Type, intensity, and duration of chemotherapy (CHT) and their correlation with prognosis of localized soft tissue Ewing tumors (STET): Experience of the Cooperative Weichteilsarkomstudiengruppe (CWS).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 10527-10527
Author(s):  
Ewa Koscielniak ◽  
Monika Scheer ◽  
Monika Sparber-Sauer ◽  
Erika Hallmen ◽  
Ivo Leuschner ◽  
...  

10527 Background: The optimal type and intensity of CHT in the treatment of STET is still a matter of debate. The CWS group has treated STET similar to rhabdomyosarcoma. We have analyzed the prognosis of STET in relation to the CHT regimens used in three consecutive CWS studies CWS-91, -96 and CWS- 2002P. Methods: 243 pts with localized STET were included. Their median age was 12 (range 0.1-29) yrs. In the CWS-91 pts with primary tumor resection (IRSG I and II) were treated with VACA (vincristine (VCR), actinomycin D (Act D), cyclophosphamide (CYC), doxorubicin (DOX), for 10 or 20 weeks. All other CWS-91 pts (high risk group, HRG) received EVAIA (ifosfamide (IFO) instead of CYC plus VP16) for 37 weeks. In the CWS-96 and CWS-2002P all STET pts were allocated to the HRG. In CWS-96 therapy was randomized: VAIA (IFO, DOX, Act D, VCR) vs. CEVAIE (Epi-DOX instead of DOX, plus carboplatin and VP16), for 25 weeks. In CWS-2002P VAIA (25 weeks) plus maintenance CHT with CYC and vinblastine (VBL) for 26 weeks were used. The cumulative doses varied: IFO 24-72 g/m², CYC 4.8-7.35 g/m², DOX 120-360 mg/m², Act D 3-9 mg/m², VP16 1.8-5.4 g/m². Irradiation was stratified depending on results of the primary or secondary resection and response. Results: 5 yr event free (EFS) and overall survival (OS) were 64% and 73%. The median observation time of survivors was 9 yrs. 5yr EFS and OS by study were: CWS-91 64 % and 72 %, CWS-96 57% and 70 %, CWS-2002P 78 % and 86 % respectively (n.s.). 5 yr EFS and OS for VACA arm were 79% and 90%. 5 yr EFS and OS by CHT for HRG were: EVAIA 57% and 65%, VAIA 64% and 80%, CEVAIE 45% and 54%, VAIA with CYC/VBL 84% and 87%, respectively (p = 0 .003). 5yr EFS and OS for irradiated (n = 181) vs. not irradiated (n = 48) patients were 63 % and 72% vs. 63% and 79%, respectively. Conclusions: The outcomes between CHT arms differed significantly: CEVAIA correlated with the worst outcome while VAIA with CYC/VBL showed the best results. A small group of low risk patients have an excellent prognosis with substantially reduced CHT. Ewing tumors are biologically heterogeneous and more diversification in therapy stratification is warranted to avoid overtreatment.

Author(s):  
Yan Fan ◽  
Hong Shen ◽  
Brandon Stacey ◽  
David Zhao ◽  
Robert J. Applegate ◽  
...  

AbstractThe purpose of this study was to explore the utility of echocardiography and the EuroSCORE II in stratifying patients with low-gradient severe aortic stenosis (LG SAS) and preserved left ventricular ejection fraction (LVEF ≥ 50%) with or without aortic valve intervention (AVI). The study included 323 patients with LG SAS (aortic valve area ≤ 1.0 cm2 and mean pressure gradient < 40 mmHg). Patients were divided into two groups: a high-risk group (EuroSCORE II ≥ 4%, n = 115) and a low-risk group (EuroSCORE II < 4%, n = 208). Echocardiographic and clinical characteristics were analyzed. All-cause mortality was used as a clinical outcome during mean follow-up of 2 ± 1.3 years. Two-year cumulative survival was significantly lower in the high-risk group than the low-risk patients (62.3% vs. 81.7%, p = 0.001). AVI tended to reduce mortality in the high-risk patients (70% vs. 59%; p = 0.065). It did not significantly reduce mortality in the low-risk patients (82.8% with AVI vs. 81.2%, p = 0.68). Multivariable analysis identified heart failure, renal dysfunction and stroke volume index (SVi) as independent predictors for mortality. The study suggested that individualization of AVI based on risk stratification could be considered in a patient with LG SAS and preserved LVEF.


