Virtual Library

  • +

    ES16 - Modern Radiotherapy in Stage III NSCLC (ID 19)

    • Event: WCLC 2019
    • Type: Educational Session
    • Track: Treatment of Locoregional Disease - NSCLC
    • Presentations: 4
    • Now Available
    • +

      ES16.01 - Proton Therapy (Now Available) (ID 3242)

      11:00 - 12:30  |  Presenting Author(s): Corinne Faivre-Finn

      • Abstract
      • Presentation
      • Slides

      Abstract

      Proton therapy is an attractive option for the treatment of lung cancer patients due to the physical properties of proton beams. Proton therapy allows a focused delivery of radiation at the Bragg peak, with very steep decline of the radiation dose beyond the target volume. These properties offer the possibility to 1) reduce toxicity by reducing the integral dose and the dose to adjacent normal tissues and 2) escalate the dose to the target in some patients.

      In this talk, I will summarise briefly the physics/radiobiology of protons and the need for adaptation. I will also discuss the rationale for the use of protons in patients with lung cancer, including reduction in integral dose, cardiac toxicity and reduction in haematological toxicity. The clinical trial evidence supporting the use of protons will be presented in early stage and locally advanced non-small cell lung cancer as well as in small-cell lung cancer.

      Finally I will discuss future research directions, including preclinical and drug-proton combination research, ongoing clinical trials, the model based-approach and the need for biomarkers.

      REFERENCES

      Liao Z, Lee JJ, Komaki R, eat l. Bayesian Adaptive Randomization Trial of Passive Scattering Proton Therapy and Intensity-Modulated Photon Radiotherapy for Locally Advanced Non-Small-Cell Lung Cancer. J Clin Oncol. 2018;36(18):1813-1822

      Chang JY, Jabbour SK, De Ruysscher D, et al; International Particle Therapy Co-operative Group Thoracic Subcommittee.Consensus Statement on Proton Therapy in Early-Stage and Locally Advanced Non-Small Cell Lung Cancer. Int J Radiat Oncol Biol Phys. 2016;95(1):505-16.

      Vyfhuis MAL, Onyeuku N, Diwanji T, Mossahebi S, Amin NP, Badiyan SN, Mohindra P, Simone CB 2nd. Advances in proton therapy in lung cancer. Ther Adv Respir Dis. 2018 Jan-Dec;12:1753466618783878

      C, Pawelke J, Seidlitz A, Peitzsch C, et al; “Radiobiology of Proton Therapy”: Results of an international expert workshop.Lühr A, von Neubeck Radiother Oncol. 2018; 128(1):56-67

      Jin, J.Y., et al., Higher Radiation Dose to Immune System is Correlated With Poorer Survival in Patients With Stage III Non-small Cell Lung Cancer: A Secondary Study of a Phase 3 Cooperative Group Trial (NRG Oncology RTOG 0617). International Journal of Radiation Oncology Biology Physics, 2017. 99(2): p. S151-S152.

      Joseph, N., et al., Post-treatment lymphocytopaenia, integral body dose and overall survival in lung cancer patients treated with radical radiotherapy. Radiotherapy and Oncology, 2019. 135: p. 115-119.

      Durante, M., D.J. Brenner, and S.C. Formenti, Does Heavy Ion Therapy Work Through the Immune System? Int J Radiat Oncol Biol Phys, 2016. 96(5): p. 934-936.

      Lee, H.J., Jr., J. Zeng, and R. Rengan, Proton beam therapy and immunotherapy: an emerging partnership for immune activation in non-small cell lung cancer. Translational lung cancer research, 2018. 7(2): p. 180-188.

      Dess, R.T., et al., Cardiac Events After Radiation Therapy: Combined Analysis of Prospective Multicenter Trials for Locally Advanced Non-Small-Cell Lung Cancer. J Clin Oncol, 2017. 35(13): p. 1395-1402.

      McWilliam, A., et al., Radiation dose to heart base linked with poorer survival in lung cancer patients. Eur J Cancer, 2017. 85: p. 106-113.

      Schulz-Ertner, D. and H. Tsujii, Particle radiation therapy using proton and heavier ion beams. J Clin Oncol, 2007. 25(8): p. 953-64.

      Gameiro, S.R., et al., Tumor Cells Surviving Exposure to Proton or Photon Radiation Share a Common Immunogenic Modulation Signature, Rendering Them More Sensitive to T Cell-Mediated Killing. Int J Radiat Oncol Biol Phys, 2016. 95(1): p. 120-30.

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      IASLC Members: To view this content or have the option to purchase this event, click here to login.
      Conference Attendees & Access Code holders: Click here to enter your Access Code. Already entered your Access Code? Please login.

    • +

      ES16.02 - MRI-Based Radiotherapy (Now Available) (ID 3243)

      11:00 - 12:30  |  Presenting Author(s): Fiona McDonald

      • Abstract
      • Presentation
      • Slides

      Abstract

      One key potential advance for radical radiotherapy indications in lung cancer is the integration of magnetic resonance imaging (MRI) in the treatment pathway, giving anatomical and functional detail without additional radiation exposure to the patient. Incorporating anatomical MRI into the treatment planning may improve target volume and organs at risk delineation reproducibility. Functional MRI may facilitate heterogeneous dosing of target volumes and assessment of normal tissue toxicity to assist adaptive strategies. Four-dimensional MRI has the potential to complement 4D CT and 4D F-18-FDG PET with superior spatial resolution. MR-guided radiotherapy delivery machines are increasing in number internationally, providing novel hybrid technology that continues to evolve with various technical challenges to overcome. It is anticipated that the clinical benefits of MR-guided radiotherapy will lie the ability to adapt treatment in real-time. Research is ongoing to develop trials of MR-guided adaptive treatment schedules in lung cancer patients.

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      IASLC Members: To view this content or have the option to purchase this event, click here to login.
      Conference Attendees & Access Code holders: Click here to enter your Access Code. Already entered your Access Code? Please login.

    • +

      ES16.03 - Optimal Integration of Radiotherapy, TKIs and I/O (Now Available) (ID 3244)

      11:00 - 12:30  |  Presenting Author(s): Umberto Ricardi

      • Abstract
      • Presentation
      • Slides

      Abstract

      Umberto Ricardi, Serena Badellino, Cristina Mantovani, Donatella Caivano, Stefania Martini, Marzia Cerrato, Giuseppe Carlo Iorio

      Department of Oncology, University of Turin, Italy

      Approximately one third of patients affected by non-small cell lung cancer (NSCLC) present with ‘locally advanced’ disease at diagnosis. Most patients are considered inoperable due to disease extension, and chemo-radiotherapy (CT-RT) still represents the standard therapeutic option, with unsatisfactory results in terms of overall survival (OS) despite advances in staging and technological evolution in radiation therapy planning and delivery. Besides radiation dose escalation, a logical step for improving survival in inoperable stage III patients was to evaluate the combination of concurrent/sequential RT-CT with targeted agents (tyrosine kinase inhibitors, TKI; mono-clonal antibody against EGFR; ALK/ROS1 inhibitors) and/or anti- angiogenic therapies, following the positive results obtained in stage IV disease (1, 2). Since the early 2000s, when first-generation TKIs were first approved for clinical use, several studies have been conducted in an attempt to demonstrate the efficacy of targeted therapies combined with radiotherapy (3, 4, Table 1). These studies were testing mainly the feasibility and the tolerability of this combination, with not statistical significant benefit in terms of outcomes (4, Table 1). Mature results of an international trial testing the contribution of TKIs with chemoradiotherapy in patients affected with stage III NSCLC harboring sensitive mutations are still waited.

      Immunotherapy, and in particular immune-checkpoint inhibitors targeting the PD-1/PD-L1 axis, gained wide popularity for NSCLC in light of the positive findings of several trials in metastatic disease (1, 5). Radiation therapy combined with immunotherapy represent a new therapeutic opportunity, given the role of RT in reversing immunosuppressive barriers within the tumor microenvironment (6). The growing enthusiasm for immune-oncology and its possible applications in radiation oncology led to a remarkable expansion of pre-clinical and clinical studies testing various combinations of immunotherapeutic agents and radiation. Stage III unresectable NSCLC is an interesting setting for the combined use of chemo-radiation and immunotherapy, also considering the multiple experimental evidences in favor of a synergistic effect between radiation and immune checkpoint inhibitors, with the potential of enhancing immuno-modulating effects and overcoming resistance. The PACIFIC trial (PD-L1 inhibitor Durvalumab vs placebo, unresectable stage III NSCLC who did not progress following concurrent platinum-based chemo-radiotherapy) showed a major improvement in 2-year PFS and OS, which holds promise for an improved cure rate (7). Even the use of Pembrolizumab (anti-PD-1 agent) is under investigation in a series of trials. A number of studies (e.g. INSPIRE study) investigated the role of Tecemotide (anti-tumor vaccine inducing a specific immune response against MUC-1, glycoprotein overexpressed in NSCLC) (8) in Stage III NSCLC. More evidence is awaited regarding the optimal timing when combining immunotherapy and CT-RT, considering the possibility to improve this synergism even further. Several ongoing trials are testing multiple schedules (5). A predominance of the consolidation/adjuvant/maintenance setting is evident, however many studies also integrated immunotherapy at the beginning of chemo-radiation. The latter schedule should be one of the most efficient ways to fully harness the synergistic effects of chemo-radiation and immunotherapy in terms of boosting the immune-stimulating effects, particularly when using anti-PD-L1 agents, given that enhanced expression of PD-L1 during RT may be one of the main causes of radioresistance. Some attention should also be paid to those trials introducing anti-PD-1 agents before chemo-radiation, as neo-adjuvant: this innovative approach could be promising, by integrating radio-chemotherapy in a tumor micro-environment already modified by immunomodulators, and with a subsequent consolidation phase. When using anti-PD-L1 agents in this setting, PD-L1 expression levels would probably be necessary to stratify patients as highlighted in the PACIFIC trial post-hoc analysis (9).

      REFERENCES

      Filippi AR, Di Muzio J, Badellino S, Mantovani C, Ricardi U. Locally-advanced non-small cell lung cancer: shall immunotherapy be a new chance? J Thorac Dis 2018;10(Suppl 13):S1461-S1467. doi: 10.21037/jtd.2017.12.53.

      Planchard D, Popat S, Kerr K, Novello S, Smit EF, Faivre-Finn C, et al. Metastatic non-small cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2019 Jan 30. doi: 10.1093/annonc/mdy474.

      3..

      Arcangeli S, Jereczek-Fossa BA, Alongi F, Aristei C, Becherini C, Belgioia L, Buglione M, et al. Combination of novel systemic agents and radiotherapy for solid tumors - Part II: An AIRO (Italian association of radiotherapy and clinical oncology) overview focused on treatment toxicity. Crit Rev Oncol Hematol. 2019;134:104-119. doi: 10.1016/j.critrevonc.2018.11.006.

      Kordbacheh T, Honeychurch J, Blackhall F, Faivre-Finn, Illidge. Radiotherapy and anti-PD-1/PD-L1 combinations in lung cancer: building better translational research platforms. Ann Oncol. 2018 Feb 1;29(2):301-310. doi: 10.1093/annonc/mdx790.

      Formenti SC, Demaria S. Systemic effects of local radiotherapy. Lancet Oncol. 2009 Jul;10(7):718-26. doi: 10.1016/S1470-2045(09)70082-8.

      Antonia SJ, Villegas A, Daniel D, Vicente D, Murakami S, Hui R, et al. Overall Survival with Durvalumab after Chemoradiotherapy in Stage III NSCLC. N Engl J Med 2018; 379:2342-2350 DOI: 10.1056/NEJMoa1809697.

      Wu YL, Park K, Soo RA, et al. INSPIRE: A phase III study of the BLP25 liposome vaccine (L-BLP25) in Asian patients with unresectable stage III non-small cell lung cancer. BMC Cancer 2011;11:430.

      Kim YH. Durvalumab after Chemoradiotherapy in Stage III Non-Small-Cell Lung Cancer. N Engl J Med. 2019 Mar 7;380(10):989-990. doi: 10.1056/NEJMc1900407.

      Table 1. Major studies on Radiotherapy and TKIs in LA-NSCLC.

      Author and year

      Study type

      Number of patients

      RT technique/ dose/ fractionation

      Combination (concomitant, other)

      Primary Endopoint

      Treatment outcome

      Martinez et al (2016)

      Phase II Randomised, NSCLC

      90

      3D-CRT 66 Gy/33 fx

      RT alone vs RT+Erlotinib

      Feasibility/Tolerabily

      Median OS: 11.4 vs 8.9 (p=0.835)

      Lilenbaum et al (2015)

      Phase II, unresectable NSCLC

      75

      3D-CRT 66 Gy/33 fx

      Induction Carbo/Paclitaxel® RT+ Erlotinib

      OS

      Median OS: 17 months. 1-yy OS: 57%

      Ramella et al (2013)

      Phase I-II, unresectable NSCLC

      60

      3D-CRT 59.4 Gy/33 fx

      CT-RT+Erlotinib

      Feasibility/Tolerabily

      Median OS:23.3months. Median PFS: 4.7 months

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      IASLC Members: To view this content or have the option to purchase this event, click here to login.
      Conference Attendees & Access Code holders: Click here to enter your Access Code. Already entered your Access Code? Please login.

    • +

      ES16.04 - Molecular Biology of Radiation Toxicity (Now Available) (ID 3245)

      11:00 - 12:30  |  Presenting Author(s): Fiona Hegi-Johnson

      • Abstract
      • Presentation
      • Slides

      Abstract

      Molecular Biology of Radiation Toxicity

      Radiotherapy causes damage to normal and malignant cells, resulting in the cell death of tumour cells and radiation toxicity. Historically, the damage caused by radiotherapy has been described by the linear quadratic(LQ) model; a model of cellular survival derived by observing the effects of fractionated radiotherapy on cell cultures. However, it is increasingly understood that radiation toxicity is a complex event mediated by both the DNA damage modelled in the LQ model, and contributory factors such as immune and inflammatory upregulation and vascular dysfunction (see Figure 1). In this talk we will review the role of DNA damage immune and inflammatory mediated reactions on the development of radiation toxicity.

      DNA damage and cell death

      Radiotherapy effects damage on normal cells by both direct and indirect means. Direct damage to DNA by either secondary electrons or reactive oxygen species (ROS) causes the initiation of DNA damage responses (DDR). This can result in varying effects depending on individual variation in the efficiency of the DDR pathways, the severity of the insult, and the type of normal cell (2). For example, haematological cell death is usually mediated through primary apoptosis within a few hours of exposure; the majority of non-haematological cells die when they enter mitosis inappropriately (mitotic catastrophe).

      Several key mediators of DDR have been identified. The 2 most important genetic modulators of DDR appear to be TP53, which mediates cell cycle arrest, facilitating both apoptosis and mitotic catastrophe, and ATM, which encodes the main kinase responsible for repairing double-strand DNA breaks (3). P53 works through downstream targets such as PUMA and p21, with evidence suggesting that different pathways are significant in different systems. In murine models of GI induced radiation toxicity, loss of PUMA is protective, whilst p53 and p21 loss increases toxicity (4). In contrast, in slowly replicative systems, such as the CNS and salivary glands, non-lethal radiation dose induced p53 activation may result in cell cycle arrest and altered differentiation (1); the survival of these damaged cells may lead to stem cell ageing and second malignancies.

      Immune and Inflammatory system upregulation during radiotherapy and the impact on radiation toxicity

      Radiotherapy exposure results in global upregulation of the immune system, increasing immune activity by increasing tumour cell-surface expression of major histocompatibility complex (MHC) class 1, increasing expression of tumour-associated antigens, activating dendritic cells, and changing the T cell repertoire, with a consequent reduction in the immune suppressive regulatory T-cells and an increase in active CD8 populations (5). These responses underpin the positive outcomes seen in immunoradiotherapy trials, but the relationship between radiotherapy and the immune system is likely to have complex effects both on tumour control and radiation toxicity.

      Under normal circumstances dying cells are phagocytosed by macrophages and an anti-inflammatory pathway mediated by IL-10, TGF-b, platelet-activating factor, and prostaglandin E2 (PGE2) suppresses inflammation (6). During radiation the high levels of DNA damage results in the release of a high concentration of pro-inflammatory “damage-associated molecular patterns”(DAMPS) including oxidized DNA , adenosine triphosphate (ATP) heat shock proteins (HSPs) and high -mobility group box 1 (HMGB1)(7), leading to upregulation of inflammatory pathways through activation of TLR’s and triggering of pro-inflammatory cytokine cascades (8). This acute inflammatory reaction contributes to several of the hallmarks of acute radiation toxicity, including erythema, ulceration and oedema (9).

      Finally, chronic inflammatory responses induced by radiotherapy contribute to radiation fibrosis; a result of imbalance in the creation and destruction of extracellular matrix components mediated by the upregulation of pro-inflammatory cytokines (TNFα, IL1, IL-4, IL6) and fibrogenic cytokines (TNFβ) (10).

      Summary

      Our understanding of the molecular biology of radiation toxicity continues to evolve, but is increasingly seen to be the result of the complex interplay of dysregulated DDR, immune and inflammatory responses. These pathways will provide a rich source of future therapies to increase both the efficacy and safety of radiotherapy treatment.

      References

      De Ruysscher D, Niedermann G Burnet N Siva S, Lee A, Hegi-Johnson F. Radiotherapy Toxicity, Nature Reviews Disease Primers (2019) 5:13

      Lomax M, Folkes L, O’Neill P. 2013. Biological consequences of radiation induced DNA damage: relevance to radiotherapy. Clin Oncol (R Coll Radiol). 25:578–585.

      Morgan, M. A. & Lawrence, T. S. Molecular pathways: overcoming radiation resistance by targeting DNA damage response pathways. Clin Cancer Res 21: 2898-2904 (2015).

      Qiu, W. et al. PUMA regulates intestinal progenitor cell radiosensitivity and gastrointestinal syndrome. Cell Stem Cell 2, 576–583 (2008)

      Vanpouille-Box, C. et al. DNA exonuclease Trex1regulates radiotherapy-induced tumour immunogenicity. Nat. Commun. 8, 15618 (2017).

      Chung EY, Kim SJ, Ma XJ. 2006. Regulation of cytokine production during phagocytosis of apoptotic cells. Cell Res; 16: 154-161.

      Gehrke N, Mertens C, Zillinger T, Wenzel J, Bald T, Zahn S, T€uting T, Hartmann G, Barchet W. 2013. Oxidative damage of DNA confers resistance to cytosolic nuclease TREX1 degradation and potentiates STING-dependent immune sensing. Immunity 39:482–495.

      Piccinini A, Midwood K. 2010. DAMPening inflammation by modulating TLR signalling. Mediat Inflamm. 2010:672395.

      Sprung et al 2015. Immmunological markers that predict radiation toxicity. Cancer Lett 368:191-197

      slide1.jpgYamada M, Kubo H, Ota C, Takahashi T, Tando Y, Suzuki T, Fujino N, Makiguchi T, Takagi K, Suzuki T. 2013. The increase of microRNA-21 during lung fibrosis and its contribution to epithelial-mesenchymal transition in pulmonary epithelial cells. Respir Res. 14:95.

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      IASLC Members: To view this content or have the option to purchase this event, click here to login.
      Conference Attendees & Access Code holders: Click here to enter your Access Code. Already entered your Access Code? Please login.

  • +

    ES21 - Current Strategies to Improve Outcome of Patients with Oligometastatic NSCLC (ID 24)

    • Event: WCLC 2019
    • Type: Educational Session
    • Track: Oligometastatic NSCLC
    • Presentations: 5
    • Now Available
    • +

      ES21.01 - Optimal Imaging for Staging of OMD (Now Available) (ID 3269)

      15:45 - 17:15  |  Presenting Author(s): Klaus L. Irion  |  Author(s): Bruno Hochhegger

      • Abstract
      • Presentation
      • Slides

      Abstract

      The role of imaging in oligometastatic disease in NSCLC:

      The current guidelines include a contrast-enhanced CT of the chest and upper abdomen as the baseline imaging investigation of lung cancer patients. A contrast-enhanced CT or MRI of the brain is indicated in patients who present with neurological signs/symptoms1. An additional investigation with PET-CT and MRI could be considered, "but only if their results could alter the treatment strategy"2. Lung cancer patients who are candidates to a radical treatment should be referred to a PET-CT if the initial investigations indicate a potentially curable disease2. Not infrequently, the identification of unsuspected metastasis on the PET-CT changes the initial staging to a stage IV, in a significant number of cases. A radical treatment can be considered for those with oligometastatic disease (OMD), which is defined by the National Cancer Institute as: "a small number of metastatic tumors in one or two other parts of the body"3. Discerning additional lung lesions as benign or malignant can be improved with the use of MRI4,5. Considering the limitations of PET-CT for detecting brain and liver metastases, MRI should be considered to avoid a futile extended radical treatment in this select group of patients5. This presentation will discuss the role of imaging in OMD patients being considered for extended radical treatment.

      1. NICE. https://www.nice.org.uk/guidance/ng122/chapter/Recommendations#diagnosis-and-staging

      2. Planchard D. et al. Metastatic non-small cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Annals of Oncology (2018) 29(4): iv192–iv237.

      3. NCI. https://www.cancer.gov/publications/dictionaries/cancer-terms/def/oligometastasis.

      4. Basso Dias A. et al. Fluorine 18–FDG PET/CT and diffusion-weighted MRI for malignant versus benign pulmonary lesions: a meta-analysis. Radiology (2019) 290:525–534

      5. Hochhegger B. et al. MRI in lung cancer: a pictorial essay. BJR (2011) 84:1003, 661-668

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      IASLC Members: To view this content or have the option to purchase this event, click here to login.
      Conference Attendees & Access Code holders: Click here to enter your Access Code. Already entered your Access Code? Please login.

