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B. Zaric
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MA02 - RNA in Lung Cancer (ID 377)
- Event: WCLC 2016
- Type: Mini Oral Session
- Track: Biology/Pathology
- Presentations: 1
- Moderators:E. Brambilla, M. Noguchi
- Coordinates: 12/05/2016, 14:20 - 15:50, Stolz 2
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MA02.10 - Discussant for MA02.07, MA02.08, MA02.09 (ID 7108)
15:26 - 15:38 | Author(s): B. Zaric
- Abstract
- Presentation
Abstract not provided
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P2.03b - Poster Session with Presenters Present (ID 465)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 2
- 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): B. Zaric
- 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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P2.03b-075 - PD-1 Protein Expression Predicts Survival in Resected Adenocarcinomas of the Lung (ID 5641)
14:30 - 14:30 | Author(s): B. Zaric
- Abstract
Background:
Immune checkpoint inhibitors targeting programmed cell death protein 1 (PD-1) and programmed cell death ligand 1 (PD-L1) have demonstrated clinical activity in patients with advanced non-small cell lung carcinoma (NSCLC). The ability of PD-1 and PD-L1 immunohistochemistry (IHC) to predict benefit of immune checkpoint inhibitors remains controversial. We assessed the prognostic value of PD-1 and PD-L1 IHC in patients with completely resected adenocarcinoma of the lung.
Methods:
We determined protein expression of PD-1 and PD-L1 in formalin-fixed paraffin-embedded surgical specimens of 161 NSCLC patients with adenocarcinoma histology by IHC. We used the EH33 antibody (Cell Signaling) for PD-1 and the E1L3N antibody (Cell Signaling) for PD-L1 IHC. Cut-points of ≥1% PD-1-positive immune cells at any staining intensity and ≥1% PD-L1-positive tumor cells at any staining intensity were correlated with clinicopathological features and patient survival.
Results:
Positive PD-1 immunostaining in immune cells was observed in 71 of 159 (45%) evaluable tumor samples. PD-1 positive staining was not significantly associated with any of the clinicopathological features. Positive PD-1 immunostaining was associated with longer recurrence-free and overall survival of the patients. Multivariate Cox proportional hazards regression analyses identified PD-1 to be an independent prognostic factor for recurrence (adjusted hazard ratio [HR] for recurrence 0.58; 95% confidence interval [CI] 0.36 to 0.94; P = 0.026) and death (adjusted HR for death 0.46; 95% CI 0.26 to 0.82; P = 0.008). PD-L1 positive staining in tumor cells was seen in 59 of 161 (37%) cases. Positive PD-L1 immunostaining correlated with KRAS mutation (P = 0.019) and type of surgery (P = 0.01) but was not significantly associated with any of the other clinicopathological parameters. Positive PD-L1 immunostaining was not associated with survival of the patients (adjusted HR for recurrence 0.92; 95% CI 0.58 to 1.47; P = 0.733; adjusted HR for death 0.61; 95% CI 0.34 to 1.07; P = 0.084).
Conclusion:
Positive PD-1 but not PD-L1 immunostaining is a favorable independent prognostic factor in patients with completely resected adenocarcinoma of the lung.
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P3.05 - Poster Session with Presenters Present (ID 475)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Palliative Care/Ethics
- Presentations: 1
- Moderators:
- Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)
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P3.05-011 - Importance of Assessment of Malnutrition Risk in Lung Cancer Patients (ID 5944)
14:30 - 14:30 | Author(s): B. Zaric
- Abstract
Background:
Malnutrition and cachexia are commonly seen in cancer patients. The aim of this research was to assess overall risk of malnutrition in lung cancer patients.
Methods:
This prospective observational study that included hospitalized lung cancer patients was conducted in the Institute for pulmonary diseases of Vojvodina, Serbia. International questionnaire for nutrition screening was used for clinical assessment of malnutrition. Subjects were included in this study regardless of lung cancer type, stage of disease and therapy regiment.
Results:
Out of total 188 patients included, 76.1% were male and 23.9% female. Majority of patients were in ECOG performance status (PS) 1 (74.5%) with diagnosed lung cancer in stages III and IV (39.9% and 42.6% respectively). Most common lung cancer type was adenocarcinoma (50.0%) followed by sqamous (35.6%), small-cell (10.6) and other hystologic types (3.7%). Majority of patients had Body Mass Index (BMI) >20 (87.8%). BMI<18 was observed in 7.4% of patients. Unplanned weight loss in past 3-6 months for more than 10% was present in 16.5% of patients. In this group of patients 20.7% were with high risk, 12.8% with medium risk and 66.5% with low risk of malnutrition. High risk of malnutrition was more frequent in stages III and IV of lung cancer (24.0% and 22.5% respectively) than in stages I and II (13.3% and 5.6% respectively). We observed statistically significant correlation between ECOG PS and risk of malnutrition (p=0.001; ρ=0.240). Patients with ECOG PS 0 are ten times less likely to have high risk of malnutrition than patients with poorer ECOG PS.
Conclusion:
This study showed that a significant percentage of lung cancer patient have a high risk of malnutrition therefore it would be advisable to routinely evaluate nutritional status of lung cancer patients regardless of stages and duration of disease.
