Association between local treatment modalities and event-free survival, overall survival, and local recurrence in patients with localised Ewing Sarcoma: report from the Ewing 2008 trial

BackgroundLocal treatment is a crucial element in the standard of care for Ewing sarcoma (EWS). While systemic treatment is improved in randomised clinical trials, local treatment modalities are discussed controversially. We analysed the association between local therapy and event-free survival (EFS), overall survival (OS), and local recurrence (LR) in prospectively collected data of patients with localised EWS.Patients and methodsWe analysed data from the international Ewing 2008 study registered between 2009 and 2019 in 117 centres. After induction chemotherapy, patients received surgery, radiotherapy, or a combination thereof. We performed Cox regression, conducted propensity score-weighted sensitivity analysis, and performed subgroup analyses. Hazard ratios (HRs) and 95% confidence intervals are reported.ResultsWe included 863 patients with localised EWS (surgery alone: 331, combination therapy: 358, definitive radiotherapy: 174). In patients treated with combination therapy compared to surgery alone, EFS HR was 0.84 (0.57–1.24; p = 0.38), OS HR was 0.84 (0.57–1.23; p = 0.41), and LR HR was 0.58 (0.26–1.31; p = 0.19). Hazards of any event were increased in patients treated with definitive radiotherapy compared to surgery only, HR 1.53 (1.02–2.31; p = 0.04). Patients with poor responses to chemotherapy benefitted from combination therapy over definitive surgery with an EFS HR 0.49 (0.27–0.89; p = 0.02). Patients with pelvic tumours benefitted from combination therapy over surgery only regarding LR, HR 0.12 (0.02–0.72; p = 0.02).ConclusionPatients with poor responses to chemotherapy benefitted from radiotherapy added to surgery. In the whole group, radiotherapy alone as opposed to surgery alone increased the hazards of any event.Experimentele farmacotherapi

Effect of Radiotherapy Dose on Outcome in Nonmetastatic Ewing Sarcoma

Effect of Radiotherapy Dose on Outcome in Nonmetastatic Ewing Sarcom

Evaluation of the NOD/SCID xenograft model for glucocorticoid-regulated gene expression in childhood B-cell precursor acute lymphoblastic leukemia

BACKGROUND: Glucocorticoids such as prednisolone and dexamethasone are critical drugs used in multi-agent chemotherapy protocols used to treat acute lymphoblastic leukemia (ALL), and response to glucocorticoids is highly predictive of outcome. The NOD/SCID xenograft mouse model of ALL is a clinically relevant model in which the mice develop a systemic leukemia which retains the fundamental biological characteristics of the original disease. Here we report a study evaluating the NOD/SCID xenograft mouse model to investigate glucocorticoid-induced gene expression. Cells from a glucocorticoid-sensitive xenograft derived from a child with B-cell precursor ALL were inoculated into NOD/SCID mice. When highly engrafted the mice were randomized into groups of 4 to receive dexamethasone 15 mg/kg by intraperitoneal injection or vehicle control. Leukemia cells were harvested from mice spleens at 0, 8, 24 or 48 hours thereafter, and gene expression analyzed on Illumina WG-6_V3 chips, comparing all groups to time 0 hours. RESULTS: The 8 hour dexamethasone-treated timepoint had the highest number of significantly differentially expressed genes, with fewer observed at the 24 and 48 hour timepoints, and with minimal changes seen across the time-matched controls. When compared to publicly available datasets of glucocorticoid-induced gene expression from an in vitro cell line study and from an in vivo study of patients with ALL, at the level of pathways, expression changes in the 8 hour xenograft samples showed a similar response to patients treated with glucocorticoids. Replicate analysis revealed that at the 8 hour timepoint, a dataset with high signal and differential expression, using data from 3 replicates instead of 4 resulted in excellent recovery scores of > 0.9. However at other timepoints with less signal very poor recovery scores were obtained with 3 replicates. CONCLUSIONS: The NOD/SCID xenograft mouse model provides a reproducible experimental system in which to investigate clinically-relevant mechanisms of drug-induced gene regulation in ALL; the 8 hour timepoint provides the highest number of significantly differentially expressed genes; time-matched controls are redundant and excellent recovery scores can be obtained with 3 replicates

