Circulating Tumor Cells and Metabolic Parameters in NSCLC Patients Treated with Checkpoint Inhibitors

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.

Soluble PD-L1 in NSCLC Patients Treated with Checkpoint Inhibitors and Its Correlation with Metabolic Parameters

“…This is in line with a recent study of Vecchiarrelli and colleagues, who demonstrated a positive correlation between sPD-L1 levels and metastatic sites [ 13 ]. Even though this finding need to be confirmed in a larger cohort, the combination of sPD-L1 levels along with metabolic parameters could be useful for treatment optimization, allowing to identify non-responder patients already at baseline, as demonstrated by our group and others [ 14 , 15 ]. Previously, we have documented the potential prognostic role of combined sPD-L1 and metabolic parameters already in NSCLC candidate patients of surgery [ 16 ].…”

Perspectives on liquid biopsy for label‐free detection of “circulating tumor cells” through intelligent lab‐on‐chips

“…In melanoma‐treated patients, changes in CTC counts precede standard clinical assessment and are highly predictive of long‐term clinical outcomes 38 . In nonsmall cell lung carcinoma (NSCLC)‐treated patients, elevated CTCs count correlates with highly glycolytic tumors that can potentially metastasize at distant sites 39 …”

Positron Emission Tomography-Based Response to Target and Immunotherapies in Oncology

“…In conclusion, despite the more effective way of assessing the [ 18 F]FDG PET-based response in patients treated with ICPIs, available studies suggest that [ 18 F]FDG PET can support decision-making about the continuation/discontinuation of therapy, as it can open several windows able to capture different aspects associated with the effect of treatment (i.e., pseudoprogression, hyperprogression, and IRAE) [56]. Table 2 reports the characteristics of published studies involving the use of [ 18 F]FDG PET to assess the response to ICI [46][47][48]50,51,54,[57][58][59][60][61][62][63][64][65][66][67][68]. Figure 2 shows a representative example of baseline and post-treatment [ 18 F]FDG PET in a patient with advanced NSCLC treated with Nivolumab.…”