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Michael Boyer

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    PL 01 - Prevention, Screening, and Management of Screen-Detected Lung Cancer (ID 586)

    • Event: WCLC 2017
    • Type: Plenary Session
    • Track: Radiology/Staging/Screening
    • Presentations: 4
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      PL 01.01 - Current Status of Smoking Cesession Program (Tobacco Control) (ID 7864)

      08:15 - 09:45  |  Presenting Author(s): Carolyn Dresler

      • Abstract
      • Presentation
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      Abstract:
      Smoking Cessation - What will it look like in the near future Perspective of the smoking epidemic by global map of smoking prevalence: Figure 1 What is ‘smoking cessation’ and what does it get us? Why should we care what is happening to the tobacco products that people are smoking? California led the tobacco control efforts in the USA and within 3-5 years saw a drop in lung cancer deaths. The tobacco control efforts in California began in the late 1980’s and the drop in lung cancer quickly was evident from people stopping smoking. (Barnoya & Glantz. Cancer Causes Control 2004;15(7): 689-95) With better tobacco control, with resultant smoking cessation, many other countries have similarly seen a decline in the deaths from lung cancer, mostly in western, high income countries. Most people who smoke want to quit, and wish they had never started and most people started smoking before they were 18 years of age. Smoking cigarettes, with its pulmonary delivery, is a very good delivery system for nicotine. It is the nicotine that addicts people and creates one of the most difficult to quit drugs in our societies. So, it is known that smoking cigarettes is addicitve, that most people who smoke want to quit and smoking them causes the number one cause of cancer death in the world - lung cancer. And, it is well-established that quitting smoking decreases the incidence and mortality from lung cancer. There are three major transnational tobacco companies in the world: Phillip Morris International (PMI), based in Laussane, Switzerland; British American Tobacco (BAT) based in London, UK; and Japan Tobacco International (JTI)based in Tokyo, Japan. The largest tobacco company, is the Chinese National Tobacco Corporation - and they are not quite yet international in their marketing scope. There are rumors of a financial bonus if PMI mergers with Altria in the USA - following their split in 2008; BAT has purchased Reynold Tobacco - the second-largest tobacco company in the USA. Thus, selling the product that causes a third of all cancers, including the number one, lung cancer, is an outcome of successful marketing by 4 major companies: PMI, BAT, JTI and China (largely overseen by the government). Marlboro cigarettes are one of the largest brand in the world - sold by PMI and Altria. Why does all of this matter to us? Because, where Marlboro goes, so goes the market. PMI has started to market its replacement of the Marlboro cigarette and they call i iQOS - or, ‘I quit ordinary smoking’. It is a ‘heat-not-burn’ product that they claim does not combust the tobacco and therefore is a less deadly product. At the time of this writing, PMI is in 30 countries and will be expanding globally in the near future. They have an application for the ability to claim a ‘reduced-harm’ product in the USA. (https://www.fda.gov/downloads/TobaccoProducts/Labeling/MarketingandAdvertising/UCM560044.pdf). Japan was one of the early markets for iQOS and it has taken the country by storm. One must make a reservation to purchase the product, as their specially designed stores are not able to keep them in stock. The iQOS product is steadily gaining prevalence in Japan - to the dismay for JTI who previously overwhelming had the largest market share. PMI has launched in South Korea, in hopes to capture the same success as they have found in Japan. As was stated earlier, most people want to quit smoking cigarettes - both for their health and the impact of secondhand smoke on others. iQOS claims to provide them with the nicotine that will continue to support their addiction, but removes the ‘harm’ from smoking. Of course, this is not known if this is true until changes are seen in the incidence of tobacco induced diseases, including of lung cancer. BUT - if there is a dramatic change from what people have smoked in the past and what they change to smoke in the future - there may be dramatic differences in lung cancer incidences and probably, of the type of lung cancer. Electronic cigarettes have also significantly impacted the marketplace and also claim to cause significantly less tobacco related disease. Uptake of electronic cigarettes has been variable around the world due to differences in regulatory environments and availbility of marketing acumen. However, none of electronic cigarettes have the marketing strength of the largest trans-national tobacco company, PMI, and their heat-not-burn product. The CEO of PMI Andre Calantzopoulos has stated: “if you extrapolate the figures, then logically we could reach the tipping point in five years. That is when we could start talking to governments about phasing out combustible cigarettes entirely.” {in interview with Nikkei Asian Review} Of course, he only means for the countries that can afford their heat-not-burn product - for the rest of the world, they can still have their combusted cigarettes. For us in IALSC, we can hope that electronic cigaretes and heat-not-burn products do cause less lung cancer - as people who smoke cigarettes quit - even if they transition to heat-not-burn cigarettes or electronic cigarettes. What is unknown is whether people who use either a heat-not-burn or electronic cigarettes - who quit smoking cigarettes - will have fewer lung cancers - in the very near future.



