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F.J. Herth
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MA11 - Novel Approaches in SCLC and Neuroendocrine Tumors (ID 391)
- Event: WCLC 2016
- Type: Mini Oral Session
- Track: SCLC/Neuroendocrine Tumors
- Presentations: 1
- Moderators:P. Lara, A. Mohn-Staudner
- Coordinates: 12/06/2016, 14:20 - 15:50, Strauss 3
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MA11.09 - Progastrin-Releasing Peptide (ProGRP) to Rule out Progressive Disease in Patients with Small Cell Lung Carcinoma (SCLC) (ID 4002)
15:20 - 15:26 | Author(s): F.J. Herth
- Abstract
- Presentation
Background:
For patients with SCLC, response to chemotherapy is monitored by computed tomography (CT) scans, which can be costly and inconvenient. A previous study showed that baseline levels (>100 pg/ml) of the tumor marker, ProGRP, were positively correlated with advanced SCLC, and a decline in ProGRP levels during treatment was associated with response.[1] However, the best approach to fully exploit ProGRP for monitoring treatment response is still unknown. The objective of this study was to determine if progression could be ruled out solely by combining the changes in ProGRP levels over two chemotherapy cycles.
Methods:
Patients with SCLC receiving first-line platinum-based doublet chemotherapy or a single-agent cytotoxic in any subsequent treatment line were included from six centers in Europe and China. Samples were collected prospectively and ProGRP levels were measured in serum or plasma samples using a fully automated ProGRP assay at baseline and after chemotherapy cycles 1 and 2. Only patients with blood samples taken at these time points and with elevated baseline ProGRP >100 pg/ml were eligible for this analysis. A logistic regression model was calculated to incorporate changes after the first cycle (i.e. from baseline to the end of cycle 1) and in between cycles (i.e. end of cycle 1 to the end of cycle 2). Progression was ascertained with CT scans. A non-progressor was defined as a patient with complete response, partial response, or stable disease, according to the RECIST v1.1 or WHO criteria. Progressors were patients with progressive disease only.
Results:
Overall, 123 patients (n=108 non-progressors, n=15 progressors) satisfied the eligibility criteria. Median age was 62.0 years (range 36.0–83.0), 56% were male, and 78% reported to be current or past smokers. In this population, a decline in ProGRP from both baseline to cycle 1 and from cycle 1 to cycle 2 was associated with non-progression (AUC 91.5%; 95% CI: 85.3−97.8; sensitivity 100%; specificity 71%). All patients who experienced a >25% relative decline in ProGRP levels after the first chemotherapy cycle, followed by any further decrease (>0%) after the second cycle, were found to be non-progressors.
Conclusion:
By measuring the change in ProGRP levels at baseline and after each of the two subsequent chemotherapy cycles, we were able to identify patients with non-progressive disease. This might reduce the need for interim CT scans. References 1. Muley, et al. Journal of Thoracic Oncology 2015; 10(9) Supplement 2:MINI27.13
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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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P2.01-034 - The Pregnancy Associated Endometrial Protein Glycodelin as a Biomarker for Malignant Pleural Mesothelioma (ID 5422)
14:30 - 14:30 | Author(s): F.J. Herth
- Abstract
Background:
Malignant pleural mesothelioma (MPM) is a rare and aggressive tumor with a short survival time arising from the mesothelial cells of the pleura. MPM is mainly associated with asbestos exposure and a strong inflammatory reaction. The common treatment of MPM combines macroscopic complete resection and adjuvant or neoadjuvant chemotherapy, respectively. Soluble mesothelin and osteopontin are current available biomarker for malignant mesothelioma with moderate sensitivity and specificity. Glycodelin is an immune system modulator well described during pregnancy. It is involved in invasion of the trophoblast and in regulation of the immunotolerance between the maternal immune system and the fetus.
Methods:
With a commercial ELISA, we measured the glycodelin serum concentrations of patients with MPM. In addition, we analyzed the glycodelin gene expression using quantitative PCR and stained glycodelin in formalin-fixed paraffin embedded tissue slides.
Results:
We found high glycodelin concentrations in the serum of patients with MPM compared to benign lung diseases. Patients with high glycodelin serum concentrations exhibited a worse overall survival. Moreover, glycodelin serum levels correlated with tumor response to treatment. A comparison of soluble mesothelin-related proteins (SMRP) and glycodelin in the serum of a large patient cohort demonstrated that the detection of both soluble factors can increase the reliable diagnostic of MPM. Glycodelin mRNA and protein was highly expressed in MPM tumors compared to normal lung tissue.
Conclusion:
In this study, we first described the expression of glycodelin in MPM. Altogether, glycodelin seems to be a new potential serum biomarker for the aggressive malignant pleural mesothelioma.
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P2.05 - Poster Session with Presenters Present (ID 463)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Radiotherapy
- Presentations: 1
- Moderators:
- Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)
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P2.05-025 - 9-Year Experience: Prophylactic Cranial Irradiation in Extensive Disease Small-Cell Lung Cancer (ID 4017)
14:30 - 14:30 | Author(s): F.J. Herth
- Abstract
Background:
~In 2007, a EORTC study demonstrated a beneficial impact on overall survival with the use of prophylactic cranial irradiation in extensive disease small cell lung cancer. Nevertheless, there is ongoing debate over the role of PCI as patients in this trial did not undergo imaging of the brain prior to treatment, and a recent Japanese randomized trial showed a detrimental effect of PCI on OS in patients with a negative pre-treatment brain MRI. 87% of our patients received brain imaging prior to PCI.~
Methods:
We examined the medical records of 137 patients with extensive disease small cell lung cancer who initially responded to chemotherapy and received PCI between 2007 and 2015. The outcomes, including the development of brain metastases and OS following PCI were analyzed. Survival and correlations were calculated using log-rank, univariate, and multivariate Cox proportional hazards-ratio analyses.
Results:
Median OS after PCI was 12 months and the median nPFS after PCI was 19 months. There was no significant survival difference in patients who received an MRI prior to PCI compared to patients who received a contrast enhanced computer tomography (CT) (p=0.20). Univariate analysis for overall survival did not show a statistically significant effect for known cofactors. Figure 1 Figure: OS (A) and nPFS (B) in patients with ED SCLC treated with PCI. .
Conclusion:
We present the 9-year clinical experience with PCI in ED SCLC patients from one of Europe’s largest Lung Cancer Centres. PCI leads to a nearly doubled median OS compared to the irradiation arm of the EORTC trial with a 2-months prolonged median OS compared to the irradiation arm of the Japanese trial. PCI should remain standard of care for all patients with SCLC who have a response to initial chemotherapy. Contrast enhanced brain MRI instead of CT for staging prior to PCI is recommended if possible.
