Gastric cancer (GC) is one of the most common upper gastrointestinal malignancies. Surgical resection remains the mainstay of curative treatment for GC. Enteral immunonutrition (EIN) has been increasingly used to enhance host immunity and relieve inflammatory response of patients undergoing surgery for GC; however, conclusions across studies still remain unclear. We aimed to evaluate the effects of EIN for such patients. We searched some electronic databases including PubMed, EBSCO-Medline, Cochrane Central Register of Controlled Trials (CENTRAL), and EMBASE to identify any latent studies which investigated the effects of EIN compared with standard EN on GC patients who undergoing surgery until the end of December 30, 2014. Relative risk (RR), mean difference (MD), or standard mean difference (SMD) with 95% confidence interval (CI) were calculated and we also assessed heterogeneity by using Cochrane Q and I2 statistic combined with corresponding P-value. We included 9 eligible studies which included 785 patients eventually. The meta-analysis results shown that EIN increased level of IgA (MD, 0.31; 95% CI, 0.12–0.51), IgG (MD, 1.5; 95% CI, 0.73–2.28), IgM (MD, 0.22; 95% CI, 0.06–0.39), CD4+ (SMD, 0.81; 95% CI, 0.53–1.09), CD3+ (SMD, 0.68; 95% CI, 0.21–1.15), CD4+/CD8+ ratio (MD, 0.56; 95% CI, 0.12–1.01), and NK cell (MD, 2.35; 95% CI, 0.66–4.05); decreased IL-6 (MD, −98.22; 95% CI, −156.16 to −40.28) and TNF-α (MD, −118.29; 95% CI, −162.00 to −74.58), but not improve remained outcomes of interest involving postoperative complications, length of hospitalization, serum total protein, and CD8+. Descriptive analysis suggested that EIN also increased the concentration of IL-2 but not CRP. Impact on lymphocytes remains inconsistent. EIN is effective for enhancing host immunity and relieving the inflammatory response in GC patients undergoing gastrectomy, but clinical outcomes cannot be benefit from it. Heterogeneity caused by different compositions and timing of administration of EIN regimes and not enough sample size and number of eligible studies in most of sensitive analyses with subgroup analysis may impaired the power of our study, and thus some large-scale and well-designed studies are warranted to further establish effects.

Enteral immunonutrition (EIN) has been established to be as a significantly important modality to prevent the postoperative infectious and noninfectious complications, enhance the immunity of host, and eventually improve the prognosis of gastrointestinal (GI) cancer patients undergoing surgery. However, different support routes, which are the optimum option, remain unclear. To evaluate the effects of different EIN support regimes for patients who underwent selective surgery for resectable GI malignancy, a Bayesian network meta-analysis (NMA) of randomized controlled trials (RCTs) was conducted. A search of PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL) was electronically searched until the end of December 2014. Moreover, we manually checked reference lists of eligible trials and review and retrieval unpublished literature. RCTs which investigated the comparative effects of EIN versus standard enteral nutrition (EN) or different EIN regimes were included if the clinical outcomes information can be extracted from it. A total of 27 RCTs were incorporated into this study. Pair-wise meta-analyses suggested that preoperative (relative risk [RR], 0.58; 95% confidence interval [CI], 0.43–0.78), postoperative (RR, 0.63; 95% CI, 0.52–0.76), and perioperative EIN methods (RR, 0.46; 95% CI, 0.34–0.62) reduced incidence of postoperative infectious complications compared with standard EN. Moreover, perioperative EIN (RR, 0.65; 95% CI, 0.44–0.95) reduced the incidence of postoperative noninfectious complications, and the postoperative (mean difference [MD], −2.38; 95% CI, −3.4 to −1.31) and perioperative EIN (MD, −2.64; 95% CI, −3.28 to −1.99) also shortened the length of postoperative hospitalization compared with standard EN. NMA found that EIN support effectively improved the clinical outcomes of patients who underwent selective surgery for GI cancer compared with standard EN. Our results suggest EIN support is promising alternative for operation management in comparison with standard EN, and perioperative EIN regime is the optimum option for managing clinical status of patients who underwent selective surgery for GI cancer.

