Trifluridine/tipiracil plus bevacizumab as a first‐line treatment for elderly patients with metastatic colorectal cancer (KSCC1602): A multicenter phase II trial

xloma.fota13 shared this article with you from Inoreader Trifluridine/tipiracil plus bevacizumab as a first‐line treatment for elderly patients with metastatic colorectal cancer (KSCC1602): A multicenter phase II trial Via Cancer Medicine We aimed to assess the efficacy and safety of FTD/TPI plus Bev in elderly patients with previously untreated metastatic colorectal cancer. The median PFS was 9.4 months as a primary endpoint, the median OS was 22.4 month, ORR was 40.5% and AEs were manageable. The combination of FTD/TPI plus Bev is an effective and well‐tolerated regimen for elderly patients with previously untreated metastatic colorectal cancer. ABSTRACT Background A previous Phase I/II study demonstrated that TAS‐102 (trifluridine/tipiracil [FTD/TPI]) plus bevacizumab (Bev) has encouraging efficacy and controllable safety for patients with previously treated metastatic colorectal cancer. Therefore, we designed for assessing the efficacy and safety of FTD/TPI plus Bev in elderly patients with previously untreated metastatic colorectal cancer. Methods This is a multicenter, single‐arm Phase II study included patients ≥70 years old with previously untreated, unresectable metastatic colorectal cancer. Treatment consisted of FTD/TPI plus Bev given every 4 weeks. The primary endpoint was progression‐free survival (PFS), assuming a null hypothesis of a PFS of 5 months. The secondary endpoints were the overall survival (OS), overall response rate (ORR), and adverse events (AEs). Results Between 5 January 2017 and 13 March 2018, 39 patients were enrolled from 18 institutions. The median patient age was 76.0 years (range, 70–88); the ECOG‐PS was 0 in 24 patients and 1 in 15 patients. The median PFS was 9.4 months as a primary endpoint, and the median OS was 22.4 months. The ORR was 40.5% and the disease control rate was 86.5%. Grade 3–4 AEs included neutropenia (71.8%), leukopenia (51.3%), anorexia (15.4%), febrile neutropenia (10.3%), and fatigue (10.3%). Conclusions FTD/TPI plus Bev is an effective and well‐tolerated regimen for elderly patients with previously untreated metastatic colorectal cancer. Capecitabine/bevacizumab can be selected as a subsequent maintenance therapy without irinotecan and oxaliplatin because FTD/TPI has no cross‐resistance with 5‐fluorouracil. Clinical trial registration: UMIN clinical trials registry (UMIN000025241). View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Low sodium diet for gastric cancer prevention

xloma.fota13 shared this article with you from Inoreader Low sodium diet for gastric cancer prevention in the United States: Results of a Markov model Via Cancer Medicine Using a Markov model of gastric cancer risk, we found that adherence to a low sodium‐DASH diet decreases the risk of gastric cancer in the U.S. population. This intervention was not cost‐effective due to the high cost of a low sodium‐DASH accordant diet, but significantly improved for certain high‐risk populations and when the cost of the diet became slightly more affordable. Abstract Background and Aims High sodium consumption has been associated with an increased risk of gastric cancer. The mean daily sodium intake in the United States substantially exceeds the national recommended amount. The low sodium‐DASH diet has been shown to decrease the risk of cardiovascular disease in the United States, but its impact on gastric cancer has not been well studied. We therefore aimed to model the impact and cost‐effectiveness of the low sodium‐DASH diet for gastric cancer prevention in the U.S. population. Methods A Markov cohort state‐transition model was developed to simulate the impact of the low sodium‐DASH diet on gastric cancer outcomes for the average 40‐year‐old in the United States compared to no intervention. Primary outcomes of interest were gastric cancer incidence and incremental cost‐effectiveness ratios (ICER). Results Our model found that compared to the no intervention cohort, the risk of gastric cancer decreased by 24.8% for males and 21.2% for females on the low sodium‐DASH diet. 27 cases and 14 cases per 10,000 individuals were prevented for males and females, respectively, in the intervention group. The ICER for the low sodium‐DASH diet strategy was $287,726 for males and $423,878 for females compared to the no intervention strategy. Conclusions Using a Markov model of gastric cancer risk, we found that adherence to a low sodium‐DASH diet could decrease the risk of gastric cancer. This intervention was not cost‐effective due to the high cost of a low sodium‐DASH accordant diet, but significantly improved for high‐risk populations and when the cost of the diet became slightly more affordable. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Tumor suppressing effects of tristetraprolin and its small double‐stranded RNAs in bladder cancer

