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B. Hegedus
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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): B. Hegedus
- 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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P1.06 - Poster Session with Presenters Present (ID 458)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 12/05/2016, 14:30 - 15:45, Hall B (Poster Area)
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P1.06-012 - Central and Peripheral Lung Adenocarcinomas Exhibit Different Timing and Predilection for Distant Metastasis (ID 5649)
14:30 - 14:30 | Author(s): B. Hegedus
- Abstract
Background:
Although distant metastases are major factors for unfavorable prognosis in lung adenocarcinoma (ADC), metastatic patterns have not been widely analyzed in this malignancy.
Methods:
Clinicopathological data of 1126 ADC patients (541 men, 585 women, mean age: 62.1 ± 9.4 years, 32-88 years) were studied retrospectively, focusing on the localization of primary tumor and distant metastases. Metastases diagnosed at the time of primary tumor diagnosis were defined as early metastases. For statistical analyses, Fisher's exact test and a chi-squared independence test were performed.
Results:
At time of diagnosis, 621 patients had stage IV disease. 435 of them had a solitary organ metastasis, mainly in the contralateral lung (n=187), in the brain (n=66), or in the bone (n=59). During the follow up period another 242 patients developed distant metastasis. 39% of all patients had central (i.e. endobronchially visible) tumor. In cases with early-, late-, and non-metastatic disease, the proportions of central tumors were 43%, 35% and 31%, respectively. Central primary tumors were significantly more likely to give rise to early metastases than peripheral ones (p=0.021). When comparing central and peripheral lung cancers according to their metastatic sites, in central tumors lung metastases appeared significantly earlier (p=0.017), while in peripheral ones bone metastases appeared significantly later (p=0.015). There were significant differences in the metastatic organ distributions of central vs. peripheral primary tumors for early (p=0.025) and late (p=0.009) metastases. There was no significant difference in the metastatic organ distributions of right vs. left lung primaries both for early and late metastases. In right lung tumors brain metastases appeared later (p=0.047). No significant difference was observed in the metastatic organ distributions of primary tumors of the upper vs. lower lobes for early (p=0.051), and late (p=0.528) metastases. Early appearance was characteristic for lung, pleural, and adrenal involvement (p<0.001 in all comparisons), while late development was typical for brain metastasis (p=0.002). Bone, liver, subcutaneous, and pericardial metastases showed no such tendencies.
Conclusion:
There are significant differences in metastatic organ distributions of central vs. peripheral lung cancers both for early and late metastases. Central primary tumors are more likely to give rise to early metastases than peripheral ones. Results of molecular subgroup analyses will be presented during the Conference.
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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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P1.07-042 - Neutrophil-Lymphocyte and Platelet-Lymphocyte Ratios Predict Prognosis in Early-Stage Resected Small-Cell Lung Cancer Patients (ID 5657)
14:30 - 14:30 | Author(s): B. Hegedus
- Abstract
Background:
Surgical resection is rarely possible in small-cell lung cancer (SCLC), a highly aggressive malignancy with limited treatment options. However, although in the past decades, for selected early-stage cases, a curative intent surgery is often performed, there is no biomarker to help the selection of patients eligible for surgery. Because previous studies - predominantly from East Asia - showed that high neutrophil to lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) correlate with poor prognosis in several types of tumors including SCLC, the aim of our study was to investigate the prognostic value of NLR and PLR in Caucasian patients with resected SCLC.
Methods:
Consecutive patients with histologically confirmed and surgically resected SCLC evaluated between 2000 and 2013 at the National Koranyi Institute of Pulmonology were analyzed in this retrospective analysis. Patients were divided into "high" and "low" groups according to their NLR and PLR at diagnosis. The cut-off NLR and PLR values were 3 and 110, respectively. Next, we evaluated the associations of preoperative NLR or PLR with vascular involvement, tumor necrosis, peritumoral inflammation, tumor grade, clinicopathological characteristics (including age, gender, stage) and overall survival (OS) in univariate and multivariate analyses.
Results:
There were a total of 65 patients (39 men and 26 women) with a median age of 57.7 years (range, 40-79). The pathological stages were 1, 2 and 3A in 23, 23 and 14 cases by AJCC 7[th] edition (in five patients no pTNM was available). PLR was high (HPLR) in 41 (63%) and low (LPNR) in 24 (37%) patients. NLR was high (HNLR) in 35 (66%) and low (LLNR) in 17 (33%) patients. PLR significantly correlated with pathologic lymph node status (p<0.001) and NLR (p=0.007). HPLR was associated with shorter OS (vs. LPLR, HR, 2.2; 95% CI, 1.13–4.29; p=0.02). There was a non-significant trend towards longer OS in patients with LNLR (vs. HNLR, p=0.078). There were no significant associations between NLR or PLR and age, gender, stage, vascular involvement, tumor necrosis, peritumoral inflammation and tumor grade.
Conclusion:
This is the first study in Caucasian patients with resected SCLC which shows that LPLR (<110) before surgical resection may be a favorable prognostic factor for longer OS. We also conclude that preoperative HPLR may predict lymph node involvement. PLR but not NLR may help in selecting patients for surgery in the future. Further prospective studies are needed to confirm these observations.
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P2.01 - Poster Session with Presenters Present (ID 461)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Biology/Pathology
- Presentations: 1
- Moderators:
- Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)
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P2.01-088 - Prenylation Inhibitors in Lung Adenocarcinoma: Comparison of Zoledronic Acid and a Novel Lipophilic Bisphosphonate (ID 5640)
14:30 - 14:30 | Author(s): B. Hegedus
- Abstract
Background:
The prenylation inhibitor zoledronic acid is a standard-of-care therapeutic option in bone metastasis. Recent studies suggest that prenylation inhibition using novel lipophilic bisphosphonates might be active against various malignancies outside the bone metastatic setting. Since prenylation is an important posttranslational modification in RAS protein function we explored the sensitivity of a panel of lung adenocarcinoma cells representing various oncogenic driver mutations.
Methods:
8 human lung adenocarcinoma cell lines were investigated in vitro to assess the short-term viability and long-term clonogenic potential following zoledronic acid and BPH-1222 treatments. The eight lung cancer cell lines represented wild type (HCC78, CALU3), EGFR- (H1650, H1975) KRAS- (A549, H358), BRAF- (CRL5885) and BRAF + NRAS double mutant (CRL5922) molecular subtypes. Effect on short and long term proliferation were measured with a SRB based photometric assay.
Results:
Neither short-term nor long-term treatment showed significant differences between the proliferation inhibitory effect of the hydrophilic zoledronic acid and novel lipophilic bisphosphonate BPH-1222. Interestingly, we found that the two KRAS mutant lung adenocarcinoma cell lines were more sensitive in the long-term bisphosphonate treatment assays than non-KRAS mutant cell lines. BRAF or EGFR mutations did not show a differential response against these inhibitors.
Conclusion:
In vitro proliferation inhibitory efficacies of hydrophilic and lipophilic bisphosphonates were not different in lung adenocarcinoma cells. Nevertheless, due to the different bone accumulation properties of zoledronic acid and lipophilic bisphosphonates further in vivo preclinical studies are warranted to evaluate the inhibitory effect in a more physiological setting.
