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Clarissa Mathias



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    EP1.16 - Treatment in the Real World - Support, Survivorship, Systems Research (ID 206)

    • Event: WCLC 2019
    • Type: E-Poster Viewing in the Exhibit Hall
    • Track: Treatment in the Real World - Support, Survivorship, Systems Research
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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      EP1.16-39 - Prospective Epidemiological Study of Metastatic Non-Small Cell Lung Cancer (NSCLC) in Latin America – LATINO Lung (LACOG 0116) (Now Available) (ID 1405)

      08:00 - 18:00  |  Author(s): Clarissa Mathias

      • Abstract
      • Slides

      Background

      Non-small cell lung carcinoma (NSCLC) is the main cause of cancer-related death in Latin America. Nonetheless, there is insufficient information regarding its epidemiology, treatment and outcomes in the region. The goals of this study are to describe disease characteristics, treatment patterns and survival for advanced NSCLC in Latin America.

      Method

      LACOG 0116 LATINO Lung is a prospective cohort study aiming to include approximately 800 patients with advanced stage NSCLC (stage III/IV at diagnosis or distant relapse of early-stage disease) from 24 sites in Brazil, Argentina, Mexico, Colombia and Chile. All consecutive newly diagnosed patients seen at each site will be invited to participate. Data on socioeconomic and demographic characteristics, medical/oncologic history and clinical-pathological characteristics will be collected at baseline. Thereafter, patients will be followed every 6 months for 3 years in order to gather information regarding treatment patterns and sequencing, reasons for treatment discontinuation, response to treatment, disease progression and overall survival. Data will be collected during medical visits or telephone calls and by medical charts review. Primary endpoint is to estimate the overall survival. Descriptive analysis of treatments and outcomes are planned. Multivariable regression methods will be applied to assess possible independent prognostic or predictive factors.

      Result

      As of April 3rd, 2019, 107 patients have been included, all of them within 16 sites in Brazil. Currently, there are 2 sites from Argentina, 2 from Mexico, 3 from Colombia and 1 from Chile awaiting regulatory approval to begin enrollment. Recruitment is planned to last until December 2019, when the estimated sample size will be achieved.figure1.png

      Conclusion

      LACOG 0116 LATINO Lung is the first Latin American lung cancer prospective cohort study that will generate real-world data on NSCLC. The study may identify gaps and inequities in a diverse population of NSCLC in Latin America and consequently raise the need for improvement and individualized approach of lung cancer care in the region.

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    GR02 - Improving Patients Quality of Life During Treatment of Metastatic Disease (ID 30)

    • Event: WCLC 2019
    • Type: Grand Rounds Session
    • Track: Advanced NSCLC
    • Presentations: 1
    • Now Available
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      GR02.01 - How Can We Incorporate Exercise Practices into Patient's Lives? (Now Available) (ID 3304)

      15:15 - 16:45  |  Presenting Author(s): Clarissa Mathias

      • Abstract
      • Presentation
      • Slides

      Abstract

      Physical activity is any movement using skeletal muscles. There have been over 16 studies examining physical activity and lung cancer risk, 12 cohorts and four case-control studies have examined the association between physical activity and lung cancer. When stratifying by study design, the pooled risk reduction amongst the 12 cohort studies is 23%, and amongst 4 case-control studies, a pooled risk reduction of 38%1. Among In a meta-analysis of 11 studies comparing highest versus and lowest levels of leisure-time physical activity, including odds ratios from studies in which the association between physical activity and cancer prevention was adjusted for smoking intensity: moderate-intensity physical activity was associated with a statistically significant risk reduction in lung cancer incidence, OR=0.87 (95% CI: 0.79–0.95), and vigorous-intensity physical activity was associated with a statistically significant risk reduction in lung cancer incidence, OR=0.70 (95% CI: 0.62–0.79).

