DIPG- Adults versus Kids

Adult diffuse pontine lesions have a median survival range of 4.9 to 7.3 years!

There seems to be a bimodal type of distribution of diffuse brainstem lesions.  The first peak is generally in the the 4-9 year olds and the second is in the 20-50 year olds.   Like children, diffuse brainstem gliomas are the most frequent type of brainstem tumor in adults.   Unlike children who tend to have high grade lesions with a prognosis on average of about 1 year, young adults with similarly appearing lesions when biopsied are low grade and may have a much greater life expectancy.

 Although adult and pediatric DIPG patients might present with similar symptoms (such as ataxia and cranial nerve palsies), is important to realize that despite potentially similar appearances of the diffuse pontine lesions on MRI this is not the same disease process.   This is made clear in the review (full text link) published last year in The Oncologist.  For those interested the read is not near as difficult as the recent molecular tumor biology publications.   In addition, there are three MRI series of adult patients with diffuse pontine lesions.  One of these survivors' MRIs is shown 10 years out.

 I highly recommend a peak at these MRIs (which is easier to do on pub med if one doesn't want to read the entire publication.)  It is amazing how the MR imaging is so similar to what we see in pediatric patients, yet the course can be so much different.

 No one know yet why the tumors are so different in different ages.

Reference:
Adult Brainstem Glioma
Oncologist. 2012;17(3):388-97. doi: 10.1634/theoncologist.2011-0335. Epub 2012 Mar 1.
Full Free Text
http://theoncologist.alphamedpress.org/content/17/3/388.long

A New Era for Children with Diffuse Intrinsic Pontine Glioma: Hope for A Cure?

"A new era for DIPG has just begun."

So starts the conclusion of this expert review article written last  year by two prominent DIPG researchers from the Netherlands- Marc Jansen and Gertjan Kaspers.   It will behoove one interested in DIPG research to be aware of those names.  They are ones that keep coming up in DIPG issues- publications and European DIPG worshops.   

These experts highlight that there has been a rapid increase in biological understanding of DIPGs.     This has only been able to occur because of the recent availability of DIPG tumor tissue which from  the French re-introduction of biopsies and the North American/Dutch focus on autopsy donation.  This DIPG tissue is critical to the further understanding of DIPG although biopsies and post-mortem tissue each have advantages and disadvantages.

The biopsy issues has been very controversial.   The French group has now preformed over 100 stereotactic biopsies with 0% mortality and a 4% transient morbidity.   An advantage of pre-treated biopsy specimens is that there is a significant risk treatment will change the original molecular characteristics.  The tumor that the children start with very likely is not the tumor molecularly that they die with.

Post mortem tissue carries a high risk of treatment-related genetic changes.   Still, there are advantages.   There is a much greater tissue volume available for study.   This also allows study on tumor hetergeneity (how varied the tumor is) as well as "treatment-resistent subclones".   In addition, it has been from these tumor donations that cell lines and animal models have been developed (greatly adding to research potential).

Even with this "avalanache of gene profiling studies" in DIPG, this will probably not provide the entire answer for cure.  There is at least one other prong to the problem.  The authors pose some thoughtful questions for consideration:

• Why  are all chemotherapy regimens ineffective in DIPG while  some show activity in supratentorally located gliomas, such as  temozolomide?
• Why does imatinib, an inhibitor of the  DIPG key target PDGFRA, not improve survival ? 
• Could  poor drug distribution be at least partly the answer to these  questions?

The short answer likely lies in the blood brain barrier (BBB).  The huge hurdle BBB presents in DIPG will be a subject of future posts, but suffice it to say that we need better studies to investigate drug resistance and drug distribution as well as  new drug delivery options.

It is a new era.   There are researchers focused on understanding this tumor.   There has been a virtual explosion of clinical trials and publications.  There is excitement.

We are, though, at the beginning.    We have just gotten some of the tools to fight, --to understand , --to research, --to make a difference.  It is unlikely that the cure is around the next bend but research is finally moving for children with DIPG.   There is reason to hope that someday there might be a cure.

Note-  DIPG research at the VU University Medical  Center is financially supported by Stichting Semmy (Weesp, The Netherlands).

References: 
A new era for diffuse intrinsic pontine glioma: hope for a cure? 
Gertjan J Kaspers and Marc Jansen 
Pediatric Oncology and Hematology, VU University Medical Center, Amsterdam, The Netherlands Expert Rev. Anticancer Ther. 12(9), 1109–1112 (2012) 
Full Text:  http://www.brainlife.org/reprint/2012/Kaspers_GJ120900.pdf

Stichting Semmy-
http://dipg.blogspot.com/2013/03/foundation-spotlight-stichting-semmy.html