Background Systemic inflammation and cachexia are associated with adverse clinical outcomes in elderly patients with cancer. The Geriatric Nutritional Risk Index (GNRI) is a simple and useful tool to assess these conditions, but its predictive ability for elderly patients with cancer cachexia (EPCC) is unknown. Methods This multicentre cohort study included 746 EPCC with an average age of 72.00 ± 5.24 years, of whom 489 (65.5%) were male. The patients were divided into two groups (high GNRI group ≥91.959 vs. low GNRI group <91.959) according to the optimal cut‐off value of the ROC curve. The calibration curves were performed to analyse the prognostic, predictive ability of GNRI. Comprehensive survival analyses were utilized to explore the relationship between GNRI and the overall survival (OS) of EPCC. Interaction analysis was used to investigate the comprehensive effects of low GNRI and subgroup parameters on the OS of EPCC. Results In this study, a total of 2560 patients were diagnosed with cancer cachexia, including 746 cases of EPCC. During the 3.6 year median follow‐up, we observed 403 deaths. The overall mortality rate for EPCC at 12 months was 34.3% (95% CI: 62.3% to 69.2%), and resulting in rate of 278 events per 1000 patient‐years. The GNRI score of EPCC was significantly lower than those of young patients with cancer cachexia (P < 0.001). The 1, 3, and 5 year calibration curves showed that the GNRI score had good survival prediction in the OS of EPCC. The GNRI could predict the OS of EPCC, whether as a continuous variable or a categorical variable. Particularly, we also found that low GNRI score (<91.959) of EPCC had a worse prognosis than those with a high GNRI score (≥91.959, P = 0.001, HR = 1.728, 95% CI: 1.244–2.401). Consistent results were observed in the tumour subgroups of gastric cancer and colorectal cancer. Notably, similar results were observed in the sensitivity analysis. In the subgroup analysis, the low GNRI has a combined effect with age (<70 years) on poor OS of EPCC. The results of the prognostic risk model found that the lower the GNRI score, the greater the prognostic risk score, and the greater the risk of death in EPCC. Conclusions For the first time, this study found that the GNRI score can serve as an independent prognostic factor for the OS of EPCC.

Background Although systemic inflammation is an important feature of the cancer cachexia, studies on the association between systemic inflammation and prognostic of cancer cachexia are limited. The objective of this study is to evaluate whether the neutrophil-to-lymphocyte ratio (NLR) is associated with outcome and quality of life for patients with cancer cachexia and investigated any interaction between NLR and the clinical parameters. Methods This is a multicentre cohort study of 2612 cancer patients suffering from cachexia diagnosed between June 2012 and December 2019. The main parameters measured were overall survival (OS) time and all-cause mortality. The association between NLR and all-cause mortality was evaluated using hazard ratios (HRs) and the restricted cubic spline model with a two-sided P-value. Optimal stratification was used to solve threshold points. We also evaluated the cross-classification of NLR for each variable of survival. Results Of the 2612 participants diagnosed with cancer cachexia, 1533 (58.7%) were male, and the mean (SD) age was 58.7 (11.7) years. Over a median follow-up of 4.5 years, we observed 1189 deaths. The overall mortality rate for patients with cancer cachexia during the first 12 months was 30.2% (95%CI: 28.4%-32.0%), resulting in a rate of 226.07 events per 1000 patient-years. An increase in NLR had an inverted L-shaped dose-response association with all-cause mortality. The optimal cut-off point for NLR as a predictor of mortality in cancer patients with cachexia was 3.5. An NLR of 3.5 or greater could independently predict OS (HR, 1.51, 95%CI: 1.33-1.71). These associations were consistent across subtypes of cancer. Several potential effect modifiers were identified including gender, BMI, tumour type, KPS score and albumin in content. Increasing NLRs were independently associated with a worsening in the majority of EORTC QLQ-C30 domains. Elevated baseline NLR was associated with low response and poor survival in patients treated with immunotherapy. Conclusions The baseline NLR status was found to be a significant negative prognostic biomarker for patients with cachexia; this effect was independent of other known prognostic factors.

Our study aims to explore the relationship between chronic hepatitis B virus (HBV) infection and the risk of gastrointestinal (GI) cancers including liver, gastric, gallbladder or extrahepatic bile duct, pancreatic, small intestine, esophageal and colorectal cancer in the Kailuan Cohort study. We prospectively examined the relationship between HBV infection and new-onset GI cancers among 93 402 participants. Cox proportional hazards regression models, subgroup analyses and competing risk analyses were used to evaluate the association between HBV infection and the risk of new-onset GI cancers. During a median follow-up of 13.02 years, 1791 incident GI cancer cases were diagnosed. Compared to HBsAg seronegative participants, a significant positive association between HBV infection and GI cancers was observed in the multivariate-adjusted models (HR 5.59, 95% CI: 4.84-6.45). In the site-specific analyses, participants with HBsAg seropositive exhibited an increased risk of liver cancer (

Background: Patient-derived organoid (PDO) models are highly valuable and have potentially widespread clinical applications. However, limited information is available regarding organoid models of non-small cell lung cancer (NSCLC). This study aimed to characterize the consistency between primary tumors in NSCLC and PDOs and to explore the applications of PDOs as preclinical models to understand and predict treatment response during lung cancer. Methods: Fresh tumor samples were harvested for organoid culture. Primary tumor samples and PDOs were analyzed via whole-exome sequencing. Paired samples were subjected to immunohistochemical analysis. There were 26 antineoplastic drugs tested in the PDOs. Cell viability was assessed using the Cell Titer Glo assay 7-10 days after drug treatment. A heatmap of log-transformed values of the half-maximal inhibitory concentrations was generated on the basis of drug responses of PDOs through nonlinear regression (curve fit). A total of 12 patients (stages I-III) were enrolled, and 7 paired surgical tumors and PDOs were analyzed. Results: PDOs retained the histological and genetic characteristics of the primary tumors. The concordance between tumors and PDOs in mutations in the top 20 NSCLC-related genes was >80% in five patients. Sample purity was significantly and positively associated with variant allele frequency (Pearson r = 0.82, P = 0.0005) and chromosome stability. The in vitro response to drug screening with PDOs revealed high correlation with the mutation profiles in the primary tumors. Conclusions: PDOs are highly credible models for detecting NSCLC and for prospective prediction of the treatment response for personalized precision medicine. Key points: Lung cancer organoid models could save precious time of drug testing on patients, and accurately select anticancer drugs according to the drug