2018 ◽  
Vol 9 (1_suppl) ◽  
pp. 5-12 ◽  
Author(s):  
Dominique N van Dongen ◽  
Rudolf T Tolsma ◽  
Marion J Fokkert ◽  
Erik A Badings ◽  
Aize van der Sluis ◽  
...  

Background: Pre-hospital risk stratification of non-ST-elevation acute coronary syndrome (NSTE-ACS) by the complete HEART score has not yet been assessed. We investigated whether pre-hospital risk stratification of patients with suspected NSTE-ACS using the HEART score is accurate in predicting major adverse cardiac events (MACE). Methods: This is a prospective observational study, including 700 patients with suspected NSTE-ACS. Risk stratification was performed by ambulance paramedics, using the HEART score; low risk was defined as HEART score ⩽ 3. Primary endpoint was occurrence of MACE within 45 days after inclusion. Secondary endpoint was myocardial infarction or death. Results: A total of 172 patients (24.6%) were stratified as low risk and 528 patients (75.4%) as intermediate to high risk. Mean age was 53.9 years in the low risk group and 66.7 years in the intermediate to high risk group ( p<0.001), 50% were male in the low risk group versus 60% in the intermediate to high risk group ( p=0.026). MACE occurred in five patients in the low risk group (2.9%) and in 111 (21.0%) patients at intermediate or high risk ( p<0.001). There were no deaths in the low risk group and the occurrence of acute myocardial infarction in this group was 1.2%. In the high risk group six patients died (1.1%) and 76 patients had myocardial infarction (14.4%). Conclusions: In suspected NSTE-ACS, pre-hospital risk stratification by ambulance paramedics, including troponin measurement, is accurate in differentiating between low and intermediate to high risk. Future studies should investigate whether transportation of low risk patients to a hospital can be avoided, and whether high risk patients benefit from immediate transfer to a hospital with early coronary angiography possibilities.


2020 ◽  
Vol 12 (2) ◽  
Author(s):  
Widowati W ◽  
Akbar SH ◽  
Tin MH

Introduction: Enamel demineralization is associated with decrease in saliva pH due to fermentation of sugar by oral commensal. Thus, exploring the changing pattern of saliva pH is meaningful in dental caries prevention. The aim of this study was to compare the changing pattern of saliva pH after consuming different types of sweeteners (sucrose and maltitol). Methods: It was a case-control study involving 14 male patients attending IIUM dental clinic who were selected with the intention of getting seven patients with high caries risk ( DMFT ≥6) and seven patients with low caries risk (DMFT ≤3) with initial saliva pH interval of 6.5 to7.5. Patients were asked to consume snacks containing 8 gram sucrose and 8 gram maltitol as sweeteners. The changing pH values of the saliva were measured by Waterproof pHTestr 10BNC (Oakton, Vernon Hills, USA) seven times consecutively at 0 (before snack consumption), and at 5, 10, 15, 20, 30 and 60 minutes after snack consumption. The pH values of saliva of patients with low and high caries risk after consuming sucrose and maltitol were statistically analized by using Anova and Tukey-HSD tests at α = 0.05. Result: There were significant differences in saliva pH changes between low-risk group and high-risk group after consuming sucrose and maltitol. Conclusion: The changing patterns of saliva pH in high-risk patients were lower than those of low-risk patients after consuming two types of snacks containing sucrose and maltitol.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
T Grinberg ◽  
T Bental ◽  
Y Hammer ◽  
A R Assali ◽  
H Vaknin-Assa ◽  
...  

