Prognostic importance of systemic inflammation and insulin resistance in patients with cancer: a prospective multicenter study.

BACKGROUND: Systemic inflammation and insulin resistance (IR) are often associated with poor prognosis in cancer. This study aimed to investigate the prognostic value of surrogate systemic inflammation and IR indices in patients with cancer. METHODS: This multicenter prospective study included 5,221 patients with cancer, with a mean age of 59.41±11.15 years, of whom 3,061 (58.6%) were male. The surrogate IR indices included low-density lipoprotein cholesterol to high-density lipoprotein cholesterol (LHR) ratio, total cholesterol to high-density lipoprotein cholesterol (TC/ HDL-c) ratio, triglyceride to high-density lipoprotein cholesterol (TG/HDL-c) ratio, and fasting triglyceride glucose (TyG). Prognostic receiver operator characteristic (ROC) curves and C-indices were used to select a better surrogate IR index in patients with cancer. The prognostic value of the indicators was evaluated using univariate and multivariate survival analyses. RESULTS: In this study, the median survival time of patients was 44.5 (40.5-51.4) months, and the overall mortality in the 12-month period was 1,115 (53.7%), with 196 mortality events per 1,000 patient-years of patients' follow-up. The prognostic ROC curve and C-index suggested that the prognostic value of LHR was better than that of the other IR indices. The multivariate-adjusted hazard ratios (HRs) for overall survival (OS) were higher in patients with high C-reactive protein (CRP) (HR, 1.51; 95% confidence interval [CI]: 1.38-1.65) and high LHR (HR, 1.20; 95% CI: 1.06-1.37), respectively. The mortality rate of patients with both high CRP and LHR was 1.75-fold higher than that of patients with both low CRP and LHR. CONCLUSION: Both CRP and LHR showed good survival predictions in patients with cancer. CRP combined with LHR can improve the predictive power of patients with cancer.

In silico development and in vitro validation of a novel five-gene signature for prognostic prediction in colon cancer.

Colon cancer is one of the most common cancers in digestive system, and its prognosis remains unsatisfactory. Therefore, this study aimed to identify gene signatures that could effectively predict the prognosis of colon cancer patients by examining the data from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database. LASSO-Cox regression analysis generated a five-gene signature (DCBLD2, RAB11FIP1, CTLA4, HOXC6 and KRT6A) that was associated with patient survival in the TCGA cohort. The prognostic value of this gene signature was further validated in two independent GEO datasets. GO enrichment revealed that the function of this gene signature was mainly associated with extracellular matrix organization, collagen-containing extracellular matrix, and extracellular matrix structural constituent. Moreover, a nomogram was established to facilitate the clinical application of this signature. The relationships among the gene signature, mutational landscape and immune infiltration cells were also investigated. Importantly, this gene signature also reliably predicted the overall survival in IMvigor210 anti-PD-L1 cohort. In addition to the bioinformatics study, we also conducted a series of in vitro experiments to demonstrate the effect of the signature genes on the proliferation, migration, and invasion of colon cancer cells. Collectively, our data demonstrated that this five-gene signature might serve as a promising prognostic biomarker and shed light on the development of personalized treatment in colon cancer patients.

Inflammatory geriatric nutritional risk index stratified the survival of older adults with cancer sarcopenia.

