EGFR mutation is one (2). What is responsible for this class of lung cancer is unknown. With an estimated number of 300,000/year, it is far from an orphan disease (3). Early detection Lung cancer cure rates are far from impressive (4). For those diagnosed with symptoms the outcome is grim, cure is extremely rare, palliative needs are common (5). The 5 year survival rates in patients with resectable tumors is decreasing with increasing stage (6). Finding early stage lung cancer with state-of -the-art CT technology resulted in an impressive 10 yr survival rate of 88% (7). This modern CT technologywas evaluated in the largest lung cancer screening study ever performed (8). For the first time it was demonstrated that screening is effective and results in a relative reduction in mortality from lung cancer of 20.0%, and death from any cause by 6.7% (95% CI, 1.2 to 13.6; P = 0.02). Still many questions remain unanswered and confirmation is needed (9)? How to treat these lesions with minimal invasive surgery (10) or stereotactic radiotherapy (11). Pulmonology Autofluorescence bronchoscopy improves the detection of mucosal abnormalities (12) such as pre-invasive lesions (13), carcinoma in situ (14) and radiologically occult lung cancer (15). Through the EBUS (endobronchialultrasound) scope virtually every lymph node adjacent to the bronchial tree can be reached (16). In combination with the ultrasound from inside the oesophagus (17) this results in a sensitivity of > 90% (18). In a RCT it was demonstrated that combining these techniques should be done before thinking of a mediastinoscopy as their yield is comparable to mediastinoscopy (19). Bronchoscopy became important for treatment as well, ranging from palliative to really curative. Stenting the airway but should be used with great caution as migration is common, it seriously affects mucus clearance and narrowing of the airways through granulation tissue might develop (20). A desobstruction technique such as Nd-YAG laser, electrocautery or argon plasma coagulation can be used if intraluminal tumor gives obstruction (20). In specific situations with very limited cancer within the bronchial wall endobronchial treatment might even lead to cure, an example of this is photodynamic therapy (21). Radiology Within the last 40 years imaging techniques have improved considerably. With the introduction of computed tomography, it became possible to visualize the primary tumor as well as mediastinal lymphnodes in a much better way. A further technical improvement, the Positron Emission Tomography (PET) and the use of 18-fluorodeoxyglucose (18-FDG) improved this (22). Further developments of imaging may lead to decision making on treatment (23). References 1 Tobacco policy recommendations of the International Association for the Study of Lung Cancer (IASLC): a ten point program. Lung Cancer 1994; 11: 405-407 2 Ren JH, et al. EGFR mutations in non-small-cell lung cancer among smokers and non-smokers: a meta-analysis. Environ Mol Mutagen. 2012 Jan;53(1):78-82 3 Sun S, et al. Lung cancer in never smokers—a different disease. Nat Rev Cancer. 2007;7(10):778-790. 4 Goldstraw P, et al. The International Association for the study of lung cancer. The International staging project on lung cancer. J ThoracOncol 2006; 1: 281-286. 5 Ferrell B, et al. Palliative care in lung cancer. SurgClin North Am 2011; 91: 403-418. 6 Goldstraw P, et al. The IASLC Lung Cancer Staging Project: Proposals for the revision of the TNM stage groupings in the forthcoming (seventh) edition of the TNM classification for Lung Cancer. J Thor Oncol 2007; 2: 706-714. 7 The International Early Lung Cancer Action Program Investigators. Survival of Patients with Stage I Lung Cancer Detected on CT Screening. N Engl J Med 2006; 355:1763-1771. 8 National lung screening trial research team, et al. Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med 2011; 365: 395-409. 9 Field JK, et al. Prospects for population screening and diagnosis of lung cancer. Lancet 2013; 382: 732-741. 10 Nakamura K, et al. A phase III randomized trial of lobectomy versus limited resection for small sized peripheral non-small cell lung cancer. Jpn J ClinOncol 2010; 40: 271-274. 11 Senan S, et al. Treatment of early-stage lung cancer detected by screening: surgery or stereotactic ablative radiotherapy? Lancet Oncol 2013; 14: 270-274. 12 Venmans BJW, et al. Clinically relevant information obtained by performing autofluorescence bronchoscopy. J Bronchol 2000; 7: 118-121. 13 Breuer RHJ, et al. The natural course of preneoplastic lesions in bronchial epithelium - A longitudinal study. Clin Cancer Res 2005; 11: 537-543. 14 Venmans BJW, et al. Outcome of bronchial carcinoma in situ. Chest 2000; 117: 1572-1576. 15 Vonk-Noordegraaf A, et al.Bronchoscopic treatment of patients with intraluminal microinvasiveradiographically occult lung cancer not eligible for surgical resection: a follow-up study. Lung Cancer 2003; 39: 49-53. 16 Herth FJ, et al. Transbronchial and transoesophageal (ultrasound-guided) needle aspiration for the analysis of mediastinal lesions. EurRespir J 2006; 28: 1264-1275. 17 Silvestri GA, et al. Endoscopic ultrasound with fine-needle aspiration in the diagnosis and staging of lung cancer. Ann ThoracSurg 1996; 61: 1441-1445. 18 Wallace MB, et al. Minimally invasive endoscopic staging of suspected lung cancer. JAMA 2008; 299: 540-546. 19 Annema JT, et al. Mediastinoscopyvsendosongraphy for mediastinal nodal staging of lung cancer: a randomized trial. JAMA 2010; 304: 2245-2252. 20 Bolliger CT, et al. Therapeutic bronchoscopy with immediate effect: laser electrocautery, argon plasma coalgulation and stents. EurRespir J 2006; 27: 1258-1271. 21 Cortese DA, et al. Photodynamic therapy for early stage squamous cel carcinoma of the lung. Mayo ClinProc 1997; 72: 595-602. 22 Silvestri GA, et al Methods for staging lung cancer. Chest 2013; 143: 211S-250S. 23 Bahce I, et al. Development of [(11)C]erlotinib positron emission tomography for in vivo evaluation of EGF receptor mutational status. Clin Cancer Res. 2013; 19: 183-193.

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      G01.3 - Biology and Pathology (ID 3858)

      F. Hirsch

      • Abstract
      • Slides

      Abstract not provided

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      G01.4 - Non-Surgical Therapy (ID 3859)

      P.A. Bunn, Jr.

