To Biopsy or Not to Biopsy- How Did We Get Here?
Dr Foreman gave the dismal background on DIPG treatments. The only treatment known to help prolong life in these children is radiation; however, attempts to intensify radiation treatments have not improved outcome. In addition, chemotherapy has been tried both before and after radiation without success. In fact, the UKCCSG stated, “This approach should be abandoned as toxic and without benefit and with toxicity.” Even high dose chemotherapy with autologous bone marrow rescue has failed.
Given the terrible track record and significant lack of specific tumor biology knowledge, why do we not biopsy these tumors?
The most influential paper that changed the standard method of diagnosing diffuse intrinsic pontine gliomas from biopsy to MRI was published by Albright in 1993 [1]. This paper reviewed the results of a brainstem trial (CCG-9882). In this paper the authors recommended that biopsies not be done because they added nothing to the diagnostic precision of MRI. Dr Foreman noted complication rates were not included as part of the justification for this position, and there was actually no surgical mortality in this study.
In a commentary on the Albright paper, Dr Fred Epstein (a pioneer in the field of pediatric neurosurgery – especially in the brainstem) stated, “Routine biopsy should be relegated to neurosurgical history.”
This is where we are today. As opposed to adults where biopsy of diffuse brainstem masses is common as there is are a greater variety of etiologies, biopsy of pediatric DIPGs is currently only recommended for atypical cases. Yet more and more, authors are publishing such comments as, “Given the lack of efficacy of conventional drugs, a better understanding of the biology of this tumor is the key to more targeted therapy.” [2]
In an attempt to address whether science has progressed sufficiently to warrant a change in philosophy toward DIPG biopsy, the committee debated the following scientific question:
“Based on your discussion, has the state of the science in drug targeting research progressed to where there is a reasonable expectation of success in identifying drug candidates to move into early phase clinical trials for DIPG?”
The vote was 16 yes, 7 no and 1 abstention. (The reason given for this abstention was inadequate knowledge of this subject.)
Reference-
1. Magnetic resonance scans should replace biopsies for the diagnosis of diffuse brain stem gliomas: a report from the Children's Cancer Group.
Neurosurgery. 1993 Dec;33(6):1026-9; discussion 1029-30
2. Brainstem gliomas in children and adults.
Curr Opin Oncol. 2008 Nov;20(6):662-7
3. April 27th, 2009 FDA joint PAC/ODAC public meeting on DIPG Biopsy-Slides
Tuesday, May 5, 2009
Sunday, May 3, 2009
FDA Public Hearing on Biopsy of Children with DIPGs- Part 1
On Monday April 27th, the FDA held an open public meeting to discuss the scientific and ethical issues involved in developing drug treatments for children with diffuse pontine glioma.
Biopsying children with diffuse intrinsic pontine gliomas has become increasingly controversial. Clearly there are physicians that strongly hold the opinion that there will likely be no movement to cure these usually fatal tumors until tissue is obtained. Those that take this position tend to feel that the state of the art advances in neurosurgery and genomics have made it possible for DIPGs to be treated in the same way that almost all other brain tumors (as well as virtually all other cancers in the body)- with pathologic diagnosis.
This debate has gained even more attention because of a recent French trial for newly diagnosed diffuse intrinsic pontine glioma patients in which biopsy was mandatory in order to be able to participate. Of the 24 patients, all survived and two had transient neurological problems. In addition, two patients were found to have low grade tumors and were treated differently specifically because of the biopsy results. With respect to the remaining 22 high grade tumors, there was no change in therapeutic intervention as a result of biopsy.
Although there was no specific protocol or agent placed in front of the committee, the obviously increasing interest in the change of direction with this tumor caused the DIPG biopsy issue to be placed before the committee. At this time there appears to be a minimum of two or three potential US protocols on the table that include biopsy of DIPG.
It was stated that biopsies may be routinely recommended for atypical lesions. This is a clinical decision, not an ethical question.
In addition, biopsies performed as part of a determination for therapeutic intervention were also not to be part of the conversation. By definition these would be therapeutic biopsies. However, it was noted by some that the results from selecting agents based on molecular markers has been marginal in the field thus far.
The ethical question brought before the committee was:
“Assuming a reasonable expectation of scientific success, should children with DIPG undergo a non-therapeutic brain biopsy to advance the study of possible drug targets (i.e., for research purposes only)?”
References:
Stereotactic biopsy of diffuse pontine lesions in children.
J Neurosurg. 2007 Jul;107(1 Suppl):1-4
April 27th, 2009 FDA joint PAC/ODAC public meeting on DIPG Biopsy- Slides
Biopsying children with diffuse intrinsic pontine gliomas has become increasingly controversial. Clearly there are physicians that strongly hold the opinion that there will likely be no movement to cure these usually fatal tumors until tissue is obtained. Those that take this position tend to feel that the state of the art advances in neurosurgery and genomics have made it possible for DIPGs to be treated in the same way that almost all other brain tumors (as well as virtually all other cancers in the body)- with pathologic diagnosis.