BACKGROUND: Aging is accompanied by muscle loss. In older adults with cancer sarcopenia (OACS), systemic inflammation, reduced food intake, and reduced physical activity led to a poor prognosis. This study was to investigate the prognostic ability of the inflammatory Geriatric Nutritional Risk Index (GNRI), which combines patient's inflammation, diet status, and physical activity status to predict overall survival of OACS. METHODS: This prospective multi-center study enrolled 637 OACS, with an average age of 72.78 ± 5.98 years, of which 408 (64.1%) were males. We constructed the Inflammatory Functional Prognostic Index (IFPI) of OACS based on inflammatory GNRI scores, reduced food intake, and reduced physical activity. According to the IFPI, OACS was divided into high-, moderate-, and low-risk groups. Univariate and multivariate survival analyses analyzed the prognostic ability of the clinical parameters. RESULTS: Compared with OACS with a high GNRI score, the 1-, 3-, and 5-year hazard ratios (95% confidence interval) of OACS with a low GNRI score was 1.816 (1.076-3.063), 1.678 (1.118-2.518), and 1.627 (1.101-2.407), respectively. This result was consistent with that of the calibration curve. The subgroup analysis showed that the low GNRI score had a significant positive relation with patients with gastrointestinal cancer (Pinteraction < 0.001). Notably, the survival analysis of IFPI showed that the mortality risk of moderate- and high-risk patients was 1.722-and 2.509-fold higher, respectively, than that of low-risk patients. CONCLUSION: The GNRI score was a short-term and long-term inflammatory prognostic indicator for OACS. The IFPI score could improve patient survival prediction.

Comprehensive prognostic effects of systemic inflammation and Insulin resistance in women with breast cancer with different BMI: a prospective multicenter cohort.

To investigate the prognostic value of systemic inflammation and insulin resistance in women with breast cancer with different body mass index (BMI). This multicenter, prospective study included 514 women with breast cancer. Multivariate survival analysis showed that patients with high C-reactive protein (CRP), high CRP to albumin ratio (CAR), high lymphocyte to CRP ratio (LCR), high low-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (LHR), and high triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL-c) were significantly associated with worse prognosis. The mortality rate of patients with both high CAR and high LHR or both low LCR and high LHR were 3.91-fold or 3.89-fold higher than patients with both low CAR and low LHR or both high LCR and low LHR, respectively. Furthermore, the combination of LCR and LHR significantly predicted survival in patients within the high BMI group. The CRP, CAR, LCR, LHR, and TG/HDL-c were associated with poor survival in women with breast cancer. The combination of CAR and LHR or LCR and LHR could better predict the prognostic outcomes of women with breast cancer, while the combination of LCR and LHR could better predict the prognosis of those patients with overweight or obese patients.

Three-Stage Nutrition Diagnosis for surgical patients at the perioperative period.

Medical nutrition therapy has been widely applied in various diseases as a fundamental or even a first-line treatment. Patient who undergoes a disease state especially at the perioperative period can be much improved with the help of nutrition therapy. Precise nutrition diagnosis should be conducted before applying any nutrition therapy. Traditional malnutrition diagnostic process, however, is a two-stage process (nutrition screening and nutrition assessment) which cannot precisely assess nutritional status of surgical patients or the consequences of being malnourished. This article systematically introduced a new nutrition diagnostic process - Three-Stage Diagnosis (nutrition screening, nutrition assessment, and comprehensive evaluation) and discussed its applications during perioperative period.

Association of differential body water composition by sex, measured using BIA, with survival in a real­world lung cancer cohort.

OBJECTIVE: The aim of this study was to evaluate the association of differential body water composition with survival in patients with lung cancer. METHODS: This retrospective cohort study included 1314 patients diagnosed with lung cancer in 80 Chinese institutions from May 2013 to August 2020. We calculated hazard ratios (HRs) to evaluate the associations of all-cause mortality with extracellular water (ECW) and intracellular water (ICW). Cox proportional risk regression models were adjusted for sociodemographic characteristics, tumor characteristics, treatment, body mass index (BMI), and body composition measures. We also evaluated cross-classification of the dichotomy of ECW and ICW with outcomes. The association among ECW, ICW, and survival was evaluated via Cox regression and the restricted cubic-spline model using a two-sided P value. RESULTS: The study included 819 (62%) men and 495 (28%) women. The HR of lung cancer mortality significantly decreased as ECW increased (HR, 0.96; 95% confidence interval [CI], 0.93-1.00) and ICW (HR, 0.97; 95% CI, 0.95-1.00) with cutoff values of 10.5 and 16.3 L, respectively. When patients were cross-classified into categories of sex, age, BMI, visceral fat index, pathology, tumor stage, tumor burden, total bilirubin, and neutrophil count, ICW and ECW were protective factors. Only sex interacted significantly with ICW or ECW. High ICW and ECW had significant protective effects, and women had a greater risk for death than men in the case of either poor ICW or poor ECW. Sensitivity analysis showed the protective effect of the higher dichotomy of ICW (HR, 0.52; 95% CI, 0.35-0.78) and ECW (HR, 0.45; 95% CI, 0.31-0.66) on female lung cancer patients by removing patients who died within 12 mo of diagnosis. CONCLUSION: Greater ICW and ECW, especially ICW, were independent predictors for better survival in patients with lung cancer. Female patients were more vulnerable to dehydration than male patients.

