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V. Laszlo
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OA02 - Novel Targets and Biomarkers in Malignant Pleural Mesothelioma (ID 369)
- Event: WCLC 2016
- Type: Oral Session
- Track: Mesothelioma/Thymic Malignancies/Esophageal Cancer/Other Thoracic Malignancies
- Presentations: 1
- Moderators:L.E. Raez, M. Jakopovic
- Coordinates: 12/05/2016, 11:00 - 12:30, Stolz 2
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OA02.03 - Circulating Fibroblast Growth Factor 18 is Elevated in Malignant Pleural Mesothelioma Patients - A Multi-Institutional Study (ID 5988)
11:20 - 11:30 | Author(s): V. Laszlo
- Abstract
- Presentation
Background:
Malignant pleural mesothelioma (MPM) is a rare but devastating malignancy. Despite the search for new promising treatment approaches, the outcome for most MPM patients remains dismal. Therefore, the identification of novel biomarkers is urgently needed in order to identify patients with a better prognosis and to support personalized therapeutic decisions. In our previously published study, we were able to show that fibroblast growth factor 18 (FGF18) is overexpressed in MPM tissue specimens and cell models. The objective of this study was the evaluation of FGF18 as a circulating biomarker in MPM.
Methods:
Plasma was collected from 107 MPM patients at the time of diagnosis or before surgical resection. Samples were included from the Medical University of Vienna, University Hospital Center in Zagreb and from The Concord Repatriation General Hospital and Strathfield Private Hospital in Sydney. Samples from 49 healthy volunteers and from 8 patients with non-malignant pleural diseases served as controls. Circulating FGF18 was measured by enzyme-linked immunosorbent assay and correlated to clinical, pathologic and radiologic parameters.
Results:
Plasma FGF18 level was significantly elevated in MPM patients vs. healthy controls (P<0.0001). A slight increase of circulating FGF18 level was also detected in patients with pleuritis or fibrosis (vs. control, P=0.0067). Sarcomatoid (n=7) morphology was associated with high FGF18 levels when compared to the epithelioid (n=77) histology (P=0.0064). Importantly, MPM patients presenting with FGF18 levels below the median had a significantly longer overall survival when compared to those with high FGF18 levels (median survival 625 versus 382 d, P=0.0038). Data on multivariate analysis, disease-free survival, correlation with other biomarkers and tumor volume will be presented at the conference.
Conclusion:
Our findings reveal that FGF18 is a promising blood-derived candidate biomarker in MPM. Furthermore FGF18 may support the histological classification of MPM and the identification of MPM patients with poor prognosis. .
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OA07 - Lymph Node Metastases and Other Prognostic Factors for Local Spread (ID 376)
- Event: WCLC 2016
- Type: Oral Session
- Track: Surgery
- Presentations: 1
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OA07.01 - Incidence, Local Distribution and Impact of pN2 Skip Metastasis in Patients Undergoing Curative Resection for NSCLC (ID 4177)
14:20 - 14:30 | Author(s): V. Laszlo
- Abstract
- Presentation
Background:
Background: The presence of N2 lymph node (LN) involvement has strong impact on therapy and prognosis in non-small cell lung cancer (NSCLC). N2 LN metastasis may occur by skipping N1 LN stations (N2skip-met). We aim to analyze incidence, local distribution and impact of N2skip-mets in a large cohort of patients undergoing curative resection for NSCLC.
Methods:
Methods: A retrospective non-interventional singe-center cohort study was conducted, assessing all patients undergoing curative resection for NSCLC between 2006 and 2013 at our institution by reviewing medical charts. Incidence of N2skip-mets among these patients was the primary endpoint. Subsequent secondary correlation of clinical parameters was performed using uni- and multivariate logistic and cox regression models.
