The identification of biomarkers related to treatment in patients with non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICIs) represents a significant challenge. The aim of this study was to determine the predictive value of macrophage-related markers assessed in plasma and tissue samples of patients with NSCLC undergoing ICI treatment. This bicentric study included a prospective cohort of 88 patients with advanced NSCLC who received first-line therapy with ICI (either as monotherapy or in combination with chemotherapy) or chemotherapy alone (CT). Samples were collected from the patients at baseline and during follow-up. Plasma levels of CSF-1 and IL-34 were measured using ELISA, while expression levels of the macrophage receptors CD163 and CSF-1-R were evaluated using immunohistochemistry on lung biopsies. At baseline, the median plasma CSF-1 expression was higher in patients who did not respond to immunotherapy compared to those who responded (8898 pg/mL vs. 14031 pg/mL, p = 0.0005). Importantly, high CSF-1 levels at the initial assessment were associated with disease progression regardless of the treatment received. Furthermore, high CSF-1 levels were associated with shorter progression-free survival (PFS) and overall survival (OS) in patients receiving ICI therapy, but not in those treated with chemotherapy. There was no correlation between IL-34, CSF-1R, CD163 and therapeutic response. We observed in vitro that the activation of lymphocytes mediated by pembrolizumab was hindered by the treatment of PBMC with recombinant CSF-1, suggesting that CSF-1 creates a systemic immunosuppressive state that interferes with ICI treatment. In conclusion, baseline CSF-1 levels represent a potential predictive marker to ICI treatment in NSCLC.
Recent data suggested a role of gut microbiota and antibiotic use on immune checkpoint inhibitors efficacy. We aimed to evaluate the impact of early use of antibiotic (EUA), blood microbiome and plasmatic citrulline (marker of the intestinal barrier) on nivolumab efficacy in non-small cell lung cancer (NSCLC).We included all consecutive patients with advanced NSCLC treated with nivolumab in our Department between 2014 and 2017. Blood microbiome was analyzed at month (M) M0 and M2. Citrulline rates were evaluated at M0, M2, M4 and M6.Seventy-two patients were included (EUA in 42%). Overall survival (OS) was longer without EUA (median 13.4 months) than with EUA (5.1 months, p = 0.03). Thirty-five patients (49%) had plasma samples available. High citrulline rate (≥20 μM) at M0 was associated with tumor response (p = 0.084) and clinical benefit (nivolumab > 6 months) (p = 0.002). Median progression-free survival (PFS) was 7.9 months (high citrulline) vs 1.6 months (low citrulline) (p < 0.0001), and median OS were respectively non reached vs 2.2 months (p < 0.0001). Patients with EUA had lower median citrulline rates at M0: 21 μM (IQR 15.0-30.8) vs 32 μM (IQR 24.0-42.0) without EUA (p = 0.044). The presence of specific bacterial DNA in blood at M0 was associated with response and clinical benefit (Peptostreptococcae, Paludibaculum, Lewinella) or with tumor progression (Gemmatimonadaceae). Multivariate analyses on PFS and OS confirmed the prognostic role of citrulline and blood microbiome.EUA is associated with shorter OS with nivolumab and lower citrulline rates. Plasma citrulline and blood microbiome appear to be promising predictive factors of nivolumab efficacy.
In Brief Objective: The aim of the study was to evaluate the prognostic value of the ratio of metastatic to examined lymph nodes (LNR) in patients with rectal cancer. Summary Background Data: Lymph nodes ratio (LNR) has been shown to have prognostic value in patients with colon cancer. The impact of LNR on disease-free and overall survival in patients with rectal cancer is unknown. Patients and Methods: From 1998 to 2004, 307 patients underwent rectal resection for adenocarcinoma. The relationships between overall and disease-free survival at 3 years and 15 variables, including the presence or absence of metastatic lymph nodes, the total number of lymph nodes examined, and LNR, were analyzed by multivariate analysis. Patients were then assigned to 4 groups based on LNR: LNR = 0 (N0 patients), LNR = 0.01 to 0.07, LNR >0.07 to 0.2, LNR >0.2. Results: The mean number of lymph nodes examined was 22 ± 12. In the multivariate analysis, LNR was a significant prognostic factor for both disease-free (P = 0.006) and overall survival (P = 0.0003), whereas the presence or absence of metastatic lymph nodes was not. LNR remained a significant prognostic factor in the 59 patients in whom fewer than 12 lymph nodes were examined (P = 0.0058). According to LNR values, disease-free and overall survival decreased significantly with increasing LNR (P < 0.001). Conclusions: LNR is the most significant prognostic factor for both overall and disease-free survival in patients with rectal cancer, even in patients with fewer than 12 lymph nodes examined. The prognostic value of the ratio of metastatic to examine lymph nodes was evaluated in 307 patients with rectal cancer. Lymph node ratio is the most significant prognostic factors for both overall and disease-free survival in patients with rectal cancer, even in patients with fewer than 12 lymph nodes examined.
Background Helicobacter pylori detection by standard methods may be altered by proton pump inhibitor (PPI) use. However, some patients cannot or should not interrupt PPI use before undergoing testing for H. pylori . Polymerase chain reaction (PCR) could allow more reliable H. pylori detection even in patients taking PPIs. Objective The aim of our study is to compare the H. pylori infection diagnostic value of histological examination without and with immunohistochemical staining, bacterial culture and PCR, in PPI‐treated vs untreated patients. Methods Patients undergoing a gastric endoscopy for upper digestive symptoms were included. Gastric biopsy samples were obtained. The impact of taking PPI on the diagnostic performance of the different methods was studied. PCR results were confirmed by sequencing the glmM gene. Results A total of 497 patients were included, of whom 192 were H. pylori positive. Fifty‐two patients received PPIs during the 14 days preceding the endoscopy while 140 did not. All methods had lower sensitivity than PCR, in all cases (PPI treatment or not). PPI use did not change significantly the methods’ sensitivities. Conclusion The PCR method showed the best performance for the detection of H. pylori in gastric samples, whether or not patients received previous PPI treatment. This diagnosis test could become a new gold‐standard test, especially in patients undergoing PPI treatment.