Background: The predictive power of novel biological markers for treatment response to immune checkpoint inhibitors (ICI) is still not satisfactory for the majority of patients with cancer. One should identify valid predictive markers in the peripheral blood, as this is easily available before and during treatment. The current interim analysis of patients of the ST-ICI cohort therefore focuses on the development and validation of a liquid immune profile-based signature (LIPS) to predict response of patients with metastatic cancer to ICI targeting the programmed cell death protein 1 (PD-1)/programmed cell death-ligand 1 (PD-L1) axis. Methods: A total of 104 patients were prospectively enrolled. 54 immune cell subsets were prospectively analyzed in patients’ peripheral blood by multicolor flow cytometry before treatment with ICI (pre-ICI; n=89), and after the first application of ICI (n=65). Pre-ICI, patients were randomly allocated to a training (n=56) and a validation cohort (n=33). Univariate Cox proportional hazards regression analysis and least absolute shrinkage and selection operator Cox model were used to create a predictive immune signature, which was also checked after the first ICI, to consider the dynamics of changes in the immune status. Results: Whole blood samples were provided by 89 patients pre-ICI and by 65 patients after the first ICI. We identified a LIPS which is based on five immune cell subtypes: CD14^high monocytes, CD8+/PD-1⁺ T cells, plasmacytoid dendritic cells, neutrophils, and CD3⁺/CD56⁺/CD16⁺ natural killer (NK)T cells. The signature achieved a high accuracy (C-index 0.74 vs 0.71) for predicting overall survival (OS) benefit in both the training and the validation cohort. In both cohorts, the low-risk group had significantly longer OS than the high-risk group (HR 0.26, 95% CI 0.12 to 0.56, p=0.00025; HR 0.30, 95% CI 0.10 to 0.91, p=0.024, respectively). Regarding the whole cohort, LIPS also predicted progression-free survival (PFS). The identified LIPS was not affected by clinicopathological features with the exception of brain metastases. NKT cells and neutrophils of the LIPS can be used as dynamic predictive biomarkers for OS and PFS after first administration of the ICI. Conclusion: Our study identified a predictive LIPS for survival of patients with cancer treated with PD-1/PD-L1 ICI, which is based on immune cell subsets in the peripheral whole blood. Trial registration number: NCT03453892.

Purpose: Colorectal cancer (CRC) is one of the most common malignant tumors worldwide. This study aimed to explore the prognostic value of lncRNAs in CRC. Material and methods: We performed gene expression profiling to identify differentially expressed lncRNAs between 51 normal and 646 tumor tissues from The Cancer Genome Atlas database. Cox regression and robust likelihood-based survival models were used to find prognosis-related lncRNAs. A lncRNA signature was developed to predict the overall survival of patients with CRC. In addition, a receiver operating characteristic curve analysis was performed to identify the optimal cutoff with the best Youden index to divide patients into different groups based on risk level. Results: Eighty survival-related lncRNAs were identified and a 15-lncRNA signature was developed on the basis of a risk score to comprehensively predict the overall survival of patients with CRC. The prognostic value of the 15-lncRNA risk score was validated using the internal testing set and total set. The risk indicator was shown to be an independent prognostic factor (hazard ratio =2.92; 95% CI: 1.73–4.94; P<0.001). Notably, all 15 lncRNAs (AC024581.1, FOXD3-AS1, AC012531.1, AC003101.2, LINC01219, AC083967.1, AL590483.1, AC105118.1, AC010789.1, AC067930.5, AC105219.2, LINC01354, LINC02474, LINC02257, and AC079612.1) were newly found to correlate with the prognosis of patients with CRC. Furthermore, the function of 15 lncRNAs was explored through the ceRNA network. These lncRNAs regulated coding genes that were involved in many key cancer pathways. Conclusion: A 15-lncRNA expression signature was discovered as a prognostic indicator for patients with CRC, which may act as competing endogenous RNA (ceRNAs) to play a crucial role in the modulation of cancer-related pathways. These findings may allow a better understanding of the prognostic value of lncRNAs.