Abstract Background Following Myocardial Infarction (MI), patients are at increased risk for recurrent cardiovascular events, particularly during the immediate period. Yet some patients are at higher risk than others, owing to their clinical characteristics and comorbidities, these high-risk patients are less often treated with guideline-recommended therapies. Aim To examine temporal trends in treatment and outcomes of patients with MI according to the TIMI risk score for secondary prevention (TRS2°P), a recently validated risk stratification tool. Methods A retrospective cohort study of patients with an acute MI, who underwent percutaneous coronary intervention and were discharged alive between 2004–2016. Temporal trends were examined in the early (2004–2010) and late (2011–2016) time-periods. Patients were stratified by the TRS2°P to a low (≤1), intermediate (2) or high-risk group (≥3). Clinical outcomes included 30-day MACE (death, MI, target vessel revascularization, coronary artery bypass grafting, unstable angina or stroke) and 1-year mortality. Results Among 4921 patients, 31% were low-risk, 27% intermediate-risk and 42% high-risk. Compared to low and intermediate-risk patients, high-risk patients were older, more commonly female, and had more comorbidities such as hypertension, diabetes, peripheral vascular disease, and chronic kidney disease. They presented more often with non ST elevation MI and 3-vessel disease. High-risk patients were less likely to receive drug eluting stents and potent anti-platelet drugs, among other guideline-recommended therapies. Evidently, they experienced higher 30-day MACE (8.1% vs. 3.9% and 2.1% in intermediate and low-risk, respectively, P<0.001) and 1-year mortality (10.4% vs. 3.9% and 1.1% in intermediate and low-risk, respectively, P<0.001). During time, comparing the early to the late-period, the use of potent antiplatelets and statins increased among the entire cohort (P<0.001). However, only the high-risk group demonstrated a significantly lower 30-day MACE (P=0.001). During time, there were no differences in 1-year mortality rate among all risk categories. Temporal trends in 30-day MACE by TRS2°P Conclusion Despite a better application of guideline-recommended therapies, high-risk patients after MI are still relatively undertreated. Nevertheless, they demonstrated the most notable improvement in outcomes over time.


1981 ◽  
Vol 26 (1) ◽  
pp. 24-26
Author(s):  
W. J. Morgan ◽  
Moira P. J. McGuigan ◽  
S. Williams ◽  
G. Solomon

Of 400 consecutive patients who had wounds treated in the Accident Department, 200 remembered receiving either booster injections or a full course of tetanus toxoid in the last 10 years. During this period, 182 patients received their initial toxoid injection in association with treatment of a wound in an accident department. Only 71 (38%) of these patients attended for a full course of injections. From our assessment of the wounds and the patient's anti-tetanus immunity, 79 patients (20%) were considered to be at risk of developing tetanus. By further considering the time interval elapsed between injury and treatment, a ‘high risk” group of 13 patients (3%) was recognised. It is recommended that the use of human immunoglobulin shoul I be reserved for the ‘high risk’ group, and that the remainer of the ‘at-risk’ patients should receive penecillin prophylaxis only.


PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e11911
Author(s):  
Lei Liu ◽  
Huayu He ◽  
Yue Peng ◽  
Zhenlin Yang ◽  
Shugeng Gao

Background The prognosis of patients for lung adenocarcinoma (LUAD) is known to vary widely; the 5-year overall survival rate is just 63% even for the pathological IA stage. Thus, in order to identify high-risk patients and facilitate clinical decision making, it is vital that we identify new prognostic markers that can be used alongside TNM staging to facilitate risk stratification. Methods We used mRNA expression from The Cancer Genome Atlas (TCGA) cohort to identify a prognostic gene signature and combined this with clinical data to develop a predictive model for the prognosis of patients for lung adenocarcinoma. Kaplan-Meier curves, Lasso regression, and Cox regression, were used to identify specific prognostic genes. The model was assessed via the area under the receiver operating characteristic curve (AUC-ROC) and validated in an independent dataset (GSE50081) from the Gene Expression Omnibus (GEO). Results Our analyses identified a four-gene prognostic signature (CENPH, MYLIP, PITX3, and TRAF3IP3) that was associated with the overall survival of patients with T1-4N0-2M0 in the TCGA dataset. Multivariate regression suggested that the total risk score for the four genes represented an independent prognostic factor for the TCGA and GEO cohorts; the hazard ratio (HR) (high risk group vs low risk group) were 2.34 (p < 0.001) and 2.10 (p = 0.017). Immune infiltration estimations, as determined by an online tool (TIMER2.0) showed that CD4+ T cells were in relative abundance in the high risk group compared to the low risk group in both of the two cohorts (both p < 0.001). We established a composite prognostic model for predicting OS, combined with risk-grouping and clinical factors. The AUCs for 1-, 3-, 5- year OS in the training set were 0.750, 0.737, and 0.719; and were 0.645, 0.766, and 0.725 in the validation set. The calibration curves showed a good match between the predicted probabilities and the actual probabilities. Conclusions We identified a four-gene predictive signature which represents an independent prognostic factor and can be used to identify high-risk patients from different TNM stages of LUAD. A new prognostic model that combines a prognostic gene signature with clinical features exhibited better discriminatory ability for OS than traditional TNM staging.


