Virtual Library

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    ES07 - Thoracic Ultrasonography: Diagnosis and Staging (ID 10)

    • Event: WCLC 2019
    • Type: Educational Session
    • Track: Interventional Diagnostics/Pulmonology
    • Presentations: 4
    • Now Available
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      ES07.01 - Transthoracic Ultrasonography (Now Available) (ID 3186)

      13:30 - 15:00  |  Presenting Author(s): Najib M Rahman

      • Abstract
      • Presentation
      • Slides

      Abstract

      This presentation will review data on the utility of thoracic ultrasound in diagnosis, staging and subsequent management of malignant thoracic and pleural disease.

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      ES07.02 - Linear Endosonography (EBUS & EUS) (Now Available) (ID 3187)

      13:30 - 15:00  |  Presenting Author(s): Laurence M.M.J Crombag

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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      ES07.03 - Radial Endosonography (Now Available) (ID 3188)

      13:30 - 15:00  |  Presenting Author(s): Laurence M.M.J Crombag

      • Abstract
      • Presentation
      • Slides

      Abstract

      Radial Endosonography

      Flexible bronchoscopy, with its attendant procedures, is a valuable tool for diagnosis and staging of patients with suspected lung cancer. The development of endobronchial ultrasound (EBUS) has extended the view of the bronchoscopist beyond the bronchial wall. Two types of EBUS exist. The curved linear (convex) probe EBUS and the radial probe EBUS. The convex ultrasound transducer is located at the tip of a flexible bronchoscope (linear scanning EBUS) and allows real-time sampling. This technique is mainly used for mediastinal nodal staging and assessment of centrally located lung tumours when lung cancer is known or suspected. The radial EBUS probe houses a rotating ultrasound transducer at the distal end which produces a high-resolution radial (360˚) ultrasound image of the airway wall and surrounding structures. This probe is inserted through the biopsy channel of a standard bronchoscope. In a lung cancer setting, this technique is used for evaluation of the depth of tumour invasion in the central airways enabling differentiation between early and invasive lung cancer and detection of peripheral pulmonary lesions (PPLs). Radial EBUS does not permit sampling in real-time such that sequential sampling with separate equipment is necessary. The current focus of this abstract is the role of radial EBUS for PPLs.

      With the increased use of chest CT-scans, the frequency of incidentally found PPLs has increased as well. Guidelines advise to evaluate and manage individuals with pulmonary nodules by estimating the probability of malignancy. The goal is to diagnose a malignancy promptly for timely treatment and to avoid invasive procedures and surgery in patients with benign lesions. Approaches to establish a tissue diagnosis include imaging-guided transthoracic and bronchoscopic sampling techniques.

      The sensitivity of traditional flexible bronchoscopy - with or without fluoroscopic guidance – for peripheral lesions in patients suspected of having lung cancer is suboptimal and is affected most by the size of the lesion (<2cm 34%; >2cm 63%).(1) For PPLs, the sensitivity of transthoracic needle aspiration (TTNA) is greater than that of bronchoscopy. In this setting, TTNA has an approximately 90% chance of providing confirmation of a diagnosis. However, CT-guided percutaneous TTNA has a considerable risk of pneumothorax.(1) This has led to the development of new modalities as radial EBUS, virtual bronchoscopy, electromagnetic navigation bronchoscopy and ultrathin bronchoscopes.

      In 2002, radial EBUS was first used to guide transbronchial lung biopsy (TBLB).(2) Numerous papers has been published since, reporting varying diagnostic performances of radial EBUS. Three systematic reviews and meta-analyses report a sensitivity of radial EBUS for diagnosis of peripheral lesions of 70% to 73%. Although there is considerable heterogeneity in lesion size, prevalence of malignancy, variable use of additional image guiding technology and reference standard in included studies.(3-5)

      The diagnostic yield of radial EBUS is significantly higher for lesion > 2 cm in size, malignant in nature and those associated with a bronchus sign on CT scan.(3-5) The diagnostic yield is also higher when the radial EBUS probe is in the center of the lesion opposed to being adjacent to it.(3) The diagnostic yield of radial EBUS does not exceed CT-guided percutaneous needle biopsy / aspiration. The major advantage of radial EBUS over a transthoracic approach is its safety profile (overall pneumothorax rate of just 1.0%)(4) and the ability to combine with staging procedures.

      In conclusion, to diagnose PPLs (not visible by bronchoscopy) radial EBUS is a safe and has a reasonably high diagnostic yield. Main limitations of the technique include operator dependence and the need for sequential sampling as radial EBUS does not allow real-time sampling.

      1. Rivera MP, Mehta AC, Wahidi MM. Establishing the diagnosis of lung cancer: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2013;143(5 Suppl):e142S-e65S.

      2. Herth FJ, Ernst A, Becker HD. Endobronchial ultrasound-guided transbronchial lung biopsy in solitary pulmonary nodules and peripheral lesions. The European respiratory journal. 2002;20(4):972-

      3. Ali MS, Trick W, Mba BI, Mohananey D, Sethi J, Musani AI. Radial endobronchial ultrasound for the diagnosis of peripheral pulmonary lesions: A systematic review and meta-analysis. Respirology (Carlton, Vic). 2017;22(3):443-53.

      4. Steinfort DP, Khor YH, Manser RL, Irving LB. Radial probe endobronchial ultrasound for the diagnosis of peripheral lung cancer: systematic review and meta-analysis. The European respiratory journal. 2011;37(4):902-10.

      5. Wang Memoli JS, Nietert PJ, Silvestri GA. Meta-analysis of guided bronchoscopy for the evaluation of the pulmonary nodule. Chest. 2012;142(2):385-93.

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      ES07.04 - Predictive Molecular Testing on Small Biopsy Samples (Now Available) (ID 3189)

      13:30 - 15:00  |  Presenting Author(s): Christophe Dooms

      • Abstract
      • Presentation
      • Slides

      Abstract

      According to international guidelines for molecular testing as updated in 2018, any lung cancer sample (tissue biopsy or cytology) with adenocarcinoma or not-otherwise specified (NOS) histology and adequate tumor cellularity should be tested for routinely treatable mutations with a turnaround time of no more than 10 working days.1,2 Single gene testing or restricted hotspot testing methods were developed to screen for EGFR p.Leu858Arg mutations or deletions with the exon 19 in advanced stage non-small cell lung cancer. Next-generation sequencing (NGS) platforms have facilitated multigene mutational profiling using small amounts of nanograms (ng) of DNA, making the NGS technology attractive for and applicable to small biopsy and cytology specimens. NGS and especially targeted NGS panels were rapidly validated for small biopsy samples and implemented in diagnostic laboratories as they focus on hotspot regions and frequently altered genes with direct and known consequence on therapy.3,4 Compared to sequential single-gene testing, targeted NGS is considerably faster and more cost-effective.5

      There are however several barriers to universal broad biomarker testing. Despite most tests can be run on only small biopsy and cytology specimen, in real world testing rates are far from 100% (even for EGFR, ALK and ROS1 testing) and up to 25% of samples lack sufficient tumor material in small biopsies. Molecular testing accuracy depends on multiple factors that include overall tumor cellularity, method of fixation, tumor fraction of the sample, and the analytical sensitivity of the molecular testing platform used for the analysis. Pre-analytical strategies to improve testing success are: (1) work with dedicated interventionalists (e.g. radiology, pulmonology) to get sufficient tissue as one single pass is not enough, (2) work with dedicated pathologists to enhance quality control and reflex testing, and (3) consider ROSE.

      In a reference center with dedicated interventionalists, a dropout rate of 3.4% was observed either due to quantitatively insufficient tumor material or inadequate nucleic acid quality based on a series of 3,000 consecutive lung cancer cases that were sequenced.6 In a randomized trial comparing two different needle sizes and a turn-around team (interventional pulmonologist, pathologist, molecular biologist) using standard operating procedures, several conclusions could be drawn given a successful NGS testing rate for all clinically relevant genes in 96% of samples.7 Four needle passes were needed to obtain adequate material for molecular analysis. A tissue core was reported present in almost 70% of specimens for both needle types. Less than 3% of samples had tumor cellularity of <10%, and there was no significant difference in tumor cellularity between 19G and 22G needles. Both the tumor surface area measured and the amount of DNA extracted from the selected cell block were larger for the 19G compared to the 22G specimen, with a median tumor surface area of 4.91 mm2 vs 2.35 mm2 and median DNA extracted of 1150 ng vs 818 ng, respectively.

      There is a paucity of articles outlining best practice guidelines for immunocytochemistry. With proper optimization and rigorous quality control, high-quality staining can be achieved on cellblock and non-cellblock preparations.8 Cytology preparations that are non-formalin-fixed provide the best alternative source of well-preserved DNA.

      Cytology specimens allow for rapid on-site adequacy assessment (ROSE), which can ensure the collection of adequate and sufficient material for ancillary studies including immunohistochemistry and molecular testing. Although there are no universally accepted criteria for EBUS-TBNA lymph node adequacy, structured semi-quantitative scoring schemes for ROSE and diagnostic category assignments have been proposed. The decision of whether or not to provide ROSE for EBUS-TBNA procedures is largely institution dependent. Validation studies are essential with correct implementation of these pre-analytical factors for any molecular testing in cytologic samples.

      In conclusion, a single NGS panel test covering all clinical relevant markers is most tissue and cost efficient. Strategies to obtain a higher rate of successful testing, even on only small biopsy and cytology specimens should be considered whenever needed: reflex testing, dedicated interventionalists, and strong communication with all team members.

      References.

      1. Lindeman NI, Cagle PT, Aisner DL, et al. Updated Molecular Testing Guideline for the Selection of Lung Cancer Patients for Treatment With Targeted Tyrosine Kinase Inhibitors: Guideline From the College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology. J Mol Diagn. 2018 Mar;20(2):129-159.

      2. Kalemkerian GP, Narula N, Kennedy EB, et al. Molecular Testing Guideline for the Selection of Patients With Lung Cancer for Treatment With Targeted Tyrosine Kinase Inhibitors: American Society of Clinical Oncology Endorsement of the College of American Pathologists/International Association for the Study of Lung Cancer/Association for Molecular Pathology. Clinical Practice Guideline Update. J Clin Oncol. 2018 Mar 20;36(9):911-919.

      3. Bennett N, Farah C. Next-generation sequencing in clinical oncology: next steps towards clinical validation. Cancers 2014;6:2296-2312.

      4. Le Mercier M, De Nève N, Blanchard O, et al. Clinical application of targeted next generation sequencing for lung cancer patients. Belgian J Med Oncol 2015;27:2-8.

      5. Pennell N, Mutebi A, Zhou Z, et al. Economic impact of next-generation sequencing vs sequential single-gene testing modalities to detect genomic alterations in metastatic non-small cell lung cancer using a decision analytic model. J Clin Oncol 2018;36(15_suppl):9031-9031

      6. Volckmar AL, Leichsenring J, Kirchner M, et al. Combined targeted DNA and RNA sequencing of advanced NSCLC in routine molecular diagnostics: Analysis of the first 3,000 Heidelberg cases. Int J Cancer. 2019 Jan 17. doi: 10.1002/ijc.32133. [Epub ahead of print]

      7. Dooms C, Vander Borght S, Yserbyt J, et al. A Randomized Clinical Trial of Flex 19G Needles versus 22G Needles for Endobronchial Ultrasonography in Suspected Lung Cancer. Respiration. 2018;96(3):275-282.

      8. Jain D, Nambirajan A, Borczuk A, et al; IASLC Pathology Committee. Immunocytochemistry for predictive biomarker testing in lung cancer cytology. Cancer Cytopathol. 2019 May;127(5):325-339.

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    ES26 - The Impact of Specialist Nursing and Allied Health Professionals in the Care of Thoracic Oncology Patients (ID 28)

    • Event: WCLC 2019
    • Type: Educational Session
    • Track: Nursing and Allied Professionals
    • Presentations: 4
    • Now Available
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      ES26.01 - The Impact of Specialist Nursing Intervention in Lung Cancer (Now Available) (ID 3292)

      14:30 - 15:45  |  Presenting Author(s): Alison Leary

      • Abstract
      • Presentation
      • Slides

      Abstract

      The Impact of Specialist Nursing Intervention in Lung Cancer

      Alison Leary on behalf of

      Iain Stewarta, , Aamir Khakwania , Richard B. Hubbarda , Paul Beckettb , Diana Borthwickc , Angela Toddd , Alison Learye , Laila J. Tataa

      A Division of Epidemiology and Public Health, University of Nottingham, NG5 1PB, UK

      B Derby Teaching Hospitals NHS Foundation Trust, DE22 3NE, UK

      c Edinburgh Cancer Centre, Western General Hospital, EH4 2JT, UK

      d School of Nursing and Midwifery, University of Sheffield, S10 2LA, UK

      e School of Primary & Social Care, London South Bank University, SE1 0AA, UK

      Introduction

      In the UK the role of the Clinical Nurse Specialist is well established. Lung Cancer Clinical Nurse Specialists (LCNS) often start a therapeutic relationship with patients and families before formal diagnosis has been made. LCNS often manage the care of people with lung cancer but in an environment of austerity their worth to employers is still questioned.

      This series of studies examined the impact of the LCNS on outcomes for lung cancer patients.

      The focus of this abstract is one of the studies which looks at receipt of treatment for lung cancer.

      Treatment choices for people with lung cancer may be influenced by contact and engagement with lung cancer nurse specialists (LCNSs). We investigated how service factors, LCNS workload, and LCNS working practices may influence the receipt of anticancer treatment.

      Materials and methods

      English National Lung Cancer Audit data and inpatient Hospital Episode Statistics for 109,079 people with lung cancer surviving 30 days from diagnosis were linked along with LCNS workforce census data and a bespoke nationwide LCNS survey. Multinomial logistic regression was used to determine adjusted relative risk ratios (RRRs) for receipt of anticancer therapies associated with LCNS assessment, LCNS workforce composition, caseload, LCNS reported working practices, treatment facilities at the patients’ attending hospitals, and the size of the lung cancer service.

