Every night I read to my daughters at bedtime, then headed back to the lab for a second shift. One night, my youngest daughter, then 4 and a half years old, asked, “Daddy, you leave for your research every night...but have you ever saved anyone’s life from the research you do in your lab, ever?” My answer was, unfortunately, “No. not from my research.” I could have said that no one individual researcher really ever has - the long path from basic scientific discoveries in a cancer lab to actually treating patients seemed too complicated to explain. But she had valid question, and it got me thinking: wouldn’t children with cancer ask the same question, too? I realized we needed to change our lab's approach and focus on expediting the process of getting promising scientific discoveries from the lab safely to the patient. Our team at cc-TDI is laser-focused on this imperative mission. Kids don't have time to spare when they are fighting for their lives.
cc-TDI works in close partnership with families battling childhood cancer. Fast forward to 2019 and Errol's dad asked "for my son, is this the right drug - and can this drug get to the tumor, and will the concentration be enough to have an effect?" Kids with brain tumors typically receive the same standard chemo treatments, with doses adjusted for simply weight. Errol's dad's questions inspired us to chart a new path forward for children, teens and young adults with tumors that spread to the brain and spine. We've done some pilot studies in collaboration with Dr. Bryn Martin (Univ. of Idaho), and now expanded to studies with Dr. Robert Peattie (Tufts University). Working collaboratively, we'll use patient specific imaging of tumors and sophisticated computer modeling to personalize drug delivery for each patient. Our mission is: better results; fewer side effects; and better quality of life for survivors.
Many brain tumors spread to other parts of the brain and the covering of the brain and spine (leptomeninges), and medulloblastoma is an example of a tumor that aggressively metastasizes as a rule. For patients facing this challenge, the key question is: how do doctors get an effective drug to penetrate each tumor, even if the tumor itself is a roadblock to the flow of cerebrospinal fluid (CSF) that helps spread the drug into the tumor regions? In clinical practice, the approach is always a guess. We would like to turn the approach into a science that ensures we can get the right drug into each tumor for each child. To reach this goal, we created a team including a pediatric oncology physician-scientist and Dr. Bryn Martin, a NASA-funded engineer with specific expertise in cerebrospinal fluid dynamics. The initial studies were informative. In expanded studies with fluid dynamics computation expert Dr. Robert Peattie at Tufts University, our vision is that for every child, medulloblastoma can be survivable. First, a tumor biopsy will be studied by biologists to define the correct drug(s) for each child’s tumor. Next, an MRI scan will be used in conjunction with high-performance computers to help define the correct dose and route of drug(s) for that child specifically.
Why is this important?
Summary: We believe our studies have the potential to shift current research and clinical practice for medulloblastoma and other high-risk pediatric brain tumors. In the long term, we envision use of our treatment planning tool by clinicians, pharmacological, and medical device companies to help optimize patient-specific delivery of potentially life-improving medications.
Driving Clinical Problem: High risk medulloblastoma patients with gross metastatic dissemination of tumor cells through the CSF to the leptomeninges experience 70% mortality rates even with combined radiotherapy and intensive chemotherapy. Methotrexate is a drug injected into the CSF to treat high risk medulloblastoma, but regimens often fail – presumably due in part to CSF dynamics often being disrupted by the disease. Unfortunately, disease-related disruption of CSF dynamics is not considered in treatment planning.
Solution: A patient-specific treatment planning tool would help physicians optimize where, how much, and how concentrated the drug is injected to increase dose to tumor region(s). We envision proposing a clinical trial for metastatic medulloblastoma that gives each and every patient this level of personalized science-level care. We begin here with this proof-of-concept pilot study and hope to achieve our goal of finding an effective therapy for a prototypic set of patients by developing a modeling tool for CSF-based drug delivery optimization in medulloblastoma patients. This treatment planning tool will allow optimization of CSF-based drugs, devices and protocols. This research has potential for broader impact on optimization of CSF drug delivery including single-dose medications that use adeno-associated virus, miRNA, antisense oligonucleotides, and other molecules that are among the most expensive medications in the world, costing up to ~$1M per dose and higher. Upon completion, the proposed research will provide a CSF drug delivery treatment planning tool that has potential to paradigm-shift clinical treatment of medulloblastoma from the contemporary approach of empirically-assigned therapy regimens to a near-day approach informed by patient-specific neuroanatomy and CSF physiology.
Who will benefit?
Patients with tumors that spread to the brain and spine will benefit. These children, teens and adults include those with brain tumors, as well as patients with tumors that start elsewhere but spread to the brain and/or spine.