Virtual Library

Abstract:
Immunotherapy has become a large part of care for patients with lung cancer and has a very different side effect profile than what Allied Health Care Professionals are use to managing. To that end, the nursing and allied health care research committee of IASLC has developed Immunotherapy Side Effect Guidelines to assist the AHCP in assessing and managing their patients on immunotherapy. This presentation will review these guidelines and discuss implementation in the treatment setting.

Abstract:
This presentation will outline the rationale, role and evidence supporting pulmonary rehabilitation for people with lung cancer. Lung cancer is associated with high disease burden and physical hardship. Individuals with lung cancer experience complex symptoms, which can include dyspnoea, fatigue and pain. These frequently lead to a cycle of inactivity and functional decline. Individuals with lung cancer 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 pre-treatment levels within six months [1]. Progressive functional decline occurs over this time, with reduction in exercise capacity and muscle strength [1]. In lung cancer, reduced exercise performance is associated with poorer functional independence, worse cancer treatment tolerability and higher all-cause mortality [2]. People with lung cancer, 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]. There is a strong need for pulmonary rehabilitation for this patient group [3]. There are well-established guidelines regarding exercise for people with cancer [4]. The guidelines state that people with cancer should engage in 30 minutes of moderate intensity physical activity on five or more days of the week and muscle strengthening exercises at least twice a week. This is supported by research which demonstrates that exercise is associated with improved exercise capacity, physical function, muscle strength, HRQoL, symptoms and depression in many cancer types [4]. The evidence for pulmonary rehabilitation specifically in non-small cell lung cancer (NSCLC) is growing rapidly [3, 5, 6]. Studies consistently demonstrate that pulmonary rehabilitation and exercise training is safe in lung cancer [3]. Pulmonary rehabilitation can be applied at any stage along the disease spectrum. The majority of evidence currently exists in the pre- and post-operative settings, however there is now growing evidence for pulmonary rehabilitation in advanced stage disease [3]. Prehabilitation is exercise training delivered before treatment. This is a relatively new concept in lung cancer. A recent Cochrane review [5] of exercise training for patients before surgery for NSCLC, included five randomised controlled trials (RCTs), and found pre-operative exercise training compared to usual care (no exercise) was associated with a 67% reduced risk of patients developing a postoperative pulmonary complication, fewer days that patients needed an intercostal catheter (mean difference MD -3.33 days, 95%CI -5.35 to -1.30); shorter post-operative hospital stay (MD -4.24 days, 95%CI -5.43 to -3.06) and improvement in exercise capacity (6-minute walk test MD 18.23m, 95%CI 8.50 to 27.96 m). Recently Licker and colleagues found that preoperative high-intensity interval training and resistance training improved exercise performance, as compared with an exercise and lifestyle advice group who experienced deterioration in exercise capacity while waiting for surgery [7]. The Cochrane review concluded the overall quality of evidence is low and more high-quality trials are needed [5]. Pulmonary rehabilitation following treatment with curative intent is associated with improvements in exercise capacity, muscle function and fatigue [3]. The Cochrane review of exercise training after lung resection included three RCTs, and found significant improvements in exercise capacity in favour of the intervention compared to usual care (no exercise) (6-minute walk test MD 50m, 95% CI 15 to 85) [6]. More recently, Edvardsen and colleagues found a 20-week high intensity endurance and resistance training program compared to usual care, commencing 5-7 weeks post-operatively, was associated with improved exercise capacity, quadriceps muscle strength and mass, and physical function [8]. There is less evidence published to date on pulmonary rehabilitation in advanced disease, however the early evidence suggests that exercise may be effective at increasing exercise capacity, function and HRQoL, and reducing symptoms [3] There are a number of current RCTs in progress at the moment specifically investigating exercise in inoperable or advanced lung cancer. The specific exercise training prescription in lung cancer has varied in the studies completed to date. It is likely that a combination of aerobic and resistance training is required for maximum effect to target both skeletal muscle function and cardiorespiratory fitness; both of which contribute to poor exercise performance in lung cancer [9]. Similarly, the duration of programs (weeks to months) and delivery (inpatient, outpatient, home based) has varied. Further research is required to confirm the optimal timing, prescription and delivery of pulmonary rehabilitation for people with lung cancer. In most countries, pulmonary rehabilitation is not currently part of routine clinical practice for people with lung cancer. As the evidence base grows our next challenge is to translate findings into clinical practice [10]. 1. Granger, C., et al., Low physical activity levels and functional decline in individuals with lung cancer. Lung Cancer, 2014. 83(2):292-299. 2. Jones, L.W., et al., Prognostic significance of functional capacity and exercise behavior in patients with metastatic non-small cell lung cancer. Lung Cancer, 2012. 76(2):248-252. 3. Granger, C., Physiotherapy management of lung cancer. Journal of Physiotherapy, 2016. 62(2):60-67. 4. Schmitz, K., et al., ACSM roundtable on exercise guidelines for cancer survivors. Medicine Science Sports Exercise, 2010. 42(7):1409-1426. 5. Cavalheri, V. and C. Granger, Preoperative exercise training for patients with non-small cell lung cancer. Cochrane Database of Systematic Reviews, 2017(6). 6. Cavalheri, V., et al., Exercise training undertaken by people within 12 months of lung resection for non-small cell lung cancer. Cochrane Database of Systematic Reviews, 2015(7). 7. Licker, M., et al., Short-Term Preoperative High-Intensity Interval Training in Patients Awaiting Lung Cancer Surgery: A Randomized Controlled Trial. J Thorac Oncol, 2017. 12(2):323-333. 8. Edvardsen, E., et al., High-intensity training following lung cancer surgery: a randomised controlled trial. Thorax, 2015. 70(3):244-250. 9. Burtin, C., et al., Lower-limb muscle function is a determinant of exercise tolerance after lung resection surgery in patients with lung cancer. Respirology, 2017. 22(6):1185-1189. 10. Granger, C.L., et al., Barriers to Translation of Physical Activity into the Lung Cancer Model of Care. A Qualitative Study of Clinicians' Perspectives. Ann Am Thorac Soc, 2016. 13(12):2215-2222.

Abstract:
While lung cancer care internationally is spoken about in terms of being multidisciplinary, how far does this go in practice, to having comprehensive multidisciplinary involvement of all appropriate medical, nursing and allied health professionals as part of standard lung cancer care? There are an increasing number of allied health professionals internationally who specialise in oncology, with an increase in the evidence base for interventions. I propose that the involvement of allied health professionals as part of standard lung cancer care will lead to improved comprehensive multidisciplinary care, with improved quality of life and function for people living with a lung cancer diagnosis. The core allied health professions include occupational therapy, physiotherapy, exercise physiology, dietetics, speech pathology, social work and psychology. Some countries have other professions that fit into the allied health disciplines, such as physician’s assistant and respiratory therapist. This presentation will focus on the disciplines found primarily in Australia and the UK. Occupational Therapy focuses on enabling ongoing participation in chosen everyday activities. In curative treatment, the occupational therapist has a key role in pre-habilitation, assisting the individual to reach optimum function prior to treatment, and rehabilitation following treatment, to facilitate the persons return to previous chosen and meaningful roles. In metastatic disease, the occupational therapist focuses on enabling continued participation in chosen and meaningful roles. In the acute hospital setting the focus is often on what functional level the individual needs to be at to be able to safely manage the tasks of personal care, meal preparation and other personal and community activities of daily living at home following discharge. While these aspects of function are important, it is key to allow the person living with lung cancer to identify the roles and tasks that they find meaningful and important to participate in. A person may choose to have community assistance with personal care and meal preparation, as this ensures they have the energy to participate in activities that lead to improved engagement and quality of life. Physiotherapy is concerned with identifying and maximising quality of life and movement potential in the areas of promotion, prevention, treatment/intervention, habilitation and rehabilitation[1]. Physiotherapists have a key role in working with people living with lung cancer prior to and following their treatment for lung cancer. There is a growing body of evidence that suggests exercise following treatment for lung cancer is associated with improvements in physical and psychological outcomes[2]. Exercise physiologists are newer members of the lung cancer multidisciplinary team. In Australia, we are seeing as increasing use of exercise physiologists in the private hospital and pulmonary rehabilitation setting. Their role is of smaller scope than physiotherapists, focusing on prescribing and supervising exercise programs to improve exercise capacity, with the aim of improving function and quality of life. Dieticians are key members of the lung cancer team, however they are often not embedded within the multidisciplinary team. Given that cancer cachexia is a common symptom in lung cancer, affecting functional status, treatment tolerance and survival[3] we should be seeing an increase of dieticians within the lung cancer multidisciplinary team internationally. Speech pathologists provide expert assessment and treatment of swallowing and communication disorders. There is a growing body of evidence in the treatment for head and neck cancer, however there is currently no published speech pathology research in the lung cancer space. People living with lung cancer may require the specialist input of a speech pathologist due to dysphagia, as a result of treatment or disease, or speech difficulties caused by brain metastasis. Social Work and Psychology are key members of the lung cancer multidisciplinary team, as studies have demonstrated the prevalence of distress in lung cancer patients to be high[4,5]. All lung cancer patients should have their psychosocial needs regularly screened, with appropriate referrals for support made to ensure these needs are met. Psychologists and social workers need to be embedded within the lung cancer multidisciplinary team to ensure appropriate screening and intervention of patients. Lung cancer multidisciplinary teams need to utilise their allied health professionals to ensure comprehensive care is offered, and received, by patients who are living with a lung cancer diagnosis. There is a paucity of evidence and research into allied health interventions that may benefit people living with lung cancer. It is critical that allied health professionals build on the evidence and continue to research the efficacy of interventions used to optimise quality of life and function for people living with lung cancer. References: WORLD CONFEDERATION OF PHYSICAL THERAPY 2011. Policy statement: Description of physical therapy. World Federation of Physical Therapy. GRANGER CL 2016. Physiotherapy management of lung cancer. Journal of Physiotherapy, 62, 60-67. PERCIVAL C, HUSSAIN A, ZADORA-CHRZASTOWSKA S, WHITE G, MADDOCKS M & WILCOCK A 2013. Providing nutritional support to patients with thoracic cancer: Findings of a dedicated rehabilitation service. Respiratory Medicine, 107, 753-761. STEINBERG T, ROSEMAN M, KASYMJANOVA G, DOBSON S, LAJEUNESSE L, DAJCZMAN E, KREISMAN H, MACDONALD N, AGULNIK J, COHEN V, ROSBERGER Z, CHASEN M & SMALL D 2009. Prevalence of emotional distress in newly diagnosed lung cancer patients. Support Care Cancer, 17, 1493-1497. ZABORA J, BRINTZENHOFESZOC K, CURBOW B, HOOKER C & PIANTADOSI S 2001. The prevalence of psychological distress by cancer site. Psycho-Oncology, 10, 19-28.

Abstract:
Beyond the basics: The status and future directions of mesothelioma treatments Background: While prognostic factors for pleural and peritoneal mesothelioma have been investigated over the last decade, the characterization of molecular alterations in pleural mesothelioma may lead to a better understanding of tumorigenesis and targeted chemotherapeutic treatments for these tumors. In a recent study examining mutation burden outcome of non-small cell lung cancer, Rizvi et al. found that smokers had more mutations, correlated higher mutation load, and better clinical outcome to immune-targeted therapies than non-smokers. This has yet to been fully elucidated for MPM. Method: A systematic review of literature published from October 2009 – July 2017 was done using PubMed. Discussion: Various studies have shown patients with a history of smoking and asbestos exposure have a greater mutation burden than non-smokers. Despite non-small cell lung cancer studies suggesting that patients with greater mutational burden have better clinical outcomes to immune-targeted therapies, this population of MPM patients typically is excluded from these trials. To date there has not been a study showing that MPM patients with multiple malignancies should be precluded from participating in immunotherapy trials. Participatory groups in immunotherapy must be reshaped to include this subset of MPM patients to better grasp the role that multiple malignancies play with regards to appropriate treatment measures. It is notable that several large mesothelioma trials have not successfully made it pass Phase 2. This suggests that the correct population has not been identified. Perhaps early data showing promising results are merely a synergistic effect between study agents and tumor burden and should be reconsidered. Rather than potentiating study agents effects, increased tumor burden may be an independent factor in patient response. Conclusion: Elucidation of the role of tumor burden may improve the effectiveness and utility of novel MPM which retains its attractiveness despite the current sparse and narrow body of supporting data. Instead of observing treatment by individual case, there must be a shift in treatment observation to account for populations of similar characteristics (i.e. multiple malignancies). With no cure for mesothelioma on the horizon, evaluating the study populations will be imperative to understanding the effectiveness of these new treatments.

Abstract not provided

Background:
Coordinated multidisciplinary (MD) lung cancer care, with all key specialists concurrently providing early input to develop a consensus care plan in collaboration with patients and their caregivers, may improve patient-centered outcomes over the usual serial care (SC) model, but needs rigorous evaluation.

