Intraperitoneal infusion of recombinant human endostatin improves prognosis in gastric cancer ascites.

Objective: To investigate the efficacy and safety of intraperitoneal administration of recombinant human endostatin in gastric cancer with malignant ascites. Methods: Clinical data of 90 patients (37 in an Endostar® combined with cisplatin group and 53 in a cisplatin group) were retrospectively analyzed. The primary end point was overall survival, and the secondary end points were objective response rate (ORR), disease control rate (DCR) and so on. Results: Median overall survival was longer in the combination group (9.7 vs 8.1 months; p = 0.01). ORR and DCR were higher in the combination group (ORR: 75.7% vs 54.7%; p = 0.04; DCR: 94.6% vs 75.5%; p = 0.02). There were no significant differences in adverse effects between the two groups. Conclusion: Intraperitoneal administration of recombinant human endostatin improved efficacy and survival for gastric cancer with ascites.

Ascites (a buildup of fluid in the abdomen) resulting from the spread of gastric cancer (GC) results in extremely poor clinical outcomes, and current treatments have shown little effectiveness. Previous results showed that abdominal injection with chemotherapeutic agents enabled an increase in the dose of chemotherapeutic agents and reduced side effects or undesirable effects in the abdominal cavity. This study aimed to investigate the effectiveness and safety of abdominal injection with the anticancer drug recombinant human endostatin in GC with ascites. Clinical data of 90 patients were inspected and analyzed in this study. Thirty-seven patients who received abdominal infusion with both cisplatin (CDDP) and recombinant human endostatin were included in an Endostar^® combined with CDDP group, and 53 patients who received abdominal infusion with CDDP alone were included in a CDDP group. The results showed that median survival time was longer in the combination group than in the CDDP group (9.7 months vs 8.1 months). Besides, therapeutic outcomes, including objective response rate and disease control rate, were better in the combination group. Side effects or undesirable effects were similar in the two groups. To conclude, abdominal injection with recombinant human endostatin improved survival time and therapeutic outcomes for GC patients with ascites.

Clinicopathologic features and prognosis of 71 patients with gastric cancer and disseminated intravascular coagulation.

Background: Gastric cancer consists of solid tumors with a tendency for disseminated intravascular coagulation (DIC). DIC is rare in patients with stomach cancer, and there have been few studies on this condition. We aimed to perform comprehensive analyses of the prognosis and clinicopathologic characteristics of stomach cancer patients with DIC. Methods: Between June 2006 and March 2020, 14,016 patients at Fujian Cancer Hospital were diagnosed with stomach cancer. We reviewed their medical records and found that 105 of these patients were diagnosed with DIC. After excluding patients who were lost to follow-up, 71 patients with DIC remained. The clinical data were retrospectively analyzed to observe clinical characteristics and prognostic factors, and the Kaplan-Meier survival analysis was performed. Prognostic variables were investigated by the Cox proportional hazards method. Results: The median age was 54 (range, 21-83) years, and 38 patients (53.5%) were male. The histological category was poorly differentiated gastric cancer in 58 patients (81.7%). Eleven patients (15.5%) developed DIC after curative gastric resection. Sixty patients (84.5%) had DIC at the initial presentation of gastric cancer or developed DIC when the tumor progressed during treatment. Fifty-one patients (71.8%) had bleeding symptoms, and 43 (60.6%) patients had comorbidities at the time of DIC diagnosis. Among the 71 patients, 42 (59.2%) had multiple metastatic patterns. Twenty-one (29.6%) patients received chemotherapy. The median overall survival (OS) was 57.0 days (95% confidence interval [CI] [33.1-80.9] days). Tumor status (P = 0.000) and treatment (P = 0.003) were found to be significant variables associated with OS by univariate analysis. Multivariate analysis showed that tumor status (P = 0.000) and treatment (P = 0.000) had independent effects on OS. Conclusions: Gastrointestinal bleeding, multiple metastatic patterns and comorbidities at diagnosis with DIC are common in patients with gastric cancer complicated with DIC. Patients with poorly differentiated gastric cancer are more likely to develop DIC. Treatment and tumor status are separate risk variables for the survival of gastric cancer patients with DIC.DIC patients without tumors have a good prognosis and can be cured by appropriate etiological correction and symptomatic treatment. Chemotherapy can improve the prognosis of DIC patients with tumors.

Triceps skinfold-albumin index significantly predicts the prognosis of cancer cachexia: A multicentre cohort study.