This is a dose-response (DR) meta-analysis to evaluate the association of coffee consumption on endometrial cancer (EC) risk. A total 1,534,039 participants from 13 published articles were added in this meta-analysis. The RR of total coffee consumption and EC were 0.80 (95% CI: 0.74–0.86). A stronger association between coffee intake and EC incidence was found in patients who were never treated with hormones, 0.60 (95% CI: 0.50–0.72) and subjects with a BMI ≥25 kg/m², 0.57 (95% CI: 0.46–0.71). The overall RRs for caffeinated and decaffeinated coffee were 0.66 (95% CI: 0.52–0.84) and 0.77 (95% CI: 0.63–0.94), respectively. A linear DR relationship was seen in coffee, caffeinated coffee, decaffeinated coffee and caffeine intake. The EC risk decreased by 5% for every 1 cup per day of coffee intake, 7% for every 1 cup per day of caffeinated coffee intake, 4% for every 1 cup per day of decaffeinated intake of coffee and 4% for every 100 mg of caffeine intake per day. In conclusion, coffee and intake of caffeine might significantly reduce the incidence of EC and these effects may be modified by BMI and history of hormone therapy.

Purpose The first aim of the trial is to study feasibility of combined programmed death protein ligand 1/cytotoxic T-lymphocyte-associated protein 4 inhibition concomitant to radiotherapy. In addition, efficacy of the entire treatment scheme consisting of induction chemoimmunotherapy followed by chemotherapy-free radioimmunotherapy (RIT) after intratumoral CD8 +immune cell-based patient selection will be analyzed. Methods Patients with stage III–IVB head and neck squamous cell carcinoma were eligible for this multicenter phase II trial. Treatment consisted of a single cycle of cisplatin 30 mg/m² days 1–3, docetaxel 75 mg/m² day 1, durvalumab 1500 mg fix dose day 5 and tremelimumab 75 mg fix dose day 5. Patients with increased intratumoral CD8 +immune cell density or pathological complete response (pCR) in the rebiopsy entered RIT up to a total dose of 70 Gy. Patients received further three cycles of durvalumab/tremelimumab followed by eight cycles of durvalumab mono (every 4 weeks). The intended treatment for patients not meeting these criteria was standard radiochemotherapy outside the trial. Primary endpoint was a feasibility rate of patients entering RIT to receive treatment until at least cycle 6 of immunotherapy of ≥80%. Results Between September 2018 and May 2020, 80 patients were enrolled (one excluded). Out of these, 23 patients had human papilloma virus (HPV)-positive oropharyngeal cancer. Median follow-up was 17.2 months. After induction chemoimmunotherapy 41 patients had pCR and 31 had increased intratumoral CD8 +immune cells. Of 60 patients entering RIT (primary endpoint cohort), 10 experienced imiting toxic (mainly hepatitis) and four discontinued for other reasons, resulting in a feasibility rate of 82%. The RIT cohort (n=60) had a progression-free survival (PFS) rate at one and 2 years of 78% and 72%, respectively, and an overall survival rate at one and 2 years of 90% and 84%, respectively. Patients with HPV-positive oropharyngeal cancers had greater benefit from RIT with a 2-year PFS rate of 94% compared with 64% for HPV-negative oropharyngeal cancers and other locations. In the entire study cohort (n=79) the 2-year PFS rate was 68% (91% for HPV-positive oropharynx vs 59% for others). Toxicity grade 3–4 mainly consisted of dysphagia (53%), leukopenia (52%) and infections (32%). Conclusions The trial met the primary endpoint feasibility of RIT. Induction chemo-immunotherapy followed by chemotherapy-free RIT after intratumoral CD8 +immune cell-based patient selection has promising PFS. Trial registration number The trial was registered with ClinicalTrials.gov (identifier: NCT03426657). The trial was conducted as investigator-sponsored trial (IST).