Method:
Prospective, longitudinal study comparing newly-diagnosed lung cancer patients receiving MD vs. SC within the same US healthcare system. The MD intervention was implemented from lung cancer care initiation until definitive treatment decision. After that, both cohorts of patients received their actual cancer treatments within the same environments. At baseline and 6 months, patients completed treatment-related satisfaction measures from the Consumer Assessment of Healthcare Providers and Systems (CAHPS) and the Functional Assessment of Cancer Therapy- Lung (FACT-L) quality of life instrument. All measures were coded so that larger scores are better. Time-specific comparisons were made with the Wilcoxon-Mann-Whitney test and changes from baseline to 6 months were compared between MD vs. SC patients in mixed linear models.

Result:
The 463 patients who participated (156 MD, 307 SC) were similar in sex and health insurance. MD cohort was slightly older (69 v 66 years), with more racial minorities (37% v 29%). Patients receiving MD care reported greater satisfaction with the treatment plan (p=0.0266) and overall quality of care (p<0.0010) at 6 months. Additionally, satisfaction with the treatment plan showed greater improvement over time for MD vs. SC (p-value for trend=0.0046). SC patients showed more improvement in satisfaction with overall care than MD patients, but did not reach the level of satisfaction of MD patients at 6 months (p-value for trend=0.0018). Caregivers of MD patients perceived receiving better quality of care compared to other lung cancer patients than caregivers of SC patients (p=0.0049). Caregiver satisfaction did not differ between MD and SC in the communication measures or overall quality, and did not have significant differences in the trend over time. Patient reported Health-Related Quality of Life (HRQOL) improved from baseline to 6 months for the lung cancer-specific scale compared with no change with SC (p-value for trend= 0.0334). Other HRQOL scales were similar between groups

Conclusion:
Compared with SC patients, MD patients experienced improved lung cancer-specific HRQOL and greater satisfaction with both treatment plan and quality of care received. MD patients’ caregivers were more likely than SC patients’ caregivers to think their care was better than that of other patients.

Background:
The Psychosocial Screen for Cancer (PSSCAN-R) questionnaire and the Canadian Problem Checklist (CPC) are validated screening tools used to identify the psychosocial needs of patients with cancer. The questionnaire identifies at-risk patients requiring timely psychosocial intervention and the CPC comprises of patient-reported support needs in 6 psychosocial domains. The study goal was to review reported needs of patients with NSCLC to facilitate the development of programs and resources specific to those identified as at-risk for psychosocial distress.

Method:
All patients with NSCLC referred to BC Cancer Agency centres from 2011-2015, who completed a prospective PSSCAN-R and CPC questionnaire at the time of their first visit, were included in the study. Demographics and baseline disease characteristics were collected retrospectively. Univariate analysis using the Chi-squared test and Fisher’s exact test were used to compare patient groups based on gender, age and stage of disease.

Result:
4313 patients completed the PSSCAN-R and CPC questionnaire. The median age was 70 (21-99), with 50% female and 51% of patients with stage IV disease. 29% of patients live alone with 13% having lost their spouse/partner. However, 93% of patients report regular contact with friends/relatives and 85% have someone who can provide assistance with daily tasks (shopping, cooking, transportation). Female patients, patients aged 65 or younger, and those with advanced disease were more likely to report significantly higher levels of anxiety and depression, and reported higher number of needs on the CPC. Figure 1



Conclusion:
Newly diagnosed patients with NSCLC report clinically higher levels of anxiety and depression and have greater number of concerns in multiple psychosocial domains. Resources should be developed for lung cancer patients based on their care needs with careful consideration of patients' age, gender and disease stage to optimally support their psychosocial needs during treatment and follow up.

Abstract not provided

Background:
The Mesothelioma Applied Research Foundation is the nonprofit collaboration of patients and families, physicians, advocates, and researchers dedicated to eradicating the life-ending and vicious effects of mesothelioma. The Meso Foundation’s Advocacy Program objective is to obtain federal funding for mesothelioma research.

Method:
An analysis was performed of the Meso Foundation’s advocacy efforts and grant funding from years 2000- 2015.

Result:
The Meso Foundation has funded 103 projects from 8 countries for a total awarded amount of 9.8 million dollars. From 2000- 2015, the Meso Foundation grant program has funded research that has produced over 240 publications in peer reviewed journals. As a direct result of Foundation advocacy, the Department of Defense has awarded a total of $12.4 million to mesothelioma research since 2008. The Meso Foundation’s grant program has funded the basic science research that helped lay the groundwork for several mesothelioma clinical trials. A few of the more notable trials include the measles virus and the WTI Vaccine. Several of the proposals funded by Meso Foundation grants have extended to global levels through presentations at international conferences including but not limited to International Association for the Study of Lung Cancer (IASLC), American Society of Clinical Oncology (ASCO), and American Association for Cancer Research (AACR).

Conclusion:
Through actively engaging members of congress, the Meso Foundation has successfully advocated for increased funding for mesothelioma research. The Meso Foundation is committed to leveraging the knowledge we gain from our own research, as well as discoveries made by our collaborations with academic institutions and industry partners to work toward the development of innovative treatments and care platforms for mesothelioma patients and their families.

Background:
When captured by psychometrically-sound patient-reported outcomes measures (PROMs), patients’ appraisals of their symptoms, quality of life and functional status can provide powerful data to better inform clinicians about the impact of health conditions and the consequences of medical care. Reviewing and reporting on integrated PROMs alongside clinical data may translate to health service improvements and efficiencies. There are, however, many challenges including the need to find sustainable and cost-efficient methods for the routine collection of PROMs across the whole patient journey. This two-phase study set out to develop a lung cancer clinical quality registry framework to collect longitudinal patient-reported outcome measures. Phase 1 focused on the development of the data collection framework and phase 2 sees a 12-month implementation and mixed-method evaluation of the feasibility of implementing the framework. We will report on development of the framework and provide preliminary results on the implementation phase.

Method:
The development phase utilised a formative evaluation method to decide on essential aspects of the PROMs framework. Specifically, a Delphi process was employed to seek consensus on PROMs to administer and the schedule of assessments, with a specific focus on clinical relevance and feasibility of administration. The first Delphi round consisted of individual interviews with lung cancer clinical experts to generate a list of domains to be included in the PROMs. In the second round, aggregated results were presented to the panel and domains of interest were considered alongside PROMs meeting minimum measurement standards. Then, four patients previously treated for lung cancer were invited to provide feedback on the content of PROMs and data collection methods.

Result:
From Delphi findings, it was determined that the EORTC QLQ-C30 and the lung cancer-specific module (QLQ LC13) would be administered at baseline and two, six and 12 months after baseline, and a brief social isolation measure (PROMIS) would be administered at baseline only. A clearly defined subset of patients about to commence chemo-radiation treatment for lung cancer was chosen for the implementation phase and commenced on October 31 2016. To date, 74% (14/19) of eligible patients have been recruited thus far. Preliminary data indicate high adherence to baseline assessments (100%). Adherence is much lower at two months (50%), with non-adherence frequently due to side effects or ill health (38%).

Conclusion:
Identifying and deciding which PROMs to collect, the overall purpose of PROMs collection, data completeness and utility requires careful consideration and evaluation to determine framework sustainability.

Background:
Despite evidence that lung cancer disproportionately affects minority populations, there is a paucity of data describing the impact of lung cancer screening. Results of NLST may not be generalizable to all populations given that 91% of the participants were Caucasians. Further study of lung cancer screening in a diversity of racial and ethnic groups is a necessary step in the implementation of lung cancer screening. Before underrepresented populations can be screened, community perceptions about lung cancer screening must be explored and barriers to screening must be identified. The purpose of our study was to identify potentially correctable barriers to obtaining LDCT for lung cancer screening in a diverse, but predominantly African American population.

Method:
We developed a questionnaire consisting of 22 items. Five questions assessed patient demographics including socioeconomic status and insurance coverage. Two questions assessed patient access and utilization of health care. Three questions assessed smoking history and prevalence in interpersonal relationships. One questions assessed patient concern about lung cancer. Two questions measured patient knowledge about lung cancer. One question addressed patient willingness to go to a doctor’s appointment to learn more about lung cancer screening. One question elicited whether LDCT had been mentioned by a healthcare provider. Six questions assessed awareness and knowledge about LDCT lung cancer screening. One question addressed reasons for non-adherence to appointments.

Result:
The questionnare was complete by 100 patients. Almost all of our patients reported having health insurance and a primary care doctor (96%). 50% of patients are current or former smokers. 83% are current or former smokers or have friends and/or family members who are heavy/long time smokers. 90% of patients knew that smoking is the most common cause of lung cancer. 56% of patients know that lung cancer can be treated successfully at least sometimes. 81% of patients reported to be at least somewhat concerned that they or someone they know can die of lung cancer. 87% of patients are willing to go to a doctor’s appointment to learn more about lung cancer screening. 100 % of patients reported to have not heard about LDCT from their doctors. The average score was 2/6 (33%) on items accessing knowledge about lung cancer screening. Cost was the most frequently reported reason (52%) for nonadherence to appointments.

Conclusion:
Our study was able to identify potentially correctable barriers to utilization of low dose CT lung cancer screening such a lack of primary care support and perceived cost.

Abstract not provided

Background:
Japan’s measures to prevent passive smoking are considered to be among the world’s worst. Creating smoke-free environments is an urgent task for Japan as it prepares to host the 2020 Tokyo Olympics and Paralympics Games. In spring of 2017, discussions on a draft bill to strengthen measures against passive smoking were stalled due to opposition from within the ruling party. One lawmaker remarked that “(Cancer patients) don’t have to work”, indicating that patients can choose their occupation and avoid secondhand smoke as they wish. Against this backdrop, the Japan Lung Cancer Alliance conducted a survey on damage by secondhand smoke to cancer patients. Based on the survey’ result, this study aims to shed light on the problems experienced by lung cancer patients including the impact of secondhand smoke on their employment.

Method:
For 5 days from 28 May to 1 June 2017, a survey by questionnaires was conducted on lung cancer patients. The announcement of the survey was made by ten patient advocacy groups.

Result:
There were 231 responses, among which valid responses were 215. 91 percent of the respondents considered passive smoking “unpleasant” due to fears or anxieties for recurrence of lung cancer and/or hatred. It was found that among those respondents who were employed at the time of the survey, about 31 percent had been exposed to secondhand smoke at their workplace, and 4.2 percent had quitted their job. Not only at the work place, 6.2 percent of the respondents were exposed to the secondhand smoke at home, event after they were diagnosed as lung cancer.

Conclusion:
It is understood that working cancer patients worry about recurrence of cancer and/or hatred. Moreover, the experiences of those lung cancer patients who had left their job because of passive smoking reveal a lack of the freedom to choose their occupation. The urgent countermeasure is also required to prevent the passive smoking at home. Japan’s delay in adopting measures against passive smoking appears be related to an insufficient level of understanding in the society about difficulties faced by cancer patients. It is hoped that this study will draw attention to the damage by passive smoking to lung cancer patients and foster international support for the advocacy of legislation enacting stricter measures.

Background:
The rising imperative to improve our understanding of cancer heterogeneity and individualised drug response has led to a high demand for biopsy material. With improvements in technologies, there is now a move away from more traditional tissue based sampling to liquid based biopsies. ‘Liquid biopsies’ provide a non-invasive means for molecularly profiling patients with cancer, thus benefiting patients and clinicians in terms of treatment choice and shared decision-making. We assessed the willingness of patients to undergo repeated tissue and/or ‘liquid’ based sampling.

Method:
Detailed questionnaires, assessing patients’ perceptions of, and willingness to undergo serial biopsies were distributed to ambulatory patients at a tertiary cancer referral centre (St. James’s Hospital, Dublin). Multivariate analysis was performed using ordinal logistic regression analysis.

Result:
The questionnaire response rate was 97% (247/255). Respondents were primarily female (73%), aged between 51-70 yrs (51%), with breast (39%), colorectal (16%), oesophagogastric (13%), and lung cancer (12%). Of those that responded, repeat biopsy of an easily accessible lesion was acceptable to 203 (82%) patients if recommended by an oncologist. However this reduced to 102 (41%) patients, if the purpose was solely for clinical trial. Acceptability decreased to 168 (68%) and 81 (33%) patients respectively for more invasive biopsies. Additionally, 79 (32%) patients were willing to undergo additional biopsy for research purposes only, with 54 (21%) patients uncertain of its utility in research. Lower performance status (OR=0.44, p=0.04) and the belief that biopsy was unimportant for research (OR=0.74, p=0.04) negatively impacted on willingness to undergo biopsy, while a prior invasive biopsy increased acceptance (OR=1.02, p=0.02). In terms of blood sampling, 82% of patients would consent to repeated blood sampling over the course of their treatment, with >5 samples considered acceptable by 51.5% of patients. Patients with lung cancer had 3.38 greater odds (OR=3.38, p=0.047) of consenting to a repeated blood sample for purely research purposes (compared to any other type of cancer); however their willingness to undergo repeat biopsy was similar to that of other patients (OR=1.99, p=0.129). Data analysis is currently on-going.

