Controlling Nutritional Status (CONUT) Predicts Survival in Gastric Cancer Patients With Immune Checkpoint Inhibitor (PD-1/PD-L1) Outcomes

Abstract

Objective: The controlling nutritional status (CONUT), based on total lymphocyte count (TL), total cholesterol level (T-CHOL), and serum albumin (ALB), can provide a useful immunological prognostic biomarker for cancer patients. The present study aims to investigate the correlation between CONUT and prognosis in gastric cancer patients receiving immune checkpoint inhibitor (ICI) treatment.Methods: We retrospectively enrolled 146 patients with gastric cancer treated with ICIs (PD-1/PD-L1 inhibitors) from August 2016 to December 2020. The clinicopathologic characteristics were analyzed by Chi-square test or Fisher’s exact test. The Kaplan–Meier and log-rank test were used to calculate and compare progression-free survival (PFS) and overall survival (OS). The prognostic and predictive factors of PFS and OS were identified by univariate and multivariate analyses. A nomogram was developed to estimate 1-, 3-, and 5-year PFS and OS probability.Results: Through the CONUT score, there were 75 (51.37%) patients in the low CONUT group and 71 (48.63%) patients in the high CONUT group. There was a correlation between the CONUT score and age (p = 0.005), pathology (p = 0.043), ALB (p = 0.020), PALB (p = 0.032), and Hb (p = 0.001). The CA724, TNM stage, and treatment (ICIs vs. chemotherapy) were the independent prognostic factors for PFS and OS by multivariate analyses. Patients with high CONUT score had poorer PFS and OS (χ2 = 3.238, p = 0.072, and χ2 = 4.298, p = 0.038). In the subgroup analysis, the patients with high CONUT score were associated with shorter PFS and OS with ICIs or chemotherapy. With the PD-1/PD-L1 positive expression, the patients with high CONUT score had shorter PFS and OS than those with low CONUT score. Furthermore, the patients with high CA724 value were associated with shorter PFS and OS. The toxicity assessment in ICIs or chemotherapy was significantly associated with anemia. The nomograms were constructed to predict the probability of 1-, 3-, and 5-year PFS, and 1-, 3-, and 5-year OS with C-indices of 0.749 and 0.769, respectively.Conclusion: The CONUT, as a novel immuno-nutritional biomarker, may be useful in identifying gastric cancer patients who are unlikely to benefit from ICI treatment.

The association between albumin levels and survival in patients treated with immune checkpoint inhibitors: A systematic review and meta-analysis

“…Several studies in patients treated with chemotherapy, radiotherapy, or targeted therapy have demonstrated a higher risk of mortality or progression with lower albumin levels (Ikeda et al, 2017;Iede et al, 2022;Sun et al, 2022). Similarly, albumin levels could also be used for prognosis estimation in ICI-treated patients (Stares et al, 2021;Chen et al, 2022;Guo et al, 2022;Yoo et al, 2022). However, the data on the albumin in ICI-treated patients are limited, with heterogeneous patient cohorts, small sample sizes, and variable cut-offs.…”

Nutritional index for immune-checkpoint inhibitor in patients with metastatic gastro-esophageal junction/gastric cancer

“…It combines the serum albumin, a proxy of nutritional status and a marker of stem-cell differentiation and apoptosis (25)(26)(27)(28), and the total lymphocyte count, that is known to be positively associated with response to chemotherapy and survival in mGOJ/GC (29,30). Hypoalbuminemia especially is commonly studied alone (21) or in combination with other lab values as neutrophil-to-lymphocyte ratio, CRP (31), serum lactate dehydrogenase (32) or total cholesterol level (33) as a negative predictor of treatment outcome in mGOJ/GC patients treated with anti-PD-1 agents. In our work, albumin level confirmed its prognostic value in univariate but not in multivariate analysis, while PNI retained significance value at P<0.05.…”

The Association Between Albumin Levels and Survival in Patients Treated with Immune Checkpoint Inhibitors: A Systematic Review and Meta-analysis

“…Fifteen studies were included in the meta-analyses for PFS [25, 32, 33, 36, 40-42, 48-50, 52, 53, 57, 60, 63, 66]. Nine studies were reported signi cantly lower PFS in patients with lower albumin levels, while the association between the albumin levels and PFS was not reached statistical signi cance in remaining six studies [32,49,50,53,57,66]. In the meta-analysis of fteen studies, the patients with lower albumin levels had increased risk of progression or death compared to patients with higher albumin levels (HR: 1.74, 95% CI: 1.39-2.17, p<0.001) (Figure 4).…”

“…Several studies in patients treated with chemotherapy, radiotherapy or targeted therapy demonstrated the higher risk of mortality or progression with lower albumin levels [28][29][30]. Similarly, the albumin levels could be also used for prognosis estimation in ICI-treated patients [31][32][33][34]. However, the data on albumin in ICI-treated patients are limited with heterogeneous patient cohorts, sample sizes and variable cut-offs.…”