    • +

      ES21.02 - Biological Disease Characterization of OMD (Now Available) (ID 3270)

      15:45 - 17:15  |  Presenting Author(s): David E. Gerber

      • Abstract
      • Presentation
      • Slides

      Abstract

      Variation in the characterization of OMD
      Trial OMD characteristics OMD timing
      Iyengar et al (2017)

      · 6 sites of extracranial disease (including primary)

      · 3 sites in liver or lung

      ·Up to 2 contiguous vertebral metastases considered a single site
      After first-line therapy and without progression
      Gomez et al (2016)

      · 3 metastatic sites

      · Any N1-3 thoracic nodes considered a single site

      · Satellite lesions counted as separate sites
      After first-line therapy and without progression
      Parikh et al (2014) · ≤5 metastatic sites After first-line therapy and without progression
      Cheruvu et al (2011) · ≤8 metastatic sites At time of initial staging
      Khan et al (2006)

      · 1-2 metastatic sites

      · Definitive (surgery and/or chemoradiation) treatment of thoracic disease
      After treatment of thoracic disease

      Recent years have seen a marked increase in interest in the concept of oligometastatic disease (OMD) in non-small cell lung cancer (NSCLC). Lacking a precise and consistent definition, OMD is generally considered to represent a relatively favorable clinical state, with more indolent biology, a limited number of disease sites, and potential for prolonged periods of disease control. Discussions of oligometastatic NSCLC area inexorably linked with management considerations, specifically the use of local therapies such as surgery and radiation therapy. There are numerous clinical and biological rationales to support such approaches: (1) disease progression most commonly occurs in original sites of gross disease1; (2) metastatic sites may propagate secondary metastases (parallel progression model)2; (3) solid tumors are composed of faster growing (sensitive) and slower growing (resistant) cell populations (Norton-Simon hypothesis)3; (4) resistance depends on spontaneous mutations and therefore increases with time (Goldie-Coldman hypothesis).4

      Nevertheless, several questions regarding the characterization and optimal management of OMD remain (Table 1). Up to how many sites of disease constitute an oligometastatic state? Does a “site” of disease comprise a single lesion or neighboring tumors? Does the anatomic site matter? For instance, brain metastases have historically been considered a more favorable location for definitive treatment of OMD, and their emergence may reflect pharmacokinetic failure rather than molecular evolution.5,6 Additionally, there are likely meaningful clinical differences between OMD states depending on whether they are defined at diagnosis (de novo), after initial exposure to systemic therapy (induced), recurrence, or progression.

      OMD may also have a distinct biologic phenotype. The metastatic cascade includes loss of cellular adhesion, increased motility, primary tumor invasiveness, entry into and survival in the circulation, and entry into and colonization of distant organs.7 Tumor dormancy, regulated in part by interferon signaling, may impact the number, location, and timing of metastases.8 Expression of genes that positively regulate the cell cycle may determine whether cancer growth occurs as polymetastasis versus oligometastasis. Ideally, ongoing and future clinical trials will collect biospecimens for discovery and validation of OMD biomarkers, thereby enabling the identification of cases most likely to benefit from OMD treatment paradigms.

      References:

      1. Rusthoven KE, Hammerman SF, Kavanagh BD, Birtwhistle MJ, Stares M, Camidge DR. Is there a role for consolidative stereotactic body radiation therapy following first-line systemic therapy for metastatic lung cancer? A patterns-of-failure analysis. Acta Oncol 2009;48:578-83.

      2. Klein CA. Parallel progression of primary tumours and metastases. Nat Rev Cancer 2009;9:302-12.

      3. Norton L, Simon R. Tumor size, sensitivity to therapy, and design of treatment schedules. Cancer Treat Rep 1977;61:1307-17.

      4. Goldie JH, Coldman AJ. A mathematic model for relating the drug sensitivity of tumors to their spontaneous mutation rate. Cancer Treat Rep 1979;63:1727-33.

      5. Hu C, Chang EL, Hassenbusch SJ, 3rd, et al. Nonsmall cell lung cancer presenting with synchronous solitary brain metastasis. Cancer 2006;106:1998-2004.

      6. Grommes C, Oxnard GR, Kris MG, et al. "Pulsatile" high-dose weekly erlotinib for CNS metastases from EGFR mutant non-small cell lung cancer. Neuro Oncol 2011;13:1364-9.

      7. Gupta GP, Massague J. Cancer metastasis: building a framework. Cell 2006;127:679-95.

      8. Dunn GP, Koebel CM, Schreiber RD. Interferons, immunity and cancer immunoediting. Nature reviews Immunology 2006;6:836-48.

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      IASLC Members: To view this content or have the option to purchase this event, click here to login.
      Conference Attendees & Access Code holders: Click here to enter your Access Code. Already entered your Access Code? Please login.

    • +

      ES21.03 - Interpreting the Current Data for Local Consolidative Treatment in the Setting of Oligometastatic Disease: Where Do We Stand? (Now Available) (ID 3271)

      15:45 - 17:15  |  Presenting Author(s): Daniel Gomez

      • Abstract
      • Presentation
      • Slides

      Abstract

      Over the past 15 years, several retrospective and single arm prospective studies suggested a benefit for local consolidative therapy (surgery, radiation therapy, or interventional radiologic ablation) in the setting of oligometastatic disease. More recently, a small number of randomized trials have provided further data regarding the utility of an agressive approach with regard to progression free and overall survival. With the considerable amount of emerging evidence, it can be difficult to aggregate and interpret the major themes across studies. This presentation will discuss the composite data of local consolidative therapy in oligometastases, with a particular focus on high impact non-randomized studies and the limited randomized trials addressing this topic. The presentation will then provide major conclusions that can be the basis for analysis going forward. Attendees will thus be provided with a summary of the current evidence in the oligometastatic disease context and a basis for future directions.

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      IASLC Members: To view this content or have the option to purchase this event, click here to login.
      Conference Attendees & Access Code holders: Click here to enter your Access Code. Already entered your Access Code? Please login.

    • +

      ES21.04 - Optimal Systemic Treatment of OMD (Now Available) (ID 3272)

      15:45 - 17:15  |  Presenting Author(s): Hideo Kunitoh

      • Abstract
      • Presentation
      • Slides

      Abstract

      A series of randomized trials (1-3), 2 of them specifically conducted for non-small cell lung cancer (NSCLC) patients (2,3), have shown that those with OMD could get clinical benefit from the addition of local ablative therapy to the standard systemic treatment. All 3 trials demonstrated improvement of progression-free survival (PFS), and 2 of them suggested overall survival (OS) benefit (1,2). OS was the primary endpoint of the 2 studies.

      In each of the trials, however, the “standard systemic treatment” was not specified; in fact, it was merely described that the systemic therapy was determined by the treating oncologists from a set of “standard-of-care options” (3). It would be easy to imagine that the “standard-of-care options” for OMD in these trials would be no different from those for other stage IV diseases.

      For NSCLC, they are cytotoxic chemotherapies according to histologic subtypes, appropriate target-based therapies when the tumors have druggable targets, and, more recently, immune-oncology (IO) drugs when the tumors have potentially predictive markers, such as PD-L1 (4) or tumor mutation burdens (5). The question is, is the optimal systemic therapy of OMD really exactly same with the “standards” of other, more advanced, poly-metastatic stage IV NSCLC?

      First of all, let me suppose that the disease is truly oligo-metastatic, meaning there are no other metastatic foci than those which are detected by the image scans. In this scenario, you do not require systemic therapy at all; the disease is “cured” by a series of local ablative therapies, since no other diseases exist.

      However, in the vast majority of the patients, this would not be the case. Instead, there should be some other “microscopic” metastases which are undetected by the scans, evade the local therapies, and get relapsed without systemic treatment. By focusing on the “microscopic metastases” status, you could make analogy to post-operative adjuvant therapy.

      After the apparently curative surgery, without no “macroscopic” metastases in sight, we usually use conventional chemotherapies for prevention of recurrence. It is hoped that these “cytotoxic” drugs would eradicate the residual cancer cells, leading to true “cures”. The long-tails of the survival curves, with increased number of long-term survivors with the adjuvant chemotherapy (6), show that this theory actually works.

      On the other hand, use of target-based drugs as post-operative adjuvant therapy has so far had only limited success (7,8). The PFS is elongated, without OS benefit (7). It appears that the patients do as good with the use of “targeted” drugs after relapse, and those drugs suppress tumors only as long as they are taken (9). In other words, they appear “cytostatic” and unable to “cure” the disease. Results of IO adjuvant trials are not yet available, but the “long-tails” of the survival curves of IO treatment make us hope for strong cytotoxic, “cure-oriented” effect.

      Therefore, when you aim at “cure” of the OMD, you should choose cytotoxic chemotherapies and/or IO drugs. However, if you are to “control” the disease and get some OS improvement, target-drugs are strong candidates.

      Let me see the topic from another viewpoint. The “local ablative” therapies employed in OMD are surgery and (stereotactic) radiotherapy. Which systemic therapy would make a better partner to which local therapy?

      Almost all target drugs are eventually turned ineffective, due to acquired resistance. However, in some cases, you could elucidate the resistance mechanism and conquer it (10), with modification of the target-based “precision” medicine.

      At present, investigation of the tumor itself is the most certain method, as expressed in the “tissue is the issue” slogan. Very often, however, tiny pathological specimens obtained from transbronchial or CT-guided biopsies are insufficient for the full molecular analysis. Surgical resection of the tumor has advantages both in terms of curative therapy and supply of ample specimens. It also minimizes the late effect on pneumonitis, which is a rare but dreadful toxicity of target-based tyrosine kinase inhibitors. Taken together, use of surgery would be (more) appropriate when you use target-based drugs in OMD.

      On the other hand, there are some clinical data that prior use of radiotherapy is associated with better outcome of IO therapy, implying the so-called “abscopal” effect (11). Investigations are on-going, which are aimed at showing synergistic effect of stereotactic radiotherapy and IO treatment (12,13). This could be applied in the management of OMD.

      So, in conclusion, what is the optimal systemic treatment of OMD? It depends on the aim of the therapy, cure vs elongation of PFS/OS, as well as on the choice of main local therapy, surgery vs radiotherapy. Future studies should specify the aim of the clinical investigation, not only to maximize the efficacy of local therapies and benefit to the patients, but to increase the statistical power of the clinical trials.

      References

      1. Palma DA, et al. Lancet 2019

      2. Gomez DR, et al. J Clin Oncol 2019

      3. Iyenger P, et al. JAMA Oncol 2018

      4. Sacher AG, Gandhi L. JAMA Oncol 2016

      5. Goto Y. J Clin Oncol 2018

      6. Pignon J-P, et al. J Clin Oncol 2008

      7. Kelly K, et al. J Clin Oncol 2015

      8. Zhong WZ, et al. Lancet Oncol 2018

      9. Pennell NA, et al. J Clin Oncol 2019

      10. Jänne PA, et al. New Engl J Med 2015

      11. Shaverdian N, et al. Lancet Oncol 2017

      12. Luke JJ, et al. J Clin Oncol 2018

      13. Miyamoto S, et al. Jpn J Clin Oncol 2019

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      IASLC Members: To view this content or have the option to purchase this event, click here to login.
      Conference Attendees & Access Code holders: Click here to enter your Access Code. Already entered your Access Code? Please login.

    • +

      ES21.05 - Clinical Trials to Advance the Field of OMD (Now Available) (ID 3273)

      15:45 - 17:15  |  Presenting Author(s): Thierry Berghmans

      • Abstract
      • Presentation
      • Slides

      Abstract

      Oligometastatic disease (OMD) in non-small cell lung cancer (NSCLC) is a complex pathology. Four settings can be displayed where synchronous OMD (sOMD), occurring at the time of initial diagnosis, was the most evaluated in clinical trials. Other potential situations are oligorecurrence (rOMD), developed after optimal local control of a localised tumour, oligoprogression (pOMD) corresponding to a progression in a limited number of metastatic sites, and oligopersistant disease (peOMD) after/on systemic therapy. Several non-randomised phase II studies demonstrated the feasibility adding local ablative therapy (LAT) to systemic therapy in sOMD. Design, number of metastatic sites, type of LAT (chemoradiotherapy [CTRT], surgery, stereotactic radiotherapy [SBRT]) and endpoints largely differed among studies. A first pilot study (1) showed that surgery at the primary and the single metastatic sites after induction chemotherapy (CT) was feasible with 57% complete resection (R0) and 11 months median survival (MST). The same approach was recently confirmed in another prospective study with 71% R0 and 46.5% 5-years survival (2). Later, a phase II study conducted in The Netherlands and recently updated (3) demonstrated, when combining LAT (surgery or radiotherapy) to systemic therapy, MST of 13.5months but more essential, 5 and 6-years survival rates of 7.7% and 5.1% respectively. Other phase II studies, including NSCLC with <6 metastases, confirmed those results whether considering overall survival (4), metabolic response (5) or progression-free survival (PFS) (6).

      The first randomised phase II trial (RCT) compared, in sOMD with < 3 metastases non-progressing after CT, LAT (surgery, SBRT, CTRT) plus maintenance to maintenance only. The study closed early after first interim analysis and 49 randomised patients. Updated data confirmed improved PFS (14.2 months vs 4.4 months; p = 0.022) and MST (41.2 months vs 17 months; p = 0.017) favouring the LAT arm. A second small-sized phase II RCT closed early after interim analysis (8). 29 sOMD patients (≤5 metastases) not progressing after CT were randomised between SBRT plus maintenance or maintenance. Also median PFS improved from 3.5 months to 9.7 months (p = 0.01) in the LAT arm.

      All these data need confirmation in larger RCT. Four phase III trials are or will be ongoing. SARON (NCT02417662) is comparing standard CT alone to CT plus SBRT in sOMD with ≤ 3 metastases. In the OMEGA trial (NCT03827577), patients with synchronous or metachronous oligometastatic NSCLC (1-3 metastatic lesions) were considered for LAT (surgery or RT) or not in addition to systemic therapy. SINDAS (NCT02893332) is assessing the role of SBRT in addition to tyrosine kinase inhibitor in sOMD EGFR muted NSCLC with ≤ 5 tumoral sites (inclusive primary site; lymph nodes being considered as a metastatic site). Finally, HALT (NCT03256981) is a phase II-III RCT evaluating SBRT for pOMD during targeted therapy in NSCLC harbouring activating mutations.

      All these studies are presenting with various designs and primary endpoints, but also differences in staging procedures resulting in major difficulties for definite conclusions on the usefulness of LAT in OMD patients. In order having similar populations among clinical trials, we need that a common definition is used by all investigators. In this way, the EORTC Lung Cancer Group proposed a definition for sOMD based on a consensus from thoracic oncology experts (8). Using common definition and staging assessment, and finding predictive factors for a better patient’s selection should be addressed in future clinical trials.

      1. Downey et al. A phase II trial of chemotherapy and surgery for non-small cell lung cancer patients with a synchronous solitary metastasis. Lung Cancer 38:193-7, 2002

      2. Endo et al. A prospective study of surgical procedures for patients with oligometastatic non-small cell lung cancer. Ann Thorac Surg 98:258-64, 2014.

      3. De Ruysscher et al. PFS and OS beyond 5 years of NSCLC patients with synchronous oligometastases treated in a prospective phase II trial (NCT 01282450) OA07.07 J Thorac Oncol 2018

      4. Arrieta et al. Radical consolidative treatment provides a clinical benefit and long-term survival in patients with synchronous oligometastatic non-small cell lung cancer: A phase II study. Lung Cancer. 130:67-75, 2019

      5. Petty et al. Long-Term Outcomes of a Phase 2 Trial of Chemotherapy With Consolidative Radiation Therapy for Oligometastatic Non-Small Cell Lung Cancer. Int J Rad Oncol Biol Physics. 102:527-535, 2018.

      6. Collen et al. Phase II study of stereotactic body radiotherapy to primary tumor and metastatic locations in oligometastatic nonsmall-cell lung cancer patients. Ann Oncol. 25:1954-9, 2014.

      7. Gomez et al. Local Consolidative Therapy Vs. Maintenance Therapy or Observation for Patients With Oligometastatic Non-Small-Cell Lung Cancer: Long-Term Results of a Multi-Institutional, Phase II, Randomized Study. J Clin Oncol JCO1900201, 2019.

      8. Dingemans et al, MA25.02 Journal of Thoracic Oncology 2018;13:S445-S446

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      IASLC Members: To view this content or have the option to purchase this event, click here to login.
      Conference Attendees & Access Code holders: Click here to enter your Access Code. Already entered your Access Code? Please login.

  • +

    IBS06 - Multimodality Treatment - Realtime Data from National Registries (Ticketed Session) (ID 37)

    • Event: WCLC 2019
    • Type: Interactive Breakfast Session
    • Track: Mesothelioma
    • Presentations: 3
    • Now Available
      • Abstract
      • Presentation
      • Slides

      Abstract

      Title: Mesothelioma Realtime Data from Europe - ETOP Mesoscape / ESTS Database

      Introduction:

      Malignant pleural mesothelioma (MPM) is an aggressive malignancy with increasing prevalence and poor prognosis. Despite a still increase in incidence, it remains an orphan disease and studying limited numbers of MPM cases hampers the derivation of solid conclusions.

      The combination of two databases including clinical as well as pathological information will allow researchers to improve the knowledge and facilitate decision-making in patients with MPM.

      The European Thoracic Oncology Platform (ETOP) Mesoscape project and the European Society of Thoracic Surgeons’ (ESTS) database are designed to address clinical, pathological, and molecular characteristics of mesothelioma patients and their impact on outcome. The joined analysis of both databases is a unique approach to real-time data reflecting the reality of mesothelioma characteristics, treatment and prognosis in Europe.

      Materials and Methods:

      A decentralized biobank with fully annotated tissue samples is established for ETOP Mesoscape. Selection criteria for participating centers included sufficient number of cases, and documented ethical approval. Patient selection is based on availability of comprehensive clinical data with adequate follow-up, and adequate quantity and quality of formalin-fixed tissue.
      The ESTS database is a clinical database with pre-operative, intra-operative and post-operative data. A minimum set of data is captured, including demographic, histology, treatment, staging and follow up data.

      The characteristics between the two databases are compared using the Fisher’s exact test (for categorical variables) and Mann-Whitney test (for continuous variables), while Kaplan-Meier method (with log-rank test).

      Results:

      Up to 29 May 2019, the ETOP Mesoscape included information on 497 patients from 10 centers, diagnosed between 1999-2018. In the ESTS database, as of April 2019, 2269 patients are included, diagnosed between 1989-2019.

      Patients in both databases are primarily men (84% in the ETOP, 71% in the ESTS), of 0/1 ECOG Performance status (46/46% and 59/29% in ETOP and ESTS respectively), with known previous exposure to asbestos (75% and 93%) and median ages 64 and 67 years old.

      Significant differences are detected between the two data sources with respect to gender, exposure to asbestos and age (p-value <0.001).

      The primary histology of patients is epithelioid (72% in ETOP and 70% in ESTS), followed by biphasic (22%; 17%) and sarcomatoid (6%; 9%) (not significantly different between the two databases).

      Clinical staging is available for 77% of the patients in ETOP, but only for the 28% in the ESTS database. The stage distribution (I/II/III/IV) is 14/29/42/15% in the ETOP and 23/21/41/16% in the ESTS (significantly difference p<0.001).

      Among the biomarkers common in both data sources, Calretinin and WT1 are detected in the vast majority of patients tested (Calretinin: 97% in both cases; WT1: 89% and 87% in the ETOP and ESTS database respectively).

      For the ETOP cases 90% (of those tested) are CK5/6 positive, 91% D2-40 positive and 97% Pan-CK positive.

      Palliative treatment has been administered in 41% of the ETOP cases. Among them, 84% received palliative chemotherapy (with the vast majority 92%, using multiple agents). Palliative surgery was undertaken in 32% (62 of 194 patients with available information) and palliative radiotherapy for 13% of the patients.

      Complete resection has been performed in 59% of the ETOP Mesoscape patients. This was combined with induction chemotherapy (81%), while adjuvant chemotherapy and radiotherapy was administered in 4% and 37% respectively.

      The surgical approach adopted for the ESTS patients was either video-assisted thoracoscopic surgery (VATS) (59%) or thoracotomy (41%) based on a subset of 887 patients with available information. Post-operation treatment information is available for 620 ESTS patients. Among them, 71% received chemotherapy, 54% underwent surgery and 15% radiotherapy.

      Conclusion:

      We present the combined results from the ETOP Mesoscape and the ESTS database, one of the largest databases. These two series allow us to report on mesothelioma epidemiology and treatment.

      Up to now, the comparison of the baseline characteristics of the patients of the two data sources revealed some statistically significant differences with respect to gender, age, exposure to asbestos and clinical stage.

      As tissue from all ETOP Mesoscape patients is preserved locally and is available for detailed molecular investigations, Mesoscape provides an excellent basis to evaluate the influence of molecular parameters on the disease outcome, besides providing an overview of the molecular landscape.

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      IASLC Members: To view this content or have the option to purchase this event, click here to login.
      Conference Attendees & Access Code holders: Click here to enter your Access Code. Already entered your Access Code? Please login.

    • +

      IBS06.02 - Real Time Data from US (SEERS) (Now Available) (ID 3332)

      07:00 - 08:00  |  Presenting Author(s): Emanuela Taioli  |  Author(s): Maaike Van Gerwen, Naomi Alpert, Andrea Wolf, Raja Flores

      • Abstract
      • Presentation
      • Slides

      Abstract

      Real time data for Mesothelioma in US

      Maaike van Gerwen, Naomi Alpert, Andrea Wolf, Raja Flores, Emanuela Taioli

      Introduction

      The association between asbestos exposure and malignant mesothelioma has been well established. Exposure to asbestos mainly occurs through work although environmental exposure has been documented. Several countries have put in place an active epidemiologic surveillance of mesothelioma cases.

      Through a PubMed and Google Scholar search using the key words “mesothelioma” and “registry”, and by reviewing data sources of studies described in a review of environmental exposure and malignant mesothelioma, we identified existing mesothelioma registries. Countries with mesothelioma specific registries are Australia, Belgium, France, Germany, Italy, Japan, South Korea, South Africa, Turkey, and the UK. Nation-wide coverage is obtained in Italy, Australia and South Korea. Registries in Australia, France, Italy, and South Korea use interviews to obtain exposure data from the patient or a close relative, although none of these countries has a tissue bank. The UK has a mesothelioma tissue bank although it is not linked with the National Mesothelioma Audit registry. All registries have or will develop linkage with death index registries to monitor survival outcomes. (Table 1)

      The Scandinavian countries including Norway, Sweden, Finland and Denmark, have a population based cancer registry that includes mesothelioma and is linked to other databases, such as an occupational database, thus has more comprehensive information on each case.

      Mesothelioma surveillance in the US to date

      Currently, no nation-wide, mesothelioma specific registry exists in the US. Various existing databases are used to investigate mesothelioma, for instance the National Cancer Database has been used to look at prognostic factors; gender and race differences in mesothelioma survival have been studied using the Surveillance, Epidemiology, and End Results (SEER) database. All these datasets suffer of a time-lag between case occurrence, reporting, registration and eventually data availability for research purposes; these are serious limiting factors in the case of mesothelioma. Because of the rarity and lethality of the disease, a real-time capture registry is needed to thoroughly collect exposure data, complete data on treatments, quality of life before and after treatment, symptoms and pain management. All these elements are lacking in the existing databases.