Conclusion:
Patients with cancer are willing to participate in serial sampling of blood and urine but are less likely to consent to repeated tissue biopsies. Patients with lung cancer were particularly amenable to repeated blood sampling compared to patients with other cancer types. This is significant given the recent data supporting the use of ‘liquid’ biopsy for real-time monitoring of resistance mutations and treatment response dynamics in patients with lung cancer.

Background:
Lung cancer stigma has wide-reaching effects and impacts treatment, quality of life, survival, societal attitudes, research funding, and advocacy efforts. Those affected by lung cancer commonly feel hopeless, isolated, reluctant to share their diagnosis in addition to feelings of guilt, shame, anxiety and depression. Stigma responses can hinder information seeking information related to treatment options and psychosocial support and, tragically, can cause delays in diagnosis and even refusal of treatment. Major pan-cancer organizations, those dedicated to all lung diseases as well as lung cancer-specific organizations conduct awareness raising campaigns designed to confront lung cancer stigma, all working in some measure to create a more compassionate and empathic environment for those at-risk and diagnosed. These efforts have not been coordinated and to date, no known comprehensive vision to address lung cancer stigma in its entirety has been developed.

Method:
HIV/AIDS and mental health advocates have devoted extensive efforts to developing coordinated stigma reduction plans. While not always applicable, their approaches can inform our efforts in lung cancer. To develop a comprehensive framework to address lung cancer stigma, a synthesis of relevant strategies used in other disease-states, a review of lung cancer stigma literature and exploration of the efforts of organizations and individuals from around the world was conducted.

Result:
Awareness-raising, myth-busting and public health advocacy are featured prominently in other stigma-reduction plans. Lung cancer, like HIV/AIDS and other smoking-related cancers, must also address nihilism from medical professionals and work to ensure non-judgmental discussions and compassionate treatment environments that explore appropriate treatment options become the norm. Founded on seven key areas of opportunity, the plan includes multiple areas of impact that need to be addressed. Included are suggested remediation methods and real-world examples from all over the globe to illustrate creative ways lung cancer stigma reduction can be approached. This comprehensive, multi-level, multi-pronged vision allows individuals, systems and organizations to find points of convergence and work collaboratively on addressing the stigma so closely associated with lung cancer.

Conclusion:
Through a comprehensive approach, lung cancer stigma can be reduced and ultimately eliminated. To initiate a global conversation and better unite the lung cancer community, we offer this unifying strategy to address lung cancer stigma. Through the menu of stigma-reduction strategies, we hope to spark conversation, collaboration, and convergence. Dedicated medical professionals, survivors, loved ones, advocacy organizations and others can use the vision to apply appropriate strategies in their regions/countries and work collaboratively toward this all-important goal.

Abstract not provided

Background:
Circulating tumor DNA (ctDNA) has been shown beneficial in monitoring EGFR mutations in blood, especially for the detection of resistance mutations, like T790M in NSCLC patients. However, the role of BRAF (V600E) ctDNA for monitoring the patient’s response has not been studied yet. The aim of this study was to determine the clinical relevance of BRAF (V600E) ctDNA for monitoring the response to BRAF inhibitors in a prospective cohort of advanced NSCLC BRAF (V600E) patients.

Method:
We prospectively enrolled advanced NSCLC patients with BRAF (V600E) treated with BRAF +/- MEK inhibitors in our institution. A blood sample was collected at different time points, including at baseline, during treatment and at progressive disease. ctDNA BRAF analysis was performed using the Inivata InVision platform (enhanced tagged-amplicon next-generation sequencing (eTAM-Seq).

Result:
Between June 2016 and June 2017, 14 patients have been included. Eight patients (57%) were females, 9 (64%) non-smokers, with a median age of 63 years (35-70). All the patients had adenocarcinoma and BRAF (V600E) mutation in tissue analysis. Thirteen patients (93%) had stage IV at diagnosis, 7 patients (50%) with bone, 6 (43%) pleural and 4 (29%) lung metastasis. The median of lines of treatment received was 2 (1-4). Thirteen patients (93%) received BRAF + MEK inhibitor and 1 patient (14%) BRAF inhibitor, with an objective response rate of 64% (1 complete, 8 partial response) and disease control rate of 86%. BRAF mutation detection was tested under treatment in 12 patients (86%). Longitudinal analysis was performed from the serial sampling in 6 patients to date: 4 patients (67%) were ctDNA positive for BRAF (V600E) at time of progression, with a range of allelic frequency of 0.11-6.16%. BRAF mutation was not detectable in patients with objective response (2/6, 33%) at time of sample collection(s). Additional BRAF (V600E) NSCLC patient samples are being analyzed.

Conclusion:
Liquid biopsy for monitoring BRAF (V600E) using ctDNA appears to be feasible and useful in advanced NSCLC patients. Updated longitudinal results for the complete patient cohort will be presented at the meeting.

Background:
To improve treatment selection and outcomes for patients with early stage non-small cell lung cancer (NSCLC) the development of an effective biomarker to diagnose and characterise the tumour and to detect residual disease after curative-intent treatment is crucial. Circulating tumour DNA (ctDNA) is a promising means to detect and track tumours non-invasively, as the genomic alterations in plasma are representative of the tumour’s clonal populations and their levels correlate with the burden of disease. Furthermore, ctDNA has shown promise for detecting minimal residual disease after treatment in several cancer types. This could help in the selection of patients that, after surgery or radical radiotherapy, will benefit from subsequent treatment. Nonetheless, more sensitive techniques are needed to enable the detection and study of ctDNA at very low concentrations in settings such as these.

Method:
The LUCID study (early stages of non-small cell LUng cancer - CIrculating tumour DNA) was designed to prospectively collect plasma samples from patients with early-stage NSCLC before and after treatment with surgery or radiotherapy (±chemotherapy), and during a minimum follow up of 3 years after diagnosis, in order to explore the clinical utility of ctDNA. For high sensitivity detection of ctDNA, TAilored Panel Sequencing (TAPAS) was developed: exome sequencing of tumour tissue enables the creation of patient-specific panels to analyse in parallel, large numbers of mutations with high sequencing depth. Plasma samples are being analysed using this approach to assess the levels of ctDNA at diagnosis and after radical treatment.

Result:
100 patients were recruited to the study. Longitudinal plasma sample collection and analysis are on-going. Preliminary analysis of the tumour tissue and pre-surgical plasma samples from 19 surgical patients show that most patients with early-stage NSCLC have detectable ctDNA. Analysis of additional samples will be presented.

Conclusion:
Preliminary data from LUCID suggest that the methods we have developed have high sensitivity and will allow detection of ctDNA at rates higher than previously reported. These methods will enable the study of ctDNA in early-stage cancers. We are also exploring the utility of these techniques for detection of minimal residual disease after radical treatment, as a potential tool to guide adjuvant or subsequent post-radiotherapy treatment.

Background:
EGFR mutations in plasma circulating free tumor-derived DNA (ctDNA) as a predictor of EGFR TKI efficacy in patients with NSCLC requires validation in prospective studies. The large, prospective Phase II, single-arm, multicenter BENEFIT study (CTONG1405; NCT02282267) validated the efficacy of first-line gefitinib in EGFR mutation-positive NSCLC detected in plasma ctDNA using droplet digital PCR (ddPCR).

Method:
Patients with stage IV lung adenocarcinoma and plasma ctDNA EGFR-sensitizing mutations (exon 19 del or exon 21 L858R; by ddPCR) received first-line gefitinib (250 mg once-daily) until progressive disease (PD). Blood samples were collected every 8 weeks for dynamic EGFR analysis until PD. Primary endpoint was ORR. Secondary endpoints included PFS, DCR (Week 8), and analysis of baseline ctDNA samples by next-generation sequencing (NGS).

Result:
From December 2014-January 2016, 426 patients from 15 Chinese centers were screened: 391 had matched tissue and blood samples; 188 had ctDNA EGFR mutation-positive NSCLC and received gefitinib; and 183 had ≥1 post-baseline tumor assessment and plasma samples every 8 weeks until PD. At data cutoff (January 31, 2017), 152 patients had progressed. ORR was 72.1% (95% CI 65.0%,78.5%); DCR (Week 8) was 92.3% (95% CI 87.5%,95.8%); and median PFS was 9.5 months (95% CI 9.07,11.04). PFS was significantly shorter in the subgroup with baseline ctDNA de novo T790M mutations (5.0%, n=9) versus the EGFR-sensitizing mutations subgroup (5.6 vs 9.6 months, HR=2.60; 95% CI 1.32,5.12, p=0.004). In patients with Week 8 on-treatment plasma samples (n=167), the subgroup who showed EGFR mutation clearance in ctDNA by ddPCR (88%, 147/167) had longer PFS compared with those who did not (11.0 vs 2.1 months, HR=7.28; 95% CI 4.35,12.18, p<0.0001). The median time to emergence of acquired T790M mutation in plasma was 7.6 months. The T790M-positive rate increased from Week 24 (15.7%) to Week 48 (32.6%), with a corresponding increase in PD rate (24.7% at Week 24, 56.9% at Week 48). Among 180 patients with baseline NGS data, 21 (11.7%) harbored aberrations in additional oncogenic drivers (MET, ERBB2, KRAS, BRAF, RET, or ROS1) and tumor suppressors (TP53, RB1, and PTEN). This subgroup had worse PFS versus those with EGFR-sensitizing mutations alone (3.9 vs 13.0 months, HR=2.83; 95% CI 1.65,4.87, p=0.00016).

Conclusion:
The BENEFIT study prospectively demonstrated that ctDNA-based EGFR mutation detection can be used to select patients for treatment with first-line gefitinib. Dynamic alterations in EGFR mutations could be used to predict efficacy and disease progression, ahead of radiological results.

Abstract not provided

Background:
Highly diverse somatic splice site alteration at MET exon 14 (METex14) result in exon skipping, which is supposed to be a therapeutic target in NSCLC. Here we report detection of METex14 alterations using targeted DNA- and RNA-based Next-Generation Sequencing (NGS) in pulmonary sarcomatoid carcinoma (PSC) with a high frequency of METex14 skipping.

Method:
Tumor specimens were collected from 77 Chinese PSC patients. DNA and RNA were subject to targeted NGS, allowing the detection of somatic splice site alterations and intragenic METex14 skipping respectively. Then, somatic mutations (mutation allele frequency ≥2%) that lead to METex14 skipping were recognized, and Fisher’s exact test was used to examine the association between METex14 skipping and clinical characteristics or other mutations. Two-sided P-values <0.05 were considered statistically significant. Moreover, RT-PCR and Sanger sequencing was also performed on the METex14-positive specimens.

Result:
We have detected genetic aberrations in 77 FFPE samples. For RNA-based NGS, METex14 skipping was identified in 16 (20.78%) of 77 patient cases. And 15 (93.75%) METex14-positive patients were detected somatic mutations by DNA-based NGS, including 12 (80%) cases with splice donor site mutations, 1 (6.67%) cases with splice acceptor site alterations, 1 (6.67%) case with a novel deletion (chr7: 116411868 - 116411883) at MET intron 13 region and 1 (6.67%) case with a novel deletion (chr7: 116412027 - 116412042) at MET exon14 region. In this study, 6 somatic mutations which induce METex14 skipping were firstly discovered. So far, RT-PCR and Sanger sequencing were performed on 3 specimens, including 1 sample with conflicting RNA- and DNA-based NGS results and 2 samples with unreported somatic deletions. According to the results of RT-PCR and Sanger, the unmatched sample was false negative on the basis of DNA-based NGS result. Interestingly, METex14 skipping was mutually exclusive with other recognized genomic alterations (such as mutations in KRAS, BRAF, EGFR, NRAS and PIK3CA), while no significant difference was found between METex14 skipping and single driver gene.

Conclusion:
Mutational events of MET leading to exon 14 skipping are frequent occurred in Chinese PSC patients. DNA-based NGS could discover new somatic mutations which results in METex14 skipping. However, RNA-based NGS could provide more accurate results than DNA-based NGS. METex14 skipping was mutually exclusive with other drivers, thus strongly highlighting its potential oncogenic role.

Background:
Clinical practice guidelines recommend genetic testing for advanced non-small cell lung cancer (aNSCLC) to guide 1[st]-line treatment. Small biopsies and low-tumor-content samples pose challenges to testing and reporting on an increasing number of relevant biomarkers. This study compared clinical aNSCLC biomarker testing to investigational use of the Oncomine™ Dx Target Test for different sample types.

Method:
A retrospective analysis was conducted using lung tissue testing data from a large, US-based commercial laboratory that offered single-gene tests (EGFR therascreen, ALK Vysis, BRAF cobas, and laboratory developed tests [LDT] for ROS1, HER2, BRAF, KRAS, MET, RET, and FGFR1) and a 173-gene next-generation sequencing (NGS) LDT panel (Illumina NextSeq 500). Clinical test orders received September 2015 – October 2016 were evaluated. This laboratory also conducted investigational testing on the Oncomine™ Dx Target Test (Ion Torrent PGM Dx) using archival tissue. Testing success rates and slide consumption were evaluated for core needle biopsies (CNBs; overall and by tumor content), fine needle aspirations (FNAs), and surgical resections.

