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    ES05 - Joint Session GLCC/IASLC: Hot Topics for Lung Cancer Advocates (ID 8)

    • Event: WCLC 2019
    • Type: Educational Session
    • Track: Advocacy
    • Presentations: 5
    • Now Available
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      ES05.01 - Lung Cancer Survival: Progress and Challenges (Now Available) (ID 3175)

      10:30 - 12:00  |  Presenting Author(s): Marianne Coutts Nicolson

      • Abstract
      • Presentation
      • Slides



      Between 1970s and 2011, many tumour 10-year survival rates increased significantly (eg prostate cancer from 25% to 84%) yet lung cancer lags behind with 5-year survival below 20%.1, 2 Most countries have no lung cancer screening programme and >80% of patients are diagnosed with advanced disease. A significant challenge for the United States lung cancer screening programme is poor uptake by low income but high risk candidates.3 To optimise results from potential curative radical radiotherapy and surgery, accurate staging of patients is vital; modern staging can improve patient selection for radical treatment, with stage 1 lung cancer 4-year overall survival (OS) increased in one study by 14.3% between 2001 and 2010, and postoperative survival improved from 51.5% to 66.5%.4 Over 80% of patients diagnosed with lung cancer are active or past cigarette smokers, and the need to maximise prevention remains. Government implemented smoking bans and funding of smoking cessation programmes are important, despite sketchy evidence for the latter being of benefit to lung cancer patients.5

      Radiotherapy progress

      Improved techniques allow accurate targeting with stereotactic ablative radiotherapy (SABR) for patients with a small tumour who are unfit for surgery. In stage III NSCLC, CT simulation results in a smaller tumour target, better dose delivery and fewer side-effects. The immune stimulating effect of radiotherapy may increase effectiveness of immunotherapy (IO) on which further research continues. Radiotherapy ablation of oligometastatic tumours is also under investigation in ongoing attempts to improve survival in advanced disease.

      Systemic therapies improving survival

      There has been little improvement in small cell lung cancer (SCLC) outcomes the since 1980s, but progress for the 85% of patients with non-small cell lung cancer (NSCLC) is impressive, resulting from improved understanding of tumour molecular biology. Chemotherapy combinations seemed equivalent in NSCLC until groundbreaking results showed better survival in non-squamous NSCLC who received platinum with pemetrexed over gemcitabine.6 Maintenance pemetrexed improved survival still further in patients with NSCLC stable or responsive to induction chemotherapy.

      Controversy over patient selection for targeted therapy with tyrosine kinase inhibitors was resolved by the IPASS study which confirmed that testing for a sensitising EGFR mutation status was mandatory to ensure benefit.7 Patients inevitably develop resistance to EGFR TKIs and tumour rebiopsy is encouraged to determine the new molecular profile to optimise subsequent treatment. The new generation TKI osimertinib gave superior survival as first line therapy compared with erlotinib or gefitinib. In patients with ALK translocated NSCLC (approximately 5% of tumours), crizotinib was better than chemotherapy. More recently alectinib or brigatinib superceded as survival improved through their enhanced effectiveness in the CNS.8

      Drugs are available to treat lung cancers with less common genetic drivers like ROS1 and BRAF but the commonest NSCLC mutation KRAS - in up to 30% cases - is not yet amenable to specific therapy, although several drugs are in development. Reflex testing by pathologists of non-squamous NSCLC is recommended with squamous tumours tested only in never smokers or mixed adenosquamous lung cancer.9 Identification of EGFR or ALK oncogene addicted lung cancers is vital to ensure delivery first line of appropriate targeted therapy since this increases patients' survival.

      NSCLC response to IO drugs targeting PD-1 and PD-L1 has revolutionised systemic therapy. Nivolumab was effective in relapsed squamous NSCLC, then first line pembrolizumab superceded chemotherapy in patients with >50% PD-L1 expressing non-squamous tumours. Atezolizumab (second line) and pembrolizumab-chemo (first line) efficacy are independent of PD-L1 expression. In stage III NSCLC, patients with no tumour progression following combination chemoradiotherapy have better OS with maintenance durvalumab.10 An important feature is the durable response to IO seen in some patients, with toxicity usually manageable and less than many chemotherapies. Studies with IO as adjuvant and neoadjuvant treatments are ongoing. Since IO treatment may continue every 2-3 weeks by intravenous infusion for up to two years, there is a significant impact on pharmacy, hospital time for patients and healthcare costs. More research is ongoing to mitigate these burdens.