This debate has gained even more attention because of a recent French trial for newly diagnosed diffuse intrinsic pontine glioma patients in which biopsy was mandatory in order to be able to participate. Of the 24 patients, all survived and two had transient neurological problems. In addition, two patients were found to have low grade tumors and were treated differently specifically because of the biopsy results. With respect to the remaining 22 high grade tumors, there was no change in therapeutic intervention as a result of biopsy.
Although there was no specific protocol or agent placed in front of the committee, the obviously increasing interest in the change of direction with this tumor caused the DIPG biopsy issue to be placed before the committee. At this time there appears to be a minimum of two or three potential US protocols on the table that include biopsy of DIPG.
It was stated that biopsies may be routinely recommended for atypical lesions. This is a clinical decision, not an ethical question.
In addition, biopsies performed as part of a determination for therapeutic intervention were also not to be part of the conversation. By definition these would be therapeutic biopsies. However, it was noted by some that the results from selecting agents based on molecular markers has been marginal in the field thus far.
The ethical question brought before the committee was:
“Assuming a reasonable expectation of scientific success, should children with DIPG undergo a non-therapeutic brain biopsy to advance the study of possible drug targets (i.e., for research purposes only)?”
References:
Stereotactic biopsy of diffuse pontine lesions in children.
J Neurosurg. 2007 Jul;107(1 Suppl):1-4
April 27th, 2009 FDA joint PAC/ODAC public meeting on DIPG Biopsy- Slides
Thursday, April 30, 2009
MAY IS BRAIN TUMOR AWARENESS MONTH!
Tomorrow is May 1 -- the first day of Brain Tumor Awareness Month.
Please wear a gray ribbon all month and spread the word about this disease that is taking so many of our children (and adults) -- and without hope for effective treatment or a cure for so many.
If you'd like a Just One More Day gray, glow in the dark wristband, they are $3.00 each and can be ordered at http://www.justonemoreday.org/giftStore/JOMDMerchandise.html
Please join in walking for a cure -- in Minnesota:
http://www.umbrellaofhope.com/
Please let us know of any brain tumor awareness events and media coverage in your area! Spread the word and join in the fight!
Sunday, April 26, 2009
DIPG Digest
April 26, 2009
Medical News
Pediatric brain tumors: mutations of two dioxygenases (hABH2 and hABH3) that directly repair alkylation damage. : http://www.ncbi.nlm.nih.gov/pubmed/19290481?ordinalpos=2&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum
Turning cancer stem cells inside-out: an exploration of glioma stem cell signaling pathways. Free Full Text- http://www.jbc.org/cgi/reprint/R900013200v1
Tumour vaccine approaches for CNS malignancies: progress to date. : http://www.ncbi.nlm.nih.gov/pubmed/19275269?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum
New Trial
Vaccine Therapy in Treating Young Patients With Newly Diagnosed or Recurrent Glioma
A Pilot Study to Evaluate the Effects of Vaccinations With HLA-A2-Restricted Glioma Antigen-Peptides in Combination With Poly-ICLC for Children With Newly Diagnosed Malignant or Intrinsic Brain Stem Gliomas (BSG) or Incompletely Resected Non-Brainstem High-Grade Gliomas (HGG) or Recurrent Unresectable Low-Grade Gliomas (LGG)
http://www.clinicaltrials.gov/ct2/show/NCT00862199?term=vaccine+brain+tumor+children&rank=6
Convection Enhanced Delivery of IL13-PE38QQR in Patients with DIBG
*The following information was copied directly from http://www.clinicaltrials.gov/ . It is, however, our understanding that the study is not actually open as of this date.An Open Label Dose Escalation Safety Study of Convection-Enhanced Delivery of IL13-PE38QQR in Patients With Progressive Pediatric Diffuse Infiltrating Brainstem Glioma and Supratentorial High-Grade Glioma
This study is currently recruiting participants. *
Verified by National Institutes of Health Clinical Center (CC), March 2009First Received: April 10, 2009 No Changes Posted
Sponsored by:National Institute of Neurological Disorders and Stroke (NINDS)
http://clinicaltrials.gov/ct2/show/NCT00880061?term=convection+enhanced+delivery&rank=1
FDA to Discuss DIPG Biopsies
Date and Time of Meeting:
April 27, 2009, from 8 a.m. to 6 p.m.
Date and Time of the Open Public Hearing:
April 27, 2009, between approximately 1 p.m. and 2 p.m.
Address of Meeting:
Washington DC North/Gaithersburg Hilton,
620 Perry Pkwy.,
Gaithersburg, MD 20877.