Result:
Clinical testing orders were received on 1,029 CNBs, 144 FNAs, and 181 surgical resections. Among CNBs, 934 had tumor content data: 214 were 1-24% tumor; 720 were ≥25% tumor. Altogether, 3,571 single-gene tests and 198 NGS LDT panels were ordered. The Oncomine™ Dx Target Test was conducted on 169 archival samples: 69 CNBs (41 were 1-24% tumor; 28 were ≥25% tumor); 13 FNAs; 87 surgical resections.

Sample characteristics	Single-gene tests per clinical sample (N)*							173-gene NGS LDT (N)	Oncomine™ Dx Target Test (N)
	1	2	3	4	5	6	7
N samples	1,295	1,039	633	191	114	98	28	198	169
% samples able to successfully generate results for at least X tests, when ordered[†]
CNB[‡]	89.2% (988)	85.3% (788)	76.2% (495)	77.9% (154)	70.8% (96)	61.9% (84)	58.3% (24)	N/A[§]	75.4% (69)
• 1-24% tumor	95.7% (209)	87.1% (170)	70.0% (110)	70.8% (24)	62.5% (16)	60.0% (15)	N/A (4)		70.7% (41)
• ≥25% tumor	98.2% (685)	91.8% (570)	82.9% (362)	85.8% (120)	76.3% (76)	66.2% (65)	61.1% (18)		82.1% (28)
FNA	79.3% (140)	72.4% (116)	75.0% (60)	40.0% (10)	N/A (4)	N/A (4)	N/A (1)		69.2% (13)
Surgical resection	100% (167)	98.5% (135)	91.0% (78)	88.9% (27)	64.3% (14)	50.0% (10)	N/A (3)		98.9% (87)
Total number of slides used to initiate exactly X tests
CNB[‡]	2.6 (165)	4.1 (268)	5.5 (324)	8.7 (56)	8.5 (11)	11.8 (55)	16.8 (16)	16.5 (24)	1.0[¶]
• 1-24% tumor	2.7 (39)	4.8 (60)	5.9 (83)	9.5 (8)	9.0 (1)	12.3 (11)	18.3 (3)	18.7 (3)
• ≥25% tumor	2.6 (118)	3.9 (208)	5.4 (241)	8.7 (47)	8.4 (10)	11.7 (44)	16.5 (13)	16.1 (21)
FNA	2.4 (21)	4.3 (41)	6.1 (42)	9.8 (5)	N/A (0)	11.5 (2)	18.0 (1)	14.0 (2)
Surgical resection	1.8 (32)	4.5 (57)	5.4 (51)	9.5 (13)	11.0 (4)	16.3 (7)	14.0 (2)	8.2 (13)
* Excludes clinical samples on which the NGS LDT panel had been initiated. † Success rates were not evaluated if N<10. ‡ While all samples had tumor content >0%, exact percentages were missing for 94 CNBs, 28 FNAs, and 1 surgical resection. § Success rates not evaluated; nearly all NGS LDT panels were ordered on samples that also initiated single-gene tests, and tissue depletion prevented initiation of most of the ordered NGS LDT panels. ¶ All tests were conducted using 1 slide according to protocol.

Conclusion:
Among lung tissue samples submitted for clinical testing, 13.4% were surgical resections, 10.6% FNAs, and 76% CNBs. The Oncomine™ Dx Target Test had higher testing success rates using fewer slides than single-gene testing for ≥5 biomarkers on CNBs, ≥4 on FNAs, and ≥2 on surgical resections. These preliminary results suggest the Oncomine™ Dx Target Test may facilitate multiple-biomarker testing for more aNSCLC patients to support therapy decisions as more gene targets are identified.

Background:
Acquired epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) resistance is a major factor contributing to targeted therapy failure in EGFR mutant non-small cell lung cancer (NSCLC), among which T790M mutation accounts for 50-60%. Emerging evidence has shown that as mediators between cells, exosomes shed by drug resistant cancer cells have the ability to horizontally transfer drug resistant phenotype to drug sensitive cells, which has been described as an important mechanism of dissemination of drug resistance. However, whether exosomes derived from EGFR-TKIs resistant NSCLC cells harboring T790M mutation could transfer resistance to sensitive cells has not been understood and the potential mechanism also remains unknown.

Method:
Exosomes were isolated from supernatants of T790M mutant NSCLC cell line (H1975) and characterized by transmission electron microscopy, nanosight and western blot. Their potential roles in mediating gefitinib resistance in sensitive cell line (PC9) were investigated in vitro and in vivo. Cell viability and the effects of exosomes on downstream signaling pathways were analyzed by CCK-8 assays and western blot. The roles of exosomes in regulating gefitinib resistance in vivo were assessed by subcutaneous transplantation tumor model in athymic nude mice. Exosomes miRNA sequencing and quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) were used for exploring the underlying mechanism.

Result:
Exosomes isolated from conditioned medium of NSCLC cell lines were cup-shaped membranous vesicles with a diameter of 30-100 nm and expressed the exosomal marker CD63. Exosomes derived from H1975 could transmit gefitinib resistance to PC9 (P＜0.01) in vitro while exosomes released from PC9 cell don’t have this effect. Treatment of PC9 with H1975-derived exosomes and the inhibitor of exosomes production (GW4869) could restore gefitinib response. In vivo, the tumor volume of xenograft model of PC9 cells treated with gefitinib plus H1975-derived exosomes was significantly larger than those mice treated with gefitinib alone (P＜0.05). Furthermore, H1975 xenografts could disseminate gefitinib resistance to PC9 xenografts in the same mice. This difference disappeared by the addition of GW4869. Mechanistically, intercellular transfer of microRNAs (miR-522-3p and miR-454-3p) by exosomes disseminated gefitinib resistance through activating PI3K/AKT and MEK/ERK signaling pathways

Conclusion:
Our findings demonstrate that EGFR-TKIs resistant cells could disseminate drug resistance to sensitive cells by intercellular transfer of exosome-transmitted microRNAs and then activating PI3K/AKT and MEK/ERK signaling pathways, which reveals a novel mechanism of acquired resistance to EGFR-TKIs in NSCLC.

Abstract not provided

Background:
After the introduction of third-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) in non-small cell lung cancer (NSCLC), the second tumor biopsy and EGFR mutation test to confirm T790M status is an established standard practice. But second biopsy is invasive, cost and time-consuming and occasionally impossible. We aimed to investigate the success rate of tissue rebiopsy and incidence of T790M mutation in tissue and plasma at the time of progression with earlier-generation EGFR TKIs in real world setting. Also, we studied the association between the efficacy of osimertinib and the status of tissue and/or plasma T790M mutation.

Method:
We analyzed patients who were screened and enrolled into ASTRIS trial in Yonsei Cancer Center (NCT02474355). Key inclusions were advanced/metastatic NSCLC with tissue and/or plasma T790M mutation and prior EGFR-TKI therapy. Tissue and plasma EGFR mutation tests were performed using PNAClamp[TM] and PANAMutyper[TM], respectively.

Result:
We screened 193 patients with NSCLC harboring EGFR-activating mutation who experienced disease progression upon earlier-generation EGFR TKIs during study period. The second biopsy including tissue and/or cytology was performed only in 60.1% of the patients (116/193) and the success rate was 86.2% (100/116). The reasons for not trying a biopsy were as follow: inaccessibility (n=25), poor PS (n=8), previously reported plasma T790M+ (n=8), and patients’ refusal (n=4). The parenchymal lung tissue (n=61) was most commonly targeted lesion and bronchoscopy was the most frequently used method (n=35). Six patients underwent video-assisted thoracoscopic surgery. Tumor T790M mutation was reported in only 25.9% of patients (50/193). Of 193 patients, 88 patients were enrolled into ASTRIS trial and 43 patients were registered based on the plasma test only. With a median follow-up of 25.1 weeks, the objective response rate (ORR), median progression-free survival (PFS), and duration of the response (DoR) were 44.3%, 32.7 weeks, and 27.0 weeks, respectively. Median overall survival (OS) was not reached. The ORR, median PFS and DoR of tumor T790M+ (n=45) vs. plasma T790M+ (n=54) were 57.8% vs. 35.2%, 45.0 vs. 20.4 weeks, and 26.3 vs. 25.9 weeks, respectively.

Conclusion:
With the increasing importance of tissue rebiopsy after EGFR-TKI failure, there is a growing interest to overcome the challenge of subsequent biopsy. Even though relatively lower ORR and shorter PFS in patients with plasma T790M+ compared with tissue T790M+, the plasma EGFR genotyping may be good alternative to the tissue biopsy in consideration of long DoR when treated with osimertinib and low yield rate of tissue T790M testing.

Background:
Epidermal growth factor receptor (EGFR) activation mutations occur in 10-50% of lung adenocarcinoma patients of Caucasian ethnicity and in 50% of Asian descent. Currently, EGFR tyrosine kinase inhibitors (TKIs) are first line therapy for stage IV non-small cell lung cancer (NSCLC) patients with EGFR mutations. Despite initial significant response to TKIs, most tumors develop resistance. The main mechanism of resistance detected in 50-60% of cases is a cytosine to thymine (C>T) single nucleotide transition mutation at position 2369. This leads to a threonine to methionine amino acid change at position 790 (i.e. T790M). Interestingly, a similar mechanism of C>T mutation is seen in imatinib treated CML and GIST tumors. Our data suggests that the C>T mutation is an acquired event secondary to 5-methylcytosine deamination with Activation Induced Cytosine Deamination enzyme (AICDA).

Method:
PC9 is a lung adenocarcinoma cell line known to have an EGFR del19 activation mutation and can acquire T790M mutation from T790M-negative clone. We utilized droplet digital PCR (ddPCR) to detect T790M mutations. In addition, qPCR was used to assess the expression of AICDA and NFκB pathway before and after TKI exposure.

Result:
Sub clones of PC9 cell line with no evidence of T790M mutation by ddPCR at baseline, were treated with EGFR TKI. After serially increasing the treatment dose, T790M mutation was detected by ddPCR associated with a significant increase in AICDA expression. Furthermore, using a UDG assay, we show that AICDA recognizes a CAC motif and can deaminate cytosine at position 2369. By mass spectrometry we established that 2369 cytosine is methylated. Deamination of 5-methylcytosine leads to thymine directly rather than uracil, explaining the C>T mutation. In addition, using ChIP assay and pharmacological inhibition we confirmed that NFκB binds AICDA promoter and induces its expression. Similarly, using a mouse xenograft model, EGFR TKI increases the expression of NFκB and AICDA; this is abrogated by concurrent use of an IKKα inhibitor. Knocking down AICDA by shRNA, decreases the rate of T790M development in PC9 cell lines after TKI exposure. Assessing AICDA expression in patients at baseline (n=4) and upon T790M mutation progression (n=4), there was a significant 20-fold increase in its expression.

Conclusion:
Our data suggest that upon exposure to EGFR TKI, AICDA is overexpressed through an NFκB dependent pathway, causing the deamination of 5-methylcytosine to thymine, manifesting as T790M mutation and leading to TKI resistance. This indicates that T790M is acquired and its development could be targeted.

Background:
Nivolumab is the first checkpoint inhibitor approved for the treatment of non-Squamous non small cell lung cancer (non-Sq-NSCLC). Although smoking habits are considered a relevant risk factor related to the onset of lung cancer, previous studies showed that current and former smokers patients (pts) treated with nivolumab may have a greater advantage in terms of clinical benefit than never smokers and EGFR mutated. Nevertheless, to date, no definitive conclusion may be drawn and no data are available from a real world setting. Here we report the data from Italian expanded access program (EAP) in the never smoker pts and EGFR mutated pts.

Method:
Nivolumab was provided upon physicians’ request for pts aged ≥18 years who had relapsed after a minimum of one prior systemic treatment for stage IIIB/stage IV non-Sq-NSCLC. Nivolumab 3 mg/kg was administered intravenously every 2 weeks for <24 months. Pts included in the analysis received ≥1 dose of nivolumab and were monitored for adverse events (AEs) using Common Terminology Criteria for Adverse Events.

Result:
Overall, of 1588 patients with non-Sq-NSCLC, smoking history was available for 1430 pts and 305 (21%) were never smokers and, among 1455 pts evaluable for EGFR mutation, 102 (7%) were positive. In the never smoker group, EGFR status was available for 287 pts, with 51 (18%) who harbored an activating EGFR mutation. Among never smokers, with a median follow-up (FU) of 7.0 months (0.1-20.3) and a median of 7 doses (1-38), the best objective response rate (BORR), the disease control rate (DCR) and the median overall survival (OS) were 9%, 42% and 10.0 months (8.1-11.9), respectively. Among all EGFR positive pts, with a median FU of 5.5 months (0.1-21.2) and a median of 6 doses (1-40), the BORR, DCR and median OS were 9%, 30% and 8.3 months (2.2-14.4), respectively. In the never smoker group, EGFR positive pts had 2% ORR, 26% DCR and 5.6 months (3.4-7.8) of median OS. However, it should be considered that these pts had poorer prognostic factors (ECOG performance status, brain metastasis) at baseline.

