Abstract
Circulating tumor cells (CTC) count and characterization have been associated with poor prognosis in recent studies. Our aim was to examine CTC count and its association with metabolic parameters and clinical outcomes in non-small cell lung carcinoma (NSCLC) patients treated with immune checkpoint inhibitors (ICI). For this prospective study, data from 35 patients (23 males, 12 females) were collected and analyzed. All patients underwent an 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) scan and CTC detection through Isolation by Size of Tumor/Trophoblastic Cells (ISET) from peripheral blood samples obtained at baseline and 8 weeks after ICI initiation. Association of CTC count with clinical and metabolic characteristics was studied. Progression-free survival (PFS) and overall survival (OS) were analyzed using the Kaplan–Meier method and the log-rank test. Median follow-up was 13.2 months (range of 4.9–21.6). CTC were identified in 16 out of 35 patients (45.7%) at baseline and 10 out of 24 patients at 8 weeks (41.7%). Mean CTC numbers before and after 8 weeks were 15 ± 28 and 11 ± 19, respectively. Prior to ICI, the mean CTC number was significantly higher in treatment-naïve patients (34 ± 39 vs. 9 ± 21, p = 0.004). CTC count variation (ΔCTC) was significantly associated with tumor metabolic response set by European Organization for Research and Treatment of Cancer (EORTC) criteria (p = 0.033). At the first restaging, patients with a high tumor burden, that is, metabolic tumor volume (MTV) and total lesion glycolysis (TLG), had a higher CTC count (p = 0.009). The combination of mean CTC and median MTV at 8 weeks was associated with PFS (p < 0.001) and OS (p = 0.024). Multivariate analysis identified CTC count at 8 weeks as an independent predictor for PFS and OS, whereas ΔMTV and maximum standardized uptake value variation (ΔSUVmax) was predictive for PFS and OS, respectively. Our study confirmed that CTC number is modulated by previous treatments and correlates with metabolic response during ICI. Moreover, elevated CTC count, along with metabolic parameters, were found to be prognostic factors for PFS and OS.
Highlights
The introduction of antibodies against programmed cell death protein-1 (PD-1) and its ligand (PD-L1), a crucial axis involved in the immune surveillance, has prompted encouraging results in the treatment of advanced non-small cell lung carcinoma (NSCLC), only a minority of patients show clinical response [1]
On the basis of these premises, our aim was to examine circulating tumor cells’ (CTC) count in NSCLC patients treated with immune checkpoint inhibitors (ICI) and determine its relationship with metabolic parameters by
(71.4%the vs.three vs. 0%, considering changes (ΔCTC) within individual patients, among the 24 patients that respectively, p = 0.033)CTC. Had their CTC analyzed after 8 weeks of treatment, we found that the increase of CTC count was associated with poor response to ICI by means 18F-FDG positron emission tomography/computed tomography (PET/computed tomography (CT)), as poor response to metabolic disease (PMD) rates were significantly different between patients with CTC increase at 8 weeks and patients with stable or decreased number of CTC (71.4% vs. 28.6% vs. 0%, respectively, p = 0.033) (Table 1)
Summary
The introduction of antibodies against programmed cell death protein-1 (PD-1) and its ligand (PD-L1), a crucial axis involved in the immune surveillance, has prompted encouraging results in the treatment of advanced non-small cell lung carcinoma (NSCLC), only a minority of patients show clinical response [1]. Molecular characterization of CTC might expand our knowledge on tumor heterogeneity, especially in patients for whom tissue biopsies are difficult to perform [4,5,6,7,8]. Molecular imaging, using 18F-fluorodeoxyglucose (18F-FDG) with positron emission tomography/computed tomography (PET/CT), is widely applied in oncology as a useful marker of tumor biology. By differentiating higher versus less-active metabolic tumor tissues, semi-quantitative metabolic parameters can offer the possibility for non-invasive, in vivo tumor characterization and for correct evaluation of tumor response [9,10,11]. Available studies analyzing the association between 18F-FDG PET/CT and CTC in NSCLC are limited to chemotherapy-naïve patients or those treated with “traditional” antitumor drugs [12,13,14,15]
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