Improving Convection-Enhanced Delivery Through Photothermal Augmentation of Fluid Dispersal

2012 ◽  
Author(s):  
R. Lyle Hood ◽  
Tobias Ecker ◽  
John Rossmeisl ◽  
John Robertson ◽  
Christopher G. Rylander
Keyword(s):  
Brain Tumors ◽  
Tumor Regression ◽  
Malignant Tumors ◽  
Brain Parenchyma ◽  
Phase Iii ◽  
Convection Enhanced Delivery ◽  
Minimally Invasive Surgical Procedure ◽  
Minimally Invasive Surgical ◽  
Adolescents And Adults ◽  
High Concentrations

Malignant tumors of the central nervous system are the third leading cause of cancer-related deaths in adolescents and adults between the ages of 15 and 34; in children, brain tumors are the leading cause of cancer death. Convection-enhanced delivery (CED) has emerged as a promising method for the transport of high concentrations of chemotherapeutic macromolecules to brain tumors. CED is a minimally-invasive surgical procedure wherein a stereotactically-guided small-caliber catheter is inserted into the brain parenchyma, to a tumor site, for low flowrate infusion of chemotherapy [1]. This direct-delivery method bypasses obstacles to systemic chemotherapy caused by the selective impermeability of the blood-brain barrier. Although preliminary studies were favorable, CED recently failed Phase III FDA trials because clinical goals for tumor regression were not met [2]. This was primarily attributed to insufficient diffuse delivery of the drug throughout tumor masses and their surrounding margins.

scholarly journals Neuroendoscopy Adapter Module Development for Better Brain Tumor Image Visualization

2017 ◽  
Vol 7 (6) ◽  
pp. 3643
Author(s):  
Sunil L. Bangare ◽  
G. Pradeepini ◽  
Shrishailappa Tatyasaheb Patil
Keyword(s):  
Decision Making ◽  
Brain Tumors ◽  
Clinical Decision Making ◽  
Clinical Decision ◽  
Image Resolution ◽  
Minimally Invasive Surgical Procedure ◽  
Narrow Band Image ◽  
Minimally Invasive Surgical ◽  
Auto Fluorescence ◽  
Adapter Module

The issue of brain magnetic resonance image exploration together with classification receives a significant awareness in recent years. Indeed, various computer-aided-diagnosis solutions were suggested to support radiologist in decision-making. In this circumstance, adequate image classification is extremely required as it is the most common critical brain tumors which often develop from subdural hematoma cells, which might be common type in adults. In healthcare milieu, brain MRIs are intended for identification of tumor. In this regard, various computerized diagnosis systems were suggested to help medical professionals in clinical decision-making. As per recent problems, Neuroendoscopy is the gold standard intended for discovering brain tumors; nevertheless, typical Neuroendoscopy can certainly overlook ripped growths. Neuroendoscopy is a minimally-invasive surgical procedure in which the neurosurgeon removes the tumor through small holes in the skull or through the mouth or nose. Neuroendoscopy enables neurosurgeons to access areas of the brain that cannot be reached with traditional surgery to remove the tumor without cutting or harming other parts of the skull. We focused on finding out whether or not visual images of tumor ripped lesions ended up being much better by auto fluorescence image resolution as well as narrow-band image resolution graphic evaluation jointly with the latest neuroendoscopy technique. Also, within the last several years, pathology labs began to proceed in the direction of an entirely digital workflow, using the electronic slides currently being the key element of this technique. Besides lots of benefits regarding storage as well as exploring capabilities with the image information, among the benefits of electronic slides is that they can help the application of image analysis approaches which seek to develop quantitative attributes to assist pathologists in their work. However, systems also have some difficulties in execution and handling. Hence, such conventional method needs automation. We developed and employed to look for the targeted importance along with uncovering the best-focused graphic position by way of aliasing search method incorporated with new Neuroendoscopy Adapter Module (NAM) technique.

