Circulating Tumor Cells Correlated with Disease Stage in SCLC
(CHICAGO, IL) — Circulating tumor cells (CTCs) can be isolated and serially enumerated in patients with small cell lung cancer (SCLC), and baseline CTCs can be directly correlated with disease stage, according to a report at the 2012 American Society of Clinical Oncology Annual Meeting.
In fact, patients with three or more metastatic sites had greater baseline CTCs and show higher levels of DNA damage and apoptosis when compared with those who had one to two sites of metastasis, and “reduction in CTCs is associated with radiographic response to therapy,” noted lead author Anjana Ranganathan, MD, of the University of Pennsylvania, Philadelphia.
“There is an enormous unmet need for a noninvasive biomarker that can simultaneously prove both prognostic and predictive of benefit with new therapeutic agents,” she noted. Currently, no validated biomarkers exist to assess or predict disease burden or activity in SCLC. “Enumeration of CTCs by CellSearch is FDA approved, highly reproducible, and validated in other malignancies,” Dr. Ranganathan reported. However, “its application as a prognostic and predictive marker in SCLC is limited due to a lack of studies documenting serial monitoring in patients on therapy.”
The prospective study serially enumerated CTCs in patients with newly diagnosed SCLC. CTC number (per 7.5mL peripheral blood) and percentage of CTCs demonstrating DNA damage and apoptosis based on γH2AX and M30 staining, respectively, were assessed prior to initiation of chemotherapy, during each cycle, and at relapse. CTC number was correlated with disease stage, number of metastatic sites, response to therapy, and time to progression (TTP).
To date, 23 patients with SCLC were evaluable; 11 had limited disease and a median baseline CTC value of 1 (0–46); only 3 had >5 CTCs. Of the 12 patients with extensive disease (ED), median baseline CTC value was 80.5 (0–37,780); eight patients had >5 detectable CTCs (P=0.01).
Among the 12 patients with SCLC-ED, median baseline CTC count was higher in those with ≥3 sites (n=3) vs 1 to 2 sites of metastatic disease (n=9) (2668 vs 71; P=0.52). Median percentage of CTCs positive for γH2AX and M30 was also higher for patients with ≥3 vs 1 (P=0.12) to 2 (P=0.14) metastatic sites.Of the 23 patients, 17 with performance status 0 or 1 had a median CTC of 3 (0–3949) at baseline; after 2 cycles of chemotherapy, median CTC was 0 (0-2376), compared with the 6 patients with PS ≥2 who had baseline median CTC of 148 (1-37780) and 114 (1-281) after 2 cycles of chemotherapy.
Serial CTC data were available on three patients with SCLC-ED; all had responsive disease and reduction in CTC number to 0–1 after two cycles of chemotherapy. Median overall survival for patients for >5 CTCs was 11.6 months and has not been reached for patients with ≤5 CTCs (P=0.61)
“We demonstrated that CTCs can be isolated and serially enumerated in patients with SCLC,” she noted. “Baseline CTC s correlated directly with disease stage.” Correlation between absolute number at baseline and time to progression and overall survival is not yet known. The study is ongoing, with an accrual goal of 50 patients.