Conclusion:
These preliminary results represent the first real-life data regarding the efficacy of nivolumab in special subpopulations, including never smokers and EGFR positive pts. These results warrants further studies to evaluate the possible therapeutic options in these pts, also taking into account available alternatives and safety profile.

Abstract not provided

Background:
Thymomas are frequently associated with paraneoplastic autoimmune syndromes, with the most common being Myasthenia Gravis (MG). MG is characterized by autoantibodies against muscle antigens, most frequently the acetylcholine receptor (AChR). Patients with thymoma also present with autoantibodies against striational muscle proteins (STR-Abs), such as the sarcomeric protein titin and the ryanodine receptor. These autoantibodies have been primarily regarded as diagnostic or prognostic markers, but little is known about their pathological mechanisms. Comprehensive mechanistic studies have been hindered by the lack of patient-derived monoclonal antibodies (mAbs). Such mAbs could help to define immunogenic epitopes in known or novel autoantigens, and would be useful for deciphering pathological mechanisms in vitro or in animal models.

Method:
We studied mAbs derived from a patient with thymoma and MG, with the patient’s written informed consent and under a Stanford IRB approved protocol. The patient had Masaoka-Koga stage II type B2 thymoma, with multiple recurrences over a period of 8 years. The patient’s MG symptoms included fatigable muscle weakness, the presence of anti-AChR antibodies, and high titer STR-Abs. The patient also had myositis with muscle-related symptoms worsening after thymectomy. We sequenced the repertoire of the patient’s plasmablasts, which are antibody-producing cells derived from the activated B-cell clones, using a barcode-based method for sequencing single-cell immunoglobulin genes developed in our lab. We then expressed 26 mAbs from clonally expanded families of antibodies from two different timepoints that are six months apart. The first timepoint was two years post-Rituximab, coinciding with a tumor recurrence and slow progression of muscle weakness. The second timepoint was a month after radiotherapy when the patient was admitted with severe muscle weakness and pain. Treatment included plasmapheresis/IVIG and Rituximab, with limited improvement over the weeks following hospitalization. The patient was on steroids at both timepoints. Anti-Titin serum antibody titers increased by 60% between these two timepoints.

Result:
Two of the mAbs that were expressed reacted with the main immunogenic region of titin in ELISA, and one of the clones was present at both of the timepoints investigated. These clones were detected despite B-cell depletion by treatment with Rituximab.

Conclusion:
Our results suggest that (i) sequencing single-cell immunoglobulins is a powerful technique for isolating and functionally characterizing mAbs against autoantigens in thymoma and that (ii) persisting or recurring autoreactive clones in patients with thymoma, such as anti-titin clones, may be associated with refractory paraneoplastic syndromes despite use of immunosuppressive therapies.

Background:
The immune checkpoint ligand programmed cell death 1 ligand (PD-L1) is expressed in various tumors, and the expression of indoleamine 2,3-dioxygenase (IDO) and Foxp3 Tregs are associated with tumor-induced tolerance and reported to be responsible for worse survival. Their prognostic role in thymoma and thymic carcinoma, however, has not been investigated.

Method:
A tissue microarray comprised of 100 surgically treated thymomas and 69 surgically treated thymic carcinomas was evaluated. PD-L1, IDO, and Foxp3 Treg staining was scored based on intensity as follows: 0 = none, 1 = equivocal/uninterpretable, 2 = weak, and 3 = intermediate-strong. The PD-L1, IDO, and Foxp3 Treg expression score was calculated using a semiquantitive method by multiplying the intensity [0-3] by the staining area [0-100%]. Those cases with all cores scoring three and 2 in more than 50% in the staining area were categorized as PD-L1, IDO, and Foxp3 Treg high expression and the remaining as low expression. Clinical information was also collected on age, sex, Masaoka staging, tumor histology, surgical radicality, and locoregional invasion. Statistical associations were evaluated using χ[2] test and Fisher’s exact test. Progression-free survival and overall survival curves were established by the Kaplan-Meier method and compared using a log-rank test.

Result:
Figure 1Figure 2Thirty-six (36%) thymoma and 25 (36%) thymic carcinoma cases revealed high expression of PD-L1. PD-L1 expression in thymoma is significantly associated with Masaoka staging (p<0.001), tumor histology (p<0.001). Although there was a trend toward worse progression-free and overall survival in thymoma and thymic carcinoma with high-expression of PD-L1, only the progression-free survival in thymoma was significantly worse (p=0.024). High expression of IDO was detected in 13 (13%) thymoma and 10 (14%) thymic carcinoma cases, whereas Foxp3 Treg was detected in 16 thymoma (16%) and 20 (29%) thymic carcinoma cases. The expressions of IDO and Foxp3 Treg were significantly associated with tumor histology in thymoma (p=0.002 and 0.016, respectively), but not in thymic carcinoma. Thymic carcinoma with high expression of IDO had a trend toward worse progression-free and overall survival trend (p=0.109 and 0.053, respectively). High expression of Foxp3 Treg, however, was significantly associated with better progression-free survival (p=0.006) and overall survival (p=0.007) in thymic carcinoma.





Conclusion:
This is the largest-scale study to evaluate PD-L1 expression in thymic epithelial tumors. Although high expression of PD-L1 might be associated with worse prognosis in thymoma and thymic carcinoma, further investigation into PD-L1, IDO, and Foxp3 Treg should be conducted to benefit anti-PD-L1 immunotherapy for thymic epithelial tumor.

Background:
The management of patients with locally advanced thymic malignancies remains controversial. Various combinations of surgical resection, chemotherapy and radiation are currently used. Given the generally favorable prognosis, treatment related toxicities and quality of life (QOL) could inform therapeutic options. For economic analyses, QOL can be measured as health utilities. This study describes health utility scores (HUS) in patients with locally advanced thymic malignancies, while determining the impact of multimodality regimens on HUS.

Method:
In a cross-sectional study (2014-2017), patients with Masaoka stage II-IVa thymic malignancies seen at a comprehensive cancer centre completed various self-reported questionnaires at routine medical visits. HUS as measured by the EuroQol-5-Dimensions (EQ-5D) with visual analogue scale (VAS) and self-reported Eastern Cooperative Oncology Group (ECOG) performance status were compared in patients treated with trimodality versus uni- or bimodality regimens. Patient-reported Edmonton Symptom Assessment Scale (ESAS) scores were also collected to explore symptom burden. Regression analysis was used to compare groups; multivariable analysis investigating potential confounders was also conducted.

Result:
From 2014 to 2017, 72 patients were included in the study; 43 (59.7%) were male with a median age of 58 years, 65 (90.3%) had thymoma while 7 (9.7%) had thymic carcinomas and median time since diagnosis was 50.5 months (range: 3-266). Compared to patients treated with uni/bimodality regimens (n=48), those treated with trimodality (n=24) had higher stage of disease at diagnosis and were more likely to have received multiple lines of chemotherapy. Median HUS and VAS did not differ between groups (trimodality vs uni/bimodality: HUS=0.77 vs 0.80, p=0.26; and VAS=80 vs 75, p=0.79, respectively). The distribution of patient-reported ECOG at assessment was also similar (p=1.00). ESAS scores for pain, tiredness, nausea, depression, anxiety, drowsiness, appetite, wellbeing and shortness of breath were neither statistically nor clinically different by number of modalities of therapy. Subset analyses of individuals who were 1+ year since diagnosis affirmed these findings.

Conclusion:
Patients with stage II-IVa thymic malignancies report favorable HUS, VAS and self-reported ECOG with minimal symptom burden. Trimodality therapy appears similarly tolerable when compared to uni- and bimodality regimens in this population.

Background:
Thymic carcinoma (TC) is a rare cancer with minimal evidence of survival with palliative-intent chemotherapy. Sunitinib and everolimus monotherapies have been proposed as active molecular-targeted approaches based on phase II (Ph II) trials, and S-1, an oral fluoropyrimidine, has been described in the NCCN guideline as an active cytotoxic agent for refractory TC based on a case series. Therefore, we conducted a Ph II trial to study the result of S-1 treatment in patients with refractory TC.

Method:
In this Ph II study performed at three cancer centers in Tokyo, we aimed to enroll 26 TC patients previously treated with platinum-based chemotherapy. The patients received S-1 orally twice daily at a dose of 40–60 mg/m2 for 4 weeks, followed by 2 weeks off until progressive disease or unacceptable toxicities. S-1 was used off-label. The primary end-point was determining the objective response rate, and secondary endpoints were progression-free survival (PFS), overall survival (OS), and toxicities.

Result:
Twenty-six patients (10 males) were recruited between November 2013 and May 2016. The median age was 63 (27–74) years. Among the 26 patients, 23 had squamous cell carcinoma histology and 10 had an ECOG performance status of 0. Additionally, one patient showed complete response and seven patients showed partial responses, resulting in a 30.8% response rate (95% confidence interval [CI], 16.5–50.0) and a 65.4% disease control rate (95% CI, 46.2–80.6). After a median follow-up of 13.4 months, the median PFS was 4.3 months (95% CI, 2.3–7.6 months) and median OS was 23.4 months (95% CI, 12.8–not reached). Treatment-related adverse events (AEs) of grade ≥3 included neutropenia (12%), skin rash (8%), elevated ALT, decreased WBC count, and fatigue (4%). No treatment-related death was observed. However, treatment was discontinued in three patients (12%) because of AEs.

Conclusion:
S-1 for refractory TC confirmed clinical activity with good tolerability. Clinical trial identification: UMIN000010736

Abstract not provided

Background:
Conventionally, minimally invasive thymectomy for early-stage thymoma was performed via unilateral thoracoscopic approach. However it is sometimes criticized for bad exposure of anterior mediastinum which may be disadvantagous for the surgery. Recently, we attempted a modified subxiphoid thoracoscopic approach with novel sternal-elevating technique to reach better surgical exposure and less trauma.

Method:
From January 2015 to December 2016, a total of 83 consecutive patients with early-stage thymomas without myasthenia gravis were enrolled. Between them, 36 patients were performed thoracoscopic thymectomy via subxiphoid approach (Group S) . Three subxiphoid incisions (12mm*1, 5mm*2) with the aid of artificial CO~2~ pneumothorax (8cmH~2~O) were used. Additionally, we used the sternum-elevating device (Rul-tractor, USA) through the 3rd intercostal incision (5mm*1) beside the sternum. And the other 47 cases underwent conventional thymectomy via unilateral 3-port thoracoscopic approach (Group UL). The perioperative outcome of two groups were compared.

Result:
The two groups were comparable on patients[,] demographics. Conversion to open surgery occurred in 1 case (due to bleeding) in Group UL. Compared with Group UL, the patients in Group S had much shorter surgical duration [(63.5±10.7)min vs (87.7±13.1)min, p=0.000], much less pain scores (2.3±1.0 vs 3.1±1.30, p=0.002) and earlier pleural drainage removal [(1.6±0.6)d vs (2.3±0.9)d, p=0.000]. The complications were similar (5.6% vs 6.4%, p=0.758). No significant difference was found on the other outcomes between the two groups, including blood loss and postoperative hospital stay.

Conclusion:
This study suggests that the modified subxiphoid thoracoscopic approach seems to be more effective for thymectomy for early-stage thymomas. This novel approach could improve surgical exposure, accelerate the operative progress and result in less trauma and pain. It could be a promising refinement for future thymic surgery.

Background:
The co-existence of MG and thymoma makes the surgical treatment more complicated and adjuvant radiation more controversial. The aim of this article is to investigate whether patients with MG and thymoma should receive mediastinal radiation therapy and when after extended thymectomy.

Method:
Between 2003 and 2014, 181 patients with MG and thymoma underwent extended thymectomy. According to application of radiation therapy, these patients were divided into 2 groups: Group 1 (n=157), patients having mediastinal radiation therapy after surgery; Group 2, without adjuvant radiation therapy (n = 24). Group 1 was subdivided into 3 subgroups: 1-month subgroup(n = 98); 2-month subgroup(n = 7): and 3-month subgroup(n = 52).

Result:
There were no intraoperative deaths and no inoperable cases. 172 patients underwent extended thymectomy by video-assisted thoracoscopic surgery, and 9 undergoing the trans-sternal approach due to thymoma invading great vessels. There was no significant difference in the aspects, such as length of surgery, Operative complications, and ICU stay, between 1-month subgroup, 3-month subgroup and Group 2. The proportions of type A, AB, B1, B2, B3, and thymic carcinoma were 0.6%, 18.2%, 26.5%, 33.7%,21.0%, and 0%, respectively. There were no radiation-related deaths. 159 patients were followed for 15 months to 12 years. Postoperative myasthenic crisis occurred in 40 cases. There was a significant difference in occurrence of postoperative myasthenic crisis between 1-month subgroup and Group 2 (P=0.031). The rates of reaching CSR were 32.6% in 1-month subgroup, 25% in 3-month subgroup, and 22.7% in Group 2, respectively. Overall survival rates of 1-month subgroup, 3-month subgroup, and Group 2 were 88.8%, 83.3%, and 77.3%, respectively. Among 14 recurrences, 11 cases happened in pleural cavity; 2 recurrences in lung; and one patient having metastasis to liver. There was no lymph node metastasis detected. Kaplan-Meier survival curves demonstrate that within 7 years after surgery, there is no significant difference in aspects of overall survival and disease-free survival between 1-month subgroup, 3-month subgroup and Group 2; over 8 years after surgery, disease-free survival rates in 1-month subgroup, 3-month subgroup and Group 2 were 79.4%, 70.6% and 55.3%, respectively.