Solid Fiber Inside Capillary and Modified Fusion-Spliced Fiber Optic Microneedle Devices

2020 ◽  
Author(s):  
Jason N. Mehta ◽  
Christopher G. Rylander
Keyword(s):  
Fiber Optic ◽  
Light Transmission ◽  
Laser Energy ◽  
Transmission Efficiency ◽  
Brain Parenchyma ◽  
Phase Iii ◽  
Integrating Sphere ◽  
Convection Enhanced Delivery ◽  
Phase Iii Clinical Trials ◽  
The Brain

Abstract Clinical treatment of Glioblastoma Multiforme (GBM) is generally ineffective in increasing patient survival. Convection-enhanced delivery (CED) is an alternative, investigative therapy in which a small caliber catheter is placed directly into the brain parenchyma. However, standard CED drug delivery techniques are unable to reach the entirety of the brain tumor, attributing to the failure of Phase III clinical trials. Fiber optic microneedle devices (FMDs), capable of simultaneous fluid and laser energy delivery, have shown potential to increase the drug dispersal volume when compared to fluid only devices. Previously described FMDs have had low laser transmission efficiency. In this work, we present two FMD manufacturing methods, a solid fiber inside capillary (SFIC) FMD and a modified fusion spliced (FS) FMD. Transmission efficiency of the two proposed FMDs were measured using a 1064 nm laser and an integrating sphere detector with air, deionized water, and black ink inside of the bore of the FMDs. The transmission efficiency of the FS FMD was between 45 and 127% larger than that of previously reported FS FMDs. Additionally, the transmission efficiency of the SFIC was significantly higher than the FS FMD (p ≤ 0.04 for all groups). However, the SFIC FMDs suffered catastrophic fracture failure at bend radii smaller than the manufacture specification, likely due to scribing of the capillary during the FMD fabrication process. Modifying FS FMDs appears to be the preferred fabrication method providing improved light transmission efficiency and mechanical strength on par with the capillary manufacturer’s specifications.

Radiotherapy for Brain Tumors: Current Practice and Future Directions

2020 ◽  
Vol 16 (3) ◽  
pp. 182-195
Author(s):  
Sarah Baker ◽  
Natalie Logie ◽  
Kim Paulson ◽  
Adele Duimering ◽  
Albert Murtha
Keyword(s):  
Brain Tumors ◽  
Treatment Strategies ◽  
Brain Parenchyma ◽  
Benign Tumors ◽  
Tumor Control ◽  
Normal Brain ◽  
Neurocognitive Deficits ◽  
Close Proximity ◽  
Recent Developments ◽  
High Level

Radiotherapy is an important component of the treatment for primary and metastatic brain tumors. Due to the close proximity of critical structures and normal brain parenchyma, Central Nervous System (CNS) radiotherapy is associated with adverse effects such as neurocognitive deficits, which must be weighed against the benefit of improved tumor control. Advanced radiotherapy technology may help to mitigate toxicity risks, although there is a paucity of high-level evidence to support its use. Recent advances have been made in the treatment for gliomas, meningiomas, benign tumors, and metastases, although outcomes remain poor for many high grade tumors. This review highlights recent developments in CNS radiotherapy, discusses common treatment toxicities, critically reviews advanced radiotherapy technologies, and highlights promising treatment strategies to improve clinical outcomes in the future.

scholarly journals Vertebral Metastasis Treated by Vertebroplasty, a Cause of Respiratory Failure: Case Report and Literature Review

2021 ◽  
pp. 279-283
Author(s):  
Mathieu Chevallier ◽  
Chloé Chevallier-Lugon ◽  
Alex Friedlaender ◽  
Alfredo Addeo
Keyword(s):  
Spinal Fractures ◽  
Safe Procedure ◽  
Vertebral Metastasis ◽  
Minimally Invasive Surgical Procedure ◽  
Venous Circulation ◽  
Minimally Invasive Surgical ◽  
Life Threatening ◽  
Frequent Site ◽  
The Right ◽  
Substantial Morbidity

