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Gwyn Bebb



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    P1.03 - Chemotherapy/Targeted Therapy (ID 689)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Chemotherapy/Targeted Therapy
    • Presentations: 1
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      P1.03-043 - 30-Day Mortality Following Systemic Anti-Cancer Treatment for NSCLC at a Single Canadian Cancer Centre (ID 10103)

      09:30 - 09:30  |  Presenting Author(s): Gwyn Bebb

      • Abstract

      Background:
      Systemic Anti-Cancer Therapies (SACT) are frequently employed as either curative or palliative treatments in patients with lung cancer, but the benefits of SACT take time and may not always render immediate benefit. Death within 30 days of receiving SACT suggests that treatments were futile since these patients did not live long enough to derive direct therapeutic benefit. This study aimed to identify clinical factors associated with the risk of 30-day mortality among patients with advanced non-small cell lung cancer (NSCLC) at the Tom Baker Cancer Center (TBCC) in Calgary, Canada.

      Method:
      A retrospective review of NSCLC patients receiving SACT between January 2010 and December 2014, and captured in the Glans-Look Lung Cancer Database was conducted. We identified patients with a regimen start or change of SACT in the last 30 days of life. Mortality rates were calculated, and multivariable logistic regression was used to identify demographic, tumor or treatment-related factors that correlated with 30-day mortality risk.

      Result:
      Of 573 NSCLC patients receiving SACT between January 2010 and December 2014, 119 patients were identified as dying ≤ 30 days following SACT, yielding a 22% 30-day mortality rate. Of these 119 patients, 47% had a change or initiation of SACT within the last 30 days of life, and 54% received treatment within the last 14 days of life. Of patients dying within 30 days, 50% received cytotoxic chemotherapy, and 48% received anaplastic lymphoma kinase/tyrosine kinase inhibitors (ALK/TKI) as compared to 79% and 20% of surviving patients, respectively. This resulted in a 30-day mortality rate of 10.6% for cytotoxic chemotherapy and 10.3% for ALK/TKI therapy. Ongoing analysis will elucidate predictive factors that are associated with increased risk of 30-day post-SACT mortality.

      Conclusion:
      A number of NSCLC patients are at increased risk of dying within 30 days of SACT receipt. Efforts to determine the clinical characteristics of patients dying within 30 days of SACT, and to ascertain potential indicators of poor outcome following SACT can reduce avoidable harm. Data from a diverse and representative patient population such as this can provide real world evidence and serve as a means of informing best practices in palliative and end-of-life care for cancer patients.

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    P1.06 - Epidemiology/Primary Prevention/Tobacco Control and Cessation (ID 692)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Epidemiology/Primary Prevention/Tobacco Control and Cessation
    • Presentations: 1
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      P1.06-006 - Survival Benefits and Associated Prognostic Factors among Young NSCLC Patients (ID 8582)

      09:30 - 09:30  |  Presenting Author(s): Gwyn Bebb

      • Abstract

      Background:
      Lung cancer is rare in young patients. The aim of this study was to determine the incidence of non-small cell lung cancer (NSCLC) among young patients (YP) versus older patients (OP) at our tertiary cancer centre. Additionally, associated prognostic factors, survival outcomes, and adherence to guideline-recommended treatment based on age were described.

      Method:
      All NSCLC patients initially diagnosed through the Tom Baker Cancer Centre (TBCC), in Calgary, Alberta, Canada between January 1999 and December 2013 were included. Patient data was retrospectively collected from electronic and paper charts as part of an institutional research program (Glans-Look Lung Cancer Database). YP were defined as ≤47 years, or two standard deviations below the mean. Chi-square tests were used to analyze categorical clinical and demographic factors among the age groups (≤47 versus >47), and overall survival (OS) was determined using Kaplan-Meier. The Cox proportional hazard model was applied to calculate the hazard ratio (HR) and its 95% confidence intervals (CI).

      Result:
      A total of 6,899 cases were examined. YP represented 3% (n=197) of incident NSCLC from 1999-2013: 1999-2004 (4.1%), 2005-2009 (2.8%), and 2010-2013 (1.8%). Compared to OP, YP tend to be female (54.8% vs. 47.9%, p=0.062) and never-smokers (25.4% vs. 7.7%, p<0.001). Additionally, most present with stage IV disease (61.4% vs. 54.1%, p=0.279), and adenocarcinoma (57.4% vs. 42.4%, p<0.001). YP demonstrated better median OS (13.5 months, 95% CI: 10.8-16.2) compared to OP (9.4 months, 95% CI: 9.0-9.9, p<0.001). Positive independent prognostic factors were early stage disease (IB-IIIA) (HR, 0.544; CI: 0.392-0.753, p=0.002), female sex (HR, 0.880; CI: 0.836-0.927, p<0.001), never-smoker (HR, 0.714, CI: 0.654-0.779, p<0.001), and former smoker (HR, 0.735; CI: 0.671-0.806, p<0.001). Non-adenocarcinoma subtypes were negative prognostic predictors of survival (HR, 1.648; CI: 1.416-1.919, p<0.001). Compared to OP, YP were more likely to receive guideline treatment according to disease stage. Among stage IV patients, YP were 30% more likely to receive chemotherapy (p<0.001). YP with stage III were twice as likely to receive concurrent chemo-radiation (p=0.007). Lastly, 90% of YP with stage I and II (A and B) received surgery, compared to half of OP (p<0.001).