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      PL 01.02 - Major Advances in CT Screening: A Radiologist's Perspective (ID 7838)

      08:15 - 09:45  |  Presenting Author(s): Claudia I Henschke  |  Author(s): Rowena Yip, Michael Chung, Artit Jirapatnakul, Ricardo S Avila, David F Yankelevitz

      • Abstract
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      Abstract:
      Advances in CT scanners. CT screening was first introduced when helical CT scanners became available in the early 1990’s (1-4). Since then, there have been remarkable advances in CT scanner technology with concurrent increase in the number of CT examinations per year by approximately 10% annually. More powerful hardware and image reconstruction algorithms have allowed faster scanning at lower radiation doses in today’s multidetector CT (MDCT) scanners. Ultra low-dose techniques are gaining acceptance. With respect to lung cancer screening, thinner collimation now possible has led to the detection of many more small pulmonary nodules. Also, there have been evolutions in diagnostic techniques such as percutaneous biopsies, navigational bronchoscopy, and PET scans and these advances have been integrated into the regimen of screening with a resulting decrease in the frequency of surgical resection of benign nodules (5). Definition of Positive Results. Updates in the definition of positive results have continued to be developed that allow for improvements in the efficiency of workups. One of the major changes has been to update the size thresholds for positive results from 4 to 6 mm and also to avoid rounding errors (6, 7). The NELSON trial introduced the concept that a positive result should be based on the initial CT scan and a follow-up CT scan for small nodules, rather than solely on the initial CT scan and this has been adopted by I-ELCAP (6). The I-ELCAP and NLST databases have been used to provide follow-up strategies for nonsolid and part-solid nodules (6). Considerations as to screening frequency may substantially reduce costs for lower risk individuals. There is increasing recognition that different approaches are needed for baseline and repeat scans where even when nodules might have the same characteristics as they should be managed differently. The management of both nonsolid and part-solid nodules has dramatically changed. For the first time, imaging as a biomarker for aggressiveness has been used to monitor whether a cancer is progressing. Growing nonsolid nodules can be followed on an annual basis and only the emergence of a solid component triggers more aggressive intervention. For the part-solid nodule it has now been recognized that the important component from a prognostic perspective is the solid portion not the overall size. Quantitative assessments. Quantitative assessment of many findings on chest CT scans have been developed (6). In particular, assessment of nodule size and growth as to the probability of malignancy and lung cancer aggressiveness has progressed. Most guideline organizations have moved from a single measurement of length to an average diameter (average of length and width) (6) and to three measurements of volume (7). The errors involved in any of these measurements are influenced by multiple factors including the intrinsic properties of the nodule and the software used to make the measurement (8, 9). Additionally, they are impacted by the variability of CT scanners and their adjustable scan parameters. Advances in incorporating measurement errors into growth assessment by RSNA’s Quantitative Imaging Biomarkers Alliance (QIBA) has led to a web-based calculator. The American College of Radiology (ACR) specifies that growth for a nodule of any size requires “an increase of 1.5 mm or more.” Both approaches allow for large measurement errors for the wide range of CT scanners and the protocols. The I-ELCAP guidelines for solid and the solid component of part-solid nodules is given explicitly in I-ELCAP protocol (6). Each of these approaches has specific technical requirements as measurement error is influenced by both the scanner itself, the choice of various