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

Focus on Research: 3 New DIPG Abstract This Week!

One of the frustrating things about medical research is the delay between when research is presented at a scientific meeting and when it actually gets to publication.   Unfortunately, sometimes the gap is more than a year.   For this reason, I trawl around the meeting abstracts which might have potential.    One such meeting is the American Association of Cancer Research (AACR) concluding it's five-day Annual Meeting tomorrow.    I am thrilled to report there are DIPG presentations at this meeting.

Here are the citations for the three presented abstracts:

1)  Nathalene Truffaux, Ludivine Le Dret, Stephanie Puget, Gilles Vassal, Birgit Geoerger, Jacques Grill.
Activity of dasatinib and potential escape mechanisms in diffuse intrinsic pontine glioma (DIPG) models
 In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; 2013 {Abstract 2763}

2)  Sridevi Yadavilli, Madhuri Kambhampati, Oren J. Becher, Tobey MacDonald, Ravi Bellamkonda, Roger J. Packer, Javad Nazarian. 
NG2 upregulation and its defective asymmetric distribution in pediatric brainstem glioma and diffuse intrinsic pontine glioma
In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; 2013. {Abstract 5004}

3)  Marianne Hutt, Wendy Goldstein, Javad Nazarian, Antoinette Price, Kah Jing Lim, Katherine Warren, Howard Chang, Charles Eberhart, Eric Raabe.
Targeting the Notch and mTOR pathways in diffuse intrinsic pontine glioma
In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; 2013.  {Abstract 5049}

The first abstract is from the French researchers that have pioneered the way for biopsies.  The second is from National Children's in DC, Duke and Emory/Georgia Institute of Technology.  The third is from the Mid Atlantic DIPG Consortium (MADC).  The MADC abstract appears to be an extension of the abstract we highlighted here on March 23this year.

As the abstracts are meant for a group of researchers, they are most definitely highly scientific.  Here is one thing to take away-  it is possible to establish cell lines from freshly biopsied DIPG material.   The French group has been able to establish 12 lines in this way!  

Hopkins New Trial for Progressive DIPG

Johns Hopkins has put up a new pilot study for children (age one month to 17 years) with progressive DIPGs using intra-arterial (IA) chemotherapy.   This procedure will involve placing catheters into the arteries and guiding them to the blood vessels that directly feed the tumor.    Melphalan hydrochoride, a chemotherapeutic agent, will be delivered directly into these vessels at two intervals 4 weeks apart.  The hope is to increase the amount of drug to the tumor while decreasing the toxicity to the rest of the body.

An interesting part of this study in the interdepartmental nature of the panel which approves inclusion to the study.   The panel included two neuro-oncologists- Ken Cohen and Eric Rabbe; a neurosurgeon- George Jallo; a radiation oncologist- Stephanie Tezakis; and a interventional neuroradiologist- Monica Pearl.   A truly novel part of this study is that the primary investigator is the interventional neuroradiologist!   It is exciting to see such a diverse team interested in novel ways to combat DIPG.

One of the hurdles for DIPG, and in fact all brain tumors, has been getting adequate drug to the tumor.   There have been some attempts at trying to get chemotherapy directly to the tumor through the arteries in the past.    In 2011, Cornell neurosurgeons published an article using the basilar artery to instill chemotherapy near recurrent pediatric ependymomas.   Prior to that there was a publication on blood-brain barrier disruption chemotherapy specifically for diffuse pontine gliomas.  Given the failures so far with DIPG treatment, it is good to see another institution interested in new ways to treat DIPG.

This pilot study is being funded by Solving Kids' Cancer.   This organization, founded by two fathers of children with neuroblastoma, has a mission "to create more effective and less toxic treatment options for kids with the deadliest childhood cancers.  Solving Kids' Cancer's therapeutic paths include genomics, tumor initiating cells, biotherapeutics, immunotherapeutics, embryonic development mechanisms, tumor cell surface receptor and implicated molecular pathways.

References:
Intra-arterial Chemotherapy for the Treatment of Progressive Diffuse Intrinsic Pontine Gliomas
http://www.hopkinsmedicine.org/interventional_neuroradiology/conditions_procedures/progressive_diffuse_intrinsic_pontine_glioma

Super-selective basilar artery infusion of bevacizumab and cetuximab for multiply recurrent pediatric ependymoma
http://www.ncbi.nlm.nih.gov/pubmed/22192550

Osmotic blood-brain barrier disruption chemotherapy for diffuse pontine gliomas
http://www.ncbi.nlm.nih.gov/pubmed/16314949

Catching the Wave: Biopsy and DIPG

I confess I have never surfed.   Still, I imagine that DIPG research could be compared to surfers paddling out on the ocean waiting for a wave.    For DIPG though, the waters have been incredibly flat for a long time.   Now, the sea is changing.

For years, we have been stuck in a conundrum.  We need tissue to know if a child can get benefit from a therapy but maybe we should not biopsy unless we know that the child will get benefit.  It has been a catch-22 that has been difficult to break.

As the era of tumor molecular biology has blossomed,  France first re-instituted the biopsy option for typically appearing pediatric diffuse intrinsic pontine glioma.  Increasingly there have been ripples all over the world expressing the importance of biopsies in designing treatment for these children in hopes of finally improving the dismal statistics.

Last year, Ryo Nishikawa, a Japanese neurosurgeon and Executive Editor JSNO,  wrote a short opinion letter in Neuro-Oncology.   Despite the issue of intratumoral variation, he pointed out that biospies must be performed to "determine genetic profiles" of brainstem lesions.   He also highlights the neurosurgical advances in stereotactic biopsy which has made it more feasible and less dangerous to biopsy brainstem lesions. He concluded with the statement raising hopes for tailored treatment in pediatric DIPG.

As I read more articles on the DIPG biopsy issues, I also have the feeling of new waves for diffuse intrinsic pontine glioma research and treatment.

Reference:
Diffuse intrinsic pontine gliomas: New Waves
Neuro Oncol. 2012 March; 14(3): 245.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3280815/