      Results

      Assessment by an LCNS was the strongest independent predictor for receipt of anticancer therapy, with early LCNS assessments being particularly associated with greater receipt of surgery (RRR 1.85, 95%CI 1.63–2.11). For people we considered clinically suitable for surgery, receipt was 55%. Large LCNS caseloads were associated with decreased receipt of surgery among suitable patients (RRR 0.71, 95%CI 0.51–0.97) for caseloads >250 compared to ≤150. Reported LCNS working practices were associated with receipt of surgery, particularly provision of psychological support (RRR 1.60, 95%CI 1.02–2.51) and social support (RRR 1.56, 95%CI 1.07–2.28).

      table1abstract.jpg

      Conclusion

      LCNS assessment, workload, and working practices are associated with the likelihood of patients receiving anticancer therapy. Enabling and supporting LCNSs to undertake key case management interventions offers an opportunity to improve treatment uptake and reduce the apparent gap in receipt of surgery for those suitable

      Early nurse specialist contact is associated with greater receipt of therapy.

      •Receipt of surgery is less likely where nurse specialists have large caseloads.

      •Therapy receipt is more likely if key nursing interventions are routinely provided.

      •Managing nurse specialists’ workload could address disparities in therapy uptake.

      Are working practices of lung cancer nurse specialists associated with variation in peoples’ receipt of anticancer therapy? (2018) Stewart, Iain et al. Lung Cancer, Volume 123, 160 – 165

      https://www.lungcancerjournal.info/article/S0169-5002(18)30482-3/pdf

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      ES26.02 - Rehabilitation After Treatment of Thoracic Malignancies (Now Available) (ID 3293)

      14:30 - 15:45  |  Presenting Author(s): Chris L Wells

      • Abstract
      • Presentation
      • Slides

      Abstract

      In this presentation the speaker will focus the talk on the collaborative model between the Departments of Nursing and Rehabilitation Services in the promotion of functional recovery of hospitalized adults. The speaker will incorporate the current literature regarding early mobilization and rehabilitation and the program's effects on outcomes. The talk will also examine the physical impairments and functional limitations associated with cancer associated frailty. Finally, the speaker will share some priminary data from the efforts at the University of Maryland Medical Center on the implementation of a collaborative mobilization and rehabilitation program to address barriers to recovery and hospital discharge.

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      ES26.03 - The Impact of Early Nursing Intervention on Outcomes for Thoracic Oncology Patients (Now Available) (ID 3295)

      14:30 - 15:45  |  Presenting Author(s): Iveta Nohavova

      • Abstract
      • Presentation
      • Slides

      Abstract

      Introduction: The roles of nurses vary from cancer screening, detection, and prevention, to active clinical assessment, treatment administration or symptom management. These various aspects play part when raising public awareness of important role of prevention. One of the very effective examples of an early health intervention is prevention of no tobacco use uptake or quitting using tobacco products in order to enhance health outcomes. The latest WHO/Europe report1 “European tobacco use – trends report 2019” shows tobacco use continues to be a paramount public health issue. At the same time, it is estimated 90% of lung cancers (incl. tracheal or bronchal) could be avoided if tobacco use is eliminated. Sadly, the WHO European Region has the highest proportion of tobacco use in the world, with an estimated 29% of population using tobacco. Nurses can help.

      Methods: A review of guidelines and recommendations for nurses to use in daily practice will be presented.

      Results: Not applicable

      Conclusions: With prevention must be the key priority action, such focused early nurses interventions can contribute to timely diagnosis of the cancer positively impacting outcomes of thoracic oncology patients, including quality of life and care experience. Nurses are ideally positioned to assume this role. This presentation will explore current evidence related to the role of cancer nurse in early interventions to thoracic cancer patients‘ outcomes. The session will include discussion and recommendations to increase role of nurses in prevention of tobacco use.

      References:

      1. WHO (2019). European Tobacco Use: Trends Report 2019. Retrieved from http://www.euro.who.int/__data/assets/pdf_file/0009/402777/Tobacco-Trends-Report-ENG-WEB.pdf

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      ES26.04 - Early Intervention and Rehabilitation for Patients Newly Diagnosed with Thoracic Malignancies (Now Available) (ID 3296)

      14:30 - 15:45  |  Presenting Author(s): Morten Quist

      • Abstract
      • Presentation
      • Slides

      Abstract

      This presentation will outline the rationale, role and evidence supporting early Intervention and rehabilitation for patients newly diagnosed with thoracic malignancies. Thoracic malignancies are associated with high disease burden and increased inactivity. Newly diagnosed Individuals with thoracic malignancies experience complex symptoms, which can include dyspnoea, fatigue and pain. These frequently lead to a cycle of inactivity and functional decline. Individuals with thoracic malignancies are less physically active than similar aged healthy peers at time of diagnosis, with less than 40% meeting the physical activity guidelines (1). Following diagnosis, physical activity levels are lowest whilst patients undergo treatment and do not recover back to pretreatment levels within six months. Progressive functional decline occurs over time, with reduction in exercise capacity and muscle strength (1). In thoracic malignancies, reduced exercise performance is associated with poorer functional independence, worse cancer treatment tolerability and higher all-cause mortality (2). People with thoracic malignancies, who are less physically active, have worse symptoms, and poorer exercise capacity and health-related quality of life (HRQoL) compared to those who are more active (1). This is supported and linked with the research by Gralla et al in 2014 (3) who identified key issues that patients with thoracic malignancies mainly fear. Gralla el al described the five rated issues which were: maintaining independence, ability to perform normal daily activities, ability to sleep, not being a burden for caregivers and not being fatigued, in a survey among 660 patients with lung cancer. Moreover, up to 44% of patients with thoracic malignancies experience depression and anxiety symptoms, which is consistently higher than other cancers types, and psychological distress has also been proven to affect anti-cancer treatment and mortality (4).

      Supervised high-intensity exercise training is associated with improved exercise capacity and QOL in most cancer patients (5). Systematic reviews have reported that both pre- and postoperative exercise interventions are safe and feasible for patients with operable thoracic malignancies, and suggest benefits on exercise capacity, symptoms as fatigue and some domains of QOL (6). However, this evidence does not include patients with advanced inoperable thoracic malignancies. Although research groups have previously shown that exercise in these patients is safe, feasible, and beneficial (7), conclusive randomized controlled trials (RCT) still remain to be carried out to determine the effect of exercise for patients with advanced inoperable thoracic malignancies. But larger RCT within this group of patients is currently finished and ongoing and within the next few years the evidence will increase. Next step though is to implement evidence into daily practice.

      1. Granger CL, McDonald CF, Irving L, Clark RA, Gough K, Murnane A, et al. Low physical activity levels and functional decline in individuals with lung cancer. Lung Cancer. 2014;83(2):292-9.

      2. Jones LW, Hornsby WE, Goetzinger A, Forbes LM, Sherrard EL, Quist M, et al. Prognostic significance of functional capacity and exercise behavior in patients with metastatic non-small cell lung cancer. Lung Cancer. 2012;76(2):248-52.

      3. Gralla RJ, Hollen PJ, Msaouel P, Davis BV, Petersen J. An evidence-based determination of issues affecting quality of life and patient-reported outcomes in lung cancer: results of a survey of 660 patients. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer. 2014;9(9):1243-8.

      4. Sullivan DR, Ganzini L, Duckart JP, Lopez-Chavez A, Deffebach ME, Thielke SM, et al. Treatment receipt and outcomes among lung cancer patients with depression. Clinical oncology (Royal College of Radiologists (Great Britain)). 2014;26(1):25-31.

      5. Buffart LM, Kalter J, Sweegers MG, Courneya KS, Newton RU, Aaronson NK, et al. Effects and moderators of exercise on quality of life and physical function in patients with cancer: An individual patient data meta-analysis of 34 RCTs. Cancer treatment reviews. 2017;52:91-104.

      6. Ni HJ, Pudasaini B, Yuan XT, Li HF, Shi L, Yuan P. Exercise Training for Patients Pre- and Postsurgically Treated for Non-Small Cell Lung Cancer: A Systematic Review and Meta-analysis. Integr Cancer Ther. 2016.

      7. Quist M, Adamsen L, Rorth M, Laursen JH, Christensen KB, Langer SW. The Impact of a Multidimensional Exercise Intervention on Physical and Functional Capacity, Anxiety, and Depression in Patients With Advanced-Stage Lung Cancer Undergoing Chemotherapy. Integr Cancer Ther. 2015;14(4):341-9.

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    IBS10 - Tracheal Tumours (Ticketed Session) (ID 47)

    • Event: WCLC 2019
    • Type: Interactive Breakfast Session
    • Track: Thymoma/Other Thoracic Malignancies
    • Presentations: 2
    • Now Available
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      IBS10.01 - Surgerical Treatment of Tracheal Tumours (Now Available) (ID 3363)

      07:00 - 08:00  |  Presenting Author(s): Mir Alireza Hoda  |  Author(s): Walter Klepetko

      • Abstract
      • Presentation
      • Slides

      Abstract

      Tracheal tumors are relatively rare and account only for <1% of all malignant diseases.1 The most common types of primary tracheal tumors are squamous cell carcinoma and adenoid cystic carcinoma, which represent together two thirds of all primary tracheal tumors.2 Additionally, patients with secondary tracheal tumors might benefit from resection of the tumor including the trachea.

      Surgical procedures involving the trachea require a meticulous pre-operative planning, advanced surgical techniques and infrastructural prerequisites. Therefore, surgical resections of tracheal tumors are highly elective procedures at specialized centers. The preoperative work-up includes the histological verification of the tumor via bronchoscopy, which is usually combined with the determination of the estimated extend of resection. Moreover, radiologic imaging, preferably PET-CT, completes the tumor staging. Patients with locally advanced and initially unresectable tracheal tumors might be candidates for neoadjuvant therapy. Usually, neoadjuvant treatment consisting of sole chemotherapy is preferred, as radiation therapy may negatively impact the anastomotic healing. If the patient received induction therapy, the radiological imaging as well as the bronchoscopic evaluation has to be repeated after completion of the induction therapy to confirm the response to the therapy and to plan the surgical procedure.

      The most common approaches for tracheal resection include cervicotomy, partial or complete sternofissure, and posterolateral thoracotomy. The optimal surgical approach has to be chosen according the location and extent of the tumor. During surgery, special care should be taken to preserve the lateral blood supply of the trachea, to protect the recurrent nerves and to avoid excessive tension on the anastomosis. Inadequate surgical technique increases the risk for anastomotic insufficiency, which is a potentially life-threatening complication. In the literature, anastomotic complications (i.e. partial or complete dehiscence, granuloma or re-stenosis) occur in approximately 9% cases after tracheal surgery. The risk for anastomotic complications increases with the length of resection, diabetes mellitus and previous treatments.3 As the airway in tracheal surgery has to be shared with the anesthesiologist, an appropriate ventilation strategy during induction of anesthesia, surgical preparation and at the end of the surgical procedure has to be defined. Although the double-lumen tube is routinely used in thoracic surgery, it has only a negligible role in airway surgery. The preferably used devices in airway surgery are the laryngeal mask, single-lumen endotracheal tube, high-frequency jet ventilation catheters and cross-table ventilation using a sterile endotracheal tube. Moreover, extracorporal membranoxygenation (ECMO) support is a valid option for selected, complex resections. It provides the advantage to operate on the patient without any airway device in the surgical field. A veno-venous ECMO is sufficient to fully substitute respiration. However, cardiorespiratory support by a veno-arterial ECMO configuration might be a valid option in some patients. In summary, the ventilation strategy is dependent on the location of the location, availability of devices, experience of the team and personal preferences. Therefore, planning the ventilation strategy is crucial for a successful surgical procedure.

      Similar to the surgical treatment of other solid malignancies, the major aim of tracheal surgery is the radical resection of the tumor including all loco-regional lymph nodes. The adenoid-cystic carcinoma represents an exemption from this rule. Due to its low-malignant tumor biology and the susceptibility to radiotherapy, even incomplete resection is acceptable in this tumor entity. As the adenoid-cystic carcinoma is characterized by a longitudinal, submucosal growth pattern (Figure 1), there might be a discrepancy between the resection length needed to obtain a complete resection and the technical possibility to perform a tension-free anastomosis. An incomplete resection combined with an adjuvant radiation therapy is therefore a valid treatment option in patients with adenoid-cystic carcinoma. Radiotherapy can be initiated as bronchoscopy confirms complete healing of the anastomosis approximately 6-8 weeks after surgery.

      Although the treatment of patients with tracheal tumors is demanding, an excellent perioperative and long-term outcome of patients with tracheal tumors can be achieved. In experienced hands, the peri-operative mortality after tracheal resection is <1%.4 Moreover, surgery in multimodality treatment concept provides a very good long-term overall survival, which is especially true for adenoid- cystic carcinoma in which a 5-year overall survival up to 91% can be achieved.5

      In summary, the surgical treatment of tracheal tumors is technically demanding and should therefore be performed at high-volume centers. Within the heterogeneity of tracheal tumors, the adenoid-cystic carcinoma represents a unique tumor entity. Embedded in a multimodal treatment concept, excellent long-term outcome can be achieved despite incomplete surgical resection. After careful planning by a multidisciplinary team, even extended tracheal resections for malignant disease can be performed safely with a very low morbidity and mortality.

      iaslc.jpg

      Figure 1: Computed tomography of a 70 year-old with adenoid cystic carcinoma of the trachea. Note the longitudinal tumor growth pattern (red bracket).

      1. Grillo HC. Surgery of the trachea and bronchi. Hamilton, Ont. ; Lewiston, NY: BC Decker; 2004.

      2. Mallick S, Benson R, Giridhar P, Rajan Singh A, Rath GK. Demography, patterns of care and survival outcomes in patients with malignant tumors of trachea: A systematic review and individual patient data analysis of 733 patients. Lung Cancer. 2019;132:87-93.

      3. Wright CD, Grillo HC, Wain JC, et al. Anastomotic complications after tracheal resection: prognostic factors and management. The Journal of thoracic and cardiovascular surgery. 2004;128(5):731-739.