      • Abstract
      • Slides

      Abstract
      Systemic Therapy of Early Stage NSCLC The addition of chemotherapy to surgery before or after surgery was studied because trials in the 1970’s demonstrated that cure rates were lower than in other cancers and because the majority of relapses were in distant sites (1). Initial adjuvant studies showed no survival advantage for single agent chemotherapy. Subsequent trials in the 1980’s and 1990’s established that cisplatin based 2-drug combinations produced a modest (4-5%) improvement in 5 year survival rates but only in stages II and IIIa (2). Adjuvant therapy has not been shown to improve outcomes in Stage I with the possible exception of Stage IB tumors larger than 4 cm (3). Neoadjuvant chemotherapy produces similar improvement compared to adjuvant therapy as demonstrated by randomized trials and metaanalyses (4,5). Post-operative radiotherapy has not shown benefits in stage I and II where it may be harmful and it role in stage IIIa after surgery is under evaluation as there are conflicting data on its role in this setting (6,7).Systemic Therapy of Stage III NSCLC Combinations of radiotherapy with chemotherapy were shown to produce superior survival compared to either alone based on randomized trials conducted in the 1990’s (8). Subsequent studies indicated that concurrent chemo-radiotherapy was superior to sequential therapy (9,10). There are conflicting data on whether two or four cycles of chemotherapy is best (11). There are also conflicting data on whether triple modality therapy is superior to two modalities for Stage IIIA N2 disease (12).Systemic Therapy of Stage IV NSCLC Chemotherapeutic agents and chemotherapy combinations were tested in the 1970’s and early 1980’s but failed to show any survival advantage. Two drug combinations combining cisplatin with vindesine or vinorelbine were shown to prolong survival compared to best supportive care in the 1980’s and 1990’s (13,14). Subsequent studies showed that 2-drug platinum based combinations were superior to a single active drugs (13,15,16). The survival advantage increased median survival times from 4-5 months to 8-12 months. Two-drug combinations with a platinum combined with gemcitabine, paclitaxel, docetaxel or pemetrexed were shown to produce equivalent survival in randomized trials conducted in the 1990’s and in the 2000’s (17,18). An exception to the equivalence was the finding that the pemetrexed/cisplatin combination was superior to gemcitabine/cisplatin in non-squamous cancer but inferior in squamous cancers (19). Three and 4 drug combinations were not superior to 2 drug combinations. These 2 drug combinations were superior in patients with PS 0-1 but benefitted elderly as well as younger patients (20). There is evidence that the paclitaxel/carboplatin combination may benefit PS2 patients (21). Thus, histology and performance status are key factors in therapy selection. Since the 1990’s, docetaxel, erlotinib, and pemetrexed have been shown to prolong survival when used in the 2[nd] line setting (22-24). For pemetrexed this improvement was limited to non-squamous histology (24). Since 2000 the use of targeted therapy began with the studies of inhibitors of VEGFR and EGFR signaling. Angiogenesis inhibitors were widely studied. Bevacizumab, a monoclonal antibody to VEGF, was shown to produce promising results in a randomized phase II trial (25). However, patients with squamous cell carcinoma had excess bleeding on this study and were excluded from all further trials. An ECOG randomized trial (4599) showed that bevacizumab improved survival in non-squamous histologies when combined with platinum doublets (26). However, the survival advantage is small and is less striking in elderly patients. The survival advantage was not observed in a randomized trial from Europe using gemcitabine/cisplatin as the chemotherapy backbone (27). As noted above, the EGFR TKI erlotinib was shown to prolong survival in unselected patients failing 1 or 2 chemotherapy regimens (23). In 2004 an association between mutations in the EGFR and response to EGFR TKIs was established (28,29). Subsequent randomized trials showed that EGFR TKIs were superior to chemotherapy in 1[st] line therapy of EGFR mutant patients but chemotherapy was preferred for those without mutations (30-35). In 2007, it was shown that EML4/ALK fusions could serve as driver molecular changes in up to 5% of NSCLC’s (36). Crizotinib, an ALK TKI was shown to produce high response rates and long PFS and was superior to chemotherapy in the second line setting (37-39). Patients with ALK fusions nearly always have adenocarcinoma histology, more often are younger and female sex and are light or never smokers (40) but clinical features should not be used to determine who should be tested (41). These and other molecular drivers may be present in more than 50% of lung adenocarcinomas (42). Molecular analyses of squamous and small cell cancers have recently been described (43-46). Checkpoint inhibitors such as PD1 and PDL1 were shown to be therapeutic targets since 2010. Antibodies to PD1 and PDL1 have produced responses in about 20% of patients who had failed multiple lines of chemotherapy and many of these were durable (46,47). PDL1 expression is being evaluated as a biomarker and many trials are in progress. Maintenance therapy with continuation of the original platinum doublet was shown in many trials to be associated with an increase in the PFS, an increase in toxicity but no increase in survival and therefore this approach was not adopted (48) . In 2009, Fidias et al reported that maintenance docetaxel could increase survival as well as PFS (49). This trial was followed by a trial showing that erlotinib could improve PFS and survival as maintenance after a platinum doublet (50). PFS and survival were improved in all histologies but the improvement in PFS and OS was most striking in patients with EGFR mutations. Pemetrexed was shown to improve PFS and survival as switch maintenance after a platinum doublet that did not contain pemetrexed (51). A subsequent trial showed that pemetrexed continuation maintenance also improved PFS and OS after induction therapy with a pemetrexed/platinum doublet induction (52). An unpublished trial, (POINTBREAK), comparing pemetrexed/carboplatin/bevacizumab with pemetrexed/bevacizumab maintenance compared to paclitaxel/carboplatin/bevacizumab followed by bevacizumab, showed no difference in survival. Thus, there is no evidence at presence that maintenance should contain two drugs although the ECOG is comparing pemetrexed with bevacizumab or the combination after induction therapy with paclitaxel/carboplatin/bevacizumab.Systemic Therapy of Early Stage SCLC Patients with Stage I and IIA SCLC, although infrequent, benefit from resection and adjuvant chemotherapy and the IASLC TNM classification is more accurate than the old VA classification (53). SCLC patients with stage IIB and III (limited stage SCLC) were shown to have prolonged survival when treated with chemotherapy and radiotherapy compared to either alone (54,55). An ECOG randomized trial showed that chest RT with BID radiation to 45 Gy was superior to once daily chest RT to the same dose when combined with etoposide/cisplatin (56). However, similar results were obtained with higher total doses of once daily RT and both once daily and twice daily are in routine practice. Concurrent chemoradiotherapy is superior to sequential therapy but results with radiotherapy starting at either cycle 1 or cycle 3 are similar. The combination of etoposide/cisplatin is the most frequent chemotherapy regimen because of reduced toxicities compared to Adriamycin or other combinations. Prophylactic cranial irradiation in good responders reduces brain relapse and prolongs survival (57). 25 Gy is the preferred dose (58).Systemic Therapy for Stage IV SCLC Both cisplatin and etoposide were first tested and shown to be active in the 1970’s. Studies in the 1980’s showed that the combination of etoposide and cisplatin produced high response rates (80%) with some complete responses (10-15% (59, 60). These results lead to randomized trials comparing etoposide/cisplatin to CAV, CAE or alternating combinations. Etoposide/cisplatin (EP) produced equivalent efficacy with less toxicity (60,61) and thus became the standard combination in the 1990’s. Pemetrexed/carboplatin was compared to etoposide/carboplatin and was inferior (62). Several trials have shown that irinotecan combined with cisplatin or carboplatin is equivalent to etoposide with cisplatin or carboplatin (63, 64). Thus EP remains the standard today. Topotecan is approved for used in the second line setting albeit at a dose and schedule rarely used due to toxicity (65,66). Both oral and intravenous topotecan produce similar results. Topotecan improved PFS as maintenance but did not improve survival and increased toxicity (67). Thus, use in the maintenance setting was not widely adopted. Retreatment with EP for those with late relapse has been the most successful retreatment approach and is standard in this setting (68). After 2000, randomized trials showed that PCI after induction response could prolong survival in extensive stage as well as limited stage SCLC and as now used routinely in this setting (69). There has been little change in chemotherapy options for SCLC over the past 20 years but there is some hope that the immune checkpoint inhibitors could improve outcomes (70).

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    G02 - Global Lung Cancer Coalition (GLCC) Session: Deserve Better - Expect Better: Advocating for Better Outcomes for Lung Cancer Patients (ID 15)

    • Event: WCLC 2013
    • Type: Other Sessions
    • Track: Nurses
    • Presentations: 7
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      G02.0 - N/A - Chair Intro (ID 438)

      • Abstract

      Abstract not provided

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      G02.1 - Public Awareness of Lung Cancer Symptoms - The GLCC/IPSOS MORI 2013 International Consumer Poll (ID 439)

