Dynamic changes of phenotypically different circulating tumor cells sub-populations in patients with recurrent/refractory small cell lung cancer treated with pazopanib.

The aim of the study was to investigate the effect of 2nd-line pazopanib on the different CTCs subpopulations in SCLC patients and evaluate the clinical relevance of their changes. Different CTCs subpopulations were evaluated before pazopanib initiation (n = 56 patients), after one-cycle (n = 35) and on disease progression (n = 45) by CellSearch and double immunofluorescence using anti-CKs and anti-Ki67, anti-M30 or anti-Vimentin antibodies. Before treatment, CTCs were detected in 50% of patients by CellSearch whereas 53.4%, 15.5% and 74.1% patients had CK+/Ki67+, CK+/M30+ and CK+/Vim+ CTCs, respectively. One pazopanib cycle significantly decreased the number of CTCs as detected by CellSearch (p = 0.043) as well as the number of CK+/Ki67+ (p < 0.001), CK+/M30+ (p = 0.015) and CK+/Vim+ (p < 0.001) cells. On disease progression, both the incidence and CTC numbers were significantly increased (CellSearch, p = 0.027; CK+/Ki67+, p < 0.001; CK+/M30+, p = 0.001 and CK+/Vim+, p < 0.001). In multivariate analysis, the detection of CK+/Vim+ CTCs after one treatment cycle (HR: 7.9, 95% CI: 2.9-21.8; p < 0.001) and CTCs number on disease progression, as assessed by CellSearch, (HR: 2.0, 95% CI: 1.0-6.0; p = 0.005) were emerged as independent factors associated with decreased OS. In conclusion, pazopanib can eliminate different CTC subpopulations in patients with relapsed SCLC. The analysis of CTCs could be used as a dynamic biomarker of treatment efficacy.

TTF-1- and/or CD56-positive Circulating Tumor Cells in patients with small cell lung cancer (SCLC).

The aim of the study was to evaluate the phenotypic CTCs heterogeneity (TTF-1+ and/or CD56+) in SCLC patients and correlate it with the CellSearch. Peripheral blood was obtained from 108 consecutive patients. CTCs were detected by CellSearch and double-immunofluorescence using anti-CD45, anti-TTF-1 and anti-CD56 antibodies. Before chemotherapy TTF-1+/CD45-, CD56+/CD45- and TTF-1+/CD56+ CTCs were detected in 66(61.1%), 55(50.9%) and 46(42.6%) patients, respectively; 60.2% of patients were CellSearch+. Among the 22 patients with 0 CTCs/7.5 ml on CellSearch, TTF-1+/CD45-, CD56+/CD45- and TTF-1+/CD56+ CTCs were detected in 8(36.4%), 6(27.3) and 6(27.3%) patients, respectively; no CK+/EpCAM+ or TTF1+/EpCAM+ CTCs were detected in these patients. One-chemotherapy cycle decreased both the number of positive patients (p < 0.001) and their CTC number (p < 0.001), irrespectively of their phenotype and the detection method. The incidence and number of the different CTC subpopulations on PD, was significantly increased at their baseline levels. Multivariate analysis revealed that the increased number of CTCs at baseline and on PD were significantly associated with decreased PFS (p = 0.048) and OS (p = 0.041), respectively. There is an important CTC heterogeneity in such patients according to the expression of TTF-1 and CD56 which could detect EpCAM- CTC subpopulations and, thus, undetectable by CellSearch. These CTC subpopulations are dynamically correlated with treatment efficacy and disease-progression.

Postoperative treatment with docetaxel, cisplatin, and capecitabine (DCX) and chemoradiotherapy (CRT) with capecitabine for resected gastric adenocarcinoma.

INTRODUCTION: We conducted a feasibility study on docetaxel/capecitabine/cisplatin (DCX) with chemoradiotherapy as adjuvant treatment for gastric cancer patients. METHODS: Patients were scheduled to receive 2 cycles of DCX, followed by 50.4 Gy plus capecitabine as radiotherapy, followed by an additional 2-DCX cycles. RESULTS: From the 40 enrolled patients, 26 (65%) completed treatment as per protocol and 14 (35%) discontinued with the treatment (patients' refusal: n=6; adverse events: n=8). There were 2 toxic deaths. Grade >3 toxicity was 12.1% before and 13.3% after chemoradiotherapy. Disease progression was documented in 11 (27.5%) patients. CONCLUSIONS: No further development of this regimen is justified on the basis of poor tolerability in patients.