scholarly journals Progression-Free but No Overall Survival Benefit for Adult Patients with Bevacizumab Therapy for the Treatment of Newly Diagnosed Glioblastoma: A Systematic Review and Meta-Analysis

Cancers ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 1723 ◽  
Author(s):  
Nagham Kaka ◽  
Karim Hafazalla ◽  
Haider Samawi ◽  
Andrew Simpkin ◽  
James Perry ◽  
...  

Glioblastoma (GBM) is the most common high-grade primary brain tumor in adults. Standard multi-modality treatment of glioblastoma with surgery, temozolomide chemotherapy, and radiation results in transient tumor control but inevitably gives way to disease progression. The need for additional therapeutic avenues for patients with GBM led to interest in anti-angiogenic therapies, and in particular, bevacizumab. We sought to determine the efficacy of bevacizumab as a treatment for newly diagnosed GBM. We conducted a literature search using the PubMed database and Google Scholar to identify randomized controlled trials (RCTs) since 2014 investigating the safety and efficacy of bevacizumab in the treatment of adult patients (18 years and older) with newly diagnosed GBM. Only Level Ι data that reported progression-free survival (PFS) and overall survival (OS) were included for analysis. Random effects meta-analyses on studies with newly diagnosed glioblastoma were conducted in R to estimate the pooled hazard ratio (HR) for PFS and OS. Six RCTs met requirements for meta-analysis, revealing a pooled estimate of PFS HR suggesting a 33% decreased risk of disease progression (HR 0.67, 95% CI, 0.58–0.78; p < 0.001) with bevacizumab therapy, but no effect on OS (HR = 1, 95% CI, 0.85–1.18; p = 0.97). A pooled estimate of the mean difference in OS months of −0.13 predicts little difference in time of survival between treatment groups (95% CI, −1.87–1.61). The pooled estimate for the mean difference in PFS months was 2.70 (95% CI, 1.89–3.50; p < 0.001). Meta-analysis shows that bevacizumab therapy is associated with a longer PFS in adult patients with newly diagnosed glioblastoma, but had an inconsistent effect on OS in this patient population.

2018 ◽  
Vol 21 (2) ◽  
pp. 264-273 ◽  
Author(s):  
Flóra John ◽  
Edit Bosnyák ◽  
Natasha L Robinette ◽  
Alit J Amit-Yousif ◽  
Geoffrey R Barger ◽  
...  

Author(s):  
Dimitrios Kazantzis ◽  
Panagiotis Theodossiadis ◽  
Christos Kroupis ◽  
George Theodossiadis ◽  
Irini Chatziralli

Abstract Purpose To evaluate the association between serum vitamin B12/folate and retinal vein occlusion (RVO). Methods A comprehensive search of the PubMed database was performed, which identified 271 abstracts to be screened. Ten studies met our inclusion criteria and a meta-analysis of these comparative case-control studies was performed on the mean ± standard deviation serum vitamin B12 and folate levels, without language restrictions. Nine studies with 720 patients with RVO and 613 controls were included in the meta-analysis for vitamin B12, and 10 studies with 784 patients with RVO and 677 controls in the meta-analysis for folate. Results There was no statistically significant difference between patients with RVO and controls in serum vitamin B12 levels (mean difference: − 40.25 pg/mL, p = 0.28), either central RVO (mean difference: − 18.24 pg/mL, p = 0.71) or branch RVO (mean difference: − 23.56 pg/mL, p = 0.48). On the contrary, the plasma folate level was significantly lower in RVO patients than in controls (mean difference: − 1.34 ng/mL, p = 0.001), as well as in patients with CRVO compared to controls (mean difference: − 1.48 ng/mL, p = 0.006), but not in BRVO patients (mean difference: − 0.72 ng/mL, p = 0.11). Conclusions RVO is associated with low serum folate levels, but not with serum vitamin B12 levels.


2020 ◽  
Vol 26 (12) ◽  
pp. 1808-1818
Author(s):  
Shadi Hamdeh ◽  
Muhammad Aziz ◽  
Osama Altayar ◽  
Mojtaba Olyaee ◽  
Mohammad Hassan Murad ◽  
...  

Abstract Objectives While anti-tumor necrosis factor alpha (anti-TNFa) therapies for Crohn disease (CD) were initially introduced in 1998 for biologic therapies are often introduced after a minimum of 6 years after diagnosis. The benefit of anti-TNFa early in the course of CD is still controversial, with some studies showing better outcomes but others not. To determine whether earlier introduction of anti-TNFa therapy improves efficacy in clinical trials or clinical series, we aimed to perform a meta-analysis comparing early vs late anti-TNFa use in the management of CD. Methods A comprehensive search of MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, and Scopus was conducted from each database’s inception to November 3, 2019. We included comparative studies of early vs late use of anti-TNFa therapy in adult patients with CD. Results Eleven studies were included in the analysis, with a total of 2501 patients. Meta-analysis demonstrated that the early use of anti-TNFa was associated with a statistically significant decrease in the need for surgery (relative risk [RR] = 0.43; 95% confidence interval [CI], 0.26–0.69; I2 = 68%) and disease progression (RR = 0.51; 95% CI, 0.35–0.75; I2 = 61%). Early use also showed an increase in early remission (RR = 1.94; 95% CI, 1.54–2.46; I2 = 0%) and clinical response. There was no statistically significant difference in achieving late remission (RR = 1.39; 95% CI, 0.94–2.05; I2 = 65%) or mucosal healing (RR = 1.10; 95% CI, 0.63–1.91; I2 = 0%). Conclusion This systematic review suggests that using anti-TNFa earlier in the treatment of CD (within 3 years) may improve clinical outcomes compared to late administration in terms of achieving early clinical remission, clinical response, disease progression, and the need for surgery.


