Circulating tumor cells (CTCs) in patients (pts) with small cell lung cancer (SCLC) as a marker of disease burden and therapeutic response, and predictor of disease relapse.

Abstract

7092 Background: Currently there are no validated biomarkers for assessment or prediction of disease burden or activity in SCLC. Enumeration of CTCs by CellSearch is FDA approved, highly reproducible and validated in other malignancies. Application as a prognostic and predictive marker in SCLC is limited due to a lack of studies documenting serial monitoring in pts on therapy. Methods: We are conducting a prospective study serially enumerating CTCs in pts with newly diagnosed SCLC. CTC number (per 7.5 ml peripheral blood) and percentage of CTCs demonstrating DNA damage and apoptosis based on γH2AX and M30 staining respectively, are being assessed prior to initiation of chemotherapy, during each cycle and at relapse. We are correlating CTC number with disease stage, number of metastatic sites, response to therapy, and time to progression (TTP). Results: 21 SCLC pts are evaluable. 9 pts with limited disease (LD) had median baseline CTC value of 1 (0-8); only 2 of 9 pts had >5 CTCs. 12 pts with extensive disease (ED) had median baseline CTC value of 80.5 (0-37780); 8 of 12 pts had >5 detectable CTCs (p value 0.02). Amongst the 12 pts with ED, median baseline CTC count was higher in pts with ≥3 (n=3) compared to 1-2 sites of metastatic disease (n=9) (2668 vs 71; p value 0.52). Median percentage of CTCs positive for γH2AX and M30 was also higher for pts with ≥3 compared to 1-2 metastatic sites (83, 164.5 vs. 2, 7.5) (p-value 0.40, 0.69). Serial CTC data are available on 3 pts with ED; all had responsive disease and reduction in CTC number to 0-1 after 2 cycles of chemotherapy. As this protocol is ongoing, correlation of CTCs with updated response status and TTP will be presented at the ASCO meeting. Conclusions: CTCs can be isolated and serially enumerated in pts with SCLC. Baseline CTCs correlate directly with disease stage. In pts with ≥ 3 metastatic sites, baseline CTCs tend to be greater and show higher levels of DNA damage and apoptosis compared to those with 1-2 metastatic sites. Reduction in CTCs is associated with radiographic response to therapy. Correlation between absolute number at baseline and TTP is not yet known.