Conclusion:
Adjuvant radiation within one month after extended thymectomy may be helpful in controlling postoperative MG, such as decreasing possibility of postoperative myasthenic crisis, and raising cumulative probabilities of reaching CSR. Whether it might have influence in prognosis of thymoma with MG needs to be further investigated in the future. In recurrences of thymoma patients with MG, no lymph node metastasis was detected

Background:
Surgical management of pleural dissemination of thymoma has been recommended in some reports, while reports on the long- term results of pleural dissemination resection are few. The aim of this study was to assess mid- and long- term results of surgical resection of pleural dissemination of thymoma.

Method:
We retrospectively analyzed data from patients with synchronous or metachronous pleural dissemination and primary thymoma who underwent surgical resection between 1996 and 2016 in our hospital.

Result:
During the study period, 38 patients underwent resection of pleural dissemination of thymoma. The synchronous group consisted of 21 patients with a median age of 50.2 years (range: 28—75 years) at the time of resection. The metachronous group consisted of 17 patients with a median age of 46.7 years (range: 30—65 years) at the time of resection of pleural dissemination. The median follow-up was 72.7 months (range: 3—248 months). In the synchronous group, 19 patients were in stage IVa and 2 patients were in stage IVb. The histological type of thymoma was type B1 in 3 patients, type B2 in 9 patients, typeB3 in 9 patients. In the metachronous group, Masaoka stage of the primary thymoma was as follows; 3 patients were in stage I, 5 patients were in stage II, 7 patients were in stage III and 2 patients were in stage IVb. The histological types of the resected dissemination nodule were type AB in 1 patient, type B1 in 1 patient, type B2 in 5 patients, and typeB3 in 10 patients. A macroscopic complete resection of pleural dissemination was achieved in 30 patients (79%) of all the patients. No perioperative deaths occured. Postoperative complications occurred in 5 patients (13.2%). During the observation period, 5 patients died (relation to the tumor in 4) in the synchronous group and 1 patient died (unrelated to the tumor) in the metachronous group. The 5- and 10-year overall survival rates of all the patients were 87.6% and 69.2%, respectively. Of all the patients, 14 received repeated resection of the pleural disseminated nodule. The 5- and 10-year overall survival rates from the first resection of pleural dissemination were 76.6% and 46.0% in the non-repeat resection group and 100% and 88.9% in the repeat resection group, respectively.

Conclusion:
Surgery for pleural dissemination of thymoma was safely performed and　provides favorable prognosis. Repeat resection for pleural dissemination could be effective in achieving a prolonged survival.

Abstract not provided

Background:
Primary mediastinal malignant germ cell tumors (GCT) are rare neoplasms with various histopathological findings and contain complicated clinical characteristics. Chemotherapy plays an important role in the treatment and there are some cases where a good prognosis is expected with multimodal treatment including surgical resection, pre- and postoperative chemoradiotherapy.

Method:
The medical records of 27 patients who were treated in our institution between 1988 and 2014 were retrospectively reviewed. We investigated the clinical characteristics and the outcomes of treatment.

Result:
All patients were male with a mean age of 30.7 years (range, 16-53 years), including 17 cases of seminoma (SGCT group) and 10 cases of non-seminoma (NSGCT group). Twenty-three patients underwent surgery and the remaining four patients received chemotherapy and/or radiotherapy without surgery. Of the 23 patients who underwent surgery, 17 cases received preoperative chemotherapy and 15 cases were treated with postoperative chemo/radiotherapy. In six patients, surgery was performed without preoperative chemotherapy due to the suspicious of thymoma, and was followed by postoperative chemo/radiotherapy. Among 24 patients whose serum tumor marker levels were measured before the treatment, 15 patients showed elevated serum tumor marker levels [five (35.7%) in SGCT group and 10 (100.0%) in NSGCT group]. Furthermore, among 20 patients whose serum tumor marker levels were measured before surgery, four patients showed elevated serum tumor marker levels [one (9.1%) in SGCT group and three (33.3%) in NSGCT group]. The median follow-up period after the treatment was 68 months (range, 4-316 months). The 5-year and 10-year survival rate was 88% and 88% in SGCT group, respectively, and 60% and 45% in NSGCT group, respectively (p=0.031). Although there was no relationship between the serum tumor marker levels before the treatment and the prognosis, the patients without elevated tumor marker levels revealed better prognosis than those with elevated one (p=0.014).

Conclusion:
The treatment for mediastinal malignant GCT in our institution was feasible with favorable outcomes. Although malignant GCT has poor prognosis especially in NSGCT group, chemotherapy which normalizes serum tumor marker levels can improve its prognosis.

Background:
Adenoid cystic carcinoma (ACC) of the trachea represents less than 1% of all respiratory tract cancers and lacks well-characterized molecular markers. There is no standard of care treatment for patients with recurrent and/or metastatic disease. The aim of this study is to identify and characterize novel, activating mutations in Notch receptors in ACC of the trachea and to determine response to Notch inhibitor Brontictuzumab.

Method:
Patients with ACC of the trachea at four institutions from 2011 through 2016 were identified. Target exome sequencing or analysis of hotspot mutations in cancer-related genes was performed by next-generation sequencing. Luciferase reporter assays were performed to confirm target gene expression in vitro. Patient-derived xenograft (PDX) models were sequenced, and Notch-mutant models were treated with Brontictuzumab. Gene-expression and functional analyses were performed to study the mechanism of activation through mutation and inhibition by Brontictuzumab.

Result:
We showed that gain-of-function mutations of the Notch-1 gene in the PEST domain occurred in 10/62 tumors, leading to stabilization of the intracellular cleaved formed of Notch-1 (ICN1). Notch-1 mutations were associated with increased Notch-1 activation and its target gene HES-1. Mutations in Notch-2 (3/62), Notch-4 (3/62), Jagged-1 (2/62), FBXW-7 (4/62), and SPEN (1/62) were also identified in 13 (21.0%) patients. We observed a strong inverse correlation of mRNA levels between FBXW-7 and HES-1. Notch-1 mutations were associated with solid subtype (P = 0.02), advanced stage at diagnosis (P = 0.01), metastasis (P = 0.002), shorter relapse-free survival (RFS) (P = 0.008) and shorter overall survival (OS) (P = 0.006) compared with Notch-1 wild-type tumors. Notch-1 mutations were not an independent prognostic factor in the presence of histologic subtype and tumor stage. We demonstrated that Notch inhibition by Brontictuzumab reduced tumor cell proliferation and tumor formation in ACC patient-derived xenograft model harboring Notch-1 mutation.

Conclusion:
These data suggest that activated Notch pathway may be important to pathogenesis of ACC of the trachea and reveal Notch-1 as a target for therapeutic intervention in this subset of patients.

Background:
Testicular Germ-cell tumors are a common cancer in adults younger than 30 years-old. Extensive dissemination and high senitivity to chemotherapy are their principal characteristics. Chemotherapy is the standard of care, with an 80% probability of complete biochemical response with first line chemotherapy. Surgical resection of residual lesions after chemotherapy is indicated in some cases to rule out the presence of mature teratoma or viable tumor.

Method:
Retrospective chart review of patients with metastastic testicular Germ-cell tumors treated with chemotherapy and pulmonary metastasectomy from January 2006 to December 2014.

Result:
We found 56 cases with complete data for revision. Mean age was 25 years (16-48) Patients with lung metastases at diagnosis were 83.9%. All patients were treated with chemotherapy after initial orchiectomy. Preoperative serum tumor markers were negative in 44 patients (78%) Thoracotomy was performed in 48 cases (85.7%) and minimally invasive surgery in 8 cases (14.3%) Pulmonary wedge resection was performed in 52 patients (92.8%) and a lobectomy was required in 4 patients (7.2%) A R0 resection was achieved in 98.3%. Necrosis was reported in 25 cases (44.6%), mature teratoma in 17 (30.4%), viable germ-cell tumor in 13 patients (23.2%) and 1 case with seminoma (1.8%) All patients with viable tumor were offered postoperative chemotherapy. Median follow-up was 53.2 months (6-110). Median Overall Survival has not reached. Factors associated with improved survival were negative preoperative serum tumor markers and abscense of viable germ-cell tumor on resected specimens. Figure 1



Conclusion:
Removal of residual lesions after chemotherapy serves a double purpose, as an adjuvant treatment to chemotherapy allowing for “local” control of metastases and it also provides information about response to chemotherapy, with implications on prognosis and guiding postoperative treatment. In our cohort we demonstrate that despite a high proportion of viable tumors on surgical specimen, multi-modality treatment including lung metastasectomy is associated with prolonged survival

Background:
Programmed death-ligand 1 (PD-L1), is reported to serve as an indicator of prognosis in many malignant tumors. The aim of this study was to determine whether PD-L1 expression status in tumor cell can predict patient’s prognosis in esophageal squamous cell carcinoma (ESCC).

Method:
246 paraffin-embedded tissue samples were detected PD-L1 expression by immunohistochemistry from ESCC patients after surgery. And we statistically analyzed the association between expression of PD-L1 and clinicopathological factors and outcomes of survival.

Result:
The rate of positive PD-L1 expression was 24.4% (60/246) . Multivariate analysis indicated positive PD-L1 expression was associated with advanced TNM stage (P=0.009). The median of overall survival (OS) for patients with positive PD-L1 expression was similar to those with negative PD-L1 expression (Median OS, 52.4 vs. 56.4 months, P=0.466). However, in the subgroup analysis, the results indicated that the prognosis of patients with positive PD-L1 expression treated with adjuvant radiotherapy was significantly better than those with negative PD-L1 expression (Median OS, 84.4 vs. 36.0 months, P=0.046), while the OS of positive PD-L1 expression patients treated with adjuvant chemotherapy was poorer than those with negative PD-L1 expression although without significant statistical differences (Median OS, 21.8 months vs. 41.0 months, P=0.765) (Figure 1). Multivariate Cox regression hazards analysis revealed PD-L1 expression statue was not an independent prognostic factor (P=0.804) for entire cohort.Figure 1 Subgroup analysis for OS in ESCC based upon PD-L1 expression. (A) Subgroup of surgery alone; (B) Subgroup of surgery plus adjuvant chemotherapy; (C) Subgroup of surgery plus adjuvant radiotherapy; (D) Subgroup of surgery plus adjuvant chemoradiotherapy.



Conclusion:
Positive PD-L1 expression was likely to be more associated with malignant biological behavior of ESCC. PD-L1 expression was not a prognostic factor of OS for entire cohort, however, it is a prognostic factor in patients treated with postoperative adjuvant radiotherapy.

Background:
c-Met is reported to serve as a poor prognostic factor in many malignant tumors. Previous studies have suggested the involvement of c-Met in esophageal squamous cell carcinoma (ESCC), but the correlation between c-Met status and clinical outcome remains unclear. Furthermore, the identification of a novel molecular therapeutic target might potentially help improve the clinical outcome of ESCC patients.

Method:
The expression of c-Met was immunohistochemically assessed in 180 surgically obtained tissue specimens. The correlation between c-Met expression and patients’ clinicopathological features, including survival, was evaluated. We also investigated changes in cell functions and protein expression of c-Met and its downstream signaling pathway components under treatments with c-Met inhibitor in ESCC cell line.

Result:
There was no significantly correlated between c-Met expression and patients’ clinicopathological features. However, there was a significant difference in OS (median: 41.9 vs. 56.7 months; p= 0.001) between the high c-Met and low/negative c-Met expressing groups. In subgroup of patients with adjuvant radiotherapy, high expression of c-Met was correlated with poor disease prognosis (p= 0.002), while there was no significant correlation in patients with adjuvant chemotherapy. In addition, multivariate analysis identified the high expression of c-Met as an independent prognostic factor. Treatment with c-Met inhibitor significantly inhibited the growth of an ESCC cell line with high c-Met mRNA expression. Moreover, c-Met and its downstream signaling inactivation was also detected after treatment with c-Met inhibitor.

Conclusion:
The results of our study identified c-Met expression as an independent prognostic factor in ESCC and demonstrated that c-Met could be a potential molecular therapeutic target for the treatment of ESCC with high c-Met expression.