      Improving survival in lung cancer patients remains a challenge dependent on prevention, screening, optimal surgery, modern radiotherapy and improved systemic therapies targeted through understanding the molecular biology of these heterogenous tumours. Despite clear progress to date, there is much need for improvement, offering ample opportunity for future research.


      1 Quaresma M, Coleman MP, Rachet B (2015) 40-year trends in an index of survival for all cancers combined and survival adjusted for age and sex for each cancer in England and Wales 1971-2011: a population-based study. Lancet 385:1206-1218

      2 Allemani C, Weir HK, Carreira H et al (2018) Global surveillance of trends in cancer survival 2000-14 (CONCORD-3): analysis of individual records for 37513025 patients diagnosed with one of 18 cancers from 322 population-based registries in 71 countries. Lancet 391:1023-1075

      3 Schutte S, Dietrich D, Montet X and Flahault A (2018) Particiation in lung cancer screening programs: are there gender and social differences? A systematic review. Public Health Reviews 39: 23-35

      4 Boyer MJ, Williams CD, Harpole DH et al (2017) Improved survival of Stage I Non-Small Cell Lung Cancer: A VA Central Cancer Registry Analysis. J Thorac Oncol 12:1814-1823

      5 Zeng L, Yu X, Xiao J, Huang Y (2019) Interventions for smoking cessation in people diagnosed with lung cancer. CochraneSystematic Review CD011751.pub3

      6 Scagliotti G, Hanna N, Fossella F et al (2009) The differential efficacy of pemetrexed according to NSCLC histology: a review of two Phase III studies. Oncologist 14:253-263

      7 Mok TS, Yi-Long W, Thongprasert S, Chih-Hsin Y (2009) Gefitiib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med 361:947-957

      8 Peters S, Camidge DR, Shaw AT et ak (2017) Alectinib versus crizotinib in untreated ALK-positive nono-small cell lung cancer. N Engl J Med 377:829-838

      9 Planchard D, Popat S, Kerr K et al (2018) Metastatic non-small cell lung cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol 29 (suppl4):iv192 - iv236

      10 Antonia SJ, Villegas A, Daniel D et al (2018) Overall survival with durvalumab after chemoradiotherapy in stage III NSCLC. N Engl J Med 379:2342-2350

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      ES05.02 - From Living Longer to Also Living Better – the Role of Communication and Interprofessional Collaboration in Metastatic Lung Cancer (Now Available) (ID 3176)

      10:30 - 12:00  |  Presenting Author(s): Matthias Villalobos

      • Abstract
      • Presentation
      • Slides


      Despite ongoing progress in diagnostics and treatment, many patients with metastatic lung cancer still harbor a limited prognosis that may lead to existential uncertainty. These patients and their caregivers are confronted with a complex situation as burden comprises physical, psychosocial and spiritual needs [1]. During the illness trajectory they are exposed to different multiprofessional healthcare settings and providers that challenge the continuity and coordination of care. Therefore, the care of these patients and their relatives is often characterized by discontinuity, lack of coordination and insufficient communication [2]. Additionally, shared decision-making between active cancer treatment and end-of-life care constitutes a continuous and challenging balancing act for all who are involved in the process. Several studies have shown that early integration of palliative care (EPC) and adequate advance care planning (ACP) improve quality of life and satisfaction with care. Two studies evaluating EPC have even shown positive results in survival [3,4]. In the recommendation of the American Society of Clinical Oncology concerning the integration of palliative care into standard oncology care, the following were defined as essential components: “rapport and relationship building with patients and family caregivers; symptom, distress, and functional status management; exploration of understanding and education about illness and prognosis; clarification of treatment goals; assessment and support of coping needs; assistance with medical decision making; coordination with other care providers” [5]. This underlines the importance of communication in this setting and defines it as a central element for the effective provision of early palliative care. Another central element is interprofessional collaboration. Studies incorporating interprofessional involvement (notably physicians and nurses) showed more consistent results regarding the positive effects of EPC [6]. Through the different perspectives of the involved professions towards care needs, healthcare delivery may be enriched and become more holistic. Additionally, nurse navigation supports orientation in the healthcare system and provides continuity and coordination of care. For this strategy communication skills of healthcare providers and interprofessional collaboration should be strengthened. Joint communication training may play an important role to overcome interprofessional barriers and sharpen communication skills. Advanced communication techniques are essential for early integration of palliative care, facilitation of prognostic awareness, and by this means introduction or adaptation of advance care planning [7]. An interprofessional, longitudinally structured communication approach should improve the experience and outcomes of patients with advanced lung cancer and their caregivers [8]. Further research should address the feasibility of institutional strategies for implementing this approach.


