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I. Vanni



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    MINI 26 - Circulating Tumor Markers (ID 148)

    • Event: WCLC 2015
    • Type: Mini Oral
    • Track: Biology, Pathology, and Molecular Testing
    • Presentations: 1
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      MINI26.09 - Correlation between Circulating Tumor Biomarkers and Positron-Emission Tomography in Advanced Non-Small Cell Lung Cancer (ID 2940)

      16:45 - 18:15  |  Author(s): I. Vanni

      • Abstract
      • Presentation
      • Slides

      Background:
      Circulating tumor cells (CTCs) and plasma circulating-free DNA (cfDNA) are promising candidates as non-invasive prognostic markers in malignant diseases. 18-fluorodeoxyglucose positron emission tomography integrated with computed tomography (18FDG-PET/TC) has a well-recognized diagnostic and prognostic value in non-small cell lung cancer (NSCLC). Very little is known about the mutual relationship between circulating biomarkers (CTCs and cfDNA) and 18FDG-PET/CT indicators in NSCLC.

      Methods:
      Peripheral blood samples from 28 patients affected by advanced/metastatic NSCLC were collected before starting first-line chemotherapy. CTCs were isolated by size using a filtration-based device (ScreenCell) and then identified and enumerated; cfDNA was isolated from plasma (QIAamp DNA Blood Mini Kit, Qiagen) and quantified by qPCR method using human telomerase reverse transcriptase (hTERT). All patients underwent 18FDG-PET/TC (Biograph 16 Siemens) at baseline. Maximum diameter (dmax) of the primary lesion (T), dmax of the greater lymph nodal (N), and metastatic (M) lesions were measured. Similarly, maximum and mean standardized uptake value (SUVmax, SUVmean) and size-incorporated SUVmax (SIMaxSUV) were computed for T, N and M, respectively; SIMaxSUV was calculated with the following formula for T, N, and M: SIMaxSUV= SUVMax*dmax. Presence (B+) and absence (B-) of metabolically active bone lesions (bone mets) were recorded. The association among CTCs, cfDNA and 18FDG-PET/CT-derived parameters was evaluated through multivariate analysis. T-test was performed to evaluate the difference in CTCs and cfDNA in B+ and B- groups, respectively.

      Results:
      Twenty-eight patients were evaluated; median age was 66 years (range: 51-80); male/female ratio was 18/10; 15 patients were current smokers, while 11 were former-smokers and 2 were never-smokers. Histo-types were grouped as it follows: adenocarcinoma= 22; squamous cell carcinoma= 5; not otherwise specified NSCLC= 1. Nine patients out of 28 had metabolically active bone lesions. Median CTC count was 7 CTCs/3ml (range: 0-47 CTCs/3ml), while median HTERT copy number was 109.0 (range: 16.7-1405-5).

      18FDG-PET/CT PARAMETERS MEAN STANDARD DEVIATION P
      T Size 44.93 20.25 0.175
      SUV max 10.16 4.48 0.036
      SUV mean 10.6 3.4 0.994
      SIMaxSuv 487.7 333.5 0.472
      N Size 22.2 10.9 0.313
      SUV max 7.4 4.0 0.318
      SUV mean 5.8 3.0 0.294
      SIMaxSuv 172.8 158.1 0.231
      M Size 23.9 15.0 0.083
      SUV max 7.5 4.1 0.318
      SUV mean 7.4 1.2 0.307
      SIMaxSuv 216.4 206.5 0.463
      At multivariate analysis, SUVmax of T was the only variable independently associated with cfDNA (p=0.036). No correlations were highlighted between CTCs and all PET-derived parameters. A trend towards significance between high HTERT and the presence of metabolically active bone lesions was observed (p=0.058).

      Conclusion:
      Our data demonstrate that the expression of cfDNA is correlated with the metabolic activity of the primary tumor lesion. Since SIMaxSUV was not correlated with HTERT, it appears that the expression of cfDNA depends from tumor metabolism rather than its burden. Further analyses on 18FDG-PET/TC-derived metabolic tumor volume are ongoing.

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    MINI 34 - RNA and miRNA (ID 162)

    • Event: WCLC 2015
    • Type: Mini Oral
    • Track: Biology, Pathology, and Molecular Testing
    • Presentations: 1
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      MINI34.03 - Novel microRNA Prognostic Signature in Malignant Pleural Mesothelioma (ID 2988)

      18:30 - 20:00  |  Author(s): I. Vanni

      • Abstract
      • Presentation
      • Slides

      Background:
      Malignant pleural mesothelioma (MPM) is an aggressive tumor mainly associated with asbestos exposure. MPM patients have a poor outcome (median overall survival (mOS) <1 year), therefore novel therapeutic approaches are needed. MiRNA have been demonstrated to have a role in tumorigenesis and progression in MPM. This study aimed to identify a miRNA signature associated with poor prognosis.

      Methods:
      We identified 26 un-resected MPM patients split as follows: 11 long survivors (LS) OS>3 years and 15 short survivors (SS) OS<1 year. MiRNA expression in 26 FFPE biopsy and 3 normal pleura (NP) was evaluated using Agilent Human miRNA Microarray platform including 2006 miRNA. Expression data were normalized by GeneSpring software (v.12.6). Class-comparison analysis between MPM/NP and SS/LS was performed using a t-test adjusted for multiple comparisons using Benjamini-Hochberg. OS curves were estimated using the Kaplan-Meier method and compared with the log-rank test. In silico validation was performed using miRseq data from TCGA portal based upon 16 patients (LS: 8; SS: 8). Candidate miRNA were assessed by univariate analysis using Kaplan-Meier method and median as cutoff.

      Results:
      Patients’ characteristics: median age 67 years (53-77); 81% males, 19% females; 73% epithelioid histotype, 12% sarcomatoid, 12% biphasic and 1 unspecified MPM. No differences in age, gender and histotype were observed between LS and SS. By class-comparison analysis, 30 miRNAs were significantly up-regulated and 11 down-regulated in MPM vs NP (adjusted p-value <0.05). Fourteen miRNAs were significantly associated with outcome, in the univariate survival analysis and differentially expressed in MPM. A miRNA signature, based on the top 6 prognostic miRNAs (unfavorable, miR-1224; favorable, miR-99a, miR-125b, let-7b, let-7c and let-7i) classified patients into low- or high-risk. High-risk patients showed a significantly shorter median OS (4.1 months, 95% CI 2.2-5.9) as compared with low-risk patients (median not reached, Log-rank p<0.001). In silico validation analysis confirmed that low expression of mir-99a, miR-125b and let-7c was associated with shorter OS. Relevant pathways, such as PI3K/AKT, WNT were associated with these top miRNAs by pathway analysis.

      Conclusion:
      A prognostic miRNA signature was identified by profiling a cohort of un-resected MPM, underlying the clinical potential of miRNA as predictors of survival. An additional validation in a larger independent cohort of MPM is ongoing.

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