Table 2.
Selected studies assessing the role of CTC number as prognostic or predictive biomarker in SCLC.
| Study [Ref] | Disease Stage | Treatment | Blood Sample Collection | Number of Patients | CTC Detection Method | Optimal Cut-Off | Main Findings |
|---|---|---|---|---|---|---|---|
| Hou et al. [13] | LS- and ES-SCLC | Chemotherapy | Baseline, days 2 and 22 after the treatment | 50 | CellSearch | No cut-off | Patients with a high number of CTCs (> 300) had a shorter median OS than patients with a low number of CTCs (< 2) (134 vs. 443 days). A persistently elevated CTC number at day 22 after treatment was considered an adverse prognostic factor at univariate analysis. |
| Hou et al. [41] | LS- and ES-SCLC | Chemotherapy | Baseline, post cycle 1 | 97 | CellSearch | 50 CTCs/7.5 mL blood | Patients with a CTC number > 50 had a shorter median PFS (4.6 versus 8.8 months) and OS compared to those with a CTC number < 50 (5.4 versus 11.5 months) at baseline. A number of CTC < 50 after one cycle of chemotherapy was associated with longer PFS and OS. At multivariate analysis, the CTC number at baseline was an independent prognostic factor for PFS (HR = 2.01) and OS (HR = 2.45). |
| Naito et al. [14] | LS- and ES-SCLC | Chemotherapy or chemoradiotherapy | Baseline, post treatment, at relapse | 51 | CellSearch | 8 CTCs/7.5 mL blood | Patients with a CTC count < 8 at baseline had longer OS than patients with CTC ≥8. Patients with a CTC count ≥8 after treatment and at relapse had a worse OS as compared with those with <8 CTCs at the same time points. |
| Hiltermann et al. [15] | LS- and ES-SCLC | Chemotherapy | Baseline, post cycle 1 and 4 | 59 | CellSearch | 2 CTCs/7.5 mL blood | Patients with a CTC count < 2 had longer OS than patients with a CTC number > 215 (729 vs. 157 days). At multivariate analysis, CTC count was an independent prognostic factor for PFS and OS at all time points. No correlations were observed between the decrease in CTC number from baseline to after one cycle of chemotherapy, and/or the absolute number of CTCs after one cycle of chemotherapy and response to treatment. |
| Cheng et al. [42] | ES-SCLC | Chemotherapy | Baseline, post cycle 2 and at progression | 91 | CellSearch | 10 CTCs/7.5 mL blood | Patients with a CTC count ≥ 10 at baseline had significantly shorter OS as compared with patients with a CTC count < 10 (8.2 vs. 16.6 months); no difference in PFS between the groups was observed. |
| Aggarwal et al. [21] | LS- and ES-SCLC | Chemotherapy or chemoradiotherapy | Baseline, during cycles 1, 2 (days 2, 3), 3,4 (day 1) and at relapse | 50 | CellSearch | 5 CTCs/7.5 mL blood 50 CTCs/7.5 mL blood |
Patients with a CTC count < 5 at baseline had better PFS than patients with CTCs ≥ 5 (11 vs. 6.7 months). Using a cut-off of 50 CTCs, for patients with <50 CTCs, PFS and OS were both significantly longer compared to patients with CTCs ≥ 50. At multivariate analysis, a higher CTC count at baseline was associated with a high hazard of death and progression. The decrease in CTCs during the course of therapy was not significantly associated with the response. |
| Messaritakis et al. [20] | LS- and ES-SCLC | Chemotherapy | Baseline, after 1 cycle and at progression | 83 | CellSearch | 5 CTCs/7.5 mL blood | Patients with a high number of CTCs had a significantly shorter median PFS and OS compared to patients with a low number of CTCs, irrespective of the time of CTC enumeration. At multivariate analysis, the detection of CTCs at baseline was considered as an independent factor associated with decreased PFS, whereas CTC count at progression was associated with a reduced OS. A significantly higher number of CTCs at baseline was observed in patients with PD compared to patients who experienced a CR/PR or SD. |
| Normanno et al. [43] | ES-SCLC | Chemotherapy | Baseline, post cycle 1 | 60 | CellSearch | No cut-off | A CTC count reduction higher than 89% following chemotherapy was associated with a lower risk of death. |
| Huang et al. [44] | ES-SCLC | Chemotherapy | Baseline and within 4 weeks after chemotherapy | 26 | CellSearch | No cut-off | A trend toward significance was observed between baseline CTCs and the percentage of change from post-treatment to baseline and OS |
| Igawa et al. [39] | LS- and ES-SCLC | Chemotherapy or chemoradiotherapy | Baseline, at cycle 2 and 3, post cycle 4 and at progression | 30 | TelomeScan | 2 CTCs/7.5 mL blood | Patients with a baseline CTC count < 2 had a significantly longer OS than patients with a CTC count ≥ 2. |
| Wang et al. [40] | LS- and ES-SCLC | Chemotherapy | Baseline, post cycle 1 | 42 | Negative immunomagnetic enrichment | 2 CTCs/7.5 mL blood | A CTC number ≥2 at baseline and after the first cycle of chemotherapy was significantly associated with worse PFS. |
| Tay et al. [45] | LS-SCLC | Chemoradiotherapy | Baseline | 75 | CellSearch | 2 CTCs/7.5 mL blood 15 CTCs/7.5 mL blood 50 CTCs/7.5 mL blood |
A number of 2 or 15 or 50 CTCs at baseline significantly correlated with PFS and OS. Patients with a CTC number < 15 had a better median PFS (19.0 months vs. 5.5 months) and OS (26.7 months vs. 5.9 months) than patients with a CTC number ≥15. At multivariate analysis only the 15 CTC cut-off emerged as an independent prognostic marker |
Abbreviations: limited stage disease (LS-SCLC); extensive stage disease (ES-SCLC); progression-free survival (PFS); overall survival (OS).