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Gwyn Bebb



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    EP1.12 - Small Cell Lung Cancer/NET (ID 202)

    • Event: WCLC 2019
    • Type: E-Poster Viewing in the Exhibit Hall
    • Track: Small Cell Lung Cancer/NET
    • Presentations: 2
    • Moderators:
    • Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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      EP1.12-02 - SCLC Treatment Uptake and Survival Outcomes: A 2-Year Comparison Between 2 Tertiary Referral Centers in Alberta, Canada (ID 2920)

      08:00 - 18:00  |  Presenting Author(s): Gwyn Bebb

      • Abstract
      • Slides

      Background

      Although the guideline recommend treatment for small cell lung cancer (SCLC) has not changed for several decades, real world evidence on patterns of practice and outcome are scarce. We compared two similar sized cancer care centers in the province of Alberta over a two-year period for experiences with both extensive stage (ES) and limited stage (LS) SCLC diagnoses, treatment and survival outcomes

      Method

      Retrospective analyses were conducted on the clinical data of SCLC patients retrieved from the Glans-Look Lung Cancer database. All SCLC patients diagnosed between 2015 and 2016 at the Tom Baker Cancer Centre (TBCC), Calgary and Cross Cancer Institute (CCI), Edmonton were included. The characteristics of patients seen at the two institutions were compared using the Fisher Exact test. The overall survival (OS) outcome based on guideline recommended 1st and 2nd line SCLC treatments as well as treatment location was estimated with Kaplan Meier survival analysis and multivariate Cox Proportional Hazard model.

      Result

      Between 2015 and 2016, 105 SCLC patients were diagnosed at the TBCC, Calgary and 243 at CCI, Edmonton, Alberta. Patient characteristics were similar for both centers. 66% (69/105) of SCLC were ES at TBCC as opposed to 78% (189/243) in CCI (p = 0.024). Overall, treatment uptake rates in TBCC compared to CCI were as follows: 1st SCLC treatment (chemotherapy, surgery, radiotherapy) rate 88% (92/105) versus 86% (208/243), prophylactic cranial irradiation (PCI) 27% (28/105) vs. 37% (89/243) and 2nd line chemo- and or radio-therapy 33% (35/105) vs. 30% (74/243). 6% (2/36) of LS patients at TBCC compared to 28% (15/54) at CCI had surgery ± adjuvant as their 1st treatment. More ES patients at CCI received chemo & thoracic RT (32 vs.19%, 61/189 and 13/69) as well as PCI (31 vs.16%, 58/189 and 11/69) than those at TBCC. OS at CCI versus TBCC was not statistically different for all SCLC patients (11 vs. 10 months, p = 0.217; HR = 1.278, 95% CI: 0.978 -1.671, p = 0.072) nor when we stratified patients by LS or ES.

      Conclusion

      Despite subtle variation in the uptake of PCI, surgical resection of peripheral LS, management patterns for SCLC patient, including the uptake of second line treatment were consistent between the two geographically separate centers. It is reassuring that similar survival outcomes can be achieved in the real world setting by the adoption of standard practices across a single health administered jurisdiction.

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      EP1.12-12 - Factors Associated with Survival Outcomes Among Relapsed SCLC Diagnosed at a Canadian Cancer Centre (ID 2902)

      08:00 - 18:00  |  Presenting Author(s): Gwyn Bebb

      • Abstract
      • Slides

      Background

      The 5-year survival rate for small cell lung cancer (SCLC) is only 7%. This poor survival is partly accounted for by sparse management options for the high proportion of patients developing disease progression or recurrence after their initial treatment (Koinis et al. 2017). Clinical guidelines recommend 2nd line chemotherapy only for SCLC patients who relapse ≥90 days after their 1st line treatments. This study examined factors predicting favorable survival outcomes among relapsed SCLC patients seen at the Tom Taker Cancer Centre, Alberta Canada.