Bone is a frequent site of metastases in advanced cancers including lung, breast, prostate, kidney, or myeloma. Lesions are commonly located on the spine. Neoplastic invasion of the vertebral body can result in painful vertebral fractures, leading to disability and substantial morbidity. Percutaneous vertebroplasty is a minimally invasive surgical procedure used to treat spinal fractures due to osteolytic tumors. It could result in pain reduction or resolution in 80–90% of patients with fractures, and it improves stability. Although considered safe, vertebroplasty has been associated over the years with life-threatening complications. We have reported the case of a 55-year-old patient with lung adenocarcinoma, who underwent vertebroplasty for a pathological neoplastic fracture of L2. The procedure was complicated by a leak of cement into the systemic venous circulation, characterized by an 11-cm filament in the right heart chambers and multiple pulmonary emboli. To our knowledge, only one similar case was previously reported, involving an intracardiac cement filament longer than 10 cm. The data are scant, hence the importance of collecting and reporting possible complications about what is perceived as a rather safe procedure. The case highlights the need for a robust postprocedure imaging plan to detect complications, which can impact patients’ morbidity and survival.

scholarly journals EXTH-16. TREATMENT OF THREE DIFFERENT BRAF-V600E POSITIVE BRAIN TUMORS WITH VEMURAFENIB AND DABRAFENIB/TRAMETINIB: A CASE SERIES

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii90-ii90
Author(s):  
Nikita Dhir ◽  
Sheila Chandrahas ◽  
Chibuzo O’Suoji ◽  
Mohamad Al-Rahawan
Keyword(s):  
Targeted Therapy ◽  
Brain Tumors ◽  
Tumor Regression ◽  
Case Series ◽  
Pediatric Brain Tumors ◽  
Braf V600e ◽  
Cns Tumors ◽  
Braf Inhibitors ◽  
Pediatric Brain ◽  
Pediatric Cns Tumors

Abstract BACKGROUND The BRAF-V600E gene is a protein kinase involved in regulation of the mitogen activated protein kinase pathway (MAPK/MEK) and downstream extracellular receptor kinase (ERK). The BRAF-V600E mutation has a significant role in the progression of pediatric brain tumors. 85% of pediatric CNS tumors express the BRAF mutation. Thus, BRAF targeted therapy in pediatric CNS malignancies has potential to become the standard of care for tumors expressing this mutation. OBJECTIVE Current pediatric CNS brain tumor treatment focuses on chemotherapy and radiation, causing significant toxic side effects for patients. The significance of this case series lies in relaying our experience using targeted therapy in BRAF-V600E positive CNS pediatric brain tumors. METHODS We followed the disease course, progression, and treatment of three pediatric patients with three different CNS tumors. Each of these individuals was treated with surgical resection, chemotherapy, and/or radiation as per standard protocol. When that modality failed to reduce tumor progression, we found that each of their different tumors was BRAF-V600E positive and they were all started on targeted therapy. DISCUSSION Vemurafenib, Dabrafenib, and Trametinib are BRAF-V600E/MEK inhibitors that were initially used to treat melanomas. However, more research has shown that various pediatric CNS tumors are BRAF-V600 positive. Therapy with these BRAF inhibitors has been shown to slow tumor progression, but toxicity can be severe. This case series shows one patient with successful tumor regression, one patient with prolonged disease stabilization, and one patient with initial response but subsequent progression and ultimate death. It has been shown that using BRAF inhibitors in lower grade CNS tumors are more effective than higher grade CNS tumors. CONCLUSION The success of Vemurafenib and Dabrafenib/Trametinib in causing pediatric CNS tumor regression is promising, but further studies are needed to solidify their role in pediatric CNS cancers.

