Convection-enhanced delivery for high-grade glioma

2021 ◽  
Author(s):  
Jennifer H Kang ◽  
Annick Desjardins
Keyword(s):  
Brain Tumor ◽  
Survival Rate ◽  
Blood Brain Barrier ◽  
Clinical Care ◽  
High Grade Glioma ◽  
High Grade ◽  
Glioma Patient ◽  
Convection Enhanced Delivery ◽  
Technical Considerations ◽  
Primary Malignant Brain Tumor

Abstract Glioblastoma (GBM) is the most common adult primary malignant brain tumor and is associated with a dire prognosis. Despite multi-modality therapies of surgery, radiation, and chemotherapy, its 5-year survival rate is 6.8%. The presence of the blood-brain barrier (BBB) is one factor that has made GBM difficult to treat. Convection-enhanced delivery (CED) is a modality that bypasses the BBB, which allows the intracranial delivery of therapies that would not otherwise cross the BBB and avoids systemic toxicities. This review will summarize prior and ongoing studies and highlights practical considerations related to clinical care to aid providers caring for a high-grade glioma patient being treated with CED. Although not the main scope of this paper, this review also touches upon relevant technical considerations of using CED, an area still under much development.

scholarly journals Convection Enhanced Delivery in the Setting of High-Grade Gliomas

Pharmaceutics ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 561
Author(s):  
Chibueze D. Nwagwu ◽  
Amanda V. Immidisetti ◽  
Michael Y. Jiang ◽  
Oluwasegun Adeagbo ◽  
David C. Adamson ◽  
...  
Keyword(s):  
Rapid Development ◽  
Systemic Exposure ◽  
Therapeutic Index ◽  
High Grade Glioma ◽  
High Grade ◽  
Clinical Experiences ◽  
Convection Enhanced Delivery ◽  
Drug Concentrations ◽  
Infiltrative Growth Pattern ◽  
High Grade Gliomas

Development of effective treatments for high-grade glioma (HGG) is hampered by (1) the blood–brain barrier (BBB), (2) an infiltrative growth pattern, (3) rapid development of therapeutic resistance, and, in many cases, (4) dose-limiting toxicity due to systemic exposure. Convection-enhanced delivery (CED) has the potential to significantly limit systemic toxicity and increase therapeutic index by directly delivering homogenous drug concentrations to the site of disease. In this review, we present clinical experiences and preclinical developments of CED in the setting of high-grade gliomas.

CTNI-41. INITIAL RESULTS OF A PHASE I WINDOW OF OPPORTUNITY TRIAL EVALUATING A FIRST-IN-CLASS CD29 INHIBITOR, OS2966, IN RECURRENT HIGH-GRADE GLIOMA

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi69-vi69
Author(s):  
James Liu ◽  
Chibueze D Nwagwu ◽  
Amanda V Immidisetti ◽  
Gabriela Bukanowska ◽  
Anne-Marie Carbonell ◽  
...  
Keyword(s):  
Adverse Events ◽  
Phase I ◽  
Tumor Resection ◽  
High Grade Glioma ◽  
Underlying Disease ◽  
Tissue Level ◽  
High Grade ◽  
Convection Enhanced Delivery ◽  
Tumor Biopsy ◽  
Safety Issues

