scholarly journals The intersect of neurosurgery with diffuse intrinsic pontine glioma

2019 ◽  
Vol 24 (6) ◽  
pp. 611-621 ◽  
Author(s):  
Claudia M. Kuzan-Fischer ◽  
Mark M. Souweidane
Keyword(s):  
Drug Delivery ◽  
Tumor Biology ◽  
Scientific Research ◽  
Diffuse Intrinsic Pontine Glioma ◽  
Therapeutic Drug ◽  
Tissue Sampling ◽  
75Th Anniversary ◽  
Pontine Glioma

An invited article highlighting diffuse intrinsic pontine glioma (DIPG) to celebrate the 75th Anniversary of the Journal of Neurosurgery, a journal known to define surgical nuance and enterprise, is paradoxical since DIPG has long been relegated to surgical abandonment. More recently, however, the neurosurgeon is emerging as a critical stakeholder given our role in tissue sampling, collaborative scientific research, and therapeutic drug delivery. The foundation for this revival lies in an expanding reliance on tissue accession for understanding tumor biology, available funding to fuel research, and strides with interventional drug delivery.

scholarly journals IMG-09. RESPONSE ASSESSMENT IN DIFFUSE INTRINSIC PONTINE GLIOMA (DIPG): RECOMMENDATIONS FROM THE RESPONSE ASSESSMENT IN PEDIATRIC NEURO-ONCOLOGY COMMITTEE

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii356-iii357
Author(s):  
Tabitha Cooney ◽  
Kenneth J Cohen ◽  
Carolina V Guimaraes ◽  
Girish Dhall ◽  
James Leach ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Clinical Trials ◽  
Response Duration ◽  
Response Assessment ◽  
Diffuse Intrinsic Pontine Glioma ◽  
Pontine Glioma ◽  
Response Data ◽  
International Panel ◽  
Children And Young Adults ◽  
Magnetic Resonance Imaging Mri

Abstract Optimizing the conduct of clinical trials for diffuse intrinsic pontine glioma (DIPG) involves use of consistent, objective disease assessments and standardized response criteria. The Response Assessment in Pediatric Neuro-Oncology (RAPNO) committee, an international panel of pediatric and adult neuro-oncologists, clinicians, radiologists, radiation oncologists, and neurosurgeons, was established to address unique challenges in assessing response in children with CNS tumors. A subcommittee of RAPNO was formed to specifically address response assessment in children and young adults with DIPG and to develop a consensus on recommendations for response assessment. Distinct issues related to the response assessment of DIPG include its definition and recent molecular classifications, dearth of imaging response data, the phenomena of pseudoprogression, and measuring response in the era of focal drug delivery. The committee has recommended response be assessed using magnetic resonance imaging (MRI) of brain and spine, neurologic examination, and use of supportive medication, i.e. steroids and anti-angiogenic agents. Clinical imaging standards and imaging quality control are defined. Unique recommendations for DIPG response include an eight-week response duration, a twenty-five percent decrease for partial response, and the distinction of pontine and extra-pontine response for trials that use focal drug delivery. The recommendations presented here represent an initial effort to uniformly collect and evaluate response assessment criteria; these recommendations can now be incorporated into clinical trials to assess feasibility and corroboration with patient outcomes.

CTNI-56. EVALUATING DRUG DISTRIBUTION IN CHILDREN WITH DIFFUSE INTRINSIC PONTINE GLIOMA (DIPG) TREATED WITH CONVECTION ENHANCED DRUG DELIVERY

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi73-vi73
Author(s):  
Elwira Szychot ◽  
Dolin Bhagawati ◽  
Steven Gill ◽  
David Walker ◽  
Harpreet Hyare
Keyword(s):  
Drug Delivery ◽  
Signal Intensity ◽  
Drug Distribution ◽  
Tumour Volume ◽  
Diffuse Intrinsic Pontine Glioma ◽  
High Signal ◽  
Pontine Glioma ◽  
Imaging Protocol ◽  
Post Infusion ◽  
Change In Mean