xloma.fota13 shared this article with you from Inoreader Tumor suppressing effects of tristetraprolin and its small double‐stranded RNAs in bladder cancer Via Cancer Medicine TTP overexpression can inhibit the malignant biological behaviors of BCa, and can be a potential therapeutic target for BCa. dsTTP‐973 which can induce TTP expression in BCa is able to suppress BCa progression, and dsTTP‐973 may be a potential treatment for BCa in the future. Abstract Bladder cancer (BCa) is a common malignant tumor of urinary system with few treatments, so more useful therapeutic targets are still needed. Antitumor effects of tristetraprolin (TTP) have been explored in many type tumors, but its roles in bladder cancer are still unknown until now. In this study, public expression profiles and tissue microarray analysis showed that TTP mRNA and protein levels decreased in BCa relative to the normal bladder tissue. To explore biological functions of TTP in BCa, 488 TTP target genes, which could be both suppressed and bound by TTP, were identified by comprehensively analyzing publicly available high‐throughput data obtained from Gene Expression Omnibus (GEO). Gene enrichment analysis showed that these genes were enriched in pathways such as cell cycle, epithelial to mesenchymal transition (EMT), and Wnt signaling. Clustering analysis and gene set variation analysis indicated that patients with high expression of TTP target genes had poorer progn osis and stronger tumor proliferation ability relative to the BCa patients with low expression of TTP target genes. In vitro experiments validated that TTP could suppress proliferation, migration, and invasiveness of BCa cells. And TTP could suppress mRNA expression of cyclin‐dependent kinase 1 (CDK1) in BCa cells by target its 3′ UTR. Then, we identified a new small double‐stranded RNA (dsRNA) named dsTTP‐973 which could increase TTP expression in BCa cells, in vivo and in vitro experiments revealed that dsTTP‐973 could suppress aggressiveness of BCa. In conclusion, TTP played a role of tumor suppressor gene in BCa like other tumors, and its dsRNA named dsTTP‐973 could induce TTP expression in BCa and suppress aggressiveness of BCa. With the help of materials science, dsTTP‐973 may become a potential treatment for BCa in the future. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Prediction of the World Health Organization Grade of rectal neuroendocrine tumors based on CT histogram analysis

xloma.fota13 shared this article with you from Inoreader Prediction of the World Health Organization Grade of rectal neuroendocrine tumors based on CT histogram analysis Via Cancer Medicine CECT histogram parameters, including arterial phase and venous phase, can be used as excellent indicators for predicting G1 and HG of rectal neuroendocrine tumors, and the size of the tumor is also an important independent predictor. Abstract Objectives To investigate the diagnostic value of contrast‐enhanced computed tomography (CECT) histogram analysis in predicting the World Health Organization (WHO) grade of rectal neuroendocrine tumors (R‐NETs). Materials and Methods A total of 61 (35 G1, 12 G2, 10 G3, and 4 NECs) patients who underwent preoperative CECT and treated with surgery to be confirmed as R‐NETs were included in this study from January 2014 to May 2019. We depicted ROIs and measured the CECT texture parameters (mean, median, 10th, 25th, 75th, 90th percentiles, skewness, kurtosis, and entropy) from arterial phase (AP) and venous phase (VP) images by two radiologists. We calculated intraclass correlation coefficient (ICC) and compared the histogram parameters between low‐grade (G1) and higher grade (HG) (G2/G3/NECs) by applying appropriate statistical method. We obtained the optimal parameters to identify G1 from HG using receiver operating characteristic (ROC) curves. Results The capability of AP and VP histogram parameters for differentiating G1 from HG was similar in several histogram parameters (mean, median, 10th, 25th, 75th, and 90th percentiles) (all p < 0.001). Skewness, kurtosis, and entropy on AP images showed no significant differences between G1 and HG (p = 0.853, 0.512, 0.557, respectively). Entropy on VP images was significantly different (p = 0.017) between G1 and HG, however, skewness and kurtosis showed no significant differences (p = 0.654, 0.172, respectively). ROC analysis showed a good predictive performance between G1 and HG, and the 75th (AP) generated the highest area under the curve (AUC = 0.871), followed by the 25th (AP), mean (VP), and median (VP) (AUC = 0.864). Combined the size of tumor and the 75th (AP) generated the highest AUC. Conclusions CECT histogram parameters, including arterial and venous phases, can be used as excellent indicators for predicting G1 and HG of rectal neuroendocrine tumors, and the size of the tumor is also an important independent predictor. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Impact of insurance and neighborhood socioeconomic status on clinical outcomes in therapeutic clinical trials for breast cancer

