DIPG/DIPT Discussion

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A searchable blog on DIPG research, DIPG news, recent publications, DIPG Foundations, DIPG researchers, clinical trials as well as other issues relating to Diffuse Intrinsic Pontine Tumors- both Diffuse Intrinsic Pontine Gliomas (DIPGs) and Atypical Pontine Lesions (APLs).

For parents, family and friends of children with DIPG looking for information and connection to others dealing with DIPG please check the buttons on the right hand side for resources.

Thursday, April 30, 2009

MAY IS BRAIN TUMOR AWARENESS MONTH!

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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/


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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.

Sunday, April 19, 2009

DIPG Dialogue

Just One More Day is starting a new regular blog feature called DIPG Dialogue which will contain interviews with researchers, physicians and other advocates in the DIPG community.

Introduction

Dr Shaohua Yang, M.D. & Ph.D.,
is currently an assistant professor in the Department of Pharmacology and Neuroscience at the University of North Texas Health Science Center. He has had neurosurgery residency training at Beijing Neurosurgical Institute China, one of the largest neurosurgical centers in the world, and has extensive clinical experience with brainstem tumor. Dr Yang's primary research is funded in the field of stroke and neuroprotection by National Institute of Health. He also has been pursuing research with brainstem glioma. In the end of 2008, Dr. Yang published his results of a novel experiment in the Journal of Neurosurgery, in which C6 glioma cells were implanted into the pons of juvenile and adult rats.


Questions & Answers:

Dr. Yang, what did your study show?

First of all, I would like to thanks this blog to provide the opportunity to share my research with all of you, especially with the parents of the brainstem glioma patients.
It has been well known that the outcome of brainstem glioma is very different between children and adult. Brainstem glioma constitutes up to 20% of childhood brain tumor, and has the worst outcome of any brain tumor in children. Over 80% of brainstem gliomas in children are diffuse intrinsic brainstem gliomas, which mean that the tumor cells are tangled extensively with normal brainstem tissue and make surgical intervention even radiotherapy almost impossible. On the other hand, brainstem glioma in adult is less aggressive and grows focally, which may benefit from surgical intervention and radiotherapy. Therefore, the median survival of adult brainstem glioma patient is much longer than that of children.
It is generally believed that the difference between childhood and adult brainstem glioma is due to the different grade of gliomas in these two groups. Normally, low-grade brainstem gliomas are considered to have a characteristic pattern focal growth, while high-grade brainstem gliomas grow diffusely and aggressively. However, this is not always the case, low-grade gliomas such as fibrillary astrocytomes have also been found in association with diffuse brainstem gliomas. Furthermore, very few histological data are available for diffuse brainstem gliomas because very few surgical intervention has been conducted in this type of glioma as biopsy results do not alter the treatment strategy.
From my clinical experience, I have noticed that children brainstem is much softer than that of adult. Thus, I thought about that the anatomical, histological, and immunological diversity between children and adults may be also contribute to the different biological behavior of diffuse and focal brainstem gliomas in children and adults. We used C6 glioma cells, which were chemical-induced glioma cells in rats. We implanted C6 cells in brainstem of young and adult rats to see how these tumor cells grow. What we found is that the brainstem glioma in young and adult rats imitates the characteristics of brainstem gliomas in humans. Since we put the same cells into the brainstem of both young and adult rats, this result indicates that the growth pattern and invasiveness of brainstem glioma could be due the host factors.


Do you have any explanation of why there is this difference between the tumors made in the young versus the adult rats?

From these results, what we can conclude so far is that the host factors could contribute the difference between brainstem gliomas in the young versus adult rats. These factors include anatomical, histological, and immunological factors. The growth and invasiveness of the tumor cells are not only depended on the cells but also on the environment. Different from adults, children are still in the development stage. They keep growing everyday, not only the bone and muscles, but also their brain. The development need a large panel of growth related factors, which could also change the tumor cell behavior and make them grow faster and more invasive. In addition, the tumor behavior is also depended on the status of immune system. In our body, we have cells that could potentially change into cancer everyday. But, fortunately, almost all of them will be killed by our immune system. It has been believed that the brain is an immune privileged site. But, it is now clear that normal glial cells such as microglia do potentially function as immune cells in brain. In children, the immune system is not mature yet. Thus, the immunological factor could also contribute to this difference.