adjustable parameters on the scanner (slice thickness, slice spacing, dose, FOV, pitch, recon kernel etc.) as well as characteristics of the nodule itself. Additional considerations for computer-assisted volume change assessment requires: 1) inspecting the computer scans and the segmentation for image quality (e.g. motion artifacts) and for the quality of the segmentation; 2) the radiologist visually inspecting both nodule image sets side-by-side to verify the quality of the computer segmentation for each image that contains a portion of the nodule; 3) examination of the segmentations for errors such as when a vessel is segmented as part of a nodule in one scan but not in the other; 4) that the scan slice thickness for the purpose of volumetric analysis should be 1.25 mm or less. When using any computer-assisted software, the radiologist must be satisfied with the CT image quality and the computer segmentation results, further substantiating the notion that the decision of whether growth has occurred is ultimately based on clinical judgment. Innovations in use of imaging and genetic information. Radiomics is an emerging field of study on the quantitative processing and analysis of radiologic images and metadata to extract information on tumor behavior and patient survival (10). The hypothesis is that data analysis through automated or semi-automated software can provide more information than that of a physician. Its use has shown improved diagnostic accuracy in discriminating lung cancer from benign nodules. It has been used successfully in breast imaging, with 2017 FDA approval of a computer-aided diagnosis tool which utilizes advanced machine learning analytics. Furthermore, radiomics has been linked with the field of genomics, inferring that imaging features are closely linked to gene signatures such as EGFR expression, a known therapeutic target. In the future, as larger data sets emerge and inter-institutional sharing of images becomes more commonplace, radiomics will become more tightly integrated with lung cancer diagnosis, treatment planning, and patient survival prognostication. References 1. Henschke C, McCauley D, Yankelevitz D, Naidich D, McGuinness G, Miettinen O, Libby D, Pasmantier M, Koizumi J, Altorki N, and Smith J. Early Lung Cancer Action Project: overall design and findings from baseline screening. Lancet 1999; 354:99-105. 2. The International Early Lung Cancer Action Program Investigators. Survival of Patients with Stage I lung cancer detected on CT screening. NEJM 2006; 355:1763-71 3. Kaneko M, Eguchi K, Ohmatsu H, Kakinuma R, Naruke T, Suemasu K, and Moriyama N. Peripheral lung cancer: screening and detection with low-dose spiral CT versus radiography. Radiology 1996; 201: 798-802. 4. Sone S, Nakayama T, Honda T, Tsushima K, Li F, Haniuda M, et al. Long-term follow-up study of a population-based 1996-1998 mass screening programme for lung cancer using mobile low-dose spiral computed tomography. Lung Cancer. 2007; 58:329-41. 5. Linek HC, Flores RM, Yip R, Hu M, Yankelevitz DF, Powell CA. Non-malignant resection rate is lower in patients who undergo pre-operative fine needle aspiration for diagnosis of suspected early-stage lung cancer. Am J Respir and Crit Care Med 2015; 191: A3561 6. International Early Lung Cancer Action Program protocol. http://www.ielcap.org/sites/default/files/I-ELCAP%20protocol-v21-3-1-14.pdf Accessed March 27, 2015 7. Van Klaveren RJ et al. Management of Lung Nodules Detected by Volume CT Scanning. N Engl J of Medicine 2009; 361: 2221-9 8. Henschke CI, Yankelevitz DF, Yip R, Archer V, Zahlmann G, Krishnan K, Helba B, Avila R. Tumor volume measurement error using computed tomography (CT) imaging in a Phase II clinical trial in lung cancer. Journal of Medical Imaging 2016; 3:035505 9. Avila RS, Jirapatnakul A, Subramaniam R, Yankelevitz D. A new method for predicting CT lung nodule volume measurement performance. SPIE Medical Imaging 2017: 101343Y 10. Lee G, Lee HY, Park H, et al. Radiomics and its emerging role in lung cancer research, imaging biomarkers and clinical management: State of the art. Eur J Radiol. 2017; 86:297-307.