      Because the US mesothelioma incidence is not decreasing as quickly as predicted and new cases still occur as well the fact that mortality rates are steady overtime, the overall health burden due to mesothelioma in the US still remains. Although the use of asbestos has been restricted or banned since 1980, several scientific questions remain open due to the long latency period between exposure and mesothelioma clinical occurrence, and to gaps in knowledge of the carcinogenesis process. Data on occupational and environmental asbestos exposure and co-exposure to other carcinogens are needed. Certain patterns, such as differences in outcomes by gender, differences in incidence rates by race, as well as geographic clusters of increased number of cases, are hard to explain with the existing data.

      Possible next steps towards a US mesothelioma registry

      “Real time” enrollment is important in order to systematically collect information on asbestos and other exposures through interviews with mesothelioma patients or a close relative. Furthermore, optimal coverage, preferably population based and nation-wide, and a simplified consent process are needed in order to capture a maximum number of cases. A centralized quality control system, standardized data collection methods, and the ability to link to relevant other existing registries are important in order to integrate the registry with clinical and prognostic information. Additionally, consistency in the design and questionnaire content with other countries would be ideal, in order to conduct comparisons and possibly pool the data. The flexibility to add or modify modules to tailor to future research questions are other preferable features for a US mesothelioma registry. (Figure 1) A discrete amount of work has been devoted to molecular markers such as mesothelin and certain germline mutations as prognostic factors. The role of these biomarkers could be validated on larger populations of patients if a comprehensive registry that includes tissue is implemented.

      Summary and conclusions

      In conclusion, with the remaining health burden due to mesothelioma, the changing landscape of asbestos exposure, and the many unanswered scientific questions, a nation-wide, real-time US mesothelioma registry is urgently needed. Methods for data sharing, linkage to existing tissue banks, and data access should be implemented and tested on a small scale before being implemented nationwide. One of the most practical outputs of these efforts would be the ability to conduct pragmatic trials that could be built out of a “real time” case capture system.

      iaslc fig.jpg

      iaslc table.jpg

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      IASLC Members: To view this content or have the option to purchase this event, click here to login.
      Conference Attendees & Access Code holders: Click here to enter your Access Code. Already entered your Access Code? Please login.

    • +

      IBS06.03 - Japanese Data (Now Available) (ID 3333)

      07:00 - 08:00  |  Presenting Author(s): Seiki Hasegawa  |  Author(s): Hiroyuki Yamamoto, Masaki Hashimoto, Eriko Fukui, Kenji Suzuki, Yukio Sato, Shunsuke Endo, Masayuki Chida

      • Abstract
      • Presentation
      • Slides

      Abstract

      Backgrounds

      Annual surveys of cardiothoracic surgery throughout Japan has been conducted by the Japanese Association for Thoracic Surgery (JATS) since 1986 in order to establish the statistics for the number of procedures by operative category1. Regarding malignant pleural mesothelioma (MPM), however, only annual case numbers of both diffuse and localized MPM have been registered since 1996. From 2009 onward, surgical technique, 30-day mortality, and in-hospital mortality have been also described. According to the JATS survey, all-kind of surgery for MPM increased 76% during 1996 and 2016: 164 cases in 1996 and 289 cases in 2016. JATS survey also revealed dramatic increase of pleurectomy/decortication (P/D) cases during 2009 to 2016: proportion of P/D surgery in all curative-intent surgery was 1.4% (2/142) in 2009 and 53.3% (73/137) in 2016.

      Methods

      In 2011, the National Clinical Database (NCD) of Japan adopted an annual web-based nationwide data collection system2. Since NCD is associated with the Japanese Surgical Board Certification System, it contains detailed perioperative clinical information such as preoperative patient characteristics, operation time, blood loss, intraoperative accidents, pathological TNM stages, postoperative adverse events, redo-surgery, 30-day and in-hospital mortality, cause of death, and so on. Approximately 10 million surgical procedures from >5000 hospitals have been collected by 2017.

      An NCD specifically for general thoracic surgery was launched in 20143.

      This time, we conducted an analysis on MPM surgery in Japan using the Japan NCD.

      Results (Table 1)

      In the period of 4 years between 2014 and 2017, a total of 622 curative-intent surgery was performed in Japan. Median age was 66 years (IQR, 61-71), and 87.6% were male. A median BMI was 22.6 (20.3-24.8), and 77.3% was ECOG PS0. Induction therapy was given in 40.8% of patients. Extrapleural pneumonectomy was performed in 279 patients (44.9%) and P/D in 343 (55.1%). Blood transfusion was required in 320 (51.4%) patients (Figure 1). Injury of major intrathoracic organ occurred in 22 (3.5%) patients. Morbidity rate was 40.0% (249/622). Thirty-day mortality and in-hospital mortality were 1.1% and 3.2%, respectively (Table 1).

      Conclusion

      In addition to the above JATS survey and Japan NCD, a nationwide, prospective, observational study of patients with MPM has just completed 2-year’s patient accrual4. It is promising that these Japanese data will substantially contribute to understanding MPM in near future.

      1 Thoracic and cardiovascular surgery in Japan in 2016. Committee for Scientific Affairs, The Japanese Association for Thoracic Surgery, Shimizu S, Endo S, Natsugoe S, et al. Gen Thorac Cardiovasc Surg 2019; 67: 377-411.

      2 http://www.ncd.or.jp/

      3 Development of an annually updated Japanese national clinical database for chest surgery in 2014. Endo S, Ikeda N, Kondo T, et al. Gen Thorac Cardiovasc Surg 2016; 64: 569-576.

      4 Shintani Y, Hasegawa S, Takuwa T, et al. Prospective registry database of patients with malignant mesothelioma: Directions for a future Japanese registry-based lung cancer study. J Thorac Dis 2018; 10: 1968-71

      Table 1
      EPP (n=279) P/D (n=343) Total (n=622)
      age (median, IQR) 65 (59-69) 67 (63-73) 66 (61-71)
      male sex 250 (89.6%) 295 (86.0%) 545 (87.6%)
      BMI (median, IQR) 22.3 (20.2-24.2) 23 (20.4-25.1) 22.6 (20.3-24.75)
      PS 0 215 (77.1%) 266 (77.6%) 481 (77.3%)
      1 57 (20.4%) 65 (19.0%) 122 (19.6%)
      2-4 5 ( 1.8%) 10 ( 2.9%) 15 ( 2.4%)
      unknown 2 ( 0.7%) 2 ( 0.6%) 4 ( 0.6%)
      Induction therapy 103 (36.9%) 151 (44.0%) 254 (40.8%)
      Blood transfusion 159 (57.0%) 161 (46.9%) 320 (51.4%)
      Major organ injury 12 ( 4.3%) 10 ( 2.9%) 22 ( 3.5%)
      Morbidity 126 (45.2%) 123 (35.9%) 249 (40.0%)
      30-day mortality 3 ( 1.1%) 4 ( 1.2%) 7 ( 1.1%)
      in-hospital mortality 9 ( 3.2%) 11 ( 3.2%) 20 ( 3.2%)

      figure 1.png

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      IASLC Members: To view this content or have the option to purchase this event, click here to login.
      Conference Attendees & Access Code holders: Click here to enter your Access Code. Already entered your Access Code? Please login.

  • +

    IBS16 - Invasive Diagnosis and Surgery in Lung Cancer Screening Participants (Ticketed Session) (ID 41)

    • Event: WCLC 2019
    • Type: Interactive Breakfast Session
    • Track: Screening and Early Detection
    • Presentations: 2
    • Now Available
    • +

      IBS16.01 - Lung Cancer Screening and Its Effect on Surgery (Now Available) (ID 3344)

      07:00 - 08:00  |  Presenting Author(s): Giulia Veronesi

      • Abstract
      • Presentation
      • Slides

      Abstract

      The diagnostic revolution started in 1999 when the group of Prof. Henschke in New York published the results of Elcap study showing that Low Dose CT scan had 7 times higher sensitivity than chest-Xray to detect stage I lung cancer in 1000 high risk individuals. Subsequently in 2006 the I-elcap published 80% cancer specific survival rate at 10 years of the 484 patients with a screening cancers detected in 31.000 screened subjects.

      More evidence was required by before implementing Lung Cancer Screening on a wider scale, and the US randomised controlled trial NLST released data in 2012. The investigators reached the objective of 20% mortality rate reduction in the screening arm so that they stopped the trial and suggested to partecipants of the control arm to be screened.We needed to wait additional 6 years to have the released data of Nelson study, the European largest RCT, which mortality reduction was unexpectedly better than NLST with a mortality reduction 26-39% in men and women at 10 years for the screening arm with LDCT compared to no screening.

      Despite the evidence is available, in Europe only few countries have started a national implementation. One of the potential obstacle is related to uncertainties on sustainability. In Italy to stimulate a policy maker decision, our group have calculated the potential economical impact to implement LDCT in the population at risk (the analysis was presented at WCLC in Toronto). In collaboration with the Bocconi university we have found one of the lowest ICER for LDCT screening, 3049 for QALY.

      In Italy the potential target population of LDCT program includes 2.166.000 millions high risk individuals (smokers or former smokers, 55 years or older with 30 packs year smoking history) and 120 milions euros /year is the potential cost to screen all the high risk individuals according to this preliminary CEA analysis.

      The other obstacle is related to safety of LDCT screening on a large scale outside the academic environment.

      How characteristic of lung cancer changed with introduction of screening? and which is the impact on surgical approaches? In our experience and other screening programs most cancer cases were diagnosed in stage I with a mean size of 1.6 cm. In addition recall rate was very low, 5-10 % compared to 20-27% on NLST, risk of overdiagnosis was very limited around 10% of screening cancers; Estimated risk of lung cancer due to LDCT radiation exposure was less than 1 out of 108 detected in the worst scenario, false positive cases less than 2 %.

      It was clear that traditional open lobectomy was an overtreatment and minimally invasive lung sparing resection was required.

      Different retrospective studies have shown that sublobar resection are adequate oncological operation for very early stage lung cancers (in particular subsolid, slow growing or low suv tumors). More data on this topic will come from the two ongoing randomised trials in Us and Japan comparing lobectomy and segmentectomies for stage Ia and Ib NSCLC.

      In this scenario among the different types of minimally invasive approaches the robotic technique has recognised a wide diffusion all over the world with a great success due to the indisputable technical advantages including optimal 3D view, increased degrees of freedom, motion scaling, stable camera platform. We described in 2014 the technique and results of robotic approach to afford typical segmentectomies and concluded that robotic system by improving ergonomic, surgeon view and precise movements, may make minimally invasive segmentectomy easier to adoptand perform.

      In addition many surgeons find very useful to inject the ICG ev after isolation and resection to better define the intersegmental plane and thus perform a more radical resection according to the technique we described in 2014. In this way many small centrally located tumors with high suspiciousness of malignancy can be treated with a diagnostic and therapeutic resection using MIS and lung sparing procedure.

      One of the most discussed issue in the treatment of lung cancer is related to extension of lymph node dissection. We analysed a consecutive series of clinical N0 screen detected cancers to identify predictive criteria of nodal involvement and found that in very small (less than 1 cm) or PET negative tumorslymph node dissection can be avoided with no risk of nodal involvement.

      Major goals of surgical participation in lung cancer screening programs include: 1. Optimization of the management of screen detected nodules; 2. Reduction of false positive rates and surgical diagnosis of benign diseases; 3. Reduction of surgical incision-related trauma; 4.Avoid overtreatment and favor tailored resection; 5. Collect sample for biomarker research for diagnostic and prognostic molecular non-invasive tests; 6. Participate to multidisciplinary meeting with radiologists; 7. Participate in national or international registries for quality control.

      Henschke, C. I. et al., Early Lung Cancer Action Project: overall design and findings from baseline screening. Lancet 354 (9173), 99 (1999)

      Aberle DR, Adams AM, et al. Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med. 2011;365:395-409.

      De Koning H et al PL02.05 Effects of Volume CT Lung Cancer Screening: Mortality Results of the NELSON Randomised-Controlled Population Based Trial. J Thoracic Oncology, 2018;13,10: Supp.S185. DOI: https://doi.org/10.1016/j.jtho.2018.08.012.

      Veronesi G, et al. Analysis indicates low incremental cost-effectiveness ratio for implementation of lung cancer screening in Italy. WCLC 2018 Toronto

      Veronesi G, et al. Diagnostic performance of low-dose computed tomography screening for lung cancer over five years. J Thorac Oncol. 2014;9(7):935-9.

      Nakamura k, et al. A phase III randomized trial of lobectomy versus limited resection for small-sized peripheral non-small cell lung cancer (jcog0802/wjog4607l). jpn j clin oncol. 2010;40:271-274.

      Altorki NK , et al. Perioperative mortality and morbidity after sublobar versus lobar resection for early-stage non-small-cell lung cancer: post-hoc analysis of an international, randomised, phase 3 trial (calgb/alliance 140503). lancet respir med. 2018;6:915-924.

      Pardolesi A, et al. Use of indocyanine green to facilitate intersegmental plane identification during robotic anatomic segmentectomy. JTCVS , 148, 737-738

      Veronesi G, Maisonneuve P, Pelosi G et al. Screening-detected lung cancers: is systematic nodal dissection always essential? J Thorac Oncol. 2011;6(3):525-30.

      Osarogiagbon RU, etr al. Early-Stage NSCLC: Advances in Thoracic Oncology 2018. JTO1556-0864

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      IASLC Members: To view this content or have the option to purchase this event, click here to login.
      Conference Attendees & Access Code holders: Click here to enter your Access Code. Already entered your Access Code? Please login.

    • +

      IBS16.02 - Minimally Invasive Lung Cancer Screening (Now Available) (ID 3345)

      07:00 - 08:00  |  Presenting Author(s): Witold Rzyman

      • Abstract
      • Presentation
      • Slides

      Abstract

      Lung cancer screening is a challenge for the specialists that are involved in this multidisciplinary venture. There is a huge number of individuals with CT-findings that are non-malignant and a lot of indeterminate pulmonary nodules that are difficult to assess. High sensitivity is required not to overlook early lung cancer but simultaneously acceptable specificity have to be ensured in order to reduce futile invasive diagnostics and treatment procedures related to false positive diagnoses (1,2,3).

      The experience of the multidisciplinary team and adoption of the specific radiological protocol that is strictly followed is a mainstay of successful lung cancer screening program. Thoracic radiologist is responsible for the reduction of false positive rate to a safe minimum. This goal can only be achieved by strict adherence to the guidelines and protocol for the assessment of nodules. LungRads or volumetry with assessment of volume doubling time should be applied to minimize false positive rate. The multidisciplinary discussion on tumor board meeting of the suspected cases is another element leading to the reduction of unnecessary invasive diagnostics and surgery in non-malignat leasions that produces harm, entails risk of complictions and increases costs (3). In Gdańsk where two screening programs were conducted during last 10 years most harmfull aspects were reduced almost doublefold (tab.1). several studies have shown that by applying an effective diagnostic algorithm together with multidisciplinary discussion of positive cases detected by CT screening, the frequency and extent of surgery for non-malignant disease can be minimized while a high cure rate for individuals diagnosed with lung cancer can be obtained (1,3,4). Mainly radiologists and thoracic surgeons involved in multidisciplinary tumor board have the important responsibility to minimize the risk of useless invasive procedures for benign disease and avoid overtreatment of very early cancers or precancerous lesions (1,3)

      The proportion of patients that are sent for invasive diagnostic procedures varies between 2-7% and depends on the quality of the screening center. In Gdańsk, although in both programs approximately 3,5% of individuals participating in the screening were sent for the diagnostics, lung cancer detection rate in these groups were 30% and 57% respectively so diagnostic accuracy increased significantly. The invasive diagnostic work –up is based on FNAB and CNB where radiologists play crucial role as in majority of the institutions they perform biopsies. Pulmonary nodules biopsy in the best institutions is performed with 80-90% specificity and sensitivity and reasonably low complication rate. Pneumothorax is among most frequently observed complications requiring pleural drainage in 10-20% of cases. Bronchoscopy, EBUS, EUS and PET-CT are additional tools that completing the diagnosis and staging. Endobronchial navigation bronchoscopy (ENB) is a supplementary method that enhances the diagnostic yield of flexible bronchoscopy from 36-68% to 63-77% depending on the size and location of peripheral pulmonary lesion. This method has great potential in the future treatment of small nodules detected in lung cancer screening programs. Lately two ablation systems are intensively tested that can be applied by ENB. The minimally invasive techniques in the future treatment of screening detected cancers are the only treatment options that could be accepted in this context. The application of ultrasound or radiofrequency ablation by ENB system in the treatment of pure GGO and mixed GGO lesions that are progressing would be the very promising solution.

      Although lobectomy is still a gold standard in the treatment of stage I NSCLC this dogma most probably is going to be changed in the near future, at least for T1N0 tumors. Many retrospective studies report no difference in overall and recurrence free survival of patients operated with lobectomy and sublobar resection. There are however many studies that are showing conflicting results. In the analysis of 6000 operated stage I NSCLC patients based on national lung cancer registry in Poland Dziedzic et al. have shown significantly inferior overall survival in wedge resection group comparing to lobectomy and segementectomy groups (5). Segmentectomy provides two benefits comparing to wegde resection: allows to obtain a wide resection margin and to perform hilar lymphnode resection. It is however much more technically demanding when VATS procedure is considered.

      In the presentation the crucial aspects of “minimally invasive” LDCT lung cancer screening will be discussed.

      References:

      1. Flores R, Bauer T, Aye R; I-ELCAP Investigators. Balancing curability and unnecessary surgery in the context of computed tomography screening for lung cancer. J Thorac Cardiovasc Surg. 2014 May;147(5):1619-26.

      2. Rzyman W, Jelitto Górska M, Dziedzic R, et al. Diagnostic work up and surgery in participants of the Gdańsk lung cancer screening programme: the incidence of surgery for non malignant conditions. Interact CardioVasc Thorac Surg. 2013; 17: 969 973.

      3. Holst Pedersen J, Rzyman W, Veronesi G et al. Recommendations from the European Society of Thoracic Surgeons (ESTS) regarding computed tomography screening for lung cancer in Europe. Eur J Cardiothorac Surg 2017;0:411–20.

      4. Veronesi G, Bellomi M, Mulshine JL, et al. Lung cancer screening with low-dose computed tomography: A non-invasive diagnostic protocol for baseline lung nodules. Lung Cancer. 2008;61:340-349.

      5. Dziedzic R, Zurek W, Marjanski T et al. Stage I non-small-cell lung cancer: long-term results of lobectomy versus sublobar resection from the Polish National Lung Cancer Registry. Eur J Cardiothorac Surg. 2017 Aug 1;52(2):363-369.

      Tab.1 Comparison of two lung cancer screening programs performed in Gdańsk, Poland between 2009–2011 and 2016-2018 in terms of selected results affecting quality of screening.

      PILOT

      2009-2011

      MOLTEST

      2016-2018

      Lung cancer (det. rate)

      1,2%

      2%

      False positive rate

      34,7%

      17,6%

      Invasive work-up

      3,6%

      3,5%

      Futile surgery

      29%

      16%

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      IASLC Members: To view this content or have the option to purchase this event, click here to login.
      Conference Attendees & Access Code holders: Click here to enter your Access Code. Already entered your Access Code? Please login.

  • +

    IBS27 - Chestwall Tumors (Ticketed Session) (ID 58)

    • Event: WCLC 2019
    • Type: Interactive Breakfast Session
    • Track: Thymoma/Other Thoracic Malignancies
    • Presentations: 2
    • Now Available
    • +

      IBS27.01 - Management of Chest Wall Tumors (Except Sternum) (Now Available) (ID 3399)

      07:00 - 08:00  |  Presenting Author(s): Gaetano Rocco

      • Abstract
      • Presentation
      • Slides

      Abstract

      The principles to surgically manage chest wall tumors vary according to the origin of the tumor (primary vs secondary), the pre-existing conditions of the chest wall (previously operated, irradiated or infected) and the available materials for reconstruction (1). Primary chest wall tumors require resection with at least 4 cm margin as well as careful removal of the periosteum/perichondrium of the remaining rib segments (1 to 2 cm) which may harbor the cancer-cells filled lymphatics responsible for early recurrence (2,3). As a rule, the uppermost and lowermost ribs around the primary tumor including the intercostal muscles need to be removed. For tumors located posteriorly in the first three to four ribs, reconstruction may be avoided albeit the extravasation of pleural fluid in the subcutaneous tissues may be a source of complication and affect the patient’s perception of a successful result (1,2). To ensure consistent intrathoracic physiology and avoid lung herniation through anterior and lateral chest wall defects, especially if larger than 1 rib with the upper most and lowermost intercostal spaces, reconstruction is advisable (2,3). Secondary tumors can present as solitary soft tissue or bony metastases requiring localized resection or can infiltrate the chest wall in continuity (3). The latter is the case of T3/4 lung cancer which needs to be resected en-bloc with the chest wall, keeping the line of resection at least at 2 cm from the edge of the infiltration (3). The reconstructive materials to be used are represented by time-honored rigid and soft meshes (Vycril, Polypropilene, Marlex, PTFE) which can still be effectively used for primary reconstruction in the absence of complication factors, such as redo procedures, previously irradiated or infected fields (1,4,5). More recently, new materials have been introduced in the clinical practice, namely, new generation titanium plates, acellular collagen matrices, Poly-4-hydroxybutyrate (P4HB), and, cryopreserved homograft of cadaveric origin (1). These materials present a common advantage of being biocompatible, amenable to modeling and incorporable into the host without the need to remove them should local infection complicate the postoperative period (1). However, all of these prosthetic materials need to be covered with viable tissue, ie, muscle flap, fat and omentum since direct exposure to skin may cause wound seroma or breakdown (1). New perspectives are provided by obtaining adequate biomimesis in the reconstruction of large chest wall defects through 3D printing from CT chest wall templates (6). However, the choice of the reconstructive materials is still a matter of surgeon’s preference, resource availability, and costs (2). Apart from some important exceptions (ie, Ewing’s sarcoma), primary chest wall tumors may be chemo- and/or radioresistant (7). The resort to a multimodality approach (ie, chemoradiotherapy followed by surgery) for the involvement of the bony as well as the neurovascular structures at the thoracic inlet has been associated to significantly improved survival rates (8). While the role of adjuvant treatment for non-Pancoast T3N0-1 lung cancer invading the chest wall is established, the recent literature identifies promising survival advantage in administering induction treatment in this selected subset of patients (9,10).

      Rocco G. Chest wall resection and reconstruction according to the principles of biomimesis. Semin Thorac Cardiovasc Surg. 2011;23(4):307-13.

