Dr Souweidane CED Trial on 8th Patient

The Cristian Rivera Foundation, a significant support of the Cornell convection enhanced delivery (CED) trial for newly diagnosed children with DIPG, announced in their April 2013 newsletter that the primary investigator, Dr. Mark Souweidane, is now up to his 8th patient in this trial that opened at the end of 2012.

This is a very exciting, innovative trial for DIPG where a catheter is placed from the top of the head down in to the brainstem.   A few weeks after traditional radiation, a radiolabelled antibiody is infused directly in to the pons.   Thus, the blood brain barrier is no longer a problem in getting an agent into the tumor.

This is different than other DIPG CED trials in that it uses a radiolabelled antibody.   The antibody is
8H9 which has been found in several different tumors.   This is linked to 124I which is radioactive.   Since radiation has been the only thing that has made a dent in survival statistics the hope seems that this targeted radiation will clean up some of the cancer cells that have thus far been radioresistant with routine radiation.

This trial is the culmination of more than a decade of research utlitizing CED in the brainstem undertaken by Dr Souweidane and his team at Cornell.  Below is a video illustrating how CED is performed.

For more information about this trial,  about the trial and contact information for Dr. Soweidane click here.

Related Blog Post:
UK Gives CED a Go
http://dipg.blogspot.com/2013/04/uk-gives-ced-go.html

DIPG Collaborative

The DIPG Collaborative "is an association of foundations unified with the mission of efficiently funding and inspiring DIPG research in hopes of finding a wider cure for cancer".   From The Cure Starts now website it says that the Collaborative Council is to:
1) provide the tools and information to families whose children face the difficult diagnosis of pediatric brain cancer.
2) provide a warm and caring envirnoment to share information, discuss options and support one another.
3) make available accurate and easy to understand information for families that are newly diagnosed.  

A major kick off of the DIPG Collaborative was the 2011symposium that brought 13 foundations together with researcher to find substantive ways to research DIPG jointly together.    From that meeting several research infrastructure developments occurred which now really allows us to start to unravel DIPG.   These included the DIPG Preclinical Consortium, the DIPG Resgistry and the DIPG Genomics Repository.

If one hasn't looked at the Preclinical Consortium,  I think it is worth the time as it is impressive.  It is less than 4 years from when the first cell line was promulgated in Michelle Monje's lab (from tissue donated by Dylan Jewett).  Through the consoritum we now have ten institutions working together on more than 30 cell lines (as well as various animal models) trying to find the best single agents or combinations in those cell lines to be a  basis for rapid translation into clinical trials.   Every week there is an update on the consortiums work including DNA and RNA analysis. This is fully funded byt the Foundational Leadership Partnters of the DIPG Colaborative.

The DIPG Registry is equally impressive.  There is a section for medical professionals including sections on enrollment information and consultations.   There is also a section for parents where one can make contact for second opinions and also search for open clinical trials.  Parents can make contact with the registry to discuss enrollment- even for children who have died.  There already is some specific research in the works.

The DIPG Collaborative Symposium starts today, however, the major work of the DIPG Collaborative for foundations starts tomorrow.   The first session is on objectives for the next two years.   It would be really interesting to see the direction this collaborative is moving.

There are three levels of support:
Foundational Leadership Partners - The Cure Starts Now, The Cure Starts Now Australia, Jeffrey Thomas Hayden Foundation, Hope for Caroline, Soar with Grace, Reflections of Grace Foundation, The Lyla Nsouli Foundation

Foundation Partners- Smiles for Sophie Forever, Benny World,  The Team Julian Foundation

Symposium Sponsors- Max Lacewell Foundation, Love Chloe Foundation, Caroline's Miracle Foundation, Ellie DIPG Research Fund,  American Childhood Cancer Organization,  Pray Hope Believe Foundation, National Brain Tumor Society, Lurie Children's Hospital of Chicago, Cincinnati Children's Hospital

References:
CSN DIPG Collaborative Council
http://www.thecurestartsnow.org/about/foundation/councils/DIPGcollaborative/

DIPG Collaborative

http://dipg.org/

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/

Voices on Pediatric DIPG Biopsy- Mark Kieran MD PhD

Identification of Novel Biologic Targets in the Treatment of 

Newly Diagnosed Diffuse Intrinsic Pontine Glioma

ASCO 2012 Education Session Presentation

The third speaker on the 2012 ASCO session was Mark Kieran from Boston presenting "Identification of Novel Biologic Targets in the Treatment of Newly Diagnosed Diffuse Intrinsic Pontine Glioma".  Certainly Dr Kieran has been enduring in his passionate belief that non-treated tissue is going to be critical to the understanding and hopefully cure of DIPG.   He has worked much of the past decade to bring the standard of care for typical pediatric DIPG in line with advancements in neurosurgical techniques and cancer molecular biology research.  The video announcing that DIPG biopsy would be an educational session at 2012 ASCO much have provided a sense of satisfaction that this issue had reached prominence enough to be discussed at a significant cancer meeting. (click here to watch announcement video)

The first video I saw of Dr Kieran discussing this advancements in neurosurgery and cancer molecular biology research that makes DIPG biopsy possible and critical in understanding pediatric DIPGs was back in 2009.   The first international DIPG conference in Barcelona, Spain sponsored by the Alicia Pueyo Foundation included a presentation on this issue.  (click here for video)  The 2012 video shows how far we have come in the DIPG community as well as with cancer molecular biology.

Dr Kieran points out that the understanding DIPG biology is in it's infancy.    Few existing publications are on non-treated (biopsy specimens).  Treatment has the potential of significantly altering the genomics of a tumor.   However, there have been some consistencies:

* P53 loss/mutation is present in a significant number of tumors.

* The RTK-Ras-PI3K-Akt pathway is altered in a number of tumors. 

* PTEN loss might mean that mTOR might be a target.

* Hedgehog-dependent cancer stem cells might be a target.

Regardless of the ultimate biology of DIPG, we can definitely say that DIPG is different from both adult and pediatric high grade gliomas.   Treatment for kids with DIPG can not be based on these other tumors.

There is a caveat- just finding drugable targets might not alter the outcome with DIPG.  So for this approach has not changed the prognosis in adult GBMs despite a huge amount of available tissue.  We are at the beginning.   We don't know yet.   There is hope and optimism that this is a start. 

References:

From boos to hope: Challenging the dogma about deadly brain stem gliomas

http://childrenshospitalblog.org/from-boos-to-hope-challenging-the-dogma-about-deadly-brain-stem-gliomas 

Critical oncogenic mutations in newly diagnosed pediatric diffuse intrinsic pontine glioma
http://www.ncbi.nlm.nih.gov/pubmed/22190243