      J. Elgood

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      • Slides

      Abstract
      Introduction Ipsos MORI were commissioned by the Global Lung Cancer Coalition to explore the prevalence of smoking within countries; and awareness of the symptoms of lung cancer. Two questions were asked: 1. Can I just check, do you consider yourself to be: a) A current smoker – i.e. someone who is a regular smoker at the present time; b) A former smoker – i.e. someone who used to smoke regularly but has quit; c) Someone who has never smoked – i.e. someone who has never smoked at all, or only very occasionally in the past (less than 100 cigarettes in your lifetime); d) Don’t know. 2. There are many warning signs and symptoms of lung cancer. Please name as many symptoms of lung cancer as you can think of.[1] A quantitative survey was conducted across: Argentina, Australia, Bulgaria, Canada, Denmark, Egypt, France, Germany, Great Britain, Ireland, Italy, Japan, Mexico, Norway, Portugal, Slovenia, Spain, Sweden, Switzerland, the Netherlands, and the USA. This abstract outlines the headline findings[2]. Methodology A nationally representative quota sample for each country of 500–1,204 adults was interviewed from 2 June – 16 August 2013[3], using Omnibus services (please note the lowest age varied slightly between countries)[4]. Face-to-face in-home interviewing was used in Bulgaria, France, Germany, Great Britain, Portugal and Spain, and telephone (CATI[5]) interviewing elsewhere (in Argentina, Australia, Canada, Denmark, Egypt, Ireland, Italy, Japan, Mexico, Norway, Slovenia, Sweden, Switzerland, the Netherlands, and the USA). Data have been weighted to the known adult population profile of each country. Please also note that booster surveys took place in Mexico, Norway, Sweden and Slovenia to boost the number of smokers in order to allow robust comparisons. In each country, data were weighted back to the original profile of smokers and non-smokers to ensure that smokers were not over-represented. Discussion of findings: where is smoking prevalence highest? Of all the 21 countries surveyed, people in Bulgaria are most likely to be current smokers (41%), followed by Spain (33%) and France (30%). The lowest proportions of current smokers are found in Sweden (12%) and Australia (13%). Egypt, however, has the highest proportion of people who have never smoked at all (70%). Figure 1 Spontaneous awareness of the symptoms of lung cancer The combined results from all countries show that breathlessness (40%) and coughing (39%) are the most frequently recognised symptoms of lung cancer. Other symptoms relating to coughing, as well as general or unspecified coughing, are also commonly mentioned: coughing blood (17%), a cough that doesn’t go away (14%), and a cough that gets worse (8%). Tiredness or a lack of energy (13%) and an ache or pain when coughing or breathing (11%), are spontaneously mentioned by more than one in ten people as well. It should also be recognised that approaching one in four could not name any symptoms, instead stating that they didn’t know (23%). Figure 2 Spontaneous awareness varies significantly by country. For example, fewer than one in four Japanese adults mention breathlessness (22%), compared to a high of 56% in Ireland. Likewise, whilst 27% state tiredness or a lack of energy to be a symptom of lung cancer in Bulgaria, only 5% of Australians do the same. The following table shows the most frequently mentioned symptoms in each country. Breathlessness is the symptom respondents are most commonly aware of in fifteen countries, with general or unspecified coughing emerging more frequently in the other six.

      Country Most frequently mentioned Second most frequently mentioned Third most frequently mentioned
      Argentina Breathlessness (31%) A cough (26%) Tiredness or lack of energy (12%)
      Australia Breathlessness (53%) A cough (37%) Coughing blood (32%)
      Bulgaria Breathlessness (50%) Coughing blood (37%) A cough that gets worse (30%)
      Canada Breathlessness (49%) A cough (45%) Coughing blood (20%)
      Denmark Breathlessness (51%) A cough (48%) An ache or pain when coughing or breathing (20%)
      Egypt Breathlessness (25%) Persistent chest infections (23%) A cough (15%)
      France A cough (54%) Breathlessness (37%) A cough that doesn't go away (25%)
      Germany Breathlessness (36%) Coughing blood (34%) A cough that doesn't go away (31%)
      Great Britain Breathlessness (46%) A cough (43%) Coughing blood (27%)
      Ireland Breathlessness (56%) A cough (56%) Coughing blood (27%)
      Italy Breathlessness (42%) A cough that doesn't go away (32%) A cough (29%)
      Japan A cough (50%) Breathlessness (22%) A cough that doesn't go away (21%)
      Mexico A cough (33%) Breathlessness (27%) An ache or pain when coughing or breathing (10%)
      Netherlands Breathlessness (45%) A cough (45%) Tiredness or lack of energy (13%)
      Norway Breathlessness (47%) A cough (40%) Chest and/or shoulder pains (9%)
      Portugal Breathlessness (35%) A cough (33%) Tiredness or lack of energy (18%)
      Slovenia A cough (52%) Breathlessness (31%) Coughing blood (10%)
      Spain A cough (29%) Breathlessness (25%) Tiredness or lack of energy (20%)
      Sweden A cough (46%) Breathlessness (42%) Tiredness or lack of energy (10%)
      Switzerland A cough (53%) Breathlessness (43%) An ache or pain when coughing or breathing (12%)
      USA Breathlessness (38%) A cough (37%) Coughing blood (14%)
      When analysing the mean number of potential symptoms of lung cancer mentioned in each country depending on whether respondents are current smokers, former smokers, or have never smoked at all, awareness appears to be fairly consistent. Please note that people who said that they did not know any symptoms have been excluded from this analysis. The following table highlights within each country which of the three groups has the highest mean score (i.e. the most mentions of symptoms per respondent). The key finding from this is that current smokers often mention fewer symptoms of lung cancer than former smokers or people who have never smoked. In three countries (France, Ireland and Portugal), current smokers do appear to have a greater awareness of potential symptoms, whilst in Sweden, current and former smokers have the same mean score.
      Mean number of mentions of symptoms of lung cancer per respondent (who named at least one symptom)
      Country Current smokers Former smokers Never smokers
      Argentina 1.97 1.97 2.11
      Australia 2.04 2.47 2.28
      Bulgaria 3.63 4.18 3.97
      Canada 2.57 2.53 2.77
      Denmark 2.39 2.34 2.43
      Egypt 3.09 3.32 3.32
      France 2.54 2.53 2.40
      Germany 3.02 3.66 3.69
      Great Britain 2.77 2.89 2.75
      Ireland 3.21 2.99 2.94
      Italy 2.46 2.53 2.43
      Japan 2.41 2.55 2.67
      Mexico 1.98 1.84 2.00
      Netherlands 1.99 2.19 2.24
      Norway 1.86 2.14 2.18
      Portugal 2.61 2.54 2.43
      Slovenia 2.35 2.46 2.16
      Spain 2.13 2.30 2.13
      Sweden 1.98 1.98 1.89
      Switzerland 1.94 2.31 2.23
      USA 1.93 1.97 2.01
      [1] A pre-coded list was provided for interviewers to code responses. Respondents were able to code multiple responses. [2] Please note that at this stage the findings are based on interim data. [3] The base sizes in each country were as follows: Argentina (500), Australia (1,000), Bulgaria (1,148), Canada (1,005), Denmark (650), Egypt (1,009), France (953), Germany (1,073), Great Britain (957), Ireland (1,000), Italy (510), Japan (1,204), Mexico (600), Norway (529), Portugal (1,203), Slovenia (580), Spain (500), Sweden (550), Switzerland (510), the Netherlands (1,004), and the USA (1,000) [4] The lowest age for each country is as follows: Germany: 14 years; Australia, Ireland, Mexico and Norway: 15 years; Sweden: 17 years; Egypt and Japan: 20 years; all other countries: 18 years. [5] Computer Assisted Telephone Interviewing

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      G02.2 - Outcomes from Public Information Campaigns (ID 440)

