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Karen Kopciuk
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MA04 - Models and Biomarkers (ID 122)
- Event: WCLC 2019
- Type: Mini Oral Session
- Track: Biology
- Presentations: 1
- Now Available
- Moderators:Montse Sanchez-Cespedes, Kwok-kin Wong
- Coordinates: 9/08/2019, 13:30 - 15:00, Interlaken (1988)
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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): Karen Kopciuk
- Abstract
- Presentation
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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P1.16 - 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 | Author(s): Karen Kopciuk
- 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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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 | Author(s): Karen Kopciuk
- Abstract
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
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.
