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Multicenter Study
. 2018 Oct 9;20(11):1547-1555.
doi: 10.1093/neuonc/noy070.

Prospective feasibility and safety assessment of surgical biopsy for patients with newly diagnosed diffuse intrinsic pontine glioma

Nalin Gupta  1 , Liliana C Goumnerova  2   3 , Peter Manley  2   3 , Susan N Chi  2   3 , Donna Neuberg  2 , Maneka Puligandla  2 , Jason Fangusaro  4 , Stewart Goldman  4 , Tadanori Tomita  4 , Tord Alden  4 , Arthur DiPatri  4 , Joshua B Rubin  5 , Karen Gauvain  5 , David Limbrick  5 , Jeffrey Leonard  5 , J Russel Geyer  6 , Sarah Leary  6 , Samuel Browd  6 , Zhihong Wang  7 , Sandeep Sood  7 , Anne Bendel  8 , Mahmoud Nagib  8 , Sharon Gardner  9 , Matthias A Karajannis  9 , David Harter  9 , Kanyalakshmi Ayyanar  10 , William Gump  10 , Daniel C Bowers  11 , Bradley Weprin  11 , Tobey J MacDonald  12 , Dolly Aguilera  12 , Barunashish Brahma  12 , Nathan J Robison  13 , Erin Kiehna  13 , Mark Krieger  13 , Eric Sandler  14 , Philipp Aldana  14 , Ziad Khatib  15 , John Ragheb  15 , Sanjiv Bhatia  15 , Sabine Mueller  1 , Anu Banerjee  1 , Amy-Lee Bredlau  16 , Sri Gururangan  17 , Herbert Fuchs  17 , Kenneth J Cohen  18 , George Jallo  18 , Kathleen Dorris  19 , Michael Handler  19 , Melanie Comito  20 , Mark Dias  20 , Kellie Nazemi  21 , Lissa Baird  21 , Jeff Murray  22 , Neal Lindeman  23 , Jason L Hornick  23 , Hayley Malkin  2 , Claire Sinai  2 , Lianne Greenspan  2 , Karen D Wright  2   3 , Michael Prados  1 , Pratiti Bandopadhayay  2   3   24 , Keith L Ligon  2   23 , Mark W Kieran  2   3
Affiliations
Multicenter Study

Prospective feasibility and safety assessment of surgical biopsy for patients with newly diagnosed diffuse intrinsic pontine glioma

Nalin Gupta et al. Neuro Oncol. .

Abstract

Background: Diagnosis of diffuse intrinsic pontine glioma (DIPG) has relied on imaging studies, since the appearance is pathognomonic, and surgical risk was felt to be high and unlikely to affect therapy. The DIPG Biology and Treatment Study (DIPG-BATS) reported here incorporated a surgical biopsy at presentation and stratified subjects to receive FDA-approved agents chosen on the basis of specific biologic targets.

Methods: Subjects were eligible for the trial if the clinical features and imaging appearance of a newly diagnosed tumor were consistent with a DIPG. Surgical biopsies were performed after enrollment and prior to definitive treatment. All subjects were treated with conventional external beam radiotherapy with bevacizumab, and then stratified to receive bevacizumab with erlotinib or temozolomide, both agents, or neither agent, based on O6-methylguanine-DNA methyltransferase status and epidermal growth factor receptor expression. Whole-genome sequencing and RNA sequencing were performed but not used for treatment assignment.

Results: Fifty-three patients were enrolled at 23 institutions, and 50 underwent biopsy. The median age was 6.4 years, with 24 male and 29 female subjects. Surgical biopsies were performed with a specified technique and no deaths were attributed to the procedure. Two subjects experienced grade 3 toxicities during the procedure (apnea, n = 1; hypertension, n = 1). One subject experienced a neurologic deficit (left hemiparesis) that did not fully recover. Of the 50 tumors biopsied, 46 provided sufficient tissue to perform the study assays (92%, two-stage exact binomial 90% CI: 83%-97%).

Conclusions: Surgical biopsy of DIPGs is technically feasible, associated with acceptable risks, and can provide biologic data that can inform treatment decisions.

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Figures

Fig. 1
Fig. 1
Study design.
Fig. 2
Fig. 2
Representative MR images (T2-weighted images are in the top row, with postcontrast T1-weighted images in the bottom row) obtained from an intraoperative neuronavigation station demonstrating a surgical biopsy of a typical DIPG. In this case, the corticospinal tract (red) and visual pathways (yellow) obtained from DTI sequences are superimposed on the images.
See this image and copyright information in PMC

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