      J. Fox

      • Abstract
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      Abstract

      Abstract
      Lung Cancer Public Information Campaign – Striving to Ensure Earlier Lung Cancer Diagnosis Jesme Fox, Medical Director, Roy Castle Lung Cancer Foundation, UK. ________________________________________________________________________ Background Despite recent advances, lung cancer remains a disease characterized by late diagnosis and poor outcomes. Diagnosing more lung cancer patients, at an early stage, when curative treatments are an option, will save lives. In recent years, there has been a focus on lung cancer screening. In countries where lung cancer screening is available, high risk individuals are being directed to these services. In other counties, advocates are calling for further research to evaluate the benefit of screening tools. Raising general public awareness of the signs and symptoms associated with lung cancer is of importance in the pursuit of earlier diagnosis. It is a key function of many advocacy groups working in the lung cancer field. With the variety of associated signs and symptoms, this is a difficult area. Using nationally agreed guidelines, advocacy groups have produced information, such as the GLCC awareness raising leaflets, available for download, in 13 languages [1]. As noted in a 2013 survey, undertaken by Public Health England, [2], 40% of people surveyed were unaware that a persistent cough could be a symptom of lung cancer.. Challenges Much negativity surrounds lung cancer and impacts on effective campaigning. Lung cancer is seen as a ‘depressing story’ and it is often difficult to engage the media. The notion of ‘self infliction’ surrounding this disease, adds to this difficulty. Furthermore, the stigma and blame associated with lung cancer is in itself, a contributing factor to late presentation in this disease [3, 4, 5,]. Stigmatisation has a very negative impact on the disease and on advocacy initiatives. Central to the lung cancer advocacy community is its focus on reducing the stigma associated with this disease. Many diseases are life style related, yet are not impacted in this way. It is important that whilst undertaking awareness campaigns, the messages of ‘no one deserves lung cancer’ and ‘smoker, former smoker or never smoker – anyone can get lung cancer’ are distributed widely. Public awareness raising campaigns in lung cancer Much of the awareness campaigning to date has come from the emerging Lung Cancer Patient Advocacy movement. Sadly, with poor survival, the number of lung cancer advocates and advocacy groups is relatively small, as compared with other common cancers. However, a key focus has been the November, ‘Lung Cancer Awareness Month’ initiative, initially developed in the US, by the Alliance for Lung Cancer Advocacy, Support and Education (now the Lung Cancer Alliance) and adopted by the global community, through the Global Lung Cancer Coalition, in 2001. The campaign aims to raise awareness of the signs and symptoms associated with lung cancer, change public perceptions and help to de-stigmatize this disease. An early example of this was the 2002 general public and media campaign, organized in the UK by the Roy Castle Lung Cancer Foundation and Macmillan Cancer Relief [6]. In recent years, the cross country initiative, involving Australia, Egypt and the US, being the ‘Shine a Light on Lung Cancer’ campaign, originally developed by Lung Cancer Alliance [7]. Other campaigns, from across the globe, will be described. In the UK, we have seen a number of general public lung cancer awareness raising initiatives, through the National Awareness and Early Diagnosis Initiative (NAEDI). We have also seen local campaigns such as the ‘’Doncaster Cough Campaign’’ [8] – in the 11 GP surgeries studied, after its first year (2008), noted, 19% of lung cancers diagnosed in Stage I and II, an increase from 11% in the previous year. We have also seen centrally, government funded campaigns. In England, the Department of Health, in 2012, funded the national ‘Be Clear on Cancer – Lung Cancer’ campaign [9]. This campaign, focusing on ‘’persistent cough’’ and results from the pilot study noted a 22% increase in the number of patients who visited their General Practitioner with relevant symptoms and also noted an increase in Chest CTscans being performed. This campaign has been repeated in the summer of 2013. In Scotland, the ‘Detect Cancer Early’ campaign is developing a national lung cancer component. References GLCC website (lung cancer signs and symptoms awareness leaflets, for download) http://www.lungcancercoalition.org/en/download-our-awareness-leaflet Online omnibus survey for Public Health England, conducted with representative sample of 1045 adults, between 7 and 10 June 2013 by TNS BMRB. http://www.gov.uk/government/news/don’t-ignore-a-persistent-cough-warns-lung-cancer-campaign Corner, J., J. Hopkinson, and L. Roffe, Experience of health changes and reasons for delay in seeking care: A UK study of the months prior to the diagnosis of lung cancer. Social Science and Medicine, 2006. 62: p. 1381-1391. Tod, A.M., J. Craven, and P. Alllmark, Diagnostic delay in lung cancer: a qualitative study Journal of Advanced Nursing 2008. 61(3): p. 336-343. Corner, J., et al., Is late diagnosis of lung cancer inevitable? Interview study of patients recollections of symptoms before diagnosis. Thorax, 2005. 60: p. 314-319. Baird J. Raising the Public Profile of Lung Cancer – Report of a National Lung Cancer Awareness Campaign in the UK. Lung Cancer (2003) 42, 119-123. Lung Cancer Alliance – Shine a Light campaign http://www.lungcanceralliance.org/shinealightonlungcancer/ Athey, U.L., Suckling R.J, Tod, A.M, Walters, S.J, Rogers, T.K, Thorax, 2012. May: 67(5); 412-7. Early diagnosis of lung cancer : evaluation of a community based social marketing intervention. Be Clear on Cancer – Lung Cancer campaign http://www.campaigns.dh.gov.uk/category/beclearoncancer/

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      G02.3 - Clinicians as Advocates: Raising Public Awareness of Lung Cancer - The West Japan Oncology Group Experience (ID 441)

      T. Sawa, K. Eguchi, Y. Iwamoto, H. Semba, H. Yamamoto, T. Kashii, T. Seto, S. Nakamura, Y. Nakanishi

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      Abstract
      Background: In Japan and Asian countries, patient advocacy has not been popular to citizens and government, especially in patients with lung cancer compared to USA and EU countries. Therefore, a few clinicians had played a role as advocate instead of cancer survivors group or governments. Clinicians as advocates have a certain advantage to give professional information by themselves, with trained communication skill about bad news, and to use medical resources which is involved to medical society for lung cancer or hospital. West Japan Oncology Group (WJOG), non-profit organization which was established in 2000 by volunteer oncologists, has the mission to conduct and support multi-center clinical co-operative study for cancer and to provide the information about lung cancer, the importance and necessity of clinical study for standard treatment widely, therefore to contribute improving social welfare. Methods: To achieve the mission of WJOG, we carried out open lecture in city hall in major city every year and published lecture recordings in newspaper as well DVD video distribution. In another way, we planed to publish the guideline book for the patients with lung cancer and revised in five years interval. The board of directors determined the plan and the guideline editors committee was organized by WJOG member in March, 2006. The committee edited constitution, drafting, plan, writing as an enterprise in 2006, and 2011. Questions and answers style was adopted in accordance to previous US guidebook . Results: In these 12 years, 27 times of open lecture were held and medical specialists for oncology, novelists with cancer, representative or president of organization for patients advocacy, and etc gave lecture and discussed with patients. Nearly two to eight hundred people had participated in each meeting, occupied by most women and senior citizens. The questionnaire survey to participant revealed satisfaction for lecture and expectation for next meeting. The contents of lecture appeared full page in the Asahi which has a large circulation of almost 8 million (the second position in the world) as well as DVD-video was distributed widely to institute participating to our study and patients for the purpose of providing larger citizens with useful information. Furthermore WJOG official web site show the detail of each lecture in Japanese because Japanese patients with lung cancer are old and difficult to read English web site. Last year, second edition guideline book for patients was edited which consists of 118 questions and answers with full color 200 pages, as well posted to the WJOG website. GLCC international quantitative survey in 2010 showed that Japan is one of the countries with the greatest proportion of adults who think lung cancer is the biggest killer Conclusions: It seems that patient advocacy is developed to be more popular through open lecture, newspaper, web site and guideline book even in Japan. This method may be one of the ways to raise public awareness of lung cancer in Asian countries.

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      G02.4 - Survivors as Advocates: What is possible? - The Lung Cancer Alliance Experience (ID 442)

      K. Cofrancesco

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      Abstract
      Working with survivors is the foundation for every one of our programs at Lung Cancer Alliance. We examined the past nine years and the varying degrees of success of each of our initiatives based on the engagement of survivors to accomplish our goals. We will discuss the ways in which survivors join our movement and the various ways in which advocacy can help them during their journey with lung cancer.

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      G02.5 - How Clinicians and Patients Can Benefit From Better Data on Lung Cancer (ID 443)

