DIPG Collaborative Symposium Begins in Cincinnati

Tomorrow the 2nd  DIPG Collaborative Symposium  begins in Cincinnati.   This two track program brings together doctors and researchers in one track and foundations and parents in another (with a potential networking dinner Friday evening).   The goal is to be able to "efficiently fund and inspire diffuse intrinsic pontine glioma cancer research in hopes of finding a wider cure for cancer".   This year there is expected to be approximately 140 from 7 countries.  With the diverse agenda with international speakers on the forefront of DIPG research, I suspect it will be an exciting place to be for those interested in pediatric diffuse intrinsic pontine glioma.

The 2011 DIPG Collaborative Symposium brought about some substantive advances in the infrastructure critical for DIPG research including the DIPG Registry,  the DIPG Preclinical Consortium,  and the DIPG Genomics Repository.

This meeting starts Friday morning with a Keynote Lecture from Canadian geneticist and researcher, Nada Jaboda MD PhD.   Although the topic has not been release I am thinking- H3.3,K27M and epigenetics.   To get a taste of the work she has been doing in unravelling pediatric vs adult astrocytomas (including DIPG) there is a NYU Grand Rounds titled "Rewiring the Epigenome in Pediatric and Young High Grade Astrocytomas" presented on December 18, 2012. (click here to watch the video)  This work has the potential to change how we approach and treat DIPGs.

The meeting continues with a update of research funded through the collaborative and the Cure Starts Now:
Preclinica/Traslantional
* Xiao-Nan Li(Baylor)- an oncolytic picorna virus in a DIPG xenograft mouse model.
* Oren Becher (Duke)- systemic and direct delivery of a PDFGR-alpha antibody.
* Suzanne Baker (St Jude)- establishment and characterization of DIPG renewable tissue resources
* Patricia Baxter (Texas)- Novel BMI-1 inhibitors in brainstem xenograft mouse models.
* Michele Monje (Stanford)- combined targeted therapy for cellular subpopulations in DIPG.

Clinical
Mark Souweidane (Cornell)- CED trial update
multiple- DIPG Registry update

This will be followed by various other sessions especially revolving around biopsy, biologic understanding of DIPG and current trends in clinical trials.   One of the most  anticipated things for me is the Xerecept session on Friday afternoon.   It has been years of waiting for this drug to see if it can decease the suffering caused by steroids in so many DIPG children (click here for video).   Hopefully something substantive will come from this session.

The other track- the parents and foundation track- will meet primarily on Saturday to discuss the Collaborative objectives, structure, prior efforts and success.

The event will culminate with a Once in a Lifetime Gala which looks to be spectacular (sold out- 1200 seat).  This year's three ring circus them features the Cincinnati Circus and Nik Walenda.

Reference:
DIPG Collaborative Symposium Meeting Agenda
https://csn.donordrive.com/assets/csn/files/$cms$/100/2097.pdf

DIPG Preclinical Consortium-
http://pptiohsu.blogspot.com/2011/12/open-science-forum-dipg-preclinical.html

DIPG Registry-
http://www.dipgregistry.org/

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