Agenda:
On April 27, 2009, the Committee will meet to discuss the scientific and ethical issues involved in obtaining and using brain biopsy specimens to evaluate gene expression patterns in children with diffuse pontine gliomas.
http://www.fda.gov/oc/advisory/default.htm
Foundations News
Reflections of Grace -- Race For Grace Draws Huge Turnout http://www.wpxi.com/news/19036532/detail.html
Just One More Day – UmbrELLA of Hope Family Fun Walk
Saturday, May 16, 2009
Lakefront Park in Prior Lake MN
http://www.umbrellaofhope.com/Pages/Home.aspx
For past issues of DIPG Digest please visit http://www.justonemoreday.org/ParentPointers/DIPGDigest.html
Please submit information you feel will be helpful to DIPG families to http://health.groups.yahoo.com/group/DIPG/post?postID=hVhc8pdqOFzVDqPPCWmsdtlxyFXGsFzbG0Ku4_g-Uda_0auMReldT5KuEz6XCpkQl2N-Z7PNS6OzzTGEfOk66khP--g subject: DIPG Digest
Copyright 2008 - 2009 Just One More Day for Love, Hope & a Cure, Inc. All rights reserved. The materials and links provided on this site have been prepared for information purposes only and should not be construed as advice or opinions on any specific facts or circumstances. Medical research concerning disease and treatments is an ongoing process. Readers should not act upon this information, but should obtain advice from physicians, medical institutions or other professionals, as appropriate.
Medical News
Pediatric brain tumors: mutations of two dioxygenases (hABH2 and hABH3) that directly repair alkylation damage. : http://www.ncbi.nlm.nih.gov/pubmed/19290481?ordinalpos=2&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum
Turning cancer stem cells inside-out: an exploration of glioma stem cell signaling pathways. Free Full Text- http://www.jbc.org/cgi/reprint/R900013200v1
Tumour vaccine approaches for CNS malignancies: progress to date. : http://www.ncbi.nlm.nih.gov/pubmed/19275269?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum
New Trial
Vaccine Therapy in Treating Young Patients With Newly Diagnosed or Recurrent Glioma
A Pilot Study to Evaluate the Effects of Vaccinations With HLA-A2-Restricted Glioma Antigen-Peptides in Combination With Poly-ICLC for Children With Newly Diagnosed Malignant or Intrinsic Brain Stem Gliomas (BSG) or Incompletely Resected Non-Brainstem High-Grade Gliomas (HGG) or Recurrent Unresectable Low-Grade Gliomas (LGG)
http://www.clinicaltrials.gov/ct2/show/NCT00862199?term=vaccine+brain+tumor+children&rank=6
Convection Enhanced Delivery of IL13-PE38QQR in Patients with DIBG
*The following information was copied directly from http://www.clinicaltrials.gov/ . It is, however, our understanding that the study is not actually open as of this date.An Open Label Dose Escalation Safety Study of Convection-Enhanced Delivery of IL13-PE38QQR in Patients With Progressive Pediatric Diffuse Infiltrating Brainstem Glioma and Supratentorial High-Grade Glioma
This study is currently recruiting participants. *
Verified by National Institutes of Health Clinical Center (CC), March 2009First Received: April 10, 2009 No Changes Posted
Sponsored by:National Institute of Neurological Disorders and Stroke (NINDS)
http://clinicaltrials.gov/ct2/show/NCT00880061?term=convection+enhanced+delivery&rank=1
FDA to Discuss DIPG Biopsies
Date and Time of Meeting:
April 27, 2009, from 8 a.m. to 6 p.m.
Date and Time of the Open Public Hearing:
April 27, 2009, between approximately 1 p.m. and 2 p.m.
Address of Meeting:
Washington DC North/Gaithersburg Hilton,
620 Perry Pkwy.,
Gaithersburg, MD 20877.
Agenda:
On April 27, 2009, the Committee will meet to discuss the scientific and ethical issues involved in obtaining and using brain biopsy specimens to evaluate gene expression patterns in children with diffuse pontine gliomas.
http://www.fda.gov/oc/advisory/default.htm
Foundations News
Reflections of Grace -- Race For Grace Draws Huge Turnout http://www.wpxi.com/news/19036532/detail.html
Just One More Day – UmbrELLA of Hope Family Fun Walk
Saturday, May 16, 2009
Lakefront Park in Prior Lake MN
http://www.umbrellaofhope.com/Pages/Home.aspx
For past issues of DIPG Digest please visit http://www.justonemoreday.org/ParentPointers/DIPGDigest.html
Please submit information you feel will be helpful to DIPG families to http://health.groups.yahoo.com/group/DIPG/post?postID=hVhc8pdqOFzVDqPPCWmsdtlxyFXGsFzbG0Ku4_g-Uda_0auMReldT5KuEz6XCpkQl2N-Z7PNS6OzzTGEfOk66khP--g subject: DIPG Digest
Copyright 2008 - 2009 Just One More Day for Love, Hope & a Cure, Inc. All rights reserved. The materials and links provided on this site have been prepared for information purposes only and should not be construed as advice or opinions on any specific facts or circumstances. Medical research concerning disease and treatments is an ongoing process. Readers should not act upon this information, but should obtain advice from physicians, medical institutions or other professionals, as appropriate.
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