Abstract
BackgroundThe highly heterogeneous characteristics of GC may limit the accuracy of a single biomarker for screening populations benefiting from immunotherapy. However, the combination of multiple indicators can provide more directed information for the detection of potential immune benefit subgroups. At present, there are no recognized complex indexes to identify advanced GC (AGC) in patients who likely benefited from immunotherapy. The objective of this research is to explore whether the composite biomarker of derived neutrophil–lymphocyte ratio (dNLR) and platelet–lymphocyte ratio (PLR) can be used as a reliable prognostic factor for the survival of AGC patients receiving immunotherapy.MethodsFrom December 2014 to May 2021, a total 238 AGC patients at a single Center were included in this retrospective cohort research study. The cutoff value of dNLR was obtained by the ROC curves to predict the disease progression rate at the 8th month and the cutoff value of PLR was estimated by the median value. The cutoff values of dNLR and PLR were 1.95 and 163.63, respectively. The high levels of dNLR (≥1.95) and PLR (≥163.63) were considered to be risk factors. Based on these two risk factors, patients were categorized into 3 groups: the risk factor number for the “good” group was 0, that for the “intermediate” group was 1, and that for the “poor” group was 2. The subjects were divided into two groups: dNLR/PLR-good and dNLR/PLR-intermediate/poor.ResultsOf the 238 patients, the median overall survival (mOS) and progression-free survival (mPFS) were 12.5 and 4.7 months, respectively. Multivariate analysis revealed that the good dNLR/PLR group was independently associated with better prognosis. The intermediate/poor dNLR/PLR group was independently correlated with an over 1.4 times greater risk of disease progression (4.1 months vs. 5.5 months; p = 0.016) and an over 1.54 times greater risk of death (11.1 months vs. 26.3 months; p = 0.033) than the good dNLR/PLR group. However, no clear differences in the disease control rate (DCR) and overall response rate (ORR) were observed between the intermediate/poor dNLR/PLR group and the good dNLR/PLR group (51.5% vs. 56.3%, 26.3% vs. 29.6%; p = 0.494, p = 0.609).ConclusionOur study firstly verifies that the composite biomarker of dNLR and PLR is an independent prognostic factor affecting survival of advanced AGC patients receiving immunotherapy. It may be difficult for patients with the intermediate/poor dNLR/PLR group to benefit from immunotherapy.
Highlights
Gastric cancer (GC) is one type of very common gastrointestinal tumors around the world
121 patients were elders (≥58 years); 188 patients were male, 63 patients had Cardia, 99 had body/fundus, and 76 patients had pylorus cancer; 223 patients had ECOG Eastern Cooperative Oncology Group performance status scores (PS) scores of 0–1; 33 patients had positive HER-2 expression, 163 patients had a negative expression, and 42 patients were untested; 118 patients had poor tumor differentiation, 101 patients had moderate tumor differentiation, 4 patients had good tumor differentiation, and tumor differentiation was unknown for 15 patients; 12 patients had pleural fluid; 54 patients had ascites; 22 patients had bone metastases before immunotherapy
71 patients were in the good derived neutrophil–lymphocyte ratio (dNLR)/platelet–lymphocyte ratio (PLR) group and 167 patients were in the intermediate/poor dNLR/PLR group
Summary
Gastric cancer (GC) is one type of very common gastrointestinal tumors around the world. The “CheckMate 649” study explored whether the nivolumab-based first-line immunotherapy was suitable for advanced GC (AGC) [7]. Moehler et al found that patients treated with a combination of nivolumab and chemotherapy showed consistent overall survival (OS) benefits in the whole population and the Chinese subgroup, regardless of the expression status of programmed death ligand-1 (PD-L1) [8]. The first result of the “KEYNOTE811” study showed that HER2-positive metastatic gastric or gastroesophageal junction cancer could benefit from using the combination of pembrolizumab, trastuzumab, and chemotherapy [9]. There is a lack of effective biomarkers that can be used as prognostic factors for AGC-treated patients with immune checkpoint inhibitors (ICIs). The objective of this research is to explore whether the composite biomarker of derived neutrophil–lymphocyte ratio (dNLR) and platelet–lymphocyte ratio (PLR) can be used as a reliable prognostic factor for the survival of AGC patients receiving immunotherapy
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