Dedicated to a special boy, Paul Alexander Coleman III, who is continuing to make an impact.....
Because of the trifecta of basic science hurdles- no tissue, no cell lines, no animal models- DIPG bench research has only recently begun. This has only been possible because of the efforts of a few individuals struggling to make the previously impossible possible- make animal models from an inoperable tumor. One of these pioneers- Xiao Nan Li MD, PhD (Baylor College of Medicine/Texas Children's Cancer Center).
Dr Li's interest is in the fields of cancer stem cells, experimental therapeutics and diagnostic markers with a particular focus on developing "clinically relevant animal models" for preclinical testing.
I first became aware of Dr Li when a fellow brain tumor parent sent her son's post-mortem specimen across the from the east coast to Texas to try to make a difference for medulloblastoma. The lab wasn't only interested in medulloblastoma. Dr Li has established more than 25 xenograft mouse models of several different pediatric brain tumors. At some time, a post mortem DIPG specimen was obtained and through the lab's work a door was unlocked for DIPG. Dr Li was able to establish a DIPG animal mouse model from this tissue and the scientific value of DIPG autopsy specimens skyrocketed.
Although the lab is interested in fighting all pediatric brain tumors there seems to have been a special focus on DIPG. Texas Children's has cell lines and thus became one of the initial members of the DIPG Pre-clincal consortium which is collaboratively working on rapid analysis of the cell lines and drug testing.
The lab has at least 5 different DIPG mouse xenografts that can be used for other types of research. One of these research endeavors is using oncolytic viruses in the DIPG mice he developed. Dr Xaio Nan Li will be presenting his work in a mouse model on eliminating therapy resistant DIPGs with an oncolytic virus at the DIPG Symposium in Cincinnati on May 3rd. A link to the grant executive summary funded by the Cure Starts Now is listed below.
This oncolytic virus research is exciting especially in light of the recent publication out of University of Alabama looking at this issue in pediatric gliomas. Although the publication is a different virus, the idea is essentially the same. Novel therapies are going to be needed to eliminate treatment resistent subpopulations while sparing normal tissue. Oncolytic virus have been one of the innovative treatment that might be a weapon in the future against DIPG as well as other gliomas and brain tumors.
References:
Neuro-Oncology Research Lab of Dr Xiao Nan Li
http://ccitonline.org/tccc_production_old/cancer-genomics-li/
Harnessing Autopsied DIPG Tumor Tissues for Orthotopic Xenograft Model Development in the Brain Stems of SCID mice- Grant Award Final Report
http://www.dtic.mil/cgi-bin/GetTRDoc?AD=ADA568355
Eliminating Therapy-Resistant Diffuse Intrinsic Pontine Gliomas with Oncolytic Picorna Virus SVV-001: an in vivo Study in Intra-brain Stem Xenograft Mouse Models- Grant Executive Summary
http://www.thecurestartsnow.org/_pdfs/grant_2011-11_texas.pdf
Pediatric glioma stem cells: biologic strategies for oncolytic HSV viral therapy.
Front Oncol. 2013;3:28. doi: 10.3389/fonc.2013.00028. Epub 2013 Feb 28.
http://www.ncbi.nlm.nih.gov/pubmed/234506
Tuesday, April 2, 2013
Monday, April 1, 2013
Are there survivors?
Are there any survivors of DIPG- even just one?
This is the fervent plea of so many parents whose children were just diagnosed with this terrible tumor. A search of the internet yields conflicting information. Here are some statements I have found:
*There are no long term survivors of DIPG.
*There are long term survivors.
*The long term survivors are atypical.
*If there are long term survivors then they were mis-diagnosed.
What is a parent to think? Who do you believe? Why are these statements so divergent? Is there an answer one can trust on survivors?
My short answer:
*There are long term survivors of DIPG (meaning more than 5 years).
*Most of the reported long term survivors are atypical in some way especially the very young (under 3), prolonged symptoms before diagnosis or atypical features on imaging- but not all.
* It is hard to say that a long term survivor was misdiagnosed since the diagnosis is based on imaging. The assumption has been if the lesion is uniformly diffuse and encompasses a large part of the pons then the lesion is a glioma. It is then called a DIPG. Since we have not have routine biopsied it is impossible to know the histology so all might not be gliomas. However, one can tell on imaging if the lesion is diffuse, intrinsic and pontine. It might be semantics but it seems hard to be a misdiagnosis per se but rather currently there is an inadequate understanding of these lesion.
