Albumin-derived Neutrophil-to-Lymphocyte Ratio Score as a Marker of Nivolumab Treatment Sensitivity in Gastric Cancer: A Multicenter Study.

BACKGROUND/AIM: Establishment of powerful and easy-to-evaluate biomarkers that can predict immune checkpoint inhibitor sensitivity in patients with gastric cancer (GC) would be highly useful. The albumin-derived neutrophil-to-lymphocyte ratio (Alb-dNLR) score reportedly is an excellent measure of both immunity and nutritional status. However, the association between nivolumab treatment sensitivity and Alb-dNLR in GC has also not been adequately investigated. This multicenter retrospective study was designed to evaluate the association of Alb-dNLR with therapeutic sensitivity of nivolumab in GC patients. PATIENTS AND METHODS: This was a retrospective multicenter study with patients from five sites. The data from 58 patients who received nivolumab for postoperative recurrent or unresectable advanced GC between October 2017 and December 2018 were analyzed. Blood tests had been performed before nivolumab administration. We analyzed the correlation between the Alb-dNLR score and clinicopathological factors, including best overall response. RESULTS: Of the 58 patients, 21 (36.2%) comprised the disease control (DC) group and 37 (63.8%) comprised the progressive disease (PD) group. The nivolumab treatment responses were subjected to receiver operating characteristic analysis. The cutoff value was set to 2.90 g/dl for Alb and to 3.55 for dNLR. All eight patients in the high Alb-dNLR group had PD (p=0.0049). The low Alb-dNLR group had significantly better overall survival (p=0.0023) and progression-free survival rates (p<0.0001). CONCLUSION: The Alb-dNLR score was a very simple and sensitive predictor of nivolumab therapeutic sensitivity and has very good biomarker properties.

Examining the Efficacy of Nivolumab for Gastric Cancer Focusing on Using an Inflammation-based Prognostic Score: A Multicenter Retrospective Study.

BACKGROUND/AIM: To discover the positive therapeutic effects of nivolumab in patients with advanced gastric cancer (AGC), it is necessary to establish a useful biomarker to predict therapeutic efficacy. This multicenter retrospective study sought to evaluate the predictive impact of inflammation-based prognostic score (IBPS) on the therapeutic efficacy of nivolumab in patients with AGC. PATIENTS AND METHODS: In this retrospective study, we evaluated 58 AGC patients treated with nivolumab from October 2017 to November 2018 at five institutes. Patients were categorized follows: progressive disease (PD) or disease control (DC). Blood chemistry tests were performed immediately before and after two courses of nivolumab; the correlation between best overall response and IBPS was investigated. Transition of each blood serum marker was also assessed. RESULTS: Of 58 patients, 37 (63.8%) were in the PD group and 21 (36.2%) in the DC group. No positive correlation was noted between IBPS and therapeutic efficacy of nivolumab both immediately before and after two courses of nivolumab. However, the neutrophil-lymphocyte ratio (NLR) (p=0.045) and prognostic index (PI) (p=0.0042) before nivolumab and NLR (p=0.025), PI (p=0.0030) and Glasgow prognostic score (GPS) (p=0.043) after nivolumab were significantly correlated with treatment sensitivity. Furthermore, a decrease in PNI was an independent prognostic factor to predict nivolumab resistance on univariate analyses (p=0.0051). CONCLUSION: Although no association between IBPS and therapeutic sensitivity was found, it is important to focus on the transition of PNI to predict therapeutic efficacy of nivolumab.

Changes in the Gustave Roussy Immune Score as a Powerful Prognostic Marker of the Therapeutic Sensitivity of Nivolumab in Advanced Gastric Cancer: A Multicenter, Retrospective Study.