Results:
Results: In total, 1110 patients were enrolled, with the following pathological LN status: 789 (71%) pN0, 211 (19%) pN1, 105 (9.5%) pN2, 5 (0.5%) pN3. Histological subtype was: adenocarcinoma, n=675 (61%); squamous cell carcinoma, n=309 (28%); other, n=126 (11%). Incidence of N2skip was 55% (47/105). N2skip-mets occurred more frequently in right sided tumors (odds ratio (OR) 2.14, p=0.058) and patients with adenocarcinoma (vs. other, OR 1.54, p=0.19). Presence of N2skip-mets did not correlate with tumor size (ROC, area under curve (AUC) 0.44, p=0.32). Strikingly, presence of N2skip-mets was significantly increased in smokers (OR 3.5, 95% CI 1.38-8.83, p=0.006). Moreover, patients with N2skip-mets were more likely to develop subsequent brain mets (OR 4.13, p=0.06). Overall- and recurrence free survival will be presented at the conference.
Conclusion:
Conclusion: N2skip-mets occur in a high number of patients with N2 disease, with distinct differences in clinicopathologic features. Considering the results of this study, subclassification of N2 disease as recently proposed by the IASLC may have clinical impact in patients with resectable NSCLC.
Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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OA22 - Novel Trials and Biomarkers in Malignant Pleural Mesothelioma (ID 403)
- Event: WCLC 2016
- Type: Oral Session
- Track: Mesothelioma/Thymic Malignancies/Esophageal Cancer/Other Thoracic Malignancies
- Presentations: 1
- Moderators:H. Pass, N. Van Zandwijk
- Coordinates: 12/07/2016, 14:20 - 15:50, Strauss 3
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OA22.08 - Discussant for OA22.05, OA22.06, OA22.07 (ID 7002)
15:25 - 15:40 | Author(s): V. Laszlo
- Abstract
- Presentation
Abstract not provided
Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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P1.07 - Poster Session with Presenters Present (ID 459)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: SCLC/Neuroendocrine Tumors
- Presentations: 1
- Moderators:
- Coordinates: 12/05/2016, 14:30 - 15:45, Hall B (Poster Area)
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P1.07-026 - Activin A is Associated with Poor Prognosis and Promotes Metastatic Growth in Small Cell Lung Cancer (ID 5888)
14:30 - 14:30 | Author(s): V. Laszlo
- Abstract
Background:
Small cell lung cancer (SCLC) is a devastating malignancy characterized by resistance to therapy and poor clinical outcome. Therefore, identification of novel therapeutic strategies and non-invasive biomarkers that facilitate early detection and predict prognosis is urgently needed. Expression of the growth factor activin A (ActA), a member of the TGF beta superfamily, is deregulated in a number of malignancies. However, to date there is no data on the role of ActA in SCLC.
Methods:
In a cohort of SCLC patients (n=79) and in sex- and age-matched controls (n=66), plasma levels of ActA were measured by ELISA. The diagnostic value of plasma ActA was evaluated by ROC curve analysis. The mRNA and protein expression levels of ActA were analyzed in SCLC cell lines by qRT-PCR and by ELISA, respectively, and one of the cell lines with low baseline ActA expression was transfected with ActA and a control vector. The effect of ActA overexpression on the in vivo growth of SCLC cells was investigated in an orthotopic xenograft model.
Results:
Increased plasma ActA levels were found in patients with SCLC (vs. controls) and ActA levels were elevated in a TNM stage-dependent manner. Moreover, high ActA levels were associated with significantly shorter overall survival and multivariate analysis revealed that plasma ActA concentration is an independent negative prognostic factor in this patient cohort. With an area under the curve of 0.81 (95% CI: 0.74-0-0.88), circulating ActA was identified as a useful biomarker for the diagnosis of SCLC. Expression of ActA in SCLC cell lines was detected in vitro. Furthermore, ActA overexpression increased the metastatic capacity of SCLC cells in our xenograft model.
Conclusion:
Our findings suggest that the measurement of circulating ActA can support the diagnosis and staging of SCLC and, moreover, that it can help to predict the clinical outcome. We also conclude that ActA has a role in the aggressive behavior of this tumor type and that its potential therapeutic relevance needs to be further investigated.
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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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P3.03-046 - Prognostic Fibrinogen/Leucocyte Score at Diagnosis Predicts Survival and Benefit from Multimodality Treatment in MPM (ID 4179)
14:30 - 14:30 | Author(s): V. Laszlo
- Abstract
Background:
The aim of this study was to identify and validate prognostic and predictive biomarkers in a large cohort of patients with malignant pleural mesothelioma (MPM).