      4. Auchincloss HG, Wright CD. Complications after tracheal resection and reconstruction: prevention and treatment. J Thorac Dis. 2016;8(Suppl 2):S160-167.

      5. Urdaneta AI, Yu JB, Wilson LD. Population based cancer registry analysis of primary tracheal carcinoma. Am J Clin Oncol. 2011;34(1):32-37.

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      IBS10.02 - Endoscopic Treatment of Unresectable Tumors of the Trachea (Now Available) (ID 3364)

      07:00 - 08:00  |  Presenting Author(s): Jiayuan Sun

      • Abstract
      • Presentation
      • Slides

      Abstract

      Surgical excision and reconstruction remain the recommended treatment approachs for patients with trachea tumors. However, it is associated with significant trauma and the risk of severely damaged pulmonary function, and not all patients are therefore willing to receive or fit for surgical resection. Traditional chemotherapy and radiotherapy can’t improve the prognosis of these patients, which requires a multidisciplinary treatment. Endoscopic treatments, including electrocoagulation, argon plasma coagulation (APC), laser, photodynamic therapy (PDT), cryotherapy, balloon dilatation, stent placement, etc., have been demonstrated to be effective methods in the treatment of the trachea tumors.

      For tracheostenosis caused by malignant tumors, the first thing we should do is to relieve the symptoms and keep stable vital signs, so that we can seek chance for the patients to receive other therapies. Ablation therapy only or ablation therapy combined with stent placement are recommended for intraluminal obstructive stenosis. For external pressure stenosis and mixed stenosis, stent placement only and ablation therapy combined with stent placement are recommended, respectively.

      Some endoscopic treatments are also recommended for patient with early central lung cancer that is ineligible for surgery by British Thoracic Society Guidelines and American College of Chest Physicians Guidelines [1,2]. Endobronchial ultrasonography can help determine the depth of tumor invasion of the tracheobronchial wall, which can be used for the staging of early central lung cancer to provide guidance for the treatment [3]. Previous study demonstrated that cryotherapy was an effective method in early superficial bronchogenic carcinoma, which could be proposed as a first-line therapy in the population with high carcinogenic risk [4]. Hybrid technology, an innovate technique, combining water jet function with APC, is being used in the clinical practice. It can create a water cushion, providing shelter for the tissues under submucosa, and then the lesion can be ablated effectively and safely (Figure 1) [5].

      Endoscopic treatments are performed through natural orifice and have advantages of less trauma, repeatability and lower cost, which is becoming one of the most important treatment methods. Patients can benefit more from endoscopic treatments, especially in patients with unresectable tumors, low-grade malignant trachea tumors, early central lung cancers, and benign trachea tumors.

      Reference

      1. Kennedy TC, McWilliams A, Edell E, et al. Bronchial intraepithelial neoplasia/early central airways lung cancer: ACCP evidence-based clinical practice guidelines (2nd edition). Chest 2007; 132(3 Suppl):221S-233S.

      2. Du Rand IA, Barber PV, Goldring J, et al. Summary of the British Thoracic Society guidelines for advanced diagnostic and therapeutic flexible bronchoscopy in adults. Thorax 2011; 66(11):1014-1015.

      3. Kurimoto N, Murayama M, Yoshioka S, et al. Assessment of usefulness of endobronchial ultrasonography in determination of depth of tracheobronchial tumor invasion. Chest 1999; 115(6):1500-1506.

      4. Deygas N, Froudarakis M, Ozenne G, et al. Cryotherapy in early superficial bronchogenic carcinoma. Chest 2001; 120(1):26-31.

      5. Zheng X, Herth FJ, Sun J. Initial Experience with Hybrid-Argon Plasma Coagulation as a Novel Local Treatment Method for Tracheobronchial Mucoepidermoid Carcinoma. Respiration 2019. Accepted.

      figure 1.png

      Figure 1. Hybrid-Argon Plasma Coagulation (APC) therapy in the treatment of an adult patient with tracheobronchial mucoepidermoid carcinoma. CT showed a nodule in intermediate bronchus, completely obstructing the airway (A1-2); large neoplasm in the intermediate bronchus detected by WLB, AFI, and NBI (A3-5); pathologic images indicated MEC (A6-8); invasivion size evaluated by rpEBUS after snare incision (B1-3); light blue water cushion created by Hybrid-APC (B4); Hybrid-APC ablation (B5-6); bronchoscopic inspection by WLB, AFI, and NBI, and evaluation by rpEBUS after first Hybrid-APC therapy (C1-4); light blue cushion created by Hybrid-APC (C5); 2nd Hybrid-APC ablation (C6); CT scan at 4-month follow-up revealed no recurrence (D1-2); bronchoscopy reexamination by WLB and AFI and invasive evaluation by rpEBUS at 4-month follow-up (D3-5); pathological images at 4-month follow-up revealed no recurrence (D6).

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    IBS20 - Endoscopic Solution to Iatrogenic Complications (Interactive Q and A) (Ticketed Session) (ID 60)

    • Event: WCLC 2019
    • Type: Interactive Breakfast Session
    • Track: Interventional Diagnostics/Pulmonology
    • Presentations: 2
    • Now Available
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      IBS20.01 - Airway Fistulas (Now Available) (ID 3405)

      07:00 - 08:00  |  Presenting Author(s): Johannes M.A. Daniels

      • Abstract
      • Presentation
      • Slides

      Abstract

      Introduction

      Airway fistula as an iatrogenic complication of lung cancer treatments present a particular challenge to the multidisciplinary lung cancer team. It is a rare but very severe complication which requires prompt treatment because of the involved disruption of the natural tissue barriers against infection. Different types of fistulas exist, the most common airway fistulas that are encountered after lung cancer treatment are bronchopleural fistula (BPF) and tracheo or broncho-oesophageal fistula (T/BEF). These are two very different entities that require their own specific management.

      Bronchopleural fistula

      BPF is a feared complication after anatomical resection of lung cancer, occurring in 1-4% of the patients [1-3]. Rare causes of BPF in lung cancer patients can include destruction of the airway wall by direct tumor invasion and airway wall necrosis after high-dose radiotherapy. Presenting symptoms can be cough, empyema, persistent air leak and hemoptysis. Significant dyspnea can occur because of increased dead space ventilation if there is a massive air leak. The diagnosis can be made by bronchoscopy and if the bronchoscopist cannot see a fistula, deposition of methylene blue at the site of the stump can help. In case of persistent air leak and no identifiable airway fistula, an alveolar-pleural fistula (more common) should be considered. Imaging techniques such as chest X-ray and CT scan can help to diagnose ensuing pneumothorax and empyema and in large fistulas can sometimes be visualized.

      The management of BPF can be challenging, especially in complicated empyema, frail patients who have already deteriorated during the postoperative phase and patients that underwent salvage surgery after high-dose radiotherapy [4]. Small BPF (up to 8 mm) without surrounding necrosis can be managed by endoscopically with the help of polyvinyl alcohol sponge and cyanoacrylate glue [5,6]. Larger BPF, presence of airway wall necrosis or failure to close the BPF endoscopically is a reason for surgery. Reconstruction of the stump or anastomosis can be followed by adding a muscle flap to improve perfusion. In case of necrosis, debridement should precede these procedures. Extensive airway necrosis sometimes renders surgical repair impossible. In case of complex empyema, open window thoracostomy can be necessary, especially if more conservative measures have been unsuccessful.

      Tracheo-esophageal and broncho-esophageal fistula

      T/BEF is a relatively common complication in patients with esophageal cancer (5-15%), but rare in lung cancer patients (1%)[7-10]. Symptoms include cough, especially during intake of food or liquids, infection (bronchitis, pneumonia), recurrent aspiration and weight loss. In patients with lung cancer, the most important causes are malignant invasion of the membranous part of the trachea or bronchi and high-dose radiotherapy with involvement of airways in close proximity to the esophagus (trachea and proximal left main bronchus). The diagnosis can be made with contrast-enhanced esophagography, demonstrating displacement of the contrast into the lung. Bronchoscopy can be used to localize the fistula, to determine its extent, to assess the vitality of the surrounding airway wall and to evacuate aspirated liquids and mucus from the central airways.

      Immediate treatment is crucial to avoid deterioration of the patient. To minimize further aspiration, oral intake should be eliminated and adequate measures should be taken to minimize reflux and ensure adequate feeding (e.g. gastro-/jejunostomy or total parenteral nutrition). Small fistulas (up to 5 mm) can be treated endoscopically with cyanoacrylate glue or clips. Larger fistulas can be treated with an esophageal stent, airway stent or a combination: double stenting. In case of insufficient effect of a esophageal stent or concomitant airway obstruction, double stenting is preferable and seems to provide better survival than a single stent [11,12]. It is important to realize that pressure on the fragile tissues between both stents can further enlarge the T/BEF. Often multiple endoscopic interventions are required to achieve and maintain adequate palliation.

      During this presentation the management of airway fistulas will be discussed, with emphasis on the bronchoscopic techniques such as (double) stenting and the application of cyanoacrylate glue. Selection of patients, alternative solutions and specific endoscopic techniques will be important topics.

      References

      Asamura H, Naruke T, Tsuchiya R, Goya T, Kondo H, Suemasu K. Bronchopleural fistulas associated with lung cancer operations univariate and multivariate analysis of risk factors, management, and outcome. J Thorac Cardiovasc Surg 1992;104:1456–63.

      Boudaya MS, Smadhi H, Zribi H, et al. Conservative management of postoperative bronchopleural fistulas. J Thorac Cardiovasc Surg 2013;146:575–9.

      Bazzocchi R, Bini A, Grazia M, Petrella F. Bronchopleural fistula prevention after major pulmonary resection for primary lung cancer. Eur J Cardiothorac Surg 2002;22:160.

      Dickhoff C, Otten RHJ, Heymans MW, Dahele M. Salvage surgery for recurrent or persistent tumour after radical (chemo)radiotherapy for locally advanced non-small cell lung cancer: a systematic review. Ther Adv Med Oncol. 2018 Oct 5;10:1758835918804150.

      Cardillo G, Carbone L, Carleo F, Galluccio G, Di Martino M, Giunti R, Lucantoni G, Battistoni P, Batzella S, Dello Iacono R, Petrella L, Dusmet M. The Rationale for Treatment of Postresectional Bronchopleural Fistula: Analysis of 52 Patients. Ann Thorac Surg. 2015 Jul;100(1):251-7.

      Battistoni P, Caterino U, Batzella S, Dello Iacono R, Lucantoni G, Galluccio G. The Use of Polyvinyl Alcohol Sponge and Cyanoacrylate Glue in the Treatment of Large and Chronic Bronchopleural Fistulae following Lung Cancer Resection. Respiration. 2017;94(1):58-61.

      Reed MF, Mathisen DJ. Tracheoesophageal fistula. Chest Surg Clin N Am 2003; 13:271.

      Chen YH, Li SH, Chiu YC, et al. Comparative study of esophageal stent and feeding gastrostomy/jejunostomy for tracheoesophageal fistula caused by esophageal squamous cell carcinoma. PLoS One 2012; 7:e42766.

      Balazs A, Kupcsulik PK, Galambos Z. Esophagorespiratory fistulas of tumorous origin. Non-operative management of 264 cases in a 20-year period. Eur J Cardiothorac Surg 2008; 34:1103.

      Rodriguez AN, Diaz-Jimenez JP. Malignant respiratory-digestive fistulas. Curr Opin Pulm Med 2010; 16:329.

      Freitag L, Tekolf E, Steveling H, Donovan TJ, Stamatis G. Management of malignant esophagotracheal fistulas with airway stenting and double stenting. Chest. 1996;110(5):1155.

      Herth FJ, Peter S, Baty F, Eberhardt R, Leuppi JD, Chhajed PN. Combined airway and oesophageal stenting in malignant airway-oesophageal fistulas: a prospective study. Eur Respir J. 2010;36(6):1370. Epub 2010 Jun 4.

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      IBS20.02 - Airway Stenosis (Now Available) (ID 3406)

      07:00 - 08:00  |  Presenting Author(s): Michela Bezzi

      • Abstract
      • Presentation
      • Slides

      Abstract

      Tracheal stenosis is suspected in individuals with risk factors presenting with signs and symptoms of airway narrowing. The condition may be suspected based on spirometry with a flow-volume loop and CT imaging of the neck and chest but fiberoptic bronchoscopy is required to confirm the presence and severity of tracheal stenosis. The symptoms of tracheal stenosis are similar to those of other conditions so it is important to carefully evaluate patients history. The symptoms of tracheal stenosis typically are wheezing, coughing or shortness of breath, cornage, upper respiratory infections, asthma that doesn’t respond to treatment.

      Benign tracheal stenoses are more commonly the result of an injury to the trachea due to prolonged intubation or tracheostomy but also Infections (tuberculosis), autoimmune disorders such as Granulomatosis with polyangiitisand amyloidosis or radiation therapy to the neck or chest. The morphological classification of airway stenosis includes granulomas, pseudoglottic stenosis, and “true stenosis” divided into web-like and complex stenoses.

      Web-like stenoses are circumferential strictures of the trachea involving the mucosa of a short segment (maximum 1 cm long)without any damage to the cartilages.

      Complex stenosesare sleeve strictures of the trachea more than 1 cm long, often associated with various degrees of cartilage involvement, malacia and inflammation.