A Novel Inflammation and Insulin Resistance Related Indicator to Predict the Survival of Patients With Cancer.

Background: Systemic inflammation and insulin resistance (IR) are closely related in patients with cancer. However, there is no relevant indicator that combines inflammation and IR to predict patient prognosis. Therefore, this study aimed to develop and validate a novel inflammation- and IR-related marker in patients with cancer. Methods: The total cohort of this study included 5221 patients with cancer, and the training and validation cohorts were randomized in a 7:3 ratio. C-reactive protein (CRP) and fasting triglyceride glucose (TyG) were used to reflect patients' inflammation and IR status, respectively. The CRP-TyG index (CTI) was composed of CRP and TyG. The concordance (C)-index, receiver operator characteristic (ROC) curve, and calibration curve reflected the prognostic predictive power of CTI. Univariate and multivariate survival analyses predicted the prognostic value of CTI in patients with cancer. Results: The C-indices of CTI in patients with cancer were 0.636, 0.617, and 0.631 in the total, training, and validation cohorts, respectively. The 1-, 3-, and 5-year ROC and calibration curves showed that CTI had a good predictive ability of survival in patients with cancer. Meanwhile, patients with high CTI had a worse prognosis compared to patients with low CTI (total cohort: hazard ratio [HR] = 1.46, 95% confidence interval [95% CI] = 1.33-1.59; training cohort: HR = 1.36, 95% CI = 1.22-1.52; validation cohort: HR = 1.73, 95% CI = 1.47-2.04]. Conclusion: The CTI is a useful prognostic indicator of poor prognosis and a promising tool for treatment strategy decision-making in patients with cancer.

Association of systemic inflammation and low performance status with reduced survival outcome in older adults with cancer.

BACKGROUND: Inflammation is involved in the progression and prognosis of cancer because it can affect the physical status and prognosis of patients. Among numerous systemic inflammatory markers, the optimal prognostic indicator of older adults with cancer is still unclear. We aimed to identify an ideal inflammatory immune marker in older adults with cancer and assess the survival outcome combined with eastern cooperative oncology group performance status (ECOG PS). METHODS: We included 1767 older adults with cancer (66.2% males, 70.97 ± 5.49 years old) from a prospective cohort study. Fifteen systemic inflammatory biomarkers were compared to identify the optimal biomarker using prognostic area under the curve (AUC) and concordance index (C-index) analysis. The prognostic value of the clinical parameters was elucidated by performing uni- and multivariate analyses. RESULTS: The AUC, C-index, and the subgroup survival analysis of ECOG PS groups showed that the lymphocyte-C reactive protein ratio (LCR) and C-reactive protein/albumin ratio (CAR) were more accurate in reflecting patient prognosis than the other 13 inflammatory markers. Compared with patients in the high LCR group, those in the low LCR group had worse survival (hazard ratio (HR) 1.64, 95% confidence interval (95%CI) 1.42-1.91, p < 0.001). Compared with patients in the low CAR group, those in the high CAR group had worse survival (HR 1.65, 95% CI 1.43-1.91, p < 0.001). Older adults with cancer with an ECOG PS score of 2 or 3-4 and a high inflammation (low LCR, 13.3 months and 9.2 months, respectively; or high CAR, 9.6 months and 9.6 months, respectively) had shorter median survival time compared to those with an ECOG PS score of 0/1 and a low inflammation (high LCR, 77.4 months; or low CAR, 77.0 months). CONCLUSION: LCR and CAR might be the better predictive immune inflammatory factors for OS, which improved the survival prediction of different ECOG PS groups in older adults with cancer. High ECOG PS (≥2) and high inflammation increased the risk of death in older adults with cancer.

