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C. Maggioni

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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): C. Maggioni

      • Abstract
      • Presentation
      • Slides

      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.

      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.

      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).

      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).

      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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    P2.01 - Poster Session/ Treatment of Advanced Diseases – NSCLC (ID 207)

    • Event: WCLC 2015
    • Type: Poster
    • Track: Treatment of Advanced Diseases - NSCLC
    • Presentations: 1
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      P2.01-057 - Serum Mass-Spectrometry Test in First-Line Advanced Non-Small Cell Lung Cancer Patients Treated with Standard Chemotherapy Regimens (ID 2309)

      09:30 - 17:00  |  Author(s): C. Maggioni

      • Abstract

      The mass-spectrometry based serum test VeriStrat® (VS) was developed using samples from non-small cell lung cancer (NSCLC) patients (pts) treated with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs); VS was shown to be prognostic in several tumors and predictive of differential overall survival (OS) benefit for erlotinib vs. chemotherapy (CT) in 2[nd] line for NSCLC. We investigated the role of VS in pts receiving Cisplatin (CDDP) or Carboplatin (CBDCA) plus Pemetrexed (P) as 1[st] line for advanced, non-squamous NSCLC.

      VeriStrat classification was available for 55 eligible pts, who were classified as VS Good (VSG) or VS Poor (VSP); VS testing was done blinded to clinical data. Progression-free survival (PFS) and OS were analyzed by Kaplan-Meier method and compared using log-rank p-values; Cox models were used in multivariate analysis. Association with categorical variables was analyzed by Fisher’s exact test.

      36 (65%) pts were classified as VSG and 19 (35%) as VSP. In the overall population, median PFS was 6.1 months (mo) for VSG vs.1.3 mo for VSP (hazard ratio (HR) 0.39 [0.21-0.70], p=0.001 ); adjusted HR (AHR) 0.43 [0.21-0.91], p=0.026). Median OS was 10.6 mo for VSG vs. 3.1 mo for VSP (HR 0.26 [0.14-0.50], p<0.001; AHR 0.20 [0.09-0.47], p<0.001). A similar relationship was found in both treatments: In CBDCA-P median PFS in VSG and VSP was 3.9 mo and 1.6 mo respectively (HR 0.34 [0.14-0.81], p=0.011); median OS was 10.0 mo in VSG and 2.0 mo in VSP (HR 0.26 [0.11-0.61], p=0.001). In CDDP-P median PFS was 6.6 mo in VSG and 1.2 mo in VSP (HR 0.52 [0.20-1.33], p=0.161), median OS was 12.3 mo in VSG, 3.5 mo in VSP (HR 0.25 [0.09-0.70], p=0.005).When compared within VS groups, no statistically significant differences between CBDCA-P and CDDP-P was found either for PFS (VSG: p=0.471, VSP: p=0.493) or OS (VSG: p=0.319, VSP: p=0.429). VS was significantly associated with disease control rate (p=0.003) and objective response (p=0.021).

      Population (N°) Median PFS (months) Hazard ratio, p Median OS (months) Hazard ratio, p
      Overall (55) 6.1 1.3 0.39 [0.21-0.70] p=0.001 10.6 3.1 0.26 [0.14-0.50] p<0.001
      CBDCA-P (30) 3.9 1.6 0.34 [0.14-0.84] p=0.011 10.0 2.0 0.26 [0.11-0.61] p=0.001
      CDDP-P (25) 6.6 1.2 0.52 [0.20-1.33] p=0.161 12.3 3.5 0.25 [0.09-0.70] p=0.005

      VeriStrat has prognostic significance in platinum-based CT: overall, VSP pts have significantly shorter PFS and OS than VSG pts. In each VS group, CDDP-P and CBDCA-P showed similar behavior. Further research is needed to find alternative treatments to improve outcomes for VSP pts. Identifier: NCT02055144.