      Method

      Retrospective analyses were conducted on clinical data of SCLC patients retrieved from the Glans-Look Lung Cancer database. All SCLC patients diagnosed between 2010 and 2016 who completed ≥ 4 cycles of 1st line platin doublets or single-agent etoposide and then relapsed during or after their initial treatments were included. The characteristics of patients relapsing ≥90 versus <90 days were compared using the Fisher Exact test. The overall survival (OS) was estimated using the Kaplan Meier survival and multivariate Cox Proportional Hazard model.

      Result

      190 SCLC patients were identified, of which 68% were extensive stage (ES), 57% were female, and 98% were smokers (Ex or current), with a median age of 67 at diagnosis. Most patients relapsed in ≥90 days: 57/60 (95%) for Limited stage (LS) and 102/130 (79%) for ES (p = 0.003). 48% of LS and 45% of ES received 2nd line systemic treatment (2L). In ES, receiving 2L cisplatin/etoposide was associated with better survival compared to not receiving 2L (HR=0.426, p=0.016) and having a longer relapse interval (≥90 days) was also associated with better survival (HR=0.539, p=0.015). Stratifying by relapse intervals, receiving 2L was associated with better survival in both the ≥90 (445 vs 286 days, p = 0.049) and <90 days (301 vs 219 days, p = 0.059) strata. In LS, favorable OS was associated with initial thoracic radiation (RT) receipt (HR=0.237, p=0.024) and no distant metastases (DM) at relapse (HR=0.257, p=0.005). Also of note, 83% LS and 21% ES had RT (p < 0.001) and at relapse, 52% LS and 92% ES had distant metastases.

      Conclusion

      The median OS in relapsed SCLC is low but is at least improved with 2L receipt in relapsed ES patients irrespective of the time to relapse (≥90 or <90 days). Hence, more effective therapy is required for these patients.

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    MA04 - Models and Biomarkers (ID 122)

    • Event: WCLC 2019
    • Type: Mini Oral Session
    • Track: Biology
    • Presentations: 1
    • Now Available
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      MA04.10 - Development and Validation of a Gene Expression-Based Prognostic Signature in Early-Stage Squamous Cell Carcinoma of the Lung (Now Available) (ID 2643)

      13:30 - 15:00  |  Author(s): Gwyn Bebb

      • Abstract
      • Presentation
      • Slides

      Background

      Squamous cell carcinoma of the lung (SqCCL) accounts for about 30% of all lung cancers and is usually associated with smoking. The clinical outcomes of early stage SqCCL are heterogeneous; while 60% of Stage I and II SqCCL patients never present with recurrence after surgery, the remaining will ultimately succumb to the disease. Therefore, a robust prognostication tool is an unmet clinical need. Here, we describe the development and validation of a gene expression-based prognostic signature in Stage I and II SqCCL patients.

      Method

      A total of 673 primary tumour samples obtained from surgically resected Stage I and II SqCCL patients were included in this study. The Cancer Genome Atlas (TCGA) cohort contained 365 patients with gene expression data generated using RNA sequencing (RNAseq). Five data sets (GSE30219, GSE37745, GSE50081, GSE4573, GSE14814) containing 308 patients profiled using Affymetrix microarrays were obtained from the Gene Expression Omnibus (GEO) database; batch effect mitigation of gene expression data was performed using ComBat. An additional cohort of consecutive Stage I and Stage II SqCLC patients was assembled at the Tom Baker Cancer Centre (TBCC), University of Calgary and gene expression was profiled using RNAseq. We performed a two-stage development of the gene signature by performing penalized elastic net Cox regression analysis in the TCGA training cohort followed by refinement of the gene list in the compiled GEO database patients. Final validation was performed using the in-house TBCC cohort. Progression-free survival (PFS) and overall survival (OS) were the primary and secondary outcomes of interest, respectively.

