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.

scholarly journals ABC Transporter Inhibition Plus Dexamethasone Enhances the Efficacy of Convection Enhanced Delivery in H3.3K27M Mutant Diffuse Intrinsic Pontine Glioma

Neurosurgery ◽  
2019 ◽  
Vol 86 (5) ◽  
pp. 742-751 ◽  
Author(s):  
Vadim Tsvankin ◽  
Rintaro Hashizume ◽  
Hiroaki Katagi ◽  
James E Herndon ◽  
Christopher Lascola ◽  
...  
Keyword(s):  
Abc Transporter ◽  
Kinase Inhibitor ◽  
Mutant Cell ◽  
Diffuse Intrinsic Pontine Glioma ◽  
Pontine Glioma ◽  
Convection Enhanced Delivery ◽  
P Glycoprotein ◽  
Magnetic Resonance Imaging Mri

Abstract BACKGROUND An impermeable blood–brain barrier and drug efflux via ATP-binding cassette (ABC) transporters such as p-glycoprotein may contribute to underwhelming efficacy of peripherally delivered agents to treat diffuse intrinsic pontine glioma (DIPG). OBJECTIVE To explore the pharmacological augmentation of convection-enhanced delivery (CED) infusate for DIPG. METHODS The efficacy of CED dasatinib, a tyrosine kinase inhibitor, in a transgenic H3.3K27M mutant murine model was assessed. mRNA expression of ABCB1 (p-glycoprotein) was analyzed in 14 tumor types in 274 children. In Vitro viability studies of dasatinib, the p-glycoprotein inhibitor, tariquidar, and dexamethasone were performed in 2 H3.3K27M mutant cell lines. Magnetic resonance imaging (MRI) was used to evaluate CED infusate (gadolinium/dasatinib) distribution in animals pretreated with tariquidar and dexamethasone. Histological assessment of apoptosis was performed. RESULTS Continuous delivery CED dasatinib improved median overall survival (OS) of animals harboring DIPG in comparison to vehicle (39.5 and 28.5 d, respectively; P = .0139). Mean ABCB1 expression was highest in K27M gliomas. In Vitro, the addition of tariquidar and dexamethasone further enhanced the efficacy of dasatinib (P < .001). In Vivo, MRI demonstrated no difference in infusion dispersion between animals pretreated with dexamethasone plus tariquidar prior to CED dasatinib compared to the CED dasatinib. However, tumor apoptosis was the highest in the pretreatment group (P < .001). Correspondingly, median OS was longer in the pretreatment group (49 d) than the dasatinib alone group (39 d) and no treatment controls (31.5 d, P = .0305). CONCLUSION ABC transporter inhibition plus dexamethasone enhances the efficacy of CED dasatinib, resulting in enhanced tumor cellular apoptosis and improved survival in H3.3K27M mutant DIPG.

Neonatal Respiratory Failure Caused by Congenital Diffuse Intrinsic Pontine Glioma

2017 ◽  
Vol 32 (6) ◽  
pp. 533-536 ◽  
Author(s):  
Katie M. Satrom ◽  
Rachel A. Phelan ◽  
Christopher L. Moertel ◽  
H. Brent Clark ◽  
Dana E. Johnson ◽  
...  
Keyword(s):  
Respiratory Failure ◽  
Diffuse Intrinsic Pontine Glioma ◽  
Postmortem Examination ◽  
Resonance Imaging ◽  
Pontine Glioma ◽  
Who Grade ◽  
The Family ◽  
Magnetic Resonance Imaging Mri ◽  
The Brain ◽  
Who Grade Iii

The authors present a case of diffuse intrinsic pontine glioma presenting in a newborn with stridor and respiratory distress that progressed to respiratory failure. Magnetic resonance imaging (MRI) of the brain revealed findings compatible with the diagnosis of diffuse intrinsic pontine glioma. The family pursued palliative care and postmortem examination confirmed WHO grade III astrocytoma.

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 Retrospective study of Diffuse Intrinsic Pontine Glioma in the Belgian population: a 25 year experience

2021 ◽  
Author(s):  
Dries Ruttens ◽  
Julie Messiaen ◽  
Alina Ferster ◽  
Caroline Piette ◽  
Stefan Schifflers ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Pediatric Oncology ◽  
Survival Benefit ◽  
Treatment Approach ◽  
Diffuse Intrinsic Pontine Glioma ◽  
Pontine Glioma ◽  
K27m Mutation ◽  
The Past ◽  
Significant Survival ◽  
Belgian Population

Abstract Introduction Diffuse intrinsic pontine glioma is a rare disease with a high mortality. Our primary aim was to determine the incidence of this disease in Belgium. Secondly, we wanted to compare the treatment approach of Belgian pediatric oncology centres, to investigate possibilities for improvement. Methods We retrospectively collected and analysed data on DIPG-patients diagnosed between 1994 and 2018 and recorded in the Belgian Cancer Registry. We included patients ≤ 18 years who were followed in one of the eight Belgian pediatric oncology centres. Results We included 100 patients over a period of 25 years with a median age at diagnosis of 7 years. We observed an increase in diagnoses with an incidence of 3.1 per 1,000,000 persons (aged 0-≤18) per year over the last 5 years compared to an overall incidence of 1.8. Forty-five patients (51.7%) were biopsied at diagnosis. In ten (22%), this was study-related. H3 K27M-mutation was present in 75% of biopsied patients. Fifty-one patients (59.3%) received chemotherapy, without a significant survival benefit. Eleven patients (21.2%) were included in a clinical trial. Biopsy rate and the use of chemotherapy differed widely between centres. Mean OS and PFS were 10.49 and 4.87 months respectively. We observed an improved survival over time. Conclusions Over the past 25 years, we observed an increase of new DIPG-diagnoses. Outcome in our cohort is comparable with literature findings. We demonstrate an important heterogeneity in treatment approach between different centres and limited inclusion in clinical trials. Therefore, collaboration between centres and inclusion of patients in clinical trials is much needed.

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
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