A machine Learning Methodology for Chronic Kidney Disease

Most of the people in the world are suffering a lot with Chronic Kidney Disease (CKD) widely considered to be a global issue. People with heart disease, hypertension, diabetes or who have suffering from CKD family they are at risk.This is related to improved mortality and high risk of a few other conditions, including the raise of heart disease and human services. The adverse outcome of CKD can be prevented with proper early detection and management. Machine Learning (ML) aids to analyze tens of thousands of data points and produce outcomes, provides regular risk scores, precise resource allocation, and has many other applications healthcare. In this paper some machine learning techniques are used and compared namely Support Vector Machine (SVM), Naïve Bayes (NB), NB-TREE, and Iterative Random Forest (IRF). Among all these four algorithms IRF got the best accuracy of 99.4%. Here we are using IRF which provide the stable decision paths with high order interactions. Hence IRF could be used for any data to get good accuracy

Optimization of wire-cut electric discharge machining process parameters for hybrid MMC(AA7475/ZrO2/gr) using Taguchi method: an experimental study

AbstractMetal-matrix composites (MMCs) and hybrid metal-matrix composites (HMMCs) are novel materials that possess distinctive mechanical characteristics, making them well-suited for industrial applications. This research implements an experimental study of the mechanical properties of HMMCs, where weight percentages (2, 3, and 4 wt. %) of zirconium dioxide (ZrO2) and graphite powder (Gr) are used as reinforcements and the aluminum alloy 7475 (AA7475) is used as a matrix. In this investigation, the stir casting method was used to prepare the composite by using AA7475 alloy with pre-heated reinforced particles of ZrO2 and graphite with various reinforcement weight percentages. Among these combinations, AA with 4 wt. % ZrO2 and 2 wt.% Gr showed enhanced mechanical properties. The mechanical properties of the ultimate tensile strength, yield strength, and hardness were evaluated. A Scanning Electron Microscope analysis was conducted to study the reinforcement distribution in the matrix. The input parameters for wire-cut electrical discharge machining (WCEDM) are pulse-on time (TON), pulse peak current (IP), and flushing pressure (PF). The material removal rate and surface roughness are the output responses. Determining the ideal set of process parameters in WCEDM for HMMC also involved the use of the Taguchi design technique known as the L9 orthogonal array. The peak current for the MRR and flushing pressure for the SR are the most prominent parameters

Systemic treatment of advanced clear cell sarcoma: results from a retrospective international series from the World Sarcoma Network.

BACKGROUND: Clear cell sarcoma (CCS) is a translocated aggressive malignancy with a high incidence of metastases and poor prognosis. There are few studies describing the activity of systemic therapy in CCS. We report a multi-institutional retrospective study of the outcomes of patients with advanced CCS treated with systemic therapy within the World Sarcoma Network (WSN). MATERIALS AND METHODS: Patients with molecularly confirmed locally advanced or metastatic CCS treated with systemic therapy from June 1985 to May 2021 were included. Baseline demographic and treatment information, including response by Response Evaluation Criteria in Solid Tumours (RECIST) 1.1, was retrospectively collected by local investigators. Descriptive statistics were carried out. RESULTS: Fifty-five patients from 10 institutions were included. At diagnosis, the median age was 30 (15-73) years and 24% (n = 13/55) had metastatic disease. The median age at diagnosis was 30 (15-73) years. Most primary tumours were at aponeurosis (n = 9/55, 16%) or non-aponeurosis limb sites (n = 17/55, 31%). The most common fusion was EWSR1-ATF1 (n = 24/55, 44%). The median number of systemic therapies was 1 (range 1-7). The best response rate was seen for patients treated with sunitinib (30%, n = 3/10), with a median progression-free survival of 4 [95% confidence interval (CI) 1-7] months. The median overall survival for patients with advanced/metastatic disease was 15 months (95% CI 3-27 months). CONCLUSIONS: Soft tissue sarcoma-type systemic therapies have limited benefit in advanced CCS and response rate was poor. International, multicentre prospective translational studies are required to identify new treatments for this ultra-rare subtype, and access to early clinical trial enrolment remains key for patients with CCS