scholarly journals Hypofractionated radiotherapy for newly diagnosed elderly glioblastoma patients: A systematic review and network meta-analysis

PLoS ONE ◽  
2021 ◽  
Vol 16 (11) ◽  
pp. e0257384
Author(s):  
Suely Maymone de Melo ◽  
Gustavo Nader Marta ◽  
Carolina de Oliveira Cruz Latorraca ◽  
Camila Bertini Martins ◽  
Orestis Efthimiou ◽  
...  

Objective To evaluate different hypofractionated radiotherapy (HRT) regimens for newly diagnosed elderly glioblastoma (GBM) patients. Methods We performed a systematic review with network meta-analysis (NMA), including searches on CENTRAL, Medline, EMBASE, CINAHL, clinical trial databases and manual search. Only randomized clinical trials (RCTs) were included. Primary outcomes: overall survival (OS) and adverse events (AE). Secondary outcomes: progression-free-survival (PFS) and quality of life (QoL). We used the Cochrane Risk of Bias (RoB) table for assessing individual studies and CINeMA for evaluating the certainty of the final body of evidence. Results Four RCTs (499 patients) were included. For OS, the estimates from NMA did not provide strong evidence of a difference between the HRTs: 40 Gray (Gy) versus 45 Gy (HR: 0.89; CI 95%: 0.42, 1.91); 34 Gy versus 45 Gy (HR: 0.85; CI 95% 0.43, 1.70); 25 Gy versus 45 Gy (HR: 0.81; CI 95% 0.32, 2.02); 34 Gy versus 40 Gy (HR: 0.95; CI 95% 0.57, 1.61); and 25 Gy versus 34 Gy (HR: 0.95; CI 95% 0.46, 1.97). We performed qualitative synthesis for AE and QoL due to data scarcity and clinical heterogeneity among studies. The four studies reported a similar QoL (assessed by different methods) between arms. One RCT reported grade ≥ 3 AE, with no evidence of a difference between arms. PFS was reported in one study (25 Gy versus 40 Gy), with no evidence of a difference between arms. Conclusion This review found no evidence of a difference between the evaluated HRTs for efficacy and safety.

2020 ◽  
Author(s):  
jie zhang ◽  
rui zhou ◽  
jing zhu

Abstract Objectives : As reported, nivolumab and pembrolizumab have shown to be superior to docetaxel in advanced NSCLC. Therefore, we performed a systematic review and network meta-analysis to compare the efficacy and safety of nivolumab and pembrolizumab. Materials and Methods : Randomized controlled trials (RCTs) assessing the effect and safety of nivolumab or pembrolizumab versus docetaxel for patients with advanced NSCLC in the second-line treatment were included. Two investigators independently searched articles, extracted data, and assessed the quality of included studies. After that, we performed pairwise direct meta-analyses (nivolumab vs. docetaxel and pembrolizumab vs. docetaxel) and indirect comparison (nivolumab vs. pembrolizumab) using network meta-analyses methods. Results : Four RCTs involving 2391 patients were included in the meta-analysis. In analyses of overall survival (OS), progression-free survival (PFS) and overall response rate (ORR) in the direct meta-analysis, nivolumab and pembrolizumab both showed survival benefits when compared with docetaxel. For the indirect comparison, nivolumab show no signifcant difference in OS, PFS and ORR when compared with pembrolizumab (OS: HR 1.03; 95% CI 0.84–1.26; PFS: HR 0.95; 95% CI 0.80–1.14; ORR: HR 1.08; 95% CI 0.67–1.73). For the safety analysis, nivolumab and pembrolizumab both have less toxicity than docetaxel. In indirect comparison, nivolumab showed less all-grade toxicity (OR 0.71; 95% CI 0.49–1.04) and grade 3–5 toxicity (OR 0.32; 95% CI 0.21–0.49) when compared with pembrolizumab.Conclusion : Our meta-analysis suggests that nivolumab and pembrolizumab demonstrated similar clinical benefit for patients with advanced NSCLC in the second-line treatment. It seems that nivolumab has less toxicity when compared with pembrolizumab.


2021 ◽  
Vol 11 ◽  
Author(s):  
Montserrat Lara-Velazquez ◽  
Jack M. Shireman ◽  
Eric J. Lehrer ◽  
Kelsey M. Bowman ◽  
Henry Ruiz-Garcia ◽  
...  