      1 Baile WF, Palmer JL, Bruera E, Parker P: Assessment of palliative care cancer patients’ most important concerns. Support Care Cancer 2011;19:475-481.

      2 Gagliardi AR, Dobrow MJ, Wright FC: How can we improve cancer care? A review of interprofessional collaboration models and their use in clinical management. Surg Oncol 2011; 20:146–54.

      3 Bakitas MA, Tosteson TD, Li Z, Lyons KD, Hull JG, Li Z, Dionne-Odom JN, Frost J, Dragnev KH, Hegel MT, Azuero A, Ahles TA: Early Versus Delayed Initiation of Concurrent Palliative Oncology Care: Patient Outcomes in the ENABLE III Randomized Controlled Trial. J Clin Oncol 2015;33:1438-1445.

      4 Temel JS, Greer JA, Muzikansky A, Gallagher ER, Admane S, Jackson VA, Dahlin CM, Blinderman CD, Jacobsen J, Pirl WF, Billings JA, Lynch TJ: Early Palliative Care for Patients with Metastatic Non-Small-Cell Lung Cancer. N Engl J Med 2010;363:733-42.

      5 Ferrell BR, Temel JS, Temin S, Alesi ER, Balboni TA, Basch EM, Firn JI, Paice JA, Peppercorn JM, Phillips T, Stovall EL, Zimmermann C, Smith T: Integration of palliative care into standard oncology care: American Society of Clinical Oncology Clinical Practice Guideline Update. J Clin Oncol 2017;35:96-112.

      6 Hui D, Bruera E: Integrating palliative care into the trajectory of cancer care. Nature Reviews Clinical Oncology 2016;13:159-71.

      7 Jackson VA, Jacobsen J, Greer JA, Pirl WF, Temel JS, Black AL: The cultivation of prognostic awareness through the provision of early palliative care in the ambulatory setting: a communication guide. Journal of Palliative Medicine 2013;16:894-900.

      8 Villalobos M, Siegle A, Hagelskamp L, Jung C, Thomas M. Communication along milestones in lung cancer patients with advanced disease. Oncology Research and Treatment 2019;42:41-46.

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      ES05.03 - From Living Longer to Also Living Better; Managing Lung Cancer as a Chronic Disease - the Principle of Survivorship (Now Available) (ID 3177)

      10:30 - 12:00  |  Presenting Author(s): Maureen Rigney

      • Abstract
      • Presentation
      • Slides


      With exciting advances in lung cancer screening, diagnosis, and treatment, those diagnosed are living longer than ever before. Around the globe, more and more people are balancing the great hope and vast uncertainty of living with advanced lung cancer as a chronic disease.

      A chronic disease is one that lasts three months or longer, doesn’t disappear, and is not preventable by vaccines nor curable by medicine. (US National Center for Health Statistics). Uncontrolled, any chronic disease can be life threatening.

      The 2008 IOM report, Cancer Care for the Whole Patient: Meeting Psychosocial Health Needs, outlined the physical, emotional, social challenges, and financial stressors that result from living with a chronic disease. Cancer as a chronic disease increases anxiety, adds fear of recurrence, causes difficulties in making life plans, affects interpersonal relationships and prompts existential questioning. People diagnosed with lung cancer may additionally experience a myriad of distinct stigma-related challenges, including guilt, shame and increased isolation.