2018 ◽  
Vol 17 (3) ◽  
pp. 4-10
Author(s):  
A. Yu. Efanov ◽  
Yu. A. Vyalkina ◽  
Yu. A. Petrova ◽  
Z. M. Safiullina ◽  
O. V. Abaturova ◽  
...  

Aim. To assess the specifics of antihypertension therapy (AHT) in hypertensives of various cardiovascular risk, in the registry of chronic non-communicable diseases in Tyumenskaya oblast.Material and methods. A random sample studied, of 1704 patients with hypertension, inhabitants of Tyumenskaya oblast (region), ascribed to dispensary follow-up. Mean age 62±7,5 y.o. Of those 31,5% (n=537) males. The prevalence and efficacy of AHT assessed according to cardiovascular risk level. The significance was evaluated with the criteria χ2.Results. AHT was characterized by the growth of the frequency of treatment approaches with cardiovascular risk consideration. Regular treatment took 33,9% patients of low and moderate risk vs 41,3% of high and very high (p<0,01). In the male group such tendency also took place. Gender specifics of AHT was characterized by that in the groups of high and very high risk females took medications significantly more commonly than males — 46,6% vs 29,1% in high risk group (p<0,01) and 47,5% vs 30% in very high risk group (p<0,01). With the increase of the risk level, there was decline of treatment efficacy — from 95% in low risk group to 32,5% in very high risk group; 53,1% of the participants were taking monotherapy, 32,9% — two drugs, 14,0% — ≥3 drugs. With the increase of risk grade there is tendency to increase of combinational AHT, however with no significant increase of efficacy. Treatment efficacy in high and very high risk patients comparing to patients with low and moderate risk was significantly lower — 33,1% vs 69,7% (p<0,01), respectively. Statins intake among the high and very high risk patients was 10,6-11,0% males and 7,8% females (p<0,05).Conclusion. AHT in hypertensives in Tymenskaya oblast, under dispensary follow-up, is characterized by insufficient usage of combinational drugs. With the raise of cardiovascular risk there is tendency to higher rate of combinational AHT. However there is no significant increase in efficacy of treatment with the increase of medications number. A very low rate of statins intake is noted. The obtained specifics witness for the necessity to optimize AHT among the high and very high risk patients — inhabitants of Tyumenskya oblast.


Author(s):  
Junyu Huo ◽  
Jinzhen Cai ◽  
Ge Guan ◽  
Huan Liu ◽  
Liqun Wu

Background: Due to the heterogeneity of tumors and the complexity of the immune microenvironment, the specific role of ferroptosis and pyroptosis in hepatocellular carcinoma (HCC) is not fully understood, especially its impact on prognosis.Methods: The training set (n = 609, merged by TCGA and GSE14520) was clustered into three subtypes (C1, C2, and C3) based on the prognosis-related genes associated with ferroptosis and pyroptosis. The intersecting differentially expressed genes (DEGs) among C1, C2, and C3 were used in univariate Cox and LASSO penalized Cox regression analysis for the construction of the risk score. The median risk score served as the unified cutoff to divide patients into high- and low-risk groups.Results: Internal (TCGA, n = 370; GSE14520, n = 239) and external validation (ICGC, n = 231) suggested that the 12-gene risk score had high accuracy in predicting the OS, DSS, DFS, PFS, and RFS of HCC. As an independent prognostic indicator, the risk score could be applicable for patients with different clinical features tested by subgroup (n = 26) survival analysis. In the high-risk patients with a lower infiltration abundance of activated B cells, activated CD8 T cells, eosinophils, and type I T helper cells and a higher infiltration abundance of immature dendritic cells, the cytolytic activity, HLA, inflammation promotion, and type I IFN response in the high-risk group were weaker. The TP53 mutation rate, TMB, and CSC characteristics in the high-risk group were significantly higher than those in the low-risk group. Low-risk patients have active metabolic activity and a more robust immune response. The high- and low-risk groups differed significantly in histology grade, vascular tumor cell type, AFP, new tumor event after initial treatment, main tumor size, cirrhosis, TNM stage, BCLC stage, and CLIP score.Conclusion: The ferroptosis and pyroptosis molecular subtype-related signature identified and validated in this work is applicable for prognosis prediction, immune microenvironment estimation, stem cell characteristics, and clinical feature assessment in HCC.