      Rocco G, Martucci N, La Rocca A, et al. Postoperative local morbidity and the use of vacuum-assisted closure after complex chest wall reconstructions with new and conventional materials. Ann Thorac Surg. 2014;98(1):291-6.

      <>3.Weyant MJ, Bains MS, Venkatraman E, et al. Results of chest wall resection and reconstruction with and without rigid prosthesis. Ann Thorac Surg. 2006;81(1):279-85.

      <>5.Moradiellos J, Amor S, Córdoba M, et al. Functional Chest Wall Reconstruction With a Biomechanical Three-Dimensionally Printed Implant. Ann Thorac Surg. 2017;103(4):e389-e391.

      <>7.8.9.10.Kawaguchi K, Yokoi K, Niwa H, et al; Central Japan Lung Study Group. A prospective, multi-institutional phase II study of induction chemoradiotherapy followed by surgery in patients with non-small cell lung cancer involving the chest wall (CJLSG0801). Lung Cancer. 2017;104:79-84.

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      IASLC Members: To view this content or have the option to purchase this event, click here to login.
      Conference Attendees & Access Code holders: Click here to enter your Access Code. Already entered your Access Code? Please login.

    • +

      IBS27.02 - Sternal Resection and Reconstruction (Now Available) (ID 3400)

      07:00 - 08:00  |  Presenting Author(s): Stephen Cassivi

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      IASLC Members: To view this content or have the option to purchase this event, click here to login.
      Conference Attendees & Access Code holders: Click here to enter your Access Code. Already entered your Access Code? Please login.

  • +

    MA10 - Emerging Technologies for Lung Cancer Detection (ID 129)

    • Event: WCLC 2019
    • Type: Mini Oral Session
    • Track: Screening and Early Detection
    • Presentations: 12
    • Now Available
    • +

      MA10.01 - Invasive Adenocarcinoma in Screen Detected Pure Ground-Glass Nodules (GGN) (Now Available) (ID 2736)

      15:15 - 16:45  |  Presenting Author(s): Renelle Myers  |  Author(s): John English, Sukhinder Kaur Atkar-Khattra, John Mayo, John Yee, Annette Maree McWilliams, Ming Sound Tsao, Stephen Lam

      • Abstract
      • Presentation
      • Slides

      Background

      A major criticism of lung cancer screening initiatives is their propensity to instigate enhanced surveillance and over-treatment of otherwise indolent disease, including adenocarcinoma-in-situ (AIS). These nodules present radiographically as GGN. There are wide variations in the recommendations for surveillance (repeat imaging), diagnosis (biopsy) and therapeutic intervention (resection) for these lesions. To further our understanding of the optimal management of screen detected GGN, we used data from two screening studies in Canada with up to 17 years of follow-up to determine the proportion of persistent GGN that are invasive adenocarcinomas.

      Method

      Two lung cancer screening studies data sets were reviewed: the BC Lung Health Study (BCLHS) with 1365 participants and the Pan-Canadian Early Detection of Lung Cancer Study (PanCan) with 2537 participants. BCLHS enrolled ever smokers 45-74 years of age with >30-year smoking history. The median follow-up in this cohort was 12 years (0.1-17.6) The PanCan study screened participants age 50-75 years with a PLCOm2008 6-year lung cancer risk > 2%. The median follow-up was 5.5 years (3.2-6.1). The nodules were followed until they resolved, demonstrated stability for >2 yrs or were surgically resected. All pure GGO resected were re-reviewed and classified by two pulmonary pathologists according to the revised 2015 World Health Organization classification of lung tumours. Cancers were staged using the 8th edition of the AJCC/UICC cancer staging manual.

      Result

      A total of 18,589 nodules in 3902 participants were reviewed. 2392 (13% of all nodules) were classified as pure GGN. 1073 of the 2392 were > 5mm at the baseline scan. Of these 1073 GGN, 156 (15%) resolved, 879 (82%) remained pure GGN, 38 (3.5%) became part-solid or solid. 32(3%) of the GGN from 29 patients that demonstrated growth were resected. The median size prior to resection was 16 mm (range 7 to 33 mm). The histopathology distribution included: 19 invasive adenocarcinomas, 7 minimally invasive adenocarcinomas, 6 adenocarcinoma-in-situ. The TNM stage distribution and average size of the GGN on the CT prior to resection are listed in Table 1. Sixty-one percent of the invasive cancers (Stage IA1 to IIIA) were less than 20 mm. Eleven percent of the invasive adenocarcinomas had lymph node metastasis.

      presentation3.jpg

      Conclusion

      A high proportion of pure GGN that demonstrate growth are invasive cancers. The majority were < 20mm in size when they were resected. This has significant implication in the development of recommendations to manage screen detected GGN.

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      IASLC Members: To view this content or have the option to purchase this event, click here to login.
      Conference Attendees & Access Code holders: Click here to enter your Access Code. Already entered your Access Code? Please login.

    • +

      MA10.02 - Deep Learning with Radiomics May Predict High-Grade Lung Adenocarcinoma Based on Histological Patterns in Ground Glass Opacity Lesions (Now Available) (ID 128)

      15:15 - 16:45  |  Presenting Author(s): Xing Wang  |  Author(s): Li Zhang, Lei Tang, Xin Yang, Quanzheng Li, Nan Wu

      • Abstract
      • Presentation
      • Slides

      Background

      Adenocarcinoma (ADC) is the most c­­­­­­­ommon histological subtype of lung cancers in non small cell lung cancer (NSCLC) in which ground glass opacifications (GGOs) found on computed tomography (CT) scans are the most common lesions. These lesions are usually treated with limited lung resection. However, the presence of a micropapillary or solid component is identified as an independent predictor of prognosis, indicating a more extensive resection. The accurate classification of subtypes still remains difficult in radiology or in frozen pathological analysis, even with the help of classical radiomics. The purpose of our study is to explore imaging phenotyping using a novel method combining radiomics with deep learning (RDL) to predict high-grade patterns within lung ADC.

      Method

      Included in this study were 111 patients differentiated as having GGOs and pathologically confirmed ADC. Four different methods were compared to classify the GGOs for the prediction of the pathological subtypes of high-grade lung ADCs, including classic machine learning, radiomics, deep learning method, and a proposed novel method referred as RDL. A four-fold cross-validation approach was used to evaluate the performance of such methods.

      Result

      We analyzed 32 patients with high-grade patterns and 79 without such patterns. The proposed RDL has achieved an overall accuracy of 0.888, which significantly outperforms classic machine learning, radiomics, and deep learning alone (p< 0.001, paired t-test).


      figure1.pngfigure2.png

      Conclusion

      High-grade lung ADC based on histologic pattern spectrum in GGO lesions might be predicted by a novel framework combining radiomics with deep learning, which reveals a significant advantage over traditional methods.

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      IASLC Members: To view this content or have the option to purchase this event, click here to login.
      Conference Attendees & Access Code holders: Click here to enter your Access Code. Already entered your Access Code? Please login.

    • +

      MA10.03 - Quantitative Computed Tomography (CT) Based Texture Analysis; Could We Predict the Future Growth of the Pure Ground Glass Nodules? (ID 229)

      15:15 - 16:45  |  Presenting Author(s): Joosung Sun  |  Author(s): Hye Lin Kim, SeulGi You, Youngin Choi, Young Gi Min, Kyung Joo Park

      • Abstract
      • Slides

      Background

      To evaluate whether the quantitative computed tomography based texture analysis (QTA) could predict the future growth of the pure ground glass opacity nodule (GGN) or not.

      Method

      We retrieved CT images of 9284 patients who underwent chest CT in 2013 from the picture archiving and communication system (PACS). We queried the database of PACS to filter reports of chest CT containing one of these key words, as follows; “ground-glass”, ground glass”, or “GGO(s)”. 78 patients were finally included [5 patients (5GGNs) who underwent operation due to growth of GGN during follow-up and 73 patients who had 3-year-follow-up CT]. Total 90 GGNs from 78 patients were analyzed by QTA. The parameters of QTA were mean HU value, standard deviation (SD), entropy, mean positive pixels (MPP), skewness, and kurtosis. QTA was performed with image filtration step to remove photon noise, filtration technique enhanced features of different sizes based on the spatial scale filter (SSF) value varying from fine-texture (SSF2), medium-texture (SSF3), and coarse-texture (SSF4). We focused on the change of volume% of GGNs [(follow-up volume of GGN/initial volume of GGN)*100%], and assessed the differences of QTA parameters’ value according to the change of volume % for three cut-off levels (150%, 170%, and 200%); group 1a (≤130%), group 1b (>130%);group 2a (≤150%), group 2b (>150%);group 3a (≤170%), group 3b (>170%).

      patients.png

      Result

      r.png

      Only entropy was a variable that showed statistically significant difference between group 3a and 3b with all the filtrations (SSF2, 3, 4) applied or without filtration (SSF0). The mean, SD, MPP, kurtosis and skewness, showed no significant difference according to the cut-off value of volume % change (130%, 150%). There was no significant difference in QTA parameters in group2a vs 2b, group3a vs 3b.

      Conclusion

      The initial entropy parameter of texture analysis for GGNs may have the potential to predict the GGNs growth.

      IASLC Members: To view this content or have the option to purchase this event, click here to login.
      Conference Attendees & Access Code holders: Click here to enter your Access Code. Already entered your Access Code? Please login.

    • +

      MA10.04 - Discussant - MA10.01, MA10.02, MA10.03 (Now Available) (ID 3750)

      15:15 - 16:45  |  Presenting Author(s): Marcelo Sanchez

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      IASLC Members: To view this content or have the option to purchase this event, click here to login.
      Conference Attendees & Access Code holders: Click here to enter your Access Code. Already entered your Access Code? Please login.

    • +

      MA10.05 - Breath Analysis: New Key-Challenges for Early Detection of Lung and Pleural Neoplasms (Now Available) (ID 959)

      15:15 - 16:45  |  Presenting Author(s): Annamaria Catino  |  Author(s): Gianluigi De Gennaro, Alessia Di Gilio, Laura Facchini, Domenico Galetta, Teresa Mongelli, Jolanda Palmisani, Francesca Porcelli, Niccolò Varesano, Pamela Pizzutilo, Michele Montrone, Vito Longo, Gabriella Del Bene, Angelica Mastrandrea, Francesco Pesola, Donata Ricci, Patrizia Petrillo, Antonella Zacheo

      • Abstract
      • Presentation
      • Slides

      Background

      The growing interest about breath analysis relies on the need of tools to get an early diagnosis of respiratory pathologies with high mortality rate such as lung cancer (LC) and malignant pleural mesothelioma (MPM). Nowadays the key-challenge of the scientific community is the search for non-invasive diagnostic biomarkers able to identify patients at risk of developing cancer or with early stage cancer. A diagnostic progress would be crucial to improve the survival outcome of these neoplasms, generally detected at an advanced stage. The analysis of Volatile Organic Compounds (VOCs) pattern in human breath for early detection and follow-up of diseases such as cancer is low-cost, non-invasive and promising alternative to traditional exams (i.e., colonoscopy, biopsy).

      Method

      This study is based on the development and validation of a methodological approach aimed to the identification of VOCs breath pattern to discriminate between patients affected by both LC and MPM, and healthy controls (CTRL). A total of 80 breath samples from 36 patients with LC, 14 patients with MPM and 30 CTRL have been collected into inert Tedlar bags, transferred to sorbent tubes (biomonitoring, Markes) and analysed by TD-GC/MS (TD Markes Unity 2 - GC Agilent 7890/MS Agilent 5975).

      Result

      Non parametric test as Wilcoxon/Kruskal Wallis tests (R version 3.5.1) allowed to identify the most weighting variables in discrimination between LC, MPM and HC breath samples. On the basis of p-values lower than 0.05 (selection between CTRL and LC, and between CTRL and MPM) and current knowledge on metabolic processes, a multivariate statistics (Principal Components Analyses (PCA) -PAST 3.20) has been applied on breath samples, considering only selected variables. The preliminary statistical elaboration by PCA of data collected from the analysis of LC and CTRL samples have shown two principal components: PC1 characterized by higher loadings of benzoic acid, methylcyclohexane and hexanal, and PC2 characterized by high loadings for dimethyldecane, pentane and pentanal. Similar results were obtained by PCA applied to MPM and CTRL breath samples considering 2-methylpentane, cyclopentane, hexane and 2-butanone as discriminant variables.

      Conclusion

      PCA was able to discriminate between LC and CTRL and between MPM and CTRL breath samples. Leave-one-out cross-validation method was applied to calculate the prediction accuracy obtaining good sensitivity (88%), accuracy (86%) and specificity (92%).

      Further investigation about breath analysis is strongly warranted, due to the need of biomarkers potentially useful both for the screening of high-risk subjects and for the early diagnosis of lung and pleural neoplasms.

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      IASLC Members: To view this content or have the option to purchase this event, click here to login.
      Conference Attendees & Access Code holders: Click here to enter your Access Code. Already entered your Access Code? Please login.

    • +

      MA10.06 - Randomized Clinical Trial with Computer Assisted Diagnosis (CAD) Versus Radiologist as First Reader of Lung Screening LDCT (Now Available) (ID 2102)

      15:15 - 16:45  |  Presenting Author(s): Ren Yuan  |  Author(s): John Mayo, Isaac Streit, Sukhinder Kaur Atkar-Khattra, Renelle Myers, John Yee, Stephen Lam

      • Abstract
      • Presentation
      • Slides

      Background

      CAD has been studied extensively in lung nodule detection while its value in lung cancer screening has not been tested in a prospective randomized clinical study. We aim to evaluate the value of a CAD in radiologist work-flow and for quality assurance in reading and reporting lung cancer screening LDCT.

      Method

      Between August 2016 and February 2019, 1386 ever smokers were enrolled in the BC Lung Screen Trial. The median follow-up was 10 months. Their chest CTs were randomized to CAD reading first arm using a CAD system (Philips IntelliSpace Portal) (n=741), or Radiologist reading first (RAD) arm (n=645). In CAD-1st arm, a radiologist read CTs with the CAD findings displayed concurrently, accepting, rejecting and adding nodule(s). Radiologist’s reading time was recorded, and management recommendation was made using the automatically generated PanCan lung nodule risk score (N Engl J Med 2013; 369:910-919). In Rad-1st arm, the radiologist read the CT without using CAD, gave the management recommendation using Lung-RADS, and the reading time was recorded. Then the radiologist turned on CAD annotations to accept, reject and add nodule(s). The PanCan nodule risk scores were generated. Nodule management was categorized into 3 groups: I: Scheduled follow-up CT ≥1yr for those with no or very low risk lung nodules; II: Early recall CT <1 yr; or III: Referral to clinical diagnostic pathway for suspicious malignancy.

      Result

      Radiologist’s reading time was shorter in CAD-1st than Radiologist-1st arm (9±3 vs. 10±3 minutes, p<0.01). The time saved was greatest for Group I scans (85% of workload) (8±3 vs. 10±3 minutes, p<0.01). In 20/741 (2.7%) participants in CAD-1st arm, the additional nodule added by the radiologist upgraded the patient’s management; 5 of 20 were later confirmed to be malignant. Two of 5 were >3cm masses, the other three included a 19 mm GGO and two solid ones abutting vessels. In 1/645 (0.15%) participants in Radiologist-1st arm, the additional nodule detected by CAD upgraded the patient’s management from Group I to II. Over 31-months of follow-up, 29 cancers (2.1%) have been detected, and 1 of 29 (3.4%), a 5 mm solid nodule in the left lower lobe abutting the fissure and vessels, was missed by both radiologist and CAD.

      Conclusion

      CAD saves radiologist’s time in reading large numbers of screening LDCT especially in those with no or very low risk lung nodules. However, reading by experienced radiologist is still needed.

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      IASLC Members: To view this content or have the option to purchase this event, click here to login.
      Conference Attendees & Access Code holders: Click here to enter your Access Code. Already entered your Access Code? Please login.

    • +

      MA10.07 - Integrative Analysis of Epistasis Involving Oncogenesis-Related Genes in Lung Cancer Risk Development (Now Available) (ID 2502)

      15:15 - 16:45  |  Presenting Author(s): Yafang Li  |  Author(s): Xiangjun Xiao, Yohan Bossé, Younghun Han, Christopher Ian Amos

      • Abstract
      • Presentation
      • Slides

      Background

      Our previous study identified significant genetic interactions within oncogenesis-related genes in lung cancer risk development. More genetic interactions may exist between oncogenesis-related genes and outside regions in the genome. A functional annotation and pathway analysis of the identified epistasis-related genes will advance our understanding about the complicated biological mechanisms underlying lung tumorigenesis.

      Method

      The genotypes from two independent lung cancer GWAS studies including a total of 23,351 lung cancer patients and 19,657 health controls with European ancestry were collected for the analysis. Pairwise epistasis was conducted between 27,722 SNPs, from 2,027 oncogenesis-related genes, and 317,624 SNPs from the rest of the genome. A two-stage study design including discovery and replication studies, and stringent Bonferroni correction for multiple statistical analysis were applied in the analysis, Additional genotyping and gene expression data from 409 independent individuals with Caucasian ancestry were used to evaluate the effect of identified epistasis on gene expression levels. The epistasis-involved genes, were submitted to DAVID, Reactome, and GeneMANIA for gene functional annotation and pathway analysis.

      Result

      Significant genetic interactions were identified between SNPs in gene pairs ATR-GALNT18 (Interaction OR=0.76, p value=7.98x10-13) and MET-DPF3 (Interaction OR=0.76, p value=1.62x10-12) in lung adenocarcinoma; and PICALM-PDZRN4 (Interaction OR=1.47, p value=1.67x10-12) in lung squamous carcinoma. None of these genes have been identified from previous main effect association studies in lung cancer. Further eQTL gene expression analysis revealed the significant association in expression levels between joint genotypes at rs637304:rs285581 and the PICALM gene expression (p=0.009). A total of 12 unique genes, from six significant interactions, including those from within oncogenesis-related genes and between oncogenesis-related genes and outside variants, were submitted to functional annotation and pathway analysis. Three of them (ATR, MET and FHIT) are shown to be related with lung cancer, and six of them (RAD51B, FHIT, CALNT18, RGL1, SYNE1 and TSPAN8) are involved in tobacco-use disorders. The top 10 pathways include TP53 regulates transcription of DNA repair genes (FDR=1.67x10-2), homologous DNA pairing and strand exchange (FDR=2.57x10-2), and Meiotic synapsis (3.08x10-2), etc. GeneMANIA predicted one gene network harboring all the 12 candidate genes, supporting the epistasis at 3 genes pairs and indirect interactions at 3 gene pairs.

      Conclusion

      We identified novel genes involved in lung cancer risk development by interacting with other genetic variants. The study provides evidence that epistasis explains part of the missing heritability in lung cancer; and complex gene network and pathways contribute to lung carcinogenesis.

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      IASLC Members: To view this content or have the option to purchase this event, click here to login.
      Conference Attendees & Access Code holders: Click here to enter your Access Code. Already entered your Access Code? Please login.

    • +

      MA10.08 - Discussant - MA10.05, MA10.06, MA10.07 (Now Available) (ID 3751)

      15:15 - 16:45  |  Presenting Author(s): Fabrizio Bianchi

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      IASLC Members: To view this content or have the option to purchase this event, click here to login.
      Conference Attendees & Access Code holders: Click here to enter your Access Code. Already entered your Access Code? Please login.

    • +

      MA10.09 - Evaluation of the Clinical Utility of the PanCan, EU-NELSON and Lung-RADS Protocols for Management of Screen Detected Lung Nodules at Baseline (Now Available) (ID 2137)

      15:15 - 16:45  |  Presenting Author(s): Renelle Myers  |  Author(s): John Mayo, Martin Tammemagi, Sukhinder Kaur Atkar-Khattra, Ren Yuan, John Yee, John English, Kyle Grant, Alexandar Lee, Anna McGuire, Annette Maree McWilliams, Fraser Brims, Lin Mo, Stephen Lam

      • Abstract
      • Presentation
      • Slides

      Background

      Several protocols are available to guide management of lung nodules identified by the first (baseline) low-dose screening CT. It is important to objectively assess their clinical utility, health care resource utilization and potential harms. We aim to compare the PanCan (NEJM 2013;369:908 & J Thorac Oncol 2018; 13(10): S362-S363), EU-NELSON (Lancet Oncol. 2017 Dec;18(12):e754-e766 & Lung Cancer 2006;54:177-184) and Lung-RADS(https://www.acr.org/Clinical-Resources/Reporting-and-Data-Systems/Lung-Rads) lung nodule management protocols on our data set from two sites of the International Lung Screen Trial (ILST), in Vancouver, Canada and Perth, Western Australia.

      Method

      Ever smokers age 55 to 80 years were enrolled into ILST if they had a ≥30 pack-years smoking history and smoked within 15 years or if their PLCO m2012 6 year lung cancer risk was ≥1.51%. The participants were managed via the PanCan lung nodule risk based protocol. The NELSON and Lung-RADS nodule protocols were applied to the ILST data set. The potential difference in the proportion of the participants having an early recall CT scan (< 1 year) or referral to a clinical diagnostic pathway was compared between the PanCan, NELSON, Lung-RADS protocols. The participants were divided into 3 groups: Group 1 (next scheduled annual/biennial CT) included PanCan CAT 1, 2, NELSON NODCAT I, II, Lung-RADS CAT 1, 2. Group 2 (early recall CT <1 year) included PanCan CAT 3, NELSON NODCAT III, Lung-RADS CAT 3, 4A and Group 3 (Diagnostic Pathway) included PanCan CAT 4, 5, NELSON NODCAT IV (solid nodule), Lung-RADS CAT 4B, 4X. The number of participants and the lung cancer rate in each group was compared between the three protocols.

      Result

      A total of 1386 participants with a median follow-up of 10 months (ranging from 4-31 mos) were evaluated. The results are shown in Table 1.

      PanCan selected the fewest individuals to early recall (Group 2 & 3) versus NELSON p=0.004 and detected the same number of lung cancers as did the NELSON and more than by Lung-RADS.

      In addition, 81% of the PanCan group 1 participants were triaged to biennial repeat screening instead of annual screening in the NELSON and Lung-RADS protocols, which has substantial resource utilization and radiation exposure implications.

      presentation2.jpg

      Conclusion

      The personalized risk-based PanCan Protocol may decrease resource utilization and potentially minimize risk of screening for participants.

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      IASLC Members: To view this content or have the option to purchase this event, click here to login.
      Conference Attendees & Access Code holders: Click here to enter your Access Code. Already entered your Access Code? Please login.