      Result

      All datasets used in this study were found to consist of patients with comparable clinical characteristics. A gene expression signature associated with PFS was developed in TCGA cohort that significantly stratified patients into high and low risk groups. The signature was refined in the complied GEO database cohort and validated in the U of C cohort. The signature also effectively stratified patients into high and low risk groups based on OS. We are currently performing multivariable analysis of the refined gene signature, adjusting for covariates of known prognostic value.

      Conclusion

      Our signature, if prospectively validated, will guide clinical decision making in SqCCL. Effective risk stratification using our signature may identify Stage I patients that will benefit from adjuvant therapy and stage II patients that could be spared adjuvant treatment following surgical resection.

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    P1.14 - Targeted Therapy (ID 182)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Targeted Therapy
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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      P1.14-41 - The Combination of the PARP Inhibitor Olaparib and the ATR Inhibitor VE-821 Selectively Targets ATM-Deficient Lung Cancer Cells (ID 620)

      09:45 - 18:00  |  Author(s): Gwyn Bebb

      • Abstract
      • Slides

      Background

      The driving principle behind precision medicine is to specifically target genetic variations that arise in tumorigenesis while leaving normal cells unaffected. Mutations in Ataxia Telangiectasia Mutated (ATM) may offer such a therapeutic target. ATM is mutated in approximately 12% of lung cancers and up to 40% of lung adenocarcinoma have been reported to lack ATM protein expression. ATM is an apex signaling kinase that responds to DNA-double strand breaks, playing a direct role in DNA repair as well as the initiation of signaling cascades that can lead to cell cycle arrest and apoptosis. We asked whether ATM-deficient human lung cancer cells are sensitive to the poly-ADP ribose polymerase (PARP) inhibitor olaparib, and investigated the mechanism of action of olaparib in these cells.

      Method

      We analyzed drug sensitivity for 61 lung adenocarcinoma cell lines from the Genomics of Drug Sensitivity in Cancer (GDSC) project and deleted ATM from lung adenocarcinoma A549 cells using CRISPR/Cas9. We determined the effects on cell viability using trypan blue exclusion and clonogenic survival assays. To investigate the mechanism of sensitivity of ATM-deficient cells to PARP and ATR inhibitors we used flow cytometry and cell viability assays as above.

      Result

      We observed a positive correlation between olaparib IC50 values and ATM mRNA expression. ATM mutant cell lines were more sensitive to olaparib compared to ATM wild-type cell lines or cell lines with amplified ATM. Additionally, ATM-deficient lung cancer cells were sensitive to olaparib, as are lung cancer cells (A549) with CRISPR/Cas9 deletion of ATM. Mechanistically, olaparib caused the temporary and reversible accumulation of G2 phase cells in ATM-deficient cells which manifested as a decrease in proliferation in both the trypan blue exclusion assay and clonogenic survival assay. Olaparib did not induce cell death in ATM-deficient cells, however cell death was induced when olaparib was used in combination with the ATR inhibitor VE-821.

      Conclusion

      We show that olaparib acts as a cytostatic agent in ATM-deficient lung cancer cells, inducing a reversible and temporary growth arrest in G2 phase. Only when combined with the ATR inhibitor VE-821 was cell death observed and only in ATM-deficient cells. Our data suggest that patients with ATM-deficient lung cancer could benefit from combinatorial treatment with PARP and ATR inhibitors.

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    P1.16 - Treatment in the Real World - Support, Survivorship, Systems Research (ID 186)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Treatment in the Real World - Support, Survivorship, Systems Research
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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      P1.16-33 - From a Systematic Review to Real World Evidence: Integrating Gender as a Clinical Risk Factor in NSCLC  (ID 2730)

      09:45 - 18:00  |  Presenting Author(s): Gwyn Bebb

      • Abstract

      Background

      Gender-based disparities in NSCLC experience have been widely discussed in the literature. The recognition of gender as a confounder in clinical practice remains uncertain. Confirming its impact on prognosis encourages personalized interventions in an effort to improve survival for NSCLC patients. Since best prevention programs are derived from findings established from multiple-evidence based analysis, the influence of gender on the observed disparities in NSCLC was explored using worldwide evidence and single institute experience. A systematic review was initially carried out to synthesize the evidence on a global scale to confirm the influence of gender-discrepancies in NSCLC incidence rates. Findings were compared and contrasted using a single cancer institute to highlight potential trends related to the different data.