      Over ten years after the IOM report, cancer as a chronic disease remains a relatively unexamined area of study and, as Dr. Ross Camidge has said, “The rulebook hasn’t been written.” This presentation seeks to help us, the loved ones, advocates, clinicians, organizations and researchers begin to understand the unique needs of this population as we consider lung cancer as a chronic disease through:

      -- The lens of the ecological concept of the ecotone

      -- Recognizing the effects of months or years of continuous or intermittent treatment on the individual

      -- A commonly accepted model of chronic disease management and coping

      -- The lived experiences of those effected, gathered through focus groups and one-to-one conversations

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      ES05.04 - Social Media and Lung Cancer - a Global Picture (Now Available) (ID 3178)

      10:30 - 12:00  |  Presenting Author(s): Christina Sit  |  Author(s): Jesme Fox, Simon Malia

      • Abstract
      • Presentation
      • Slides


      The use of social media in lung cancer: an evaluation of global trends, themes and demographics.

      Social media has transformed the health communication landscape. It is evident in the rise of social media groups that social media is an important communications and connection tool for the community impacted by lung cancer. Individuals across the cancer continuum use social media for a myriad of purposes and there are differences between user profiles. For example, physicians and academics use social media to announce new innovative treatment options, for debate, and to highlight the successes and failures of lung cancer research. The general population utilizes social media to fundraise, garner support, and share their personal experiences with cancer. Social media may now be one of the most common communications vehicles for global campaigns concerning lung cancer, impacting education, fundraising and advocacy.

      In order to more optimally use social media to further objectives for patient organizations, it is integral to understand global trends in social media usage and what users are saying online. This global research project aims to answer these questions, as possessing more information on user trends will better inform those that are trying to reach and engage with these individuals.

      This global research project will also provide an opportunity for lung cancer professionals and organizations to refine their social media communications strategies. The research will identify best practices for organizations in engaging their lung cancer communities, as well as content strategies to boost reach, engagement and community size.

      Purpose:The objective of this research project is to evaluate the use of social media platforms, including Twitter, Facebook, and blogs, to understand howand whyindividuals are using each platform and whatis being said.

      Methodology:Through the social listening tool Brandwatchthis study will analyze social media usage between November 2018 to May 2019 in eleven (11) countries: Canada, United States, United Kingdom, Russia, Brazil, China, India, Israel, Australia, South Africa and Poland. This study utilizes topic analysis to understand the qualitative themes that are currently happening in the online conversation.

      These eleven (11) countries have been chosen due to high incidents of lung cancer, confidence in government data on lung cancer statistics, and frequency of social media use.

      In each jurisdiction, Brandwatchmonitors the use and flux of specific key terms relating to lung cancer. In analyzing the data that Brandwatch generates, the team can effectively monitor the conversations (frequency, subject, emotion, and corresponding debate) that happen at a grassroots level.

      In a parallel research method, the project will gather data from over forty (40) lung cancer organizations’ social media accounts across all major platforms including Facebook, Twitter, LinkedIn, Pinterest and YouTube. This data will be analyzed quantitatively and qualitatively to identify which social media strategies work best to engage members of the online lung cancer communities globally.

      Analysis:Preliminary findings indicate that the conversations occurring on social media across jurisdictions are both profoundly different yet have underlying similarities. Data will be extracted from initial findings to target populations with campaigns on issues that matter distinctly to them. As technology continues to drive decision-makers, organizations must adapt to foster the best results. In understanding who and how to target populations, it is expected that global lung cancer campaigns—for awareness, public policy changes or research funding—will reach, and hopefully exceed, their targets.

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      ES05.05 - Still Struggling for Traction - from Proving Lung Cancer Screening Works to Global Practical Implementation, Including Engagement of the Target Population (Now Available) (ID 3179)

      10:30 - 12:00  |  Presenting Author(s): James L Mulshine

      • Abstract
      • Presentation
      • Slides


      Still Struggling for Traction-from Proving Lung Cancer Screening Works to Global Practical Implementation, Including Engagement of the Target Population
      James L. Mulshine, Rush University, Chicago, IL 60612

      Based on the results of the National Lung Screening Trial, United States Preventive Services Task Force (USPSTF) reviewed and recommended low-dose CT screening for lung cancer. Next the Centers for Medicaid and Medicare reviewed this service and after February 5, 2015 issued a National Coverage Decisions to add coverage under Medicare Part B to allow low-dose CT screening in high-risk populations began (1, 2). A few years on, articles are frequently reporting that screening uptake in the United States is anemic. In a setting where enthusiasm differs about the prospects for lung cancer screening, issues of cost and bandwidth loom large (3, 4).