Abstract BACKGROUND There is currently no method for evaluating drug distribution and tumour coverage using the convection-enhanced drug delivery (CED) technique in Diffuse Intrinsic Pontine Glioma (DIPG). AIMS To determine an imaging protocol that can be used to assess the distribution of infusate in children with DIPG treated with CED of carboplatin and sodium valproate. METHODS 12 children with DIPG received between 4–18ml of infusate, through 2 pairs of catheters to encompass tumour volume on 2 days. Volumetric T2W and Diffusion Weighted Imaging (DWI) MRI sequences were performed before and after the first cycle of CED therapy and Apparent Diffusion Coefficient (ADC) maps were calculated. The tumour volume pre and post CED was automatically segmented (ITKSnap) on T2W and ADC on the basis of signal intensity. The ADC maps pre and post infusion were registered and subtracted (FSL) to visualize the infusate distribution. RESULTS ADC and T2W demonstrated a significant (< 0.001) change in mean tumour volume post-infusion (mean ADC volume pre: 19.8ml, post 24.4ml; mean T2W volume pre 19.4ml, post 23.4ml). A significant correlation (p< 0.001) was observed for the difference in tumour volume and the actual infused volume (ADC, r=0.76, T2W, r=0.70). There was a significant increase (p< 0.001) in mean ADC and mean T2W signal intensity ratio post-infusion, no significant correlation with infusion volume. Finally, pixel-by-pixel subtraction of the ADC maps pre and post infusion visually demonstrated high signal intensity, presumed infusate coverage of the tumour. CONCLUSIONS ADC and T2W MR sequences could potentially be used to evaluate the volume of distribution of infusate delivered by CED, paramount to ensure tumour coverage and leading to more effective therapy evaluation. This will facilitate the use of CED in future clinical trials.

scholarly journals Effective Drug Delivery in Diffuse Intrinsic Pontine Glioma: A Theoretical Model to Identify Potential Candidates

2017 ◽  
Vol 7 ◽  
Author(s):  
Fatma E. El-Khouly ◽  
Dannis G. van Vuurden ◽  
Thom Stroink ◽  
Esther Hulleman ◽  
Gertjan J. L. Kaspers ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Theoretical Model ◽  
Diffuse Intrinsic Pontine Glioma ◽  
Effective Drug ◽  
Pontine Glioma

8 Convection enhanced delivery of carboplatin for the treatment of diffuse intrinsic pontine glioma: the pharmacist’s perspective

2018 ◽  
Vol 103 (2) ◽  
pp. e2.48-e2
Author(s):  
Rebekah Rogers
Keyword(s):  
Extracellular Fluid ◽  
Intrathecal Chemotherapy ◽  
Diffuse Intrinsic Pontine Glioma ◽  
Therapeutic Drug ◽  
List Type ◽  
Pontine Glioma ◽  
Convection Enhanced Delivery ◽  
Safe Delivery ◽  
Department Of Health ◽  
The Brain

SituationTo ensure safe delivery of carboplatin by convection enhanced delivery (CED) for the treatment of diffuse intrinsic pontine glioma (DIPG).BackgroundCED describes a method of direct drug delivery to the brain parenchyma through surgically placed microcatheters, completely bypassing the blood brain barrier (BBB)1 Drug is infused with precisely controlled low infusion rates that create a pressure gradient that displaces the brain extracellular fluid with infusate.2DIPG is a malignant high grade brain tumour of children. The median survival is only 9 months1 and no systemic treatment to date has been effective.1 This is likely due to the fact that the majority of systemic therapies do not cross the BBB to achieve a therapeutic concentration within the tumour.1 CED overcomes these limitations and has the potential to achieve a therapeutic drug concentration within the tumour without causing any systemic toxicity.1The unique surgical technology developed in our department, allows repeated infusions of drug without the need for further surgery. The challenges faced by pharmacy were to ensure that an appropriate policy and register was developed to ensure that all professionals involved in the handling, prescription, preparation and administration of carboplatin by CED are appropriately trained and informed, and that patients receiving this therapy are safe. This follows the Department of Health guidance on the safe administration of intrathecal chemotherapy.3 This also had to be reflected on the prescription chart that was designed specifically for CED. It was necessary to ensure that carboplatin was stable at differing concentrations in the diluent used, artificial cerebrospinal fluid, and to determine the shelf life.OutcomeCED of carboplatin has been administered to 8 patients (ages 4–12 years) under compassionate use.4Patients were infused with up to 9 cycles of carboplatin for two consecutive days at a concentration of 0.18 mg/ml which were well tolerated, with neurological side effects most commonly seen during the first cycles.4 The process of safe prescribing and administration of carboplatin administered by this novel method is the first of its kind worldwide, and has the potential to revolutionise the treatment of malignant brainstem tumours.ReferencesBarua NU, Lowis SP, Woolley M, et al. Robot-guided convection-enhanced delivery of carboplatin for advanced brainstem glioma. Acta Neurochirurgica2013;155:1459–65.Bobo RH, Laske DW, Akbasak A, et al. Convection-enhanced delivery of macromolecules in the brain. Proc Natl AcadSci U S A1994;91:2076–80.Department of Health. HSC 2008/001 Updated national guidance on the safe administration of intrathecal chemotherapy2008.Singleton WGB, Barua N, Morgan J, et al. Multi-catheter intermittent convection enhanced delivery of carboplatin as a treatment for Diffuse Intrinsic Pontine Glioma (DIPG): Pre-clinical rationale and early clinical experience. Proceedings of the International Symposium of Paediatric Neurooncology (ISPNO), Neuro-Oncology June 2016;18:131.