      Method

      We identified relevant articles published in English using Medline between 1996 and 2016. Pooled standardized-incidence data was analyzed using a semi-parametric longitudinal regression model to estimate changes in NSCLC incidence as a function of time, histology and gender. A heat map was also designed to illustrate the global trend of NSCLC captured in the published articles. Findings of this review were evaluated to confirm the influence of gender on NSCLC trends and outcomes using a single center record. A retrospective analysis was performed using the Glans-Look Database (GLD) for patients diagnosed between 1999 and 2015. The Kaplan-Meier estimator of cumulative survival was conducted to analyze treatment outcomes of patients using SPSS and R. Statistical significance was set at 95% confidence level (p < 0.05).

      Result

      Our systematic review demonstrated gender-based disparities over time, and the main effect of gender on incidence rates is significant (p=0.01). Visualizing global trends of NSCLC’s histology confirm that women are prone to develop ADC. GLD data verifies the influence of gender, where women were more prone to develop ADC (49%), and the relative changes of its rate over 15 years increased significantly compared to men (58% vs 32%, P<0.02). Survival rates were also predisposed by gender, where female ADC mOS exceeded that of males in overall comparisons (17.6 vs. 12.2, p=0.047).

      Conclusion

      Our findings serve as a basis to resolve the inherent controversies in the research, and highlight the importance of gender as a clinical risk factor. Therefore, it is important to include gender as a prognostic tool to improve screening programs and promote tailored therapies for better outcomes. Biological, social, or a combination of factors could also influence the differences observed and warrant further investigation.

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    P1.17 - Treatment of Early Stage/Localized Disease (ID 188)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Treatment of Early Stage/Localized Disease
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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      P1.17-30 - Sex and Age-Associated Survival Following Resected Early Stage Non-Small Cell Lung Cancer (Now Available) (ID 1452)

      09:45 - 18:00  |  Author(s): Gwyn Bebb

      • Abstract
      • Slides

      Background

      Background: Non-small cell lung cancer (NSCLC) is the most common malignant tumour, and a leading cause of mortality worldwide. Rising rates of NSCLC have been observed among females, but nonetheless females also are often observed to possess better prognosis across all stages of disease. We aimed to assess the impact of biological sex along with age at diagnosis on the outcome of NSCLC patients with resected early-stage disease.

      Method

      A 15-year population-based retrospective analysis was conducted on de novo early stage (AJCC 7th edition, Stage I or II) patients between 1999-2014, whose primary tumor was surgically resected. Demographic, clinical characteristics, treatment modalities and outcome data were extracted from the institutional Glans-Look Lung Cancer Database, and univariate analysis, including Kaplan-Meier survival, alongside multivariate Cox regression was performed to compare outcomes by sex and determine prognostic factors associated with survival.

      Result

      872 early-stage resected NSCLC patients were identified. Median age at diagnosis 65.9 years (IQR: 59.1-72.6), 56% female, 76% ‘ever’ smokers, 68% Stage I, 91% oncologic resection (9% wedge resection). Median overall survival (mOS) for all early-stage resected cases was 93 months (95% CI: 81.9 – 105.4) with a 5-year survival rate of 62.5%. Females exhibited superior survival outcomes to males (105.4 months vs. 77.5 months, log-rank p=0.002), as did those < 75 years at diagnosis compared to those ≥ 75 years (103.9 vs. 76.2 months, log-rank p <0.001). Best and worst survival outcome was observed in females under age 75, and males over age 75, respectively (mOS 114.3 vs. 64.5 months; 5-year survival: 67.9% vs. 50.5%). No difference in rate of recurrence (overall) or rate of metastatic recurrence between males and females was identified (39% vs. 36%, p=0.214; 19% vs. 16%, p=0.591). After controlling for confounding variables, a reduced risk of mortality was found for females (HR: 0.8, p=0.016), age under 75 years at diagnosis (HR: 0.6, p < 0.001) and stage I presentation (HR: 0.6, p< 0.001).