      M.D. Peake

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      Abstract
      Background There is evidence from a variety of sources that lung cancer outcomes in the UK are worse than in many other parts of the developed world [1,2]. Part of this ‘survival gap’ can be explained by late diagnosis as evidenced by an excess of deaths within the first few months of diagnosis [3] and a high rate of patients (~40%) being first diagnosed during emergency hospital admissions [4]. However stage-for-stage survival is also worse in the UK [2], surgical resection rates are [5] and there is a clear relationship between these rates and survival [6].Methods The National Lung Cancer Audit (NLCA) had its first full year of data collection in 2005. Its aim was to collect a core dataset of around 140 items on all patients newly diagnosed and with lung cancer and mesothelioma in all hospitals in England expanding to cover the entire UK from 2008. Data is collected by the Multi-disciplinary teams and entered onto a secure national database. As of May 2013 there are almost 220,000 patient records for England alone in the database and all hospitals in the UK regularly report data for their patients. Annual reports contain a wide range of indicators including: numbers of patients diagnosed; treatment rates for surgery, chemotherapy and radiotherapy, case mix factors such as age, stage, performance status, co-morbidity and socio-economic status. Median and one-year survival rates are also reported. Data are presented both in terms of crude percentages and case-mix adjusted odds ratios. These reports, including the identification of hospitals, are available to the public. The programme has been backed up by a series of meetings with hospital teams to identify their particular strengths and weaknesses, to support them in service improvement and to share examples of best practice.Results The table below shows some examples of data completeness and the ‘headline indicators’ from England and Wales between 2005 and 2011 (the latest period for which data are available). It will be seen that data quality and completeness has improved as have all the process and outcome indicators.Figure 1 We have demonstrated that there is wide variation in treatment and survival within the UK [7,8]. One of the most dramatic and important impacts of the audit has been the realisation of just how low surgical resection rates were in some parts of the UK and that this was related to a serious shortage of specialist thoracic surgeons in many areas [9]. The number of thoracic surgeons has almost doubled since the publication of the first audit report and the overall resection rate has increased by almost 50%. In addition, we have many examples of where local practice and service configuration have been significantly improved as a result of this process. We are now assessing the extent to which these changes have been translated into improvements in survival. The Roy Castle Lung Cancer Foundation has developed a web-based system called the ‘Lung Cancer Smart Map’ [10] which allows patients to search how treatment in their area compares both with other hospitals and against national standards. Patient empowerment of this sort is potentially one of the most effective ways to drive up standards of care.Conclusions In summary, we have demonstrated that population-based data collection is feasible and as a result, the NLCA database is one of the largest and most detailed lung cancer databases in the world. The regular feedback and support that we have given to clinical teams and to patients has had a significant impact on the quality of care for patients in the UK and is now incorporated into our Cancer registration systems, with its potential value being enhanced by linkage to a wide variety of other data sources.References 1. Lung cancer survival and stage at diagnosis in Australia, Canada, Denmark, Norway, Sweden and the United Kingdom: a population-based study, 2004-2007. Walters S, Maringe C, Coleman MP, et al. Thorax, 2013;68:551-564 2. Coleman MP, Forman D, Bryant H, et al.; ICBP Module 1 Working Group. Cancer survival in Australia, Canada, Denmark, Norway, Sweden, and the UK, 1995-2007 (the International Cancer Benchmarking Partnership): an analysis of population-based cancer registry data. Lancet,2011;377:127–138 3. National comparisons of lung cancer survival in England, Norway and Sweden 2001- 2004: differences occur early in follow-up Holmberg L, Sandin F, Bray F, et al. Thorax, 2010;65:436-441. 4. Elliss-Brookes L, McPhail S, Ives A, et al. Routes to diagnosis for cancer – determining the patient journey using multiple routine data sets. Br J Cancer 2012;107(8):1220-6. 5. Recent trends in resection rates among non-small cell lung cancer patients in England. Riaz SP, Linklater KM, Page R, et al. Thorax, 2012;67(9):811-4. 6. Variation in radical resection for lung cancer in relation to survival: population-based study in England 2004-2006. Riaz SP, Lüchtenborg M, Jack R, et al.Eur J Cancer 2012;48:54-60 7. Exploring Variations in Lung Cancer Care Across the UK - The “Story So Far” for the National Lung Cancer Audit. P Beckett, I Woolhouse, R A Stanley, M D Peake. Clinical Medicine, 2012; 12:4-8 8. Health & Social Care Information Centre. The National Lung Cancer Audit Report 2012. Available at: https://catalogue.ic.nhs.uk/publications/clinical/lung/nati-clin-audi-supp-prog-lung-canc-coho-2011/clin-audi-supp-prog-lung-nlca-lap-2012-rep.pdf 9. The effects of increased provision of Thoracic Surgical Specialists on the variation in lung cancer resection rate in England. Lau KK, Rathinam S, Waller DA & Peake M.D. J Thoracic Oncology, 2013;8(1):68-72 10. Lung Cancer Smart Map, available at: www.roycastle.org/lungcancermap

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      G02.6 - Closing Remarks, Including Comment on IASLC and Advocacy - The Future (ID 444)

      P. Goldstraw

      • Abstract

      Abstract
      At its strategic review in September 2011 the IASLC undertook a thorough overall of its existing committee structure. As the membership of the organisation expanded and its influence globally was increasing it was felt that it was appropriate for the organisation to move beyond its traditional scientific and educational roles to embrace fundamentally important aspects of care such as advocacy, the involvement of nurses and allied professionals and tackling the scourge of tobacco dependency. There were already several established advocacy organisations, especially in North America, the UK and Australia. Our aim was not to compete but to network with these bodies to ensure that advocacy issues were included in the discussions of every one of our other committees and at every educational activity organised by the IASLC and its partners. We are thus delighted that at this World Conference, the first since our committee was established, we have high profile sessions such as this, in collaboration with the Global Lung Cancer Coalition, and those held yesterday, organised by the Australian Lung Foundation and other partners. From 2015 our World Conferences will be held annually and our programme of regional meetings in Europe, Asia, North and South America will continue. We hope that the IASLC meetings and our journal, the Journal of Thoracic Oncology, will be seen as the appropriate platform for issues such as patient advocacy, specialist nurse care, smoking cessation and tobacco control to be aired. The members of the IASLC are specialists in every research and clinical care aspect of thoracic oncology, working to improve the outcomes for lung cancer and other thoracic malignancies. You, the advocates, are our link to patients who need, deserve and demand better care. Let us work together to the benefit our patients.

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    MS16 - ESTS/IASLC Thymic Session (ID 33)

    • Event: WCLC 2013
    • Type: Mini Symposia
    • Track: Thymoma & Other Thoracic Malignancies
    • Presentations: 5
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      MS16.1 - Pathological Classification of Thymic Tumours in the Molecular Age: Proposals for the Next WHO Classification (ID 530)

      W.D. Travis

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      Abstract
      Thymomas are epithelial neoplasms arising in the thymus with a spectrum of morphology, genetic characteristics and clinical behavior. Thymomas are composed of a mixture of neoplastic epithelial cells and non-neoplastic T lymphocytes, admixed in varying proportions. Much of the controversy about classification of thymic epithelial tumors can be attributed to confusion about differences in histologic classification versus grading. While genetic studies have provided some insights into the biology of these tumors and classification, a major hurdle is how to identify molecular abnormalities specific to the epithelial cells of B1 and B2 tumors because the genetic findings are dominated by the numerous lymphocytes in the tumor stroma. Thymic epithelial tumors are classified into thymomas and thymic carcinomas according to the 2004 World Health Organization (WHO). Thymomas are classified into Type A and Type B tumors with the latter being divided into B1, B2 and B3 with an increasing percentage and degree of atypia of epithelial cells and decreasing numbers of lymphocytes. THYMOMA Type A thymoma, is composed of bland spindle or oval shaped and few lymphocytes. Type AB thymoma, , is composed of two components, one resembling the type A thymoma and one with plump cells and predominant lymphocytic infiltrate. Type B1 thymoma, is composed of a prominent lymphocyte population with a minor component of epithelial tumor cells with vesicular nuclei and small nucleoli. Type B2 thymoma, is a thymoma with relatively even mixtures of lymphocytes and plump epithelial cells with vesicular nuclei. Type B3, is predominantly composed of polygonal or round epithelial cells with mild atypia. This category shows variable degree of cytologic atypia. THYMIC CARCINOMA Thymic carcinoma was previously classified as Type C thymoma, but in the 2004 classification this term was dropped. These tumors show much greater degree of cytologic atypia than thymoma. CLASSIFICATION ISSUES Histologic heterogeneity is common, with more than one histologic subtype frequently present in a given tumor, making histologic subclassification difficult. The clinical relevance of the WHO classification system has been validated by many studies. In general the classification from type A to AB, B1, B2 and B3, then thymic carcinoma represent an increasing histologic grade that corresponds to increasing aggressiveness of clinical behavior. Increasing molecular alterations are also found along this spectrum from A to B3 thymoma and thymic carcinoma. Thymic epithelial cells stain for epithelial markers such as keratin and squamous markers such as p63 or p40 while thymic lymphocytes stain for T-cell markers such as TdT and CD3. Type A thymomas tend to have fewer immature (CD1a+) lymphocytes and more mature (CD1a-) lymphocytes, while the type B thymomas have many CD1a+ lymphocytes. PAX8 has been reported to be positive in tumor cells of thymomas. Confusion between histologic classification and grading has led to proposals to collapse the classification into a smaller number of entities. One meta-analysis suggested that the current WHO classification scheme of thymomas could be simplified into three types with significant prognostic value: A/AB/B1, B2, and B3. However, what these authors propose is more of a grading system based on clinical behavior rather than histologic typing. The proposal suggests combining two tumors that are completely different morphologically and genetically (type A and B1) both of which are low grade tumors with indolent clinical behavior. Genetic studies have shown distinct gene expression profiles that support the WHO subclassification of thymomas, as far as the subdivision in type A and B thymomas is concerned. Type AB thymomas are genetically heterogeneous, being more closely related to type B thymomas. Expression of the autoimmune regulator AIRE is lost in approximately 95% of thymomas. Genetic alterations in thymomas are most frequent on chromosome 6p23.3 (major histocompatibility complex locus) and 6q25.2 to 25.3. Thymic carcinoma has a distinctive morphology and biology. It is composed of highly atypical cells with cytoarchitectural features of carcinoma similar to those seen in other organs. Although many lymphocytes can be seen in its stroma, they are of B cell type and mature T cell type. Thymic carcinoma lacks the immature T cell lymphocytes that are present in thymoma. Thymic carcinomas are cytologically malignant.{Travis, 2004 #21463} While a certain amount of necrosis, atypia, and mitoses can be encountered in occasional epithelial thymomas, these findings are common in thymic carcinomas. An infiltrative growth pattern associated with desmoplastic stroma is often seen, without evidence of immature T lymphocytes. Thymic carcinomas display a variety of histologic subtypes, emphasizing the ability of thymic epithelium to differentiate toward different cells: squamous cell carcinoma, basaloid carcinoma, mucoepidermoid carcinoma, lymphoepithelial-like carcinoma, sarcomatoid carcinoma, clear cell carcinoma, adenocarcinoma, and NUT carcinoma with t(15:19) translocation. Several immunohistochemical studies have been employed in an attempt to confirm the diagnosis of thymic carcinoma. Several studies have found that CD5 will stain the epithelial cells of some thymic carcinomas. C-kit (CD117) also frequently stains thymic carcinomas. However, neither of these markers are found in all thymic carcinomas and uncommonly they can be positive in B3 thymomas or carcinomas from other sites such as the lung. Comprehensive genomic analysis using comparative genomic hybridization has shown thymic carcinomas are molecularly distinct from thymomas and squamous cell carcinomas of the lung. While c-Kit expression is common in thymic carcinomas mutations are rare. Despite multiple trials of molecular targeted therapies for the EGFR pathway, angiogenesis inhibition, c-kit pathway, histone deacetylase inhibition, octreotide, an IGF-1 receptor pathway, there are no validated targeted therapies that can be recommended at this time. With some of these approaches in early therapeutic trials, and active molecular investigation of these rare tumors, hopefully, in the near future, new treatment options for patients with advanced disease will become available. So far, molecular studies have provided useful insights into the histologic subtypes of thymic epithelial tumors and provide genetic validation of the existing classification, but they have not demonstrated superiority over morphology in classifying these tumors. Hopefully molecular markers can be identified that will aid in refining the existing classification or in separating the existing subtypes.