Methods:
We performed a retrospective chart review, including all patients with histologically confirmed MPM, treated at two specialized centers between 1994 and 2014. The effect of different clinical and pathological characteristics and laboratory values on outcome was investigated by using uni- and multivariate logistic and cox regression models.
Results:
Two-hundred ninety-one patients were enrolled (222 males and 69 females). Main histological subtype was epitheloid (n=199, 68%). Multimodality treatment, defined as macroscopic complete resection combined with chemotherapy and/or radiation therapy and/or intracavitary treatment, was performed in 134 (46%) patients. Median overall survival (OS) was 17.7 months from diagnosis. In the multivariate cox regression model, leucocyte count at diagnosis (continuous, hazard ratio (HR) 1.087, p=0.04), fibrinogen at diagnosis (continuous, HR 1.002, p=0.002), histological subtype (epitheloid vs. non-epitheloid, HR 0.064, p=0.006) and age (continuous, HR 1.035, p=0.001) remained as independently significant co-factors influencing OS. ROC curve analyses for predicting 1-year survival revealed an area under the curve (AUC) of 0.72 (p=0.001) for fibrinogen and 0.65 (p=0.001) for leucocytes. Dichotomizing fibrinogen and leucocytes at the median values (550 mg/dl and 8 G/l) revealed a sensitivity of 0.65 and 0.55 and a specificity of 0.69 and 0.61 for predicting 1-year survival, respectively. Combining dichotomized fibrinogen/leucocytes to an inflammation based prognostic score (none, one or both elevated) significantly influenced 1-year survival (p<0.001) and OS (score 0 vs. I, p=0.005; I vs. II, p=0.03). When introducing to the multivariate cox regression model, the fibrinogen/leucocytes score remained as independently prognostic for OS (I vs. O, HR 1.48, p=0.02; II vs. 0, HR 2.26, p<0.001). Strikingly, a significant predictive interaction between the fibrinogen/leucocytes score and treatment modality was observed (p<0.001).
Conclusion:
The inflammation based fibrinogen/leucocytes score predicts OS independently from sex, age, stage, subtype and treatment modality. Multimodality treatment including surgery increases survival selectively in patients with low fibrinogen/leucocytes score.
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P3.04 - Poster Session with Presenters Present (ID 474)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Surgery
- Presentations: 1
- Moderators:
- Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)
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P3.04-003 - Incidence and Outcome of Female Patients with Previous Breast Cancer Undergoing Curative Resection for Lung Cancer (ID 4178)
14:30 - 14:30 | Author(s): V. Laszlo
- Abstract
Background:
Due to recent improvements in breast cancer (BC) therapy and outcome, female patients with BC may be at higher risk of developing secondary malignancies such as lung cancer (LC). The aim of this study is to evaluate the incidence and outcome of previous BC in female patients with resectable lung cancer.
Methods:
A retrospective non-interventional singe-center cohort study was conducted, assessing all female patients undergoing curative resection for LC between 2006 and 2013 at our institution by reviewing medical charts. Follow-up will be completed in September 2016. Incidence of previous BC among these patients was the primary endpoint. Subsequent secondary correlation of clinical parameters was performed using uni- and multivariate logistic and cox regression models.
Results:
Allover, 463 female patients with LC were identified. The incidence of previous BC was 8.6% (40/463). Mean age was 64.1 years (SD ± 11.5) and was not different between patients with LC and LC/BC. Main histological LC subtype was adeno-carcinoma (64%; squamous cell, 23%; other, 13%). Stage (TNM-7) distribution was: I, 64.5%; II, 22%; III, 12.5%. Lobectomy was the preferred anatomical resection and mean hospital stay was 8.3 days. Complication rate was 7.6%. Recurrence free and overall survival will be presented at the conference. There were no statistical differences between patients with LC/BC and LC with regard to main clinical parameters and short term outcome.
Conclusion:
Due to improvements in breast cancer therapy, a reasonably number of patients developing subsequent lung cancer is observed. Short-term outcome of patients with LC/BC is similar to those with LC.