      Conclusion

      Females experience significantly longer mOS, in particularly females under the age of 75 years at diagnosis. After adjusting for confounding factors, we found significantly reduced mortality risk for females aged under 75 years at diagnosis, and Stage I disease. Despite possessing the poorest outcomes among this cohort, males ≥ 75 years still possessed a 5-year survival rate of 50%, suggesting that surgical resection is a highly effective treatment option for suitable NSCLC patients, regardless of age.

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    P2.04 - Immuno-oncology (ID 167)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Immuno-oncology
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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      P2.04-30 - Seq-ing a Better Way to Detect PD-L1 in NSCLC (ID 2534)

      10:15 - 18:15  |  Presenting Author(s): Gwyn Bebb

      • Abstract

      Background

      Immunotherapies targeted against PD-L1 and PD-1 have caused a paradigm shift in the treatment of NSCLC, and PD-L1 protein expression has emerged as a standard diagnostic biomarker that predicts which patients are more likely to respond to immunotherapy. However, the use of PD-L1 protein expression as a biomarker is complicated by differences in PD-L1 antibodies, immunohistochemistry methods and platforms, pathologist scoring, and positivity cut-points. We propose that using RNA-sequencing (RNA-seq) methodologies will be an equally reliable approach to determine PD-L1 expression within a tumour and will yield a greater depth of biomarker information than PD-L1 IHC alone.

      Method

      We performed quantitative immunohistochemistry (qIHC) on 262 resected stage I-III formalin-fixed paraffin-embedded (FFPE) NSCLC patient samples registered in the Glans-Look Lung Cancer Research (GLR) database using the commercially available E1L3N PD-L1 antibody (Cell Signalling Technologies). Staining intensity was quantified and used to establish a positivity threshold that was subsequently used to define positivity cut-points of <1%, 1%-49%, and >50% (as used for determining treatment eligibility for Pembrolizumab). We performed single-end RNA-sequencing on FFPE samples from the same GLR patient cohort. Raw counts were normalized to counts-per-million for use in our analyses.

      Result

      We compared the PD-L1 mRNA expression to the PD-L1 protein staining intensity across the tissue core and found a significant correlation (p<0.001, Spearman’s rho=0.538). We also found significant correlation between PD-L1 mRNA expression and the percent-positivity score determined by qIHC (p<0.001, Spearman’s rho=0.605), which was particularly apparent when comparing PD-L1 mRNA expression between cut-point groups where expression was significantly higher in the 1%-49% and >50% groups. Interestingly, we also found moderate, yet significant correlation between PD-1 mRNA expression and both PD-L1 protein staining intensity and percent positivity (p<0.001, Spearman’s rho=0.437 and 0.415 respectively), and we were able to identify several differentially expressed genes between the PD-L1 positive and negative groups.

      Conclusion

      Given the high degree of correlation between PD-L1 mRNA expression and PD-L1 protein staining and positivity, RNA-seq can be a viable option for assessing candidacy for immunotherapy. In addition to the wealth of supplementary data on important biomarkers, RNA-seq offers the possibility for using non-invasive procedures such as liquid biopsy to measure PD-L1 levels in a sequential, objective fashion.

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    P2.14 - Targeted Therapy (ID 183)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Targeted Therapy
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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      P2.14-28 - Real-World Management and Outcomes of Uncommon EGFR Mutation-Positive NSCLC Patients at Two Tertiary Canadian Cancer Centres (Now Available) (ID 2782)

      10:15 - 18:15  |  Presenting Author(s): Gwyn Bebb

      • Abstract
      • Slides

      Background

      The evolution of targeted therapies has transformed the management of EGFR–mutation positive NSCLC patients, especially for those with exon 19 deletion and exon 21 (L858R). However, uncommon EGFR-mutation carriers represent a unique group with differential sensitivities and dynamic responses to treatment. We aimed to analyze the demographic profile, management patterns and outcome of these patients.