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      PL 01.03 - Changing Epidemiology in Lung Cancer (ID 7839)

      08:15 - 09:45  |  Presenting Author(s): Mary Reid

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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      PL 01.04 - What is the Optimal Management of Screen-Detected Lung Cancers (ID 7840)

      08:15 - 09:45  |  Presenting Author(s): Shun-ichi Watanabe

      • Abstract
      • Presentation
      • Slides

      Abstract:
      Introduction With the recent development of the CT scanner, the number of CT screen-detected early-stage lung cancer showing ground-grass opacity (GGO) is rising. Therefore a new optimal therapeutic strategy for pulmonary resection for screen-detected lung cancer has been required. History of standard surgical procedure for lung cancer Cahan (1960) reported the first 48 cases that successfully underwent lobectomy with regional lymph node dissection, which was called “radical lobectomy.” Since then, this procedure was universally accepted and has remained a standard surgery for lung cancer. As for sublobar resection, segmentectomy was initially used for the resection of localized bronchiectasis as reported by Churchill and Belsey (1939). Jensik (1973) reported their 15-year successful experience of segmentectomy for lung cancer patients. However, the use of sublobar resection as definitive management of NSCLC has been a controversial issue. Lung Cancer Study Group (LCSG) (1995) conducted the only randomized trial comparing sublobar resection with lobectomy for stage IA NSCLC patients. They observed a 75% increase in recurrence and a 50% increase in cancer death in the patients undergoing sublobar resection, compared to those in the patients undergoing lobectomy. This is the reason why lobectomy has remained a standard lung cancer surgery for a half century since Cahn’s successful report in 1960. Controversies in sublobar resection for patients with small-sized NSCLC Sublobar resection is a lung parenchyma-preserving surgery with limited nodal dissection. However, even small-sized lung cancer less than 2 cm in size shows hilar and mediastinal nodal disease with an incidence of more than 20%. Although PET is considered to be the most sensitive and accurate investigation for screening of lymph node involvement, with a sensitivity of 79 to 85% and specificity of 90 to 91% in a meta-analysis, the assessment of nodal status by PET is not reliable in patients with microscopic nodal metastasis. Riquet (1989) reported that lung cancer metastasizes so easily to the mediastinum that selection of the patients for limited surgery should be discussed carefully. Furthermore, lung cancer has a phenomenon termed “skip metastasis” consisting of N2 disease without N1 involvement with the incidence of 20-38% in N2 patients. Therefore, lobectomy with hilar and mediastinal lymph node dissection is considered to be a basic standard procedure for lung cancer. Differences in survival between sublobar resection and lobectomy Proposals of sublobar resection for clinical stage IA small-sized lung cancer less than 2 cm have been undertaken in some previous reports. Although these were non-randomized study, Okada (2001) and Koike (2003) conducted the comparative study between intentional sublobar resection and standard lobectomy in patients with tumors 20 mm or less in diameter. They showed no significant difference in survival between two groups and suggested that sublobar resection was acceptable operation for small-sized lung cancer. The significance and role of sublobar resection for subsolid tumor have become important so far. Clinical trials regarding sublobar resection vs. lobectomy Japan Clinical Oncology Group (JCOG) has conducted a cohort study (JCOG0201) evaluating correlation between radiological and pathological findings in stage I adenocarcinomas. With pathologic non-invasive adenocarcinoma defined as those with no lymph node metastasis or vessel invasion, radiological non-invasive lung adenocarcinoma was defined as those with a consolidated maximum tumor diameter to tumor diameter ratio (C/T ratio) of less than 0.5 (9). Currently, a prospective, randomized, multi-institutional phase III trial for small-sized (<=2 cm) lung cancer patients is being conducted by Cancer and Leukemia Group B (CALGB140503) to determine the effectiveness of an intentional sublobar resection for small-sized peripheral tumors. Similar phase III study (JCOG0802) is also being conducted, comparing lobectomy vs. segmentectomy for small-sized tumor with more than 0.5 C/T ratio. JCOG has already accumulated planned number of patients and now following the patients. JCOG is also conducting other two prospective multi-institutional phase II trials regarding the sublobar resection for GGO-dominant type tumors. One is JCOG0804, wide wedge resection for non-solid GGO lesion less than 2cm, and the other is JCOG1211, segmentectomy for part-solid GGO lesion with less than 0.5 C/T ratio and 2.1-3.0 cm in tumor diameter. Sublobar resection: anatomic or non-anatomic? No large-scale randomized trial comparing AS with non-anatomic WR, which is technically much easier than AS, for small-sized NSCLC has been conducted so far. Despite the fact that patients undergoing AS were more likely to have nodal sampling/dissection, and more LNs retrieved than patients undergoing WR in the present study, Altoki (2017) suggested that it did not lead to an improvement in survival. This is consistent with the results of the ACOSOG Z0030 trial comparing lymph node sampling with systematic nodal dissection in patients with T1-2 N0-1 NSCLC with no difference in survival between the two groups. These findings are of interest since data from the LCSG randomized trial showed that locoregional recurrence after WR was two-fold higher than that after AS. The results that AS should be the preferred option for SR were supported by recent large population-based studies suggesting. Smith (2013) reported the results of evaluating a large population Surveillance, Epidemiology and End Result-Medicare registry (SEER) database. They found that WR were associated with inferior survival compared to AS. However, advantage of AS over WR in the SEER database is probably due to different patient selection criteria as well as inadequate wedge resections with sub-optimal resection margins and insufficient or no nodal assessment. Whether WR and AS were comparable oncologic procedures for cT1N0M0 NSCLC patients or not has been still controversial issue so far. Conclusions Since the clear evidence regarding the survival benefit of sublobar resection for lung cancer patient is lacking so far, lobectomy should be an appropriate therapy for medically operable lung cancer patient at the moment. Abovementioned randomized trials will clearly define the role of sublobar resection in patients with stage I patients. As the number of early-stage peripheral lung cancers is increasing, and a certain number of patients are with multifocal small lesion, the choice of surgical procedure, that is, lobectomy, AS or WR, should be tailored to each case in the future.