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      MS16.2 - Towards a TNM-Based Prognostic Classification for Thymic Tumours (ID 531)

      F. Detterbeck

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      Abstract
      There are many impediments to achieving scientific progress in thymic malignancies, starting with the fact that these are relatively rare tumors. Another problem is the fact that there is no official stage classification system. At least 15 different systems have been proposed, all of which have been based on a limited number of patients, and none of which has been universally adopted with clear definitions that are consistently interpreted. This lack of a common basic language is a crucial fundamental building block for scientific advancement. The International Thymic Malignancies Interest Group (ITMIG) is an academic organization devoted to promoting the scientific advancement in thymic and other mediastinal malignancies. ITMIG has partnered with IASLC to develop proposals to the AJCC/UICC for the 8[th] edition of the stage classification system. This process began in 2010 and is now in full swing. ITMIG has pulled together an international database of approximately 9,000 patients. This involves 77 centers and 16 countries, with a notable major contribution from the Japanese Association for Research in the Thymus (JART). This data, together with an additional approximately 1,800 patients provided by the ESTS have been made available to CRAB, the statistical center for IASLC stage classification analyses. The Thymic Domain of the Staging and Prognostic Factors Committee (SPFC) is currently analyzing this data. The committee is considering multiple factors, starting with an analysis of the prognostic value of the Masaoka and Masaoka-Koga stage classification systems. Subcommittees of the thymic domain are also looking specifically at T, N, M factors, the impact of tumor size, invasion into particular structures and clinical stage. Internal validation will be performed, considering treatment factors, clinical stage, histologic subtypes, geographic regions and taking into account both survival and recurrence. Potentially useful factors will be compared to assess the relative impact, and to select the best factors to propose for use in the 8[th] edition stage classification system.

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      MS16.3 - Surgery for Thymic Tumours: Outcomes from the ESTS Data Base (ID 532)

      E. Ruffini, D. Van Raemdonck, W. Weder, A. Brunelli, F. Detterbeck, P. Thomas

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      Abstract
      Introduction: Thymic tumors are rare malignancies and most of the current literature is composed of single-institutional series collecting small number of patients spanned over short time periods. The European Society of Thoracic Surgeons (ESTS) thymic working group developed a retrospective database among its members collecting patients with thymic tumors submitted to surgical resection between 1990 and 2010. Methods: A total of 2151 patients were collected from 35 Institutions, including 1798 thymomas, 191 thymic carcinomas (TC), and 41 Neuroendocrine Thymic Tumors (NETT)). 1709 patients (89%) received a complete resection. Myasthenia Gravis (MG) was present in 629 patients (35%). Different clinical-pathologic characteristics were analyzed for their impact on survival and recurrence. Primary outcome was overall survival (OS); secondary outcomes were the proportion of incomplete resections, disease-free survival (DFS) and the cumulative incidence of recurrence (CIR). Results: Ten-year OS and DFS rates were 73% and 70%. The risk of mortality increased with age and with the stage. It also increased in the presence of TC, NETT and incomplete resection. Ten-year CIR was 12%. Predictors of incomplete resection included male gender, tumor size, the absence of MG, non-thymoma categories (TC and NETT) and high-risk thymomas (B2-B3). The risk of recurrence increased with tumor size, increased stage and NETT. Finally, our analysis indicates that the overall effect of adjuvant therapy after complete resection on OS was significantly beneficial (p=0.05) using a propensity score. Conclusions: Masaoka stages III-IV, incomplete resection and non-thymoma histology showed a significant impact in increasing recurrence and in worsening survival. The administration of adjuvant therapy after complete resection is associated with improved survival.

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      MS16.4 - Chemotherapy for Thymic Tumours (ID 533)