      Several treatment options that can be used for tracheal stenosis depending on the cause, location and severity of the tracheal narrowing. Resection and anastomosis of the involved tract of the trachea is the gold standard treatment. Interventional Pulmonology (IP) offers minimally invasive techniques. Some IP treatment options can provide immediate relief but are considered temporary solutions, while others can provide a better long-term solution. Short-term treatment options for the condition include laser surgery and mechanical dilation with rigid scopes.Treatment options that are generally considered to work long term include stenting and tracheal reconstruction when only a short portion of the trachea is involved. Choice of procedure depends on the exact location and extent of the stenosis, but also on patient age and comorbidities.The most common treatment options for tracheal stenosis include:

      In 2007 Cavaliere et al. published the results of Laser Assisted Mechanical Dilation in 113 post-intubation tracheal stenoses

      Sex

      Age(Y)

      Cause of stenosis

      Type of stenosis

      M

      47

      50±21

      (12-84)

      Intubation

      38

      Tracheotomy

      35

      Web-like

      13

      Complex

      60

      Tab 1 - Patient carachterstics

      Therapeutic bronchoscopies were performed using rigid bronchoscopes (Efer, Dumon-Harrel type; FR) and general anesthesia.Endoscopic treatment was based on the use of three main techniques: laser photo-resection (multiple radial incisions), gentle dilation and removable silicon stents.

      tracheal stenoses.png

      Fig 1 Web like stenosis, Complex stenosis, Silicon stent

      therapeutic algorythm.png

      Most web-like stenoses were successfully treated with Laser Assisted Mechanical Dilation (LAMD) alone; among complex stenoses LAMD was sufficient to treat 13 patients (22%), whereas 47 patients (78%) required stent placement: 22 had their stent removed after one year and did not require any further therapy, 13 inoperable patients required permanent stent and 12 were referred to surgery after failure of multiple endoscopic treatments. No permanent complications secondary to endoscopic treatment were observed. Forty-eight patients (66%) obtained a stable, good result with the endoscopic procedure, 13 (18%) required a permanent stent while 12 patients (16%) were referred to surgery.

      These authors indicate that bronchoscopic treatment of post-intubation tracheal stenoses can be considered a safe first-line therapy, leaving some selected cases and the relapsing stenosis for surgical resection.

      1.Shapshay SM, Beamis JF, Jr, Hybels RL, Bohigian RK. Endoscopic treatment of subglottic and tracheal stenosis by radial laser incision and dilation. Ann Otol Rhinol Laryngol. 1987;96:661–664.

      2. Bacon JL, Patterson CM, Madden BP. Indications and interventional options for non-resectable tracheal stenosis. J Thorac Dis. 2014;6:258–70.

      3. Galluccio G, Lucantoni G, Battistoni P, Paone G, Batzella S, Lucifora V et al. Interventional endoscopy in the management of benign tracheal stenoses: definitive treatment at long-term follow-up. Eur J Cardiothorac Surg. 2009;35:429–33.

      4. Murgu SD, Colt HG, Mukai D, Brenner M. Multimodal imaging guidance for laser ablation in tracheal stenosis. Laryngoscope. 2010;120:1840–6.

      5. Cavaliere S, Bezzi M, Toninelli C, Foccoli P
Management of post-intubation tracheal stenoses using the endoscopic approach. Follow-up of 73consecutive patients over a four-year period.
Monaldi arch Chest Dis 2007 Jun; 67(2):73-80

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    IBS29 - How to Successfully Run a Multidisciplinary Tumor Board (Ticketed Session) (ID 51)

    • Event: WCLC 2019
    • Type: Interactive Breakfast Session
    • Track: Interventional Diagnostics/Pulmonology
    • Presentations: 3
    • Now Available
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      IBS29.01 - Can a Multidisciplinary Team Meetings Improve Lung Cancer Survival? (Now Available) (ID 3375)

      07:00 - 08:00  |  Presenting Author(s): Kwun M Fong  |  Author(s): Emily Stone, Barbara Page

      • Abstract
      • Presentation
      • Slides

      Abstract

      Multidisciplinary team (MDT) management for lung cancer has been increasingly introduced globally with the aim of improving outcomes for patients. This is reflected by the recognition that lung cancer MDT management is the standard of care in some countries

      The proponents of MDT care note the perceived benefits of MDT care to all stakeholders, including the patient, their clinicians and the general population. On the other hand, there are potential disadvantages associated with MDT lung cancer care, particularly the costs of setting up the service, the time commitment from the clinicians involved and possible delay to treatment.

      Observed obstacles to implementing effective MDT management include inadequate infrastructure and organisational/administrative support, lack of enabling technologies, incomplete specialist representation and low attendance by some MDT disciplines, inadequate case preparation and sub-optimal quality information for decision making.

      The organisation and performance of MDT lung cancer varies round the world and even within countries. This heterogeneity may affect the effectiveness and quality of MDTs such that quality assurance for MDT is essential.

      This talk will identify the eidence for the effects of lung cancer MDT care on patient centred outcomes including survival in the context of unparalleled improvements in the range of therapeutic options currently available for lung cancer.

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      IBS29.02 - Leadership and Networking (Now Available) (ID 3376)

      07:00 - 08:00  |  Presenting Author(s): Tim Murgu

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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      IBS29.03 - Quality Control (ID 3377)

      07:00 - 08:00  |  Presenting Author(s): Tim Murgu

      • Abstract
      • Slides

      Abstract

      Lung cancer diagnosis and therapy have progressed within the recent years due to significant advancements of bronchoscopic techniques for diagnosing intrathoracic adenopathy and peripheral lung lesions, radiotherapy and surgery techniques, molecular targeted therapeutic agents and immunity checkpoint inhibitors. Published evidence suggests that multidisciplinary team presentation (aka tumor board) in lung cancer has the potential to improve long-term outcomes. Clinical guidelines recognize the importance of multidisciplinary meetings in the optimal care of lung cancer patients. Evidence suggests that dedicated lung cancer tumor boards lead to increased treatment utilization rates and improved survival outcomes for patients with lung cancer. Lung cancer tumor boards also allow for education and promotion of specialty services. This is especially relevant in the fast pace of modern medicine wherein technological and drug therapy advances lead to changes in the structure of traditional lung cancer tumor board and continuously challenge our approach to managing patients suffering from lung cancer. In this session, we will describe each of these issues with reference to our own experiences and literature considerations pertinent to:

      Selecting needle-based or surgical techniques for obtaining a cytohistologic diagnosis from the primary tumor and/or mediastinal or hilar lymph nodes

      Managing potential candidates for curative surgical resection; a lung cancer tumor board should include at least a thoracic surgeon specializing in lung cancer, medical oncologist, radiation oncologist and pulmonologist

      Managing patients with clinical stage I and II NSCLC, even if the patients are considered for nonsurgical therapies such as percutaneous ablation or stereotactic body radiation therapy

      Managing patients with lung cancer who require multimodality therapy (i.e. in patients with discrete N2 involvement by NSCLC identified preoperatively)

      Coordinating the optimal approach to obtaining and processing biopsy/cytology specimens to provide expeditious diagnostic and molecular results

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    MA20 - Thymic Tumors: From Molecular to Clinical Results and New Challenges in Other Rare Thoracic Tumors (ID 149)

    • Event: WCLC 2019
    • Type: Mini Oral Session
    • Track: Thymoma/Other Thoracic Malignancies
    • Presentations: 13
    • Now Available
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      Intro (ID 4090)

      11:30 - 13:00  |  Presenting Author(s): Edith Michelle Marom

      • Abstract
      • Slides

      Abstract not provided

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      MA20.01 - Global Quantitative Mass Spectrometry Reveals Potential Novel Actionable Targets in Thymic Epithelial Tumors (TET)   (Now Available) (ID 2294)

      11:30 - 13:00  |  Presenting Author(s): Udayan Guha  |  Author(s): Xu Zhang, Yue Qi, Fatos Kirkali, Ting Huang, Tapan Maity, Khoa Dang Nguyen, David S Schrump, Olga Vitek, Arun Rajan

      • Abstract
      • Presentation
      • Slides

      Background

      Thymomas (T) and thymic carcinomas (TC), that constitute the thymic epithelial tumors (TETs) are rare epithelial tumors. There are limited treatment options for patients with advanced TETs. The complexity and rarity of the disease hampers the development of effective therapeutics. Next-generation sequencing (NGS) analyses of TETs by the TCGA have confirmed the very low mutational burden and few actionable targets for therapy. Thus, novel strategies are needed for better elucidating the molecular pathways involved in tumor pathogenesis and identification of novel drug targets. Here, we have used quantitative mass spectrometry (MS) to characterize the global proteome and phosphoproteome of TETs with aim of identifying potential actionable drivers in thymomas and thymic carcinomas.

      Method

      Three-state SILAC quantitative mass spectrometry was used to quantify the global proteomes and phosphoproteomes of two thymoma (IU-TAB1 and T1682) and three thymic carcinoma cell lines (MP57, T1889 and Ty82). 10-plex TMT quantitative proteomics was used to quantify the global proteomes and phosphoproteomes of 54 TET tumors. All tumor tissues were pooled together to make the reference channel and labeled with TMT10-131. Basic RPLC followed by TiO2 enrichment and tandem MS were performed in a Q ExactiveTM HF mass spectrometer. MS data was processed using MaxQuant and Perseus. Protein quantification, normalization and statistical testing for the TMT experiments was done using free R package MSstatsTMT.

      Result

      We identified 4756 proteins and 5690 phosphosites from TET cell lines. Hierarchical clustering of SILAC ratios of quantitation demonstrated that T1682 and MP57 were more similar to each other than T1889 and Ty82. Several metabolic enzymes (LDHB, GSTP1, and AKR1B1) had higher expression in TC lines, while mitochondrial glutamate carrier SLC25A22 had greater abundance in thymoma lines. Ingenuity pathway analysis revealed that the top enriched canonical pathways associated with the significantly changed proteins in TET included remodeling of epithelial adherens junction, mitochondria dysfunction, and oxidative phosphorylation. RAS signaling pathway was enriched among the significantly changed phosphosites in the thymic MP57 and the B1 thymoma T1682 cells. We further analyzed the proteome and phosphoproteome of 54 TET tumor samples from 28 patients (23 thymoma and 5 thymic carcinoma) undergoing surgery or biopsy using TMT mass spectrometry. In total, 8320 proteins and 17716 phosphosites were identified. Hierarchical clustering of the TMT ratios to the pool for both proteins and phosphosites demonstrated that thymomas and thymic carcinomas clustered separately. Different locations of tumors from the same patient were grouped together. Only a few sites from the thymoma patients clustered in the thymic carcinoma group. GTF2I had higher abundance in thymomas compared to the TCs. MCM complex proteins and solute carrier family proteins had lower abundance and several collagens had higher abundance in TC patients. Several kinases, including PDGFRB, RIOK1, TNIK, and MAP4K4, and the metabolic enzyme glutathione S-transferase (GSTP1) had higher expression in TC patients. Further bioinformatics analysis and validation experiments are currently underway. Sensitivity data to inhibitors of metabolic enzymes and target kinases will be presented.

      Conclusion

      Global quantitative proteome and phosphoproteome analyses revealed potential novel kinases and metabolic enzymes for targeted therapy of TETs.

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      MA20.02 - GAD1 Expression and Its Methylation Become Indicators of Malignant Behavior in Thymic Epithelial Tumor (Now Available) (ID 2370)

      11:30 - 13:00  |  Presenting Author(s): Shiho Soejima  |  Author(s): Kazuya Kondo, Mitsuhiro Tsuboi, Reina Kishibuchi, Kyoka Muguruma, Bilguun Tegshee, Koichiro Kajiura, Yukikiyo Kawakami, Naoya Kawakita, Mitsuteru Yoshida, Hiromitsu Takizawa, Akira Tangoku, Nuliamina Wusiman

      • Abstract
      • Presentation
      • Slides

      Background

      Genome-wide screening for aberrantly methylated CpG islands was performed in 7 thymic carcinoma (TC) samples and 8 type-B3 thymoma samples using HumanMethylation450 K BeadChip (Illumina, Santa Clara, CA, USA) analysis. We identified 93 genes as commonly hypermethylated in TC comparing to type-B3 thymoma. GAD1 (glutamic acid decarboxylase 1) was one of the most significant hypermethylated genes in TC. GAD1 catalyzes the production ofγ-aminobutyric acid (GABA). Some recent reports showed that GAD1 expression is significantly increased in neoplastic tissues. However, the underlying mechanism of elevated GAD1 remains elusive. In this study, we examine mRNA and protein expressions and DNA methylation of GAD1 in thymic epithelial tumors (TETs).

      Method

      In total, 95 thymic tumor samples (A; 9, AB; 11, B1; 19, B2; 21, B3; 14, carcinoma; 21) and 22 paired normal tissues were obtained from patients with histologically proven TET, who underwent surgery at the Tokushima University Hospital (Tokushima, Japan) between 1990 and 2016. The methylation status of thymic epithelial tumor samples was validated by pyrosequencing. The expression status was analyzed by quantitative polymerase chain reaction (qPCR) and immunohistochemistry (IHC).

      Result

      The previous study (Oncogene 2015, 1–14) showed that the key locus responsible for GAD1 reactivation was mapped to DNA methylation-sensitive CTCF-binding site (CTCF-BS3) within the third intron of GAD1. We targeted this region for pyrosequencing, which confirmed that DNA methylation of GAD1 in TC was significantly higher than in thymoma (32.8% versus 4.0%, P<0.001). It revealed a high degree of both sensitivity and specificity for discriminating TCs and thymomas (AUC=0.936). There was no significant difference in the methylation rate between thymoma and normal thymus (P = 0.917); however, the DNA methylation rate in TC was higher than in normal thymus (P=0.015). qPCR revealed that GAD1 mRNA expression levels in TC were higher than in thymoma (qPCR; 2.03 vs 0.38, P < 0.001). IHC showed statically different GAD1 expression between TC and thymoma (93.75% vs 28.98%, P < 0.001). There was a slight positive correlation between the mRNA expression levels and methylation levels (Spearman’s rank correlation coefficient, ρ = 0.427); however, no differences of DNA methylation and expression of GAD1 was observed among subtype of thymoma according to WHO histologic classification.

      Conclusion

      TC had frequent DNA methylation of CTCF-binding site 3 in GAD1, and high levels of mRNA and protein of GAD1. GAD1 may resent an epigenetic therapeutic target in TC.