      Method

      Data were extracted from the institutional Glans-Look Lung Cancer database. Adult patients diagnosed with uncommon EGFR mutation(s) and treated in the palliative setting during 2010-2017 were included. Demographics and clinical characteristics were reviewed retrospectively (Table 1).

      Result

      table 1 demographic and clinical profile n38.png

      table 2 type of palliative treatment for uncommon egfrmut nsclc.png

      Uncommon EGFR mutations were observed in 38 patients, comprising approximately 10% of all EGFRmut+ NSCLC patients (348) diagnosed and treated in Alberta, Canada (2010-2017). Of the total 38 patients, 63% were female, 60% had a smoking history, and 75% were Canada-born. Dual/-triple mutation positivity was found in 40% of patients. 4/38 patients expired prior to receiving any form of palliative treatment. Upon classifying patients as per TKI treatment, it was found that most received gefitinib (67%) as first line systemic palliative treatment (Table 2). Median OS of the entire cohort was 15.1 months; meanwhile those with complex double/-triple mutations experienced longer mOS of 24.9months vs 11.8months for single uncommon carriers.

      Conclusion

      This Canadian study supports that uncommon EGFR mutation carriers are infrequent in clinical lung cancer practice. Of note, they represent a unique sub-population amongst EGFRmut+ NSCLC patients, and experience differential sensitivity and varied responses to treatment. We observed favorable responses to EGFR-TKIs in patients with double/-triple uncommon mutations, supporting that these patients may benefit from EGFR-TKIs.

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    P2.16 - Treatment in the Real World - Support, Survivorship, Systems Research (ID 187)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Treatment in the Real World - Support, Survivorship, Systems Research
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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      P2.16-12 - Treatment Uptake and Outcomes of Elderly Stage III NSCLC Patients: A 15-Year Retrospective Real-World Study (Now Available) (ID 1438)

      10:15 - 18:15  |  Author(s): Gwyn Bebb

      • Abstract
      • Slides

      Background

      Incidence of non-small cell lung cancer (NSCLC) is highly correlated with age; the age-specific incidence rate of NSCLC in individuals ≥ 75 is nearly double that of patients < 70. Further, nearly one-third of patients diagnosed with NSCLC present with locally advanced (Stage III) disease. This represents an anatomically heterogeneous, frequently non-resectable tumour for which contemporary practice guidelines, based on two decades of clinical trials, recommend concurrent chemoradiotherapy (cCRT) to maximize both local tumor control and survival. Underrepresentation of elderly patients in clinical trials requires the use of real-world populations to assess whether current recommendations and trial-derived survival outcomes are also applicable to this significant and growing age group.

      Method

      A 15-year population-based retrospective analysis of patients with de novo Stage III (AJCC 7th edition) NSCLC diagnosed between 1999-2014 was conducted. Demographic, clinical characteristics, treatment and outcome data were extracted from the institutional Glans-Look Lung Cancer Database. We defined elderly patients as those ≥ 75 years at diagnosis, and investigated the treatment intent, type, uptake and outcomes among elderly and non-elderly patients.

      Result

      We identified 1040 patients with a Stage III diagnosis. 333 (32%) were elderly. Treatment patterns differed significantly between elderly patients and non-elderly patients: elderly patients were less significantly likely to receive any form of active treatment (82% vs. 58%), particularly curative-intent treatment (41% vs. 14%), and no elderly patients underwent surgical resection. Median overall survival (mOS) favoured non-elderly patients (13.2 vs. 9.7 months, log-rank p <0.001.) Among elderly patients, receipt of curative-intent treatment was associated with significant improvement in mOS (17.4 months vs. 9.3 months for no active treatment/observation, vs. 8.5 months for palliative-intent treatment, p < 0.001). When receiving curative-intent treatment, specifically cCRT, survival outcomes of elderly patients were not significantly different from those of younger patients (24.5 vs. 21.3 months, p=0.81), and had comparable 5-year survival rates (15.9% and 12.2% respectively).