BACKGROUND: The fat mass and nutritional status play important roles in the onset and progression of cancer cachexia. The present study evaluated the joint prognostic value of the fat mass, as indicated by the triceps skinfold thickness (TSF), and the serum albumin level, for mortality in patients with cancer cachexia. METHODS: We performed a multicentre cohort study including 5134 patients with cancer cachexia from January 2013 to April 2019. The sum of the TSF (mm) and serum albumin (g/L) was defined as the triceps skinfold-albumin index (TA). Harrell's C index, a time-dependent receiver operating characteristic (ROC) curve analysis and the area under the curve (AUC) were used to evaluate the prognostic performance of the TA and other indices. Optimal stratification was used to identify the thresholds to define a low TA, and the association of the TA with all-cause mortality was evaluated using Kaplan-Meier analysis and Cox proportional hazard regression models. RESULTS: The study enrolled 2408 women and 2726 men with a median age of 58.6 years and a median follow-up of 44 months. A total of 607 women (TA < 49.9) and 817 men (TA < 45.6) were classified as having a low TA. The TA showed better discrimination performance (C index = 0.621, 95% confidence interval [CI] = 0.607-0.636) to predict mortality in patients with cancer cachexia than the handgrip strength, the nutritional risk index, the prognostic nutritional index, the controlling nutritional status index, the systemic immune-inflammation index, the modified Glasgow prognostic score, and the TSF or albumin alone in the study population (all P < 0.05). The 1-, 3- and 5-year time-dependent ROC analyses (AUC = 0.647, 0.625 and 0.630, respectively) showed that the TA had the highest prognostic value among all indices investigated (all P < 0.05). Univariate analysis showed that a lower TA was associated with an increased death hazard (hazard ratio [HR] = 1.859, 95% CI = 1.677-2.062), regardless of the sex and cancer type. Multivariable survival analysis showed that a lower TA was independently associated with an increased death hazard (HR = 1.381, 95% CI = 1.223-1.560). This association was significantly strengthened in patients who did not receive curative chemotherapy (HR = 1.491, 95% CI = 1.298-1.713), those who had higher serum total protein levels (HR = 1.469, 95% CI = 1.284-1.681) and those with better physical performance (HR = 1.453, 95% CI = 1.271-1.662). CONCLUSIONS: This study defined and evaluated a new prognostic index, the TA, which may improve the selection of intervention strategies to optimize the survival of patients with cancer cachexia.

IL-6, TNF-α and IL-12p70 levels in patients with colorectal cancer and their predictive value in anti-vascular therapy.

We aimed to analyze the levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and interleukin-12 (IL-12p70) in colorectal cancer and evaluate the predictive significance of clinical efficacy of patients with colorectal cancer treated with anti-vascular therapy combined with chemotherapy. A retrospective study of 162 patients with colorectal cancer in Fujian Medical University Hospital was conducted from January 2019 to December 2020. A comparative analysis of the levels of IL-6, TNF-α and IL-12p70 between the two groups were studied. The relationship between the levels and the clinical characteristics of patients was observed; the factors affecting the levels of IL-6, TNF-α, and IL-12p70 in colorectal cancer patients were analyzed, and the predictive validity of the efficacy of anti-vascular therapy was evaluated. We observed that the individual expression levels of IL-6, TNF-α and IL-12p70 in the patients with colorectal cancer are related to lymph node metastasis, TNM staging, and degree of differentiation (P<0.05); however, they are irrelevant to the age, sex, and tumor location of patients with colorectal cancer (P>0.05). The multiple stepwise regression analysis indicates that lymph node metastasis and TNM staging are independent risk factors that correlate with IL-6 and IL-12p70 levels in colorectal cancer patients (P<0.01). The degree of differentiation was found to be an independent risk factor connected to TNF- α levels of patients with colorectal cancer. The change of IL-12p70 level could predict the validity of anti-vascular treatment for advanced colorectal cancer. When evaluated for combined expression, IL-6 and IL-12p70 in patients with colorectal cancer closely related to lymph node metastasis and TNM staging. IL-12p70 can be used as a predictor of anti-vascular therapy with colorectal cancer.

Elevated Serum Alpha-Fetoprotein Is a Significant Prognostic Factor for Patients with Gastric Cancer: Results Based on a Large-Scale Retrospective Study.

