The clinical trials landscape for glioblastoma: is it adequate to develop new treatments?

Vanderbeek, Alyssa M; Rahman, Rifaquat; Fell, Geoffrey; Ventz, Steffen; Chen, Tianqi; Redd, Robert A.; Parmigiani, Giovanni; Cloughesy, Timothy F.; Wen, Patrick Y.; Trippa, Lorenzo; Alexander, Brian M.

doi:10.1093/neuonc/noy027

Cited by 115 publications

(98 citation statements)

References 32 publications

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“…At recurrence, a range of treatment options are available and include additional debulking surgery, if possible, with administration of chemotherapies such as nitrosoureas with/without antiangiogenic therapy using bevacizumab. These additional treatment strategies have not been standardized, and results in randomized clinical trials have failed to show a significant survival benefit, leading many patients to participate in clinical trials of investigational therapies (3)(4)(5).…”

Section: Introductionmentioning

confidence: 99%

Safety and Feasibility of Repeated and Transient Blood–Brain Barrier Disruption by Pulsed Ultrasound in Patients with Recurrent Glioblastoma

Idbaïh

Canney

Belin

et al. 2019

Clinical Cancer Research

269

214

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Purpose: The blood-brain barrier (BBB) limits the efficacy of drug therapies for glioblastoma (GBM). Preclinical data indicate that low-intensity pulsed ultrasound (LIPU) can transiently disrupt the BBB and increase intracerebral drug concentrations.Patients and Methods: A first-in-man, single-arm, singlecenter trial (NCT02253212) was initiated to investigate the transient disruption of the BBB in patients with recurrent GBM. Patients were implanted with a 1-MHz, 11.5-mm diameter cranial ultrasound device (SonoCloud-1, CarThera). The device was activated monthly to transiently disrupt the BBB before intravenous carboplatin chemotherapy.Results: Between 2014 and 2016, 21 patients were registered for the study and implanted with the SonoCloud-1; 19 patients received at least one sonication. In 65 ultrasound sessions, BBB disruption was visible on T1w MRI for 52 sonications. Treatment-related adverse events observed were transient and manageable: a transient edema at H1 and at D15. No carboplatin-related neurotoxicity was observed. Patients with no or poor BBB disruption (n ¼ 8) visible on MRI had a median progression-free survival (PFS) of 2.73 months, and a median overall survival (OS) of 8.64 months. Patients with clear BBB disruption (n ¼ 11) had a median PFS of 4.11 months, and a median OS of 12.94 months.Conclusions: SonoCloud-1 treatments were well tolerated and may increase the effectiveness of systemic drug therapies, such as carboplatin, in the brain without inducing neurotoxicity. NOTE: Data are median (range). Idbaih et al. NOTE: The occurrence of each AE is listed as well as the total number of patients affected, as some patients might have experienced the same AE multiple times over the course of therapy.Blood-Brain Barrier Disruption by Ultrasound in GBM www.aacrjournals.org

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Section: Introductionmentioning

confidence: 99%

Safety and Feasibility of Repeated and Transient Blood–Brain Barrier Disruption by Pulsed Ultrasound in Patients with Recurrent Glioblastoma

Idbaïh

Canney

Belin

et al. 2019

Clinical Cancer Research

269

214

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“…Even with intensive treatments, GBM virtually always recurs. Existing chemotherapies have been shown to be only modestly effective as they extend median survival by a few months [2] and clinical trials of new therapeutic agents have failed to show any improvements in survival [3].…”

Section: Introductionmentioning

confidence: 99%

Temporary blood–brain barrier disruption by low intensity pulsed ultrasound increases carboplatin delivery and efficacy in preclinical models of glioblastoma

et al. 2019

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“…Furthermore, research of clinical trials of all glioblastomas registered between 2005 and 2016 showed that, among the 417 confirmed clinical trials, 93% of clinical trials were in phases I or II, and 26% of all clinical trial patients participated in the phase III study. Of the eight completed phase III trials, only one reported positive results (28). Among patients with high-grade gliomas, there are long development times, insufficiently disseminated information, poor decision-making regarding traveling, and low patient participation (28).…”

Section: Discussionmentioning

confidence: 99%

“…Of the eight completed phase III trials, only one reported positive results (28). Among patients with high-grade gliomas, there are long development times, insufficiently disseminated information, poor decision-making regarding traveling, and low patient participation (28). Bloodbrain barrier penetration, redundancy of intracellular signaling pathways, tumor molecular heterogeneity, and lack of validated biomarkers have been fully concerned and thought to be the main obstacles in glioma research (29,30).…”

Section: Discussionmentioning

confidence: 99%

Publication Landscape Analysis on Gliomas: How Much Has Been Done in the Past 25 Years?

Feng

Gao

et al. 2020

Front. Oncol.

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Introduction: The body of glioma-related literature has grown significantly over the past 25 years. Despite this growth in the amount of published research, gliomas remain one of the most intransigent cancers. The purpose of this study was to analyze the landscape of glioma-related research over the past 25 years using machine learning and text analysis. Methods: In April 2019, we downloaded glioma-related publications indexed in PubMed between 1994 and 2018. We used Python to extract the title, publication date, MeSH terms, and abstract from the metadata of each publication for bibliometric assessment. Latent Dirichlet allocation (LDA) was applied to the abstracts to identify publications' research topics with greater specificity. Results: We identified and analyzed a total of 52,625 publications in our study. We found that research on prognosis and the treatment of glioblastoma increased the most in terms of volume and rate of publications over the past 25 years. However, publications regarding clinical trials accounted for <5% of all publications considered in this study. The current research landscape covers clinical, pre-clinical, biological, and technical aspects of glioblastoma; at present, researchers appear to be less concerned with glioblastoma's psychological effects or patients' end-of-life care. Conclusion: Publication of glioma-related research has expanded rapidly over the past 25 years. Common topics include the disease's molecular background, patients' survival, and treatment outcomes; more research needs to be done on the psychological aspects of glioblastoma and end-of-life care.

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The clinical trials landscape for glioblastoma: is it adequate to develop new treatments?

Abstract: The clinical trials landscape for GBM is characterized by long development times, inadequate dissemination of information, suboptimal go/no-go decision making, and low patient participation.

Cited by 115 publications

References 32 publications

Safety and Feasibility of Repeated and Transient Blood–Brain Barrier Disruption by Pulsed Ultrasound in Patients with Recurrent Glioblastoma

Safety and Feasibility of Repeated and Transient Blood–Brain Barrier Disruption by Pulsed Ultrasound in Patients with Recurrent Glioblastoma

Temporary blood–brain barrier disruption by low intensity pulsed ultrasound increases carboplatin delivery and efficacy in preclinical models of glioblastoma

Publication Landscape Analysis on Gliomas: How Much Has Been Done in the Past 25 Years?

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