What do you see as the next step in understanding these differences?

As we mentioned early, factors as growth related factors and immune capacity in brain could contribute to the difference between young and adult brainstem glioma. But this is just a hypothesis so far. What we need to do is to test this hypothesis using this rat model and other methods. We can precisely target each factor, such as immune factor or any of the growth factors, to see which play major role in this difference. What I predict is that the difference is not likely due to a single factor but the combination effects of a group of factors. If we could identify these factors, we could be able to develop novel treatment for the brainstem gliomas in children.


Is it possible for this information to become clinically relevant for children who have these types of tumors?

For the modern medicine, no therapy could be developed without the basic and translational research. Our study demonstrated, for the first time, that this rat model of brainstem glioma in young and adults imitate the brainstem glioma in humans. Therefore, the use of this model could facilitate future studies to identify the factors contribute to the difference of brainstem glioma between children and adults, and to discovery of novel therapies to treat the diffuse brainstem glioma in children.


What barriers do you have in moving forward on such research?

The major barrier to move forward the research is the funding resources. The brainstem glioma is relative rare comparing to other cancers. Few people realize that brainstem tumors are the most common pediatric cancer other than leukemia and lymphoma. The funding resource for this devastating disease has been very limited. I conducted a search for the current and historical NIH grants (1972-2009) to brainstem tumor, and not even one has been found. It has been very few scientists and physician that have been devoted to study this disease. Even for the other well funded medical researches in US, we are facing the problem that less and less people are devoted into the research. It is hardly imaging that a very well educated Ph.D, after 4 years college and more than 5 years Ph.D study, the start salary for them is only little bit more than $35,000/yr. Sadly, we have been investing trillions of dollars for the war and bail out the banks, but we have just invested a tiny fraction of these into the research in the last decade to our own health problem. So, we need our whole society to realize this problem.


Reference-
Brainstem glioma progression in juvenile and adult rats. J Neurosurg. 2008 Nov;109(5):849-55

Wednesday, April 15, 2009

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 2009
First Received: April 10, 2009 No Changes Posted

Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier: NCT00880061

Purpose
Objective: The primary purpose of this study is to test the safety and feasibility of giving a new experimental agent, called IL13-PE38QQR, directly into regions of the brain in patients with diffusely infiltrating pontine glioma (DIPG) or with recurrent or progressive supratentorial high-grade glioma (HGG) using a technique called convection-enhanced delivery or CED. CED uses continuous pressure to push large molecules through the membranes protecting the brain to reach brain tumors. At the same time, we can watch where the molecules go in the brain by attaching a tracer, gadolinium-DTPA, to the IL13-PE38QQR, which can then be seen in the brain with magnetic resonance imaging (MRI). Because we do not know the best dose to use in patients with DIPG or HGG, we will give increasing amounts of IL13-PE38QQR to small groups of patients with each type of brain tumor, known as a dose escalation study. Secondary purposes of this study include determining the effects of this experimental therapy on the tumor, and evaluating the physical changes in the tumor before and after the therapy.
Study Population: Twenty pediatric patients with recurrent or progressive DIPG or supratentorial HGG that have undergone standard treatment and who meet all the Inclusion and Exclusion Criteria may be enrolled. Eighteen patients will receive treatment; an additional two patients may be screening failures or unevaluable.
Design: We propose a Phase I single institution, open label, dose escalation (doses of 0.125, 0.25 and 0.5 micrograms/ml), safety and tolerability study of IL13-PE38QQR infused via CED into patients with either DIPG (up to 9 patients) or recurrent HGG (up to 9 patients). IL13-PE38QQR will be administered to regions of tumor determined by radiographic findings. Escalating dose levels will be evaluated in the following dose cohorts (3 patients per Cohort): Cohort 1 = 0.125 micrograms/ml, Cohort 2 = 0.25 micrograms/ml and Cohort 3 = 0.5 micrograms/ml.
Outcome Measures: To assess the safety, tolerability and potential efficacy of CED of IL13-PE38QQR, we will use detailed clinical and radiographic examinations. These will be performed at baseline and on post-infusion days 1, 28 and 60. After post-infusion day 60, clinical and radiographic studies will then be performed every 8 weeks until imaging or clinical evidence of recurrence/progressive disease or new treatment is initiated.
...
Study Type: Interventional
Study Design:
Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study
Official Title:
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
Further study details as provided by National Institutes of Health Clinical Center (CC):
Primary Outcome Measures:
1) Feasibility of perfusing specific sites within the CNS with IL13-PE38QQR, administered concurrentlywith gd-DTPA
2) Safety and tolerability of escalating doses of IL13-PE38QQR via CED to pediatric patient with DIPGs and HGGs
Secondary Outcome Measures:
Determine effect of IL13-PE38QQR on MRI tumor measurements, symptom improvement or worsening, changes on clinical exam, radiographic changes, steroid dosing, QOL testing and survival of pediatric patients with DIPG and recurrent HGG
Estimated Enrollment: 20