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Author of

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    MA 10 - Immunotherapy I (ID 664)

    • Event: WCLC 2017
    • Type: Mini Oral
    • Track: Immunology and Immunotherapy
    • Presentations: 1
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      MA 10.05 - Improved Outcome for Immune Checkpoint Inhibitors (ICI) in Patients Previously Treated with Bavituximab in the SUNRISE Trial (ID 8684)

      11:00 - 12:30  |  Presenting Author(s): Michael Boyer

      • Abstract
      • Presentation
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      Background:
      Bavituximab targets exposed phosphatidylserine (PS) in the tumor microenvironment, resulting in repolarization of myeloid suppressor cells/M2 macrophages to M1, production of pro-inflammatory cytokines such as IFNγ and IL-12, dendritic cell maturation, and tumor specific cytotoxic T-cell activation. SUNRISE was a Phase III trial of docetaxel with bavituximab (D+B) or placebo (D+P) in patients with treated Stage IIIb/IV non-squamous NSCLC. Recent correlative analyses from SUNRISE suggest bavituximab is more active in PD-L1 negative, immune cold tumors and thus may complement PD-1/PD-L1 ICI.

      Method:
      This subgroup analysis included all patients who received subsequent ICI after discontinuing SUNRISE study drug. We calculated overall survival (OS) both from randomization and start of subsequent ICI.

      Result:
      Ninety-three of 597 randomized patients (16%) received ICI as next line of therapy after SUNRISE assigned treatment. Baseline characteristics were balanced between the treatment groups and consistent with the ITT population. From randomization, mOS was not reached (95% confidence interval [CI], 15.2-NA) in D+B (N=46) and 12.6 months (95% CI, 10.4-17.8) in D+P (N=47) (hazard ratio [HR], 0.46; P=0.006) (Figure). From start of ICI, mOS was not reached (95% CI, 10.2-NA) in D+B and 6.2 months (95% CI, 3.9-8.7) in D+P (HR, 0.42; P=0.002). The mPFS was 6.0 months (95% CI, 3.5-6.5) in D+B and 4.4 months (95% CI, 2.6-6.3) in D+P (HR, 1.00; P=0.991). ORR was 20% vs. 13% (Odds ratio 0.6; P=0.41) for D+B and D+P, respectively. The safety profile was similar between groups and no immune related (IR) toxicities (colitis, pneumonitis, hypothyroidism) were reported.

      Conclusion:
      Within the limits of a subgroup analysis, a significant improvement in OS was observed for patients previously treated with D+B. Furthermore, bavituximab has not been associated with IR toxicities and might serve as a useful drug in combination with ICI for the treatment of immune cold tumors. Figure 1



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    PL 02 - Presidential Symposium including Top 3 Abstracts and James Cox Lectureship Award Presentation (ID 585)

    • Event: WCLC 2017
    • Type: Plenary Session
    • Track: Early Stage NSCLC
    • Presentations: 1
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      PL 02.03 - Discussant - PL 02.02 (ID 10865)

      08:15 - 09:45  |  Presenting Author(s): Michael Boyer

      • Abstract
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      Abstract not provided

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    YI 01 - Young Investigator and First Time Attendee Session (ID 588)

    • Event: WCLC 2017
    • Type: Young Investigator
    • Track: Education/Publication/Career Development
    • Presentations: 1
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      YI 01.09 - How to Prepare an Abstract for an International Conference and How to Prepare Your Presentation for the Conference (Tips and Tricks) (ID 7852)

      08:00 - 11:30  |  Presenting Author(s): Michael Boyer

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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