      During exercise, particularly moderate-intensity aerobic exercise, T-cell populations transiently, NK cell populations and activity, and neutrophil quantity and activity transiently rise2. Exercise or physical activity haves a profound effect on macrophage physiology, including phagocytosis, chemotaxis, metabolism and anti-tumor activity. In murine models of acute exercise, peritoneal macrophage phagocytosis was increased in vitro, relative as opposed to sedentary conditions3. Although these effects are transient during an acute bout of exercise, the repetitive effects may produce a cumulative (training) effect. Chronic bouts of physical activity have been associated with an inverted ‘J-curve’ such that optimal immune function is achieved with moderate-intensity physical activity and sedentary and vigorous-intensity below optimal immune-system function.

      Physical activity is also a useful adjunct to improve the deleterious sequelae experienced during cancer treatment including fatigue, muscular weakness, deteriorated functional capacity, and many others. There is a growing base of evidence that suggests engaging in exercise, such as brisk walking, yields fewer symptoms and side effects during treatment and retards delays the rate at which physiologic systems are affected4. The mechanistic models hypothesized that includes pathways relating to sex hormones, metabolic hormones, inflammation and adiposity, immune function, oxidative stress, DNA repair, and xenobiotic enzyme systems. During cancer treatment, deconditioning of the cardiovascular and pulmonary system is common and is associated with diminished levels tolerance to of physical activity. However, it appears that the adaptive capacity of the cardiorespiratory system to exercise training remains intact during treatment. Among In a meta-analysis of 17 high-quality studies, aerobic fitness—a marker of cardiorespiratory function—improved significantly in cancer survivors during treatment over the exercise intervention period. Muscle Ffatigue and muscle weakness are also common sequelae of cancer treatment, but may be amenable to exercise training. A meta-analysis of randomized controlled trials concluded that both upper body and lower body strength improve as a result of exercise training during cancer treatment, with d=0.39 (95% CI: 0.12–0.65), and d=0.24 (95% CI: 0.07–0.41), respectively5. Strength improvements in the absence of muscle hypertrophy suggest that the adaptations resulting from strength training may be largely attributable to neural adaptations from better motor unit activation (recruitment, discharge rate), synchronization, and cross education. Neural adaptations occur early on in aduring a strength training program and may explain strength improvements in most short-term training studies. Mmoderate intensity activity may optimize immune activity and promote an anti-inflammatory state. Several biomarkers of immunologic function and inflammation exist including neutrophil and lymphocyte counts, natural killer cell activity, C-reactive protein, IL-6, IL-10, and TNF- alpha. It remains unclear what benefits exercise may have on immune system function after cancer treatment6.

      Despite the large volume of studies examining muscular strength among cancer survivors during treatment, few studies have examined the role of strength training among those with cancer cachexia7. It is interesting, Interestingly, given the success of resistance training among cancer survivors, to increaseincreasing upper and lower body strength that use of this modality among cancer survivors with cachexia is not more commonly studied.

      Despite the favorable profile of physical activity along the cancer continuum, many research gaps still exist. Elucidating the optimal dose of physical activity necessary to maximize the reduction in cancer risk of cancer and the optimal dose of physical activity necessary to improve specific physiologic systems, or treatment-specific side effects is warranted. In July 2010, an expert panel from the American College of Sports Medicine reviewed current studies of exercise training and cancer survivorship and released a roundtable consensus statement, concluding that exercise training is “safe during and after cancer treatments and results in improvements in physical functioning, quality of life, and cancer-related fatigue”8.

      Incorporation of exercise practices should, therefore, be advised and stimulated to prevent lung cancer, decrease treatment related side effects, rehabilitate survivors and possibly help during the cachexia period. Interaction between medical oncologists, thoracic surgeons, pulmonologists, physical therapist and sports medicine experts is mandatory for an optimal design of needed trials that will answer several opened questions related to this topic.

