Building a Post Mortem Tissue Donation Program- Part 2

It was back in the summer of 2005 that I first became aware of any institution making a concerted effort to obtain DIPG samples for research purposes.    On a visit to Memphis, I found out that researchers there were going to attempting to put a comprehensive IRB proposal  (and place in clinicaltrials.gov) together to formalize a process for post-mortem DIPG donation.  At that time, France had just started the biopsy trial and to me this was an American attempt to push DIPG research also.  To me it was an exciting time- the first time I had heard of anyone really trying in an organized way to look at DIPG genomics in the US.

Since it was something that was not done, there were concerns on how to approach families- and if they would even donate.  To try to answer some of these issues, specific sections of the research would examine parental feeling towards autopsy through a decisional regret survey and a 7 question survey.   Questions included items such as reasons for participating in the study, what was good and bad about participating and do you have suggestions. In February an article came out electronically ahead of print in the Journal of Pediatrics detailing the parent experience.

Thirty three parents of 32 children answered the the survey (82% participation).  Of these 18 received care at St Jude and 14 at other institutions.   Those that received care at other institutions were in contact with St Jude directly- some specifically because of awareness of the autopsy program.   Parents completed the in a mean time of 11 months.

None of the parents expressed regret in participation.  The parents indicated that they consented to autopsy to help other families in the future and to help other parents know that they are not alone.

Parents also said that:
* it was better if the primary physician asked- specifically someone who "they had a relationship with and who showed concern." 
*there is "no right time" to initiate this discussion.  Parents do recognize that this is tough for the docs as well.  Most said that they would have preferred an earlier discussion.  Some said that an earlier discussion was less comforting.   Timing of the discussion will  likely take an individual approach.  (And from a personal point of view- a mother and a father might be at different places when considering this discussion.)
* there was a need to have clear information about procedures.   Knowing specifics helped decrease anxiety.  Some of these specifics included exactly what would be done during autopsy and how the child would look afterwards.

One of the specific issues addressed early was funding of transportation and autopsy.   Since many of children treated at St Jude die at home and not close to the facility, the logistics of funding had to be considered before this research could even be started.  It was at this point that a DIPG family was looking to make a difference.   Tyler's Treehouse agreed to fund non-covered expenses associated with post-mortem donation in order to make this research happen.

Tyler's Treehouse is named for a 5 year old boy- the 3rd of 4 sons.  Tyler was diagnosed on January 30, 2006 having symptoms only for 1 week.   The family went to St Jude but Tyler's tumor was too advanced to even start treatment.   He died a week later on February 8, 2006.

Without a foundation support like Tyler's Treehouse this type of program may not have been able to get started.   Thank you to the Scott's for their actions in their time of grief.

The logistics of making a DIPG Post Mortem Donation Program are not easy- but it is possible.  And from such programs we are beginning to understand DIPG.  Research is possible from autopsy specimens.   The effort has made a difference.

References:
DNA Analysis of Tumor Tissue Samples from Patients with Diffuse Brain Stem Glioma (NBTP02)
http://clinicaltrials.gov/ct2/show/NCT00899834?term=St+Jude+brainstem+glioma&rank=2

Bereaved Parents' Intention and Suggestions about Research Autopsies in Children with Lethal Brain Tumors
J Pediatr. 2013 Feb 19. pii: S0022-3476(13)00039-5. doi: 10.1016/j.jpeds.2013.01.015. [Epub ahead of print]
http://www.ncbi.nlm.nih.gov/pubmed/23433673

Somatic Histone H3 alterations in pediatric diffuse intrinsic pontine glioma and non-brainstem gliobastomas
http://www.ncbi.nlm.nih.gov/pubmed/22286216

Building a Post-Mortem DIPG Tissue Research Progam

Perhaps the biggest rate limiting step in DIPG research has been the lack of tissue.   Without tissue, what is there really to study in the basic science realm?   However,  DIPGs pose significant hurdles in getting tissue as biopsies have not been traditionally preformed and post-mortem donations have infrequently been requested.

