Advanced ADC Histogram, Perfusion, and Permeability Metrics Show an Association with Survival and Pseudoprogression in Newly Diagnosed Diffuse Intrinsic Pontine Glioma: A Report from the Pediatric Brain Tumor Consortium

Abstract Background A Pediatric Brain Tumor Consortium (PBTC) phase I/II trial of veliparib and radiation followed by veliparib and temozolomide (TMZ) was conducted in children with newly diagnosed diffuse intrinsic pontine glioma (DIPG). The objectives were to: (i) estimate the recommended phase II dose (RP2D) of veliparib with concurrent radiation; (ii) evaluate the pharmacokinetic parameters of veliparib during radiation; (iii) evaluate feasibility of intrapatient TMZ dose escalation; (iv) describe toxicities of protocol therapy; and (v) estimate the overall survival distribution compared with historical series. Methods Veliparib was given Monday through Friday b.i.d. during radiation followed by a 4-week rest. Patients then received veliparib at 25 mg/m2 b.i.d. and TMZ 135 mg/m2 daily for 5 days every 28 days. Intrapatient dose escalation of TMZ was investigated for patients experiencing minimal toxicity. Results Sixty-six patients (65 eligible) were enrolled. The RP2D of veliparib was 65 mg/m2 b.i.d. with radiation. Dose-limiting toxicities during radiation with veliparib therapy included: grade 2 intratumoral hemorrhage (n = 1), grade 3 maculopapular rash (n = 2), and grade 3 nervous system disorder (generalized neurologic deterioration) (n = 1). Intrapatient TMZ dose escalation during maintenance was not tolerated. Following a planned interim analysis, it was concluded that this treatment did not show a survival benefit compared with PBTC historical controls, and accrual was stopped for futility. The 1- and 2-year overall survival rates were 37.2% (SE 7%) and 5.3% (SE 3%), respectively. Conclusion Addition of veliparib to radiation followed by TMZ and veliparib was tolerated but did not improve survival for patients with newly diagnosed DIPG. Trial Registration NCT01514201

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DIPG-22. A PHASE 1 TRIAL OF THE HISTONE DEACETYLASE INHIBITOR PANOBINOSTAT IN PEDIATRIC PATIENTS WITH RECURRENT OR REFRACTORY DIFFUSE INTRINSIC PONTINE GLIOMA: A PEDIATRIC BRAIN TUMOR CONSORTIUM (PBTC) STUDY

Neuro-Oncology ◽

10.1093/neuonc/noy059.115 ◽

2018 ◽

Vol 20 (suppl_2) ◽

pp. i53-i53 ◽

Cited By ~ 6

Author(s):

Tabitha Cooney ◽

Arzu Onar-Thomas ◽

Jie Huang ◽

Rishi Lulla ◽

Jason Fangusaro ◽

...

Keyword(s):

Brain Tumor ◽

Histone Deacetylase ◽

Histone Deacetylase Inhibitor ◽

Pediatric Patients ◽

Phase 1 ◽

Pediatric Brain Tumor ◽

Diffuse Intrinsic Pontine Glioma ◽

Pontine Glioma ◽

Deacetylase Inhibitor ◽

Pediatric Brain

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IMMU-09. OUTCOME OF PATIENTS WITH RECURRENT DIFFUSE INTRINSIC PONTINE GLIOMA (DIPG) TREATED WITH PEMBROLIZUMAB (ANTI-PD-1): A PEDIATRIC BRAIN TUMOR CONSORTIUM STUDY (PBTC045)

Neuro-Oncology ◽

10.1093/neuonc/noy059.325 ◽

2018 ◽

Vol 20 (suppl_2) ◽

pp. i100-i100 ◽

Cited By ~ 4

Author(s):

Eugene Hwang ◽

Arzu Onar ◽

Tina Young-Poussaint ◽

Duane Mitchell ◽

Lindsay Kilburn ◽

...

Keyword(s):

Brain Tumor ◽

Pediatric Brain Tumor ◽

Diffuse Intrinsic Pontine Glioma ◽

Pontine Glioma ◽

Pediatric Brain

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Diffuse intrinsic pontine glioma: current insights and future directions

Chinese Neurosurgical Journal ◽

10.1186/s41016-020-00218-w ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Dilakshan Srikanthan ◽

Michael S. Taccone ◽

Randy Van Ommeren ◽

Joji Ishida ◽

Stacey L. Krumholtz ◽

...

Keyword(s):

Brain Tumor ◽

Gene Mutations ◽

Pediatric Brain Tumor ◽

Diffuse Intrinsic Pontine Glioma ◽

Pontine Glioma ◽

Current Standard ◽

In Vivo Models ◽

Landscape Models

AbstractDiffuse intrinsic pontine glioma (DIPG) is a lethal pediatric brain tumor and the leading cause of brain tumor–related death in children. As several clinical trials over the past few decades have led to no significant improvements in outcome, the current standard of care remains fractionated focal radiation. Due to the recent increase in stereotactic biopsies, tumor tissue availabilities have enabled our advancement of the genomic and molecular characterization of this lethal cancer. Several groups have identified key histone gene mutations, genetic drivers, and methylation changes in DIPG, providing us with new insights into DIPG tumorigenesis. Subsequently, there has been increased development of in vitro and in vivo models of DIPG which have the capacity to unveil novel therapies and strategies for drug delivery. This review outlines the clinical characteristics, genetic landscape, models, and current treatments and hopes to shed light on novel therapeutic avenues and challenges that remain.

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