Convection-enhanced delivery of nanocarriers for the treatment of brain tumors

Biomaterials ◽  
2009 ◽  
Vol 30 (12) ◽  
pp. 2302-2318 ◽  
Author(s):  
Emilie Allard ◽  
Catherine Passirani ◽  
Jean-Pierre Benoit
Keyword(s):  
Brain Tumors ◽  
Convection Enhanced Delivery

BOIN: A novel Bayesian design platform to accelerate early phase brain tumor clinical trials

2021 ◽  
Author(s):  
Ying Yuan ◽  
Jing Wu ◽  
Mark R Gilbert
Keyword(s):  
Brain Tumor ◽  
Brain Tumors ◽  
Early Phase ◽  
Late Onset ◽  
Single Agent ◽  
Phase Iii ◽  
Combination Regimen ◽  
Operating Characteristics ◽  
Optimal Interval ◽  
Phase Iii Trials

Abstract Despite decades of extensive research, the progress in developing effective treatments for primary brain tumors lags behind that of other cancers, largely due to the unique challenges of brain tumors (e.g., the blood-brain barrier and high heterogeneity) that limit the delivery and efficacy of many therapeutic agents. One way to address this issue is to employ novel trial designs to better optimize the treatment regimen (e.g., dose and schedule) in early phase trials to improve the success rate of subsequent phase III trials. The objective of this article is to introduce Bayesian optimal interval (BOIN) designs as a novel platform to design various types of early phase brain tumor trials, including single-agent and combination regimen trials, trials with late-onset toxicities, and trials aiming to find the optimal biological dose (OBD) based on both toxicity and efficacy. Unlike many novel Bayesian adaptive designs, which are difficult to understand and complicated to implement by clinical investigators, the BOIN designs are self-explanatory and user friendly, yet yield more robust and powerful operating characteristics than conventional designs. We illustrate the BOIN designs using a phase I clinical trial of brain tumor, and provide software (freely available at www.trialdesign.org) to facilitate the application of the BOIN design.

CTIM-28. MDNA55, AN INTERLEUKIN-4 RECEPTOR TARGETED IMMUNOTHERAPY, FOR RECURRENT GBM DELIVERED BY CONVECTION ENHANCED DELIVERY (CED)

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi56-vi57
Author(s):  
John Sampson ◽  
Achal Singh Achrol ◽  
Manish K Aghi ◽  
Krystof Bankiewiecz ◽  
Martin Bexon ◽  
...  
Keyword(s):  
De Novo ◽  
Symptom Control ◽  
Recurrent Glioblastoma ◽  
Interleukin 4 ◽  
External Control ◽  
High Dose ◽  
Open Label ◽  
Convection Enhanced Delivery ◽  
High Concentrations ◽  
Dose Volumes

Abstract BACKGROUND MDNA55 is an IL4R-targeted toxin in development for treatment of recurrent glioblastoma (rGBM). MDNA55 binds to IL4R expressed by tumor cells and non-malignant cells of the tumor microenvironment. METHOD MDNA55-05 was an open-label, single-arm study of MDNA55 delivered by CED as a single treatment in patients with 1st or 2nd recurrence following de novo GBM, IDH wild type status and not indicated for resection at relapse. Dose volumes (up to 60mL) and concentration of MDNA55 (1.5 to 9.0 μg/mL) were studied. RESULTS MDNA55 showed an acceptable safety profile at all doses tested. Median OS (mOS) amongst all subjects was 11.9 months, OS-24 was 20%, and PFS-12 was 27%. Among subjects expressing high levels of IL4R (irrespective of MDNA55 dose) and low levels of IL4R expression administered high dose (≥ 180μg) of MDNA55 (IL4Rhi + IL4Rlo/hd), mOS further improved to 14.0 months with OS-24 of 20%. Unmethylated MGMT promoter status did not affect MDNA55 treatment outcomes. In the IL4Rhi + IL4Rlo/hd population (N=17), mOS was 14.9 months with OS-24 of 22%. Following treatment with high concentrations of MDNA55 (6.0 or 9.0 μg/mL), transient (median of 3 cycles) low dose Avastin (5mg/kg q2w or 7.5mg/kg q3w) was used for symptom control and steroid sparring. Among these subjects, mOS amongst all comers (N=9) and the IL4Rhi + IL4Rlo/hd group (N=8) increased to 21.8 and 18.6 months with OS-24 of 44% and 38%, respectively. CONCLUSIONS MDNA55 shows potential to benefit all rGBM patients treated at high dose irrespective of IL4R expression. In the 1:1 randomized Phase 3 trial, the study will enrol two-thirds of subjects in the SOC arm from a matched external control arm. Unlike conventional RCTs, the hybrid design sets a new precedent for GBM trials, allowing robust OS analysis while significantly reducing the number of subjects randomized to SOC arm.

