Children’s Brain Tumor Project Lab Update: Summer 2014

Posted in About the CBTP, Research, Updates

By Prajwal Rajappa, M.D. Pediatric Brain Tumor Fellow Weill Cornell is one of 200 institutions that make up the Children’s Oncology Group (COG), the world’s premier organization dedicated to eradicating childhood cancer. Dr. Mark Souweidane and Dr. Prajwal Rajappa lead the Weill Cornell Pediatric Brain and Spine Center’s participation in a long-term study of brain tumor tissue samples collected from pediatric patients around the world, with the goal of understanding the molecular profile of these tumors. This lab update about our COG project was contributed by Dr. Rajappa. This COG study is extremely important given the lack of effective treatments available for pediatric brain tumor patients. We are collecting brain and spinal tumor tissue from pediatric patients treated at COG facilities around the world, providing a repository for long-term storage of those specimens. This study allows us to make specimens available to expert researchers both here in the United States and abroad who are working to understand the biology of these tumors. These repository-driven studies utilizing human tissue serve as the platform for meaningful translational research, which relies on laboratory findings that can be quickly applied to develop new treatment options. The rapidly evolving science of human genomics has the potential to change how physicians diagnose and treat cancer, but molecular studies require access to tumor tissue, which has been extremely limited—especially when the tumors are rare. There’s a particular shortage of pediatric tissue specimens available for ependymomas, thalamic gliomas, brainstem gliomas, diffuse pontine gliomas, gliomatosis cerebri, low-grade gliomas, and primary GBMs. The limited number of specimens available for research within any single institution can make it impossible to conduct statistically powerful and high-impact molecular research. Therefore, participation from multiple institutions is essential. Here at Weill Cornell, with a world-class pediatric service that draws patients from near and far, we have gathered a wide variety of samples of many pediatric brain and spine diseases in our repository, making us one of the top member institutions in the COG. In fact, in our first full year of participation in this study (2012), Weill Cornell ranked eighth out of 142 participating institutions in terms of number of pediatric patient samples enrolled. This year, we are poised for our highest patient enrollment on study. As shown in the pie chart at right, we have accrued a wide array of pediatric central nervous system (CNS) disease entities in our departmental repository that will serve as valuable material for further genomic sequencing and translational research. Within Weill Cornell, we have developed streamlined collaborations with other departments, such the department of pathology, which will ultimately advance our understanding of the biology of pediatric brain tumors and further initiate multi-disciplinary studies. Solidifying our role at COG,...

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Children’s Brain Tumor Project Lab Update: Spring 2014

Posted in About the CBTP, Research, Updates

By Mark M. Souweidane, MD Co-Director, Children’s Brain Tumor Project I’ll never forget May 1, 2012 — that was the day I performed the very first procedure in a new clinical trial testing convection-enhanced delivery (CED) of a therapeutic agent in a child with DIPG. More than ten years of my prior lab work, including bench research and animal testing, had me absolutely convinced that this was a safe procedure. Still, with anything so completely new there’s just that tiny seed of doubt, the faintest whisper of “what if…” What I was not prepared for were the emotional ties that quickly took hold of me. The little girl in the OR that day was Caitlin Downing, whom I had come to love in just a few short weeks of knowing her and her family. Hugs, insightful questions, and smiles from this 5-year-old were gripping. Caitlin’s sister, Courtney, had even joined her on one of her preoperative visits to New York so that she could approve of the doctor who would offer hope. Imagine my relief when the procedure went exactly as expected, and imagine my heartbreak several months later when the tumor came back to claim Caitlin’s life. But her successful surgery validated every effort that went into this translational project and left no doubt that we should push on. Today we find ourselves in an exciting position: With 13 children treated so far (all of whom have tolerated the treatment well, with no adverse effects), we have answered critical questions about the technical, surgical, and diagnostic aspect of this drug delivery tactic. Early results have raised awareness from oncologists, neuro-surgeons, radiologists, and pharmacologists from all over the world. The momentum is building rapidly. So encouraging are the results that we have decided to request a continuation of the study. If the continuation is approved, we will plan to treat a minimum of 12 more children at escalating doses. The study is being positively viewed on a national level. The preliminary results of this trial were presented to the Pediatric Brain Tumor Consortium (PBTC) in Atlanta last month. That group is highly interested in moving the strategy into a “group-wide” study and has assembled a working group, which I am leading, to formulate the best plan. Even as we modify the current strategy, we are continuing our laboratory and clinical efforts in different arenas. As an example, we are using other strategies for bypassing the blood-brain barrier, which is what prevents us from getting adequate doses of cancer-fighting molecules to a tumor site. In addition to testing CED, we are also pursuing another potential route, using super-selective intra-arterial chemotherapy to deliver medicine directly into the blood vessels of the...