      References

      1. Emaus A et al. Physical activity and lung cancer prevention. Recent Results Cancer Res. 2011; 186:101–133

      2. Shephard RJ et al. Effects of exercise and training on natural killer cell counts and cytolytic activity: a meta-analysis. Sports Med. 1999; 28(3):177–195

      3.Woods JA, et al. Exercise-induced modulation of macrophage function. Immunol Cell Biol 78: 543-553, 2000

      4. Schmitz KH, et al. American college of sports medicine roundtable on exercise guidelines for cancer survivors. Med Sci Sports Exerc. 2010; 42(7):1409–1426

      5. Speck RM, et al. An update of controlled physical activity trials in cancer survivors: a systematic review and meta-analysis. J Cancer Surviv. 2010; 4(2):87–100

      6. McTiernan A. Mechanisms linking physical activity with cancer. Nat Rev Cancer. 2008; 8(3): 205–211

      7. Bossola M, et al. Cancer cachexia: it’s time for more clinical trials. Ann Surg Oncol. 2007

      8. Schmidt KH, et al. American College of Sports Medicine roundtable on exercise guidelines for cancer survivors. Med Sci Sports Exerc 42: 1409-1426, 2010

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    MA21 - Non EGFR/MET Targeted Therapies (ID 153)

    • Event: WCLC 2019
    • Type: Mini Oral Session
    • Track: Targeted Therapy
    • Presentations: 1
    • Now Available
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      MA21.03 - The International Association for the Study of Lung Cancer (IASLC) Global Survey on Molecular Testing in Lung Cancer (Now Available) (ID 1198)

      14:30 - 16:00  |  Author(s): Clarissa Mathias

      • Abstract
      • Presentation
      • Slides

      Background

      Evidence-based standards for molecular testing of lung cancer have been established, but the global frequency and practice of testing are not well understood. The IASLC conducted an international survey to evaluate current practice and barriers to molecular testing.

      Method

      Distributed to IASLC members and other healthcare professionals, content included: 7-question introduction, 32 questions for those requesting tests/treating patients, 45 questions on performing/interpreting assays, and 24 questions on tissue acquisition. All respondents were asked to provide 3-5 barriers to implementing/offering molecular testing.

      Respondents’ countries were grouped by geography or developing/developed using IASLC and World Bank criteria. Surveys were available in 7 languages. Regional comparisons used the Chi-squared test or ANOVA; free-text was analyzed with Nvivo.

      Result

      We obtained 2,537 responses from 102 countries. Respondents were 45% Medical Oncologists, 12% Pulmonologists, 12% Thoracic Surgeons, 9% Pathologists, and 22% scientists or other. 56% of responses were from developing countries, 44% developed. Regions included: 52% Asia, 19% Europe, 11% Latin America, 11% US/Canada, 7% Other.

      1683 (66%) chose the requesting/treating track (50% government, 42% academic, 8% other). 61% reported most patients in their country do not receive molecular testing, with the lowest rates in Latin America/Other (p<0.0001). 39% were not satisfied with the conditions of molecular testing in their country. Indications for requesting testing included: adenocarcinoma (89%), never-smoker (61%), female (57%), and young (54%) (variable by region, p<0.0001). 99% ordered EGFR, 95% ALK, 84% PDL1, 79% ROS1, all other tests <50%. 56% typically received results within 10 days. Only 67% were aware of CAP/IASLC/AMP guidelines, least frequently in Asia/Other (p=0.041). 37% have trouble understanding molecular testing result reports, most of whom cited a need for more technical and scientific knowledge. 75% had multidisciplinary tumor boards, but 23% met <1/month.