I am virtually certain that the parents of prolonged survivors were given the exact dismal prognosis as those parents whose children had only a short time. I think it is extremely unfair to then go back and tell these parents that "well, it wasn't really a DIPG". It seems more valid to say that we don't understand these tumor. Some unpredictably and inexplicably do better than the vast majority of others.
So, why can I be so certain that there is at least one term survivor? One doesn't need to take my word for it. I would recommend viewing a 2009 video of a top St Jude researcher, Alberto Bronsicer.
http://justonemoreday.org/DIPGConference/NewClinicalTrialsfromStJude.html
(go in to 15:49 minutes)
Transcript:
I swear to you- typical brainstem glioma. I work her up- was one of my first patients at St. Jude. Full blown findings. We have spectroscopy. You name it. This is the MRI to show and 5 years later. She has some sequela of her treatment. One thing I point to all my parents- she never had complete response. A partial response. You see changes there 5 years later and she is out and about.
So yes, there is at least one long term survivor of what appeared to be a very typical DIPG. Unfortunately, the vast majority of children with these tumors will follow this path but for those that find hope in just one- here is one.
This is the fervent plea of so many parents whose children were just diagnosed with this terrible tumor. A search of the internet yields conflicting information. Here are some statements I have found:
*There are no long term survivors of DIPG.
*There are long term survivors.
*The long term survivors are atypical.
*If there are long term survivors then they were mis-diagnosed.
What is a parent to think? Who do you believe? Why are these statements so divergent? Is there an answer one can trust on survivors?
My short answer:
*There are long term survivors of DIPG (meaning more than 5 years).
*Most of the reported long term survivors are atypical in some way especially the very young (under 3), prolonged symptoms before diagnosis or atypical features on imaging- but not all.
* It is hard to say that a long term survivor was misdiagnosed since the diagnosis is based on imaging. The assumption has been if the lesion is uniformly diffuse and encompasses a large part of the pons then the lesion is a glioma. It is then called a DIPG. Since we have not have routine biopsied it is impossible to know the histology so all might not be gliomas. However, one can tell on imaging if the lesion is diffuse, intrinsic and pontine. It might be semantics but it seems hard to be a misdiagnosis per se but rather currently there is an inadequate understanding of these lesion.
I am virtually certain that the parents of prolonged survivors were given the exact dismal prognosis as those parents whose children had only a short time. I think it is extremely unfair to then go back and tell these parents that "well, it wasn't really a DIPG". It seems more valid to say that we don't understand these tumor. Some unpredictably and inexplicably do better than the vast majority of others.
So, why can I be so certain that there is at least one term survivor? One doesn't need to take my word for it. I would recommend viewing a 2009 video of a top St Jude researcher, Alberto Bronsicer.
http://justonemoreday.org/DIPGConference/NewClinicalTrialsfromStJude.html
(go in to 15:49 minutes)
Transcript:
I swear to you- typical brainstem glioma. I work her up- was one of my first patients at St. Jude. Full blown findings. We have spectroscopy. You name it. This is the MRI to show and 5 years later. She has some sequela of her treatment. One thing I point to all my parents- she never had complete response. A partial response. You see changes there 5 years later and she is out and about.
So yes, there is at least one long term survivor of what appeared to be a very typical DIPG. Unfortunately, the vast majority of children with these tumors will follow this path but for those that find hope in just one- here is one.
Sunday, March 31, 2013
A New Era for Children with Diffuse Intrinsic Pontine Glioma: Hope for A Cure?
"A new era for DIPG has just begun."
So starts the conclusion of this expert review article written last year by two prominent DIPG researchers from the Netherlands- Marc Jansen and Gertjan Kaspers. It will behoove one interested in DIPG research to be aware of those names. They are ones that keep coming up in DIPG issues- publications and European DIPG worshops.
These experts highlight that there has been a rapid increase in biological understanding of DIPGs. This has only been able to occur because of the recent availability of DIPG tumor tissue which from the French re-introduction of biopsies and the North American/Dutch focus on autopsy donation. This DIPG tissue is critical to the further understanding of DIPG although biopsies and post-mortem tissue each have advantages and disadvantages.
The biopsy issues has been very controversial. The French group has now preformed over 100 stereotactic biopsies with 0% mortality and a 4% transient morbidity. An advantage of pre-treated biopsy specimens is that there is a significant risk treatment will change the original molecular characteristics. The tumor that the children start with very likely is not the tumor molecularly that they die with.
Post mortem tissue carries a high risk of treatment-related genetic changes. Still, there are advantages. There is a much greater tissue volume available for study. This also allows study on tumor hetergeneity (how varied the tumor is) as well as "treatment-resistent subclones". In addition, it has been from these tumor donations that cell lines and animal models have been developed (greatly adding to research potential).
