Recently a publication came out in the journal Child's Nervous System retrospectively reviewing patient characteristics and outcomes in children treated for DIPG over a 13 year period (February 1999 to May 2012) at Cerrahpassa Medical Faculty and Oncology Institute in Instanbul, Turkey.
In this review there were 26 girls and 24 boys with a median age of 7. The median duration of symptoms - including cranial nerve palsies, motor disability and/or cerebellar dysfunction- was 30 days. The diagnosis was made by a multidisciplinary tumor board which included a a pediatric oncologist, radiation oncologist, neurosurgeon, and radiologist in the multidisciplinary tumor board.
Radiation was part of all the children's therapy although only twelve received radiation alone. The other children also received some form of chemotherapy with radiation. In 17 patients a radiosensitizer (either vincristine or cisplatin) during radiation and followed by CCNU and vincristine after radiation. After temozolomide became available this agent was used both during and after radiation for the remaining 21 children.
These three groups were analyzed regarding outcomes: group 1-radiation alone; group 2-vincristine/ciplastin; group 3- temozolomide. In this study, children in either chemotherapy group did better than those that had radiation alone. Ten of the children in group 2 were alive at 2 years and 3 at 3 years. Three children in group 3 were also alive at 3 years.
Interestingly 3 children in the temozolomide group had biopsies and were found to have pilocytic astroctyomas!
Fo me it is hard to know exactly what caused these two chemotherapy groups had better survival. It would seem that the 3 children with pilocytic astrocytomas were included in the analysis. The authors also said that there were improvements in radiation techniques over time which could have been a factor. Thus children who had radiation alone were the earliest patients in the review. Also it seems over type palliative care, PEG tubes and shunts became more common in that institution which may have played a role in the statistics.
Positive results of temozolomide with DIPG have not been replicated in other countries. Still, this article has significance to me to show the increase interest in DIPG around the world as well as the improved treatment for children with cancer. It was also good to see the conclusion that "the complex biology of DIPG renders an unselected single-agent approach less likely to be effective. Instead, a multi-targeted approach seems to be required to improve the prognosis". Hopefully we will see increasingly available multi-targeted options for children with DIPG.
Reference:
Pediatric diffuse intrinsic pontine glioma patients from a single center
Childs Nerv Syst. 2013 Apr;29(4):583-8. doi: 10.1007/s00381-012-1986-3. Epub 2012 Dec 8.
http://www.ncbi.nlm.nih.gov/pubmed/23224361
Radiotherapy with concurrent and adjuvant temozolomide in children with newly diagnosed diffuse intrinsic pontine glioma (France)
http://www.ncbi.nlm.nih.gov/pubmed/21858607
Temozolomide in the treatment of children with newly diagnosed diffuse intrinsic pontine gliomas: a report from the Children's Oncology Group
http://www.ncbi.nlm.nih.gov/pubmed/21345842
Prospective evaluation of radiotherapy with concurrent and adjuvant temozolomide in children with newly diagnosed diffuse intrinsic pontine glioma (India)
http://www.ncbi.nlm.nih.gov/pubmed/19647954
Sunday, April 28, 2013
Saturday, April 27, 2013
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
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
Friday, April 26, 2013
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
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
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
Thursday, April 25, 2013
Maddie's Mark
Just five days.... that is all they got between leaving the hospital after first hearing DIPG until their girl was gone.
Just five years....to live a lifetime.
Maddie had the memory of an elephant. She had a winning smile. She was "fiercely independent". She was a kindergartener. She was the big sister to two younger sisters. She loved arts and crafts. She also had DIPG.
The little girl diagnosed last year on February 3rd in Albany was supposed to go on a Wish Trip to Disney. She never made it there. She did get to go to Kindergarten and make her First Communion. Those final "best days ever" were spent at a dream house in Lake Placid surrounded by family. When they arrived home, it was too much of a struggle to go back and forth to the hospital so the oncologist came to them. She died on February 8th.
At one point when she was struggling her dad asked her how she was doing. Her said reply, "I can't do the things I want to do." Those were her last words to him- a truly heartbreaking part many have on the DIPG journey.
The community had raised funds to help with expenses but after Maddie died money was left over. The Mustos family decided to start a foundation- Maddie's Mark Foundation. The purpose of this foundation was to allow kids in New York to do things they wanted to do and have a "best day ever".
Here are some examples of Best Days Ever":
Another thing Maddie's Mark does is make stuffed animal elephants- fitting for a girl who had a memory like an elephant. Proceeds go to support the foundations.
This is another wonderful foundation started by a family wounded and grieving from DIPG.
Reference:
Maddie's Mark
http://www.maddiesmark.org/
Maddie's whole purpose 'was to care'
http://www.timesunion.com/local/article/Maddie-s-whole-purpose-was-to-care-3258157.php
Madeline Musto's memory helping children have 'best days ever'
http://www.watertowndailytimes.com/article/20130217/NEWS03/702179849
Just five years....to live a lifetime.
Maddie had the memory of an elephant. She had a winning smile. She was "fiercely independent". She was a kindergartener. She was the big sister to two younger sisters. She loved arts and crafts. She also had DIPG.
The little girl diagnosed last year on February 3rd in Albany was supposed to go on a Wish Trip to Disney. She never made it there. She did get to go to Kindergarten and make her First Communion. Those final "best days ever" were spent at a dream house in Lake Placid surrounded by family. When they arrived home, it was too much of a struggle to go back and forth to the hospital so the oncologist came to them. She died on February 8th.
At one point when she was struggling her dad asked her how she was doing. Her said reply, "I can't do the things I want to do." Those were her last words to him- a truly heartbreaking part many have on the DIPG journey.
The community had raised funds to help with expenses but after Maddie died money was left over. The Mustos family decided to start a foundation- Maddie's Mark Foundation. The purpose of this foundation was to allow kids in New York to do things they wanted to do and have a "best day ever".
Here are some examples of Best Days Ever":
- Naomi , a 6 year old with Ewing's sarcoma, was able to go to a Phillies game- in VIP style.
- Devon, a boy with an eye tumor, was able to go camping at Old Forge and Enchanged Water Safari.
- Myles, a 9 year old boy with pontine gliomas, "best day ever" included a reptile adventure party with a "pile of friends" which included his favorite pizza and cupcakes and a video camera. They also provided him with a recliner to be more comfortable. He died a week later in his comfy chair surrounded by family.
- Devon, also with DIPG,wanted a day having fun with friends and family. Maddie's Mark set up a dinner . Superhero Devon pins were made for this special day.
Another thing Maddie's Mark does is make stuffed animal elephants- fitting for a girl who had a memory like an elephant. Proceeds go to support the foundations.
This is another wonderful foundation started by a family wounded and grieving from DIPG.
Reference:
Maddie's Mark
http://www.maddiesmark.org/
Maddie's whole purpose 'was to care'
http://www.timesunion.com/local/article/Maddie-s-whole-purpose-was-to-care-3258157.php
Madeline Musto's memory helping children have 'best days ever'
http://www.watertowndailytimes.com/article/20130217/NEWS03/702179849
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