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Z. Lohinai
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P1.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 233)
- Event: WCLC 2015
- Type: Poster
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
- Moderators:
- Coordinates: 9/07/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P1.04-003 - Metastatic Site-Specific Variation of KRAS Status in Lung Adenocarcinoma (ID 2704)
09:30 - 17:00 | Author(s): Z. Lohinai
- Abstract
Background:
While KRAS mutation is a negative predictive marker for EGFR tyrosine kinase inhibitor therapy, there is limited data available regarding the influence of KRAS mutation on the organ specificity of lung adenocarcinoma metastases.
Methods:
In our retrospective, single center study, 820 lung adenocarcinoma patients with KRAS mutation analyses were included. At the time of diagnosis, 462 patients had metastatic disease. These cases were analyzed for the potential association between KRAS status and metastatic site and clinical outcome. Patients with known EGFR mutations were excluded from the study.
Results:
534 (65.3%) KRAS wild-type and 284 (34.7%) KRAS-mutant cases were identified. There was no difference in the KRAS mutation prevalence between the metastatic (35.7%) and non-metastatic cases (33.4%). The most frequent metastatic sites included bone (29%), contralateral lung (24.8%), ipsilateral lung (19.7%), brain (17.3%), adrenal gland (15.6%), pleura (12.8%) and liver (11.7%). Patients with multiple metastases tended to have inferior median overall survival (OS) compared to those with single-organ metastasis (6.3 vs. 8.2 months, respectively; p=0.09) and, moreover, showed a slight but non-significant increase in the prevalence of KRAS mutations (38.5%, p=0.35). Importantly, patients with brain (35.8%), bone (33.1%) or adrenal gland (35.2%) metastases demonstrated similar KRAS mutation frequencies. However, both ipsilateral and contralateral intrapulmonary metastatic cases demonstrated increased KRAS mutation frequency when compared to those with extrapulmonary metastases (42.2% and 42.5%, p=0.014). In contrast, pleural dissemination and liver metastasis were associated with decreased KRAS mutation prevalence (25.4% and 24.1%, respectively; p=0.007). We found no difference in the median OS between KRAS-mutant and WT cases in any metastatic site-specific analysis.
Conclusion:
Lung adenocarcinoma patients with KRAS-mutant tumors more often present with intrapulmonary metastases. KRAS mutation prevalence, however, lacks to provide prognostic information. Further studies are required to determine if KRAS status can be used to risk stratify patients for the onset of pulmonary metastasis.
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P2.07 - Poster Session/ Small Cell Lung Cancer (ID 222)
- Event: WCLC 2015
- Type: Poster
- Track: Small Cell Lung Cancer
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P2.07-003 - Attempt to Validate Drug Repositioning for Metastatic Small Cell Lung Cancer (SCLC) Therapy Identifies Statins Associated with Survival Benefit (ID 2277)
09:30 - 17:00 | Author(s): Z. Lohinai
- Abstract
Background:
SCLC is an aggressive malignancy with limited treatment options. Based on in vitro data and results of a recent drug repositioning study, some medications approved by the FDA for the treatment of various non-malignant disorders were demonstrated to have anti-SCLC activity in preclinical models. Drug dose levels that demonstrated anti-cancer activity were similar to those used in the clinics. The aim of our study is to confirm whether use of these medications is associated with survival benefit in a large cohort of SCLC patients from a single institution.
Methods:
Consecutive patients with cytologically or histologically confirmed, metastatic SCLC evaluated between 2000-2013 at the National Koranyi Institute of Pulmonology were analyzed in this retrospective analysis. Patients that were prescribed statins, aspirin, clomipramine (a tricyclic antidepressant [TCA]), selective serotonin re-uptake inhibitors (SSRIs), doxazosin, and prazosin were identified. Next, we evaluated the associations amongst these various medications, clinicopathological characteristics (including gender, age, and Eastern Cooperative Oncology Group performance status [ECOG PS]), and overall survival (OS) in univariate and multivariate analyses with Bonferroni correction applied.