Association between Platelet Count with 1-year Survival in Patients with Cancer Cachexia.

Background: Changes in platelet count (PLT) are strongly associated with patient survival and may be clinically indicative of certain underlying diseases. However, there were few studies on the prognosis of patients with cancer cachexia. Objective: The purpose of this study was to investigate the relationship between PLT and 1-year survival in patients with cancer cachexia. Methods: We performed a nested case-control study of data from a multicenter clinical study of cancer. There were 252 patients with cancer cachexia whose survival time was less than or equal to 1 year and 252 patients with cancer cachexia whose survival time was more than 1 year meeting the inclusion criteria. The mortality risk and the adjusted risk were estimated by logistic regression and displayed as odds ratios (ORs) and 95% confidence intervals (95% CIs). Results: PLT was negatively correlated with 1-year overall survival (OS) of patients with cancer cachexia (increased per standard deviation (SD): OR = 1.29; 95% CI: 1.05-1.60; P = 0.018). The higher the PLT, the lower the OS of patients. When classified by dichotomy (D1 < 296×109/L, D2 ≥ 296×109/L), OS of patients in the D2 group was worse (OR = 2.18; 95% CI: 1.38-3.47; P = 0.001). When classified by quartile (Q1- Q3 < 305×109/L, Q4 ≥ 305×109/L), OS of patients in the Q4 group was poorer (OR = 1.82; 95% CI: 1.14-2.94; P = 0.013). In addition, patients with a low PLT (< 296×109/L) and either a high total bilirubin (TBIL) (≥ 17.1 µmol/L) or a smoking history had poor 1-year survival. Based on our primary cohort study, we conducted a survival analysis of 3130 patients with cancer cachexia and found that OS was better in patients with low PLT (< 296×109/L). Conclusion: PLT was negatively correlated with 1-year overall survival of patients with cancer cachexia.

Association of Systemic Inflammation and Overall Survival in Elderly Patients with Cancer Cachexia - Results from a Multicenter Study.

BACKGROUND: Systemic inflammation and cachexia are associated with adverse clinical outcomes in elderly patients with cancer. The survival outcomes of elderly patients with cancer cachexia (EPCC) with high inflammation and a high risk of mortality are unknown. This study aimed to investigate the impact of high inflammation on the prognosis of EPCC patients with high mortality. PATIENTS AND METHODS: This multicenter cohort study included 746 EPCC (age >65 years) with a mean age of 72.00 ± 5.24 years, of whom 489 (65.5%) were male. The cut-off value for the inflammation index was obtained using the optimal survival curve. The different inflammatory indicators were assessed using the concordance index (C-index), decision curve analysis (DCA), and prognostic receiver operating characteristic (ROC). The high mortality risk group of EPCC was defined by the 2011 Fearon Cancer Diagnostic Consensus. EPCC were divided into the high-risk group, which satisfies three diagnostic criteria, and a low-risk group, which satisfies only one or two diagnostic criteria. RESULTS: The C-index, DCA, and prognostic ROC indicated the superiority of advanced lung cancer inflammation index (ALI) compared with other indicators, including neutrophil-lymphocyte ratio (NLR), prognostic nutritional index (PNI), systemic immune-inflammation index (SII), and platelet-lymphocyte ratio (PLR). Whether ALI was used as a continuous or a categorical variable, ALI had a better prognostic value in EPCC compared with other inflammatory indicators. In particular, patients with low ALI (<25.03) had a worse overall survival (OS) than patients with high ALI (≥25.03) (P < 0.001, HR [95% CI] = 2.092 [1.590-2.751]). The combination effect analysis showed that the risk of mortality of the patients in the low-ALI and high-risk groups was 3.095-fold higher than that of patients in the high-ALI and low-risk groups. CONCLUSION: The prognostic and discriminative value of the inflammatory indicator ALI was better than that of NLR, PNI, SII, and PLR in EPCC. The high-risk group of EPCC with a low ALI would increase the death risk of OS.