Objectives: The aim of this work is to study the clinicopathological features and prognostic factors of serum alpha-fetoprotein (AFP)-positive gastric cancer (GC). Methods: A cohort study including 2,318 patients with GC who underwent radical surgery from January 2008 to December 2015 was retrospectively analyzed. Patients were divided into two groups according to preoperative serum AFP values: 191 patients with AFP-positive GC (AFP > 20 ng/ml, 8.24%) and 2,127 patients with AFP-negative GC (AFP ≤ 20 ng/ml, 91.76%). The clinicopathological features and prognostic factors were explored. Results: Compared with AFP-negative GC, AFP-positive GC had higher rates of liver metastasis, lymph node metastasis, venous invasion, and nerve invasion (all P < 0.05). The 5-year OS, DFS, and mLMFS of AFP-positive GC were shorter than AFP-negative GC (55.00% vs. 45.04%, P < 0.001; 39.79% vs. 34.03%, P < 0.001; 13.80 months vs. 16.25 months, P = 0.002). In whole cohort, multivariate analysis found that serum AFP levels (positive vs. negative), pT stage, pN stage, nerve invasion (yes or no), and venous invasion (yes or no) were independent prognostic factors. Serum AFP levels (20-300 ng/ml vs. 300-1,000 ng/ml vs. >1,000 ng/ml), pT stage, pN stage, and venous invasion (yes or no) were independent prognostic factors in AFP-positive GC. Conclusion: Liver metastases and venous invasion are more likely to occur in AFP-positive GC and lead to poor prognosis. Serum AFP level is an independent prognostic factor in patients with GC. As the level of AFP increases, the prognosis becomes worse.

De novo Creation and Assessment of a Prognostic Fat-Age-Inflammation Index "FAIN" in Patients With Cancer: A Multicenter Cohort Study.

Background and Aims: Malnutrition is highly prevalent and is related to multiple impaired clinical outcomes in cancer patients. This study aimed to de novo create an objective, nutrition-related index specially for prognostic purposes in oncology populations. Methods: We performed a multicenter cohort study including 14,134 cancer patients. The prognostic impact for each baseline characteristic was estimated by calculating Harrell's C-index. The optimal parameters reflecting the nutritional and inflammatory impact on patients' overall survival were selected to develop the fat-age-inflammation (FAIN) index. The associations of the FAIN with the nutritional status, physical performance, quality of life, short-term outcomes and mortality of patients were comprehensively evaluated. Independent external validation was performed to further assess the prognostic value of the FAIN. Results: The study enrolled 7,468 men and 6,666 women with a median age of 57 years and a median follow-up of 42 months. The FAIN index was defined as: (triceps skinfold thickness + albumin) / [age + 5 × (neutrophil count/lymphocyte count)]. There were significant associations of the FAIN with the nutritional status, physical performance, quality of life and short-term outcomes. The FAIN also showed better discrimination performance than the Nutritional Risk Index, the Prognostic Nutritional Index and the Controlling Nutritional Status index (all P < 0.05). In multivariable-adjusted models, the FAIN was independently associated with a reduced death hazard both as a continuous variable (HR = 0.57, 95%CI = 0.47-0.68) and per one standard deviation (HR = 0.83, 95%CI = 0.78-0.88). External validation in a multicenter lung cancer cohort (n = 227) further confirmed the prognostic value of the FAIN. Conclusions: This study created and assessed the prognostic FAIN index, which might act as a feasible option to monitor the nutritional status and help develop intervention strategies to optimize the survival outcomes of cancer patients.

Several anthropometric measurements and cancer mortality: predictor screening, threshold determination, and joint analysis in a multicenter cohort of 12138 adults.

BACKGROUND: Anthropometric measurements (AMs) are cost-effective surrogates for evaluating body size. This study aimed to identify the optimal prognostic AMs, their thresholds, and their joint associations with cancer mortality. METHODS: We performed an observational cohort study including 12138 patients with cancer at five institutions in China. Information on demographics, disease, nutritional status, and AMs, including the body mass index, mid-arm muscle circumference, mid-arm circumference, handgrip strength, calf circumference (CC), and triceps-skinfold thickness (TSF), was collected and screened as mortality predictors. The optimal stratification was used to determine the thresholds to categorize those prognostic AMs, and their associations with mortality were estimated independently and jointly by calculating multivariable-adjusted hazard ratios (HRs). RESULTS: The study included 5744 females and 6394 males with a mean age of 56.9 years. The CC and TSF were identified as better mortality predictors than other AMs. The optimal thresholds were women 30 cm and men 32.8 cm for the CC, and women 21.8 mm and men 13.6 mm for the TSF. Patients in the low CC or low TSF group had a 13% (HR = 1.13, 95% CI = 1.03-1.23) and 22% (HR = 1.22, 95% CI = 1.12-1.32) greater mortality risk compared with their normal CC/TSF counterparties, respectively. Concurrent low CC and low TSF showed potential joint effect on mortality risk (HR = 1.39, 95% CI = 1.25-1.55). CONCLUSIONS: These findings support the importance of assessing the CC and TSF simultaneously in hospitalized cancer patients to guide interventions to optimize their long-term outcomes.