      N. Girard

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      Abstract
      Thymic epithelial tumors represent a wide range of anatomical, clinical, histological, and molecular malignant entities, which may be aggressive and difficult to treat. The histopathological classification distinguishes thymomas from thymic carcinomas. Chemotherapy may be used in two clinical scenarios in thymic epithelial tumors: 1) chemotherapy may constitute primary part of the multimodal curative-intent treatment of locally-advanced tumors, and is subsequently combined with surgery or radiotherapy; the main objective is to achieve long-term survival with no evidence of tumor recurrence; 2) chemotherapy may be delivered as the sole treatment modality in unresectable, advanced, metastatic, or recurrent tumors; then a palliative-intent treatment, the aim is to improve tumor-related symptoms through achievement of tumor response, while no prolonged survival is expected. Several chemotherapy regimens have been used in the curative-intent setting, mostly consisting of adriamycin- and/or platin-based multi-agent combinations. Usually 2-4 cycles of chemotherapy are administered before imaging reassessment. Aiming at increasing the response rate to primary treatment, and thus complete resection rate, chemotherapy may be combined with radiotherapy; however, retrospective data available do not provide with interpretable figures to compare chemotherapy to chemo-radiotherapy in the pre-operative setting. Response rates to curative-intent chemotherapy ranged from 70% to 80% in the largest studies. Patients for whom R0 resection was thought to be feasible undergo surgery, and complete resection is achieved in about 50% of cases. Postoperative radiotherapy is then frequently delivered. When the patient is not deemed to be a surgical candidate - either because R0 resection is not thought to be achievable or because of poor performance status or co-existent medical condition, definite radiotherapy, as reported above, is delivered. If radiotherapy is not feasible, either because of a large tumor burden that precludes safe delivery of appropriate doses or because of co-morbidities increasing the risks of radiation-induced toxicity, treatment is chemotherapy alone, in a strategy that may ultimately be considered palliative. In the reported literature, 10-21% of patients with locally-advanced thymic tumors receiving upfront chemotherapy did not receive either surgery or radiation therapy or other local treatment. Survival of these patients is frequently limited. Overall, the major challenge in interpreting data about pre-operative chemotherapy in thymic malignancies is the wide variation in the number of patients subsequently treated with surgery, radiotherapy, or chemotherapy alone, which suggests significant heterogeneity in the inclusion criteria among series. Response has been evaluated based on elusive criteria in some studies published before CT scan was largely available. In most studies, thymomas and thymic carcinomas, as well as newly diagnosed and recurrent tumors, were not analyzed separately. Ultimately, the majority of studies are retrospective, with uncontrolled design. Finally, one should consider the potential effect of corticosteroids, that have been known for a long time to have a “lympholytic” effect. Palliative chemotherapy is given as the sole treatment modality for thymic tumors, usually in the setting of stage IV, unresectable, recurrent disease. Prolonged disease control is possible, but tumor eradication is not expected. Several studies - both prospective and retrospective - described several regimens for definite chemotherapy, but because there are no randomized studies, it is unclear which are best; multi-agent combination regimens and anthracycline-based regimens appear to have improved response rates compared to others, especially the etoposide, ifosfamide and cisplatin combination. In general, combination regimen is recommended, for at least 3 and no more than 6 cycles. Overall, response rates are 20-40%, lower than that observed in the preoperative setting. Progression-free and overall survival of patients ranges from 12 to 66 months, and 37 to 72 months, respectively; such variability may be related to the various settings in which chemotherapy was delivered in those studies. In the palliative-intent setting, several consecutive lines of chemotherapy may be administered when the patient presents with tumor progression. It is estimated that 50-70% of patients with thymoma recurrence are eligible to chemotherapy. Strategy may consist of the re-administration of a previously effective regimen, especially in case of previous response, late occurring recurrence, and for anthracyclins, a patient in a good medical condition and not having received cumulative doses precluding the safe delivery of at least 3 additional cycles. In case of recurrence, the strategy may actually primarily consist of a similar multimodal management to that conducted at time of first diagnosis, with surgery and radiotherapy in eligible cases. Complete re-resection remains a major prognostic factor in this setting. In patients not eligible to receive additional chemotherapy, octreotide may represent a valuable option; as a single agent, octreotide produced objective tumor responses rates, and of more relevance in this setting, disease control rates. Novel treatment strategies are needed, especially for refractory, recurrent tumors, and thymic carcinomas, which carry a poor prognosis despite multimodal treatment. Potentially druggable targets are emerging, laying the foundations to implement personalized medicine for patients. Given the currently available targeted agents outside of a clinical trial, the signaling pathways that are relevant in the clinical care of patients, are the KIT and the Vascular Endothelial Growth Factor (VEGF)-R (Receptor) pathways. Promising new targets in thymoma and thymic carcinoma include IGF-1R and histone-deacetylase. Cixutumumab, an IGF1-R directed monoclonal antibody was recently reported to produce a promising 90%-disease control rate in refractory thymomas. Belinostat, a histone deacetylase inhibitor was evaluated in thymic malignancies in a recently completed phase II trial enrolling 41 patients (25 thymomas and 16 thymic carcinomas). Response and 2-year survival rates were 8% and 77% in thymomas. mTOR inhibitors, in the setting of phase I trials, have been reported to produce significant control rates in thymoma and thymic carcinoma. Along with the large variety of questions relative to the treatment strategy, thymic epithelial tumors represent a model of therapeutic implementation and achievement in orphan thoracic oncology, showing how the advent of new results induces new questions, as well as diversifies further clinical research directions; in this setting, regional and international collaborative initiatives are mandatory to progress both in the understanding of the biological mechanisms underlying the development of thymic malignancies, and in the identification and validation of new targets with prognostic and predictive value.

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      MS16.5 - Radiotherapy for Thymic Tumours: Induction, Adjuvant and Definitive (ID 534)

      R. Komaki

      • Abstract
      • Presentation
      • Slides

      Abstract
      Although the predominant approach in the treatment of thymoma and thymic carcinoma is surgery, radiation therapy also has an important role, either as postoperative therapy to reduce the risk of mediastinal recurrence or as part of definitive treatment for patients that who cannot undergo surgery. We present here a review of radiation therapy for thymic malignancies and briefly discuss the potential benefits from novel technologies for such treatment. Thymic carcinoma is a rare but more aggressive tumor which has a tendency to fail locally and distantly. Thymic carcinoma has more frequent EGFR and/or HER2 abnormalities compared to thymoma., and the outcome of thymic carcinoma is usually worse than invasive thymoma. Postoperative Radiation Therapy: Indications R0 (Completely Resected) Thymic Malignancies In general, radiation should be considered more strongly as the risk of recurrence increases. Therefore, for patients with the lowest likelihood of recurrence (i.e. completely resected Masaoka stage I thymoma), radiation can be safely omitted. For those at intermediate risk of local recurrence after complete resection, i.e. those with aggressive tumor histologies (such as thymic carcinoma) or Masaoka stage II and stage III disease, retrospective evidence exists both to support and contradict claims of benefit from adjuvant radiotherapy after complete resection. In general, our institutional practice includes postoperative radiation for completely resected Masaoka-Koga stage III thymoma and stage II or III thymic carcinoma. Risk assessment and stratification is usually done in a multidisciplinary setting and drives the choice of adjuvant treatment. The International Thymic Malignancy Interest Group (ITMIG) published a set of definitions and reporting guidelines for the use of radiation therapy for thymic malignancies in 2011. Pertinent recommendations for postoperative therapy are as follows. First, the term “postoperative” should be used for situations in which the tumor is resected and no residual disease is evident on imaging. If gross disease is present on postoperative imaging, then the disease should be defined as “recurrent” and the intent as “radiation for postoperative disease.” Second, the minimum acceptable dose for postoperative R0 disease is 50 Gy in 5 weeks. Finally, radiation to elective nodal regions not recommended, and the extent of malignancy before surgery should be used as a guide for designing the treatment fields. Microscopic Positive Margins (R1) and Gross Disease (R2) Radiation for R1 or R2 thymic malignancies should be started within 3 months of surgical resection. Doses between 40 Gy and 64 Gy are most appropriate for microscopically positive margins, whereas doses of 54 Gy or higher should be used for gross disease; both given in standard fractions of 1.8- to 2.0-Gy. Patients with positive margins should be considered for concurrent chemotherapy and radiotherapy, especially among patients with thymic carcinoma. Definitive Radiation Therapy Definitive radiation therapy is generally used for patients who are not candidates for surgery because of either the extent of disease at diagnosis or medical comorbidities. Because chemotherapy is a known radiation sensitizer, the combination of chemotherapy and radiation is considered most likely to control disease in these circumstances. In this setting, which is analogous to recurrent disease after surgical resection, we recommend radiation doses of 60 Gy -66 Gy to encompass gross disease plus a margin for microscopic regions at risk. Thymic carcinoma behaves more like non-small cell lung cancer arising from the thymus. Therefore, unresectable thymic carcinoma needs to be treated based on the histology or molecular biomarkers of expression e.g. EGFR, HER2 c-KIT and BCL-2. Approximately 50% of thymic carcinoma has squamous histology which can be treated with cisplatin based chemotherapy and radiotherapy. If unresectable thymic carcinoma has atypical carcinoid histology, etoposide and cisplatin plus radiotherapy might be the best option. For recurrent thymic carcinoma, molecular targeted agents e.g EGFR-TKI, c-KIT inhibitors and VEGFR inhibitors can be delivered in the protocol setting with or without radiotherapy. Techniques Because of the central location of thymic malignancies and the relatively high doses used in radiation therapy, we strongly recommend the use of conformal techniques, such as three-dimensional conformal radiation therapy (3D-CRT), intensity-modulated radiation therapy (IMRT), or, if available, proton beam therapy owing to the physical properties of the particles (i.e., the Bragg peak) which produce lower doses both proximal and distal to the target volume. In addition, because tumors can show substantial changes in shape or size over the course of several weeks of radiation therapy, we recommend that when radiation is to be used as definitive therapy, adaptive planning should be considered. Long-Term Consequences of Radiation on the Heart and Vasculature An abundance of evidence exists to show that long-term survivors of mediastinal radiation therapy can develop both acute and chronic cardiac sequelae. With regard to acute effects, the dose and fractionation of the radiation and the volume of heart irradiated all affect the risk of pericarditis and pericardial effusion. Given the close physiologic association between perfusion and ventilation, one might expect that radiation to the heart could affect lung function and vice versa. In a clinical study, investigators found that several heart dose-volume variables predicted radiation pneumonitis and that the fit of a model predicting pneumonitis was improved by the incorporation of heart variables. In conclusion, considerable evidence has shown that irradiation of the heart and vasculature can lead to increased acute and long-term toxicity and that these side effects are related to the dose, volume, and exact location of the irradiated field. Short-term surrogates of long-term toxicity such as findings on cardiovascular imaging or biomarker correlates would be helpful for identifying which patients at greatest risk for cardiac events. In the meantime, we recommend the continued use of advanced radiation therapy technologies such as IMRT, proton beam therapy, 4D imaging and treatment planning, and adaptive planning whenever possible to minimize the dose to mediastinal structures for patients with thymic disease, many of whom will survive for several decades and thus will live to see the long-term consequences of irradiation of these vital organs.