Aims Alcohol intake has been shown to increase the risk of breast cancer. However, the dose-response analysis of different alcoholic beverages (spirits, wine and beer) is not clear. Our meta-analysis aims to provide a dose-response estimation between different alcohols and breast cancer risk. Methods Search of PubMed and Web of Science and manual searches were conducted up to 1 December 2018, and summary relative risks (RRs) and attributable risk percentage (ARP) for alcohol intake on the development of breast cancer were calculated. Dose-response meta-analysis modeled relationships between drinking type and breast cancer risk. Sources of heterogeneity were explored, and sensitivity analyses were conducted to test the robustness of findings. Results In total, 22 cohort studies and 45,350 breast cancer cases were included. Current drinkers for ER+ had an increased risk compared with never drinkers. In dose-response analysis, there was a statistically significant linear trend with breast cancer risk increasing gradually by total alcohol and wine dose: when adding 10 g per day, the risk increased by 10.5% (RR = 1.10, 95%CI = 1.08–1.13) in total alcohol and 8.9% (RR = 1.08, 95%CI = 1.04–1.14) in wine. For postmenopausal women, the risk increases by 11.1% (RR = 1.11, 95%CI = 1.09–1.13) with every 10 g of total alcohol increase. Furthermore, the breast cancer alcohol-attributed percentage is higher in Europe than in North America and Asia. Conclusions The effect of drinking on the incidence of breast cancer is mainly manifested in ER+ breast cancer. Quantitative analysis showed total drinking had a significant risk for breast cancer, especially for postmenopausal women. However, for different alcohols, just wine intake has the similar results.

Purpose Nicotinamide n‐methyltransferase (NNMT) has good biochemical activity and epigenetic regulation, and has been reported as a major metabolic regulator of cancer. The goal of this study was to investigate the significance of stromal NNMT expression in colorectal cancer (CRC). Patients and methods Stromal expression of NNMT in primary CRC, metastasis CRC, and their non‐cancerous tissues from 1088 CRC patients was examined by immunohistochemistry. The associations between stromal NNMT expression and survival outcomes in 967 patients with stage I‐III CRC were further evaluated with Kaplan‐Meier curve and Cox model analyses. Results NNMT expression was mainly sourced from stromal compartments and also elevated in CRC. Patients with high stromal NNMT (IHC‐score ≥ 106) have a worse survival than those patients with low stromal NNMT. In multiple Cox analyses, high expression of stromal NNMT remained as an independent risk factor in CRC for disease‐free survival with a hazard ratio (HR) of 1.415 (95% confidence interval [CI], 1.015‐1.972) and disease‐specific survival with a HR of 5.004 (95% CI, 2.301‐10.883). In addition, high stromal NNMT expression in CRC also indicates the poor survival outcomes in patients with early stage CRC (stage I and II) and in patients who undergo chemotherapy. Conclusion NNMT is mainly located in CRC stromal compartment. High stromal NNMT expression predicts an unfavorable postoperative prognosis.

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Backgrounds Malnutrition and systemic inflammatory responses are associated with poor overall survival (OS) in lung cancer patients, but it remains unclear which biomarkers are better for predicting their prognosis. This study tried to determine the best one among the existing common nutrition/inflammation-based indicators of OS for patients with lung cancer. Materials and methods There were 16 nutrition or systemic inflammation-based indicators included in this study. The cut-off points for the indicators were calculated using maximally selected rank statistics. The OS was evaluated using the Kaplan-Meier estimator, and univariate and multivariate Cox proportional hazard models were used to determine the relationship between the indicators and OS. A time-dependent receiver operating characteristic curves (time-ROC) and C-index were calculated to assess the predictive ability of the different indicators. Results There were 1772 patients with lung cancer included in this study. In univariate analysis, all 16 indicators were significantly associated with OS of the patients (all P < 0.001). Except for platelet-to-lymphocyte ratio, all other indicators were independent predictors of OS in multivariate analysis (all P < 0.05). Low advanced lung cancer inflammation index (ALI) was associated with higher mortality risk of lung cancer [hazard ratio, 1.30; 95% confidence interval (CI), 1.13-1.49]. The results of the time-AUC and C-index analyses indicated that the ALI (C-index: 0.611) had the best predictive ability on the OS in patients with lung cancer. In different sub-groups, the ALI was the best indicator for predicting the OS of lung cancer patients regardless of sex (C-index, 0.609 for men and 0.613 for women) or smoking status (C-index, 0.629 for non-smoker and 0.601 for smoker) and in patients aged <65 years (C-index, 0.613). However, the modified Glasgow prognostic score was superior to the other indicators in non-small cell lung cancer patients (C-index, 0.639) or patients aged ≥65 years (C-index, 0.610), and the glucose-to-lymphocyte ratio performed better prognostic ability in patients with small cell lung cancer (C-index, 0.601). Conclusions The prognostic ability of the ALI is superior to the other inflammation/nutrition-based indicators for all patients with lung cancer.