scholarly journals Anaesthesia and deep brain stimulation

2016 ◽  
Vol 03 (03) ◽  
pp. 197-204 ◽  
Author(s):  
Barkha Bindu ◽  
Parmod Bithal
Keyword(s):  
Deep Brain Stimulation ◽  
Brain Stimulation ◽  
Surgical Procedure ◽  
Minimally Invasive Surgical Procedure ◽  
Clear Cut ◽  
Minimally Invasive Surgical ◽  
Proper Patient Selection ◽  
Anaesthesia Care ◽  
Risk Benefit Analysis ◽  
Deep Brain

AbstractDeep brain stimulation (DBS) is becoming an increasingly popular minimally invasive surgical procedure for various movement disorders, especially Parkinson’s disease. Different nuclei have been identified depending on patients’ symptoms, but the success or failure of the procedure depends on various other factors such as proper patient selection and risk-benefit analysis. While various techniques of anaesthesia including monitored anaesthesia care, conscious sedation and general anaesthesia are being used routinely, no clear-cut evidence exists as to the best technique for this procedure. This review article discusses the surgical procedure of DBS, devices currently available, perioperative anaesthetic concerns and techniques, effect of anaesthetic drugs on microelectrode recordings and macro-stimulation and associated complications.

scholarly journals Catheter placement selection for convection-enhanced delivery of therapeutic agents to brain tumors

F1000Research ◽  
2020 ◽  
Vol 9 ◽  
pp. 1415
Author(s):  
Lisa H. Antoine ◽  
Roy P. Koomullil ◽  
Timothy M. Wick ◽  
Louis B. Nabors ◽  
Ahmed K. Abdel Aal ◽  
...  
Keyword(s):  
Brain Tumors ◽  
Tumor Volume ◽  
Therapeutic Agents ◽  
Catheter Placement ◽  
Volume Distribution ◽  
Convection Enhanced Delivery ◽  
Cfd Simulations ◽  
Computational Fluid Dynamics Cfd ◽  
Magnetic Resonance Imaging Mri ◽  
Selection Of

Background: Convection-enhanced delivery (CED) of therapeutic agents to brain tumors allows clinicians to bypass the blood-brain barrier (BBB) to infuse virus therapy, biological, or chemotherapy directly into a brain tumor through convection. However, the effectiveness of infusions via CED may depend on catheter placement. Methods: This study used diffusion maps from magnetic resonance imaging (MRI) of human brain tumors and computational fluid dynamics (CFD) simulations to assess therapy volume distribution percentages based on catheter placement locations. Results: The primary outcome showed differences in volume distribution based on the catheter placement location. Total tumor volume filled ranged from 144.40 mm3 to 317.98 mm3. Percent filled of tumor volume ranged from 2.87% to 6.32%. Conclusions: The selection of the location for catheter placement using the region with the highest volume filled may provide optimal therapeutic effect.  The researchers conclude that CFD may provide guidance for catheter placement in CED of therapeutic agents.

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