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F. Herth
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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): F. Herth
- 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.
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MINI 32 - Topics in Localized Lung Cancer (ID 166)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Treatment of Localized Disease - NSCLC
- Presentations: 1
- Moderators:D. Boffa, T. D'Amico
- Coordinates: 9/09/2015, 18:30 - 20:00, 201+203
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MINI32.09 - The Combination of Serum Biomarkers CYFRA 21-1 and CEA in the Prognostication of Early Stage Non-Small Cell Lung Cancer (NSCLC) (ID 1353)
19:15 - 19:20 | Author(s): F. Herth
- Abstract
Background:
Serum based biomarkers are routinely used for prognosis and monitoring of some solid tumors (e.g. colorectal, pancreatic, and ovarian carcinomas) but have not yet been widely adopted in NSCLC management. We prospectively evaluated the prognostic role of serum biomarkers in the management of early stage NSCLC treated at a single specialized center.
Methods:
Prospective collection of blood samples from patients (pts) with resectable NSCLC was done before surgery and thereafter during routine follow up visits. A panel of serum biomarkers was measured, including CYFRA 21-1 (Cytokeratin fragment 19) and CEA (carcinoembryonic antigen). Several risk models were established and prediction accuracy was assessed by C-Index (generalized AUC), Hazard Ratio (HR) at median split and Net Reclassification Index (NRI).
Results:
275 pts were enrolled (n= 180 men). Histology was adenocarcinoma (AC) in 133 pts (48.4%), squamous cell carcinoma in 103 pts (37.5%), and other in 39 (14.1%). Stages were based on IASLC 6[th] edition and included IA (n= 39), IB (n= 120), IIA (n= 7), IIB (n= 66), and IIIA (n= 43). 92 pts (33.5%) recurred after a median of 11.9 months follow-up. Occurrence of first relapse showed two main peaks, at 6-12 months and 21-27 months, respectively, indicating a high-risk group for early relapse. In multivariate analyses, clinical prognostic factors included: TNM stage, age, gender, histology, and smoking history. Addition of the baseline CYFRA 21-1 and CEA biomarkers significantly increased the number of pts allocated to the correct prognostic group in the model by 13.2% compared to clinical variables only (HR for first relapse from 2.14 to 3.02; NRI 0.132).
Conclusion:
In this largest cohort of NSCLC pts with prospective serum biomarker sample collection to date, time to first relapse in localized NSCLC showed subgroups of early and late relapse pts. Baseline levels of the CYFRA 21-1 and CEA biomarkers identified a higher number of pts who were likely to recur within the first year and might benefit from closer surveillance. The CYFRA 21-1 assay is currently not cleared or approved for use in the USA.
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P1.06 - Poster Session/ Screening and Early Detection (ID 218)
- Event: WCLC 2015
- Type: Poster
- Track: Screening and Early Detection
- Presentations: 1
- Moderators:
- Coordinates: 9/07/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P1.06-011 - miR-126 Is a Potential Diagnostic Marker for Malignant Pulmonary Nodules in Endobronchial Epithelial Lining Fluid (ID 1712)
09:30 - 09:30 | Author(s): F. Herth
- Abstract
Background:
Early detection and diagnostic clarification of indeterminate pulmonary nodules by less invasive methods could contribute to better intervention strategies and to the reduction of the high mortality in lung cancer patients. Endobronchial epithelial lining fluid (EELF) might contains molecular markers with diagnostic potential. With the bronchoscopic microsampling (BMS) technique, it is possible to collect EELF in close proximity to the suspected lesion without the risk of biopsy-associated complications. We investigated whether microRNA (miRNA) in EELF collected by BMS may be useful to facilitate preoperative diagnosis of indeterminate pulmonary nodules.
Methods:
The study included 24 non–small-cell lung cancer patients with 48 EELF samples. From each patient, EELF was collected from subsegmental bronchi close to the indeterminate pulmonary nodule, which was detected by computed tomography, and from the contralateral healthy lung. Diagnosis was confirmed by transbronchial biopsy or surgery. Global miRNA expression profile analysis (754 miRNAs) was performed using quantitative real-time polymerase chain reaction (qRT-PCR) with eight sample pairs. miRNAs potentially associated with a malignant phenotype were selected for further qRT-PCR analysis in an independent validation cohort (16 sample pairs).
Results:
All patients underwent BMS without complications. miRNA profiling by qRT-PCR could be reliably applied to EELF samples and resulted in potential miRNA markers for malignant pulmonary nodules. In particular, the miRNA pair miR-126/miR-126* significantly differentiated between EELF close to the indeterminate pulmonary nodules and the sample taken from the healthy contralateral lung (p<0.0001).
Conclusion:
Our study suggests that the analysis of miR-126/miR-126* in EELF collected by BMS could be a potentially useful adjunct to other diagnostic techniques aiming at the preoperative diagnosis of indeterminate pulmonary nodules.