BackgroundImmunotherapy for GBM is an emerging field which is increasingly being investigated in combination with standard of care treatment options with variable reported success rates.ObjectiveTo perform a systematic review of the available data to evaluate the safety and efficacy of combining immunotherapy with standard of care chemo-radiotherapy following surgical resection for the treatment of newly diagnosed GBM.MethodsA literature search was performed for published clinical trials evaluating immunotherapy for GBM from January 1, 2000, to October 1, 2020, in PubMed and Cochrane using PICOS/PRISMA/MOOSE guidelines. Only clinical trials with two arms (combined therapy vs. control therapy) were included. Outcomes were then pooled using weighted random effects model for meta-analysis and compared using the Wald-type test. Primary outcomes included 1-year overall survival (OS) and progression-free survival (PFS), secondary outcomes included severe adverse events (SAE) grade 3 or higher.ResultsNine randomized phase II and/or III clinical trials were included in the analysis, totaling 1,239 patients. The meta-analysis revealed no statistically significant differences in group’s 1-year OS [80.6% (95% CI: 68.6%–90.2%) vs. 72.6% (95% CI: 65.7%–78.9%), p = 0.15] or in 1-year PFS [37% (95% CI: 26.4%–48.2%) vs. 30.4% (95% CI: 25.4%–35.6%) p = 0.17] when the immunotherapy in combination with the standard of care group (combined therapy) was compared to the standard of care group alone (control). Severe adverse events grade 3 to 5 were more common in the immunotherapy and standard of care group than in the standard of care group (47.3%, 95% CI: 20.8–74.6%, vs 43.8%, 95% CI: 8.7–83.1, p = 0.81), but this effect also failed to reach statistical significance.ConclusionOur results suggests that immunotherapy can be safely combined with standard of care chemo-radiotherapy without significant increase in grade 3 to 5 SAE; however, there is no statistically significant increase in overall survival or progression free survival with the combination therapy.


2020 ◽  
Author(s):  
Roberto Ariel Abeldano Zuniga ◽  
Silvia Coca ◽  
Giuliana Abeldano ◽  
Ruth Ana Maria Gonzalez Villoria

Objective. The aim was to assess the clinical effectiveness of drugs used in hospitalized patients with COVID-19 infection. Method. We conducted a systematic review of randomized clinical trials assessing treatment with remdesivir, chloroquine, hydroxychloroquine, lopinavir, ritonavir, dexamethasone, and convalescent plasma, for hospitalized patients with a diagnosis of SARS-CoV-2 infection. The outcomes were mortality, clinical improvement, duration of ventilation, duration of oxygen support, duration of hospitalization), virological clearance, and severe adverse events. Results. A total of 48 studies were retrieved from the databases. Ten articles were finally included in the data extraction and qualitative synthesis of results. The meta-analysis suggests a benefit of dexamethasone versus standard care in the reduction of risk of mortality at day 28; and the clinical improvement at days 14 and 28 in patients treated with remdesivir. Conclusions. Dexamethasone would have a better result in hospitalized patients, especially in low-resources settings. Significance of results. The analysis of the main treatments proposed for hospitalized patients is of vital importance to reduce mortality in low-income countries; since the COVID-19 pandemic had an economic impact worldwide with the loss of jobs and economic decline in countries with scarce resources. Keywords: Drugs; Antivirals; Clinical improvement; Mortality; COVID-19; SARS-CoV2.


Author(s):  
Nádya Santos Moura ◽  
Maria Luziene Sousa Gomes ◽  
Ivana Rios Rodrigues ◽  
Daniel Lorber Rolnik ◽  
Fabrício Silva Costa ◽  
...  

Abstract Objective To identify the most effective procedures recommended for the prevention of preeclampsia. Data Sources A systematic review was performed in the following databases: Pubmed/MEDLINE, CINAHL, Web of Science, Cochrane and LILACS via the Virtual Health Library (VHL). A manual search was also performed to find additional references. The risk of bias, the quality of the evidence, and the classification of the strength of the recommendations were evaluated using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. Selection of Studies In the initial search in the databases, the total number of articles retrieved was 351, and 2 were retrieved through the manual search; after duplicate articles were removed, 333 citations remained. After a thorough review of the titles and abstracts, 315 references were excluded. Accordingly, 18 articles were maintained for selection of the complete text (phase 2). This process led to the exclusion of 6 studies. In total, 12 articles were selected for data extraction and qualitative synthesis. Data Collection The articles selected for the study were analyzed, and we inserted the synthesis of the evidence in the online software GRADEpro Guideline Development Tool (GDT) (McMaster University and Evidence Prime Inc. All right reserved. McMaster University, Hamilton, Ontário, Canada); thus, it was possible to develop a table of evidence, with the quality of the evidence and the classification of the strength of the recommendations. Data Synthesis In total, seven studies recommended the individual use of aspirin, or aspirin combined with calcium, heparin or dipyridamole. The use of calcium alone or in combination with phytonutrients was also highlighted. All of the studies were with women at a high risk of developing preeclampsia. Conclusion According to the studies evaluated, the administration of aspirin is still the best procedure to be used in the clinical practice to prevent preeclampsia.


