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

DIPG Yahoogroup 5th Anniversary

Today marks the 5th anniversary of the DIPG Yahoogroup.  Started by on April 16th, 2008 by one mother who wanted to have a place for DIPG parents to talk with one another and share experiences as well as information.   From that one, there are now 616 members listed with almost 25,000 posts.

So much has changed in those five years.   Back in 2008,  it was common to hear parents say brainstem glioma not realizing how heterogeneous that term really was.   I don't remember any listings of trials on clinicaltrials.gov under DIPG.   Today there are 26 listed making it much easier for parents to locate and sort through these trials.   And back there research was severely limited because there was no tissue to examine; and because of the lack of tissue there were no cell lines or representative animal models.

The research landscape was just beginning to change for DIPG with the French biopsy study having just been published the year before and several institutions working to gather post-mortem samples.  The start of the list coincided with the rapid expansion of DIPG research.

I firmly believe it is because of some of the members of this group that DIPG research was pushed more quickly. Some played their part on spreading the word on tumor donation while others funded workshops, trials and research.   Often interesting items appeared on the list significantly before publication like the MD Anderson reirradation pilot- perhaps pushing the spread of information faster than ever has been seen before.

Here is a listing of some of the important events in DIPG over the past decade:

2002- Sick Kids start autopsy collection of DIPGs
2005- France starts trial with upfront biospy
2006- St Jude stars autopsy collection of DIPGs
2007- France first reports on trial with upfront biopsy
2008- DIPG Yahoogroup opened
2009- First International DIPG Meeting in Barcelona
2009- FDA DIPG biopsy hearing
2009- Dylan donates tumor to Stanford
2009- First CED trial on recurrent DIPG open in US
2010- Toronto DIPG Think Tank
2010- First DIPG Genetic Analysis Publication
2011- Amsterdam DIPG meeting
2011- Stanford reveals first DIPG neurosphere
2011- Vaccine study for newly diagnosed DIPG begins at Stanford
2011- First DIPG/Oncolytic Virus Case
2011- DIPG.org Symposium
2011- DIPG Preclical Consortium formed
2011- DIPG Registry
2011- MD Anderson opens first DIPG Reiiradiation trial
2011- DIPG Concensus Conference at the NIH
2012- DIPG Barcelona Conference
2012- ACCO Book- Understanding the Journey
2012- DIPG Genomics Repository
2012- US multi-institution biopsy trial begins
2012- CED trial for newly diagnosed DIPG opens at Cornell
2013- Academic Colloquium: State of the Art in DIPG (Amsterdam)

I extend deep gratitude to all that participated in the list which has helped get us to where we are today.

Patterns of Progression in Pediatric Patients with High-Grade Glioma or Diffuse Intrinsic Pontine Glioma treated with Bevacizumab-Based Therapy at Diagnosis

The first hints of data from a Cincinnati/Lurie Children's study using temozolomide, irinotecan and avastin appears to be coming out with a poster presentation at the 3rd biennial Pediatric Basic and Translational Research Conference looking at patterns of progression with an avastin-based therapy for kids with newly diagnosed DIPG or high grade glioma.

The issues of potential increased invasiveness and spread have been popping up for the past few years. We have seen discussions of this in internet-based communities as well as publications in adult GBM patients.   Common terms related to this are "diffuse invasiveness" and "evasive resistance".   The adult literature has some that do not believe that avastin increases remote relapses.  There is very little regarding children relapse patterns with bevacizumab-based therapies.

In this study of 17 patients (14 DIPG and 3 HGG), 12 patients had progressive disease in a median time of 8.2 months.  In nine patients the furst progression was local and  in the remaining three the progression was local, diffuse and distant.   However with further progressive disease a total of six children had diffuse or distant progression.

The authors speculate that these findings might be explained by increasing invasiveness through co-opting native blood vessels or activation of other pro-angiogenic pathways.     

It would be interesting to have direct comparison to non-bevacizamab-based therapies for comparison as other authors have indicated a high risk of leptomeningeal dissemination with DIPG.  Interestingly, in that study 8 of the 16 children had leptomeningeal spread but only the 3 with anti-VEGF (2 with avastin and 1 with vandetanib) had spread to bilateral cerebral hemispheres.  The other 5 had spread to the spinal cord or posterior fossa.

It is likely questions like this is where a registry can be valuable if one is able to look at a large number of imaging studies. 

Reference:
Patterns of Progression in Pediatric Patients with High-Grade Glioma or Diffuse Intrinsic Pontine Glioma treated with Bevacizumab-Based Therapy at Diagnosis
https://soc-neuro-onc.conference-services.net/reports/template/onetextabstract.xml?xsl=template/onetextabstract.xsl&conferenceID=3467&abstractID=736163

A Study of Bevacizumab Therapy in Patients With Newly Diagnosed High-Grade Gliomas and Diffuse Intrinsic Pontine Gliomas
http://clinicaltrials.gov/ct2/show/NCT00890786?term=dipg&rank=10

Bevacizumab does not increase remote relapse in malignant glioma
http://www.ncbi.nlm.nih.gov/pubmed/21446027

Prospective neuroaxis surveillance reviews a high risk of leptmeningeal dissemination in diffuse intrinsic pontine glioma.
http://www.ncbi.nlm.nih.gov/pubmed/20623246

Foundation Spotlight- A Cure From Caleb Society

Many of the recent posts have been highly scientific.   It the spring season of new abstracts so I guess it isn't to be unexpected.   However, sometimes I feel that I just need to sit back and look at pictures to gain perspective on more than molecular pathways.  Today I did just that.   I looked at pictures of a little boy I got to know only from the internet.

Caleb loved hockey and jokes but his life was completely derailed at age 8 when he was diagnosed with DIPG.  Due to the persistence of his parents got a second round of radiation at progression that gave them another 9 months.  This was something that simply wasn't done before and was only happened due to the valiant fight of this family.

Caleb still inspires fighting for change through the A Cure From Caleb Society which specifically fund s DIPG research.  This past Friday, the foundation hosted a Spring Dance to create awareness and fund research.

The research A Cure From Caleb Society is supporting is that of Cynthia Hawkins, MD PhD of Sick Kids.   Dr. Hawkins has been on the leading edge of many recent advances in DIPG research-from creating an post-mortem tissue collection program at Sick Kids to the first publication of DIPG molecular analysis.  She was also instrumental in the Toronto DIPG Think Tank in 2010 and is a participant in the DIPG Preclinical Consortium.    I am sure there is going to be much more research coming from this lab as in addition to yesterday's abstract there another one that will be presented at the same conference.

And for Caleb- we are not chicken and will continue to work on crossing the road to a cure.