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      MA20.03 - DNA Methylation of MT1A and NPTX2 Genes Predict Malignant Behavior of Thymic Epithelial Tumors (Now Available) (ID 3031)

      11:30 - 13:00  |  Presenting Author(s): Kyoka Muguruma  |  Author(s): Kazuya Kondo, Reina Kishibuchi, Mitsuhiro Tsuboi, Shiho Soejima, Bilguun Tegshee, Koichiro Kajiura, Yukikiyo Kawakami, Naoya Kawakita, Mitsuteru Yoshida, Hiromitsu Takizawa, Akira Tangoku

      • Abstract
      • Presentation
      • Slides

      Background

      Our previous studies showed that DNA methylation of cancer-related genes, such as DAP-K, p-16, MGMT, HPP1 was higher in thymic carcinoma (TC) than in thymoma (Lung Cancer 64:155-, 2009, 83:279-,2013). Genome-wide screening for aberrantly methylated CpG islands was performed in 7 TC samples and 8 type-B3 thymoma samples using HumanMethylation 450 K BeadChip (Illumina, Santa Clara, CA, USA) analysis. We identified 93 genes as commonly hypermethylated in TC comparing to B3 thymoma.We chose 2 candidate cancer-related genes; MT1A and NPTX2. MT1A which is an isozyme of metallothioneins is related to metabolism of trace elements, such as zinc, copper. DNA methylation of MT1A was higher in malignant melanoma than in normal melanocytes. NPTX2 has studied as synapse-related proteins. DNA methylation of NPTX2 was higher in some cancers than in normal tissues.

      Method

      In total, 48 thymic tumor samples (thymoma;31, carcinoma; 17) and 22 paired normal tissues were obtained from patients with histologically proven thymic epithelial tumor (TET), who underwent surgery at Tokushima University Hospital (Tokushima, Japan) between 1990 and 2016. The methylation status of TET samples was validated by pyrosequencing. The expression of mRNA in MT1A and NPTX2 genes was validated by RT-PCR (SYBR® Green method).

      Result

      DNA methylation of MT1A gene was significantly higher in TC compared to thymoma (26.4% versus 9.5%, P<0.01). It revealed high degrees of sensitivity and specificity for discriminating TCs and thymomas (AUC=0.903). Although DNA methylation was significantly higher in TC than in normal thymus, there was no significant difference between DNA methylation of thymoma and normal thymus. No differences of MT1A DNA methylation was observed among subtype of thymoma according to WHO histologic classification. In MT1A gene, there was no correlation has observed between DNA methylation and mRNA expression.

      On the other hand, NPTX2 gene was also significantly higher in TC compared to thymoma (38.0% vs 17.5%, P<0.01). It revealed high degrees of sensitivity and specificity for discriminating TCs and thymomas (AUC=0.765). Although DNA methylation was significantly higher in TC than in normal thymus, there was no significant difference between DNA methylation of thymoma and normal thymus. No differences of NPTX2 DNA methylation was observed among subtype of thymoma according to WHO histologic classification. There was no correlation has observed between DNA methylation and mRNA expression in all TETs, there was a reverse correlation in thymic carcinomas. The mean value of the frequency of the DNA methylation of was MT1A and NPTX2 divided into higher and lower level groups. A significant difference was observed in the relapse-free survival between the higher and lower level groups (p=0.015, p=0.042).

      Conclusion

      DNA methylation of MT1A and NPTX2 was significantly higher in TC compared to thymoma and normal thymus.

      Epigenetic alteration may be related to progression and malignancy in TET. 

      In NPTX2 gene, there was a reverse correlation between DNA methylation and mRNA expression in thymic carcinomas. It may act as tumor suppressor gene.

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      MA20.04 - Discussant - MA20.01, MA20.02, MA20.03 (Now Available) (ID 3801)

      11:30 - 13:00  |  Presenting Author(s): Nicolas Girard

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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      MA20.05 - Follow-Up Update of 2 Phase II Studies of Pembrolizumab in Thymic Carcinoma (Now Available) (ID 1120)

      11:30 - 13:00  |  Presenting Author(s): Guiseppe Giaccone  |  Author(s): Jinhyun Cho, Chul Kim, Myung-Ju Ahn

      • Abstract
      • Presentation
      • Slides

      Background

      Two phase II studies of pembrolizumab 200 mg every 3 weeks in advanced thymic carcinoma have recently been published (Giaccone et al. Lancet Oncol. 2018, study #1; Cho et al. JCO 2018, study #2). Both studies reported a response rate in about 20% of patients and a rate of autoimmune disorders that is higher than in other tumor types.

      Method

      This report provides a follow-up update of these 2 studies, with particular emphasis on duration of response, and occurrence of autoimmune disorders. Both studies included patients with thymic carcinoma who had progressed after at least one line of chemotherapy.

      Result

      In study #1 a total of 40 patients with advanced thymic carcinoma were treated, with a median follow up of 40.6 months. The response rate did not change (22.5%) compared to the original publication, however one patient who had developed myositis, myocarditis and myasthenia gravis (MG), continues to be in nearly complete response after only two cycles of pembrolizumab, 36 months from initiation of treatment. One patient who had developed myositis and hepatitis with unclear signs of MG developed overt MG symptoms several months after the interruption of therapy. No other new autoimmune disorders were observed (6/40 = 15%). Five patients completed 2 years of treatment according to protocol and 4 of them elected to continue treatment. Three patients who had been off therapy were rechallenged with pembrolizumab upon progression (one responded). Median duration of response was 38 months (from 22.4 in initial report), median PFS was 4.2 months (identical) and median survival was 25.8 months (24.9 in the initial report).

      At completion of this study, an amendment was introduced to add epacadostat 10 mg BID to pembrolizumab in the same patient population. Four patients were treated before the study was closed after the results of a randomized trial of the combination in melanoma failed to meet its primary endpoint. No patient responded (2 stable and 2 progressions). One patient developed grade 2 myocarditis.

      In study #2 a total of 26 patients with advanced thymic carcinoma were included, with a median follow up of 33.4 months. The response rate (19.2%) did not change, and no other autoimmune disorder appeared since the initial publication (5/26 = 19%). Median duration of response (9.7 months), median PFS (6.1 months) and median survival (14.5 months) did not change compared to the initial publication. No additional autoimmune disorders were documented compared to the original publication. A total of 5 patients received 2 years of pembrolizumab according to protocol; no patient continued beyond 2 years or was retreated upon progression with pembrolizumab.

      Conclusion

      These two studies confirm definite activity of pembrolizumab in advanced thymic carcinoma. Recently pembrolizumab was included in the NCCN guidelines for thymic carcinoma. No additional autoimmune disorders were noted after discontinuation of pembrolizumab. There are significant differences in duration of response and overall survival in the 2 studies and potential factors are being investigated. In study #1 pembrolizumab was continued beyond 2 years in several patients and rechallenge was an available option.

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      MA20.06 - Neutrophil to Lymphocyte Ratio Is an Independent Prognostic Predictor in Thymoma (Now Available) (ID 1637)

      11:30 - 13:00  |  Presenting Author(s): Paulo De Sousa  |  Author(s): Filippo Tommaso Gallina, Alessandro Paolo Tamburrini, Maria Nizami, Chukwuemeka Igwe, Khalid Amer, Eric Lim, Vincenzo Ambrogi

      • Abstract
      • Presentation
      • Slides

      Background

      Thymoma is the most common primary neoplasm of the anterior mediastinum in adults and conventional prognostic factors include Masaoka Stage, WHO histology and completeness of resection. Little is known of preoperative peripheral neutrophil-to-lymphocyte ratio (NLR) as an independent additional discriminator of prognosis.

      Method

      We performed an international multicentre retrospective cohort study (UK Health Research Reference 19/HRA/0440 and EU internal approval reference xxxxxx). We included patients who underwent complete resection for thymoma and data was acquired through patient medical records with follow up data obtained through national database and hospital records. NLR calculated on pre-operation bloods results.

      Result

      From July 1987 to December 2017, 433 patients underwent surgery for thymoma. The majority were male 228(53%) with a mean age (SD) of 55(15) years. The surgical approach was sternotomy in 335 patients (77%), thoracotomy in 23(5%) and VATS in 75(17%). The WHO classification was type A 63(15%), AB 126(29%), B1 98(23%), B2 55(13%) and B3 86(20%) patients. The Masaoka-Koga stage was I in 135(33%) II in 194(47%), III in 54 (13%) and IV in 31(7%) patients.

      Median (IQR) follow-up time was 86 (30 to 152) months with a 5 and 10-year survival of 88% and 79% respectively. The median NLR was 2.1 (1.5 to 3.1), when split into three groups (NLR < 1.4, NLR between 1.4 and 2.3 and NLR > 2.3), higher NLR was associated with poorer survival (log rank P<0.001) that persisted on Cox regression after adjustment for WHO grade and Masaoka stage with a HR of 1.69 (95% CI 1.20 to 2.39; P=0.002).

      nlr thymoma.png

      Conclusion

      Pre-operative NLR is a simple, low cost biomarker that can stratify risk of death independent to WHO grade and Masaoka stage in patients undergoing surgery for thymoma.

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      MA20.07 - Thymomectomy and Total Thymectomy or Simple Thymomectomy for Early Stage Thymoma Without Myasthenia Gravis: An ESTS Thymic Working Group Study (Now Available) (ID 1683)

      11:30 - 13:00  |  Presenting Author(s): Francesco Guerrera  |  Author(s): Claudia Filippini, luca Voltolini, Francesco Londero, Pierre-Emmanuel Falcoz, Giorgio Lo Iacono, Charalambos Zisis, Paolo Mendogni, Laureano Molins, Nicola Martucci, Gaetano Rocco, Alper Toker, Matthias Esch, Clemens Aigner, Ivan Bravio, Sara Mantovani, Bernhard Moser, Nuria M Novoa, Bram Verdonck, Bert Du Pont, Miguel Congregado, Luca Ampollini, Pascal Alexandre Thomas, Enrico Ruffini

      • Abstract
      • Presentation
      • Slides

      Background

      Resection of thymic tumors has traditionally included removal of the tumor and the thymus gland (thymothymomectomy). Nevertheless, in recent years, some authors questioned the need to remove the thymus gland in non-MG thymomas, suggesting that resection of the tumor (simple-thymomectomy) is enough from an oncological point of view in Stage I (TNM stage classification) thymoma patients. The aim of our study was to compare short- and long-term outcome of thymothymomectomy vs. simple-thymomectomy using European Society of Thoracic Surgeons (ESTS) Thymic Database.

      Method

      We investigated 1131 patients with thymic epithelial tumors included in the ESTS-Thymic Database. Three-hundred twenty-four clinical stage I (cT1N0M0, according to the 8th edition of the UICC/AJCC TNM stage classification) without Myasthenia Gravis (non-MG) thymoma cases were evaluated from 23 contributing centers (2000-2017), of which 300 (93%) thymothymomectomy and 24 (7%) simple-thymomectomy. Surgical upstaging was evaluated. In pathological stage I, we compared the completeness of resection, the rate of complications, the 30-day mortality, the overall survival and the disease-free survival (DFS).

      Result

      Overall, we observed an upstaging to stage III in 10 (3%) patients. We did not observe any significant difference between the two techniques in terms of the completeness of resection, the rate of complications and the 30-day mortality. The 5-year overall survival rate was 94% in the thymothymomectomy group and 56% in the simple-thymomectomy group (Figure 1 - P= 0.0004). The 5-year DFS was 95% in the thymothymomectomy group and 82% in the simple-thymomectomy group (Figure 1 -P= 0.013).

      figure 1.png

      Conclusion

      Patients affected by stage I TNM non-MG thymoma submitted to thymothymomectomy presented a significantly better DFS and overall survival than those submitted to simple-thymomectomy. Thymothymomectomy should be considered the procedure of choice in Stage I TNM non-MG thymomas, also considering the not negligible rate of pathological upstaging.

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      MA20.08 - Discussant - MA20.05, MA20.06, MA20.07 (Now Available) (ID 3802)

      11:30 - 13:00  |  Presenting Author(s): Meinoshin Okumura

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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      MA20.09 - Breast Implant Associated Anaplastic Large Cell Lymphoma: Outcomes of a Newly-Recognized Malignancy of the Thoracic Wall (Now Available) (ID 2746)

      11:30 - 13:00  |  Presenting Author(s): Mark Warren Clemens  |  Author(s): Roberto N. Miranda

      • Abstract
      • Presentation
      • Slides

      Background

      In 2016, the World Health Organization provisionally classified breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) as a novel lymphoma and the National Comprehensive Cancer Network (NCCN) established evidence-based consensus guidelines for the diagnosis and surgical management of the disease. BIA-ALCL progresses locally as a solid tumor, invading the chest wall and mediastinum and leading to respiratory compromise in advanced cases. Local disease is treated surgically while aggressive disease involving regional lymph nodes and metastasis are currently managed with systemic chemotherapy, most commonly CHOP regimens (cyclophosphamide, vincristine, doxorubicin and prednisone). The goal of this study is to evaluate the efficacy of different therapies in the treatment of BIA-ALCL with chest wall invasion.

      Method

      A prospective study of all institutional cases from 2013 to 2018 was performed for patients with advanced disease (Stage IIA-III) locally invasive into the chest wall. Pathologic findings, treatments, and outcomes were reviewed.

      Result

      Eighteen consecutive patients were identified with BIA-ALCL Stage IIA-III. The median and mean follow-up times were 42 and 27 months, respectively (range, 6 to 226 months). Patients who underwent a complete en bloc resection had better OS (P = .022) and EFS (P = .014) than did patients who received partial resection, systemic chemotherapy, or radiation therapy. Perioperative complications included one pneumothorax. Two disease recurrences (7.8%) were noted at an average of 5 months from surgery. All patients eventually achieved complete remission (100%). The median overall survival (OS) time after diagnosis was 13 years, and the OS rate was 94% and 90% at 3 and 5 years, respectively. Patients presenting with chest wall invasion demonstrated significantly longer time from diagnosis to definitive surgery (21 versus 8 months, P = 0.039). Partial tumor resection resulted in disease hyperprogression in two cases.

      Conclusion

      BIA-ALCL with chest wall invasion may be a consequence of a delay in diagnosis or treatment. Complete en bloc surgical excision is essential for curative treatment of BIA-ALCL. Patients who receive textured surface breast implants need to be advised of the risk of developing BIA-ALCL, as well as the common presenting symptoms, such as a mass or delayed onset (>1 year) of effusion. When treated appropriately and in a timely fashion, BIA-ALCL has an excellent prognosis. Future research is warranted to determine modifiable risk factors and stratification of at-risk populations.

