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N. Stanic
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P2.03b - Poster Session with Presenters Present (ID 465)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)
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P2.03b-052 - XRCC1 Arg399Gln and Rad51 G135C Gene Polymorphisms in Advanced Lung Adenocarcinoma in Serbia (ID 4945)
14:30 - 14:30 | Author(s): N. Stanic
- Abstract
Background:
XRCC1 and Rad51 are proteins involved in DNA base excision repair and DNA homologous recombination/double-stranded-break repair mechanisms respectively. In non-small cell lung cancer, XRCC1 Arg399Gln polymorphism (disrupts protein-protein interactions), and Rad51 G135C polymorphism (enhances Rad51 promoter activity), have been proposed as factors that influence the overall and progression-free survival (OS and PFS) of patients treated with platinum-based chemotherapy. This study aimed to evaluate the influence of XRCC1 Arg399Gln and Rad51 G135C polymorphisms on the toxicity of chemotherapy and clinical outcome (OS, PFS) of advanced adenocarcinoma patients in Serbia.
Methods:
The study included 94 advanced lung adenocarcinoma patients, EGFR wild type, stage IIIB or IV (TNM7), performance status 0, 1 or 2, of Caucasian descent, who recieved standard platinum-based chemotherapy. XRCC1 and Rad51 genotyping was done by PCR-RFLP. Statistical analysis was performed using Chi-square, Fisher’s exact, Wilcoxon rank sum test, Breslow-Day test. Survival methodology was used for OS and PFS (Kaplan-Meier product limit method and Log-Rank test, Cox regression for HR). Statistical significance was considered for p<0.05.
Results:
The group consisted of 62 males (66%) and 32 females (34%), median age at diagnosis 61 years (range 37-84), with 77 (82 %) of current or ex-smokers, and 65 (66%) of which presented with metastases at diagnosis. Follow up period was 1-55 months (median 11 months), during which 76 patients (81%) progressed, and 24 (19%) experienced chemotherapy-related toxicity of grade 3 and 4. Median (95%CI) PFS was 8,1 months (7.1-9.1), and median OS was 10 months (8.2-11.7). Genotype frequencies for XRCC1 Arg399Gln were 39.4% for Arg/Arg, 25.5% for Arg/Gln and 3.2% for Gln/Gln genotype. For Rad51 G135C frequencies were 61.7% for G/G, 26.6% for G/C and 1.1% for C/C genotype. Carriers of the XRCC1 Gln allele had a significantly shorter PFS (7.2m vs 9.5m, Breslow p=0.023) and OS (6.4m vs 15.7m, Breslow p=0.04), and were more susceptable to progression during chemotherapy. Although Rad51 genotypes alone had no statistically significant effect on PFS and OS, carriers of both XRCC1 Gln allele and Rad51 C allele had a 4 months shorter OS, the difference was not statistically significant. There were no statistically significant differences in the occurence of high grade chemotherapy-induced toxicity according to the patients' XRCC1 and Rad51 genotypes.
Conclusion:
These results suggest that in the Serbian population XRCC1 and Rad51 genotyping could be a useful tool for predicting the clinical outcome with platinum-based chemotherapy in advanced EGFR wild-type adenocarcinoma patients.
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P3.02b - Poster Session with Presenters Present (ID 494)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)
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P3.02b-071 - First-Line Gefitinib for EGFR-Mutated Lung Adenocarcinoma Patients with Bone Metastases - A Single Institution Experience (ID 5322)
14:30 - 14:30 | Author(s): N. Stanic
- Abstract
Background:
Bone involvement has been considered as an adverse predictive factor in the systemic treatment of majority of malignant tumors. New horizon, opened with targeted agents, especially in lung cancer, faced us with encouraging results of treatment in advanced cancer patient population. Gefitinib, first generation tyrosine kinase inhibitor (TKI), has been a standard first-line treatment for EGFR mutated lung adenocarcinoma patients in Serbia since 2011.
Methods:
Fifty-one consecutive patients (pts) with advanced lung adenocarcinoma and EGFR mutation were treated with 1[st] line gefitinib at IORS since 2011. Fourteen of them were with bone metastases (BM). We compared treatment outcome of BM group (n=14) with group of pts without BM (n=37) in terms of progression-free survival (PFS) and overall survival (OS)
Results:
In the group of 14 pts with BM F/M ratio was 9/6, median age 57 years (26-64), 5/14 were never smokers. Performance status (PS) 1 had 7 pts, PS2 4 pts and PS3 3 pts. Eight pts had deletion of exon 19, five pts mutation in exon 21, one patient had double mutation G719X/S7681. Bone only metastases had 4/14 pts, additional metastatic sites in 10 pts were as follows: lung in 3 pts, liver in 2 pts, pleura in 3 pts and pericardium in 2 pts. The best therapy response in pts with BM was as follows: partial response in 5 pts, stable disease in 7 pts, progressive disease in 2 pts. Median PFS in BM group was 10.91 months (5.87-15.94, CI 95%) and 5.78 months (3.41-8.15, CI 95%) in the group of 37 pts without BM (log rank p=0.47). Median OS in BM group was 21.95 months (17.68-26.71, CI 95%), 18.17 months (5.95-30.30, CI95%), in pts without BM (log rank p=0.26). Toxicity of gefitinib was as expected and mild: skin rash grade 1 and diarrhea grade 1 in 9 pts, elevated transaminases grade 1 in one patient and grade 2 in one patient.
Conclusion:
In this small set of TKI treated advanced lung adenocarcinoma patients in 1[st] line, somewhat counterintuitive results were achieved: better PFS and OS results for BM group may be attributable to mutations more susceptible to TKI activity (mostly exon 19), absence of brain metastases in this group, good PS in one half of pts. But, it seems that stigma about poor results of systemic treatment in pts with BM should be set aside, at least in case of advanced adenocarcinoma of the lung and TKI.
