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Y. Dong
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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): Y. Dong
- 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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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): Y. Dong
- 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.