BACKGROUND: Identification of positive biomarkers for the effects of nivolumab on patients with advanced gastric cancer (AGC) is significant. The Gustave Roussy Immune Score (GRIm-s) is associated with therapeutic resistance of immune checkpoint inhibitors (ICIs) in other cancers. This multicenter, retrospective study was designed to analyze the association of GRIm-s with therapeutic sensitivity of nivolumab in patients with AGC. METHODS: We reviewed 58 patients with AGC treated with nivolumab from October 2017 to November 2018 at five participating institutions. We performed blood tests before the start of nivolumab and after administration of two courses. We evaluated the correlation between the best overall response and GRIm-s. Additionally, we focused on the changes in GRIm-s before the start of nivolumab and after administration of two courses. RESULTS: Of the 58 patients, 21 (36.2%) were classified into the disease control (DC) group and 37 (63.8%) into the progressive disease (PD) group. GRIm-s before nivolumab treatment did not correlate with the best therapeutic response (p = 0.086). However, GRIm-s after two courses of nivolumab showed that significantly more PD cases were in the high-risk group (p < 0.0001). After two courses of nivolumab, overall survival was significantly worse in the high-risk group (p < 0.0001). For progression-free survival, the high-risk group had a significantly worse prognosis both before (p = 0.04) and after two courses of nivolumab treatment (p < 0.0001). CONCLUSIONS: GRIm-s after two courses of nivolumab and its changes compared to pretreatment values proved beneficial in predicting nivolumab sensitivity.

Clinical features as potential prognostic factors in patients treated with nivolumab for highly pretreated metastatic gastric cancer: a multicenter retrospective study.

BACKGROUND: Although nivolumab (anti-programmed cell death-1 antibody) is a promising approach for advanced gastric cancer (AGC), the response rate remains limited. The aim of this multicenter retrospective study was to determine if clinical features could serve as prognostic factors of the efficacy of nivolumab in patients with AGC. METHODS: Fifty-eight patients with AGC who were treated with nivolumab as a third or later line from October 2017 to December 2018 at any of five clinical sites were enrolled in the study. The correlation between the best overall response and clinical features was investigated. Overall survival and progression-free survival after initiation of nivolumab were calculated and clinical features that could be predictors of the prognosis were sought. RESULTS: The disease control rate (DCR) for nivolumab was 36.2% and was significantly correlated with performance status (p = 0.021), metastasis to one organ (p = 0.006), and grade 2 or higher immune-related adverse events (p = 0.027). There was also a significant association between response to nivolumab and ability to receive subsequent chemotherapy (p = 0.022). In the analysis of overall survival, the following variables were identified as being significantly associated with a poor outcome: Eastern Cooperative Oncology Group performance status ≥1, prior treatment with trastuzumab, no immune-related adverse events, lack of a response to nivolumab, and inability to receive subsequent chemotherapy. CONCLUSION: The findings of this study suggest that nivolumab may be ineffective for AGC in patients with poor performance status and those with a history of treatment with trastuzumab.

Endoscopic characteristics influencing postpolypectomy bleeding in 1147 consecutive pedunculated colonic polyps: a multicenter retrospective study.

BACKGROUND AND AIMS: Postpolypectomy bleeding is the most common adverse event with pedunculated polyps. We clarified the endoscopic characteristics influencing postpolypectomy bleeding for pedunculated colonic polyps. METHODS: We reviewed clinical data for 1147 pedunculated colonic polyps removed by polypectomy in 5 Japanese institutions. Pedunculated polyps were defined as polyps with a stalk length ≥5 mm. Analyzed clinical data were age, sex, polyp location/size, stalk length/width, prophylactic clipping or endoloop before polypectomy, injecting the stalk, closing the polypectomy site, antithrombotic agent use, and endoscopist experience. Postpolypectomy bleeding was classified as immediate bleeding or delayed bleeding. RESULTS: Immediate and delayed bleeding was observed in 8.5% (97/1147) and 2% (23/1147) of polypectomies, respectively. Comparing immediate bleeding with nonbleeding, multivariate analysis showed that stalk width ≥6 mm (odds ratio [OR], 1.9; 95% confidence interval [CI], 1.1-3.4) was a significant risk factor for immediate bleeding. For polyp size ≥15 mm, prophylactic endoloop use (OR, .17; 95% CI, .04-.72) was a significant inhibiting factor. Comparing delayed bleeding with nonbleeding, multivariate analysis showed that prophylactic clipping before polypectomy (OR, 4.2; 95% CI, 1.3-13) and injecting the stalk (OR, 4.0; 95% CI, 1.4-12) were significant risk factors for delayed bleeding. CONCLUSIONS: The increased risk for delayed bleeding with injecting the stalk and prophylactic clipping before polypectomy suggests that simple resection with coagulation mode is a suitable strategy in endoscopic resection of pedunculated polyps. Moreover, prophylactic endoloop use was highly likely to inhibit immediate bleeding with polyp size ≥15 mm.