      Realistically, cancer screening whether cervical cancer, breast cancer or colon cancer all took extended periods of time to become established and problems of compliance with all three measures still exist. However, the results of the National Lung Screening Trial are now buttressed with the results of Dutch/Belgian trial (NELSON), as well as the 10 year follow up of the Milan randomized cohort experience (MILD) (4-5). Consequently, we are now seeing national screening not only being implemented in the United States but and with similar activity moving forward in Canada, Poland, the United Kingdom, South Korea as well as other nations. It is heartening to see evidence of careful planning to define the optimal screening programs for national implementation ongoing in a number of countries such as the United Kingdom, Canada and Poland. Cautious optimism that lung cancer screening may have turned a corner seems justified.

      These early adaptor national screening programs will provide an opportunity to evaluate national statistics for the annual distribution of stage frequencies. As it is a critical measure of public health progress to have falling national smoking rates, now we can also look for national level stage shifts to determine if the detection rates of Stage I cases rise along with corresponding drops in Stage III/IV frequencies. Furthermore, critical information about actual experience in these large national settings can inform the discussion about the realities of harms experienced in the screening process and this information would be useful in advancing lung cancer screening participation.

      Communication disseminated by venues like IASLC and GLCC will be essential to encourage efforts to enhance the process of screening to sustain the brisk pace of research focusing on screening management optimization. The efforts of the American College of Radiology in adapting breast cancer screening process for managing the lung cancer screening process has been important as it creates a much more familiar transition for institutions attempting to launch lung cancer screening services (6). This ACR process, called LungRADS leverages a management approach that is already well established in the radiology community and makes for a smooth transition in defining a systematic screening management approach for lung cancer. This recent development has addressed a major concern relative to the rate of false positive screening cases that was dampening screening enthusiasm for some healthcare professionals.

      Fortunately, there are even more advanced developments in the offing for more effective and workflow friendly software tools. If best-practice nodule management of I-ELCAP, NELSON, and UKLS using software-driven direct measurement of lung cancer volume become more generally available, these tools can further reduce the rate of false-positive diagnosis and improve the efficiency of the case finding process (7-11). Fortunately, in collaboration with I-ELCAP and the Veterans Administration in the US, activities are underway to address this complex issue.

      Annual lung cancer screening has also provided an opportunity to re-consider how to best encourage more effective smoking cessation. The National Cancer institute in the United States launched a number of studies to experiment with more intensive approaches to smoking cessation specifically in the setting of screening. These studies will be completed over the next few years and these new approaches can be applied to help more people overcome this dangerous but deeply additive behavior and in a complementary fashion improve the prospects for more favorable health outcomes.

      Quietly over the last decade, we have witnesses continuous refinements in the surgical approach to resecting early lung cancer (12). We would expect further evidence to accrue informing the most favorable approach to curative resection. Within this time window, we expect to also start seeing more experimental approaches to managing small, favorably located lung cancers with inter-luminal approaches.

      In the wake of recent cardiology guidelines revisions to include low-dose thoracic CT as a biomarker for managing coronary calcium deposition, we would expect to see greater awareness of other routine tobacco-related findings seen in the course of a thoracic CT screening (13). Together lung cancer, coronary artery disease and COPD constitute the three most lethal diseases across the world. The pathogenesis of all three of these diseases is greatly accelerated by tobacco-combustion product deposition in the lungs. As the prevalence of lung cancer screening evolves, considerably more cases of coronary artery disease and COPD cases will come to clinical attention than lung cancer, so collaboration across relevant disciplines will increase to provide thoughtfully integrated management of CT screen identified consequences of prolong tobacco exposure (13). The bulk of the preventive managements of these three most lethal diseases detected in high risk but asymptomatic individuals will include more concerted tobacco cessation support, advice to enhance levels of physical activity and to improve the quality of dietary consumption. Through time, CT-informed lung cancer screening will create an annual opportunity for a health check to improve the health of tobacco-exposed individuals. This possibility could great enhance the support of low-dose CT evaluation of thorax in smokers across many communities.

      In parallel, targeted drug development guided by information derived from systematically examining resected screen-detected cancer looking for signatures of aggressive behaving cancers that will need adjuvant interventions beyond surgery to ensure curative outcomes. In this strategy, lung cancer care may follow breast cancer care and we will see the emergence of neoadjuvant and adjuvant early lung cancer therapies as a critical part of ensuring favorable individual outcomes.