2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii38-iii38
Author(s):  
J Kelly ◽  
C Proescholdt

Abstract BACKGROUND High quality and value of recommended treatments is of specific importance in cancer care. ESMO, ASCO and NCCN have developed tools intended to help assessing the clinical value of cancer treatments in a standardised way, allowing for a comparative discussion. Tumor treating fields (TTFields) is a novel, device based cancer treatment, that was recently demonstrated to be effective in newly diagnosed glioblastoma (GBM). This new modality augments the treatments discussed with glioblastoma patients today. MATERIAL AND METHODS ESMO and ASCO frameworks each calculate a score for the clinical value of a cancer treatment, called Magnitude of Clinical Benefit Scale (MCBS) by ESMO and the Net Health Benefit (NHB) by ASCO. NCCN self reports “evidence blocks” which are assessed by clinician panels and were recently published for the first line treatment of newly diagnosed GBM with TTFields. We apply and compare the ESMO, ASCO and NCCN tools for TTFields treatment of newly diagnosed GBM. RESULTS The resulting ASCO NHB score for TTFields treatment of newly diagnosed GBM is 56. ESMO MCBS scores for TTFields in GBM are resulting in A/5, these being the highest achievable scores for this framework. All frameworks value the increase in overall survival by TTFields and the moderate toxicity profile. ESMO additionally values quality of life, while ASCO values palliation and treatment free intervals. NCCN’s specific focus is on the quality and consistency of the evidence. NCCN evidence blocks also contain an affordability score. CONCLUSION All three frameworks consider the clinical efficacy of a treatment and it’s toxicity profile in their clinical value assessment. Beyond that, their respective focus is on slightly different aspects and their definition of clinical value therefore varies in detail. However, all value scores suggest that TTFields treatment of newly diagnosed GBM provides a substantial clinical benefit. The high ESMO and ASCO scores are based on the significantly extended progression free and overall survival for TTFields treated patients, without adding systemic toxicities. The NCCN evidence blocks strongly support the NCCN category 1 recommendation for the use of TTFields in newly diagnosed GBM.


2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Pattraporn Tajarernmuang ◽  
Arintaya Phrommintikul ◽  
Atikun Limsukon ◽  
Chaicharn Pothirat ◽  
Kaweesak Chittawatanarat

Background. An increase in the mean platelet volume (MPV) has been proposed as a novel prognostic indicator in critically ill patients.Objective. We conducted a systematic review and meta-analysis to determine whether there is an association between MPV and mortality in critically ill patients.Methods. We did electronic search in Medline, Scopus, and Embase up to November 2015.Results. Eleven observational studies, involving 3724 patients, were included. The values of initial MPV in nonsurvivors and survivors were not different, with the mean difference with 95% confident interval (95% CI) being 0.17 (95% CI: −0.04, 0.38;p=0.112). However, after small sample studies were excluded in sensitivity analysis, the pooling mean difference of MPV was 0.32 (95% CI: 0.04, 0.60;p=0.03). In addition, the MPV was observed to be significantly higher in nonsurvivor groups after the third day of admission. On the subgroup analysis, although patient types (sepsis or mixed ICU) and study type (prospective or retrospective study) did not show any significant difference between groups, the difference of MPV was significantly difference on the unit which had mortality up to 30%.Conclusions. Initial values of MPV might not be used as a prognostic marker of mortality in critically ill patients. Subsequent values of MPV after the 3rd day and the lower mortality rate unit might be useful. However, the heterogeneity between studies is high.


2017 ◽  
Vol 19 (suppl_6) ◽  
pp. vi208-vi208
Author(s):  
Sied Kebir ◽  
Michael Niessen ◽  
Alexandra Kellner ◽  
Volker Tschuschke ◽  
Ulrich Herrlinger ◽  
...  

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii52-ii52
Author(s):  
Shuzhen Lai ◽  
Yuanyuan Chen

Abstract PURPOSE Anlotinib, an orally multi-target tyrosine kinase inhibitor, inhibits tumor angiogenic and proliferative signal pathways. We performed a phase II trial of anlotinib in combination with the STUPP regimen in patients with newly diagnosed glioblastoma multiforme(GBM)to determine whether the combination therapy would safely improve outcomes in this group of patients. An initial pilot study assessed interim safety and tolerability. METHODS AND MATERIALS Ten newly diagnosed GBM patients were included in this study. All patients received standard radiation of 60 Gy in 30 fractions starting within 4–6 weeks after surgery with concurrent TMZ (daily, 75 mg/m2) and anlotinib (8mg per day, from day 1 to 14, every 3 weeks). After a 4-week break, adjuvant therapy including 6 cycles of TMZ (150–200 mg/m², from day 1 to 5, every 4 weeks) and 8 cycles of anlotinib (8mg per day, from day 1 to 14, every 3 weeks) was given. For patients completing adjuvant therapy, anlotinib alone (8mg per day, from day 1 to 14, every 3 weeks) was administrated until disease progression. RESULTS All patients completed concurrent chemo-radiotherapy without interruption. One patient developed grade 3 weight loss at 56th week and grade 3 presumed radiation-induced cognitive disturbance at 60th week. Fatigue and hypertension were frequently observed during treatment, which potentially be related to the treatment. No severe toxicity was observed in other patients. Up to this writing, none of these patients developed disease progression. CONCLUSION Anlotinib combined with the STUPP regimen is a potential choice for newly diagnosed GBM patients. It is well tolerated and the toxicity is manageable. It’s acceptable to continue enrolling of this Phase II study.


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