Abstract not provided

Abstract:
Pathology In the current WHO 2015 classification[1] neuroendocrine lung tumors are listed in the order of their frequency with SCLC first as it is the most common (15% of lung cancer). Despite the grouping of these tumors together, it is clear that the carcinoids have major clinical, epidemiologic, histologic and genetic differences compared to the high grade SCLC and LCNEC. SCLC and LCNEC have much higher mitotic rates (more than 11 per 2mm2), more necrosis than carcinoids and can show combinations with other lung cancer types including adenocarcinoma or squamous cell carcinoma, which testify of a common progenitor cell derivation, not shared by carcinoid which is never mixed with a non-neuroendocrine (NE) tumor type Immunohistochemistry (IH) / neuroendocrine markers can be very helpful in diagnosing pulmonary NE tumors especially in small biopsies with crushed artefact. Endocrine morphology and neuroendocrine IH markers are both required for the diagnosis of LCNEC. The cases with one missing (Endocrine morphology or NE markers) are considered as large cell carcinoma in the absence of other differentiation marker on resection specimens, and as non- small cell lung carcinoma on small samples. Genomic update Small cell lung carcinoma [2-3] The universal biallelic alteration of both TP53 and RB1 gene was remarkable (100% for P53 and 93% for RB1) by different alterations of each of the 4 alleles. Other significantly mutated genes are KIAA1211 and COL22A1 with unclear functions, as well as RGS7 and FPR1 involved in G-protein-coupled receptor signalling. Locally clustered mutations occurred on CREBBP (15%) and EP300 (13%) genes, inactivating their histone acetylase functions. Notch family genes were recurrently mutated (25%) whereas RNA transcriptome analysis revealed a rate of Notch inactivation of 77% associated with up regulation of neuroendocrine (NE) lineage genes (DLK1 a Notch inhibitor, CHGA (chromogranin A), ASCL1 a master regulator of NE lineage, and GRP (gastrin releasing protein)). Another Notch inhibitor DLL3 was reported to be upregulated in 65% of SCLC[3]. DLL3 is considered as a therapeutic target tested in several clinical trials[4]. The mouse model validated NOTCH as a tumor suppressor and master regulator of NE malignant differentiation in SCLC[ 3]~.~ TP73 gene breaks inducing intragenic fusions and rearrangements, creates the N-terminally truncated transcripts variants lacking a fully competent transactivation domain and exerting dominant negative functions on both wild type p73 and p53. With additional mutations in TP73, 13% SCLC showed alteration in TP73 gene. Somatic copy number alterations (CNA) include focal events on 3p14.3-3p14.2 (FHIT gene) and 3p12.3-3p12.2 (ROBO1) with reduced expression of theses 2 genes. Homozygous deletion of the CDKN2A locus (chromosome 9p) and amplification of the MYC family genes (MYCL1, MYCN, MYC) as well as of FGFR1 (6%) and IRS2 (2%) were recurrent events. The remarkable largely mutually exclusive mutations in the five key genes: CREBBP, EP300, TP73, RBL1, RBL2 (equivalents of RB1 in the mouse model) and Notch suggest they may exert similar pro-tumorigenic functions in the development of SCLC and are candidate drivers[3]~.~ Large cell neuroendocrine carcinoma (LCNEC) TP53 was the most frequently inactivated gene (92%) followed by RB1 (42%) Biallelic inactivation of both TP53 and RB1 (the hallmark of SCLC) was seen in 40%.Mutations in STK11/ LKB1(30%, characteristic of ADC) and KEAP1 (22%, detected in both ADC and SCC but not in SCLC). The mutations were deleterious (nonsense, splice and frameshift mutations) or missense affecting important protein domain mutations in RB1 and STK11/KEAP1 which occurred in a mutually exclusive fashion (p<0.0001). Damaging mutations also occur in chromatin-remodelling genes ARID1A and MEN1/PSP1 in 10% and 7% of LCNEC respectively; Ras family alterations were found in 10% of cases. Overall RAS family, BRAF and NKX2-1 alterations were mutually exclusive with RB1 ( P=0.0049) suggesting again distinct genomic patterns in LCNEC . Analyses of CNA on 60 LCNEC reveals similarities to SCLC[3]. As mutations, the pattern of copy number alterations of LCNEC share characteristics with SCLC, ADC, or SCC. Overall from genomic profiles, while certain alterations (RB1 MYCL1) resemble thoses found in SCLC, others are typical of adenocarcinoma (STK11, NKX2-1, RAS, BRAF) or of squamous cell carcinoma( KEAP1, NFE2L2), showing the heterogeneity of LCNEC which can be divided into molecular subsets by similarities with other major lung cancers. At transcriptional level[5] an unsupervised consensus clustering showed a common cluster including both SCLC and LCNEC characterized by high expression of neuroendocrine lineage transcription factors, as well as high levels of cell cycle regulation and DNA damage response genes, and centrosomal functions. Although LCNEC shared characteristics with ADC and SCC, theses were dissimilar and strongest correlation was being found with SCLC. The transcriptional relationship of LCNEC and SCLC revealed 4 consensus clusters I-IV. Tumors in cluster I exclusively contained LCNECs with STK11 or KEAP1 alterations (type1-LCNEC) characterized by a high level-expression of chromogranin A and synaptophysin. The majority of LCNECS in cluster 2 enriched in cases with RB1 alterations exhibited reduced levels of NE markers and elevated Notch signalling, low expression of ASCL1 and DLL3 an inhibitor of NOTCH signalling pathway (type 2 LCNEC).. Whereas type1-LCNECs harbor STK11 or KEAP1 alterations but share NE expression profiles with SCLC , type2- LCNEC (40% of LCNEC) bear genetic resemblance with SCLC with RB1 alterations ,but profound transcriptional differences with SCLC. Carcinoid Tumors Molecular alterations underlying pathogenesis of this tumor were enlighted only recently[6] Genome/exome sequencing data from 44 tumor/normal pairs, allowed identification of MEN1, ARID1A, and EIF1AX as significantly mutated genes. MEN1, PSIP1(13%) and IRID1A play important roles in chromatin remodelling process showed mutually exclusive frameshifts and truncating mutations. Mutations in histone methyltransferases (SETD1B, SETDB1, NSD1) and demethylases (KDM4, PHF8) as well as members of the polycomb complex 1 and 2 (CBX6 and EZH1) mutations were accompanied with LOH. In total 40% of carcinoids carried mutually exclusive mutations in genes involved in covalent histone modification. Truncating and frameshift mutations occur in ARID1A (6,7%), and other mutations in this SWI/SNF chromatin remodelling complex in 22%. With sister chromatid cohesion affected by reccurrent mutations (COHESIN, STAG1, NIPBL, the microRNA processor DICER and ERCC6L), 51% of carcinoid carried mutations in chromatin remodelling genes. There was no genetic segregation between typical and atypical carcinoid, neither between the expression clusters generated from both subtypes. References Travis WD, Brambilla E, Burke A, Marx A, Nicholson A. WHO Classification of the Tumours of the Lung, Pleura, Thymus and Heart. 4th Edition. Lyon: IARC Press; 2015. Peifer M, Fernandez-Cuesta L, Sos ML, et al. Nat Genet 2012;44:1104-10. George J, Lim JS, Jang SJ, et al. Nature 2015;524:47-53. C.Rudin, M.C. Pietenza, M. Todd et al. Lancet Oncol 2017; 18: 42–51. Georges et al. Nature communication. In press 2017 Fernandez-Cuesta L, Peifer M, Lu X, et al. Nature communications 2014;5:3518.

Abstract:
Squamous cell lung cancers (SQCLC) account for between 15-25% of non-small cell lung cancer (NSCLC) cases. They are, biologically, quite distinct from lung adenocarcinomas, though this remains a fact that has had little positive effect to date in the management of this disease. Indeed, despite the FDA approval of a handful of new drugs for patients with SQCLCs since 2014, progress has been, for most, limited, reflecting the modest gains in survival achieved by these new agents. Navigating the treatment landscape has been, by turns, straight-forward and frustrating. This is most evident in the first-line setting where, apart from patients whose tumors exhibit high expression of PD-L1, a variety of platinum-based chemotherapy options are available, all with more or less equivalent efficacy as shown in Table 1:

	cisplatin + gemcitabine + necitumumab(1)	cisplatin + gemcitabine(1)	carboplatin + nab-paclitaxel(2)	carboplatin + paclitaxel(2)	cisplatin + docetaxel(3)
ORR (%)	31	29	41	24	37
Median PFS (mo)	5.7	5.5	5.6	5.7	-
Median OS (mo)	11.5	9.9	10.7	9.5	11.3

Second-line therapy is dictated then largely through exclusion. Patients who received pembrolizumab as first-line treatment will cycle through platinum-based chemotherapy. Patients who received platinum-based chemotherapy will, by and large, cycle through any one of a number of FDA-approved PD-1/PD-L1 antibody therapies, all with equivalent efficacy (pembrolizumab, nivolumab, atezolizumab). Docetaxel +/- ramucirumab is thus relegated to the de facto third-line option. There are, arguably, few clinically meaningful therapeutic options beyond this; the data behind these options will be discussed in further detail. Most recently, attempts have been made to target putative oncogenic drivers in this disease, based on larger scale genomic analyses and pre-clinical experiments generated TCGA and others.(4-6) Three relatively large-frequency signaling pathways and targets have been tested in early phase trials, including FGFR1 amplification, PI3K pathway alterations, and G1/S checkpoint aberrations both by individual groups and SWOG (LUNG-MAP, S1400). In short, there has been modest to no efficacy in targeted therapy trials to date. These studies are summarized in Table 2:

Target	Frequency	Drug	ORR
FGFR1 amplification	Up to 20%	AZD4547(7)	8%
		BGJ-398(8)	15%
		Dovitinib(9)	11.5%
PI3K pathway	Up to 50%	BKM120(10)	0%
		GDC-0032(ASCO 2017)	5%
G1/S checkpoint	Up to 50%	Abemaciclib(11)	17%

Most of these studies have lacked detailed molecular analyses of patient tumor samples, hampering our ability to determine why these targeted efforts have largely failed. One exception is the study of AZD4547 in FGFR1 amplified SQCLCs, where correlative tests demonstrated that focal amplification of FGFR1 in the 8p11 amplicon does not occur in the majority of cases, commensurate with relatively low mRNA and protein expression of the gene.(7) Overall, heterogeneity with regard to aberrations in overlapping signaling pathways and clonal diversity remains a concern. The rationale for and data from other studies will also be discussed, including early data from combination chemotherapy plus PD-1/L1 inhibition trials as well as potential future directions for research. References 1. Thatcher N, Hirsch F, Luft A, Szczesna A, Ciuleanu T, Szafranski W, et al. A randomized, multicenter, open-label, phase III study of gemcitabine-cisplatin (GC) chemotherapy plus necitumumab (IMC-11F8/LY3012211) versus GC alone in the first-line treatment of patients (pts) with stage IV squamous non-small cell lung cancer (sq-NSCLC). J Clin Oncol. 2014:abstr 8008. 2. Socinski MA, Bondarenko I, Karaseva NA, Makhson AM, Vynnychenko I, Okamoto I, et al. Weekly nab-Paclitaxel in Combination With Carboplatin Versus Solvent-Based Paclitaxel Plus Carboplatin as First-Line Therapy in Patients With Advanced Non–Small-Cell Lung Cancer: Final Results of a Phase III Trial. Journal of Clinical Oncology. 2012;30:2055-62. 3. Kubota K, Watanabe K, Kunitoh H, Noda K, Ichinose Y, Katakami N, et al. Phase III Randomized Trial of Docetaxel Plus Cisplatin Versus Vindesine Plus Cisplatin in Patients With Stage IV Non-Small-Cell Lung Cancer: The Japanese Taxotere Lung Cancer Study Group. Journal of Clinical Oncology. 2004;22:254-61. 4. TCGA Network. Comprehensive genomic characterization of squamous cell lung cancers. Nature. 2012;489(7417):519-25. 5. Paik PK, Shen R, Won H, Rekhtman N, Wang L, Sima CS, et al. Next-Generation Sequencing of Stage IV Squamous Cell Lung Cancers Reveals an Association of PI3K Aberrations and Evidence of Clonal Heterogeneity in Patients with Brain Metastases. Cancer Discovery. 2015;5:610-21. 6. Kim Y, Hammerman PS, Kim J, Yoon J-a, Lee Y, Sun J-M, et al. Integrative and Comparative Genomic Analysis of Lung Squamous Cell Carcinomas in East Asian Patients. Journal of Clinical Oncology. 2014;32:121-8. 7. Paik PK, Shen R, Berger MF, Ferry D, Soria J-C, Mathewson A, et al. A Phase 1b Open Label Multicentre Study of AZD4547 in Patients with Advanced Squamous Cell Lung Cancers. Clinical Cancer Research. 2017. 8. Nogova L, Sequist LV, Garcia JMP, Andre F, Delord J-P, Hidalgo M, et al. Evaluation of BGJ398, a Fibroblast Growth Factor Receptor 1-3 Kinase Inhibitor, in Patients With Advanced Solid Tumors Harboring Genetic Alterations in Fibroblast Growth Factor Receptors: Results of a Global Phase I, Dose-Escalation and Dose-Expansion Study. Journal of Clinical Oncology. 2017;35:157-65. 9. Lim SH, Sun J-M, Choi Y-L, Kim HR, Ahn S-M, Lee JY, et al. Efficacy and Safety of Dovitinib in Pretreated Advanced Squamous Non-small Cell Lung Cancer with FGFR1 Amplification: A Single-arm, Phase II Study. Cancer. 2016. 10. Vansteenkiste JF, Canon J-L, De Braud F, Grossi F, De Pas T, Gray JE, et al. Safety and Efficacy of Buparlisib (BKM120) in Patients With PI3K Pathway-Activated Non-Small Cell Lung Cancer (NSCLC): Results From the Phase II BASALT-1 Study. Journal of Thoracic Oncology. 2015;Publish Ahead of Print. 11. Patnaik A, Rosen LS, Tolaney SM, Tolcher AW, Goldman JW, Gandhi L, et al. Efficacy and Safety of Abemaciclib, an Inhibitor of CDK4 and CDK6, for Patients with Breast Cancer, Non–Small Cell Lung Cancer, and Other Solid Tumors. Cancer Discovery. 2016.

