Abstract
To assess the predictive and prognostic significance of folate receptor (FR)-positive circulating tumor cells (CTCs) in patients with small cell lung cancer (SCLC) received first-line chemotherapy. Eligible patients with chemotherapy-naïve, unresectable SCLC were enrolled and blood samples were collected. CTCs were enumerated using ligand-targeted polymerase chain reaction (LT-PCR) at baseline, after two cycles of chemotherapy regimen and on disease progression. In total, 80 patients were enrolled and 67 (83.8%) had positive CTC count at baseline (CTCs ≥ 8.7 FU/3mL). The baseline CTC counts in patients with partial response (PR) were significantly higher than those with progression disease (PD) (P = 0.0365). An obvious reduction of CTC enumeration after two cycles of chemotherapy was significantly correlated with PR (P = 0.0380), instead of SD (P = 0.4934). Among positive CTC count group, patients with relative low CTC level had significantly longer progression-free survival (PFS) and overall survival (OS) than those with high CTC level (PFS: 9.1 vs 6.9 months, P = 0.0458; OS: 11.1 vs 8.6 months, P = 0.056). In multivariate analysis, distant metastases (HR = 1.466, P = 0.021) and relative low CTC level (HR = 0.656, P = 0.049) were the independent predictive factors for patients with SCLC received first-line chemotherapy. The present results demonstrated that baseline CTC counts could be the valuable predictive and prognostic biomarker for patients with SCLC received first-line chemotherapy. The reduction of CTC enumeration after two cycles of chemotherapy was a potential predictor of chemotherapeutic response in SCLC.
Highlights
Small cell lung cancer (SCLC) accounts for approximately 10–15% of all lung cancer cases and is a leading cause of cancer-related death worldwide [1, 2]
91 consecutive patients with small cell lung cancer (SCLC) were included into the study between September 2014 and March 2016, of which 11 patients were not evaluable for Response Evaluation Criteria in Solid Tumors (RECIST) criteria due to lack of target lesion. 80 patients with qualified samples were included into the circulating tumor cell (CTC) analysis
There were no significant associations between baseline CTC counts and clinical characteristics including age, sex, smoking history, metastases and stage at diagnosis (Table 1)
Summary
Small cell lung cancer (SCLC) accounts for approximately 10–15% of all lung cancer cases and is a leading cause of cancer-related death worldwide [1, 2]. As a novel biomarker, circulating tumor cells (CTCs) has been proved to be a significant prognostic factor in metastatic prostate cancer, breast cancer, gastric cancer, colorectal cancer, cutaneous melanoma and nonSCLC (NSCLC) [4,5,6,7,8,9]. Hou et al concluded from their study that baseline CTC count was the independent prognostic factor for both progression-free survival (PFS) and overall survival (OS) [10]. Due to the difference in CTC detection method, non-standardized cutoff value and diverse treatment regimens of the previous studies, the predictive and prognostic role of CTC counts in SCLC remains controversial. CellSearch is an immunomagnetic-based CTC enrichment system, which detects epithelial cell adhesion molecule (EpCAM)-positive CTCs by immunostaining.
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