Background and Aims. Biomarkers for systemic inflammation have been introduced into clinical practice for risk-rating in cancer patients’ treatment. This study is aimed at confirming the prognostic role of the neutrophil-to-lymphocyte ratio (NLR) as an effective biomarker for patients with metastatic gastric cancer (MGC) receiving anti-PD-1 agents. Method. Patients with MGC who received anti-PD-1 treatment at the Chinese PLA General Hospital between January 2016 and November 2020 were reviewed. The study analyzed the association of NLR and overall survival (OS) or progression-free survival (PFS) and antitumor response rate with PD-1 inhibitors. Results. 137 patients were included in the final analysis. The area under the curve value of NLR for 6-month OS was 0.71. The best cut-off value for NLR was 3.23. was associated with longer OS ( , 95% CI, 0.26-0.57, ) and PFS ( , 95% CI, 0.29-0.62, ) in patients with MGC. No significant difference was observed in the objective response rate (ORR) (35.8% vs. 28.6%, ) and disease control rate (DCR) (86.4% vs. 78.6%, ) in the group and in the group, respectively. Univariate analysis and multivariate analysis found that NLR was an independent prognosis biomarker for PFS and OS. Conclusions. Pretreatment elevated NLR was significantly associated with inferior PFS and OS in patients with MGC who received anti-PD-1 inhibitors. Clinicians need to consider patients with elevated NLR for decisions on immunotherapy strategy.

Background: The role of HEPACAM family member 2 (HEPACAM2) is unclear in colorectal cancer (CRC). Objective: The objective of this study was to perform an extensive examination of HEPACAM2 and validate it experimentally in CRC. Methods: This study investigated the significance of HEPACAM2 in CRC and its potential diagnostic utility utilizing data from the Cancer Genome Atlas (TCGA) database. Additionally, the study examined potential regulatory networks involving HEPACAM2, including its associations with immune infiltration, immune checkpoint genes, tumor mutational burden (TMB), microsatellite instability (MSI), mRNA expression-based stemness index (mRNAsi), and drug sensitivity in CRC. The expression of HEPACAM2 was further validated using the GSE89076 dataset, and quantitative reverse transcription PCR (qRT-PCR) was employed to confirm HEPACAM2 expression levels in six pairs of CRC tissue samples. Results: HEPACAM2 exhibited abnormal expression patterns in various types of cancer, including CRC. A decrease in HEPACAM2 expression levels in CRC was found to be significantly correlated with the T stage (p < 0.001). Reduced HEPACAM2 expression in CRC patients was also linked to poorer overall survival (OS) (p = 0.007). The expression levels of HEPACAM2 in CRC patients were identified as an independent prognostic factor (p = 0.016). Furthermore, HEPACAM2 was associated with TCF-dependent signaling in response to WNT, G2/M checkpoints, and other pathways. The expression of HEPACAM2 in CRC was found to be associated with immune infiltration, immune checkpoint genes, TMB / MSI, and mRNAsi. Additionally, the expression of HEPACAM2 in CRC was significantly and inversely correlated with the drug sensitivities to gw772405x and 6-phenyl-6h-indeno[1,2-c]isoquinoline-5,11-dione. qRT-PCR confirmed that the expression level of HEPACAM2 was found to be lowly expressed in CRC tissues. Conclusion: These findings suggest that HEPACAM2 may serve as a potential prognostic biomarker and immunotherapeutic target for CRC patients.

Objective: PD-1 inhibitors have improved efficacy in many cancers. There are currently no reports of the use of PD-1 inhibitors, such as nivolumab, for metastatic biliary tract cancer (mBTC). This study reviewed the efficacy and safety of nivolumab for mBTC with the aim of exploring ways to improve efficacy and survival. Methods: Thirty patients with mBTC were voluntarily treated with nivolumab at the PLA General Hospital. Nivolumab 3 mg/kg was administered. Progression-free survival (PFS) and overall survival were evaluated by Kaplan–Meier and univariate and multivariate analyses were carried out for clinical characteristics. Objective response rate (ORR), disease control rate (DCR), and treatment-related adverse events (AEs) were also evaluated. Results: The median treatment cycle is four cycles. One case was complete response, 5 cases partial response, 12 cases stable, and 12 cases progression. ORR was 20%, DCR was 60%, and PFS was 3.1 months (95% CI: 2.13–4.06). The AEs of nivolumab monotherapy were fatigue (three cases), fever (two cases), hypothyroidism (one case), skin reaction (one case), and liver injury (one case). Nivolumab combined with chemotherapy related grade 1–2 hematologic toxicity were leukopenia (five cases) and thrombocytopenia (two cases), and grade 3–4 were leukopenia (three cases). Non-hematologic toxicity grade 1–2 were nausea and vomiting (four cases), fatigue (four cases), fever (three cases), peripheral neurotoxicity (three cases), and hypothyroidism (one case). Univariate analysis showed that PFS of nivolumab combined with chemotherapy was statistically significant compared with that of nivolumab monotherapy (4.1 vs 2.3 months, P=0.031). Programmed death-ligand 1 (PD-L1) expression positively has no relationship with better PFS in contrast with PD-L1 negatively (3.6 vs 3.0 months P>0.05). Multivariate analysis show nivolumab combined with chemotherapy was only the independent factor for longer PFS (HR: 0.432, P<0.05). Conclusion: The safety of nivolumab in mBTC is controllable. Further selection of superior populations is needed to improve the efficacy of nivolumab in mBTC.