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      MA20.10 - Long-Term Prognostic Factors After Minimally Invasive Esophagectomy (MIE) for Esophageal Cancer (Now Available) (ID 2956)

      11:30 - 13:00  |  Presenting Author(s): Yu-Han Huang  |  Author(s): Pei-Wen Yang, Ke-Cheng Chen, Pei-Ming Huang, Jang-Ming Lee

      • Abstract
      • Presentation
      • Slides

      Background

      MIE has been demonstrated to associate a better peri-operative outcome to treat esophageal cancer as compared to that done by open surgery. However, the long-term clinical impact of MIE and its prognostic factors still requires further clarification.

      Method

      In current study, we evaluated the survival results and the factors influencing the prognosis of patients with esophageal cancer who received total minimally invasive esophagectomy using thoracoscopic and laparoscopic esophagectomy and esophageal reconstruction.

      Result

      A total of 483 patients were included in the study with 179 and 304 receiving Ivor Lewis and McKeown MIE respectively. Neoadjuvant chemoradiation was administered to 379 (78 %) of the patients. The overall and disease progression-free survival curves of all the patients were constructed with five-year survival rates of 48.3% and 40.3% respectively. Multivariate analysis revealed that pathological tumor stage was a significant factor for prognosis after surgery both in the patients treated with and without neoadjuvant CCRT (P< 0.05). Of the patients with patholoigical stage I or ypStage I esopahgeal cancer after CCRT, overall survival was significantly improved with the increased number of dissected lymph nodes (P=0.022).

      Conclusion

      The survival of patients with esophageal cancer undergoing MIE was influenced by their tumor staging, irrespective the use of neoadjuvant CCRT. Of these patients with stage I and ypStage I disease, improved survival can be facilitated with increased number of dissected lymph nodes during MIE.

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      MA20.11 - Surgical Treatment for Metastatic Lung Tumors from Sarcomas of Soft Tissue and Bone (Now Available) (ID 2391)

      11:30 - 13:00  |  Presenting Author(s): Hiromasa Yamamoto  |  Author(s): Kei Namba, Haruchika Yamamoto, Tomohiro Toji, Junichi Soh, Kazuhiko Shien, Ken Suzawa, Takeshi Kurosaki, Shinji Ohtani, Mikio Okazaki, Seiichiro Sugimoto, Masaomi Yamane, Katsuhito Takahashi, Toshiyuki Kunisada, Takahiro Oto, Shinichi Toyooka

      • Abstract
      • Presentation
      • Slides

      Background

      Sarcoma is one of the refractory malignant tumors and often develops pulmonary metastasis. The purpose of this study was to evaluate the impact of surgical resection for metastatic lung tumors from sarcomas of soft tissue and bone retrospectively.

      Method

      Between 2006 and 2015, we had a total of 158 patients with metastatic lung tumors from soft-tissue and bone sarcomas who underwent pulmonary metastasectomy for the first time. In total, 265 surgical procedures were performed in Okayama University Hospital in this period. We analyzed the age, sex, site of primary lesion, histology, extent of primary tumors at the initial diagnosis, extent of pulmonary metastases at the first pulmonary metastasectomy, presence or absence of local recurrence and/or extrapulmonary metastases with or before pulmonary metastases, operative procedures, size of the largest lesions resected, maximum number of the resected tumors, postoperative complications, and the prognosis at the end of 2018.

      Result

      Average number of resected tumors per intervention was 4.0 (range 1-19). These sarcoma patients consisted of 36 males and 122 females, and their average age was 53.7 years (range 14-88 years). Leiomyosarcoma was the most common histological subtype (n = 92, 58.2%) and uterus was the most common location of the primary disease (n = 71, 44.9%). Operative procedures were composed of 202 partial resections, 35 segmentectomies with or without partial resections, 26 lobectomies with or without partial resections, 1 pneumonectomy, and 1 basal segmental auto-transplantation after pneumonectomy. The postoperative complications were limited, showing that pulmonary metastasectomies for sarcomas are acceptable. Overall 3-year survival after the first pulmonary metastasectomy was 50.6%. In univariate analysis, the survival was significantly better for the group with disease-free interval of more than 2 years from the date of the initial treatment for primary disease until the date of diagnosis for the first pulmonary metastasis, the one who underwent pulmonary resections three times or more, and the one in which size of the largest resected lesion was 20 mm or less. Those factors significant in univariate analysis were all significant in multivariate analysis.

      Conclusion

      Surgical resections for metastatic lung tumors from sarcomas of soft tissue and bone were performed without major complications, indicating the acceptable feasibility. If disease-free interval is more than 2 years and the size of the largest resected lesion is less than 20 mm, patients may maximally benefit from pulmonary resection. In order to increase the opportunities of pulmonary resections, we should preserve the lung parenchyma as much as possible when performing pulmonary metatstasectomy, resulting in the better survival.

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      MA20.12 - Discussant - MA20.09, MA20.10, MA20.11 (Now Available) (ID 3803)

      11:30 - 13:00  |  Presenting Author(s): Scott Swanson

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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    MS01 - Immunotherapy Resistance (ID 64)

    • Event: WCLC 2019
    • Type: Mini Symposium
    • Track: Immuno-oncology
    • Presentations: 4
    • Now Available
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      MS01.01 - Biological Mechanisms of Resistance (Now Available) (ID 3439)

      10:30 - 12:00  |  Presenting Author(s): Justin F. Gainor

      • Abstract
      • Presentation
      • Slides

      Abstract

      Immune checkpoint inhibitors targeting the programmed cell death 1 (PD-1) axis have transformed the management of non-small cell lung cancer (NSCLC). Despite the dramatic and sometimes durable activity of these agents, a majority of patients will progress on therapy.1 Patients who experience a de novo lack of response to initial therapy are deemed as having primary (intrinsic) resistance. By contrast, acquired resistance refers to patients who initially achieve an objective response to therapy but eventually progress over time.

      The mechanistic basis for primary versus acquired resistance to immune checkpoint inhibitors is still poorly defined. To date, studies into the biological mechanisms of resistance to immunotherapies have centered around preclinical studies and analyses of repeat biopsies obtained from patients at the time of disease progression.2 These efforts have been complemented by similar studies in other immuno-oncology settings (e.g., melanoma),3,4 since there is potential for shared biology underlying immunotherapy resistance across malignancies.

      Both tumor cell-intrinsic and tumor cell-extrinsic factors have been implicated in mediating resistance to immunotherapies.2 In the setting of primary resistance, disease progression is commonly driven by a lack of neoantigens sufficient to illicit an initial immune response, commonly due to a low tumor mutation burden.5 Alternatively, tumors may actually harbor antigens capable of generating an immune response, but defects in antigen processing may ultimately limit the presentation of these antigens on the cell surface via MHC. Defective antigen presentation may be due to loss of beta-2 microglobulin (B2M), elimination of transporters associated with antigen processing (TAP) proteins, or downregulation of HLA.2,3 In addition, intrinsic resistance to immune checkpoint inhibitors may be due to altered oncogenic cell signaling (e.g., WNT/B-catenin pathway) and/or tumor de-differentiation with impaired antigen expression.

      Molecular mechanisms of acquired resistance to checkpoint blockade likely include many of the same processes as those implicated in intrinsice resistance. Indeed, homozygous loss of B2M, which is required for stabilization of HLA on the cell surface, has been described in NSCLC at the time of acquired resistance to PD-1 pathway blockade.6 Additionally, neoantigen loss through elimination of specific tumor subclones (i.e., immunoediting), genetic alterations in interferon gamma (IFN) signaling, and upregulation of alternative checkpoints (e.g., TIM3) have also been purported to confer acquired resistance to checkpoint inhibitors.4,7,8 At present, the relative frequencies of these processes and the interplay among them within NSCLC and other malignancies remains to be defined.

      Moving forward, it will be critical to pursue more in-depth preclinical and clinical studies of resistance to PD-1 pathway blockade in NSCLC. Just as insights into the molecular mechanisms of resistance to targeted therapy have transformed the therapeutic landscape for oncogene-driven tumors, it will be imperative for immuno-oncology to develop a framework for understanding resistance to checkpoint inhibitors and apply this framework to clinical development of next-generation immuno-onclogy agents. This is especially critical due to the sheer number of immuno-oncology combinations currently in clinical testing. Ultimately, knowledge of the mechanisms of resistance to immune checkpoint inhibitors may help better inform the rationale design of trials evaluating PD-1 inhibitor combinations.

      References:

      1. Garon EB, et al. J Clin Oncol 2019 Jun 2 [Epub ahead of print]. 2. Sharma P, et al. Cell 2017;168(4):707-23. 3. Sade-Feldman M, et al. Nat Commun 2017;8(1):1136. 4. Zaretsky JM, et al. NEJM 2016;375:819-29. 5. Rizvi NA, et al. Science 2015;348(6230):124-128. 6. Gettinger S, et al. Cancer Discov 2017:7:1420-35. 7. Anagnostou V, et al. Cancer Discov 2017;7(3):264-76. 8. Koyama S, et al. Nat Commun 2016;7:10501.

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      MS01.02 - Treatment Determining Markers - What Have We Achieved so Far? (Now Available) (ID 3440)

      10:30 - 12:00  |  Presenting Author(s): Naiyer A Rizvi

      • Abstract
      • Presentation
      • Slides

      Abstract

      Progress has been made selecting patients for immune checkpoint blockade employing expression of PD-L1 however limitations exist with this approach. Increasing use of genetic markers has been incorporated into clinical trials and clinical practice. Beyond MSI testing, tumor mutation burden has gained increasing traction and prospective trials employing TMB are under way and will be reviewed. Additional unique sensitivity and resistance mutations are emerging and may be incorporated into our genetic analysis paradigm. Additionally genetic studies are now being performed with success on plasma ctDNA and emerging ctDNA analyses will be discussed.

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      MS01.03 - Overcoming Resistance - Clinical Results? (Now Available) (ID 3441)

      10:30 - 12:00  |  Presenting Author(s): Ross Soo

      • Abstract
      • Presentation
      • Slides

      Abstract

      Overcoming resistance- clinical results.

      The management of oncogene negative advancednon-small cell lunghas been transformed with the use of immune checkpoint inhibitors targeting programmed death receptor-1 (PD-1) and programmed death receptor ligand-1 (PD-L1). However, in a significant number of patients, either primary or acquired resistance has been observed. Primary resistance, usually defined as disease progression upon the first radiologic evaluation, represents an important clinical problem and has been reported in up to 20% of patients. Acquired resistance, defined as tumors with initial response following treatment but eventually develop disease progression, has been reported in approximately 20-40% of patients.

      The mechanisms of primary and acquired resistance to immunotherapy are complex and are interdependent, involving alterations in immune cells, cytokines, metabolic and oncogene signaling pathways in the tumor cell and the tumor microenvironment. The usual treatment following progression on first line immune checkpoint inhibitor with or without a platinum doublet is single agent docetaxel or a platinum doublet +/- bevacizumab.

      With an improvement in the understanding of the mechanisms of resistance to immune checkpoint inhibitors, to improve patients’ outcomes following resistance, strategies have been devised to tailor subsequent therapy according to the mechanism of resistance, including the use of therapies to increase antigenicity, enhance immune cell function, and modulate the tumor microenvironment.

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      MS01.04 - Smoking and Immunotherapy (Now Available) (ID 3442)

      10:30 - 12:00  |  Presenting Author(s): Nise Yamaguchi

      • Abstract
      • Presentation
      • Slides

      Abstract

      Smoking disrupts the homeostasis of the innate and the adaptive immune system. Carcinogenic and pro-inflammation compounds of tobacco leaves and other chemicals present in cigarette interfere with the regulation of immunity in two opposing ways. Some compounds trigger chronic inflammation inducing cell damage and transformation; others inhibit apoptosis, a protective strategy against transformed cell proliferation. Smoking attenuates response by dendritic cells (DC), natural killer cells (NK), macrophages against transformed cells1. Smoking affects as well the adaptive immune cells, B lymphocytes, T helper cells, CD4+ / CD25+ regulatory T cells, and CD8+ T cells.[1]

      Patients with NSCLC had low levels of serum bilirubin correlated with tumor progression and poor response to platinum-based chemotherapy[2]. Studies found that high normal levels of serum bilirubin indicated favorable prognosis in NSCLC and colorectal tumor.[3], [4] Bilirubin has anti-inflammatory, anti-oxidative, and anti-proliferative effects[5] and smoking decreased bilirubin in a cohort study using metabolomics profiling.[6] Zhang et al. reported that pretreatment with bilirubin correlated with overall survival (OS) in NSCLC patients with EGFR mutations.[7]

      Epithelial to mesenchymal transition (EMT) is an important process of cell-transformation that facilitates metastases and smoking induced hypoxia, inflammation, and oxidative stress, culminating in malignancy and EMT.[8],[9] The effect of smoking on EMT also occurs in other cancer histologies. A study showed that the HDAC inhibitor MS-275 restores E-cadherin expression, reversing EMT, metastases, and invasion induced by smoking.[10], [11], 8

      Smoking impairs lung cancer chemotherapy, requiring increased doses for patients who smoke. The polycyclic aromatic hydrocarbons (PAH) of smoke increases the synthesis of enzymes that metabolize many antineoplastic drugs. PAH increase clearance, requiring dose adjustments to reach toxicity levels of efficacy.[12] Smokers receiving irinotecan had increased clearance and lower exposure to therapeutic metabolites; and treatments with paclitaxel, docetaxel, irinotecan, and gemcitabine showed lesser neutropenia in smokers than in nonsmokers.12 Nicotine-derived nitrosamine ketones antagonizes cisplatin and carboplatin regimens by blocking apoptosis.[13],[14],[15]

      Erlotinib blocks the receptor for tyrosine-inhibiting epidermal growth activation (EGFR) and is metabolized by CYP3A4 and, by CYP1A2 and CYP1A1.[16] Smoking accelerates drug catabolism, decreasing erlotinib plasma concentrations and survival rates in NSCLC. Retrospective analysis of 88 patients NSCLC receiving erlotinib or pemetrexed showed better progression-free survival (PFS) with erlotinib in never smokers than in former smokers (3.5 versus 2.7 months, p = 0.005)[17] and smokers with squamous histology receiving erlotinib lived longer than former smokers.[18] A study on the efficacy of second-line docetaxel and erlotinib in NSCLC patients with smoking history versus never smokers shoed decreased overall survival (hazard ration [HR] 3.61 [1.77–7.4], p = 0.0005) in the erlotinib arm.[19]

      Nicotine affected EGFR/AKT/ERK pathways, preventing/decreasing erlotinib action in NSCLC, promoting tumor growth in the PC9 xenograft model. [20]

      [1] Qiu F. et al. (2016) Impacts of cigarette smoking on immune responsiveness: up and down or upside down? Oncotarget, 2017, Vol. 8, (No. 1), pp: 268-284.