Even with this "avalanache of gene profiling studies" in DIPG, this will probably not provide the entire answer for cure. There is at least one other prong to the problem. The authors pose some thoughtful questions for consideration:
- Why are all chemotherapy regimens ineffective in DIPG while some show activity in supratentorally located gliomas, such as temozolomide?
- Why does imatinib, an inhibitor of the DIPG key target PDGFRA, not improve survival ?
- Could poor drug distribution be at least partly the answer to these questions?
It is a new era. There are researchers focused on understanding this tumor. There has been a virtual explosion of clinical trials and publications. There is excitement.
We are, though, at the beginning. We have just gotten some of the tools to fight, --to understand , --to research, --to make a difference. It is unlikely that the cure is around the next bend but research is finally moving for children with DIPG. There is reason to hope that someday there might be a cure.
Note- DIPG research at the VU University Medical Center is financially supported by Stichting Semmy (Weesp, The Netherlands).
References:
A new era for diffuse intrinsic pontine glioma: hope for a cure?
Gertjan J Kaspers and Marc Jansen
Pediatric Oncology and Hematology, VU University Medical Center, Amsterdam, The Netherlands Expert Rev. Anticancer Ther. 12(9), 1109–1112 (2012)
Full Text: http://www.brainlife.org/reprint/2012/Kaspers_GJ120900.pdf
Stichting Semmy-
http://dipg.blogspot.com/2013/03/foundation-spotlight-stichting-semmy.html
Saturday, March 30, 2013
Miette- Sweet Little Crumb
She loved princesses as well as castles, faires and all magical things .
She loved animals- giraffes, elephants and kittens.
She was sweet, courageous, thoughtful, light and bright.
Miette's gorgeous blue eyes, impish smile and golden locks hid a fatal tumor.
Her parents were determined to tell her story from the beginning to the end. The beginning started on July 25th 2011, when 5-year-old Miette was diagnosed with a brainstem tumor. The next day her parents were told there "with radiation there would be a 50% chance she would be here in 1 year and a zero percent chance in two." The end came this week on Tuesday. Australia's Sweet Little Crumb left this world.
She loved animals- giraffes, elephants and kittens.
She was sweet, courageous, thoughtful, light and bright.
Miette's gorgeous blue eyes, impish smile and golden locks hid a fatal tumor.
Her parents were determined to tell her story from the beginning to the end. The beginning started on July 25th 2011, when 5-year-old Miette was diagnosed with a brainstem tumor. The next day her parents were told there "with radiation there would be a 50% chance she would be here in 1 year and a zero percent chance in two." The end came this week on Tuesday. Australia's Sweet Little Crumb left this world.
A special thing on this journey- Chicken Mick and his band of merry helpers. This "big hearted Aussie bloke"put together a Wiggly Whirlwind Weekend sending Miette to Melbourne to meet the Wiggles.
The story didn't end there though. They were met by a TV crew at the airport on the flight home and taken home in a fairy pink Hummer. Although they had agreed to a "lick of paint on her cubby" while they were away and told Chicken Mike that Miette liked animals, they were not expecting what waited at home. The front yard was transformed into a little farm and her cubby into an "area fit for a princess". Here is the story in their own words...
or better yet watch this special video.....
Because of Miette, the Wiggles are now ambassadors to raise awareness of through the Isabella and Marcus Paediatric Brainstem Tumour Fund. Both Isabelle and Marcus died from DIPG. The two families started this foundation with the mission to fund Australian research into pediatric brainstem tumors with a focus on DIPG. Miette joined in with her support making hairclips and bands, selling them online and giving 50% of the proceeds to the charity.
A vision of the foundation is "to established an Endoswed Chair at the Univeristy of Melbourne, with an affiliated research laboratory in the Victorian Comprehensive Cancer Centre that will perform research to understand the nature of these tumors, develop novel treatments and to participate in international clinical trials."
Miette you will be remembered.
Reference:
A vision of the foundation is "to established an Endoswed Chair at the Univeristy of Melbourne, with an affiliated research laboratory in the Victorian Comprehensive Cancer Centre that will perform research to understand the nature of these tumors, develop novel treatments and to participate in international clinical trials."
Miette you will be remembered.
Reference:
Miette's Journey - https://www.facebook.com/miettesjourney
Miette's Journey- http://www.miettesjourney.com/
Chicken Mick-
Isabella and Marcus Paediatric Brainstem Tumour Fund- http://www.isabellaandmarcusfund.org.au/index.html
Subscribe to:
Posts (Atom)