Study Start Date: April 2009

Intervention Details: Drug: IL13-PE38QQR
Detailed Description:
Objective: The primary purpose of this study is to test the safety and feasibility of giving a new experimental agent, called IL13-PE38QQR, directly into regions of the brain in patients with diffusely infiltrating pontine glioma (DIPG) or with recurrent or progressive supratentorial high-grade glioma (HGG) using a technique called convection-enhanced delivery or CED. CED uses continuous pressure to push large molecules through the membranes protecting the brain to reach brain tumors. At the same time, we can watch where the molecules go in the brain by attaching a tracer, gadolinium-DTPA, to the IL13-PE38QQR, which can then be seen in the brain with magnetic resonance imaging (MRI). Because we do not know the best dose to use in patients with DIPG or HGG, we will give increasing amounts of IL13-PE38QQR to small groups of patients with each type of brain tumor, known as a dose escalation study. Secondary purposes of this study include determining the effects of this experimental therapy on the tumor, and evaluating the physical changes in the tumor before and after the therapy.
Study Population: Twenty pediatric patients with recurrent or progressive DIPG or supratentorial HGG that have undergone standard treatment and who meet all the Inclusion and Exclusion Criteria may be enrolled. Eighteen patients will receive treatment; an additional two patients may be screening failures or unevaluable.
Design: We propose a Phase I single institution, open label, dose escalation (doses of 0.125, 0.25 and 0.5 micrograms/ml), safety and tolerability study of IL13-PE38QQR infused via CED into patients with either DIPG (up to 9 patients) or recurrent HGG (up to 9 patients). IL13-PE38QQR will be administered to regions of tumor determined by radiographic findings. Escalating dose levels will be evaluated in the following dose cohorts (3 patients per Cohort): Cohort 1 = 0.125 micrograms/ml, Cohort 2 = 0.25 micrograms/ml and Cohort 3 = 0.5 micrograms/ml.
Outcome Measures: To assess the safety, tolerability and potential efficacy of CED of IL13-PE38QQR, we will use detailed clinical and radiographic examinations. These will be performed at baseline and on post-infusion days 1, 28 and 60. After post-infusion day 60, clinical and radiographic studies will then be performed every 8 weeks until imaging or clinical evidence of recurrence/progressive disease or new treatment is initiated.
Eligibility
Ages Eligible for Study: up to 17 Years
Genders Eligible for Study: Both
Accepts Healthy Volunteers: No