Identifying cancer cachexia in patients without weight loss information: machine learning approaches to address a real-world challenge.

BACKGROUND: Diagnosing cancer cachexia relies extensively on patient-reported historic weight, and failure to accurately recall this information can lead to severe underestimation of cancer cachexia. OBJECTIVES: The present study aimed to develop inexpensive tools to facilitate the identification of cancer cachexia in patients without weight loss information. METHODS: This multicenter cohort study included 12,774 patients with cancer. Cachexia was retrospectively diagnosed using Fearon et al.'s framework. Baseline clinical features, excluding weight loss, were modeled to mimic a situation where the patient is unable to recall their weight history. Multiple machine learning (ML) models were trained using 75% of the study cohort to predict cancer cachexia, with the remaining 25% of the cohort used to assess model performance. RESULTS: The study enrolled 6730 males and 6044 females (median age = 57.5 y). Cachexia was diagnosed in 5261 (41.2%) patients and most diagnoses were made based on the weight loss criterion. A 15-variable logistic regression (LR) model mainly comprising cancer types, gastrointestinal symptoms, tumor stage, and serum biochemistry indexes was selected among the various ML models. The LR model showed good performance for predicting cachexia in the validation data (AUC = 0.763; 95% CI: 0.747, 0.780). The calibration curve of the model demonstrated good agreement between predictions and actual observations (accuracy = 0.714, κ = 0.396, sensitivity = 0.580, specificity = 0.808, positive predictive value = 0.679, negative predictive value = 0.733). Subgroup analyses showed that the model was feasible in patients with different cancer types. The model was deployed as an online calculator and a nomogram, and was exported as predictive model markup language to permit flexible, individualized risk calculation. CONCLUSIONS: We developed an ML model that can facilitate the identification of cancer cachexia in patients without weight loss information, which might improve decision-making and lead to the development of novel management strategies in cancer care. This trial was registered at https://www.chictr.org.cn as ChiCTR1800020329.

A fusion decision system to identify and grade malnutrition in cancer patients: Machine learning reveals feasible workflow from representative real-world data.

BACKGROUND AND AIMS: Most nutritional assessment tools are based on pre-defined questionnaires or consensus guidelines. However, it has been postulated that population data can be used directly to develop a solution for assessing malnutrition. This study established a machine learning (ML)-based, individualized decision system to identify and grade malnutrition using large-scale data from cancer patients. METHODS: This was an observational, nationwide, multicenter cohort study that included 14134 cancer patients from five institutions in four different geographic regions of China. Multi-stage K-means clustering was performed to isolate and grade malnutrition based on 17 core nutritional features. The effectiveness of the identified clusters for reflecting clinical characteristics, nutritional status and patient outcomes was comprehensively evaluated. The study population was randomly split for model derivation and validation. Multiple ML algorithms were developed, validated and compared to screen for optimal models to implement the cluster prediction. RESULTS: A well-nourished cluster (n = 8193, 58.0%) and a malnourished cluster with three phenotype-specific severity levels (mild = 2195, 15.5%; moderate = 2491, 17.6%; severe = 1255, 8.9%) were identified. The clusters showed moderate agreement with the Patient-Generated Subjective Global Assessment and the Global Leadership Initiative on Malnutrition criteria. The severity of malnutrition was negatively associated with the nutritional status, physical status, quality of life, and short-term outcomes, and was monotonically correlated with reduced overall survival. A multinomial logistic regression was found to be the optimal ML algorithm, and models built based on this algorithm showed almost perfect performance to predict the clusters in the validation data. CONCLUSIONS: This study developed a fusion decision system that can be used to facilitate the identification and severity grading of malnutrition in patients with cancer. Moreover, the study workflow is flexible, and might provide a generalizable solution for the artificial intelligence-based assessment of malnutrition in a wider variety of scenarios.

Comparison of the AWGS and optimal stratification-defined handgrip strength thresholds for predicting survival in patients with lung cancer.