Abstract BACKGROUND OS2966 is a first-in-class, humanized and deimmunized monoclonal antibody which antagonizes CD29/β1integrin, a mechanosignaling receptor prominently upregulated in glioblastoma. Preclinical studies in mice and non-human primates have demonstrated safety and encouraging efficacy. A two-part, ascending concentration, phase I clinical trial was therefore initiated to evaluate the safety and feasibility of delivering OS2966 directly to the site of disease via convection-enhanced delivery (CED) in recurrent high-grade glioma patients. METHODS This study has a 2-part design: In part 1, patients undergo stereotactic tumor biopsy followed by placement of a multiport CED catheter for delivery of OS2966 to the bulk contrast enhancing tumor. Subsequently, patients undergo a clinically-indicated tumor resection followed by placement of two CED catheters and delivery of OS2966 to the surrounding tumor-infiltrated brain. A unique concentration-based accelerated titration design is utilized for dose escalation. Given availability of pre and post infusion samples, pharmacodynamic data will be analyzed to explore mechanism of action of OS2966. RESULTS Two subjects have been treated at two corresponding dose levels (0.2mg/mL and 0.4 mg/mL). No dose-limiting toxicity or unexpected safety issues have been identified. To date, reported adverse events were mild (i.e., grade 1) and consistent with underlying disease and surgical procedures. No adverse events were attributed to OS2966 or CED catheter placement. Further, no clinically significant changes from baseline neurological exam have been noted for either patient through initial follow-up. Maximal tumor coverage and concomitant gross total resection were achieved for both patients. Tumor volume measured 1.63 cm3 and 16 cm3 for Patient 1 and 2 respectively with an intratumoral Vd/Vi ratio of 1.3. and 0.94. Pharmacodynamic analysis via tissue-level biomarkers is ongoing and will be presented. CONCLUSION Initial data demonstrates the safety and feasibility of direct intracranial delivery of OS2966.

Coping with a newly diagnosed high-grade glioma: patient-caregiver dyad effects on quality of life

2016 ◽  
Vol 129 (1) ◽  
pp. 155-164 ◽  
Author(s):  
K. Baumstarck ◽  
T. Leroy ◽  
Z. Hamidou ◽  
E. Tabouret ◽  
P. Farina ◽  
...  
Keyword(s):  
Quality Of Life ◽  
High Grade Glioma ◽  
High Grade ◽  
Newly Diagnosed ◽  
Glioma Patient

A phase I study of convection-enhanced delivery of nanoliposomal irinotecan using real-time imaging in patients with recurrent high grade glioma.

2015 ◽  
Vol 33 (15_suppl) ◽  
pp. TPS2081-TPS2081
Author(s):  
Nicholas A. Butowski ◽  
Seunggu Han ◽  
Jennie Webster Taylor ◽  
Manish K. Aghi ◽  
Michael Prados ◽  
...  
Keyword(s):  
Phase I ◽  
Real Time ◽  
Phase I Study ◽  
High Grade Glioma ◽  
High Grade ◽  
Convection Enhanced Delivery ◽  
Real Time Imaging ◽  
Nanoliposomal Irinotecan

scholarly journals Pediatric high-grade glioma resources from the Children’s Brain Tumor Tissue Consortium

2019 ◽  
Vol 22 (1) ◽  
pp. 163-165 ◽  
Author(s):  
Heba Ijaz ◽  
Mateusz Koptyra ◽  
Krutika S Gaonkar ◽  
Jo Lynne Rokita ◽  
Valerie P Baubet ◽  
...  
Keyword(s):  
Brain Tumor ◽  
Tumor Tissue ◽  
High Grade Glioma ◽  
High Grade ◽  
Pediatric High Grade Glioma

Intraarterial delivery of bevacizumab and cetuximab utilizing blood-brain barrier disruption in children with high-grade glioma and diffuse intrinsic pontine glioma: results of a phase I trial

2021 ◽  
pp. 1-9
Author(s):  
Heather J. McCrea ◽  
Jana Ivanidze ◽  
Ashley O’Connor ◽  
Eliza H. Hersh ◽  
John A. Boockvar ◽  
...  
Keyword(s):  
Phase I ◽  
Blood Brain Barrier ◽  
Stable Disease ◽  
Phase I Trial ◽  
Progressive Disease ◽  
High Grade Glioma ◽  
Diffuse Intrinsic Pontine Glioma ◽  
Brain Barrier ◽  
High Grade ◽  
Pontine Glioma