Abstract:

Abstract not provided

Background:
Tobacco smoking has a negative impact on the prognosis of A-NSCLC. It is less well known how smoking impacts the burden of disease. As such, an analysis was conducted to evaluate the impact of a current tobacco smoking habit and/or history of smoking on the burden of A-NSCLC.

Method:
Data were collected between May 2015 and June 2016 from adult patients with Stage IIIB or IV NSCLC via medical chart reviews and patient self-completion forms as part of a multicentre, cross-sectional study conducted in France, Germany and Italy. Health status was measured using the EQ-5D-3L (including the visual analogue scale, EQ-VAS), quality of life (QoL) using the EORTC QLQ-C30 and work/activity impairment using the WPAI:GH questionnaire. Costs of NSCLC-related productivity losses and out-of-pocket expenses were also collected. Outcomes were stratified by smoking status (current/former smoker vs never smoked); no adjustments were made for possible confounding factors. Statistical significance was assessed using Mann–Whitney U tests.

Result:
1030 patients were recruited: mean patient age, 64.5 years; male, 65.9%; Stage IV NSCLC, 88.4%; non-squamous histology, 70.3%; receiving first-line therapy, 70.5%. Patients were largely receiving chemotherapy, regardless of line of therapy. In total, 1010 patients had smoking status recorded; 787 (77.9%) were current/former smokers and 223 (22.1%) had never smoked. Significant differences were observed between current/former smokers and patients who had never smoked for health status, QoL, work- and activity-related impairments, and NSCLC-related costs (TABLE). Figure 1



Conclusion:
A significant deterioration in health status and QoL, along with greater work- and activity-related impairments, was observed in current/former smokers with A-NSCLC. Moreover, costs of NSCLC-related productivity losses and out-of-pocket expenses were also higher versus those who had never smoked. These findings suggest an association between tobacco smoking and the humanistic and financial burden incurred by patients with A-NSCLC.

Background:
Identifying key issues for patients with lung cancer is central to assessing quality of life (QOL). Gralla el al described in 2014 a 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. Studies have shown that patients with advanced lung cancer have a decline in functional capacity from diagnosed and during treatment. Studies examining physical exercise in patients with lung cancer have indicated increased physical capacity, functional capacity and muscular capacity, but no unambiguously significant improvements in QOL. The aim of this study is to investigate the effect of an exercise intervention for patients with advanced stage lung cancer.

Method:
Eligible patients >18 years with a WHO performance status 0-2 with stage IIIb-IV NSCLC and SCLC-ED who were undergoing chemotherapy at the Department of Oncology University Hospital Copenhagen were randomized to standard care or a 12 week physical and psycho-social intervention. Aerobic capacity (VO2peak), functional capacity (6MWD) and QOL (FACT-L) were measured at baseline and 12 weeks.

Result:
A total of 218 patients met the inclusion criteria and were randomized. There were no significant differences in baseline characteristics between the groups. There was a significant improvement in 6MWD in both groups, improvement in intervention was 41.1 m and improvement in control was 16.5 m. There were no significant differences between-groups in overal QOL (FACT-L) although there was a significant improvement in groups in overall QOL (FACT-L), Physical wellbeing, Emotrional wellbeing,Trial Outcome Index for the intervention group. There was a significant difference between groups in the subscale Social Wellbeing (FACT-L) P=<0.04.

Conclusion:
Conclusion: The results of this study demonstrate that functional capacity (6MWD) improves during a 12 week period for patients with advanced stage lung cancer. The improvements in both groups indicate an effect of chemotherapy on functional capacity however the significantly higher improvement in the intervention group indicate a further effect of the exercise intervention. The in-group improvement in QOL in the intervention group indicate a link between an incline in functional capacity and the QOL.

Background:
Lung cancer is the leading cause of cancer death in the US. Only 15% are diagnosed at early stage, resulting in a 5-year survival of 17%. Disparities exist among racial/ethnic minorities and the medically underserved and regionally. High mortality is in part due to the prior absence of a lung cancer screening guideline. c-CARE aims to improve cancer health literacy and outcomes in disparate populations. The purpose of c-CARE project is to increase community awareness of lung cancer risk factors and screening criteria, and to connect high-risk individuals to lung cancer screening and tobacco cessation services.

Method:
The study approach was Community-engaged Research. Formative development involved vetting the study design with the Community Advisory Board (CAB) to ensure community priorities and concerns were addressed. Curriculum development and intervention evaluation were guided by the Health Belief Model. Community members and Community Health Workers unassociated with the current project were recruited to participate in focus groups and semi-structured interviews to review the curriculum and guide refinement of the survey instruments. Thirteen community sites were enrolled: 9 African- American churches; 3 community clinics that serve the medically underserved, and a community recreation center. Researchers trained four Community Health Workers from within each community site to deliver four education sessions. High-risk individuals were connected to lung cancer screening programs and tobacco cessation. Pre- and post-intervention outcome measures were collected on enrolled participants (n=481) to assess changes in participant knowledge, attitudes and beliefs regarding cancer, perceived barriers and self-efficacy to obtain lung cancer screening and tobacco cessation services.

Result:
Participants were majority African American, (n= 481);mean age 58.3 years; 16% were tobacco users. Post intervention knowledge, attitudes and beliefs regarding cancer had significant change (p= 001). Health Belief Model constructs post intervention were significant for Perceived Benefits and Self Efficacy subscales. Spearman correlations were significant between smoking status and Perceived Susceptibility, Perceived Barriers post intervention, Self Efficacy at baseline, Attitude post intervention and Belief at baseline.

Conclusion:
Community engaged methods engendered community buy-in of the project, enhanced the study design and development of a culturally acceptable curriculum. The data derived from the focus groups and interviews facilitated the refinement of the curriculum and data collection instruments. Training Community Health Workers to recruit participants and deliver the curriculum facilitates access to a hard-to-reach population, builds community capacity,and ensures curriculum delivery within the social context of the setting.Brief community interventions can increase cancer knowledge and sreening self-efficacy.

Background:
Aggressive care and chemotherapy worsens quality of life (QoL) of dying cancer patients. Early palliative care (EPC) in patients with metastatic non small cell lung cancer (NSCLC) is associated with improvements in QoL. Thus, we aimed to explore an impact of EPC on the aggressiveness of care at the end of life (EOL).

Method:
An observational cohort enrolled newly diagnosed metastasis NSCLC at Ramathibodi hospital from 31[st] August 2015 to 1[st] September 2016. In EPC group, the consultation of specialized palliative team was performed ≤ 4 weeks of diagnosis and before start chemotherapy treatment, then monthly visits until death and the last visit for bereavement. The palliative consultation in standard of care (SOC) patients performed as their routine practices. The cutoff date for survival analysis was on 31[st] December 2016. The aggressiveness of care in EOL was defined as the composite outcome as any of the followings: last dose of chemotherapy received < 14 days of death, a new chemotherapy regimen starting < 30 days before death, ≥ 1 hospital admissions or emergency room visits or hospitalizations > 14 days in 30 days of death, or an ICU admission in 30 days of death.

Result:
105 patients were enrolled, 38 out of 70 patients (54%) in SOC group and 17 out of 35 patients (48%) in EPC group died. More aggressiveness of care at the EOL (97.3% vs 64.7%, p=0.003), more in-patient death (89.5% vs 58.8%; p=0.009) and longer hospitalization before death were observed in the SOC group (12 days vs 4 days, p=0.028). The cost analysis of patients who died at the hospital showed higher hospitalized cost in the SOC group (p=0.005). The EPC group received less aggressive treatments such as using less than 3 regimens of chemotherapy (77.1% vs 94.3%; p=0.028), but the survival rate was not different (11.3 months vs 6.6 months; p=0.08).

Conclusion:
Early palliative care reduced the aggressiveness of care at the end of life, shortened hospitalization and covered less cost of treatment.

Abstract not provided

Background:
Lung cancer continues to have a high mortality in Canada, with many patients presenting with advanced stage disease. The Ottawa Hospital (TOH) used a learning health systems (LHS) approach to redesign regional diagnostic processes to reduce the overall time from presentation with a suspicious lung mass to diagnosis and treatment. As previously published by our group, an LHS approach is driven by feedback utilizing operational and clinical information to drive system optimization and innovation. TOH is the only provider of cancer services for a population of 1.3 million people in eastern Ontario and hence the need for an integrated patient journey from regional health facility to tertiary care centre was identified. Patient advocates have been incorporated as key members of the LHS from inception to implementation to post-implementation review.

Method:
The Ottawa Health Transformation model (OHTM) was developed as a means of operationalizing a LHS. A kick off meeting brought together cancer patients and their families to map out existing processes and document the patient experience. A regional lung cancer Community of Practice (CoP) of clinical and non-clinical stakeholders was then established to guide and approve the work of a core transformation team. The team had patient and family advocates as key members and they were tasked with identifying appropriate wait time targets and vetting proposed processes. A consensus approach was used to address process barriers, resistance to change and conflicting priorities in regular meetings spanning over two years. Commercially available software was used to track patient progress through the diagnostic process and to report real time metrics to the transformation team.

Result:
The project operationalized lung cancer diagnostic pathway guidance and optimized patient flow from referral to initiation of treatment. Twelve major processes in referral, review, diagnostics, assessment, triage and consult were redesigned. TOH now provides a diagnosis to 80% of referrals within the provincial target of 28 days and leads all other jurisdictions in Ontario in this metric by a wide margin. The median patient journey from referral to initial treatment decreased 48% from 92 to 47 days. In 2016 this work was recognized by a provincial cancer agency with a quality award.

Conclusion:
A learning health system has significantly reduced the time from referral with suspicion of lung cancer to diagnosis to treatment. Achievements require a multi-disciplinary approach with a regional perspective. Patient and family advocates have an important voice in re-designing health care systems.

Background:
The Addario Lung Cancer Foundation’s community hospital COE Program seeks to improve LC outcomes by catalyzing the dissemination of coordinated, evidence-based multidisciplinary care incorporating institutional performance benchmarks across the LC care continuum. The COE program is a network of community-level institutions committed to objectively-measured quality improvement through annual cycles of data collection, comparative analysis and feedback. We analyzed 2016 benchmarks, comparing COE and non-COE programs.

Method:
The annual COE Impact Survey instrument includes an 81-item questionnaire administered by ZoomRx, an independent survey company. Respondents were key institutional representatives of COE- and community-level non-COE institutions. The survey measured the care continuum from screening to end-of-life care. Patient- and institutional-level data for 2016 were analyzed.

Result:
Cohort- 15 COE v 15 non-COE, mean number of annual patients per site 264 v 279; % stage III/IV patients 62 v 74; Medicare-enrolled patients, 54% v 40%; patients 61-80 years 61% v 46%; % patients who encountered financial difficulty in 2016, 42% v 34%. Institutional screening/nodule management programs: 71% of COE v 60% of non-COE programs had a low-dose CT (LDCT) screening program; 86% v 80% used a standard protocol to follow patients with suspicious nodules; 35% v 28% LDCT patients were requested to follow up on suspicious findings; 76% v 67% patients actually followed up. Diagnostic biopsy of LC was by minimally invasive endobronchial approaches in 47% v 15%. Programmatic management of patients with stage III/IV disease: 75% v 49% of patients with stage III/IV disease were reviewed at a Tumor Board and 74% v 62% had a palliative care discussion. Molecular testing was used in 51% v 81%. In patients undergoing molecular testing, institutional use of blood-based ‘liquid biopsies’ was 86% v 18% and next generation sequencing of tissue 67% v 58%. Clinical trials enrollment rates were 20% v 13%, but 18% v 31% of patients were not screened for clinical trials. In weighting factors driving treatment selection on a 100-point relative scale, COE programs weighted ‘quality of life’ (39% v 26%) and ‘patient expense’ (22% v 11%) more than non-COE programs. Non-COE programs weighted ‘product attributes’ (efficacy and safety) 48% (v 14% in COE) more.

Conclusion:
Differences exist in the approach to LC care between COE and non-COE programs. Future iterations of the COE Impact Survey will enable a data-driven approach to disseminating high quality LC care at community-level institutions, where the majority of patients seek care for lung cancer.

Abstract not provided