Circulating Endothelial Cells for Evaluation of Tumor Response in Non-Small Cell lung cancer patients receiving first-line chemotherapy

2015 ◽  
Vol 30 (4) ◽  
pp. 374-381
Author(s):  
Fadi Najjar ◽  
Ghassan Al-Massarani ◽  
Israa Banat ◽  
Moosheer Alammar

Background Circulating endothelial cells (CECs) reflect the neovascularization in the tumor mass. We therefore investigated the potential role of CEC kinetics after first-line chemotherapy in advanced non-small cell lung cancer (NSCLC) patients. Methods Peripheral blood samples were obtained from 45 healthy subjects and 51 naïve patients with advanced NSCLC. Quantification of CD146+ CECs was performed using immunomagnetic separation (IMS). Results Pretreatment and posttreatment CEC levels in NSCLC patients were significantly higher than in healthy subjects (p<0.0001). An objective response was achieved after chemotherapy with partial response (PR) or stable disease (SD) in 26 patients, whereas the remaining 25 patients had progressive disease (PD). Baseline CEC levels were significantly higher in PR/SD patients than in PD patients (p = 0.039). After chemotherapy, CEC count significantly decreased in PR/SD patients (p = 0.014) and increased in patients with PD (p = 0.019). Moreover, there was a significant difference in the percentage change of CEC counts between the 2 groups (p = 0.0016). No significant difference in the median progression-free survival and overall survival (OS) was observed between patients with high baseline CEC counts and those with low baseline CEC levels. However, patients with high percentage change in CEC count had longer OS than those with low percentage change after chemotherapy (p = 0.05). Conclusions Changes in CEC counts after chemotherapy reflect tumor response in advanced NSCLC patients. Moreover, high percentage changes in CEC counts after chemotherapy may predict longer OS in advanced NSCLC. High baseline CEC levels might be an indicator of tumor response in advanced NSCLC patients after first-line chemotherapy.

2021 ◽  
Vol 11 ◽  
Author(s):  
Ze Peng ◽  
Wen Wen Wu ◽  
Ping Yi

Background: For advanced non-small cell lung cancer (NSCLC) patients, first-line chemotherapy is the main treatment in the clinic despite its efficacy is limited and adverse effects are always inescapable. Ginsenoside Rg3, an anti-cancer active ingredient by suppressing angiogenesis, has been increasingly widely used as an adjuvant in first-line chemotherapy for advanced NSCLC to optimize treatment in China. However, no comprehensive meta-analyses have been conducted to estimate the efficacy and safety of the therapy combining ginsenoside Rg3 and first-line chemotherapy in advanced NSCLC patients.Methods: Randomized controlled trails using a combination of first-line chemotherapy and ginsenoside Rg3 for advanced NSCLC patients were searched and selected from six databases. The Cochrane Risk of Bias tool was used to assessed the quality of these selected original researches. And we used Review Manager 5.3 and STATA to analyze the data.Results: Twenty-two RCTs that matched our selection criteria with a number of 2202 patients were included in our review. The results showed that compared with first-line chemotherapy alone, the combination of ginsenoside Rg3 and first-line chemotherapy could better improve the objective response rate (ORR) (RR [95% CI], 1.44 [1.27, 1.63], p &lt; 0.00001 ), the disease control rate (DCR) (RR [95% CI], 1.24 [1.12, 1.38], p &lt; 0.0001), karnofsky performance status (KPS) (RR [95% CI], 1.62 [1.42, 1.84], p &lt; 0.00001), one-year survival rate (RR [95% CI], 1.49 [1.08, 2.06], p = 0.01), two-year survival rate (RR [95% CI], 6.22 [1.68, 22.95], p = 0.006), weight change (RR [95% CI], 1.31 [1.04, 1.66], p = 0.02), and higher reduce the VEGF levels (RR [95% CI], -2.21 [-4.03, -0.38], p = 0.02), the incidence of gastrointestinal reactions (RR [95% CI], 0.66 [0.47, 0.93], p = 0.02) and bone marrow suppression (RR [95% CI], 0.43 [0.30, 0.61], p &lt; 0.00001).Conclusion: Ginsenoside Rg3 can enhance drug efficacy and reduce drug-induced toxicity from chemotherapy. These findings provide helpful information for clinicians indicating that a therapy combined of ginsenoside Rg3 and first-line chemotherapy may be used to optimal the treatment of advanced NSCLC.


