Is Biopsy Safe in DIPG? An Institutional Experience

This spring abstract season which means one can comb through the abstracts to find the newest research being presented- sometimes more than a year before publication.   The hope in finding and highlighting relevant meeting abstracts is to significantly shorten that time period in figuring out who is doing what.  

On of the meetings with potential is the 26th Annual American Society of Pediatric Hematology and Oncology (ASPHO) Anual  Meeting being held in Miami from April 24-27.   With all the different pediatric blood and cancer disorders, I don't usually expect much success in looking for brain tumor abstracts let alone DIPG.   This year, though,  I was surprised by abstract 750 (page S67):

Is Biopsy Safe in Diffuse Intrinsic Pontine Glioma?

An Institutional Experience

The surprise didn't end there.   Although the institutions is one of the collaborators for the multi-institutional trial with molecular determination for treatment by upfront biopsy,  it is not one that has been obviously on the forefront of the US biopsy debate- Children's Hospital of Michigan in Detroit.  

These authors report on 22 newly diagnosed children with DIPG between 2002 and 2012.    Stealth guided biopsies were performed in 68% of the cases.   There were no deaths related to biopsy.  Three of the fifteen children undergoing biopsy has transient issues post-operative which resolved within two weeks.   The issues included one child developed a facial nerve palsy, one child has some speech difficulty and extremity weakness and the third has ataxia and swallowing difficulties.

All biopsies showed gliomas (grade 2-4). 

The authors conclude that biopsy at their institution has been relatively safe and the resulting tissue will allow for molecular profiling which may lead to targeted therapy and perhaps in the future prolonged survival or a cure.

So, why is the percentage of biopsy so high at this institution?   These authors report a case of theirs in which a child was found to have a PNET tumor rather than a glioma.   Subsequently, biopsy is considered in the majority of these tumors at diagnosis.

Reference:
Molecularly Determined Treatment of Diffuse Intrinsic Pontine Glioma
http://clinicaltrials.gov/ct2/show/NCT01182350?term=dipg&rank=5

Genetic and histopathological spectrum of paediatric diffuse intrinsic pontine gliomas

Sick Kids instituted an brainstem glioma project back in 2003 in hopes of trying to understand diffuse intrinsic pontine glioma.   To do this the researchers reached out to families with an autopsy-based protocol asking for consideration of post-mortem tissue donation.    This decade commitment and collaborative effort against DIPG has lead to another DIPG abstract for the upcoming SNO/CBTF supported 2013 Pediatric Neuro-Oncology Basic and Translational Research Conference.  This one comes from Sick Kids in conjunction with Oren Becher from Duke.

The researchers examined 71diffuse intrinsic pontine tumors:

• 65 were high grade gliomas, 8 were low grade and 3 were PNETs.
• survival was not related to grade.
• leptomeningeal spread was present in one third of cases.
• 68% had K27M-H3.
• these tumors were histologically heterogenous, however increased homogeneity  was found of the histone mutation.
• the histone mutations were also present in low grade tumors that had worse outcomes.

The authors conclude with a call for "incorporation of histological and molecular data"- specifically stating  "histone mutational status at biopsy"- in designing new therapies for DIPG.

There has been a rash of publication regarding K27M mutations recently.   Several of the other abstracts for this meeting feature this histone mutation in DIPG.   I am sure more will be coming in the future.

Reference:
Genetic and histopathological spectrum of paediatric diffuse intrinsic pontine gliomas
https://soc-neuro-onc.conference-services.net/reports/template/onetextabstract.xml?xsl=template/onetextabstract.xsl&conferenceID=3467&abstractID=73797

Inhibition of PRC2 Activity by a Gain-of-Function H3 Mutation Found in Pediatric Glioblastoma

http://www.sciencemag.org/content/early/2013/03/27/science.1232245