xloma.fota13 shared this article with you from Inoreader Impact of insurance and neighborhood socioeconomic status on clinical outcomes in therapeutic clinical trials for breast cancer Via Cancer Medicine Abstract The objective of this study was to evaluate the impact of insurance and neighborhood SES (nSES) on chemotherapy completion and overall mortality among participants in breast cancer clinical trials. The data sources for this study were two adjuvant breast cancer trials (ECOG E1199 and E5103) collectively including 9790 women. Insurance status at trial registration was categorized into private, government (Medicaid, Medicare, and other government type insurance), and self‐pay. An Agency for Healthcare Research Quality (AHRQ) nSES index was calculated using residential zip codes linked to county level data on occupation, income, poverty, wealth, education, and crowding. Logistic regression and Cox Proportional Hazard models estimated odds ratios (OR) for chemotherapy treatment completion and hazard ratios (HR) for mortality, respectively, for insurance status and nSES. The models adjusted for: race, age, tumor size, nodal status, hormone receptor status, and primary surgery. The ma jority of patients had private insurance at trial registration: E1199: 85.6% (4154/4854) and E5103: 82.4% (3987/4836); median SES index was 53.8 (range: 41.8‐66.8) and 54.1 (range: 44.5‐66.1), respectively. Patients with government insurance were less likely to complete chemotherapy treatment (E1199 OR (95%CI): 0.73 (0.57‐0.94); E5103 0.76 (0.64‐0.91)) and had an increased risk of death (E1199 HR (95%CI): 1.44 (1.22‐1.70); E5103 1.29 (1.06‐1.58)) compared to the privately insured patients. There was no association between nSES and chemotherapy completion or overall mortality. Patients with government insurance at trial registration appeared to face barriers in chemotherapy completion and had a higher overall mortality compared to their privately insured counterparts. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

N6‐methyladenine‐related genes affect biological behavior and the prognosis of glioma

xloma.fota13 shared this article with you from Inoreader N6‐methyladenine‐related genes affect biological behavior and the prognosis of glioma Via Cancer Medicine The nine m6A‐related genes risk score was identified as a new potential prognostic biomarker in gliomas. The nomogram based on the nine m6A‐related genes signature and clinicopathological features had good efficacy in predicting the survival probability, which is pivotal to design individual therapy for patients with glioma Abstract Background Although aberrant expression of N6‐methyladenine (m6A) methylation‐related genes contribute to tumorigenesis in many solid tumors, the prognostic value of the m6A‐related genes and their correlation with clinicopathological features in gliomas need advanced study. Methods The clinical and sequencing data of 288 patients with glioma were extracted from Chinese Glioma Genome Atlas database. By univariate and multivariable Cox regression analysis, the m6A‐related prognostic genes were identified, and their correlation with clinicopathological features was further analysis. A nomogram was constructed by R software and the performance of it was assessed by calibration and time‐dependent receiver operating characteristic curve. Results Nine m6A‐related genes were identified as independent prognostic factors, which were mostly enriched in RNA splicing, regulation of immune response and vesicle‐mediated transport. By expression value and regression coefficient of these genes, we constructed risk score of each patient, which was highly associated with clinicopathological features. Kaplan–Meier curve showed that the prognosis of patients with high‐risk scores was significantly worse than that with low‐risk scores (HR = 4.30, 95% CI = 3.16–5.85, p < 0.0001). A nomogram was constructed based on the nine m6A‐related genes signature and clinicopathological features with well‐fitted calibration curves (c‐index = 0.82), showing high specificity and sensitivity (area under the curve for 1‐, 3‐, and 5‐years survival probability = 0.874, 0.918, and 0.934). Conclusions A nine m6A‐related genes signature was identified in gliomas. The m6A‐related risk score is a novel prognostic factor for patients with glioma, and is associated with clinicopathological features. Moreover, the nomogram based on the nine m6A‐related genes signature and clinicopathological features had good efficacy in predicting the survival probability. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Bioelectrical impedance analysis for perioperative water management in adult cardiovascular valve disease surgery

xlomafota.13 shared this article with you from Inoreader Bioelectrical impedance analysis for perioperative water management in adult cardiovascular valve disease surgery Via Latest Results for Surgery Today Abstract Purpose Bioelectrical impedance analysis (BIA) has been used recently to measure the body water of patients with acute heart failure. We used BIA in this study to better understand, and possibly identify a predictive marker for, perioperative water behavior in cardiac surgery patients. Methods We measured body water and studied its behavior in 44 patients undergoing surgery for cardiac valvular disease at our hospital. Measurements included the levels of extracellular water (ECW), intracellular water (ICW), and total body water, the edema index (EI), and the ratio of ECW to total body water. The first measured EI was defined as the "preoperative EI" and the maximum as the "peak EI". Results A negative correlation was found between the preoperative EI and the preoperative estimated glomerular filtration rate (eGFR) (R = 0.644, p < 0.001). Positive correlations were found between the peak EI and the ICU stay (R = 0.625, p < 0.001), the peak EI and the ventilation time (R = 0.366, p < 0.01), and the preoperative EI and the ICU stay (R = 0.464, p = 0.026). Conclusion The EI is possibly a predictive marker for perioperative water management in cardiac surgery. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.