    • +

      MA10.10 - Uptake in Lung Cancer Screening – Does CT Location Matter? A Pilot Study Comparison of a Mobile and Hospital Based CT Scanner (Now Available) (ID 2165)

      15:15 - 16:45  |  Presenting Author(s): Emily Bartlett  |  Author(s): Samuel Kemp, Sujal Desai, Saeed Mirsadraee, Carole Ridge, Jaymin Morjaria, Pallav Shah, Katie Morris, Jane Derbyshire, Michelle Chen, Christine Peacock, Natallia Ivashniova, Maria Martins, James Addis, Simon Padley, Anand Devaraj

      • Abstract
      • Presentation
      • Slides

      Background

      Community based lung cancer screening has been proposed as a method of increasing uptake for lung cancer screening by reducing barriers to participation. We report baseline statistics for a lung cancer screening pilot study in which patients were scanned on either a community based mobile CT unit or on a University Hospital based fixed-site CT scanner.

      Method

      Ever smokers aged 60-75 registered at 17 participating general practitioner practices (GP) in West London were invited for a lung health check at either a mobile unit situated in a supermarket car park or in a hospital site. The location offered was based upon proximity to the participant’s home address. On attendance a lung health check, assessing lung cancer risk, was undertaken. Participants with a LLPv2 score of ≥2.0% and/or PLCOM2012 score of ≥1.51% were offered a same day low dose CT (LDCT) scan. Uptake, attendance and non-attendance (DNA) rates were compared using Chi-squared (χ2) test.

      Result

      8366 potentially eligible participants were invited for a lung health check appointment; 5135 (61.4%) to the hospital site, and 3231 (38.6%) to the mobile site. 1749/8366 (20.9%) participants responded (males n=954/1749 (54.5%)). 1047/5135 (20.4%) were booked an appointment at the hospital site and 702/3231 (21.7%) at the mobile site (p=0.14). No difference was observed in lung cancer risk between participants at the two sites. Patients at the mobile site were more likely to be ex-smokers (p=0.048). The DNA rate at the hospital site was 96/1047 (9.2%) and at the mobile site was 48/702 (6.8%) (p=0.08). On attendance, 63 patients were ineligible for screening; 52/1749 (3.0%) did not meet the entry criteria and 11/1749 (0.6%) were acutely unwell. Therefore 1542 patients attended and had a risk score calculated and of these 1145/1542 (74.3%) underwent CT. Median [range] risk scores for scanned patients were 1.97 [0-25.34] for PLCOM2012 and 4.71 [0.94-35.92] for LLPv2. Lung cancer was confirmed in 17/1145 (1.5%) participants at baseline. A further 151/1145 (13.2%) participants will undergo interval CT for indeterminate nodules.

      Conclusion

      There was a small but non-significant increase in participant response rates for the community based mobile site compared to the hospital site CT scanner, but no difference in DNA rates. While community based mobile scanners may provide valuable additional capacity to lung screening programmes, the magnitude of any benefit to participant uptake needs to be balanced against the additional complexity of setting up these stand-alone facilities. Further work is ongoing to understand the interaction between CT location and other factors that influence recruitment, with a view to using effective methods to increase uptake at all sites for future screening invitations.

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      IASLC Members: To view this content or have the option to purchase this event, click here to login.
      Conference Attendees & Access Code holders: Click here to enter your Access Code. Already entered your Access Code? Please login.

    • +

      MA10.11 - Sensitivity and Optimal Clinicopathological Features of Genetic Targeted Liquid Biopsy in pN0M0 Lung Adenocarcinoma (Now Available) (ID 788)

      15:15 - 16:45  |  Presenting Author(s): Masaoki Ito  |  Author(s): Yoshihiro Miyata, Shoko Hirano, Fumiko Irisuna, Naoto Kishi, Yasuhiro Tsutani, Rafael Rosell, Morihito Okada

      • Abstract
      • Presentation
      • Slides

      Background

      Liquid biopsy for diagnosis of early-stage lung cancer is still challenging. The optimal marker and methodology has not been established. In Asia, almost 40-50% of lung adenocarcinomas harbor the EGFR mutation and L858R is a representative of a somatic EGFR mutation. We evaluated the usefulness of the EGFR somatic mutation in liquid biopsy using droplet digital PCR (ddPCR), which is a sensitivity device to detect several types of genetic mutations.

      Method

      We examined weather L858R could be detected from preoperative ctDNA by ddPCR. Cases without EGFR mutation (wild type) were utilized as negative control. All involved cases underwent surgical resection after preoperative HRCT and PET-CT. Serum for ctDNA extraction was collected before the operation. L858R in the primary site was confirmed by resected surgical specimen. Clinicopathological features (e.g.: whole and invasive tumor size on HRCT, SUV max on PET-CT, histological subtype) were also explored for an optimal liquid biopsy candidate.

      Result

      Forty-five pN0M0 lung adenocarcinoma patients harboring L858R were enrolled. Twenty-one and 24 cases showed part-solid and pure solid appearance on HRCT, respectively. Median whole and invasive tumor size on HRCT was 21 and 19 mm, respectively. 91.1% (41/45) cases were clinical stage IA1-IB and 97.8% (44/45) cases were pathological stage IA1-IB. In wild type cases, positive droplet for L858R was almost completely undetectable. Whereas, L858R was significantly detected in 7 EGFR mutant cases (sensitivity is 15.56%, 7/45). Among 7 positive cases, 6 cases showed pure solid appearance in preoperative HRCT. Except for pure solid appearance, there was no significant features related to the positive result. If cases are limited to pure solid appearance, 25.0% (6/24) of cases could be diagnosed by liquid biopsy. Even small-sized tumors (1.1 cm in diameter) or tumors with slight accumulation on PET-CT (SUV max 0.5) could be detected if it showed pure solid appearance on HRCT.

      Conclusion

      L858R can be a definitive marker for liquid biopsy using ddPCR in pN0M0 lung adenocarcinoma. 15.56% (7/45) of cases were diagnosed in pN0M0 cases. Limited to pure solid tumor, 25.0% (6/24) could be detected. Liquid biopsy can be a useful diagnostic option, especially for tumors with pure solid appearance.

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      IASLC Members: To view this content or have the option to purchase this event, click here to login.
      Conference Attendees & Access Code holders: Click here to enter your Access Code. Already entered your Access Code? Please login.

    • +

      MA10.12 - Discussant - MA10.09, MA10.10, MA10.11 (Now Available) (ID 3752)

      15:15 - 16:45  |  Presenting Author(s): Christine Dorothy Berg

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      IASLC Members: To view this content or have the option to purchase this event, click here to login.
      Conference Attendees & Access Code holders: Click here to enter your Access Code. Already entered your Access Code? Please login.

  • +

    MA25 - Precision Medicine in Advanced NSCLC (ID 352)

    • Event: WCLC 2019
    • Type: Mini Oral Session
    • Track: Advanced NSCLC
    • Presentations: 10
    • Now Available
    • +

      MA25.01 - Pembrolizumab Plus Chemotherapy for Advanced NSCLC Without Tumor PD-L1 Expression: Pooled Analysis of KN021G, KN189 and KN407 (Now Available) (ID 1399)

      14:30 - 16:00  |  Presenting Author(s): Hossein Borghaei  |  Author(s): Corey Jay Langer, Luis Paz-Ares, Delvys Rodriguez Abreu, Balazs Halmos, Vassiliki A Papadimitrakopoulou, Marina Chiara Garassino, Baerin Houghton, Takayasu Kurata, Ying Cheng, Jianxin Lin, M. Catherine Pietanza, Bilal Piperdi, Shirish Gadgeel

      • Abstract
      • Presentation
      • Slides

      Background

      Randomized studies have demonstrated that pembrolizumab plus chemotherapy improves OS, PFS, and ORR compared with chemotherapy alone in patients with advanced NSCLC regardless of tumor PD-L1 expression level. We present a post hoc pooled analysis of pembrolizumab plus chemotherapy versus chemotherapy alone in patients with advanced NSCLC and no PD-L1 expression (ie, TPS <1%), representing an area of unmet need.

      Method

      Patients enrolled in KEYNOTE-021 cohort G (nonsquamous; NCT02039674), KEYNOTE-189 (nonsquamous; NCT02578680), and KEYNOTE-407 (squamous; NCT02775435) were included. Patients with nonsquamous NSCLC were randomized to pemetrexed-platinum with or without pembrolizumab; those with squamous NSCLC were randomized to carboplatin-paclitaxel/nab-paclitaxel with or without pembrolizumab. OS, PFS, and ORR were evaluated for the pooled intent-to-treat population. Response was assessed per RECIST v1.1 by blinded independent central review. Across studies, PD-L1 expression was assessed centrally using PD-L1 IHC 22C3 pharmDx assay (Agilent Technologies, Carpinteria, CA). Analyses were descriptive.

      Result

      Of 1298 patients enrolled across the 3 trials, 428 (33%) had PD-L1 TPS <1% (pembrolizumab plus chemotherapy, n=243; chemotherapy alone, n=185) and were included in this analysis. 52% had nonsquamous histology, 63% had ECOG PS of 1. Median (range) follow-up at data cutoff was 10.2 (0.1‒34.9) months. OS, PFS, and ORR were improved with pembrolizumab plus chemotherapy versus chemotherapy alone (Table). Grade ≥3 AEs (all-cause) occurred in 68% of patients receiving pembrolizumab plus chemotherapy versus 72% receiving chemotherapy alone. Immune-mediated AEs and infusion reactions occurred in 26% who received pembrolizumab plus chemotherapy versus 12% who received chemotherapy alone.

      Pembrolizumab + Chemotherapy

      n=243

      Chemotherapy
      Alone

      n=185

      Median (95% CI) OS, mo

      19.0 (15.2–24.0)

      11.0 (9.2–13.5)

      Hazard ratio (95% CI)

      0.56 (0.43–0.73)

      Median (95% CI) PFS, mo

      6.5 (6.2–8.5)

      5.4 (4.7–6.2)

      Hazard ratio (95% CI)

      0.67 (0.54–0.84)

      ORR, % (95% CI)

      46.9% (40.5%–53.4%)

      28.6% (22.3%–35.7%)

      Difference (95% CI)

      18.3% (9.0%–27.1%)

      Conclusion

      Our results highlight the clinically meaningful efficacy benefit and acceptable safety profile of pembrolizumab plus chemotherapy versus chemotherapy alone in patients with advanced NSCLC and no PD-L1 expression. Benefit was consistent with that observed in the overall study populations, suggesting pembrolizumab plus chemotherapy should be considered standard-of-care first-line therapy for all patients with NSCLC, irrespective of PD-L1 expression.

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      IASLC Members: To view this content or have the option to purchase this event, click here to login.
      Conference Attendees & Access Code holders: Click here to enter your Access Code. Already entered your Access Code? Please login.

    • +

      MA25.02 - Arrangement and Architecture of Tumor-Infiltrating Lymphocyte on H&amp;E Slides Predict OS in Nivolumab Treated Non-Small Cell Lung Cancer (Now Available) (ID 2911)

      14:30 - 16:00  |  Presenting Author(s): Kaustav Bera  |  Author(s): Xiangxue Wang, Cristian Barrera, Cheng Lu, Michael Feldman, Kurt A Schalper, David Rimm, Vamsidhar Velcheti, Anant Madabhushi

      • Abstract
      • Presentation
      • Slides

      Background

      Immune checkpoint inhibitors (ICI) are a promising and novel approach to treating chemotherapy refractory advanced NSCLC as well as first-line combination therapy in certain NSCLC. Nivolumab, a PD-L1 inhibitor is a promising ICI showing durable benefit with low toxicity in these patients. While PD-L1 positivity is an established tissue based biomarker for response to Nivolumab, studies have shown response rates ranging from 20-50%. Recent research has shown that TILs have been implicated in cancer aggressiveness as well as immune response. In this work, we go beyond simply counting TILs, and apply novel computer-extracted features characterizing the interaction and spatial co-localization of TILs and cancer nuclei (SpaTIL) in stratifying patients based on OS following nivolumab therapy.

      Method

      H&E tissue slides obtained from pre-treatment biopsies of 96 NSCLC patients treated with nivolumab were digitized and included for this study from 3 different institutions with the tumor region annotated by pathologists. Then 85 SpaTIL features related to TIL density, architecture and co-localization with tumor cells have been extracted to represent each patient. The most discriminative and uncorrelated features were selected by Elastic-Net regularized Cox-regression model to predict OS. The model was trained on D1 (n=25) and independently validated in D2 (n=32) and D3 (n=64). Multivariate analysis with clinico-pathologic factors was also performed.

      Result

      The top features consisted of the abundance of TILs around tumor cells and the distribution of the TILs. On the validation set, SpaTIL classifier yielded a HR=3.03 (95%CI=1.1 -8.35; p=0.042) on D2 and HR=4.12 (95%CI=1.87-9.09; p=0.02) on D3 by a log-rank test. On multivariate analysis with stage, smoking, histologic type, total lymphocyte count (See Table 1) SpaTIL was independently prognostic of OS (HR=7.88; 95%CI=1.66 – 37.216; p=0.009).wlc19 (2).png

      Table 1. Multivariate analysis for overall survival on the validation sets D2 and D3

      Variables

      HR(95% CI)

      p value

      Age (>65 vs <=65 yrs)

      0.99(0.97-1.03)

      0.67

      Gender (Male vs Female)

      1.05(0.75-2.79)

      0.88

      Smoking Status

      (Former vs Never smoker)

      3.19(0.92-11.061)

      0.07

      Histological Subtypes (Adeno vs Squamous)1

      1.06(0.13-8.54)

      0.95

      EGFR status

      1.32(0.49-3.52)

      0.58

      ALK status

      0.63(0.36-1.10)

      0.10

      Total lymphocyte count

      0.99(0.99-1.00)

      0.33

      SpaTIL Classifier

      7.88(1.66-37.216)

      0.009

      CI = confidence interval; HR = Mantel-Haenszel Hazard ratio. Values in bold are statistically significant, p<=0.05.

      Conclusion

      Spatial interaction of TILs and cancer are independently prognostic of OS in nivolumab treated NSCLC. Further validation needs to be done to evaluate its utility.

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      IASLC Members: To view this content or have the option to purchase this event, click here to login.
      Conference Attendees & Access Code holders: Click here to enter your Access Code. Already entered your Access Code? Please login.

    • +

      MA25.03 - Tumor-Infiltrating Lymphocytes (TIL) and Outcomes with Immunotherapy (ICI) or Chemotherapy in Advanced NSCLC (aNSCLC) Patients (Now Available) (ID 1374)

      14:30 - 16:00  |  Presenting Author(s): Julien Adam  |  Author(s): Laura Mezquita, Ithar Gataa, Caroline Rossoni, Edouard Auclin, Myriam Kossai, Frank Aboubakar, Sylvestre Le Moulec, Julie Massé, Morgane Masson, Nina Radosevic-Robin, Mathieu Rouanne, Maria Virginia Bluthgen, CAROLINE Caramella, Lizza Hendriks, Anas Gazzah, David Planchard, Jean-Pierre Pignon, Benjamin Besse

      • Abstract
      • Presentation
      • Slides

      Background

      Tumor infiltrating lymphocytes (TIL) morphologically assessed is prognostic in early stages in several tumors. We previously reported the correlation of TIL with immune checkpoint inhibitors (ICI) outcomes in 98 advanced (a) NSCLC patients treated with ICI. We aimed to assess the role of TIL in a larger cohort treated with ICI, and in patients exclusively treated with chemotherapy (CT).

      Method

      aNSCLC patients with treated with single-agent ICI, with H&E stained sample available, were included between 11/2012 and 02/2017 in 3 cancer centers (immuno-cohort). Patient’s characteristics, biological data were retrospectively collected. The CT-cohort was extracted from the prospective MSN study (NCT02105168), between 06/2009 and 10/2016, enrolling aNSCLC patients treated with platinum-based CT, and tissue available. TIL in the stroma was evaluated in archival samples. High-TIL was defined as ≥10% density. Multivariate Cox model was used to study its prognostic values on overall and progression-free survival (OS, PFS).

      Result

      A total of 221 patients were included in the immuno-cohort: 142 (64%) male, with median (m) age of 63, 182 (84%) smokers, 161 (77%) PS≤1, 162 (63%) adenocarcinoma; 125 (57%) received ICI as second-line. High-TIL was observed in 49/221 (28%), non-assessable in 46. High-TIL had independent impact on OS and PFS (HR 0.40; 95% CI 0.25-0.63, P<0.0001). The mPFS and OS were 3.1months (mo.) (2.5-4.9) and 11mo. (7.0-13.2) respectively. The high-TIL group had mPFS of 13mo. (5.0-NR) vs. 2.2mo. (1.7-3.0) in low-TIL group (P<0.0001). High-TIL group had mOS not reached (NR) (12.2-NR) vs. 8.4 mo. (5.0-11.6) in low-TIL (P=0.007). The CT-cohort (N=189) had high-TIL in 103/189 (54%). The mPFS and mOS were 5.7mo. (4.9-6.7) and 11.7mo. (9.3-13.0) respectively, with no association with TIL.

      OS, Immuno-cohort (n=221) OS, Chemo-cohort (n=188)

      Hazard ratio (HR)
      95% confidence interval (CI)

      P-value

      HR
      95% CI

      P-value

      TIL
      ≥10% (high)

      0.46 (0.28-0.81) 0.006 1.03 (0.76-1.41) 0.84
      Age
      ≥65 y
      0.86 (0.50-1.46) 0.57 0.99 (0.72-1.38) 0.99
      Line of treatment*
      second line
      0.69 (0.44-1.09) 0.11 0.84 (0.60-1.16) 0.29

      N# metastatic sites
      >2

      1.40 (0.88-2.20) 0.16 1.50 (1.07-2.12) 0.02
      Performance status
      ≥2
      2.75 (1.73-4.37) <0.0001 1.94 (1.23-3.04) 0.004
      Histology
      Squamous
      1.13 (0.70-1.81) 0.62 1.09 (0.65-1.83) 0.75
      *Line of treatment: lines of immunotherapy for the Immuno-cohort; lines of chemotherapy for the Chemo-cohort.

      Conclusion

      High-TIL (≥10%) is a simple and accessible marker associated with better ICI outcomes, but not with CT. This suggests a potential predictive value that must be validated in larger prospectively studies.

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      IASLC Members: To view this content or have the option to purchase this event, click here to login.
      Conference Attendees & Access Code holders: Click here to enter your Access Code. Already entered your Access Code? Please login.

    • +

      MA25.04 - Blood-Based Tumor Mutation Burden as a Predictive Biomarker for Outcomes After Pembrolizumab Based First Line Therapy in Metastatic NSCLC (Now Available) (ID 2717)

      14:30 - 16:00  |  Presenting Author(s): Charu Aggarwal  |  Author(s): Jeffrey C Thompson, Austin Chien, Katie Quinn, Martina I. Lefterova, Rebecca Nagy, Stephanie S Yee, Michael Lariviere, Christine Ciunci, Aditi Singh, Joshua M Bauml, Roger B Cohen, Corey Jay Langer, Erica Carpenter

      • Abstract
      • Presentation
      • Slides

      Background

      PD-1 blockade with pembrolizumab (P) as monotherapy in patients with PD-L1 TPS > 50% or in combination with platinum based chemotherapy (PC) is the current standard front-line therapy for metastatic non-small cell lung cancer (mNSCLC). We explored the correlation of blood (b) based tumor mutational burden (TMB) using circulating tumor DNA (ctDNA) with outcomes after front line P and PC therapy.

      Method

      Patients with newly diagnosed metastatic NSCLC starting standard of care front line P-based therapy were enrolled. Plasma was prospectively collected at baseline prior to initiation of P or PC therapy for mNSCLC. A 2.145 megabase (Mb) next-generation sequencing panel was used to assess bTMB. A bTMB cutoff of ≥16 mut/Mb was selected based on previously published data (Gandara et al, Nature 2018). Response was assessed using RECIST 1.1. Durable clinical benefit (DCB) was defined as complete response/ partial response/ stable disease that lasted > 6 months. Correlations were made for patient demographics, tumor characteristics, DCB, progression free survival (PFS), and overall survival (OS) using logistic regression and Cox proportional hazards models. Significance was determined at the 0.05 level.

      Result

      66 pts with mNSCLC were enrolled, median age 67 years (range 47-89), current or ex-smokers (n=61, 92%). Thirty-one patients (47%) received P (all PD-L1>50%); 35 received platinum-pemetrexed based PC. At the time of data cut off, median OS for P was 14.8 months, and not reached for PC. bTMB was evaluable for 52 patients (n=26 P, 26 PC), median bTMB was 16.8 mutations per Mb (mut/Mb, range 1.9-52.5). There was no correlation between bTMB and tumor PD-L1 (p=0.28). Median bTMB for patients achieving DCB was higher than for those with no clinical benefit, 21.3 mut/Mb vs. 12.4 mut/Mb, p=0.004. For patients with bTMB ≥ 16 mut/Mb, median PFS was 13.8 vs. 4.7 months for patients with bTMB <16 mut/Mb (HR 0.27 [0.13-0.55]). Median OS was not reached for bTMB ≥ 16 mut/Mb (HR 0.47 [0.20-1.1]). Loss of function mutations in STK11, KEAP1, or PTEN, or ERBB2 exon 20 insertion were enriched in patients with no clinical benefit. Combined score using bTMB ≥ 16 mut/Mb and mutations in STK11, KEAP1, or PTEN, or ERBB2 exon 20 insertions resulted in improved prediction for DCB; PFS HR of 0.18 [0.08-0.41] and OS HR of 0.27 [0.10-0.73].

      Conclusion

      Our early results suggest that bTMB using plasma ctDNA may predict therapeutic outcomes after first line P-based therapy in mNSCLC. Loss of function mutations in STK11/KEAP/PTEN and ERBB2 exon 20 insertion mutations appear to be negative predictors of benefit. As the sample size is limited and findings are reported on a pooled group of P and PC patients, the role of bTMB and response to P and PC based therapy separately should be validated in a larger prospective study.

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      IASLC Members: To view this content or have the option to purchase this event, click here to login.
      Conference Attendees & Access Code holders: Click here to enter your Access Code. Already entered your Access Code? Please login.

    • +

      MA25.05 - Discussant - MA25.01, MA25.02, MA25.03, MA25.04 (Now Available) (ID 3815)

      14:30 - 16:00  |  Presenting Author(s): Karen Kelly

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      IASLC Members: To view this content or have the option to purchase this event, click here to login.
      Conference Attendees & Access Code holders: Click here to enter your Access Code. Already entered your Access Code? Please login.

