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J. Cé Coelho
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P2.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 234)
- Event: WCLC 2015
- Type: Poster
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P2.04-107 - Cofilin-1 as a Biomarker for Non-Small Cell Lung Cancer and a Potential Predictor to Platinum-Based Chemotherapy Resistance (ID 745)
09:30 - 09:30 | Author(s): J. Cé Coelho
- Abstract
Background:
Non-small cell Lung cancer (NSCLC) is a highly lethal disease, whose symptoms are not common in the early stages, making detection difficult in this scenario. Biomarkers may be important for prognosis and prediction of therapy, resulting in more effective treatments and lower mortality rates. The expression of several genes have been tested for its potential as a biomarker for lung cancer, but none was positive as a prognostic factor. Cofilin-1 (CFL1) was first described in breast and ovarian cancer and emerges as a potencial biomarker for NSCLC.
Methods:
To identify and validate CFL1 as a prognostic biomarker for NSCLC, independets cohorts obtained from published NSCLC microarray data (GSE3141/GSE42127/GSE13213) were used and the results were validated in a retrospective cohort. A semi-quantitative immunohistochemistry method was established measuring the intensity of IHC reaction using images software. The CFL1 potential in predicting drug resistance was also explored. A panel of 120 anticancer compound and the CFL1 levels in human NSCLC cell lines were analysed and an in vitro model for intrinsic and acquired cisplatin resistance protocols was established. A network graphic determining the association of CFL1 expression and cisplatin drug resistance was drawn applying a spring model algorithm. Using the STRING database all proteins directly interacting with CFL1 were retrieved and crossed with gene expression data of cisplatin-resistant cells.
Results:
CFL1 levels in biopsies are able to discriminate between good and bad prognosis at early tumor stages, where high CFL1 levels are correlated with lower overall survival rate (P < 0.0001). In vitro evidences suggest that CFL1 is a biological predictor of cisplatin resistance. Cell lines with high CFL1 expression are resistant to 21 of 30 alkylating drugs (including cisplatin and carboplatin). Intrinsically cisplatin resistant (ICR)-A549 cells presented a six-fold increase in cisplatin GI~50~ value and an increased in CFL1 protein levels (P < 0.01). Also, a high activity of the CFL1 gene network was found in cisplatin-resistant cells (P < 0.01) and in response to acute cisplatin treatment. Figure 1
Conclusion:
CFL1 emerges as a biomarker of a more aggressive cancer phenotype. The potential of CFL1 in screening patients less sensitive to alkylating agents represents a major impact with regard to the therapeutic strategy and should be explored further. Using a retrospective clinical cohort of NSCLC we intend to confirm the laboratory results in clinical patients. Also, we aim to establish a cutoff value of CFL1, and test it for predicting treatment response and patient survival.
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P3.03 - Poster Session/ Treatment of Locoregional Disease – NSCLC (ID 214)
- Event: WCLC 2015
- Type: Poster
- Track: Treatment of Locoregional Disease – NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P3.03-015 - Outcomes of Chemoradiotherapy for Stage III Non-Small Cell Lung Cancer in South of Brazil (ID 2427)
09:30 - 09:30 | Author(s): J. Cé Coelho
- Abstract
Background:
Patient with stage III lung cancer are commonly treated with chemotherapy and radiation. The concurrent treatment improves local control and overall survival, but also increase toxicity. A meta-analysis study with more than 1800 patients found a 30% reduction in 2-years mortality in who received a platinum-based chemotherapy. Trials populations are selected and usually are not representative of Brazil lung cancer population.
Methods:
From January 2005 to December 2013, all patients diagnosed with locally advanced non-small cell lung cancer (IIIA or IIIB) treated with etoposide/cisplatin (EP) with concurrent radiotherapy at an University Hospital in South of Brazil were identified from electronic database. Medical records were revised and demographic data, tumor and treatment characteristics were collected. Overall survival and progression freen survival were estimated by Kaplan-Meier curves. Multivariate analysis (Log-Rank tests) was performed to identify factors associated with survival. Statistical analysis was performed with SPSS 22.0.
Results:
Seventy-three patients were identified and included in analysis. Patients characteristics revealed a mean age of 59.2 ± 10,7 years, male sex in 63%, Caucasian ethnicity in 90%, smoking history in 86%, good performance status (0-1) 89% and stage IIIA and IIIB in 52% and 48%, respectively. Thirty-eight (52%) patients had adenocarcinoma, 24 (34%) squamous cell and 10 (13%) other histologies. All patients were treated with EP concurrent to radiation and 20% received two consolidation cycles of chemotherapy. Fifty-three (72%) completed all the treatment and 34 (45%) achieved complete or partial response. In the observational period 64 patients (88%) had died, with progression free survival of 10,1 months (95% IC, 6.97 to 13.17) and overall survival of 15.9 months (95% IC, 9.83 to 22.10). In multivariable analysis, clinical stage (IIIA vs IIIB) and performance status (0-1 vs ≥ 2) were independently associated with survival, HR 2.23 (95% IC, 1.16 to 4.29) and HR 6.39 (95% IC, 2.09 to 19.54), respectively.
Conclusion:
To our knowledge, this is the first Brazilian report of concurrent chemoradiation of locally advanced non small cell lung patients. Our outcomes are similar to previously reported clinical trials of concurrent treatment. Stage IIIB and performance status > 2 were predictors of worst outcomes in our population.