2021 ◽  
Author(s):  
Ching-Yi Chen ◽  
Chi-Hsien Huang ◽  
Wang-Chun Chen ◽  
Ming-Shyan Huang ◽  
Yu-Feng Wei

Abstract Backgrounds: Immune checkpoint inhibitors (ICIs) alone or in combination with chemotherapy (CT) are the standard of care for first-line therapy in metastatic non-small cell lung cancer (NSCLC) patients without actionable mutations. The safety ranking of different ICI and CT combination regimens has not been investigated. This study was aimed to provide a toxicity profile and safety ranking of different ICI and CT combination regimens.Methods: We performed comprehensive searches of phase 2 and 3 randomized clinical trials (RCTs) comparing different ICI regimens (alone or combination) or CT for the first-line treatment of advanced NSCLC. Outcomes of interest were the cumulative incidence of any treatment-related adverse events (TRAEs), grade 3-5 TRAEs (grade 3-5), any immune-related adverse events (irAEs), and grade 3-5 irAEs (grade 3-5). Odds ratios and 95% credible intervals were calculated as summary statistics to quantify the effect of different ICI combination regimens. Results: We included 23 RCTs from 2016 to 2021 with a total of 14,378 patients. The incidence of any TRAEs and grade 3-5 TRAEs ranked from high to low were ICI-CT (probability: 74.88%), ICI-ICI-CT (50.60%), CT alone (74.79%), ICI-ICI (98.37%), and ICI monotherapy (99.37%). Adding CT to ICI regimens resulted in a higher incidence of any grade or grade 3-5 TRAEs compared to ICI-ICI combinations or ICI monotherapy. However, ICI-ICI-CT combinations did not result in a higher incidence of TRAEs than ICI-CT combinations. For any irAEs and grade 3-5 irAEs, the ranking was ICI-ICI (probability: 97.38), ICI monotherapy (96.98%), ICI-CT (99.44%), and CT alone (99.98%). Notably, the incidence of any grade and grade 3-5 irAEs was lower when adding CT to ICI monotherapy. Conclusion: Lack of head-to-head comparisons, these findings provide evidence for clinical decision-making when considering different ICI combination regimens for advanced NSCLC patients.


2017 ◽  
Vol 37 (4) ◽  
Author(s):  
Yueming Wu ◽  
Jiang Feng ◽  
Weiwei Hu ◽  
Qingquan Luo

We performed a randomized and placebo-controlled clinical study to investigate whether nab-paclitaxel can improve survival in patients with advanced non-small cell lung cancer (NSCLC) after unsuccessful first-line chemotherapy. Patients with stages III to IV advanced NSCLC after first-line platinum-based chemotherapy failure were randomly assigned in a 1:1 ratio to receive second-line treatment of nab-paclitaxel or placebo. Ninety two eligible patients were enrolled in the study. The median progression-free survival (PFS) was 4.6 months (95% confidence interval (CI): 3.4–6.7 months) for nab-paclitaxel, compared with 2.0 months (95% CI: 0.9–4.3 months) for placebo, representing a 56% reduction in disease progression (hazard ratio: 0.62; 95% CI: 0.33–0.81; P<0.001). The median overall survival (OS) was 6.3 months (95% CI: 3.9–8.2 months) for nab-paclitaxel, compared with 4.9 months (95% CI: 2.1–5.9 months) for placebo, representing a 22% reduction in disease progression (hazard ratio: 0.71; 95% CI: 0.33–0.85; P<0.001). Adverse events (AEs) were also observed for nab-paclitaxel. Nab-paclitaxel can improve survival in patients with advanced NSCLC after unsuccessful first-line chemotherapy.


2021 ◽  
Vol 10 (7) ◽  
pp. 1365
Author(s):  
Margarita Majem ◽  
Manuel Cobo ◽  
Dolores Isla ◽  
Diego Marquez-Medina ◽  
Delvys Rodriguez-Abreu ◽  
...  

Programmed cell death-ligand 1 (PD-L1) has emerged as a potential biomarker for selection of patients more likely to respond to immunotherapy and as a prognostic factor in non-small cell lung cancer (NSCLC). In this network meta-analysis, we aimed to evaluate the efficacy of first-line anti-PD-(L)1 monotherapy in advanced NSCLC patients with high PD-L1 expression (≥50%) compared to platinum-based chemotherapy. We also evaluated efficacy outcomes according to tumor mutational burden (TMB). To that end, we conducted a systematic review. Six clinical trials with 2111 patients were included. In head-to-head comparisons, immunotherapy showed a significant improvement in progression-free survival (PFS: HRpooled = 0.69, 95% CI: 0.52–0.90, p = 0.007), overall survival (OS: HRpooled = 0.69, 95% CI: 0.61–0.78; p < 0.001) and overall response rate (ORR) (Risk ratio (RR)pooled = 1.354, 95% CI: 1.04–1.762, p = 0.024). In the assessment of relative efficacy for PFS through indirect comparisons, pembrolizumab (results from KEYNOTE-024) ranked highest followed by cemiplimab and atezolizumab, with statistical significance determined for some of the drugs. In terms of OS, cemiplimab ranked highest followed by atezolizumab and pembrolizumab, although non-significant OS was determined for these drugs. In conclusion, PD-(L)1 inhibitor monotherapy improves efficacy outcomes in the first line setting of advanced NSCLC patients with high PD-L1 expression. Evaluations with longer follow up are still needed to determine the superiority of any specific drug.


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