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01-07-2020 | Glioma | Clinical Study

Children with DIPG and high-grade glioma treated with temozolomide, irinotecan, and bevacizumab: the Seattle Children’s Hospital experience

Authors: Erin E. Crotty, Sarah E. S. Leary, J. Russell Geyer, James M. Olson, Nathan E. Millard, Aimee A. Sato, Ralph P. Ermoian, Bonnie L. Cole, Christina M. Lockwood, Vera A. Paulson, Samuel R. Browd, Richard G. Ellenbogen, Jason S. Hauptman, Amy Lee, Jeffrey G. Ojemann, Nicholas A. Vitanza

Published in: Journal of Neuro-Oncology | Issue 3/2020

Abstract

Introduction

Beyond focal radiation, there is no consensus standard therapy for pediatric high-grade glioma (pHGG) and outcomes remain dismal. We describe the largest molecularly-characterized cohort of children with pHGG treated with a 3-drug maintenance regimen of temozolomide, irinotecan, and bevacizumab (TIB) following radiation.

Methods

We retrospectively reviewed 36 pediatric patients treated with TIB at Seattle Children’s Hospital from 2009 to 2018 and analyzed survival using the Kaplan–Meier method. Molecular profiling was performed by targeted DNA sequencing and toxicities, steroid use, and palliative care utilization were evaluated.

Results

Median age at diagnosis was 10.9 years (18 months–18 years). Genetic alterations were detected in 26 genes and aligned with recognized molecular subgroups including H3 K27M-mutant (12), H3F3A G34-mutant (2), IDH-mutant (4), and hypermutator profiles (4). Fifteen patients (42%) completed 12 planned cycles of maintenance. Side effects associated with chemotherapy delays or modifications included thrombocytopenia (28%) and nausea/vomiting (19%), with temozolomide dosing most frequently modified. Median event-free survival (EFS) and overall survival (OS) was 16.2 and 20.1 months, with shorter survival seen in DIPG (9.3 and 13.3 months, respectively). Survival at 1, 2, and 5 years was 80%, 10% and 0% for DIPG and 85%, 38%, and 16% for other pHGG.

Conclusion

Our single-center experience demonstrates tolerability of this 3-drug regimen, with prolonged survival in DIPG compared to historical single-agent temozolomide. pHGG survival was comparable to analogous 3-drug regimens and superior to historical agents; however, cure was rare. Children with pHGG remain excellent candidates for the study of novel therapeutics combined with standard therapy.

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Title: Children with DIPG and high-grade glioma treated with temozolomide, irinotecan, and bevacizumab: the Seattle Children’s Hospital experience
Authors: Erin E. Crotty
Sarah E. S. Leary
J. Russell Geyer
James M. Olson
Nathan E. Millard
Aimee A. Sato
Ralph P. Ermoian
Bonnie L. Cole
Christina M. Lockwood
Vera A. Paulson
Samuel R. Browd
Richard G. Ellenbogen
Jason S. Hauptman
Amy Lee
Jeffrey G. Ojemann
Nicholas A. Vitanza
Publication date: 01-07-2020
Publisher: Springer US
Keywords: Glioma
Glioma
Glioma
Bevacizumab
Cytostatic Therapy
Published in: Journal of Neuro-Oncology / Issue 3/2020
Print ISSN: 0167-594X
Electronic ISSN: 1573-7373
DOI: https://doi.org/10.1007/s11060-020-03558-w

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Children with DIPG and high-grade glioma treated with temozolomide, irinotecan, and bevacizumab: the Seattle Children’s Hospital experience

Abstract

Introduction

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Introduction

Methods

Results

Conclusion

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