    • +

      MA25.07 - Genomic Profiling of Lung Adenocarcinoma by Targeted NGS Using Extracellular Vesicle-Derived DNA in Bronchoalveolar Lavage Fluid (Now Available) (ID 1532)

      14:30 - 16:00  |  Presenting Author(s): Seungeun Lee  |  Author(s): Kye Young Lee, Jae Young Hur, Heejoung Kim, Wan Seop Kim, In Ae Kim, Ha Young Park

      • Abstract
      • Presentation
      • Slides

      Background

      Extracellular vesicles (EV) are membrane-bound and nanometer-sized particles shed from most types of cells in our body and found in circulation, containing double-stranded genomic DNA reflecting mutational status of the parental tumor cells. Recently, we demonstrated that EVs successfully isolated from bronchoalveolar lavage fluid (BALF) in non-small cell lung cancer (NSCLC) patients. Several studies also have shown that EV-derived DNA is superior to cfDNA in plasma for detection of mutations in NSCLC and pancreatic cancer. We identified that liquid biopsy for EGFR genotyping using EV-derived DNA in BALF showed almost 100% sensitivity with tissue typing in advanced NSCLC patients. Therefore, we hypothesized that targeted next–generation sequencing (NGS) using EV-derived DNA in BALF may correlate with results using tissue in patients with EGFR-mutated lung adenocarcinoma.

      Method

      To address this hypothesis, we compared with the targeted NGS profile using between BALF EV-derived DNA and tissue DNA in 20 patients with EGFR-mutated lung adenocarcinoma. Four types of somatic variants (SNVs, small indels, CNVs and gene fusions) of BALF-EV or FFPE tissue samples were analyzed by CancerSCANTM, a capture-based targeted sequencing platform, which targets 375 genes covering about 2.5-megabase genomic regions including full CDSs of 374 genes, selected intronic regions of 23 genes for fusion detection, and 1kb TERT promoter region.

      Result

      Targeted sequencing resulted in over 99% of the target regions covered at a mean depth of 190-750× except one sample. DNA yields were higher in tissue DNA than EV-derived DNA (827.02ng vs 89.10ng). Depth of coverage (753x vs 379x) and estimated tumor purity (53% vs 23%) were also higher in tissue DNA than EV-derived DNA. However, estimated library size was not significantly different between tissue DNA and EV-derived DNA (50G vs 47G) and fragment size of DNA were longer in EV-derived DNA than tissue DNA (175.5bp vs 169.5bp). These findings support that EV-derived DNA has sufficient quality and quantity for NGS. By using mutations detected in tissue DNA as a reference, we achieved 83% sensitivity for somatic and clinically significant variants in EV-derived DNA. Clinically significant mutations in EGFR, TP53, PTEN, APC, JAK3 and PIK3CA were identified with an overall concordance of 81% in matched tissue DNA and EV-derived DNA. Variants in EGFR and TP53 were most common, with concordance of 80% and 100%, respectively. Variant allele frequencies of EGFR and TP53 were most abundant in range of 10-25% in tissue DNA, while much lower (<5%) in EV-derived DNA. Tumor mutation burdens (TMB) of EV-derived DNA showed correlation with tissue DNA (R2=0.21).

      Conclusion

      To our knowledge, this is the first of study of comprehensive clinical NGS panel using EV-derived DNA of BALF and matched tumor tissue biopsies in patients with lung adenocarcinoma. Although EV-derived DNA demonstrated comparable results to tissue DNA, it is needed much higher sequencing coverage and optimization of NGS-pipeline to detect low-allele frequency variants of EV-derived DNA. This study demonstrates the feasibility and clinical utility of BALF EV-derived DNA for patients with lung adenocarcinoma.

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      IASLC Members: To view this content or have the option to purchase this event, click here to login.
      Conference Attendees & Access Code holders: Click here to enter your Access Code. Already entered your Access Code? Please login.

    • +

      MA25.08 - Characterisation of Tumor Aetiology Using Mutational Signatures from the Non-Small Cell Lung Cancer Genome (Now Available) (ID 2667)

      14:30 - 16:00  |  Presenting Author(s): Colin Lindsay  |  Author(s): Shereen Rafee, Pantelis Nicola, Andrew Wallace, George Burghel, Helene Schlecht, Katie Baker, Eleanor Baker, Lynsey Priest, Jane Rogan, Sharzad Moghadam, Mat Carter, William Newman, Fiona Blackhall

      • Abstract
      • Presentation
      • Slides

      Background

      Somatic genome and exome analyses in cancer are currently dominated by a search for actionable mutations that inform new treatments for stage IV patients. Tumour mutational signatures, originally described by the Sanger centre, offer the potential to understand cancer cure and prevention strategies by using the genome/exome to define aetiological contributions to cancer from both environmental and endogenous sources.

      Method

      132 NSCLC samples were resected from 131 Greater Manchester patients and submitted to the UK 100,000 Genomes Project (Genomics England). A 5×5×5 mm fresh tumour sample was taken from the surgical specimen and stored at -80°C before undergoing genomic testing. To determine the neoplastic cell count, an additional tumour biopsy was taken for routine histological assessment. Germline DNA for comparable whole genome analysis was extracted from peripheral blood lymphocytes from a paired whole blood sample.Whole genome sequencing (WGS) was performed on tumor specimens and matched blood samples. Through the 100,000 Genomes Project pipeline, coverage was calculated from high-quality, non-overlapping bases present on well-mapped reads, as defined by SAMtools v1.1. Whole genome sequencing analysis was undertaken with the Illumina North Star pipeline v2.6.53.23. Data were then mined for tumour mutational burden (TMB) and mutational signature profiles. Signatures were extracted if they accounted for >5% of the mutations per sample. Clinical characteristics including tumor size, nodal status and stage were documented. Mann-Whitney and Fisher’s exact tests were used for statistical comparisons.

      Result

      Signature 8 (unknown aetiology) was the most prevalent mutational process overall (122/132 samples, 92.4%), while smoking signature 4 was the main mutational process in 86/131 (65.6%) of NSCLC cases. SIgnature 4 contributed as a principal or secondary mutational process to a total of 105/131 (80.2%) cancers; 104/105 (99%) of these patients were annotated as smokers or ex-smokers. Signature 5 (unknown aetiology) was the second most common driving signature (24/131, 18.3% cancers), contributing to an additional 19 cancers as a secondary mutational process (43/131, 32.8% of cancers overall). Median number of signatures contributing to signature 4 NSCLC was four, whilst non-smoking mediated NSCLC had contributions from a median of 5.5 mutational signatures (range 2-8). A median of four signatures contributed to both adenocarcinomas and squamous cancers, with 61/88 (69.3%) adenocarcinomas and 25/41 (61%) squamous cancers associated with signature 4 as their main mutational process. More results will follow on duration of signature 4 persistence following discontinuation of smoking, as well as prevalence of each signature according to common molecular subtypes of NSCLC.

      Conclusion

      Tumor mutational signatures have the potential to inform cancer prevention by offering a new level of genetic detail that reflects environmental and endogenous carcinogenesis. As expected, signature 4 offers the main contribution to NSCLC although a number of other aetiological factors are involved in its carcinogenesis. In particular, signatures 5 and 8, both currently of unknown aetiology, significantly contribute to the NSCLC genome. Along with that reported by the Sanger centre, this work lays the foundations for characterisation and identification of new carcinogens.

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      IASLC Members: To view this content or have the option to purchase this event, click here to login.
      Conference Attendees & Access Code holders: Click here to enter your Access Code. Already entered your Access Code? Please login.

    • +

      MA25.09 - Navigating Anlotinib Precision Therapy Through the Genetic Profiling of Circulating DNA in Non-Small Cell Lung Cancer Patients (Now Available) (ID 1055)

      14:30 - 16:00  |  Presenting Author(s): Jun Lu  |  Author(s): Hua Zhong, Jun Wu, Tianqing Chu, Lele Zhang, Hua Li, Qiming Wang, Rong Li, Yizhuo Zhao, Aiqin Gu, Chunlei Shi, Liwen Xiong, Xueyan Zhang, Wei Zhang, Yuqing Lou, Bo Yan, Yu Dong, Yanwei Zhang, Baolan Li, Li Zhang, Xiaodong Zhao, Kai Li, Baohui Han

      • Abstract
      • Presentation
      • Slides

      Background

      Anlotinib is an oral multi-targeted anti-angiogenic drug, and its clinical predictor for non-small cell lung cancer (NSCLC) patients is still elusive. The aim of this study is to screen predictor for anlotinib via non-invasive genetic profiling of plasma cell free DNA and circulating tumor DNA (cfDNA & ctDNA).

      Method

      Tumor-specific target capture to profile the circulating DNA of ALTER0303 (Evaluating NSCLC clinical anti-tumor efficacy through anlotinib therapy) study participants. Acquired mutations were screened out via comparing genetic profiling between baseline (BL) and progression disease (PD), and were used for anlotinib stratification. Based on the sequencing data at BL, tumor mutation index (TMI) was established from three independent predictors germline and somatic mutation burden (G+S MB), nonsynonymous and synonymous mutation burden (N+S MB) and unfavorable mutation score (UMS), and was used for predicting anlotinib responders. In addition, TMI combined with IDH1Exon4 mutation status also be examined for serving as predictor for anlotinib stratification.

      Result

      Our data firstly indicated no benefit (NB, PFS ≤ 45 days) patients can be mainly excluded via analysis of ARID1A and BRCA2 genetic profiling. Secondly, for the no durable benefit (NDB, 45 days < PFS ≤ 130 days) and durable clinical benefit (DCB, PFS > 130 days) patients, harboring lower mutation burden (G+S MB, N+S MB, and UMS) received more benefit from anlotinib therapy. Subsequently, we found the predictor-TMI can predict anlotinib responders upon discovery cohort (Median PFS: 210 days vs 126 days; p = 0.0238; AUC = 0.77), and validation cohort (Median PFS: 210 days vs 127 days; p = 0.0352) and all patients (Median PFS: 210 days vs 127 days; p = 0.0044) more effectively. Furthermore, the IDH1Exon4 mutation was identified as an unfavorable factor to anlotinib therapy under TMI-based stratification. Lastly, the TMI plus IDH1Exon4 mutation status predict response to anlotinib significantly (Median PFS: 210 days vs 127 days, p < 0.0001, AUC = 0.90; Median OS: 423 days vs 162 days, p < 0.0001, AUC = 0.80).

      Conclusion

      This study provides circulating DNA sequencing-based stratification for underlying anlotinib responders via non-invasive approach, and thus potentially improve clinical outcome for NSCLC patients at 3rd line.

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      IASLC Members: To view this content or have the option to purchase this event, click here to login.
      Conference Attendees & Access Code holders: Click here to enter your Access Code. Already entered your Access Code? Please login.

    • +

      MA25.10 - First-In-Human Phase 1 Study of DS-1062a (TROP2 Antibody-Drug Conjugate) in Patients with Advanced Non-Small Cell Lung Cancer (Now Available) (ID 3854)

      14:30 - 16:00  |  Presenting Author(s): Rebecca S Heist  |  Author(s): Jacob Sands, Toshio Shimizu, Edward Garon, Antoine Yver, Jonathan Greenberg, Penny Phillips, Yukata Noguchi, Alexander Spira, Noboru Yamamoto, Melissa Johnson, Funda Meric-Bernstam, Kiyotaka Yoh, Aaron Lisberg

      • Abstract
      • Presentation
      • Slides

      Background

      DS-1062a is a trophoblast cell-surface antigen 2 (TROP2)-targeting antibody-drug conjugate with Daiichi-Sankyo exatecan derivative (DXd) technology. TROP2 is highly expressed in epithelial cancers, including non-small cell lung cancer (NSCLC), and is associated with poor survival. In preclinical studies DS-1062a showed promising antitumor activity in xenograft mouse models. Updated results from the dose escalation part of a phase 1 study of DS-1062a in patients with advanced NSCLC are reported.

      Method

      This is an ongoing US and Japan dose-escalation/dose-expansion phase 1 study of DS-1062a in patients with unselected NSCLC (NCT03401385). Adult (age ≥20 years [Japan] or ≥18 years [US]) patients with measurable disease per RECIST v1.1 and available tumor for TROP2 measurement were eligible. The primary objectives are to identify the maximum tolerated dose (MTD) and recommended dose for expansion, assess safety and tolerability. Endpoints include safety, efficacy, pharmacokinetics, and molecular and genomic analyses.

      Result

      At most recent data cutoff (April 12, 2019) 39 patients with advanced NSCLC were treated with DS-1062a at doses of 0.27 (n=4), 0.5 (n=5), 1.0 (n=7), 2.0 (n=6), 4.0 (n=6), 6.0 (n=8) and 8.0 (n=3) mg/kg. Overall, patients were exposed to a median (range) of 3.0 (1–10) treatment cycles over a duration of 8.86 (3.0–31.1) weeks. Patient disposition included dose interruption (n=2), reduction (n=1) and discontinuation (n=23; primary reason was progressive disease (PD) per RECIST in 13/23 patients). The majority (87.2%; 34/39) of patients reported ≥1 treatment-emergent adverse event (TEAE), regardless of severity or causality; the most common (in ≥30% of patients) were fatigue (33.3%) and nausea (30.8%). Grade ≥3 TEAEs were reported in 41.0% (16/39) of patients, of which 12.5% (2/16) were considered drug related. Drug-related TEAEs occurred in 59.0% (23/39 [21/23 grade 1 or 2], and serious TEAEs in 25.6% (10/39 [n=8 grade 3 (n=1 grade 5/sepsis/6.0-mg/kg dose; n=1 grade 3/drug-related/maculopapular rash/6.0-mg/kg dose; n=1 grade 2/drug-related/pyrexia/4.0-mg/kg dose) of patients. One DLT (maculopapular rash, grade 3; resolved) occurred with the 6.0-mg/kg dose; the MTD has not been reached. Of tumor-evaluable patients, as of May 23, 2019, 10 partial responses (PR) were observed (7 PRs were observed at the April 12, 2019 datacut), with a clear dose response and good durability: n=1 in the 2mg/kg, n=2 in the 4-mg/kg, n=3 in the 6 mg/kg, and n=4/5 evaluable in the 8.0-mg/kg groups (4 of the PRs remain to be confirmed). Across all dose groups (April 12, 2019 datacut), 16 stable disease (SD), and 11 PD were observed. Systemic DS-1062a exposure increased in an approximate dose-proportional manner; plasma DS-1062a levels and total anti-TROP2 antibody were similar, suggesting DS-1062a stability in circulation. Updated tumor response profile and durability, biomarker analyses and correlation with clinical outcome will be presented, including immunohistochemistry and circulating tumor DNA analysis of baseline and sequential on-treatment samples, and other related markers.

      Conclusion

      DS-1062a was well tolerated and 10 PRs were observed during dose selection in unselected NSCLC patients having progressed on standard of care, including immune checkpoint inhibition in 8 of 10 patients. Updated data will be presented.

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      IASLC Members: To view this content or have the option to purchase this event, click here to login.
      Conference Attendees & Access Code holders: Click here to enter your Access Code. Already entered your Access Code? Please login.

    • +

      MA25.11 - Discussant - MA25.07, MA25.08, MA25.09, MA25.10 (Now Available) (ID 3816)

      14:30 - 16:00  |  Presenting Author(s): Sebastian Defranchi

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      IASLC Members: To view this content or have the option to purchase this event, click here to login.
      Conference Attendees & Access Code holders: Click here to enter your Access Code. Already entered your Access Code? Please login.

  • +

    MS07 - Controversies with Stereotactic Radiation in Early Stage Lung Cancer (ID 70)

    • Event: WCLC 2019
    • Type: Mini Symposium
    • Track: Treatment of Early Stage/Localized Disease
    • Presentations: 6
    • Now Available
    • +

      MS07.01 - Preoperative Optimazition: Reducing Surgery Complications Through Tobacco Cessation (Now Available) (ID 3474)

      14:00 - 15:30  |  Presenting Author(s): David Harpole

      • Abstract
      • Presentation
      • Slides

      Abstract

      Optimizing Outcomes after Pulmonary Resections with Smoking Cessation

      Data on increased risk of complications after major thoracic surgery for current smokers has been documented for several decades, suggesting that smoking cessation for even a few weeks may significantly reduce this risk based on early return of muco-ciliary clearance of respiratory secretions and decreased risk of atelectasis and pneumonia. Moreover, the awareness of potential lung cancer mortality on patients is a potent “teachable moment” for a smoking intervention. However, the literature is anything but definitive on:

      1. Method of smoking cessation / counseling (including pharmacological and non-pharmacological adjuncts)

      2. Length of time required for maximal risk reduction

      3. Durability of cessation after surgery

      This presentation will review the strongest trials in the literature, as well as recent data on a concerted risk reduction programs of Enhanced Recovery from surgery (ERAS) that include smoking cessation.

      References:

      Stokes SM, Wakeam E, Antonoff MB, Backhus LM, Meguid RA, Ordell D, Varghese TK. Optimizing health before elective thoracic surgery: systematic review of modifiable risk factors. J Thorac Dis 11: S537-554; 2109

      Sardari NP, Weyler J, Colpaert C. Prognostic value of smoking status in operated NSCLC. Lung Cancer 47:351-9; 2005

      Mills E, Eyawo O, Lockhart I. Smoking cessation reduces perioperative complications: A systematic review and meta-analysis. Am J Med 124:144-8; 2011

      Kozower BD, Lau CL, Philllips JV. Thoracic surgeon-directed tobacco cessation intervention. Ann Thorac Surg 89:926-30, 2010

      Thomasen T, Abrishami A, Yang Y. Interventions for perioperative smoking cessation. Cochrane Database Syst review 3:CD002299; 2014

      Lugg ST, Tikka T, Agostini PJ, Kerr A, Kalkat MS et al. Smoking and timing of cessation on postoperative complications after curative-intent lung cancer surgery. J Cardiothorac Surg 12:52-60; 2017

      Rodriguez M, Gomez-Hernandez MT, Novoa N, Jimenez MF, Aranda JL. Refraining from smoking shortly before lobectomy has no influence on the risk of pulmonary complications. Eur J Cardiothorac Surg 51:498-503; 2017

      Zaman M, Bilal H, Mahmood S, Tang A. Does getting smokers to stop smoking before lung resections reduce their risk? Interact Cardiovasc Thorac Surg. 14:320-323; 2012

      Gemine RE, Ghosal R, Collier G, Parry D, Campbell I, Davies G, Lewis KE. Longitudinal study to assess impact of smoking at diagnosis and quitting on 1-year survival for people with NSCLC. Lung Cancer 129:1-7; 2019

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      IASLC Members: To view this content or have the option to purchase this event, click here to login.
      Conference Attendees & Access Code holders: Click here to enter your Access Code. Already entered your Access Code? Please login.

    • +

      MS07.02 - Post SBRT Management: Surgery (Now Available) (ID 3475)

      14:00 - 15:30  |  Presenting Author(s): Mara Antonoff

      • Abstract
      • Presentation
      • Slides

      Abstract

      BACKGROUND:

      For early stage NSCLC, lobectomy and mediastinal lymph node dissection has been a long-standing, established standard of care. For patients unable to tolerate surgical resection, several single-institution studies have demonstrated SBRT to be an efficacious and well-tolerated treatment strategy.1-3 The RTOG-0236 trial, subsequently published in 2010, prospectively evaluated SBRT among patients at multiple North American centers, revealing high rates of local tumor control with acceptable treatment-related morbidity, which has been corroborated by other investigators with reproducibly acceptable rates of intermediate-term local control and minimal toxicities.4-6

      Given the success of using SBRT for Stage I NSCLC in medically inoperable patients, increasing interest has arisen regarding the potential application of this modality for healthier, potentially operable patients. In order to expand indications for use of this modality, important issues warranting investigation will include determination of the ideal means of following patients radiographically following SBRT as well as establishing protocols for intervention upon local failure. The outcomes for salvage lung resection following SBRT have been minimally reported. In this study, we aimed to evaluate our experience with operative lung resection in patients where SBRT has failed. Further, we review the combined outcomes in patients from our center along with those previously reported in the published literature.

      METHODS:

      We utilized our Departmental surgical database to identify all patients who underwent salvage pulmonary resection after prior radiation between January 2009 and September 2015. Among 716 patients who underwent pulmonary resection after previous radiotherapy, 21 met inclusion criteria, and these patients comprised the study cohort (MDACC group). Detailed patient data were retrospectively collected from our departmentally maintained, prospectively entered database and supplemented with additional chart review.

      In addition, a MEDLINE search was performed to identify all previous reports of surgical resection following local failure after initial treatment with SBRT. This resulted in 56 articles, which were reviewed to specifically identify publications regarding lung resection following local recurrence after SBRT. Four studies were identified, totaling 18 patients; however, as one report7 included resection of specimens lacking any residual disease, we used only the other 3 reports for cumulative analyses.8-10 From these previous publications, data were extracted for each patient and were combined with those of the MDACC cohort, thus constituting the final aggregate cumulative group.

      Student’s paired t-tests were used to compare pre-SBRT and pre-salvage surgery pulmonary function test results. Kaplan Meier analyses were performed in order to evaluate survival from the time of surgery as well as survival from completion of SBRT.

      RESULTS:

      At our institution, 21 individuals met inclusion criteria and comprised the MDACC group, and the cumulative group included 37 patients at 4 institutions. Baseline details regarding histology, sex, age, and medical operability are included in Figure 1. Elements of the radiation treatment received are also shown in Figure 1.

      Salvage surgery was performed at a median of 16 months following completion of SBRT, with a range of 6.4 to 104 months. Extent of resection is shown in Figure 1. Three (8.1%) operations were performed via minimally invasive approaches (2 thoracoscopic and 1 robotic-assisted). Adhesions were noted intraoperatively for nearly all (36/37, 97.3%) patients. Final pathology resulted in upstaging for 9/15 (60%) of patients in the MDACC group.

      Early postoperative outcomes were available for the 21 patients in the MDACC group (Figure 2). Two (9.5%) required post-operative admission to the intensive care unit (ICU), and stayed for a median of 5.5 days. Pulmonary complications were most common, occurring in 7 (33.3%) patients. Two (9.5%) patients had a prolonged air leak and 2 (9.5%) patients were discharged home on oxygen.

      During follow-up of the 21 MDACC patients, 5 developed recurrence. The three-year cumulative incidence of distant recurrence was 23.8%, with all recurrences distant and median time to recurrence 36.2 months. The median disease-free survival among MDACC patients was 19.2 months. Median survival from surgery for the MDACC group was 46.9 months, with 3-year survival of 53.2%. Thirty- and 90-day mortality were both 1 (4.8%). In the cumulative group, median survival was also 46.9 months and 3-year survival was 71.8%.

