Back in the summer of 2005 the Institut Gustave Roussy started a study with upfront stereotactic biopsy in children with diffuse intrinsic pontine gliomas.
http://clinicaltrial.gov/ct2/show/NCT00418327?term=Tarceva+and+brainstem+glioma&rank=1
In the July 2007 edition of The Journal of Neurosurgery, the results neurosurgical results of 24 children who underwent biopsy were published. In this there was no mortality and transient morbidity in two patients.
http://www.ncbi.nlm.nih.gov/pubmed/17647306
At the 2010 International Society of Pediatric Neuro-Oncology in Vienna, the French group presented pathologic data regarding the upfront biopsy results with pediatric DIPG. There were 60 children who underwent biopsy and which there were 35 frozen sample in which they could undertake array comparative genomic hybridization or gene expression profiles. The median age of the children was 7.3 years and the overall survival was 10.5 months. Histopathologically, there were 10 grade II, 14 grade III, 10 grade IV and one that could not be graded.
Neither the MRI characteristics or the tumor grade were correlated with survival.
Two patterns were found by genetic analysis. One pattern showed enrichment for neural patterning genes (particularly regarding PDGFRa). The other had angiogenic and adhesion genes. The patterns did not relate to tumor grade. The first group had a worse prognosis with a majority of children in this group having overall survival less than the median survival.
The authors concluded that they have found two DIPG molecular subgroups ‘characterized by chromosomal regions and potentially therapeutic targets’.
These results seem to dovetail well with the previously reported post-mortem study in March in JCO from Sick Kids in Toronto.
References-
Whole-genome profiling of pediatric diffuse intrinsic pontine gliomas highlights platelet-derived growth factor receptor alpha and poly (ADP-ribose) polymerase as potential therapeutic targets
J Clin Oncol. 2010 Mar 10;28(8):1337-44. Epub 2010 Feb 8.
Tuesday, July 13, 2010
Sunday, July 11, 2010
From "Brain Tomour" World Edition 2010. International Brain Tomour Alliance
DIFFUSE INTRINSIC PONTINE GLIOMA: COLLABORATION IS LEADING TO CHANGE
By Dr Loice Swisher
Dr Loice Swisher whose daughter Tori is a ten year medulloblastoma survivor. Loice is an FDA Patient Representative and emergency medicine physician. She is pictured here on a family vacation in Utah.
“It's been almost two years since Sam was diagnosed in December 2006. The only improvement that I've seen during this time is that we have this wonderful site!” [the DIPG Internet Yahoo support list and discussion group]
So said “Sheila” (in December 2008), whose young grandson had died in February 2008 from a diffuse intrinsic pontine glioma.
A diffuse intrinsic pontine glioma, known as DIPG, is perhaps the most feared pediatric brain tumor because of the dismal survival statistics and devastating clinical course. This tumor tends to strike four to ten year olds with approximately half of these young children dying in the first year and 80-90% by the end of the second.
Despite more than 200 trials, no treatment has been found to be effective for long term survival in DIPG. For some children, steroids and radiation allow for a ‘honeymoon’ with relief of symptoms. But this is often followed by a relentless advancing of the disease and tragically, death months later.
Basic science research into this tumor has been frustratingly difficult. A significant hurdle has been the lack of tumor tissue on which to carry out tests.
In 1993, the standard of care for DIPG in the United States changed, as biopsy provided no improvement in survival over neuro-imaging in typical pediatric diffuse pontine tumors. Since that time, biopsies of pediatric DIPG have been uncommon resulting in the scarcity of tumor material for research. At the time “Sheila” wrote, there were no published reports on cell lines, no animal models and no molecular/genetic studies.
The changes in the medical community’s approach to a disease are often evident much before the patient community is aware of them because the time from concept to study to publication of a research paper can take years. In 2008, change was beginning in DIPG research. The heart-wrenching post from grandmother “Sheila” launched an effort towards earlier awareness of research endeavors as well as international advocacy collaboration.
In 2005 the biopsy debate had heated up again. St Jude Children’s Research Hospital in Memphis, Tennessee (USA) responded with a concerted effort to approach families for post-mortem tumor donation for research resulting in more molecular information on DIPG. Since many children die at home, far from St Jude, the emotional and logistical challenges were numerous.
A family responded to the financial issues raised by these challenges by establishing a foundation called Tyler’s Treehouse (established in 2006), specifically started to fund the logistical aspects of this study.
Over the ensuing years, many families with DIPG children have provided the ultimate gift to the research community involved with these studies of their child’s tumour tissue. Some families as far away as Australia and South America have donated their child’s tissue. The St. Jude efforts haven’t lead to publication yet, however, The Hospital for Sick Children (“Sick Kids”) in Toronto, Canada published the first whole genomic analysis of DIPG tumors in February 2010.
Their French colleagues took a different approach, with a clinical trial including upfront stereotactic biopsy of pediatric DIPG. In the July 2007 issue of the Journal of Neurosurgery the surgical results were published. With 24 children there was no mortality and only two children had transient morbidity.
The combined effect of the French stereotactic biopsy results and the molecular analysis studies from “Sick Kids” in Toronto has lead to renewed efforts for future clinical trials to include molecular analysis from stereotactic biopsy samples.
The development of animal models is also emerging.
At the 2008 ISPNO (International Symposium on Pediatric Neuro-Oncology) conference in Chicago (USA), Dr. Oren Becher won the best basic science presentation award for his genetically engineered mouse model of brainstem glioma. The excitement of potentially being able to study this tumor in a mouse model has resulted in requests for Dr Becher’s mice from several others interested in studying brainstem glioma.
