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C.M. Korse
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MINI 24 - Epidemiology, Early Detection, Biology (ID 140)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Thymoma, Mesothelioma and Other Thoracic Malignancies
- Presentations: 1
- Moderators:J. Creaney, M. Carbone
- Coordinates: 9/08/2015, 16:45 - 18:15, 102+104+106
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MINI24.09 - Cell-Free MicroRNA miR-625-3p Is Elevated in the Blood of Patients with Thoracic Malignancies (ID 1282)
17:30 - 17:35 | Author(s): C.M. Korse
- Abstract
Background:
In most instances definitive diagnosis of malignant pleural mesothelioma (MPM) requires a tissue biopsy of sufficient size. As a biopsy is not always feasible, the identification of an accurate biomarker easily measured in blood would represent an important step forward. A recent study indicated that microRNA miR-625-3p was present in elevated concentration in plasma or serum of MPM patients compared to healthy controls and asbestosis patients. (Kirschner et al, JTO; 7:1184). In this study, we have further investigated the diagnostic potential of miR-625-3p.
Methods:
MiR-625-3p and other microRNAs were measured by RT-qPCR in two independent series of MPM patients and controls. After exclusion of haemolysed samples and those yielding RNA of insufficient quality, series 1 consisted of serum samples from 73 MPM patients, 69 healthy volunteers and 64 patients with non-small cell lung cancer (NSCLC) collected at the Netherlands Cancer Institute (NKI) between 1994 and 2013. The second series consisted of plasma samples from 29 MPM patients and 35 healthy volunteers collected in Vienna and Hungary (V/H) between 2011 and 2013. Additionally levels of soluble mesothelin-related protein (SMRP) were assessed (ELISA) in the NKI series.
Results:
Analyses of samples from patients and controls in the NKI series revealed that serum miR-625-3p concentrations were on average 5.35-fold higher (p=0.0054) in MPM, and 3.47-fold (p=0.003) in NSCLC than in control samples. Levels in MPM patients were 1.54-fold higher than in NSCLC patients but this did not reach statistical significance (p=0.273). Compared to healthy controls, the areas under the ROC curve (AUC) were 0.82 (95% CI: 0.75-0.89) for MPM and 0.75 (95% CI: 0.67-0.84) for NSCLC. In the samples of the V/H series, plasma miR-625-3p concentrations were on average 1.98-fold (p<0.001) higher in MPM patients than in healthy volunteers, with an AUC of 0.80 (95% CI: 0.69-0.91). Assessment of SMRP in the NKI series revealed AUCs of 0.69 (95% CI: 0.59-0.78) differentiating MPM from healthy individuals and 0.65 (95% CI: 0.54-0.75) separating MPM from NSCLC, comparable to AUC values reported earlier.
Conclusion:
Data from two independent validation series confirms the previously observed increased abundance of miR-625-3p in blood from MPM patients. However, the miR-625-3p levels observed in NSCLC patients show that elevation of the level of this microRNA in plasma/serum is not restricted to MPM. Further studies into combinations of microRNAs and SMRP (diagnostic signature) in MPM are warranted.
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MINI 27 - Biology and Other Issues in SCLC (ID 152)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Small Cell Lung Cancer
- Presentations: 1
- Moderators:P.A. Bunn, Jr, J. Sage
- Coordinates: 9/09/2015, 16:45 - 18:15, 605+607
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MINI27.13 - Progastrin-Releasing Peptide (ProGRP) as a Biomarker for Clinical Response in Small-Cell Lung Carcinoma (SCLC) (ID 1390)
17:55 - 18:00 | Author(s): C.M. Korse
- Abstract
Background:
Most cases of small-cell lung cancer (SCLC) are detected at extensive stage, where current guidelines recommend 4-6 cycles of chemotherapy. Although upfront progression to doublet platinum based chemotherapy in SCLC is <20%, current clinical practice often includes treatment monitoring with imaging, mainly with computed tomography, every two cycles. Since the purpose of imaging during treatment is identification of progression (to avoid further exposure to an ineffective but still potentially toxic regimen), we sought to evaluate whether monitoring SCLC patients during treatment with a blood-based biomarker (ProGRP) would correlate with response.
Methods:
Patients with SCLC treated with mainly standard chemotherapy at six centers worldwide (Europe and China) were included. ProGRP levels from serum or plasma were measured with a fully automated ProGRP assay in a prospective fashion prior to treatment start and repeatedly during treatment. Imaging was done and interpreted according to local guidelines at each institution. Percent change of ProGRP from baseline to the time of maximum response (‘best response’) was correlated with imaging findings, and patients were divided into two groups: Responders (= stable disease [SD] or better) vs. Non-Responders (= progression on scan). The ability of ProGRP to discriminate between Responders and Non-Responders was assessed by sensitivity and specificity.
Results:
215 patients with available CT result were included, of whom 145 had received first-line treatment (131 received platinum+VP-16 doublet). Clinical characteristics were as follows: 60.5% male, median age was 62 years, 72.1% were (ex)smokers, 93.5% with Stage IIIB or IV SCLC, and the majority of patients were either Caucasian (59.6%) or Asian (32.6%). Across all lines of treatment, 186/215 (86.5%) had SD or better as best response to treatment. There was a positive trend for higher ProGRP levels with clinical stage at presentation, and in general higher pre-treatment levels in 1[st] line compared to later lines of treatment. A decline in ProGRP levels was strongly correlated with response, whereby higher baseline levels were associated with subsequent higher relative declines of ProGRP during treatment. Using different cut-off levels for ProGRP decline during treatment (-50%, -70%, or -90%), we detected patients with no response to treatment based on ProGRP levels alone, with a sensitivity of 82.8%, 89.7% and 96.6%, and a specificity of 65.6%, 55.4%, and 39.8%, respectively. Specificity was increased by approximately 10% when only patients with baseline ProGRP levels exceeding 100 pg/ml were included.
Conclusion:
To our knowledge, this is the largest SCLC cohort to date with available ProGRP data for therapy monitoring. The data showed that ProGRP levels at baseline were positively correlated with advanced disease stage, and decline in ProGRP levels during treatment was associated with tumor control in SCLC. The ProGRP assay used in this study is currently not cleared or approved for use in the USA.