Results:
There were a total of 876 patients (508 men and 368 women) with a median age of 61 years (range, 33-86). 75% of the chemotherapy administered in the first line setting was platinum-based. Aspirin, statin, SSRIs, doxazosin, prazosin, and TCA were administered in 138, 72, 20, 14, 14, and 5 cases; respectively. Univariate analysis identified age, ECOG PS, and statin treatment as significant prognostic factors (p<0.001; p<0.001; and p=0.002; respectively). A statistically significant increase in OS was observed only in statin-treated patients when compared to those not receiving any of the aforementioned medications (median OS, 8.4 vs. 6.1 months; respectively). The administration of SSRIs, TCA, aspirin, prazosin, or doxazosin did not result in a statistically significant OS benefit (median OS, 8.5, 7.2, 6.8, 6.8, and 4.6 months; respectively). The multivariate Cox model showed that besides age and ECOG PS, statin treatment was an independent survival predictor (Hazard Ratio, 1.41; 95% confidence interval, 1.1–1.8; p=0.007).
Conclusion:
Statins appear to provide a statistically significant survival benefit in metastatic SCLC. Other classes of medications analyzed in this study did not validate the preclinical drug repositioning studies previously reported. Drug repositioning studies using only preclinical data or small numbers of patients should be treated with caution before application in the clinic.
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P3.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 235)
- Event: WCLC 2015
- Type: Poster
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P3.04-103 - Evaluation of the TGF Beta Superfamily Member Activin-A as a Novel Circulating Prognostic Marker in Lung Cancer (ID 2720)
09:30 - 17:00 | Author(s): Z. Lohinai
- Abstract
Background:
Identification of biomarkers that can facilitate early detection and therapeutic decision making in lung cancer (LC) is urgently needed. Growth factors of the activin family are deregulated in a number of malignancies including thoracic tumors. Recent studies provided data regarding the tumor tissue expression levels of activin-A in lung adenocarcinoma (ADC): High activin-A expression was associated with poor prognosis, enhanced metastasis and shorter progression-free survival in stage I ADC. Since activin-A is secreted to the circulation and can be detected in plasma, this study aims to determine, for the first time, the value of circulating activin-A as a biomarker in LC patients.
Methods:
Plasma samples from patients with small cell lung cancer (SCLC, n= 79), ADC (n=87) and squamous cell carcinoma (n=36) were collected between 2009 and 2013 at the time of diagnosis or before surgical resection. Additional samples, serving as age- and sex-matched controls, consisted of individuals without malignancies (n=66). Measurement of samples was performed using the Quantikine activin-A Elisa kit (R&D Systems) and all statistical analyses were performed using the PASW Statistics 20.0 package and GraphPad Prism 6.0.
Results:
Mean plasma activin-A levels (PAL) (pg/ml) were the following: 628,8±38,42 (ADC, range: 112,4-1875), 613,5±68,22 (SCC, range: 194-2076), 771±77,06 (SCLC, range: 174,1-3627) and 433,3±16,27 (controls, range: 194,1-808,8). A gender-related variation in the PAL of controls (female (n=31, mean PAL 469,5±24,54 (range 212,95-808,79)) vs. male (n=35; mean PAL 401,3±20,49 (range 194,1-759,02)), p= 0.0319) was observed. PAL was significantly increased in patients with ADC (p=0.0009), SCC (p=0.0061) and SCLC (p<0.0001) compared to controls. There was no difference in PAL with regard to patients´ age, gender, BMI, smoking status or other co-morbidities in all 3 LC types. A significant TNM stage-dependent increase of PAL was observed in all 3 LC types. PAL was elevated in T3 SCC, in T4 ADC and in T3 and T4 SCLC. PAL was also clearly associated with N status and metastatic disease in all 3 LC types. Importantly, in case of SCLC, PAL was associated with extensive disease and showed metastatic site specificity. In ADC patients, elevated PAL was associated with significantly worse overall survival (OS) (p<0.0001). Of note, in locally advanced ADC, elevated PAL also proved to be a significant negative prognosticator (p=0.048). Moreover, elevated PAL was associated with a poor OS in SCLC patients (p=0.0009). Multivariate analysis revealed that PAL was an independent prognostic factor in ADC and SCLC patients. Survival and multivariate analysis data of the SCC cohort will be presented at the conference. ROC curve analysis showed an AUC of 0.691 in SCLC and an AUC of 0,657 in ADC for PAL.
Conclusion:
Our findings suggest that PAL is significantly elevated in a disease stage-dependent manner in LC patients. Moreover, elevated PAL is associated with poor prognosis in ADC and SCLC patients.