For some time, the non-availability of resected tumor tissue for the development of cell lines has met with failure, even to the point of new researchers being discouraged from pursing this direction.
In the summer of 2009, Stanford University in California revealed that Dr. Michelle Monje had been able to culture neurospheres from post-mortem pediatric DIPG tissue using a stem cell technique. This breakthrough in DIPG research at Stanford has lead to an EGFRviii vaccine being introduced to the pediatric brain tumor community for the first time as well as other research. Some of this has been funded through the Kyle O’Connell Foundation.
Truly exciting events have been two international meetings of researchers and clinicians to discuss DIPG. The Fondo Alicia Pueyo hosted the first conference in Barcelona, Spain in February 2009. The second event was hosted by The Hospital for Sick Children in Toronto with funding support by Just One More Day and B.R.A.I.N.child.
We are now seeing a change in DIPG research - and the international collaboration of parents, advocates, clinicians and researchers that is making this happen.
By Dr Loice Swisher
Dr Loice Swisher whose daughter Tori is a ten year medulloblastoma survivor. Loice is an FDA Patient Representative and emergency medicine physician. She is pictured here on a family vacation in Utah.
“It's been almost two years since Sam was diagnosed in December 2006. The only improvement that I've seen during this time is that we have this wonderful site!” [the DIPG Internet Yahoo support list and discussion group]
So said “Sheila” (in December 2008), whose young grandson had died in February 2008 from a diffuse intrinsic pontine glioma.
A diffuse intrinsic pontine glioma, known as DIPG, is perhaps the most feared pediatric brain tumor because of the dismal survival statistics and devastating clinical course. This tumor tends to strike four to ten year olds with approximately half of these young children dying in the first year and 80-90% by the end of the second.
Despite more than 200 trials, no treatment has been found to be effective for long term survival in DIPG. For some children, steroids and radiation allow for a ‘honeymoon’ with relief of symptoms. But this is often followed by a relentless advancing of the disease and tragically, death months later.
Basic science research into this tumor has been frustratingly difficult. A significant hurdle has been the lack of tumor tissue on which to carry out tests.
In 1993, the standard of care for DIPG in the United States changed, as biopsy provided no improvement in survival over neuro-imaging in typical pediatric diffuse pontine tumors. Since that time, biopsies of pediatric DIPG have been uncommon resulting in the scarcity of tumor material for research. At the time “Sheila” wrote, there were no published reports on cell lines, no animal models and no molecular/genetic studies.
The changes in the medical community’s approach to a disease are often evident much before the patient community is aware of them because the time from concept to study to publication of a research paper can take years. In 2008, change was beginning in DIPG research. The heart-wrenching post from grandmother “Sheila” launched an effort towards earlier awareness of research endeavors as well as international advocacy collaboration.
In 2005 the biopsy debate had heated up again. St Jude Children’s Research Hospital in Memphis, Tennessee (USA) responded with a concerted effort to approach families for post-mortem tumor donation for research resulting in more molecular information on DIPG. Since many children die at home, far from St Jude, the emotional and logistical challenges were numerous.
A family responded to the financial issues raised by these challenges by establishing a foundation called Tyler’s Treehouse (established in 2006), specifically started to fund the logistical aspects of this study.
Over the ensuing years, many families with DIPG children have provided the ultimate gift to the research community involved with these studies of their child’s tumour tissue. Some families as far away as Australia and South America have donated their child’s tissue. The St. Jude efforts haven’t lead to publication yet, however, The Hospital for Sick Children (“Sick Kids”) in Toronto, Canada published the first whole genomic analysis of DIPG tumors in February 2010.
Their French colleagues took a different approach, with a clinical trial including upfront stereotactic biopsy of pediatric DIPG. In the July 2007 issue of the Journal of Neurosurgery the surgical results were published. With 24 children there was no mortality and only two children had transient morbidity.
The combined effect of the French stereotactic biopsy results and the molecular analysis studies from “Sick Kids” in Toronto has lead to renewed efforts for future clinical trials to include molecular analysis from stereotactic biopsy samples.
The development of animal models is also emerging.
At the 2008 ISPNO (International Symposium on Pediatric Neuro-Oncology) conference in Chicago (USA), Dr. Oren Becher won the best basic science presentation award for his genetically engineered mouse model of brainstem glioma. The excitement of potentially being able to study this tumor in a mouse model has resulted in requests for Dr Becher’s mice from several others interested in studying brainstem glioma.
For some time, the non-availability of resected tumor tissue for the development of cell lines has met with failure, even to the point of new researchers being discouraged from pursing this direction.
In the summer of 2009, Stanford University in California revealed that Dr. Michelle Monje had been able to culture neurospheres from post-mortem pediatric DIPG tissue using a stem cell technique. This breakthrough in DIPG research at Stanford has lead to an EGFRviii vaccine being introduced to the pediatric brain tumor community for the first time as well as other research. Some of this has been funded through the Kyle O’Connell Foundation.
Truly exciting events have been two international meetings of researchers and clinicians to discuss DIPG. The Fondo Alicia Pueyo hosted the first conference in Barcelona, Spain in February 2009. The second event was hosted by The Hospital for Sick Children in Toronto with funding support by Just One More Day and B.R.A.I.N.child.
We are now seeing a change in DIPG research - and the international collaboration of parents, advocates, clinicians and researchers that is making this happen.
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