2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Eunjin Lee ◽  
Ji Won Lee ◽  
Boram Lee ◽  
Kyunghee Park ◽  
Joonho Shim ◽  
...  

Abstract Background MYCN amplification is the most important genomic feature in neuroblastoma (NB). However, limited studies have been conducted on the MYCN non-amplified NB including low- and intermediate-risk NB. Here, the genomic characteristics of MYCN non-amplified NB were studied to allow for the identification of biomarkers for molecular stratification. Methods Fifty-eight whole exome sequencing (WES) and forty-eight whole transcriptome sequencing (WTS) samples of MYCN non-amplified NB were analysed. Forty-one patients harboured WES and WTS pairs. Results In the MYCN non-amplified NB WES data, maximum recurrent mutations were found in MUC4 (26%), followed by RBMXL3 (19%), ALB (17%), and MUC16 and SEPD8 (14% each). Two gene fusions, CCDC32-CBX3 (10%) and SAMD5-SASH1 (6%), were recurrent in WTS analysis, and these fusions were detected mostly in non-high-risk patients with ganglioneuroblastoma histology. Analysis of risk-group-specific biomarkers showed that several genes and gene sets were differentially expressed between the risk groups, and some immune-related pathways tended to be activated in the high-risk group. Mutational signatures 6 and 18, which represent DNA mismatch repair associated mutations, were commonly detected in 60% of the patients. In the tumour mutation burden (TMB) analysis, four patients showed high TMB (> 3 mutations/Mb), and had mutations in genes related to either MMR or homologous recombination. Excluding four outlier samples with TMB > 3 Mb, high-risk patients had significantly higher levels of TMB compared with the non-high-risk patients. Conclusions This study provides novel insights into the genomic background of MYCN non-amplified NB. Activation of immune-related pathways in the high-risk group and the results of TMB and mutational signature analyses collectively suggest the need for further investigation to discover potential immunotherapeutic strategies for NB.


2019 ◽  
Vol 26 (3) ◽  
pp. 529-535 ◽  
Author(s):  
Parisa R Khalighi ◽  
Kylee L Martens ◽  
Andrew A White ◽  
Shan Li ◽  
Emily Silgard ◽  
...  

Purpose Current guidelines for tumor lysis syndrome management recommend rasburicase for high-risk patients. Adherence to guidelines has not been well studied, and the correlation between uric acid reduction and clinically relevant outcomes, such as acute kidney injury, remains unclear. Our study aims to describe rasburicase utilization patterns and outcomes in cancer patients with varying risks for tumor lysis syndrome. Methods In this retrospective cohort study, we included cancer inpatients who received rasburicase for tumor lysis syndrome management at two affiliated academic hospitals from 2009 to 2015. Patients were classified by tumor lysis syndrome risk categories prior to drug administration. Primary outcomes included acute kidney injury incidence and renal recovery. Secondary outcomes included uric acid nadir, mortality, and hospital length-of-stay. Results Among 164 patients, 42 (26%) had high-, 63 (38%) had intermediate-, and 59 (36%) had low-risk for tumor lysis syndrome. A total of 94 patients (57%) had existing renal dysfunction prior to rasburicase use. This occurred more frequently in low- (68%) compared to intermediate- (57%) and high- (43%) risk patients ( p = 0.044). A greater proportion of patients in the high-risk group (78%) had renal recovery when compared to the intermediate- (61%) or low- (45%) risk groups ( p = 0.056). Despite a similar length of stay, the high-risk group had a significantly lower 30-day mortality (10%) when compared to intermediate- (25%) or low- (32%) risk groups ( p = 0.029). Conclusions Our results suggest that rasburicase may be frequently prescribed to treat hyperuricemia unrelated to tumor lysis syndrome in cancer patients. Improved education and adherence to guidelines may improve clinical and economic outcomes associated with rasburicase administration.


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