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Family Update: Spring 2014

Posted in About EH, From the Minter Family, Updates

In our December 2013 newsletter we told you how close Elizabeth’s Hope had come to raising its first $1 million, and we urged our supporters to help us reach that milestone. We’re both proud and humbled to say that we made it, thanks to you. We are dedicated to continuing our work supporting the Children’s Brain Tumor Project, and we are so thankful to know that you are behind us every step of the way. Thank...

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Children’s Brain Tumor Project Lab Update: December 2013

Posted in About the CBTP, Research, Updates

By Jeffrey Greenfield, MD, PhD Director, Children’s Brain Tumor Project It’s hard for me to believe that two years have gone by since Elizabeth’s Hope was born, allowing us to launch the Children’s Brain Tumor Project. In scientific research terms, this has been the blink of an eye. I am so very grateful for your support—this truly is a dream come true for me, and some day we will be able to make a significant impact on the care of children facing brain tumors. Anniversaries always make you look back and think about where you’ve been, and our list of accomplishments over the past two years is considerable. Here are some of the highlights of our first two years: 2011-2012 Elizabeth’s tumor was the very first sample of gliomatosis cerebri ever subject to genomic analysis, and it yielded a treasure trove of information about the genetic mutations associated with her tumor. Since then we have been able to sequence several additional tumors, searching for what they have in common with Elizabeth’s, and where they diverge. This hunt for patterns and data is what will help us unlock the mystery of this rare tumor. Only weeks after Elizabeth’s Hope was founded, my colleague Dr. Mark Souweidane received FDA approval to begin a groundbreaking trial testing the safety of convection-enhanced delivery (CED) of therapeutic agents for pontine gliomas (DIPG). He treated the first patient in May of 2012 and has treated eight more children since then, with zero toxicity. Testing different agents, at different doses, will generate the data we need in the coming months and years. In the fall of 2012, a basic science researcher named C. David Allis, Ph.D., was investigating and documenting a DNA histone called H3.3. Much to everyone’s surprise, it was discovered that H3.3 mutations are found in pediatric gliomas. Dr. Allis and I are now collaborating on a new project to try to find out why the mutation causes gliomas — including gliomatosis cerebri — to develop. I was honored to share in a Starr Cancer Consortium grant given to Dr. Allis to pursue the research. I have a two-year, $112,000 grant for 2013 and 2014. 2013 In January 2013, the Institute for Precision Medicine opened its doors at NewYork-Presbyterian/Weill Cornell Medical Center. This cutting-edge research hub is exploring how to develop optimal targeted, individualized treatment based on each patient’s genetic profile. This is extraordinarily significant for Elizabeth’s Hope and the Children’s Brain Tumor Project, as it brings the ability to sequence tumors right onto our campus and spares us the cost of buying new machinery. Our gifts can be used for the bioinformatics staff members we need to interpret the data, rather than on...