      [2] Song Y-J. et al. (2018) Direct bilirubin levels are prognostic in non-small cell lung cancer. Oncotarget, 2018, Vol. 9, (No. 1), pp: 892-900.

      [3] Li N, et al. Elevated serum bilirubin levels are associated with improved survival in patients with curatively resected non-small-cell lung cancer. Cancer Epidemiol. 2015; 39:763–8. https://doi.org/10.1016/j.canep.2015.06.007.

      [4] Zhang Q, et al. Nomograms incorporated serum direct bilirubin level for predicting prognosis in stages II and III colorectal cancer after radical resection. Oncotarget. 2017; 8:71138–46. https://doi.org/10.18632/oncotarget.11424

      [5] Marnett LJ. Oxyradicals and DNA damage. Carcinogenesis. 2000; 21:361–70.

      [6] Wen CP et al. (2015) The ability of bilirubin in identifying smokers with higher risk of lung cancer: a

      large cohort study in conjunction with global metabolomics profiling. Clin Cancer Res. 2015; 21:193–200. https://doi.org/10.1158/1078-0432.CCR-14-0748.

      [7] Zhang Y, et al. Pretreatment direct bilirubin and total cholesterol are significant predictors of overall survival in advanced non-small-cell lung cancer patients with EGFR mutations. Int J Cancer. 2017; 140:1645–52. https://doi.org/10.1002/ijc.30581.

      [8] Milara, J.; Peiró, T.; Serrano, A.; Cortijo, J. Epithelial to mesenchymal transition is increased in patients with

      COPD and induced by cigarette smoke. Thorax 2013, 68, 410.

      [9] Dasgupta, P.; Rizwani,W.; Pillai, S.; Kinkade, R.; Kovacs, M.; Rastogi, S.; Banerjee, S.; Carless, M.; Kim, E.;

      Coppola, D.; et al. Nicotine induces cell proliferation, invasion and epithelial to mesenchymal transition in a

      variety of human cancer cell lines. Int. J. Cancer 2009, 124, 36–45.

      [10] Sohal, S.S.; Walters, E.H. Role of epithelial mesenchymal transition (EMT) in chronic obstructive pulmonary disease (COPD). Respir. Res. 2013, 14, 120.

      [11] Ibidem 10.

      [12] O’Malley et al. Effects of Cigarette Smoking on Metabolism and Effectiveness of Systemic Therapy for Lung Cancer. J Thorac Oncol. 2014;9: 917–926.

      [13] Xu J, Huang H, Pan C, Zhang B, Liu X, Zhang L. Nicotine inhibits apoptosis induced by cisplatin in human oral cancer cells. Int J Oral Maxillofac Surg 2007;36:739–744.

      [14] Zeng F, Li YC, Chen G, et al. Nicotine inhibits cisplatin-induced apoptosis in NCI-H446 cells. Med Oncol 2012;29:364–373.

      [15] Zhang J, Kamdar O, Le W, et al. Nicotine induces resistance to chemotherapy by modulating mitochondrial signaling in lung cancer. Am J Respir Cell Mol Biol 2009;40:135–146.

      [16] Ling J, Johnson KA, Miao Z, et al. Metabolism and excretion of erlotinib, a small molecule inhibitor of epidermal growth factor receptor tyrosine kinase, in healthy male volunteers. Drug Metab Dispos 2006;34:420–426.

      [17] Zugazagoitia J, Puente J, González-Larriba JL, et al. Erlotinib versus pemetrexed for pretreated non-squamous non-small cell lung cancer patients in clinical practice. Oncology 2013;84:255–264.

      [18] Chiang CL, Tsai CM, Chou TY, et al. Erlotinib in patients with advanced lung squamous cell carcinoma. Cancer Chemother Pharmacol 2013;71:203–208.

      [19] Krawczyk P, Kowalski DM, Wojas-Krawczyk K, et al. The qualification of docetaxel or erlotinib for second-line therapy should be based on clinical and molecular predictive factors. Chemotherapy 2012;58:60–69.

      [20] Li H, Wang S, Takayama K, et al. Nicotine induces resistance to erlotinib via cross-talk between 1nAChR and EGFR in the non-small cell lung cancer xenograft model. Lung Cancer 88 (2015) 1–8.

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    OA05 - Increasing the Impact of Nursing and Allied Health Professional Interventions in Lung Cancer Care (ID 130)

    • Event: WCLC 2019
    • Type: Oral Session
    • Track: Nursing and Allied Professionals
    • Presentations: 9
    • Now Available
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      OA05.01 - A Prospective Study of Swallowing and Voice Outcomes After Treatment for Small-Cell Lung Cancer (Now Available) (ID 2225)

      15:15 - 16:45  |  Presenting Author(s): Jacqui Frowen  |  Author(s): Karla Gough, Jo Phipps-Nelson, Rhys Hughes, Shankar Siva, Allison Drosdowsky, Benjamin J Solomon, Nicole Kiss, Mary Duffy, David Ball

      • Abstract
      • Presentation
      • Slides

      Background

      Dysphagia (difficulty swallowing) and dysphonia (impaired voice) have been identified in patients with lung cancer as being a significant problem. However, research to date has been limited in its measurement and it remains unknown which patients experience dysphagia or dysphonia, and what the impact of these problems are to the patient. The purpose of this study was to identify the prevalence and nature of dysphagia and dysphonia in patients with limited stage SCLC.

      Method

      A prospective cohort pilot study was conducted on 12 patients receiving chemoradiotherapy for limited-stage SCLC. Data collection included: videofluoroscopy swallowing studies (VFSS) to investigate swallowing physiology, aspiration risk and oesophageal motility disorders; limitations to oral intake; patient-reported swallowing problems; and patient-reported voice problems. Data were collected before treatment and again at one, three and six months post-treatment.

      Result

      No patient was observed to aspirate, and the pharyngeal swallow was safe and functional in all cases. Three patients exhibited oesophageal motility disorders before treatment, while three more exhibited these disorders at the post-treatment assessments. Oral intake was most compromised one month post-treatment; at this time one patient was tube dependent, two required a single consistency diet and two had a diet requiring special preparation. At all other time-points patients were managing a normal or near-normal diet. Despite an absence of oropharyngeal dysphagia observed on VFSS, three patients reported moderate or severe swallowing difficulties one month post-treatment; these self-reported difficulties were no more than mild at follow-up assessments. Three additional patients reported the onset of moderate or severe swallowing difficulties at three and six months post-treatment. Patients who reported swallowing difficulties at one month post-treatment had all received a mean radiation dose to the oesophagus of ≥15.7Gy and a maximum dose to the oesophagus of ≥42Gy, however these relationships were no longer apparent at three and six months post-treatment. Patient-reported voice difficulties were variable, with the worst scores being reported at one month post-treatment for a subset of patients, who continued to report problems across voice-related physical, functional and emotional domains at three and six months post-treatment.

      Conclusion

      This is the first time that detailed swallowing and voice outcomes have been reported in patients with SCLC. Although patient numbers are small, this study identified discordance between observed swallowing function and patient-reported problems, which may have significant clinical implications for the management of patients with SCLC, as well as identify important issues for future research.

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      OA05.02 - Patient Experience, Expectations and Knowledge: Lung Cancer in Australia (Now Available) (ID 2323)

      15:15 - 16:45  |  Presenting Author(s): Catherine Holliday

      • Abstract
      • Presentation
      • Slides

      Background

      Lung cancer is the fourth most diagnosed cancer in Australia. In 2015, it was the fourth most common cause of death and the most common cause of cancer death. There were over 11,000 new cases of lung cancer in 2013, with more men (approximately 6,600) than women (approximately 4,500) diagnosed. In 2014, more than 8000 people in Australia died from lung cancer, nearly 5000 of whom were men.

      Patient Experience, Expectations and Knowledge (PEEK) is a research study developed by the International Centre for Community-Driven Research (CCDR). PEEK studies conduct patient experience research using a protocol that will allow for comparisons over time (both quantitative and qualitative components). This study in NSCLC is the largest mixed methodology study in Australia in the past five years.

      Method

      In this study, 80 people with NSCLC stages I to IV throughout Australia participated in a structured (qualitative) interview and an online (quantitative) questionnaire. The interview and questionnaire comprehensively covered all aspects of disease experience from symptoms, diagnosis, treatment, communication, information provision, care and support, quality of life, and future treatment and care expectations. Statistical analysis of quantitative data was conducted using R, and content analysis of qualitative data was conducted using conventional analysis to identify major themes.

      Result

      The most common symptom experienced before diagnosis was back and/or shoulder pain (n=35, 43.75%), and the most common symptoms leading to diagnosis was breathing difficulties (n=26, 32.50%). The majority (n=58; 72.50%) of participants knew nothing or very little about lung cancer at diagnosis, and the most commonly reported theme relating to discussion about treatment was that patients were presented with only one treatment plan, with little discussion about treatment options (n=36; 45.00%). There were 76.25% (n=61) of this study population that reported receiving support primarily from family and friends. Quality of life was negatively affected in 85.00% (n=68) of the study population, the most common reason being due to the emotional and physical impact on patients and family (n=44; 55.00%). There were 51.25% (n=41) of the study population that reported relationships being strengthened, despite 75.00% (n=60) of the study population reporting feeling burdensome to their family. In relation to future needs, 53.75% (n=43) of participants called for access to treatments to be more affordable and equitable; for information to address stigma and educate the public in relation to causes of lung cancer (n=16, 20.00%); for clinicians to display more compassion/empathy (n=20, 25.00%); and for support more groups and peer support (n=17, 21.25%).

      Conclusion

      Based on patient experience and feedback, three recommendations are made to improve patient quality of life and/or ability to manage their own health:

      Public health campaigns developed to prevent lung cancer should be developed in a way that protects people currently diagnosed from the impact of negative stigma.

      Information and support services, including support for carers, should be more targeted to specific disease staging and sub-types of disease.

      Research funding should reflect the mortality and prevalence of lung cancer, and the number of clinical trials available should increase to aid timely decisions about new treatments.

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      OA05.03 - Development of a Fatigue and Breathlessness Group for Thoracic Oncology Patients (Now Available) (ID 2612)

      15:15 - 16:45  |  Presenting Author(s): Pippa Labuc  |  Author(s): Faye Dickinson

      • Abstract
      • Presentation
      • Slides

      Background

      Cancer related fatigue and breathlessness are well-established common symptoms of lung cancer, with 57%-100% of all lung cancer patients experiencing cancer related fatigue and 19%-51% experiencing dyspnoea. Both symptoms can be highly subjective and distressing for the individual, impacting on all domains of their life: physical, social and emotional.

      Due to this fatigue, dyspnoea and anxiety are a symptom cluster effecting up to 96% lung cancer patients, and is associated with poor performance status and reduced patient reported quality of life (QoL).

      In order to address this the symptoms of fatigue, breathlessness and anxiety need to be addressed concurrently in order to ensure the best results for the individual and improve QoL.

      Method

      A literature review was completed using online journal libraries to determine the incidence and impact of fatigue and breathlessness on lung cancer patients, as well as the most effective symptoms management interventions.

      Following this, patients attending the thoracic oncology outpatient clinics at Guy’s Cancer Centre completed a questionnaire to determine:

      1. The incidence fatigue, breathlessness and mood changes

      2, Their individual experience of the symptoms

      3. If the symptoms are impacting on QoL

      4. Would they want to attend a group to address these symptoms

      5. The preferred location, time and frequency of the group

      Outcome measures to address the symptoms were reviewed to ensure that those with the highest validity were selected for use.

      Result

      A six session group was developed, using the Breathing, Thinking Functioning model at its core, to ensure that the sessions address all domains of the patients life, as well as the mechanisms of dyspnoea. Sessions also addressed fatigue and sleep hygiene, once again addressing the issues holistically.

      Each session consists of both an educational element, to address the subject of the week, followed by a practical session to allow for practice of the techniques provided and assist the individuals to gain mastery of these.

      In order to gain both qualitative and quantitative data, patients complete the FACIT-Fatigue, EORTC QLQ-C30, Dyspnoea 12 and individual goal setting prior to commencing the programme. The individual goals are discussed with the clinician when attending the initial session to ensure that these are addressed during the group. On completion of the session these assessment are repeated in order to determine the impact that the group has had on all symptoms as well as the individuals QoL.

      Conclusion

      Fatigue and breathlessness are debilitating side effects of a lung cancer diagnosis, which result in both physical and emotional changes for the patient.

      In order to address these symptoms holistically they need to be address concurrently, as well as addressing the impact they have on anxiety and depression.

      By providing a structured group programme to address these symptoms and the impact they have on the individual, it allows patients to master skills to reduce the impact of these symptoms, as well as promote self-management and improve QoL.

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      OA05.04 - Discussant - OA05.01, OA05.02, OA05.03 (Now Available) (ID 3753)

      15:15 - 16:45  |  Presenting Author(s): Melissa Jane Culligan

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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      OA05.05 - Transforming the Patient Experience in Lung Cancer Through the Use of Clinical Nurse Specialist Virtual Clinics - The Liverpool Experience (Now Available) (ID 2130)

      15:15 - 16:45  |  Presenting Author(s): Andrea Vanessa McIver, Nicola Maddock  |  Author(s): Joanne Dunbar, Sophie Sanders, Martin Ledson, Martin Walshaw, Colin Smyth

      • Abstract
      • Presentation
      • Slides

      Background

      To improve the patient experience in lung cancer, in 2014 we introduced to the UK the concept of “virtual” clinic working, where following secondary care review of suspicious CT scans taken in the community a lung cancer nurse specialist (LCNS) conducts a clerking/holistic assessment via telephone and offers an investigation plan where appropriate.