OBJECTIVE Delivery of drugs intraarterially to brain tumors has been demonstrated in adults. In this study, the authors initiated a phase I trial of superselective intraarterial cerebral infusion (SIACI) of bevacizumab and cetuximab in pediatric patients with refractory high-grade glioma (diffuse intrinsic pontine glioma [DIPG] and glioblastoma) to determine the safety and efficacy in this population. METHODS SIACI was used to deliver mannitol (12.5 ml of 20% mannitol) to disrupt the blood-brain barrier (BBB), followed by bevacizumab (15 mg/kg) and cetuximab (200 mg/m2) to target VEGF and EGFR, respectively. Patients with brainstem tumors had a balloon inflated in the distal basilar artery during mannitol infusion. RESULTS Thirteen patients were treated (10 with DIPG and 3 with high-grade glioma). Toxicities included grade I epistaxis (2 patients) and grade I rash (2 patients). There were no dose-limiting toxicities. Of the 10 symptomatic patients, 6 exhibited subjective improvement; 92% showed decreased enhancement on day 1 posttreatment MRI. Of 10 patients who underwent MRI at 1 month, 5 had progressive disease and 5 had stable disease on FLAIR, whereas contrast-enhanced scans demonstrated progressive disease in 4 patients, stable disease in 2, partial response in 2, and complete response in 1. The mean overall survival for the 10 DIPG patients was 519 days (17.3 months), with a mean posttreatment survival of 214.8 days (7.2 months). CONCLUSIONS SIACI of bevacizumab and cetuximab was well tolerated in all 13 children. The authors’ results demonstrate safety of this method and warrant further study to determine efficacy. As molecular targets are clarified, novel means of bypassing the BBB, such as intraarterial therapy and convection-enhanced delivery, become more critical. Clinical trial registration no.: NCT01884740 (clinicaltrials.gov)

scholarly journals Coping strategies and quality of life: a longitudinal study of high-grade glioma patient-caregiver dyads

2018 ◽  
Vol 16 (1) ◽  
Author(s):  
Karine Baumstarck ◽  
Olivier Chinot ◽  
Emeline Tabouret ◽  
Patrizia Farina ◽  
Marilyne Barrié ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Longitudinal Study ◽  
Coping Strategies ◽  
High Grade Glioma ◽  
High Grade ◽  
Glioma Patient

scholarly journals Targeting the mDia Formin-Assembled Cytoskeleton Is an Effective Anti-Invasion Strategy in Adult High-Grade Glioma Patient-Derived Neurospheres

Cancers ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 392 ◽  
Author(s):  
Krista Pettee ◽  
Kathryn Becker ◽  
Arthur Alberts ◽  
Kevin Reinard ◽  
Jason Schroeder ◽  
...  
Keyword(s):  
Actin Polymerization ◽  
Rho Gtpase ◽  
Three Dimensional ◽  
High Grade Glioma ◽  
High Grade ◽  
Glioma Patient ◽  
Glioma Invasion ◽  
Who Grade ◽  
Rat Brain Slice

High-grade glioma (HGG, WHO Grade III–IV) accounts for the majority of adult primary malignant brain tumors. Failure of current therapies to target invasive glioma cells partly explains the minimal survival advantages: invasive tumors lack easily-defined surgical margins, and are inherently more chemo- and radioresistant. Much work centers upon Rho GTPase-mediated glioma invasion, yet downstream Rho effector roles are poorly understood and represent potential therapeutic targets. The roles for the mammalian Diaphanous (mDia)-related formin family of Rho effectors have emerged in invasive/metastatic disease. mDias assemble linear F-actin to promote protrusive cytoskeletal structures underlying tumor cell invasion. Small molecule mDia intramimic (IMM) agonists induced mDia functional activities including F-actin polymerization. mDia agonism inhibited polarized migration in Glioblastoma (WHO Grade IV) cells in three-dimensional (3D) in vitro and rat brain slice models. Here, we evaluate whether clinically-relevant high-grade glioma patient-derived neuro-sphere invasion is sensitive to formin agonism. Surgical HGG samples were dissociated, briefly grown as monolayers, and spontaneously formed non-adherent neuro-spheres. IMM treatment dramatically inhibited HGG patient neuro-sphere invasion, both at neuro-sphere embedding and mid-invasion assay, inducing an amoeboid morphology in neuro-sphere edge cells, while inhibiting actin- and tubulin-enriched tumor microtube formation. Thus, mDia agonism effectively disrupts multiple aspects of patient-derived HGG neuro-sphere invasion.

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