2018 ◽  
Vol 9 (1) ◽  
pp. e12290 ◽  
Author(s):  
Alejandro Szmulewicz ◽  
Kerollos N. Wanis ◽  
Ashley Gripper ◽  
Federico Angriman ◽  
Jeff Hawel ◽  
...  

2020 ◽  
Vol 16 (10) ◽  
pp. 585-596 ◽  
Author(s):  
Ezzeldin M Ibrahim ◽  
Ahmed A Refae ◽  
Ali M Bayer ◽  
Emad R Sagr

Aim: Poly(ADP-ribose) polymerase inhibitors (PARPIs) improved progression-free survival among patients with recurrent ovarian cancer. This meta-analysis examined the effectiveness of PARPIs as maintenance strategy for newly diagnosed patients with advanced high-grade ovarian cancer with or without mutations. Materials & methods: Using defined selection criteria, a literature search identified four eligible randomized clinical trials involving 2386 patients. Results: Compared with placebo maintenance, PARPIs achieved a 46% reduction in the risk of progression or death as compared with placebo (hazard ratio: 0.54; 95% CI: 0.39–0.73; p < 0.0001). That benefit was shown in all clinical subgroups: among those with BRCA mutation, with negative/unknown BRCA mutation, and in those with homologous recombination deficient tumors. Data about the effect on overall survival are still premature. Conclusion: In patients with newly diagnosed advanced ovarian cancer, PARPIs maintenance after standard therapy achieved a significant improvement in progression-free survival as compared with placebo, overall and in all subgroups.


Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2570-2570
Author(s):  
R. Suppiah ◽  
E. Walker ◽  
K. Almhanna ◽  
S. Andresen ◽  
J. Reed ◽  
...  

Abstract Background: The activity of V in myeloma was first described in the 1970’s. Although Phase II data suggest that V demonstrates single agent activity, subsequent reports have questioned its role. Due to these conflicting results, we conducted a subanalysis investigating the effect of V dose in the phase II DVd-T regimen that we have previously reported (Agrawal et al ASH 2003). We evaluated the effects of V dose on progression free survival (PFS) and overall survival (OS) in newly diagnosed and relapsed/refractory patients treated with DVd-T. Patients and Methods: As previously reported, this Phase II study enrolled 102 patients with newly diagnosed or relapsed/refractory multiple myeloma with evidence of end organ damage. DVd-T was administered as previously reported. After best response, patients were maintained on prednisone 50mg every other day and the maximum tolerated dose of thalidomide until disease progression. For patients experiencing grade 1 neuropathy, V was reduced by 25%, and for grade 2, by 50%. Patients developing grade 3/4 neuropathy had V discontinued and thalidomide suspended until toxicity decreased by at least one grade. Univariate analyses were conducted to assess the effect of V dose reduction or elimination on PFS and OS. Multivariate analyses were performed to adjust for the impact of age, platelet count, stage, quality of response (CR or near CR versus SD or PR), and thalidomide dose. Results: Trial included 53 newly diagnosed and 49 relapsed/refractory patients. Median age was 62.9 years. 59% had stage 3 or 4 disease. 37% had abnormal cytogenetics. Median beta-2 microglobulin was 4.1. Overall response rate of 87% was seen in newly diagnosed patients (36% achieved CR; 13% near CR; 38% PR; 8% SD; 6% PD). In the relapsed/refractory patients, overall response rate of 87% was achieved (21% achieved CR; 26% near CR; 40% PR; 13% SD). Median follow up was 28.1 months. Median PFS for the newly diagnosed group was 28.2 months and 15.5 for the relapsed/refractory group. Median OS was 39.9 months for the relapsed/refractory group. After 50 months of follow-up for the newly diagnosed group, median OS has not been reached. In total, 464 cycles were administered, of which 225 were given with full dose V and 242 with reduced dose or eliminated V. Grade 3/4 neuropathy occurred in 22 patients. Univariate analysis revealed that reducing or eliminating V had a significant positive effect on PFS and OS (p = 0.0002 and 0.02 respectively). Multivariate analysis adjusting for age at start of study, platelet count, stage, quality of response [CR or near CR versus SD or PR], and thalidomide dose, similarly found that reducing or eliminating the dose of V had a significant positive effect (p = 0.0121) on PFS. However, multivariate analysis did not reveal the same effect on OS (p = 0.11). Conclusions: This subanalysis suggests that the use of full dose V in the DVd-T regimen may have a negative effect on PFS. The exact mechanism by which V affects PFS is not clear. Studies are now on-going investigating this regimen without V. Figure Figure