      CONCLUSIONS:

      Our findings demonstrate that resection following local failure of SBRT in highly select individuals is feasible, safe, and has an overall acceptable morbidity and mortality, albeit higher than what is typically observed in non-irradiated patients. In considering salvage resection, we recommend careful consideration of the patient’s performance status and the likely extent of required resection, to be discussed thoughtfully both with the patient and in a multi-disciplinary tumor board setting. Further studies are clearly warranted to establish treatment algorithms for those patients who demonstrate locally persistent or recurrent disease following SBRT and to clinically characterize the most appropriate operative candidates.

      abstract figures .jpgreferences image.jpg

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      IASLC Members: To view this content or have the option to purchase this event, click here to login.
      Conference Attendees & Access Code holders: Click here to enter your Access Code. Already entered your Access Code? Please login.

    • +

      MS07.03 - Post SBRT Management: vs Radiation (Now Available) (ID 3476)

      14:00 - 15:30  |  Presenting Author(s): Marco Trovo

      • Abstract
      • Presentation
      • Slides

      Abstract

      Stereotactic Body Radiation Therapy (SBRT) represents the standard of care for medically inoperable patients affected by early-stage Non-small cell lung cancer. Numerous phase I/II and retrospective studies have reported very high rates of local-progression free survival, ranging from 85% to 100% at two years. Interestingly, these data are reproducible among the published series, despite their heterogeneity. Severe lung toxicity (Grade ≥3 lung toxicity) is low, excluding centrally located tumor, ranging from 0% to <10%.

      Because of the following factors: 1) Very high local control rate, 2) very low clinical toxicity rate, 3) fragility of the treated population, the assessment of the response after SBRT has not be considered crucial in the patient management. Recently the perspective changed. Due to the excellent results in terms of local control, the publications of several paper that documented a superior outcome of SBRT vs. limited lung resection, and comparable data vs. lobectomy, more medically operable patients and less fragile populations have been treated in recent years. Moreover prospective trials on operable patients have been conducted. It is implicit that for operable patients the evaluation of a possible failure after SBRT is mandatory to guide further local (or systemic) therapies. Most patients with recurrent disease after SBRT will succumb to progressive cancer if left untreated. Although this is a frail patient population with competing risk of death, lung cancer specific mortality remains crucial. Even though chemotherapy might improve survival, the majority of patients are unfit to receive cytotoxic chemotherapy. However this scenario is going to be completely changed by the arrival of “immune-therapy” due to the overall favorable toxicity profile.

      The ESTRO-ACROP consensus guideline on implementation and practice of SBRT for early-stage NSCLC were recently published (1). Patient follow-up according to published guidelines is a mandatory component of any SBRT protocol. A frequency of 3-6 months in CT of the thorax is suggested, at least for the first year, thereafter the frequency might be tailored to whether the patient is medically operable or not. Three major items are considered of crucial importance when conducting the follow-up of the patient for the correct interpretation of follow-up images: 1) knowledge of the patterns of lung injury after SBRT; 2) detailed knowledge of the SBRT dose distribution, 3) knowledge of the pattern of failure.

      The discrimination between malignant lesion and post-radiation pneumonitis or fibrosis is often challenging. Both the radiation oncologist and the radiologist must be aware of the radiological patterns

      of SBRT-induced lung injury and of their relative frequency. This will become of crucial importance as SBRT is employed for treatment of operable patients, who can eventually benefit from salvage surgery for local relapse. The pattern of changes in lung parenchyma on CT post-SBRT can generally be categorized as acute (within 6 months) or late (after 6 months). Several patterns were described both for early and late radiographic changes (2).

      The differential diagnosis between local recurrence and fibrosis appear to be challenging in those patients who develop pattern characterized by dense consolidation and diffuse fibrosis. Such patterns can be classified as mass-like and modified conventional pattern, as we showed. Those patterns occur in about 74–76% of the cases. Patients who relapse have lesions that enlarged during the follow-up. Thus, a PET/CT in cases of enlargement of the lung fibrosis may be reliable in the differential diagnosis between recurrence and lung injury. FDG-PET imaging is considerate mandatory in case of suspected local recurrence on CT images, but it should be considered only optional during regular follow-up. Biopsy confirmation of suspected local failure is recommended only in patients who are likely to undergo salvage therapy if recurrence is detected. We share the idea of Huang and colleagues, who proposed an algorithm for follow-up of patients who are candidates for salvage therapies (3).

      1. Guckemberger M, Andratschke N, Dieckmann K, et al. ESTRO ACROP consensus guideline on implementation and practice of stereotactic body radiotherapy for peripherally located early stage non-small cell lung cancer. Radiother Oncol 2017;124:11-17.

      2. Trovo M, Linda A, El Naqua I, Javidan-Nejad C, Bradley J. Early and late lung radiographic injuries following stereotactic body radiation therapy (SBRT). Lung Cancer 2010;69:77-85

      3. Huang K, Dahele M, Senan S, et al. Radiographic changes after lung sterotactic ablative radiotherapy (SABR) – can we distinguish recurrence from fibrosis? A systemic review of the literature. Radiother Oncol 2012;102:335-342.

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      IASLC Members: To view this content or have the option to purchase this event, click here to login.
      Conference Attendees & Access Code holders: Click here to enter your Access Code. Already entered your Access Code? Please login.

    • +

      MS07.04 - Stage I (Resectable) NSCLC: Surgery (Now Available) (ID 3477)

      14:00 - 15:30  |  Presenting Author(s): Ryota Tanaka

      • Abstract
      • Presentation
      • Slides

      Abstract

      Lobectomy and lymph node dissection have been the standard therapeutic procedure for localized lung cancer since Cahan’s “Radical lobectomy” was published in 1960 [1]. In 1995, the Lung Cancer Study Group (LCSG) published findings from a randomized controlled study of clinical stage T1N0 non-small cell lung cancer (NSCLC), [2] that showed inferior overall survival and ~3× local recurrence rate in the limited (sublobar; segmentectomy or wedge) resection arm compared with the lobectomy arm. Although the LCSG study had some flaws (30% of patients had tumors >2 cm; wedge resections without lymph node dissection were performed as limited resections; inclusion of non-peripheral NSCLC in the limited resection arm, which could cause higher local recurrence rates), its results suggested that lobectomy is the superior option.

      Lobectomy has since been adopted worldwide as the surgical standard of care, whereas the indication for segmentectomy to treat lung carcinomas with solid appearances on computed tomography (CT) is controversial, although several non-randomized studies have suggested that survival and recurrence may be equivalent between lobectomy and sublobar resection (SLR) in patients with smaller lesions (≤ 2 cm) [3,4]. Improvements in imaging technology, such as thin-section CT (TSCT), have led to more patients who present with localized, early-stage lung cancers; and increased detection of small, peripheral NSCLC has renewed interest in SLR as an alternative to lobectomy. In addition, tumors with ground-glass opacity (GGO) have been correlated with less-invasive pathological findings of lepidic adenocarcinoma (AD) growth. Therefore, these patients may be feasible candidates for SLR. The Japan Clinical Oncology Group (JCOG) conducted a cohort study of early peripheral lung cancer (JCOG0201) and investigated the use of TSCT criteria to diagnose non-invasive lung AD, to preoperatively predict pathological non-invasive cancers [5]. Following this observational study, three ongoing trials (JCOG0804/WJOG4507L, JCOG1211 and JCOG0802/WJOG4607L) were initiated to confirm the validity of limited resection for stage I lung cancers, stratified according to preoperative TSCT findings. A non-randomized phase III trial (JCOG0804/WJOG4507L) was conducted to evaluate the efficacy and safety of SLR for peripheral GGO-dominant small lung cancers (tumor diameter ≤ 2.0 cm) and with consolidation tumor ratio ≤ 0.25, based on TSCT [6]. Five-year relapse-free survival (RFS) was 99.7% (95% CI: 97.7–100.0%), with no local recurrences. This study showed SLR (mainly wedge resection) to provide sufficient local control and RFS for peripheral GGO-dominant lung cancer (as seen on TSCT). A randomized phase III trial (JCOG0802/WJOG4607L) was conducted to compare overall survival after segmentectomy with that of lobectomy in patients with peripheral small (≤ 2 cm) NSCLC lesions [7]. The ongoing Cancer and Leukemia Group B (CALGB) 140503 trial is another large, multicenter randomized trial to compare disease-free survival between SLR and lobectomy among patients with peripheral small (≤ 2 cm) NSCLC lesions [8]; and is similar to the JCOG0802/WJOG4607L trial. However, as CALGB 140503 allows wedge resection as a surgical intervention, the JCOG0802/WJOG4607L trial offers a more definitive comparison of segmentectomy vs lobectomy for small invasive AD. The JCOG0802/WJOG4607L trial completed enrolling 1106 patients in 2014 and will clarify whether limited resection for primary lung cancer is not only function-preserving but also curative. The National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines recommend segmentectomy or wedge resection for patients with insufficient pulmonary reserve or with other major comorbidities, and for patients with tumors ≤2 cm that are either (a) pure AD in situ (AIS) confirmed by histopathological analysis, (b) nodules with ≥50% GGO on CT, or (c) confirmed by radiologic surveillance to have long doubling times (≥400 days) [9]. However, we need the results from all prospective randomized trials to form new treatment strategies for early-stage lung cancers.

      References

      [1] Cahan WG. Radical lobectomy. J Thorac Cardiovasc Surg 1960;39:555-72.

      [2] Ginsberg RJ, Rubinstein LV. Randomized trial of lobectomy versus limited resection for T1 N0 non-small cell lung cancer. Lung Cancer Study Group. Ann Thorac Surg 1995;60:615-22.

      [3] Tsubota N, Ayabe K, Doi O, et al. Ongoing prospective study of segmentectomy for small lung tumors. Study Group of Extended Segmentectomy for Small Lung Tumor. Ann Thorac Surg 1998;66:1787-90.

      [4] Okada M, Koike T, Higashiyama M, et al. Radical sublobar resection for small-sized non-small cell lung cancer: a multicenter study. J Thorac Cardiovasc Surg 2006;132:769-75.

      [5] Suzuki K, Koike T, Asakawa T, et al. A prospective radiological study of thin-section computed tomography to predict pathological noninvasiveness in peripheral clinical IA lung cancer (Japan Clinical Oncology Group 0201). J Thorac Oncol 2011;6:751-6.

      [6] Suzuki K, Watanabe S, Wakabayashi M, et al. A nonrandomized confirmatory phase III study of sublobar surgical resection for peripheral ground glass opacity dominant lung cancer defined with thoracic thin-section computed tomography (JCOG0804/WJOG4507L). J Thorac Oncol 2017;35(Suppl):abstr 8561.

      [7] Nakamura K, Saji H, Nakajima R, et al. A phase III randomized trial of lobectomy versus limited resection for small-sized peripheral non-small cell lung cancer (JCOG0802/WJOG4607L). Jpn J Clin Oncol 2010;40:271-4.

      [8] Kohman LJ, Gu L, Altorki N, et al. Biopsy first: Lessons learned from Cancer and Leukemia Group B (CALGB) 140503. J Thorac Cardiovasc Surg 2017;153:1592-7.

      [9] Ettinger DS, Wood DE, Akerley W, et al. NCCN Guidelines Insights: Non-Small Cell Lung Cancer, Version 4.2016. J Natl Compr Canc Netw. 2016;14:255-64.

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      IASLC Members: To view this content or have the option to purchase this event, click here to login.
      Conference Attendees & Access Code holders: Click here to enter your Access Code. Already entered your Access Code? Please login.

    • +

      MS07.05 - Stage I (Resectable) NSCLC: Radiation (Now Available) (ID 3478)

      14:00 - 15:30  |  Presenting Author(s): Suresh Senan

      • Abstract
      • Presentation
      • Slides

      Abstract

      For patients with a peripheral stage I NSCLC, the non-surgical treatment of choice is stereotactic ablative radiotherapy (SABR). Patients who are fit to undergo surgery, but instead undergo SABR, have a 3-year overall survival ranging from 76-86% [Siva S, Oncologist 2016], which is superior overall survivals in medically unfit patients treated using SABR. In 2013, the ESMO Clinical Practice Guidelines recommeded that surgery ‘should be offered to patients with stage I or II NSCLC who are willing to accept procedure-related risks’ [Vansteenkiste J, Ann Oncol 2013]. In the absence of completed randomized clinical trials of surgery versus SABR, a number of recent propensity score matched analyses have been performed. A pooled meta-analysis of propensity score matched data showed no significant differences in cancer specific survival between the two local treatments [Chen H, IJROBP 2018].

      Changes in the treatment patterns for patients with early-stage NSCLC have be reported in a number of countries, all showing an increase in the utilization of SABR in mainly elderly patients [Damhuis R, Ann Oncol 2019; Holmes JA, JNCI Ca Spectrum 2017]. These findings are in part due to the increase in the frail elderly presenting with lung cancer, and to the growing awareness of treatment-related mortality in this population. For example, data from the US National Cancer Database revealed that differences in 30- and 90-day post-treatment mortality between surgery and SABR increased as a function of age, with the largest differences in favor of SABR observed among patients older than 70 years [Stokes WA, JCO 2018[.

      Ongoing and future randomized studies comparing both modalities will also have to take account of the view of patient preferences. This is illustrated by recent randomized trial of surgery versus SABR (SABRTOOTH, ISRCTN13029788), in which 84 high-risk patients were approached by pulmonologists and oncology nurses for study participation, and 24 (29%) were randomized [Franks K, WCLC 2018]. The main reason for declining study participation was patient preference with 29% preferring surgery and 42% SABR. Overall 9 patients (38%) did not receive their randomized treatment. Of 7 patients who had been randomized to surgery but not undergoing surgery, 6 received SABR, 1 radical radiotherapy. Similarly, of 2 patients randomized to SABR, but who did not undergo SABR, 1 patient received radical radiotherapy, and another was lost to follow-up. Other research which may influence the ongoing debate are the effects of both local therapies on the immune system.

      The systemic inflammatory response induced after surgery can promote the emergence of tumors whose growth was otherwise restricted by a tumor-specific T cell response [Krall 2018]. SABR, on the other hand, is actively being investigated as an immunomodulator to enhance systemic anticancer effects [Marciscano AE, IJROBP 2019], with a randomized placebo-controlled trial of immune-checkpoint blockade underway in this population (NCT03833154).

      References

      Siva S. Curing Operable Stage I Non-Small Cell Lung Cancer With Stereotactic Ablative Body Radiotherapy: The Force Awakens. The Oncologist 2016;21:393–398

      Vansteenkiste J. Early and locally advanced non-small-cell lung cancer (NSCLC): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2013 Oct;24 Suppl 6:vi89-98.

      Chen H. Stereotactic Ablative Radiation Therapy Versus Surgery in Early Lung Cancer: A Meta-analysis of Propensity Score Studies. Int J Radiat Oncol Biol Phys 101:186-194, 2018

      Damhuis R. Annals of Oncology (2019) 30 (suppl_2): ii26-ii30. 10.1093/annonc/mdz064

      Holmes JA, JNCI Cancer Spectrum, Volume 1, Issue 1, September 2017, https://doi.org/10.1093/jncics/pkx003

      Stokes WA. Post-Treatment Mortality After Surgery and Stereotactic Body Radiotherapy for Early-Stage Non-Small-Cell Lung Cancer. J Clin Oncol2018 Mar 1;36(7):642-651.

      Franks K. SABRTOOTH: A Feasibility Study of SABR Versus Surgery in Patients with Peripheral Stage I NSCLC Considered to be at Higher Risk for Surgery. Proceedings of WCLC 2018 P2.16-16

      Marciscano AE. Immunomodulatory Effects of Stereotactic Body Radiation Therapy: Preclinical Insights and Clinical Opportunities. In press Int J Radiat Oncol Biol Phys 2019 https://doi.org/10.1016/j.ijrobp.2019.02.046

      Krall JA. The systemic response to surgery triggers the outgrowth of distant immune-controlled tumors in mouse models of dormancy. Sci. Transl. Med. 10, eaan3464 (2018)

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      IASLC Members: To view this content or have the option to purchase this event, click here to login.
      Conference Attendees & Access Code holders: Click here to enter your Access Code. Already entered your Access Code? Please login.

    • +

      MS07.06 - Hot Topics in SBRT - Biopsy, Central Lesions, Radiologic Evaluation (Now Available) (ID 3479)

      14:00 - 15:30  |  Presenting Author(s): Cecile Le Pechoux  |  Author(s): Angela Botticella, Antonin Levy, Olivier Henry, Isabelle Chabert, CAROLINE Caramella

      • Abstract
      • Presentation
      • Slides

      Abstract

      Stereotactic body radiotherapy (SBRT) has taken a growing place among treatment strategies in lung cancer in the past ten years because of its reported good results and favourable risk-benefit ratio especially in high-risk patients. This treatment modality allows delivering precisely a very high dose of radiation therapy to a targetable lesion, using a small number of fractions (3 to 5 more frequently). It has become the standard of care in medically inoperable peripheral early stage non-small cell lung cancer (NSCLC) patients. It is also frequently used in metastatic patients to treat cranial as well as extra-cranial metastases. Recently small randomised studies evaluating SBRT in oligometastatic NSCLC have shown promising results. Its role is now well accepted however there are situations where SBRT is still a subject of controversy and may be regarded as a hot topic

      because of the lack of pre-treatment biopsy

      because of less favourable outcome in central lesions and higher risk of complications

      because of the difficulty of radiologic evaluation

      When a peripheral lung nodule is discovered, suspect of being lung cancer, attempt should be made to obtain a pathological diagnosis before any treatment is proposed. Percutaneous CT–guided transthoracic biopsy is the established investigation in the work-up of pulmonary nodules, but there is a risk of complications such as pneumothorax (20-40%). However in patients with poor lung function (severe COPD, emphysema..), tissue sampling can be particularly challenging especially when the nodule is beyond the reach of conventional bronchoscopy. These are typically the patients that may be considered for SBRT, possibly presenting a contra-indication to transthoracic biopsy. Criteria for definition of a nodule as lung cancer without biopsy confirmation have been proposed such as progressive growth on CT imaging or presence of a hypermetabolic lesion on PET scan, and multidisciplinary tumor board consensus on the clinical diagnosis of lung cancer; there should be at least a 85% risk of malignancy, based upon accepted criteria [Postmus; Louie, Reid].

      If stereotactic radiotherapy in peripheral early NSCLC is presently a standard of care in inoperable patients due to co-morbidities and age, its role is more controversial for centrally located tumors because of less favorable outcome and higher risk of complications. In the past years, there has been a need to better classify these patients differentiating ultra-central from central lesions. The RTOG 0813 phase I/II trial, evaluated dose escalation in 120 patients with centrally-located non-small lung cancer with a five-fraction schedule that ranged from 10 to 12 Gy per fraction [Bezjak 2019]. The maximum tolerated dose was 60 Gy (5 fractions of 12 Gy), which was associated to a 2 year local control rate of 87.9%. They reported a fatal hemoptysis rate of 4%, potentially attributable to stereotactic radiotherapy [Bejzak 2015]. Even if the authors of this prospective study reported that outcome was comparable with that of patients with peripheral early-stage tumors, the risk of severe toxicity seems to be higher than in peripheral tumors. In another prospective phase II study, the Nordic hilus trial, which included 74 patients with central tumors within 1 cm from the proximal bronchial tree (PBT), the administered dose was 8 fractions of 7 Gy [Lindberg]. The authors reported a grade 4-5 toxicity of 19% among patients with tumor close to the main bronchus (ultra-central location) versus 3% in patients with tumor close to a lobar bronchus (central location). In a retrospective study of 88 patients with ultra-central lesions defined as tumors abutting PBT or trachea, or close to esophagus, a grade 3 toxicity or higher was reported in about 20% patients [Wang]. In another smaller retrospective study, where patients received 12 fractions of 5 Gy, outcome was quite good but toxicity ≥ grade 3 was reported in 38% of patients [Tekatli]. Thereby stereotactic radiotherapy for ultra-central tumors cannot be considered a standard treatment and more studies are needed for all central tumours to find the optimal dose regimen.

      Radiological evaluation after SBRT is performed mostly with chest CT scan, and changes occurring early and/or late are very common but can be tricky for radiologists as well as clinicians [Ronden,Febbo]. If FDG PET-CT is well established as staging tool prior to treatment, it is generally not used for surveillance. It may be useful though to differentiate local recurrence from radiation-induced lung opacity. Ideally, a treatment failure suspicion should be confirmed with a biopsy.

      These hot topics regarding SBRT show the difficulty to include patients into prospective trials; efforts have been made and should be pursued.

      References

      Postmus PE, Kerr KM, Oudkerk M, et al. Early and locally advanced non-small-cell lung cancer (NSCLC): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2017;28(suppl_4):iv1-iv21.

      Louie AV, Senan S, Patel P, et al. When is a biopsy-proven diagnosis necessary before stereotactic ablative radiotherapy for lung cancer?: A decision analysis. Chest 2014; 146(4):1021-1028.

      Reid M, Choi HK, Han X et al. Development of a Risk Prediction Model to Estimate the Probability of Malignancy in Pulmonary Nodules Being Considered for Biopsy. Chest 2019. [Epub ahead of print]

      Lindberg K, P.Bergström, OT Brustugun et al. The Nordic HILUS-Trial - First Report of a Phase II Trial of SBRT of Centrally Located Lung Tumors. J Thorac Oncol 2017;12(15) Abstract S340.

      Bezjak A, Paulus R, Gaspar LE, et al. Safety and efficacy of a five-fraction stereotactic body radiotherapy schedule for centrally located non-small-cell lung cancer: NRG Oncology/RTOG 0813 trial. J Clin Oncol 2019;37(15):1316-1325.

      C. Wang, B. Sidiqi, E. Yorke, et al. Toxicity and local control in “ultra-central” lung tumors treated with SBRT or high-dose hypofractionated RT. J Thorac Oncol 2018; 13(10).

      Tekatli H, Haasbeek N, Dahele M, et al. Outcomes of Hypofractionated High-Dose Radiotherapy in Poor-Risk Patients with "Ultracentral" Non-Small Cell Lung Cancer. J Thorac Oncol 2016;11(7):1081-1089.

      Ronden MI, Palma D, Slotman BJ, Senan S. Brief Report on Radiological Changes following Stereotactic Ablative Radiotherapy (SABR) for Early-Stage Lung Tumors: A Pictorial Essay. J Thorac Oncol 2018;13(6):855-862.

      Febbo JA, Gaddikeri RS, Shah PN. Stereotactic Body Radiation Therapy for Early-Stage Non-Small Cell Lung Cancer: A Primer for Radiologists. Radiographics 2018;38(5):1312-1336.