Tissue sampling in diffuse intrinsic pontine glioma (DIPG) at progression

2017 ◽  
Vol 64 (9) ◽  
pp. e26492
Author(s):  
Alicia Castañeda Heredia ◽  
Patricia Puerta Roldan ◽  
Antonio Guillen Quesada ◽  
Mariona Sunol Capella ◽  
Carmen de Torres Gomez-Pallete ◽  
...  
Keyword(s):  
Diffuse Intrinsic Pontine Glioma ◽  
Tissue Sampling ◽  
Pontine Glioma

scholarly journals Repeat convection-enhanced delivery for diffuse intrinsic pontine glioma

2020 ◽  
Vol 26 (6) ◽  
pp. 661-666
Author(s):  
Evan D. Bander ◽  
Alexander D. Ramos ◽  
Eva Wembacher-Schroeder ◽  
Iryna Ivasyk ◽  
Rowena Thomson ◽  
...  
Keyword(s):  
Demographic Data ◽  
Absolute Error ◽  
Volume Of Distribution ◽  
Diffuse Intrinsic Pontine Glioma ◽  
Therapeutic Drug ◽  
Pontine Glioma ◽  
Convection Enhanced Delivery ◽  
Technical Application ◽  
Drug Concentrations ◽  
Radial Depth

OBJECTIVEWhile the safety and efficacy of convection-enhanced delivery (CED) have been studied in patients receiving single-dose drug infusions, agents for oncological therapy may require repeated or chronic infusions to maintain therapeutic drug concentrations. Repeat and chronic CED infusions have rarely been described for oncological purposes. Currently available CED devices are not approved for extended indwelling use, and the only potential at this time is for sequential treatments through multiple procedures. The authors report on the safety and experience in a group of pediatric patients who received sequential CED into the brainstem for the treatment of diffuse intrinsic pontine glioma.METHODSPatients in this study were enrolled in a phase I single-center clinical trial using 124I-8H9 monoclonal antibody (124I-omburtamab) administered by CED (clinicaltrials.gov identifier NCT01502917). A retrospective chart and imaging review were used to assess demographic data, CED infusion data, and postoperative neurological and surgical outcomes. MRI scans were analyzed using iPlan Flow software for volumetric measurements. Target and catheter coordinates as well as radial, depth, and absolute error in MRI space were calculated with the ClearPoint imaging software.RESULTSSeven patients underwent 2 or more sequential CED infusions. No patients experienced Clinical Terminology Criteria for Adverse Events grade 3 or greater deficits. One patient had a persistent grade 2 cranial nerve deficit after a second infusion. No patient experienced hemorrhage or stroke postoperatively. There was a statistically significant decrease in radial error (p = 0.005) and absolute tip error (p = 0.008) for the second infusion compared with the initial infusion. Sequential infusions did not result in significantly different distribution capacities between the first and second infusions (volume of distribution determined by the PET signal/volume of infusion ratio [mean ± SD]: 2.66 ± 0.35 vs 2.42 ± 0.75; p = 0.45).CONCLUSIONSThis series demonstrates the ability to safely perform sequential CED infusions into the pediatric brainstem. Past treatments did not negatively influence the procedural workflow, technical application of the targeting interface, or distribution capacity. This limited experience provides a foundation for using repeat CED for oncological purposes.

Sign in / Sign up

Export Citation Format

Share Document