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Family Update: December 2013

Posted in About EH, From the Minter Family, Updates

Two years ago this month a seed was planted: Elizabeth’s Hope. Over the last two years thousands of supporters have nurtured that seed with their time, talents, and money. Today, having raised more than $900,000 and with the million-dollar goal in sight, Elizabeth’s Hope is the founding root of the Children’s Brain Tumor Project. The project’s fundraising is flourishing with more families (14 at last count) powering the project, creating more roots, widening the base and securing a larger, continuous source of funds to nurture this important research mission. (Please read Dr. Greenfield’s lab update, where he outlines the initatives of the last two years.) We miss Elizabeth deeply and wish that she were here to witness what has been accomplished. The love of her friends, family, communities, and strangers allowed her seed to grow. As we celebrate the two-year anniversary of the fund’s launch, we want to thank a number of people who were critical to the fund’s early success. First, we are indebted to Dr. Greenfield for sharing his medical vision with us. We feel blessed to have been presented an opportunity to work with him, during a time when we felt desperately hopeless. Second, we want to thank our friends at Weill Cornell, Licia Hahn and Roseann Henry, for their strategic thinking, marketing advice, and operational support. Third, we thank Tessa Naso, our Volunteer Coordinator, who energized our fundraising with our first big event and continues to generate ideas. Fourth, we are indebted to Gretchen Scott, who designed and sold thousands of Elizabeth Hope’s blouses, donating an incredibly generous 100 percent of the proceeds. Finally, we acknowledge the youth — middle school, high school, and college students, as well as young adults — who continue to give our effort a unique momentum. There were many “hidden blessings” in Elizabeth’s journey. She brought our family closer together. She taught us the meaning of unconditional love. She taught us to focus and appreciate the moment, and worry less about the future. There have also been hidden blessings in the establishment of Elizabeth’s Hope. In addition to allowing us to focus on something positive as opposed to dwelling on a devastating diagnosis and loss, the Web site and Facebook page have connected us with other parents coping with the same fate. Finally, we are inspired by the generosity, creativity, and compassion of friends, neighbors, and strangers. We are proud to be associated with the Children’s Brain Tumor Project. The project now has a solid foundation. However, a true success will require years of continual funding. So our work has just begun. We hope you will consider Elizabeth’s Hope when planning your year-end charitable contributions Thanks again for believing in...

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Family Update: Fall 2013

Posted in About EH, From the Minter Family, Updates

September is Pediatric Cancer Awareness Month, represented by the color gold. Did you know that? We didn’t until two years ago, when we were at the hospital for Elizabeth’s treatment and the staff was giving out small gold ribbons. Why is it that we know pink ribbons stand for breast cancer but are ignorant about gold ribbons? Why is it that we parents, our children’s best advocates, have failed to create greater awareness and urgency for funding of new treatments for our children, who have decades of potential and contributions ahead of them? It’s not because we aren’t trying. It’s because the subject matter is raw and unpleasant. Pediatric cancer is on emotional par with torture, rape, incest, abuse, and poverty — subjects we would prefer not to discuss. It’s also a topic that makes us feel like failures. Thousands of children die and suffer each as a result of cancer. We feel helpless to stop the random killing of about 50 children each week (the equivalent of two classrooms) by a relentless serial murderer. Pediatric cancer was not even on our radar screen three years ago. Sometimes we wish it weren’t now. Each time we hear of a child with a new diagnosis, we are knifed in the heart and relive Elizabeth’s nightmare. We would love to be innocent again, but we will never be. Pediatric cancer is bad, but a rare inoperable brain tumor has to among the worst diagnoses. “Inoperable brain cancer” really means “pray for a miracle.” “Rare” means there is no treatment protocol and few clinical trials. A tumor in the brain means that the patient will be robbed of their physical, emotional, and intellectual abilities. Inoperable brain cancer is more than an inconvenient or painful disease. Thus we continue the work of Elizabeth’s Hope, our daughter’s dream of a cure for rare and inoperable brain cancers. Elizabeth was admitted into hospice in October 2012, just 9 months after her diagnosis. We were told that she had a few months to live at most. She had started work on Elizabeth’s Hope in June, and we were anxious to launch the fund while she was still present. We launched in mid-November 2012. Elizabeth hung on. Dr. Greenfield paid her a bedside visit over the Christmas /New Year’s holidays. It was an important visit, but Elizabeth was sad when he left our home. She was disappointed because she’d had the innocent hope that he would come with the cure that very day that would free her from her steady decline. In this day and age, it is shocking to us that the only hope for so many patients is a miracle. We know we can do...

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