      Conclusion

      This real-world population reveals that elderly patients are less likely to receive any, and particularly, curative-intent treatment for their NSCLC diagnosis when compared with a younger cohort. When deemed suitable for a curative-intent regiment of cCRT, elderly patients show comparable outcomes to younger cohorts. This finding reinforces the current guideline recommendations that cCRT is associated with best outcome for non-resectable, locally-advanced NSCLC, even among elderly patients. Further, it supports the critical need for more tolerable and effective treatments for this presentation of disease to improve feasibility of curative-intent treatment for all, but in particular, elderly patients.

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    P2.18 - Treatment of Locoregional Disease - NSCLC (ID 191)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Treatment of Locoregional Disease - NSCLC
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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      P2.18-04 - Improved Outcome in Female Stage III NSCLC Diagnoses Is Driven by Non-Curative Intent Treatment, and Adenocarcinoma Histology (ID 2113)

      10:15 - 18:15  |  Presenting Author(s): Gwyn Bebb

      • Abstract

      Background

      Biological sex disparities in incidence, molecular alterations and outcome in NSCLC have been well documented in the literature; however, there are no sex-based approaches to diagnosis and treatment in lung cancer. Recognising differences in therapeutic outcome and survival between the biological sexes could help inform clinical research and further personalized interventions in an effort to improve survival for NSCLC patients.

      Method

      Using the Glans-Look Lung Research (GLR) database, a retrospective analysis was undertaken for Stage III (AJCC 7th edition) NSCLC patients diagnosed between 1999 and 2014. Demographic, clinical, treatment and outcome data were extracted to assess sex-based differences in histology, treatment uptake and survival. Univariate methods, including Kaplan-Meier survival analysis were performed to compare outcomes by sex, histology and treatment-intent.

      Result

      1040 Stage III NSCLC were identified, median age 69.6 years (IQR 61.3-76.8), 57.9% female, 89.1% ‘ever’ smokers, 34% adenocarcinoma (ADC), 36% squamous cell carcinoma (SCC), 20% ‘other’, 10% unknown. Among female patients ADC is more prevalent (42% vs. 28%, p<0.001), while in SCC patients are more likely to be males (44% vs. 26%, p < 0.001). Males were more likely to receive palliative-intent treatment (44% vs. 37%), while females more likely to receive best supportive care (BSC) (31% vs. 22%), p=0.006. Median overall survival (mOS) for the entire stage III cohort favoured females (14.1 vs. 10.7 months, p=0.001). This trend was also observed across different treatment categories, where female survival significantly exceeded that of males: curative-intent (25.5 vs. 18 months, p=0.035), palliative-intent (9.5 vs. 8.0 months, p = 0.025) and BSC (11.2 vs. 7.2 months, p=0.014). Although no differences in treatment patterns were seen between males and females within ADC or SCC, sex-based disparities in survival were also present within the ADC histology: female ADC mOS exceeded that of males, in overall comparisons (17.6 vs. 12.2 months, p=0.047), within palliative-intent treatment (15.1 vs. 8.0, p=0.008) and BSE (13.2 vs. 3.4, p=0.005), but not in curative-intent combined modality chemo-radiation (26.8 vs. 21.7 months, p =0.972). No differences in mOS, either overall or by treatment category were observed in SCC.

      Conclusion

      Higher mOS among females in stage III NSCLC appears to be driven by both the ADC histology and non-curative-intent treatments. Sex-based differences in outcomes should be assessed more deeply as prognostic variable in patients with NSCLC.