OBJECTIVES: Handgrip strength (HGS) is related to cancer mortality. The aim of this study was to compare the performance of the Asian Working Group for Sarcopenia 2019 (AWGS)- and optimal stratification (OS)-defined HGS thresholds for predicting the survival of patients with lung cancer (LC). METHODS: We performed an observational cohort study including 3230 patients with LC admitted to five institutions in China from November 2011 to January 2019. Comprehensive baseline and follow-up information was documented. Sex-specific thresholds for identifying patients with a low HGS were defined based on the AWGS (<28 kg in men and <18 kg in women) and the OS. The associations of a low HGS with survival were estimated by calculating multivariable-adjusted hazard ratios (HRs), and the relationships were flexibly modeled using restricted cubic splines. RESULTS: The study included 1041 women and 2189 men with a mean age of 60 y and a median follow-up time of 761 d. The OS-calculated HGS thresholds were <31.2 kg in men and <22.4 kg in women. There were significant associations between a low HGS defined by the AWGS (n = 1392; 43.1%) or the OS (n = 2034; 63%) and various nutritional characteristics. An AWGS-defined low HGS was associated with prolonged hospitalization. The OS-defined low HGS group was associated with a 23% greater death hazard than the normal HGS group (HR, 1.23; 95% confidence interval, 1.08-1.40). An n-shaped non-linear association was observed between the HGS and survival in women (P = 0.003). CONCLUSIONS: The OS-defined HGS thresholds show better performance than the AWGS for predicting the survival of patients with LC. Additionally, the HGS had n-shaped associations with the overall mortality among female patients with LC.

Perineural Invasion and Postoperative Complications are Independent Predictors of Early Recurrence and Survival Following Curative Resection of Gastric Cancer.

PURPOSE: To investigate the clinicopathological and prognostic factors related to early gastric cancer recurrence after curative resection. PATIENTS AND METHODS: Between October 2006 and August 2018, a total of 149 patients with recurrence of gastric cancer/adenocarcinoma of the esophagogastric junction after curative resection were enrolled from our treatment group. A retrospective clinical analysis was performed on these patients with gastric cancer recurrence after curative resection. RESULTS: Among the 149 patients, 99 (66.4%) had only one recurrence pattern, and 50 (33.6%) had multiple recurrence patterns. The median recurrence-free survival (RFS) was 18.2 months (95% CI 15.0-21.4). Ninety-four patients (63.1%) experienced early recurrence (recurrence within 24 months after curative resection), and 55 patients (36.9%) experienced late recurrence (recurrence beyond 24 months after curative resection). The univariate analysis showed that perineural invasion (P=0.002), depth of invasion (P=0.026), postoperative chemotherapy (P=0.036) and postoperative complications (P=0.004) were significant factors associated with early recurrence after curative resection for gastric cancer. Perineural invasion (P=0.003), postoperative chemotherapy (P=0.036) and postoperative complications (P=0.042) were independent factors associated with early recurrence after curative resection in the multivariate analysis. The survival analysis showed that perineural invasion (P=0.011) and postoperative complications (P=0.007) were independent prognostic factors. The median survival time of early recurrence patients was significantly shorter than that of late recurrence patients (25.4 vs 62.9 months, P<0.001). CONCLUSION: Perineural invasion, postoperative chemotherapy and postoperative complications were independent factors associated with early recurrence after curative resection. Patients with early recurrence after curative resection had poorer survival.

Paclitaxel-based regimens as first-line treatment in advanced gastric cancer.

The aim of this study was to evaluate the efficacy and safety of paclitaxel-based regimens as first-line treatments in advanced gastric cancer. We reviewed 397 previously untreated patients with advanced gastric cancer, who non-randomly received one of three paclitaxel-based regimens: paclitaxel plus fluorouracil/leucovorin (PF), paclitaxel plus oxaliplatin (PO), and paclitaxel plus oxaliplatin plus fluorouracil/leucovorin (POF) between January 2003 and December 2010. The PF, PO, and POF response rates were 47.13, 52.08, and 63.78%, respectively. Overall survivals (OS) were 11.2, 11.7, and 11.7 months, respectively. Progression-free survivals (PFS) were 6.6, 7.2, and 7.1 months, respectively. Leucopenia was higher on the triplet regimen than the doublet regimens. The paclitaxel-based regimens appeared to be effective in patients with advanced gastric cancer. The triplet regimen produced a higher response rate than either doublet regimen with more side effects, while survivals were similar among all three treatments.