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G. Burrafato



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    P3.06 - Poster Session 3 - Prognostic and Predictive Biomarkers (ID 178)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Biology
    • Presentations: 1
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      P3.06-030 - Circulating tumor cells as a novel predictive marker in patients with advanced adenocarcinoma of the lung treated with platinum and pemetrexed (ID 2443)

      09:30 - 09:30  |  Author(s): G. Burrafato

      • Abstract

      Background
      Circulating tumor cells (CTCs) are cells that have spread from the primary tumor into the bloodstream, and they play a crucial role in the development of distant metastases. CTCs have been detected in several cancers and associated with aggressive disease. The aim of this study was to evaluate the correlation between the numeric variation of CTCs in the blood of patients (pts) with advanced adenocarcinoma (ADK) of the lung during chemotherapy (CHT) and the radiological response to explore their potential role as an early predictive indicator of treatment response.

      Methods
      Peripheral blood samples and computed tomography (CT) scans were obtained before any treatment (baseline) from 25 pts with advanced ADK who were candidates for first-line CHT (platinum-based combination with pemetrexed). Blood samples were collected every two CHT cycles, and radiological responses were concomitantly assessed by CT according to the RECIST v. 1.1 criteria. CTCs were isolated from blood and diluted in a buffer containing formaldehyde to lyse red blood cells and fix CTCs using a filtration-based device (ScreenCell[®], France) to sort CTCs by size. CTCs were isolated by size using a microporous membrane filter composed of polycarbonate material containing circular pores that are calibrated (7.5±0.36 μm) and randomly distributed throughout the filter (1×10[5 ]pores/cm[2]). At the end of filtration, hematoxylin and eosin (HE) staining and immunofluorescence (IF) using CK7 were performed to enumerate and characterize the CTCs. Moreover, variations in the CTC count were compared with tumor size variations observed in CT scans.

      Results
      Baseline CTC counts and CT scans were obtained from 25 pts, including 18 males and 7 females, with a median age of 68 (range: 45-81) years. H&E staining revealed that the CTCs were morphologically compatible with tumor cells and were present in all 25 pts at baseline (range: 2-25 CTCs/ml). Furthermore, the epithelial origin of the CTCs was confirmed by CK7 positivity (demonstrated by IF). CTCs and CT images were assessed in 19 pts after at least two CHT cycles; the best response was a partial response (PR) in 2 pts, progressive disease (PD) in 3 pts and stable disease (SD) in 13 pts. The CTC number varied with the tumor size in 77.8% (14/18) of pts; decreased CTC counts were observed in 87.5% (7/8) of pts with reduced tumor size, whereas increased CTC counts were found in 70% (7/10) of pts with increased tumor size. Notably, variations in CTC count and tumor size were concordant in 100% (5/5) of pts achieving a PR or with PD as the best response.

      Conclusion
      This study demonstrates the feasibility of isolating CTCs in all advanced lung ADK pts using a low-cost, size-based technique. Interestingly, the concordance between the CTC analysis and CT suggests that CTCs may represent an early predictive marker of disease outcome. To our knowledge, this is the first study suggesting a relationship between CTC variation and treatment response in lung cancer.