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e14037-e14037
Author(s):  
Bhavina D O Batukbhai ◽  
Madeleine Champagne ◽  
Karan Rai ◽  
Odeth Barrett-Campbell ◽  
Natalie Riblet

e14037 Background: Malnutrition is a common finding seen in 50-80% of cancer patients. Malnutrition negatively impacts quality of life (QOL), treatment-related outcomes, and survival. While early nutrition interventions (ENI) may be beneficial in preventing malnutrition, they are not part of routine cancer care. We conducted a systematic review and meta-analysis to assess the benefits of ENI compared to standard of care (SC) on nutritional status, QOL, and survival in patients with newly diagnosed cancer. Methods: We searched MEDLINE, EMBASE, Cochrane, and CINAHL databases from inception through October 2019 to identify randomized control trials (RCT) and cohort studies comparing ENI to SC in adult patients with newly diagnosed oncologic malignancies. We required that nutrition interventions began within 8 weeks of diagnosis and lasted at least 6 weeks. Outcomes of interest included nutritional status (change in weight or BMI), mortality, and QOL. We assessed for risk of bias among included studies using the Cochrane Risk of Bias tool (RCT) and the Newcastle-Ottawa scale (cohort studies). We summarized change in weight (kilogram, kg) at 3 and 6 months using standardized mean differences (SMD) and 95% Confidence Intervals (CI). Because some studies had insufficient data on weight to allow for quantitative analysis, we summarized their findings qualitatively. We used a qualitative approach to summarize QOL. Mortality at 1 and 2 years was compared using relative risk (RR) and 95%CI. Random effects models were used to pool data as there was meaningful and statistically significant heterogeneity (I2 > 50%; p-value < 0.1). Results: 2,781 studies were identified and screened by two independent reviewers for eligibility. 18 independent studies (subjects = 1936) met inclusion criteria. Among 9 studies included in the quantitative analysis for nutritional status, patients who received ENI had better nutritional status compared to SC (SMD at 3 months 0.49kg, 95%CI 0.08-0.79; at 6 months: 0.27kg, 95% CI 0.09-0.45). ENI was also associated with a lower risk of death compared to SC, although the findings were not significant (1 year RR: 0.41[95% CI 0.09-1.81]; 2 year RR: 0.79 [95 CI 0.58-1.09]). Of the ten studies reporting on QOL, six found that patients in the ENI group had improved QOL outcomes. There was insufficient data available to perform subgroup analysis based on cancer type. The quality of studies was generally good and 11 of the included studies had low risk of bias. Conclusions: Patients with newly diagnosed cancer may benefit from ENI due to better weight outcomes, QOL, and survival.


2017 ◽  
Vol 51 (5) ◽  
pp. 527-541 ◽  
Author(s):  
Ana Cláudia Chibinski ◽  
Letícia Maíra Wambier ◽  
Juliana Feltrin ◽  
Alessandro Dourado Loguercio ◽  
Denise Stadler Wambier ◽  
...  

A systematic review was performed to evaluate the efficacy of silver diamine fluoride (SDF) in controlling caries progression in children when compared with active treatments or placebos. A search for randomized clinical trials that evaluate the effectiveness of SDF for caries control in children compared to active treatments or placebos with follow-ups longer than 6 months was performed in PubMed, Scopus, Web of Science, LILACS, BBO, Cochrane Library, and grey literature. The risk of bias tool from the Cochrane Collaboration was used for quality assessment of the studies. The quality of the evidence was evaluated using the GRADE approach. Meta-analysis was performed on studies considered at low risk of bias. A total of 5,980 articles were identified. Eleven remained in the qualitative synthesis. Five studies were at “low,” 2 at “unclear,” and 4 studies at “high” risk of bias in the key domains. The studies from which the information could be extracted were included for meta-analysis. The arrestment of caries at 12 months promoted by SDF was 66% higher (95% CI 41-91%; p < 0.00001) than by other active material, but it was 154% higher (95% CI 67-85%; p < 0.00001) than by placebos. Overall, the caries arrestment was 89% higher (95% CI 49-138%; p < 0.00001) than using active materials/placebo. No heterogeneity was detected. The evidence was graded as high quality. The use of SDF is 89% more effective in controlling/arresting caries than other treatments or placebos. The quality of the evidence was graded as high.


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