      In closing, screening is a complex process with many moving parts. Establishing this process with careful attention to quality and then testing to see how to optimize the delivery as outlined in a recent I-ELCAP report, takes time (14). Participation in lung cancer screening is low. Given the recent strong screening results from multiple international sites especially with the NELSON trial as well as contributions such as LungRADS, and process research such as with I-ELCAP, there is a basis for optimism that significantly greater uptake will be occurring in large measure due to mutually beneficial collaborations.


      National Lung Screening Trial Research Team, Aberle DR, Berg CD, Black WC et al. The National Lung Screening Trial: overview and study design. Radiology. 2011 Jan;258(1):243-53. doi: 10.1148/radiol.10091808. Epub 2010 Nov 2.

      National Coverage Decision, low-dose CT screening for lung cancer,

      Bach PB. Perilous potential: the chance to save lives, or lose them, through low dose computed tomography screening for lung cancer. J Surg Oncol. 2013 Oct;108(5):287-8. doi: 10.1002/jso.23389. Epub 2013 Aug 27. PMID: 23983184, DOI: 10.1002/jso.23389

      Mulshine JL, D'Amico TA. Issues with implementing a high-quality lung cancer screening program. CA Cancer J Clin. 2014 Sep-Oct;64(5):352-63. doi: 10.3322/caac.21239. Epub 2014 Jun 27. Review. PMID: 24976072.

      De Koning HJ, Van Der Aalst C, Ten Haaf K, et al: Effects of volume CT lung cancer screening: Mortality results of the NELSON randomized-controlled population based trial. 2018 World Conference on Lung Cancer. Abstract PL02.05. Presented September 25, 2018.

      Pastorino U, Silva M, Sestini S, et al. Prolonged lung cancer screening reduced 10-year mortality in the MILD trial. Ann Oncol. 2019 Apr 1. pii: mdz117. doi: 10.1093/annonc/mdz117.

      Martin MD, Kanne JP, Broderick LS, Kazerooni EA, Meyer CA. Lung-RADS: Pushing the Limits. Radiographics. 2017 Nov-Dec;37(7):1975-1993. doi: 10.1148/rg.2017170051. Epub 2017 Oct 20.

      Yankelevitz DF, Gupta R, Zhao B, and Henschke CI. Small pulmonary nodules: evaluation with repeat CT--preliminary experience. Radiology 1999; 212:561-6.

      van Klaveren RJ, Oudkerk M, Prokop M, et al. Management of lung nodules detected by volume CT scanning. N Engl J Med. 2009 Dec 3;361(23):2221-9. doi: 10.1056/NEJMoa0906085.

      Horeweg N, van Rosmalen J, Heuvelmans MA, et al. Lung cancer probability in patients with CT-detected pulmonary nodules: a prespecified analysis of data from the NELSON trial of low-dose CT screening. Lancet Oncol 2014;15:1332–41.

      Field JK, Duffy SW, Baldwin DR, et al.The UK Lung Cancer Screening Trial: a pilot randomised controlled trial of low-dose computed tomography screening for the early detection of lung cancer.Health Technol Assess. 2016 May;20(40):1-146. doi: 10.3310/hta20400. PMID: 27224642

      Altorki N, Lee B.Commentary: Lobectomy or sublobar resection for early lung cancer: One small step for surgeons, one giant step for patients. J Thorac Cardiovasc Surg. 2019 Apr 24. pii: S0022-5223(19)30903-1. doi: 10.1016/j.jtcvs.2019.04.010. [Epub ahead of print] No abstract available. PMID: 31160116

      Mulshine JL. One Screening for Ischemic Heart Disease, Lung Cancer, and Chronic Obstructive Pulmonary Disease: A Systems Biology Bridge for Tobacco and Radiation Exposure. Am J Public Health.2018;108:1294-1295. doi: 10.2105/AJPH.2018.304655. PMID: 30207781

      Henschke CI, Li K, Yip R, Salvatore M, Yankelevitz DF. The importance of the regimen of screening in maximizing the benefit and minimizing the harms. Ann Transl Med. 2016 Apr;4(8):153. doi: 10.21037/atm.2016.04.06. Review. PMID: 27195271.

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