      Conclusion:
      The incidence of NSCLC diagnoses among YP has been decreasing at the TBCC since 1999. In our cohort of NSCLC patients, YP demonstrated better overall survival; possibly due to a higher likelihood of receiving guideline-recommended therapy. Additionally, clinical characteristics of YP NSCLC patients differ from those observed in OP.

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    P2.01 - Advanced NSCLC (ID 618)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Advanced NSCLC
    • Presentations: 1
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      P2.01-046 - Clinical Characteristics of Survival with De Novo Versus Relapsed Metastatic Non-Small Cell Lung Cancer (ID 10102)

      09:00 - 09:00  |  Presenting Author(s): Gwyn Bebb

      • Abstract

      Background:
      Metastatic non-small cell lung cancer (mNSCLC) can present as de novo or relapsed disease. This study aimed to determine the clinical prognostic factors impacting post-metastatic survival, specifically comparing outcomes in de novo versus relapsed early stage populations.

      Method:
      Retrospective review of mNSCLC patients diagnosed between January 1999 and December 2013 in the Glans-Look Lung Cancer Database was conducted to identify relapsed early stage and de novo cases. Fisher's exact and Wilcoxon rank-sum tests were used to analyze categorical and continuous factors, respectively. Survival outcomes were analyzed and compared via the Kaplan-Meier and log-rank tests. Cox regressions were used to determine the impact of de novo versus relapsed mNSCLC presentation on prognosis, while adjusting for multiple confounders. We excluded stage III patients.

      Result:
      3039 de novo and 185 relapsed patients were identified. Median post-metastatic survival was significantly longer for relapsed vs de novo, 8.90 (CI: 6.24-12.06) versus 3.71 (CI: 3.48-3.98) months, (p<0.001). Relapsed patients also demonstrated significant survival gains since 1999-2004. Different patterns of smoking history, histology, systemic anti-cancer therapy (SACT) usage and number of extra-pulmonary sites existed between the relapsed and de novo cohorts. Multivariate analysis demonstrated that de novo disease, male gender, ‘Never’ smoking history, ‘NOS’ histology, and the presence of extra-pulmonary metastases were significant factors in predicting a worse prognosis. SACT receipt and ‘Other’ histology were associated with better outcomes. In the relapsed subset, squamous cell histology also boded inferior survival. (Table 1) Figure 1



      Conclusion:
      Relapsed and de novo patients represent significantly different sub-populations within mNSCLC, with survival favoring relapsed patients. This finding may inform discussions around prognosis, reinforce the value of follow-up/surveillance of early stage patients, and provide support for screening initiatives aimed at reducing the burden of de novo disease.

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    P2.02 - Biology/Pathology (ID 616)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Biology/Pathology
    • Presentations: 1
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      P2.02-068 - BRG1 and p53 Expression in Resected Stage I – III Non-Small Cell Lung Cancer (ID 10199)

      09:30 - 09:30  |  Presenting Author(s): Gwyn Bebb

      • Abstract

      Background:
      Evidence suggests a striking significance of BRG1 in non-small cell lung cancer (NSCLC) development and prognosis including its ability to modulate NSCLC response to commonly used chemotherapy. The human SW1/SNF (switching defective/ sucrose non-fermenting) family of chromatin remodeling complexes are composed of multi-subunit proteins among which are the BRG1 and INI-1. Both BRG1 (SMARCA4) and INI-1 (SMARCB1, BAF47, SNF7) are implicated in different cancers. We aimed at identifying the frequency of the SW1/SNF protein components loss and the significance in NSCLC. Given that inactivating BRG1 mutations could coexist with TP53 alterations in NSCLC cell lines, we also included the tumor suppressor protein p53 in our analysis.

      Method:
      We analyzed the expression of the SW1/SNF subunits (BRG1 and INI-1) and p53 proteins from resected stage I – III NSCLC using the immunohistochemistry. Mouse monoclonal anti-p53 (DO-7, Dako Omnis) and anti-INI-1 (MRQ-27, Cell Marque) antibodies were used for p53 and INI-1 protein detection respectively. BRG1 was detected using the rabbit monoclonal anti-BRG1 antibody (EPNCIR111A, Abcam). Clinical data were obtained from the Glans-Look lung cancer database and patients diagnosed of NSCLC from 2003 to 2006 were included in the study.

      Result:
      A total of 150 cases were identified, {Adenocarcinoma n =82 (54.7%), Squamous cell carcinoma n = 50 (33.3%), Large cell carcinoma n = 7 (4.7%) and others n = 11 (7.3%: Adenosquamous, Bronchioalveolar and Giant cell carcinomas)}.The BRG1 protein was absent in 6% (9/150) of cases with the overall highest number (3.3%) seen in adenocarcinoma. Whereas, normal INI-1 protein was expressed in all samples. Within NSCLC subtypes, the rate of BRG1 loss was highest in the large cell carcinomas at 28.1% (2/7) and lowest in squamous cell subtype at 2% (1/50) while only 6.1% (5/82) of adenocarcinoma showed BRG1 loss. The frequency of aberrant p53 protein expression (including overexpression, cytoplasmic and complete expression loss) was at 63% (95/150) and 6 (2 large cell and 4 adenocarcinoma) of the 95 abnormal p53 cases (6.3%) had BRG1 loss.

      Conclusion:
      BRG1 loss seems to be a low occurrence in NSCLC. Although a high rate of BRG1 inactivating mutations were previously reported in NSCLC cell lines, the present result suggests that these mutations may still result in the expression of possibly an abnormal BRG1. BRG1 loss appears to coexist with p53 abnormality in NSCLC. Additional multivariate and outcome analysis will be presented.