      The 316 (12%) testing track respondents were from laboratories that were 49% academic, 35% government, and 16% private/other. 94% of laboratories offered EGFR, 83% ALK, 69% KRAS, 68% BRAF, 64% ROS1, 56% HER2, and others <50%; 68% tested for PDL1. 57% offered Multiplex assays, less frequently in Latin America/Asia (p=0.0294). 69% tested blood-derived DNA, less frequently in US/Canada/Other (0.0013). 23% of respondents reported >10% of cases are rejected due to inadequate samples; however, 47% stated there is no policy or strategy to improve the quality of the tissue samples in their country. 52% reported patients/physicians are not satisfied with the state of molecular testing in their country. Respondents performing/interpreting assays (334, 14%) were typically informed of biopsy results (91%), and notified when the sample was inadequate (84%).

      The most frequent barrier to molecular testing in every region was cost, followed by quality/standards, turnaround-time, access, and awareness. After cost, time was the most common barrier in developed countries, while it was quality in developing countries. The second largest barrier was quality in Asia, access in Europe/Latin America/Other, and turn-around time in US/Canada.

      Conclusion

      These preliminary analyses show molecular testing usage varies across the globe. Barriers vary by region, and one-third of respondents were unaware of evidence-based guidelines. Global and regional strategies should be developed to address barriers.

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    P1.09 - Pathology (ID 173)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Pathology
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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      P1.09-02 - Comprehensive Genomic Profiling of Non-Small Cell Lung Cancer in Brazil (GBOT 0118/LACOG 0418) (Now Available) (ID 2048)

      09:45 - 18:00  |  Author(s): Clarissa Mathias

      • Abstract
      • Slides

      Background

      Lung cancer is the leading cause of cancer-related morbidity and mortality worldwide. Cancer driver mutations have been examined extensively and are the basis for modern precision therapy. The access of genomic tests in Brazil and, therefore, the prevalence of driver mutations of NSCLC in the country is not well described. The objective of this study is to carry out an epidemiological analysis of the somatic genetic profile of Brazilian NSCLC samples tested with FoundationOne®.

      Method

      GBOT 0118/LACOG 0418 is a retrospective cross-sectional study with patients diagnosed with NSCLC in Brazil and who performed comprehensive genomic profiling (CGP) using FoundationOne® or FoundationACT®. Raw data containing anonymous clinical-pathological characteristics and the results of CGP was analyzed. We described the molecular profile of patients using descriptive statistics. Categorical variables are presented as frequency and compared using the Chi-square test.

      Result

      We obtained a total of 513 CGP results, 457 (89.0%) from Foundation One® and 56 (10.9%) from FoundationACT®. Adenocarcinoma was the most common histological subtype (83.8%) followed by NSCLC NOS (16.1%). Median age at testing date was 64 years, and 51.27% were male. EGFR activating mutations were detected in 23.39% patients, ALK rearrangements in 5.65%, ROS1 rearrangements in 2.34%, RET alterations in 2.53%, BRAF mutations in 5.46%, KRAS mutations in 25,15% and NTRK fusions in 0,58% . Tumor mutational burden (TMB) analysis was available for 80.51% of samples tested and was measured in mutation per megabase. TMB were divided into three groups based on the Foundation Medicine reports: low (1-5 mutations/mb), intermediate (6-19 mutations/mb) and high (≥ 20 mutations/mb). The of tumors had low (42.69%) or intermediate (32.36%) TMB, and only 5.46% had high TMB.

      Table 1. Frequency of somatic genetic alterations in tumors tested with FoundationOne® and availability of targeted therapies in Brazil.

      GENE

      Frequency in NSCLC (%)

      Availability in Brazil

      EGFR

      23.39

      Approved

      ALK

      5.65

      Approved

      ROS1

      2.43

      Approved

      BRAF

      5.46

      Approved

      KRAS

      25.15

      No drugs available

      RET

      2,53

      Drugs available but not approved

      NTRK

      0,58

      Drugs available but not approved

      Conclusion

      This is the most comprehensive study describing CGP of NSCLC in Brazil using FoundationOne® or ACT. Our study shows rates of EGFR mutations and ALK rearrangements similar to those previously described. The knowledge of the molecular patterns of NSCLC in Brazil may help to improve health policies and access to targeted agents in the country.

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