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A.S. Saad
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P3.03 - Poster Session with Presenters Present (ID 473)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Mesothelioma/Thymic Malignancies/Esophageal Cancer/Other Thoracic Malignancies
- Presentations: 1
- Moderators:
- Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)
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P3.03-041 - FAS/FASL Genetic Polymorphisms Impact on Clinical Outcome of Malignant Pleural Mesothelioma (ID 4500)
14:30 - 14:30 | Author(s): A.S. Saad
- Abstract
Background:
Dysregulation of FAS/FASL apoptosis-related pathway may lead to cancer cells immune escape and influence platinum-based chemotherapy outcome, which is currently the mainstay treatment for malignant pleural mesothelioma (MPM). FAS-670 A>G (rs1800682) and FASL-844 C>T (rs763110) single nucleotide polymorphisms (SNPs) are two functional promoter polymorphisms of FAS and FASL genes, respectively which may alter their transcriptional levels. They have been previously correlated with clinical outcome of non-small cell lung cancer (NSCLC), breast and bladder cancers. Therefore, we aim to investigate the influence of these polymorphisms on clinical outcome of MPM patients.
Methods:
In this cohort study [NCT02269878], 68 epithelioid MPM Egyptian patients treated with first-line platinum-based chemotherapy were recruited from Department of Clinical Oncology and Nuclear Medicine, Ain Shams University and El-Nasr hospital for health insurance in the period between April 2014 and May 2015. The genotype analysis was performed using TaqMan[®] SNP Genotyping assay. We evaluated the association between the selected polymorphisms and response rate, progression free survival (PFS) and overall survival (OS) at 18 months.
Results:
The mean age of patients was 55.5 ± 9.5 years and 45.6 % of them received Platinum in combination with pemetrexed, while 54.4% received platinum in combination with gemcitabine. FASL-844 CC genotype was more common than expected in early stage tumors (p = 0.042). There was no association between the investigated polymorphisms and response rate or 18-months OS. However, the median PFS for carriers of FASL-844 CC genotype was 14 months (95 % CI: 12.8 - 15.2 months) and 9 months (95 % CI: 7.2 - 10.8 months) for carriers of FASL-844 CT/TT genotypes (Log-Rank: 6.2; p = 0.013).Also, the number of platinum-based cycles and tumor stage were found to be significant variables by univariate analysis (p =<0.001, p = 0.006, respectively). Multivariate cox proportional hazards regression showed that the carriers of FASL-844 CT/TT genotypes were still more susceptible to disease progression than carriers of FASL-844 CC genotype (adjusted HR = 4.40 , 95 % CI: 1.62 - 11.89, p = 0.004).
Conclusion:
Our results suggest that FASL-844 C/T polymorphism could predict PFS in MPM patients receiving Platinum-based chemotherapy; therefore, this should be further evaluated as potential marker for the prediction of clinical outcome in patients with MPM.