Association Between Systemic Inflammation and Malnutrition With Survival in Patients With Cancer Sarcopenia-A Prospective Multicenter Study.

OBJECTIVE: Systemic inflammation and malnutrition are correlated with cancer sarcopenia and have deleterious effects on oncological outcomes. However, the combined effect of inflammation and malnutrition in patients with cancer sarcopenia remains unclear. METHODS: We prospectively collected information on 1,204 patients diagnosed with cancer sarcopenia. the mean (SD) age was 64.5 (11.4%) years, and 705 (58.60%) of the patients were male. The patients were categorized into the high advanced lung cancer inflammation index (ALI) group (≥18.39) and the low ALI group (<18.39) according to the optimal survival cut-off curve. We selected the optimal inflammation marker using the C-index, decision curve analysis (DCA), and a prognostic receiver operating characteristic curve. Univariate and multivariate survival analyses were performed to determine the prognostic value of the optimal inflammation indicator. We also analyzed the association between inflammation and malnutrition in patients with cancer. RESULTS: The C-index, DCA, and prognostic area under the curve of ALI in patients with cancer sarcopenia were higher or better than those of neutrophil-lymphocyte ratio (NLR), prognostic nutritional index (PNI), systemic immune-inflammation index (SII), and platelet-lymphocyte ratio (PLR). The prognosis for patients in the low ALI group was worse than that of patients in the high ALI group [HR (95%CI) = 1.584 (1.280-1.959), P < 0.001]. When the ALI was divided into quartiles, we observed that decreased ALI scores strongly correlated with decreased overall survival (OS). Patients with both a low ALI and severe malnutrition (vs. patients with high ALI and well-nourished) had a 2.262-fold death risk (P < 0.001). Subgroup analysis showed a significant interactive association between the ALI and death risk in terms of TNM stage (P for interaction = 0.030). CONCLUSIONS: The inflammation indicator of the ALI was better than those of the NLR, PNI, SII, and PLR in patients with cancer sarcopenia. Inflammation combined with severe malnutrition has a nearly 3-fold death risk in patients with cancer sarcopenia, suggesting that reducing systemic inflammation, strengthening nutritional intervention, and improving skeletal muscle mass are necessary.

Geriatric Nutrition Risk Index: Prognostic factor related to inflammation in elderly patients with cancer cachexia.

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.

Surgical and Conservative Management of Malignant Bowel Obstruction: Outcome and Prognostic Factors.

PURPOSE: Malignant bowel obstruction (MBO) is a common problem in late-stage cancer patients. Many factors are suggested to be associated with the prognosis of MBO. The current investigation was designed to explore the factors associated with the prognosis of conservative and surgery treatment in one single institution. PATIENTS AND METHODS: Sixty-four patients of MBO were recruited into the study. Demographic and clinical data including gender, age, primary cancer, radiological and laboratory examinations, and nutritional and pain index scaling were extracted for further analysis. Kaplan-Meier analysis and logistic regression analysis were used to compare the prognosis and detect significant factors. RESULTS: Of the 64 patients, there is no statistical difference in baseline features between conservative and surgical group. However, the length of stay, total medical costs, re-admission interval, and re-admission rate are statistically significant. There is no significance in Kaplan-Meier log rank test for median survival time, though the overall survival time in the conservative group is longer than that of the surgery group. Logistic regression analysis has found that prior chemotherapy is a significant predictor for final survival outcome. CONCLUSION: The election of surgery might not improve the overall survival time. Non-surgical procedures, especially chemotherapy, might be preferable for MBO patients.