      In 2017, this model of care was adopted into UK National Lung Cancer Optimal Pathway guidance.

      We were interested to review the effect of our innovative service on patient experience.

      Method

      We looked at patient feedback, staff perceptions and impact on the lung cancer pathway of our virtual clinic 2016-18.

      Result

      Of the 1498 patients with a suspicious CT scan, over 75% were diagnosed with cancer.

      Overall 802 (70%) were diagnosed via the outpatient service and 705 (88%) chose virtual clinic assessment and diagnostic test facilitation.

      Qualitative audit has shown an overwhelmingly positive feedback, where 98% of users felt that the virtual clinic was a better option, and patients felt well informed and supported.

      In addition the LCNSs feel they are utilising their knowledge and skills in a more timely fashion with an appropriate population. The early assessment facilitates the start of that therapeutic relationship that leads to patient needs being addressed, symptom management advice, reducing distress and optimising patient performance status and quality of life.

      Furthermore ‘virtual’ working has seen a dramatic reduction in medical outpatient activity, allowing that resource to be used more efficiently for the benefit of cancer patients.

      Conclusion

      This service review has shown that the data and patient and staff experience all support this new model of care delivery.

      The benefits are multifocal: care is patient-centred , appropriate skill-set use improves staff morale, and the freeing up of infrastructure allows organisational resource reallocation and cost saving.

      We have advocated the role of the LCNS to take the lead in this model of working across the UK, as we feel the LCNS are best placed to do these sensitive and complex assessments.

      We welcome the opportunity to share our experience worldwide.

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      OA05.06 - Nursing Intervention on Immuno-Related Adverse Events in Lung Cancer Patients (Now Available) (ID 2135)

      15:15 - 16:45  |  Presenting Author(s): Monica Arellano  |  Author(s): Isabel Brao, M. Paz Fernández

      • Abstract
      • Presentation
      • Slides

      Background

      New treatment of immunotherapy permits to stimulate the patient’s immune responses against cancer. That it supposes a new strategy for melanoma, renal and lung cancers. Although, is different than Chemotherapy’s toxicity, the effect on tissues and organs are systemic and can be dealing to unpredictable side-effects that should be detected and treated as soon as possible. Nurses are vital to manage toxicity related to immunotherapy & educate and to provide patient’s with best education.

      Our objetive is to describe lung cancer clinical nurses specialists’ role on the management of toxicities related to immunotherapy in lung cancer patients. How is the control and follow–up for those patients

      Method

      In 2018, a cross-sectional study was conducted with lung cancer patients receiving immunotherapy at the Lung Functional Unit of Catalan Institute of Oncology, hospital Duran I Reynals in Barcelona-Spain. The variables included were socio-demographic profile, the clinical were; tumour histological, toxicities prevalence and severity and finally variables from the roles and references made by nurses. A descriptive analysis of prevalence was performed with type of toxicities and patient characteristics.

      Result

      New patients receiving immunotherapy were 69 and the most common toxicities were; asthenia (82.5%), skin toxicity (35.5%), Pneumonitis (22.5%), colitis (20%), arthralgia (12.5%), endocrine toxicity (12.5%), emesis (10%), vascular (7.5%), gastritis (5%), hepatic (5%), renal (5%) & neurologic (5%). Attending grading severity, it was GI-GII, both were controlled by nurses, GIII and GIV required specialists, hospitalization and other professionals. Nurses visited 95% of the patients previously to initiate their treatments, attended 128 phone calls and in 111 patients they realised the follow-up and control. From total a 50% need emergency services and finally got hospitalization in 30% of them.

      Conclusion

      Grades I and II are the most common toxicity. Nurses were in charge for patient education, providing careful information to patients, family members and caregivers, along the whole process. This role is vital to get better and earlier control on the side-effects, higher satisfaction and to facilitate the multidisciplinary team-working dynamic.

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      OA05.07 - Co-Operation Between the Cities of Glasgow and Bethlehem and the Development of a Cancer Nursing Diploma at Bethlehem University Palestine (Now Available) (ID 206)

      15:15 - 16:45  |  Presenting Author(s): Gerry O Hare

      • Abstract
      • Presentation
      • Slides

      Background

      Cancer is a serious public health issue in Palestine. The impact of the conflict between Palestine and Israel has a negative impact on the diagnosis and treatment of cancer patients. In addition, the political situation has hindered the development of effective cancer nursing reflective practice and education for Palestinian nurses. A meeting between Gerry O Hare (oncology CNS Glasgow and Clyde Health Board) and Mariam Awad (Dean of Nursing Bethlehem University) in 2011 led to an exploration of opportunities for cancer nursing educational initiatives between Glasgow, Scotland and Bethlehem Palestine.

      Support for cancer nurses education was secured from Glasgow Health Board, the office of Lord Provost of Glasgow, Bethlehem University, Medical Aid for Palestine, European Oncology Nursing Society, Palestinian Dept of Health, and supportive UK and Bethlehem nurse academics. This multi-agency commitment and support resulted in the launch of the first Post-Graduate High Diploma in Cancer/Palliative nursing in Palestine by the Nursing Department at Bethlehem University Palestine in 2016.

      This is an example of motivated nurses from geographical distant countries positively influencing agencies to develop a pioneering cancer/palliative care nurse educational high diploma programme at Bethlehem University, Palestine. This initiative sends a message to cancer nurses globally to encourage them to cross cultural, political and geographical barriers to achieving positive outcomes for cancer nurse education.

      Method

      Section not applicable

      Result

      Section not applicaple

      Conclusion

      Section not applicable

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      OA05.08 - Discussant - OA05.05, OA05.06, OA05.07 (Now Available) (ID 3754)

      15:15 - 16:45  |  Presenting Author(s): Mary Duffy

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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      OA05.09 - IASLC Lectureship Award for Nursing and Allied Health (Now Available) (ID 3755)

      15:15 - 16:45  |  Presenting Author(s): Kahren White

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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    SH01 - Highlight of the Previous Day (ID 98)

    • Event: WCLC 2019
    • Type: Highlight of the Previous Day Session
    • Track:
    • Presentations: 6
    • Now Available
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      SH01.01 - Surgery (Now Available) (ID 3658)

      11:00 - 12:30  |  Presenting Author(s): Khaled Alkattan

      • Abstract
      • Presentation
      • Slides

      Abstract

      Section not applicable

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      SH01.02 - Radiation (Now Available) (ID 3659)

      11:00 - 12:30  |  Presenting Author(s): Laurie Gaspar

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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      SH01.03 - Advanced Lung Cancer (Now Available) (ID 3660)

      11:00 - 12:30  |  Presenting Author(s): Digambar Behera

      • Abstract
      • Presentation
      • Slides

      Abstract

      Will submit as and when available.

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      SH01.04 - Targeted Therapy (Now Available) (ID 3661)

      11:00 - 12:30  |  Presenting Author(s): Rosario Garcia Campelo

      • Abstract
      • Presentation
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      SH01.05 - Mesothelioma (Now Available) (ID 3662)

      11:00 - 12:30  |  Presenting Author(s): Michele Carbone

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      SH01.06 - Immunotherapy (Now Available) (ID 3855)

      11:00 - 12:30  |  Presenting Author(s): Margarita Majem

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    WS03 - ITONF Workshop: Bridging the Gaps in Thoracic Oncology Nursing - A Global Perspective (Sign Up Required) (ID 104)

    • Event: WCLC 2019
    • Type: Workshop
    • Track: Nursing and Allied Professionals
    • Presentations: 8
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      WS03.02 - Business Meeting (Now Available) (ID 3850)

      11:00 - 18:00  |  Presenting Author(s): Maria Guerin

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      WS03.03 - Keynote Address (Now Available) (ID 3668)

      11:00 - 18:00  |  Presenting Author(s): Gerry O Hare

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      WS03.04 - Lung Cancer and Mesothelioma Nursing Care in Spain (Now Available) (ID 3669)

      11:00 - 18:00  |  Presenting Author(s): Maria Paz Fernandez-Ortega

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      WS03.06 - Panel - Innovative Nursing Care in Early Stage Lung Cancer: A Global Perspective (Now Available) (ID 3671)

      11:00 - 18:00  |  Presenting Author(s): Mark Shaw, John G Edwards, Sorah Levy

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      WS03.08 - Panel - Emerging Therapies - Immunotherapy (Now Available) (ID 3673)

      11:00 - 18:00  |  Presenting Author(s): Marianne Davies, Beth Eaby-Sandy, Rachel Thomas

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      Abstract

      IASLC Abstract for Presentation.

      By Rachel Thomas

      This panel session will focus on emerging immunotherapies, the aim is to bring the UK perspective to the panel particularly focusing on the role of the Lung Cancer Clinical Nurse Specialist (CNS) and how to support and counsel patients who are about to commence one of the new therapy combinations. The presentation from the UK will look at the current therapies in immunotherapy and then also look at two case studies which will bring the clinical trial data into real time perspective.

      In the UK there have been no new immunotherapies launched, however, what the landscape of immunotherapies is changing in the UK for non-small cell lung cancer patients in the form of multi-drug combinations. Most recently we have seen the introduction of Durvalumab as a treatment for locally advanced unresectable non-small cell lung cancer post platinum based chemoradiation (1). This combination is still awaiting formal NICE approval but NHS patients can access this via a Cancer Drugs Fund. The PACIFIC Trial demonstrated that patients who received Durvalumab after platinum based chemoradiation had a significant improvement in their progression free survival when compared to chemoradiation plus a placebo. The median duration of progression free survival was 17.2 months in the Durvalumab arm compared to 5.6 months in the placebo arm. The median time to death or distant metastases was 28.3 months in the Durvalumab arm compared to 16.2 months in the placebo arm (2).

      In the advanced metastatic setting there has recently been the introduction of the KEYNOTE-189 data which is looking at pembrolizamab + platinum/pemetrexed in patients who did not have any molecular mutations. This trial demonstrated an overall survival with a 51% reduction in the risk of death and superior progression free with a 48% reduction in the risk of progression or death.

      In March 2019 The IMpower150 trial showed significant improvements in progression-free and overall survival with atezolizumab plus bevacizumab plus carboplatin plus paclitaxel (ABCP) versus the standard-of-care bevacizumab plus carboplatin plus paclitaxel (BCP) in chemotherapy-naive patients with non-squamous metastatic non-small-cell lung cancer who have an ALK rearrangement or who have an EGFR mutation. This combination has now been approved by NICE and will provide patients who progress on a tyrosine kinase inhibitor a multi-drug treatment combination which has been demonstrated in the Impower 150 trial to deliver overall survival of around 19.2 months when compared to bevacizumab/carboplatin and paclitaxel.

      The UK has demonstrated the importance of the input of the Lung Cancer CNS in supporting patients who are about to commence treatment and also in proactively monitoring patients for potential adverse events (3). However, with the emergence of multidrug treatments how do we as Lung Cancer CNS’s assess which adverse events are related to the immunotherapy and which are related to the chemotherapy. Looking at the current clinical trial data from the studies above and then focusing on two real life patient case studies will provide some clear guidance on how to support patients whilst monitoring for any potential adverse events and dealing with these in a timely and accurate manner. The table below sets out just some of the main challenges faced in identifying immunotherapy related adverse events.

      io events for iaslc abstract.png

      We as nurse specialists are now experienced at caring for patients on single agent immunotherapy treatments but one of the many challenges is that many lung cancer patients will have co-morbidities which can cloud the identification of immunotherapy adverse events. For example 40-70% of lung cancer patients will also have a diagnosis of COPD. Pneumonitis can present in a very similar pattern to organising pneumonia and chest infections meaning that accurate and detailed assessments are needed to ensure adverse events are identified and treated accordingly. However, when you also add into the treatment plan platinum doublet chemotherapy with or without radiotherapy the potential for adverse events increases, the panel will look at the PACIFIC data to assess the reporting of adverse events in this patient group. The panel will also then assess the trial data for platimum doublet chemotherapy and immunotherapy in the treatment of metastatic non-small cell lung cancer and whether this patient group with a potentially higher symptom burden reported an increase in the number of adverse events when compared to either single agent immunotherapy or platinum doublet chemotherapy alone.

      One other important focus of the panel discussion will be to look at what the future treatment landscape for patients may be and how this will impact on progression free survival and living with lung cancer. This will mainly cover recent updates from ASCO and will aim to provide a flavour of what we may see coming into clinical practice in the coming months.

      References

      Durvalumab for treating locally advanced unresectable non-small-cell lung cancer after platinum-based chemoradiation. Technology appraisal guidance [TA578] Published date: 01 May 2019. https://www.nice.org.uk/guidance/TA578

      Overall survival with Durvalumab after chemoradiotherapy in Stage III NSCLC. Scott. A; Augusto, V; Davey, D et al. www.nejm.org/doi/full/10.1056/NEJMoa1809697.

      The National Lung Cancer Audit (2018) www.rcplondon.ac.uk/projects/national-lung-cancer-audit

      https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(19)30084-0/fulltext

      Yoest JM (2017) Clinical features, predictive correlates and pathophysiology of immune related adverse events in immune checkpoint inhibitor treatments in cancer: a short review. Immunotargets Therapeutics. 6. P 73-82.

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      WS03.10 - Bridging the Gap – Implement Knowledge into Local Practice (Now Available) (ID 3675)

      11:00 - 18:00  |  Presenting Author(s): Roma Maguire

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      WS03.11 - Poster Session - What’s New in Global Thoracic Oncology Nursing (Now Available) (ID 3676)

      11:00 - 18:00  |  Presenting Author(s): Melissa Jane Culligan

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      WS03.12 - ITONF Membership Meeting and Getting to Know Your Peers – ITONF Reception (ID 3677)

      11:00 - 18:00  |  Presenting Author(s): Maria Guerin

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