Criteria
INCLUSION CRITERIA:
Age less than 18 years
Diagnosis: recurrent or progressive:
DIPG
HGG
Patients undergoing surgical resection must have measurable/evaluable disease prior to study entry.
Histopathologic Diagnosis
A histopathologic diagnosis is not required for patients with DIPG but a biopsy may be recommended if the patient has an atypical presentation or atypical findings on MR-imaging.
Histopathologic confirmation for patients with HGG is required. If necrosis is suspected based on MR-imaging and Nuclear Medicine scans, biopsy or surgical resection for confirmation of disease progression may be required.
Prior Therapy
Patients must have received at least standard doses of radiation (i.e., greater than 54 Gy).
Surgery/biopsy - Patients must be more than 2 weeks from any neurosurgical procedure and cleared by the Principal Investigator before undergoing CED.
Radiation - Patients must be more than 4 weeks from last fraction of radiation to the target site
Chemotherapy - Patients must not be on concurrent chemotherapy. The last dose of chemotherapy must be greater than 2 weeks prior to CED and the patient must have recovered from any toxic effects of prior therapy (to less than Grade 2 or baseline).
Biologic therapy - Patients must be greater than 7 days from biologic therapy.
Investigational therapy - Patients must be greater than 30 days from any investigational therapy.
Patients must be healthy enough to tolerate surgery and general anesthesia in the opinion of the primary investigator. This includes, but is not limited to:
Adequate baseline organ function, including an age-adjusted normal serum creatinine OR a creatinine clearance greater or equal to 60 mL/min/1.73m(2), total bilirubin less than 2 times the upper limit of normal (ULN) and direct bilirubin within normal limits. Patients with elevated SGPT (up to 5 time ULN) will be eligible if the elevation is attributed to steroid treatment.
If neurological deficits are present, they must be stable for at least 1 week prior to registration.
Patients must be able to undergo MR-imaging with gadolinium-based contrast administration (e.g. no ferrous-containing implants, no pacemakers, no allergy to contrast, etc).
All patients or their legal guardians must sign a document of informed consent indicating their
understanding of the investigational nature and the potential risks associated with this study.
When appropriate, pediatric patients will be included in all discussions in order to obtain verbal and written assent.
EXCLUSION CRITERIA:
Patients with an uncorrectable bleeding disorder
Patients with multifocal or leptomeningeal disease
Patients with signs of impending herniation or an acute intratumoral hemorrhage
Patients on concurrent chemotherapy or biologic therapy for the treatment of their tumor
Patients who are pregnant or breastfeeding, because of unknown effects of the study agent, the strong magnetic fields and Gadolinium containing contrast agents on the fetus; patients of child-bearing potential must be willing to practice an effective form of birth control, including abstinence, hormone therapy, intrauterine device, 2 barrier methods.
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00880061
Contacts
Contact: Patient Recruitment and Public Liaison Office
(800) 411-1222
mailto:prpl%40mail.cc.nih.gov?subject=NCT00880061,
Contact: TTY 1-866-411-1010

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Recruiting
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
National Institute of Neurological Disorders and Stroke (NINDS)
More Information
Additional Information:
NIH Clinical Center Detailed Web Page
Study ID Numbers:
090117, 09-N-0117
Study First Received:
April 10, 2009
Last Updated:
April 10, 2009
ClinicalTrials.gov Identifier: NCT00880061

Monday, April 6, 2009

Wall of Courage




~A message from Heide Randall


May is Brain Tumor Awareness Month

As you all know, May is Brain Tumor Awareness Month, and I wanted to make some gear to mark it as such. So, I've created designs for shirts, buttons, magnets, caps, mugs, mousepads, etc. etc. etc.

It was originally only intended for our youngest BT warriors and angels, but due to popular demand I've added designs for adult BT warriors and angels, as well.

The products are available here: http://cafepress.com/btwallofcourage ...

There is a special section featuring products with pictures of over 120 of our youngest BT warriors and angels.

There is gear available to support your: Son, Daughter, Survivors (Had/Have a Brain Tumor), Brother, Sister, Grandson, Granddaughter, Niece, Nephew, Cousin, Father, Mother, Husband, Wife, Grandmother, Grandfather, Uncle, Aunt, and Friend (boy/girl).

For those interested, proceeds from the sale of these products will be distributed among the following:
Jessica C. Randall Memorial Scholarship FundChildren's Brain Tumor Foundation (http://cbtf.org/)

The Brain Candy Project (http://braincandyproject.org/)

Jacob's Smiles (http://jacobssmiles.com/ -- site not functional yet, but I think many of you know Christine and her son, ^Jacob^.)and,

pending: Aimee's Army (http://aimeesarmy.org/)

I hope you all enjoy the gear. I figure I'll be wearing gray all year long!!!! :)


~Heide Randallm/o ^Jessica^ (Forever 17) & Jake (17)