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    PL05 - Genomics: From Research Tool to the Lung Cancer Clinic (ID 76)

    • Event: WCLC 2013
    • Type: Plenary Session
    • Track: Pathology
    • Presentations: 5
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      PL05.0 - N/A - Chair Intro (ID 795)

      • Abstract

      Abstract not provided

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      PL05.1 - Implications of the Lung Cancer Genome Sequencing (ID 796)

      R. Govindan

      • Abstract
      • Slides

      Abstract not provided

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      PL05.2 - Challenges in Bioinformatics (ID 797)

      Y. Shyr

      • Abstract
      • Slides

      Abstract not provided

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      PL05.3 - Challenges for the Clinician (ID 798)

      S. Devarakonda, D. Morgensztern, C. Belani, R. Govindan

      • Abstract
      • Slides

      Abstract
      . Although EGFR mutations and fusions involving ALK and ROS1 are targetable by currently approved agents, these alterations are present in less than a fifth of patients with non-squamous NSCLC. Treatment options for the majority of patients remain largely empirical. The urgent need to develop therapies capable of targeting cancers without these alterations can only occur with a better understanding of the molecular biology and cytogenetic alterations. Recently, the lung cancer mutation consortium reported longer survival in patients with adenocarcinoma who underwent multiplexed genomic testing for the detection of alterations in 10 genes, and subsequently received matched targeted treatments. [Johnson et al J Clin Oncol 31, 2013 (suppl; abstr 8019)]. A total of 1,007 patients were screened for at-least one genetic alteration, and an actionable alteration that led to the use of targeted therapies was detected in 28% of these patients. The median survival in these patients was 3.5 years, while patients whose tumors did not harbor actionable alterations had a median survival of 2.1 years. It would be reasonable to assume that adapting NGS technologies, which allow comprehensive screening of the entire genome at a higher resolution, will result in improved outcomes in patients whose tumors do not harbor targetable mutations identifiable by commercially available assays. NGS has allowed a better characterization of lung cancer, with the identification of novel mutations and copy number alterations. Preliminary results from TCGA demonstrated that a significant percentage of patients with lung cancer harbor a targetable abnormality. It is still possible that additional less common mutations or alterations will be discovered once the sequencing of 1000 lung cancer samples is completed by TCGA. The next challenge is the development of novel drugs based on specific targetable abnormalities. Although this strategy may require extensive evaluation and multiple trials targeting distinct molecular subtypes of tumors, this departure from the empirical treatment of lung cancer, probably represents the best hope towards achieving meaningful progress.

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      PL05.4 - Closing Remarks and Invitation to Denver, 2015 (ID 799)

      • Abstract

      Abstract not provided



Author of

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    E13 - High Risk Patients and Low Risk Surgeons (ID 13)

    • Event: WCLC 2013
    • Type: Educational Session
    • Track: Surgery
    • Presentations: 1
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      E13.4 - Decision-Making and the New IASLC Staging System (ID 435)

      P. Goldstraw

      • Abstract
      • Presentation
      • Slides

      Abstract
      The 7th edition of TNM for Lung Cancer, introduced in January 2010, was based entirely upon recommendations from the IASLC Staging and Prognostic Factors Committee. The enormous size of the data base, its international accrual of cases diagnosed over a relatively short time period and its inclusion of cases treated by all modalities of care, coupled with detailed analysis and intensive validation ensured that this version aligned stage with prognosis more accurately than ever before. This was achieved by introducing new size cut-points for tumour size, re-assigning some T and M descriptors and moving some T, N, and M combinations to new stage groupings. Inevitably there are questions as to whether there should be consequent changes to established treatment algorithms. These discussions will focus upon the following scenarios: a) Larger node negative tumours, > 5cms, are now included in stage II. In the past 10 years we have seen data showing that stage II cases benefit from adjuvant chemotherapy after complete resection. Do these "new" stage II cases benefit from adjuvant therapy? b) Cases in which there are additional tumour nodules in the tumour-bearing lobe and other ipsilateral lobes have with certain combinations of N category, been down-staged to IIIA. Selected cases of stage IIIA disease have benefitted from resection, usually in a multi-modality setting. Should these cases, now included in stage IIIA be treated with regimens including surgery? c) Tumours invading certain mediastinal structures that were classified as T4 in previous editions of TNM have not been re-assigned but when associated with N0 or N1 disease these cases have been down-staged to stage IIIA. Should they also be considered for surgery in a multi-modality setting? Whilst it is impossible to give dogmatic and unequivocal advice on the right answer to these questions the speaker hopes to give some insights into the factors which might influence the decisions made by the Multi-Disciplinary Team in such situations. Other issues raised by the 7th edition include: a) The distinction between pulmonary metastases and synchronous primary tumours has been clarified and the opinion of the pathologist has been emphasised in this distinction. Thus in cases in which there is more than one malignant nodule biopsy of additional lesions may be required if such a distinction would alter the treatment advised in any case. b) The IASLC nodal map and definitions of nodal stations and zones are now the recommended means of describing regional lymph node involvement in lung cancer. All members of the MDT should be familiar with this nomenclature. c) The definition of an R0 resection now requires that a defined minimum of lymph nodes/stations be removed by the surgeon and examined by the pathologist. Surgeons and pathologists need to comply with this requirement and other members of the MDT need to understand this expanded definition. d) The 7th edition of TNM and the new IASLC/ATS/ERS classification of Adenocarcinomas may influence the management of screen-detected lesions. The new T category of T1a tumours no larger than 2cms and the fall in prognosis seen in lesions above this threshold may influence the choice of approach to lesions around this watershed, one's policy of structured surveillance and the extent of surgical resection for lesions confirmed to be malignant. As LDCT screening becomes more widely available the MDT managing these cases will need to consider these matters when developing their investigative algorithms.

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    G02 - Global Lung Cancer Coalition (GLCC) Session: Deserve Better - Expect Better: Advocating for Better Outcomes for Lung Cancer Patients (ID 15)

    • Event: WCLC 2013
    • Type: Other Sessions
    • Track: Nurses
    • Presentations: 1
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      G02.6 - Closing Remarks, Including Comment on IASLC and Advocacy - The Future (ID 444)

      P. Goldstraw

      • Abstract

      Abstract
      At its strategic review in September 2011 the IASLC undertook a thorough overall of its existing committee structure. As the membership of the organisation expanded and its influence globally was increasing it was felt that it was appropriate for the organisation to move beyond its traditional scientific and educational roles to embrace fundamentally important aspects of care such as advocacy, the involvement of nurses and allied professionals and tackling the scourge of tobacco dependency. There were already several established advocacy organisations, especially in North America, the UK and Australia. Our aim was not to compete but to network with these bodies to ensure that advocacy issues were included in the discussions of every one of our other committees and at every educational activity organised by the IASLC and its partners. We are thus delighted that at this World Conference, the first since our committee was established, we have high profile sessions such as this, in collaboration with the Global Lung Cancer Coalition, and those held yesterday, organised by the Australian Lung Foundation and other partners. From 2015 our World Conferences will be held annually and our programme of regional meetings in Europe, Asia, North and South America will continue. We hope that the IASLC meetings and our journal, the Journal of Thoracic Oncology, will be seen as the appropriate platform for issues such as patient advocacy, specialist nurse care, smoking cessation and tobacco control to be aired. The members of the IASLC are specialists in every research and clinical care aspect of thoracic oncology, working to improve the outcomes for lung cancer and other thoracic malignancies. You, the advocates, are our link to patients who need, deserve and demand better care. Let us work together to the benefit our patients.