Over the years there have been many barriers to post-mortem donations.  Some lacked knowledge- the medical system just didn't know that any research was actively being done.   Some didn't believe that usable samples could be obtained for research.   Some didn't know how to logistically make this happen especially if the child died at home and the research was being done somewhere else in the country.  Some didn't know how or when to approach the parents on this delicate topic.

There have been a few places that have worked to collect post-mortem DIPG samples for research.   One of the most impressive total package programs is Children's National Medical Center.   These researchers have taken on each obstacle and overcome them.

For me the first hurdle is if there is any DIPG research being done at that institution.   It doesn't do us any good to have a sample donated and then it sits in the freezer.   At Children's National Medical Center there was an interested researcher, Javad Nazarian, who already had a funded grant from the Childhood Brain Tumor Foundation to study DIPGs.    This meant there was some money and someone to do the research but there are still huge problems- how does anyone know you need the samples and how do you obtain them.

A researcher-clinician partnership was lead to a multi-disciplinary team.   This team included a pediatric neurosurgeon (Suresh Magee) and two pediatric neuro-oncologists (Roger Packer and Brain Rood) as well as Javad Nazarian.

To address the awareness issue, three things were done.  First, the researchers developed an IRB protocol and took the innovative step to have it placed in clinicaltrials.gov.  In this way,  interested physicians and parents might more easily find out about the research and have the contact information. Secondly, they developed a brochure detailing the information which parents could take away and review at a later time.  By the way,  it also had a 24 hour contact pager to help facilitate logistics.  Thirdly, they included their information on the Kid V Cancer site on research needing tissue.

The logistical problems of having a child die at home and then donating a post-mortem sample are complex; but, they are overcomeable.   It is easier to overcome them with some advanced planning.  Transportation is one of the recurrent hurdles as often times if the child will have to be transported to the hospital first then this is not covered by insurance.   There have been foundations that have stepped up to fund these expenses so that this research will not be stopped.  In this case, the Musella Foundation has supported that aspect of the program.

And now to maximize research,  Children's National Medical Center is part of a DIPG tissue sharing consortium called the Mid-Atlantic DIPG Consortium (MADC).  The other two institutions are Johns Hopkins and the National Institute of Health- Pediatric Oncology Branch.  This collaboration must be highly successful as several DIPG abstracts have come out for a series of spring meetings including AACR, USCAP and the SNO/PBTF Pediatric Neuro-Oncology Basic and Translational Research Conference.

If asked, some families will donate their child's tumor.   It will not be all, but many will and it is made so much more possible with a program in place to address the issues.  Kid's V Cancer is a good place to find out more about autopsy donation- both for families (FAQs and others experiences) as well as physicians  (how to ask and autopsy donation checklist).

Thank you Children's National Medical Center for putting this program in place to advance DIPG research.

References:
Molecular Analysis of Samples from Patients with Diffuse Intrinsic Pontine Glioma and Brainstem Glioma
Brochure: http://www.virtualtrials.com/pdf/dipg.pdf

Clinicaltrials.gov http://clinicaltrials.gov/ct2/show/NCT01106794

Selected DIPG articles/abstracts from Javad Nazarian and group:
Protein profiling of formalin fixed paraffin embedded tissue: Identification of potential biomarkers for pediatric brain stem glioma
http://www.ncbi.nlm.nih.gov/pubmed/21136889

Insights into pediatric diffuse intrinsic pontine glioma through proteomic analysis of spinal fluid
http://www.ncbi.nlm.nih.gov/pubmed/22492959

Targeting the Notch and mTor pathways in diffuse intrinsic pontine glioma
http://www.abstractsonline.com/Plan/ViewAbstract.aspx?mID=3086&sKey=6fa486c2-2701-4a76-8431-b22144df78e4&cKey=c3e199ac-82f7-486d-9d65-bb1c13525e3b&mKey=%7b9B2D28E7-24A0-466F-A3C9-07C21F6E9BC9%7d

NG2 Upregulation in Pediatric Diffuse Intrinsic Pontine Glioma and Its Role in Tumorigenecity in Vivo
https://soc-neuro-onc.conference-services.net/reports/template/onetextabstract.xml?xsl=template/onetextabstract.xsl&conferenceID=3467&abstractID=740466