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      IASLC Members: To view this content or have the option to purchase this event, click here to login.
      Conference Attendees & Access Code holders: Click here to enter your Access Code. Already entered your Access Code? Please login.

  • +

    MS15 - How to Get Patients to Quit Smoking; Practical Implementation of Evidence-Based Cessation Practices (ID 78)

    • Event: WCLC 2019
    • Type: Mini Symposium
    • Track: Prevention and Tobacco Control
    • Presentations: 4
    • Now Available
    • +

      MS15.01 - The Importance of Cessation and “5as” as a Framework for Cessation (Now Available) (ID 3525)

      11:30 - 13:00  |  Presenting Author(s): Babalola Faseru

      • Abstract
      • Presentation
      • Slides

      Abstract

      Almost two-thirds of newly diagnosed cancer patients have used or currently use tobacco. Evidence shows that continuous use of tobacco after cancer diagnosis adversely affects treatment outcomes among cancer patients compared to their counterparts who stop using tobacco. These outcomes include recovery, quality of life and survivorship.

      According to the United States Department of Health and Human Services clinical practice guideline for treating tobacco use and dependence, 5As include 1) Ask about tobacco use at every visit to identify and document tobacco use status of every patient 2) Advise every tobacco user to stop using tobacco – the message must be clear, strong and personal 3) Assess readiness to quit - implement strategies to motivate those who are not ready with 5Rs [Relevance, Risks, Rewards, Roadblocks and Repetition] 4) Assist those who are ready quit - develop (a) a quit plan using the STAR method [Set a quit date, Tell friends, family and co-workers and ask for their support, Anticipate challenges to the quit attempt, Remove all tobacco products] (b) recommend smoking cessation medication as indicated, provide counseling support and supplemental materials including information about the quitline where available 5) Arrange follow-up for additional support to avoid relapse. The efficacy of the 5As brief intervention recommendations have been described in the clinical practice guidelines. For example, clinicians who work in a setting where tobacco use status are easily captured are three times more likely to provide tobacco treatment to their patients OR 3.1 95% CI (2.2-4.2); physician advice to patients who smoke increases the odds of quitting compared to no physician advice OR 1.3 95% CI (1.1-1.6); and a combination of counseling and medication outperforms counseling alone OR 1.7 95% CI (1.3 - 2.1). This brief smoking cessation intervention approach using the 5As framework is feasible and cost effective. However, gaps in smoking cessation knowledge and practices in cancer care persist and tobacco use treatment remain suboptimal.

      During this mini symposium, we will discuss the effectiveness of 5As at various settings, examine other adaptations such as 3As, ABC, ABCD, AAR and identify ways to overcome the multi-level challenges of implementing evidence-based tobacco dependence treatment during cancer care.

      References

      Karam-Hage M, Cinciripini PM, Gritz ER. Tobacco use and cessation for cancer survivors: an overview for clinicians. CA Cancer J Clin. 2014;64(4):272-290.

      Warren GW, Kasza KA, Reid ME, Cummings KM, Marshall JR. Smoking at diagnosis and survival in cancer patients. Int J Cancer. 2013;132(2):401–10.

      Gritz ER, Toll BA, Warren GW. Tobacco use in the oncology setting: advancing clinical practice and research. Cancer Epidemiol Biomarkers Prev 2014;23:3-9

      Parsons A, Daley A, Begh R, Aveyard P. Influence of smoking cessation after diagnosis of early stage lung cancer on prognosis: systematic review of observational studies with meta-analysis. BMJ. 2010;340:b5569

      Fiore MC, Jaen CR, Baker TB, et al. Treating Tobacco Use and Dependence: 2008 Update, Clinical Practice Guideline. Rockville, MD: U. S. Department of Health and Human Services. Public Health Service; 2008.

      Warren GW, Dibaj S, Hutson A, Cummings KM, Dresler C, Marshall JR. Identifying targeted strategies to improve smoking cessation support for cancer patients. J Thorac Oncol 2015;10:1532-1537.

      Price SN, Studts JL, Hamann HA. Tobacco Use Assessment and Treatment in Cancer Patients: A Scoping Review of Oncology Care Clinician Adherence to Clinical Practice Guidelines in the U.S. The oncologist. 2019;24(2):229-238

      Warren GW, Marshall JR, Cummings KM, Toll B, Gritz ER, Hutson A, et al. Practice patterns and perceptions of thoracic oncology providers on tobacco use and cessation in cancer patients. J Thorac Oncol. 2013;8:543–548

      McRobbie H Bullen C Glover M et al. New Zealand smoking cessation guidelines. N Z Med J . 2008;121(1276):57–70

      Gould GS Bittoun R Clarke MJ . A pragmatic guide for smoking cessation counselling and the initiation of nicotine replacement therapy for pregnant Aboriginal and Torres Strait Islander smokers. J Smoking Cessation . 2015;10(2):96–105

      Vidrine JI Shete S Cao Y et al. Ask-Advise-Connect: a new approach to smoking treatment delivery in health care settings. JAMA Intern Med . 2013;173(6):458–464

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      IASLC Members: To view this content or have the option to purchase this event, click here to login.
      Conference Attendees & Access Code holders: Click here to enter your Access Code. Already entered your Access Code? Please login.

    • +

      MS15.02 - Pharmacotherapy Supports Cessation (Now Available) (ID 3526)

      11:30 - 13:00  |  Presenting Author(s): Carolyn Dresler

      • Abstract
      • Presentation
      • Slides

      Abstract

      Tobacco Cessation and its pharmcotherapy

      It should be acknowledged that smoking cessation is one of the hardest things the patient has ever tried to do. There are two key aspects to tobacco cessation: appropriate pharmacotherapy and behavioral modification. This abstract will address only the pharmacotherapy, but the practitioner must also try to provide or refer to behavioral modication interventions to amplify the effect of the pharmacotherapy.

      TYPES OF MEDICATIONS: The most common type of medication for quitting smoking is called ‘nicotine replacement therapy’ or ‘NRT”. NRT that has had regulatory approval comes as a gum, a lozenge, or a transdermal patch, or in a device that you ‘smoke’ like a cigarette’ or a nasal spray. In the United States, the nicotine gum, nicotine lozenge and nicotine patch can be purchased without a doctor’s prescription. The device that is ‘smoked’ (I call an inhaler or inhalator - as it is mostly absorbed by buccal mucosa) and the nasal spray must have a doctor’s prescription.

      Varenciline is a pill that is taken once in the morning and once in the evening. This medication requires a doctor’s prescription. This drug does not yet (as of 2019) come in a generic form.

      To use varenicline – take 0.5 mg by mouth once in the morning for 3 days. On the fourth day – take 0.5 mg by mouth once in the morning and once in the evening. On the 7th day the person should QUIT SMOKING and use 1 mg by mouth once in the morning and once in the evening. Use varenicline for at least 3 months. A discussion between doctor and patient should occur if a longer term treatment period is needed to maintain cessation.

      Bupropion is also taken as a pill once in the morning and once in the evening. This medication should not be taken if there is any risk of a seizure, alcoholism, or anorexia. This drug does come as a generic and requires a doctor’s prescription.

      To use bupropion: Take 150 mg by mouth once a AM for 3 days. On the fourth day, take 150 mg by mouth once q AM and a PM. On the 7th day – quit smoking. Use bupropion for at least 3 months. A discussion between doctor and patient should occur if a longer term treatment period is needed to maintain cessation.

      NICOTINE REPLACEMENT THERAPY:

      Nicotine gum: the labeling on the box states that if more than 25 cigarettes per day are smoked, use the 4 mg dose and if less than 25 cigarettes are smoked per day, use the 2 mg dose. However, one can try either and see which dose works better in relieving or preventing cravings for a cigarette. It is very important to take the nicotine gum frequently! Most people do not take enough of the gum during the day to be effective. Instruct the quitter to use at least 9 pieces in the first days of quitting.

      One should SLOWLY taper down. Plan on having the quitter using the gum for at least 3 months! The worst day is the first day, and then the first week. After about 7-10 days, all of the nicotine and its breakdown products are cleared from the system and the body is starting to become normal again. It is probable that the quitter is still having cravings – and the nicotine gum will help prevent them and make the cravings more manageable.

      NICOTINE LOZENGE: The nicotine lozenge has a little bit different dosing instruction: if the first cigarette of the day is within 30 minutes after waking up in the morning – use the 4 mg nicotine lozenge. If the first cigarette of the day is had after 30 minutes after getting up – use the 2 mg nicotine lozenge. Again – one can try one and see how it works in relieving cravings without any side effects. If it doesn’t seem to relieve cravings – try the other, higher dose. Follow the same instructions above for the gum. AGAIN – it is important to be sure and use enough lozenges per day – the most common problem is people NOT using enough lozenges per day.

      NICOTINE PATCH: The nicotine patch comes in a variety of doses and dosing instructions. Most commonly, people use the 15 mg dose (Nicotrol or generic patch) or the 21 mg patch (Nicoderm, Habitrol or generic). These patches should be put on an area of clean and dry skin. It can be put anywhere on the body, but it is best to put it somewhere on the upper body. Try to put it on a place that is not hairy – so it doesn’t hurt when taken it off! Don’t put it on the hips where one might sit on it, don’t put it under the breast – these places are just common sense places NOT to put the patch. The best place is somewhere on the chest, upper back or arms. It is important to put the new patch on each morning in a DIFFERENT place than the patch before. Some skin redness is common, and it should resolve in the next day or so – but it is important to NOT keep using the same place to put the patch.

      After about 8 weeks on the highest dose patch, the quitter should start to ‘step-down’ the dose and use the 14 mg or the 7 mg patch. These decreasing doses are intended to help wean the quitter off of nicotine. Of course, the smaller amount of nicotine will also help with the decreasing cravings and withdrawal symptoms as they get further from the quit date.

      Even if there is a slip - the quitter has had even one puff – it doesn't mean failure. If there is a slip, work with the quitter, resolve to ‘get back on the wagon’ and not to have another cigarette. They should learn from the experience about what made that ‘slip’ occur and try and stay away from that temptation again.

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      IASLC Members: To view this content or have the option to purchase this event, click here to login.
      Conference Attendees & Access Code holders: Click here to enter your Access Code. Already entered your Access Code? Please login.

    • +

      MS15.03 - Speaking with Patients, Motivational Interviewing Demonstration (Now Available) (ID 3527)

      11:30 - 13:00  |  Presenting Author(s): Douglas Arenberg

      • Abstract
      • Presentation
      • Slides

      Abstract

      Ongoing tobacco use accounts for significant treatment and disease related morbidity, mortality, and decreased quality of life among patients undergoing cancer treatment. A common misconception is that it is too late to pursue tobacco cessation for individuals with advanced lung cancer. Data from existing studies do not support this, yet support for tobacco cessation services among cancer centers is often lukewarm or frankly lacking. For individuals undergoing active cancer therapy, even brief interventions from their oncologist can have an enormous impact on their willingness, and motivation to make a quit attempt. The purpose of this presentation is to arm lung cancer clinicians with tools to help patient's find internal motivation to make quit attempts, and to support them with counseling, as well as cessation pharmacotherapy. Common misconceptions among both providers and their patients who use tobacco will be presented, along with strategies to undserstand and overcome ambivalence towards tobacco cessation.

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      IASLC Members: To view this content or have the option to purchase this event, click here to login.
      Conference Attendees & Access Code holders: Click here to enter your Access Code. Already entered your Access Code? Please login.

    • +

      MS15.04 - Approaching Cessation in the Patient Using Electronic Cigarettes (Now Available) (ID 3528)

      11:30 - 13:00  |  Presenting Author(s): Carolyn Dresler

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      IASLC Members: To view this content or have the option to purchase this event, click here to login.
      Conference Attendees & Access Code holders: Click here to enter your Access Code. Already entered your Access Code? Please login.

  • +

    YI01 - First Time Attendee Session (ID 107)

    • Event: WCLC 2019
    • Type: Young Investigator Session
    • Track: Young Investigators
    • Presentations: 4
    • Now Available
    • +

      YI01.01 - Planning an Academic Career in Lung Cancer (Now Available) (ID 3690)

      07:00 - 08:30  |  Presenting Author(s): David R Gandara

      • Abstract
      • Presentation
      • Slides

      Abstract

      Planning an Academic Career in Thoracic Malignancies

      David R Gandara, MD

      University of California, Davis Comprehensive Cancer Center

      Sacramento, CA

      For those graduating from training in oncologist specialties worldwide in 2019, never have there been so many and such diverse opportunities, including Industry-related and Governmental positions. While the term “private practice” has specific connotations for oncologists in the USA that may no be applicable elsewhere in the world, the requisites for a career in academic medicine are uniform on a global basis. For example, it is often stated that that for clinical investigators a career in academic medicine is like a 3 legged stool, supported equally by clinical care, research and teaching. Some would add that administration is the fourth leg of an academic career, since it is often a significant component of time-spent. For those in a purely laboratory-based academic career, clinical care may be replaced by other activities. Assuming that you choose to be an academic physician with clinical care responsibilities, there are 3 broad categories of effort: clinical educator/administrator, clinical investigator and clinician-scientist.

      Making the decision on which career pathway to follow is often not easy, and may be influenced by your country of origin and associated opportunities and challenges for different specialties in oncology where you intend to work. In fact, changing the decision between academic and non-academic career pathways have never been easier. There are many examples today of oncologists moving back and forth between academics and industry, with equal success in both venues.

      This presentation will give a “personalized” approach to career planning taken from my own and other shared experiences. Since the ratio of pros/cons for academic medicine are largely applicable on an individual basis, this presentation mode will hopefully provide young investigators attending WCLC 2019 with personal insight and position them well for making this career-defining decision.

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      IASLC Members: To view this content or have the option to purchase this event, click here to login.
      Conference Attendees & Access Code holders: Click here to enter your Access Code. Already entered your Access Code? Please login.

    • +

      YI01.02 - Why to Become a Member of the IASLC (Now Available) (ID 3691)

      07:00 - 08:30  |  Presenting Author(s): Giorgio Vittorio Scagliotti

      • Abstract
      • Presentation
      • Slides

      Abstract

      Since the 1970s, the International Association for the Study of Lung Cancer (IASLC) has promoted research and education into all aspects of lung cancer and other thoracic malignancies, as well as encouraged worldwide cancer prevention efforts.

      According to its mission statement the International Association for the Study of Lung Cancer (IASLC) must embrace the study of the etiology, epidemiology, prevention, diagnosis, treatment and all other aspects of lung cancer and other thoracic malignancies; provide education and information about lung cancer and other thoracic malignancies to IASLC members, to the medical community at large, and to the public; use all available means to eliminate lung cancer and other thoracic malignancies as a health threat for the individual patient and throughout the world.

      In the last ten years those goals have been embraced by a growing number of members worldwide and now the association counts on approximately 7.000 members with a large portfolio of scientific and educational activities, being now IASLC the premiere society in the field of thoracic oncology.

      Beyond this bold statement the really question here is why me? While IASLC in the context of many other offers coming from other scientific organizations? The answer comes from one of our members “Being a member helped me in many, many ways. First coming to the IASLC World Conference on Lung Cancer. I was a resident and presenting in front of 100 people [….] that helped me secure my fellowship position. The IASLC helped me with great networking opportunities to interact with many members of the lung cancer community”.

      That is really the key message. Inclusivity and multidisciplinary. The composition of our Board and committees reflect this sense of inclusivity. We want all the players in the thoracic oncology arena to have the appropriate voice, and the younger generation at the foremost.

      IASLC mentors and support younger people in the context of several activities within the organization. IASLC has a wide range of fellowships that support people to travel and present at meetings, to get involved in research, and more importantly to get a research grant to make your ideas a reality, and to meet people who can help you further in boosting your career.

      Our annual meeting is a reference meeting and every year the most relevant scientific research results have been constantly presented. The targeted therapy meeting held every year at the end of February in Santa Monica remains a unique forum of scientific exchange between researchers and pharma not paired by any other type of meeting throughout the world. Equally relevant are the regional meetings that are mainly educational but are also offering the opportunity to report about your own research.

      One of the main duties of a membership association is to provide value to its members, through high quality and relevant offerings and deeper, more efficient mechanisms for engagement. Creating a robust experience for IASLC members and honoring our commitment to geographic and discipline diversity is our goal

      The most challenging part for any scientific society is to understand the differences in generational needs. We need to identify the best new talents, the rising stars in our field, who will not only disrupt conventional thinking; they will lead the IASLC in the future. Specific actions will be considered and others are already in place to convince younger generations to see themselves in the IASLC mission.

      We want you joining us in the fight against tobacco, we want you to be the ambassadors of our organization for the present and, more importantly, the future of our patients with the ultimate goal to be part of a dream : the eradication of thoracic malignancies

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      IASLC Members: To view this content or have the option to purchase this event, click here to login.
      Conference Attendees & Access Code holders: Click here to enter your Access Code. Already entered your Access Code? Please login.

    • +

      YI01.03 - Making the Most of WCLC: A Guide for First Time Attendees (Now Available) (ID 3692)

      07:00 - 08:30  |  Presenting Author(s): Heather A Wakelee  |  Author(s): Becky Bunn

      • Abstract
      • Presentation
      • Slides

      Abstract

      Congratulations on making the decision to attend the International Association for the Study of Lung Cancer (IASLC) World Conference on Lung Cancer (WCLC)! This is the largest meeting in the world focused entirely on thoracic malignancies and is truly an international and multidisciplinary event. However, it is possible to get lost with so many concurrent sessions and in the sea of thousands of delegates. So having a game plan is critical. You will want to have a roadmap and plan for each day but also allow time for networking and to have some fun. With the virtual meeting available afterwards do not worry too much if you want to be in two places at once. You can be… “virtually.”

      Check out the “First Time WCLC Attendees” tab on the IASLC WCLC2019 conference website for great guidance from Dr. Anne-Marie Baird. To paraphrase her:

      #1 Prepare

      #2 Attend the Young Investigators Symposium

      #3 Check out the Posters

      #4 Network

      #5 Engage with Social Media.

      These are all outstanding suggestions! To help you prepare be sure to look at the program in advance and get a sense of the conference center layout. Each morning there is a Plenary session highlighting key topics with talks given by world leaders. These can be amazing! The top abstracts of the meeting will be presented in the Presidential symposium on Monday morning Sept 9. The conference app (available a week or so before the start of WCLC2019) is a great way to keep track of everything. With so many concurrent sessions it will be important to have the info at your fingertips.

      There is a daily press conference that you can attend or review in the press and media section of the WCLC website. Highlights of the day (HOD) will be presented Mon Sept 9 and Tues Sept 10 from 10:30-12 of the conference and also included in emails and on the website. Checkout the daily newspaper (WCLC Daily News) for more highlights. Also you may want to follow everything that is happening on social media!

      IASLC is active on: Twitter, Facebook, LinkedIn, YouTube, Instagram

      Important Hashtags for lung cancer #LungCancer, #CureMESO, #NSCLC, #SCLC, #CancerResearch, #Oncology, #clinicaltrials

      IASLC 2019 World Conference on Lung Cancer – Social Details:

       Official Conference Hashtag: #WCLC19

       Official Hashtag of Lung Cancer Social Media Community: #LCSM

      The IASLC operates a social media booth at each WCLC for new users to learn about social media, get a tip-sheet and take photos with special branded backdrop (which is really fun)!

      As you look at the program you will see there is a great mix of education sessions, workshops and new data presentations. You will likely want to attend a mix of all of these. The education sessions may be a focus since those will include global experts summarizing particular topics and future predictions. It can be a bit tricky to understand the significance of some of the new data without knowing the background and the education sessions will help with that knowledge. It is also great to go to some of the mini-orals (MA) and oral (O) sessions to hear the latest research, particularly in your areas of interest. The mini-orals can be tricky as each one goes by fast so be ready! Again, plan in advance.

      As Dr. Baird points out, the poster/networking sessions are really wonderful. A lot of critical data that might not be as “flashy” is buried in the posters and you are likely to learn a lot. Even more importantly you will have a chance to network and find out who around the world is focusing in the same areas where you have interests. There are 2 poster sessions each day. The poster sessions are particularly great because you actually get to interact with people. If you see someone you want to talk to at the poster session do not be intimidated if they happen to be a “name” you have read multiple times in key papers. Everyone is excited to meet eager people working to help fight lung cancer!

      The importance of networking cannot be over-emphasized. Getting to know the field and others who share your passion for fighting lung cancer and other thoracic malignancies can make a tremendous impact on your future academic career. Branch out and meet people in other disciplines and from other parts of the world. Having a common interest in fighting lung cancer can lead to some strong connections and it is incredibly fun to attend future conferences knowing that you will get to connect with friends you met at your first IASLC WCLC. Important collaborations can also be started including international efforts. If you are still in training this networking time is also critical to your future job hunting!

      Remember to have FUN! Sign up and attend the IASLC social events. These involve good food, great music and sometimes dancing and most importantly a real opportunity to network.

      Saturday – Opening Ceremony and Welcome Reception

      Monday - IASLC Foundation Road to Hope gala

      Tuesday - Closing Ceremony

      After running around at the conference there will be times you just want to sit and relax. Fortunately there is an IASLC membership lounge in the exhibit hall open during exhibit hours. All members are invited to use the space for meetings, to sit for a few minutes, and to learn more about the IASLC and its committees. More details can be found here: https://wclc2019.iaslc.org/networking_opportunities/

      Also, make some time before or after the conference to be a tourist in the local region. Most convention centers are fairly similar, but thinking about the last 3 IASLC WCLC conferences you can imagine how Yokohama, Toronto and Barcelona are all very different and fabulous places to explore.

      Enjoy your first IASLC WCLC and hopefully you will plan to make it an annual event!

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      IASLC Members: To view this content or have the option to purchase this event, click here to login.
      Conference Attendees & Access Code holders: Click here to enter your Access Code. Already entered your Access Code? Please login.

    • +

      YI01.04 - Congratulations, Your Abstract Has Been Accepted, and Now? - Tips and Tricks to Prepare a Presentation for WCLC (Now Available) (ID 3693)

      07:00 - 08:30  |  Presenting Author(s): Benjamin J Solomon

      • Abstract
      • Presentation
      • Slides

      Abstract

      This presentation will provide a practical guide about how to prepare and deliver an effective and engaging presentation at WCLC. Tips and suggestions will be provided for oral presentations, miniorals, posters and E-posters.

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      IASLC Members: To view this content or have the option to purchase this event, click here to login.
      Conference Attendees & Access Code holders: Click here to enter your Access Code. Already entered your Access Code? Please login.