Background: Previous investigations suggest that systemic inflammation markers are able to provide prognostic value in several cancers. This study seeks to characterize the ability of pretreatment platelet-to-lymphocyte ratio (PLR) to prognosticate advanced or metastatic gastric cancer patients (AGC or MGC, respectively) receiving immunotherapy. Methods: AGC and MGC patients exposed to PD-1 inhibitors from January 2016–August 2021 in the Chinese PLA General Hospital were recruited. Correlations between PLR and overall survival (OS), progression-free survival (PFS), and immunotherapy-associated tumor response rates were determined. Results: 237 patients were enrolled for this retrospective investigation. The 6 month and 12 month PFS based on the area under the curve value was 0.60 and 0.65 (p < 0.05). based on a calculated PLR cut-off value of 139.41, The PLR < 139.41 group has a longer OS in contrast with the PLR ≥ 139.41 group (13.46 m vs 10.71 m, HR = 0.57, 95% CI 0.42–0.78, p = 0.004). The PLR < 139.41 group had a PFS of 7.93 m in contrast to the 4.75 m seen in those with PLR ≥ 139.41 group (HR = 0.57, 95% CI 0.43–0.76, p = 0.002). The disease control rate (DCR) and objective response rate (ORR) were 86.17% and 30.85%, respectively, in the PLR < 139.41 group, but were 82.52% and 32.17%, respectively in the PLR ≥ 139.41 group. Both groups did not show any marked differences in terms of ORR and DCR (p = 0.887, p = 0.476). PLR is an independent prognostic indicator for OS and PFS upon uni- and multivariate analyses (p < 0.05). Conclusions: Pre-treatment PLR correlated significantly with PFS and OS in AGC and MGC patients who received immunotherapy. An elevated PLR may provide guidance on subsequent treatment options.

Background. Nowadays, PD-1/PD-L1 inhibitors are widely used to treat various malignant tumors. However, during the immunotherapy in a few patients, a flare-up of tumor growth occurred. This new pattern of progression is called hyperprogressive disease (HPD). Patients and Methods. The retrospective study included 377 patients with various malignant tumors treated with PD-1 inhibitors (nivolumab or pembrolizumab) in the Chinese PLA General Hospital from January 2015 to January 2019. Clinicopathologic variables, tumor growth rate (TGR), and treatment outcomes were analyzed in patients with pan-cancer treated with PD-1 inhibitors. HPD was defined as the difference of TGR before and during immunotherapy exceeding 50%. Results. In 38 of 377 patients (10.08%), HPD occurred after treatment with PD-1 inhibitors. Patients with HPD had lower overall survival (OS) than those without HPD (median OS, 3.6months (95% CI, 3.0–4.2) vs. 7.3 months (95% CI, 5.9–8.7); ). Factors related to HPD include more than 2 metastatic sites, ECOG performance , hepatic metastases, and lactate dehydrogenase level greater than normal upper limit. KRAS status was significantly associated with HPD in patients with colorectal cancer. In the exploratory predictors’ analysis, the rapid increase of characteristic tumor markers (such as CEA in colorectal cancer, CA199 in pancreatic cancer and cholangiocarcinoma) within one month was found to be associated with the occurrence of HPD. Conclusions. HPD was developed with different rates in a variety of malignant tumor patients treated with PD-1 inhibitors and related to some clinicopathological features and poor prognosis. Tumor markers, especially CA199, might be served as early predictors of HPD.