I was working at home on a recent Saturday when the email arrived from an emergency department physician looking for advice. He had a patient whose CT scan showed a large mass at the base of the skull. The child's symptoms, combined with the appearance and location of the tumor, led the physician to suspect the mass was a malignant brain tumor called medulloblastoma. The child's family was devastated. The question was: What's next for the patient?
The answer to that question has changed dramatically since 1989, when I was a young physician finishing my training as a children's cancer specialist. Medulloblastoma was still considered to be a single disease. The patient's family would have been referred to a neurosurgeon, who would have removed as much of the tumor as safely possible. Surgery would have been followed by high-dose radiation therapy to the brain and spine, then chemotherapy. While that treatment cured 55 to 70 percent of patients, the approach had long-term side effects.(1) Many survivors struggled to complete their education, live independently, earn paychecks or enjoy other milestones of adult life.
The intervening years brought progress as surgical techniques and imaging technology improved. Most patients qualified for lower doses of radiation. Chemotherapy was refined. Survival rates for children and adolescents rose.(2) We learned how to reduce the risk of certain long-term treatment side effects and enhanced support services and interventions to help survivors make the most of life. Some patients did very well and some did poorly -- and we just did not know why. There were hints that medulloblastoma was not a single disease.
Thanks in part to technological advances, including next-generation, whole genome sequencing, scientists developed tools that allowed us to dig deeper into the biology of medulloblastoma. My St. Jude colleagues, including Scientific and Cancer Center Director Richard Gilbertson, M.D., Ph.D., led several key studies that showed medulloblastoma really includes four different subtypes. (3) (4) The subtypes help to explain why medulloblastoma cure rates varied so widely. While nearly all patients with the wingless (WNT) subtype survive, just 60 percent of those with a different subtype, (5) known simply as subtype 3 medulloblastoma, are alive three years after diagnosis. (6)
In recent years, efforts like the St. Jude Children's Research Hospital - Washington University Pediatric Cancer Genome Project revealed that the subtypes involve different gene mutations. (7) An international research effort led by Dr. Gilbertson showed the alterations occur in distinctly different cells destined to become different brain structures. (The Pediatric Cancer Genome Project began in 2010 to sequence the complete normal and tumor genomes of some of the most aggressive and least understood childhood tumors, including medulloblastoma.)
This year, I estimate that 450 to 500 children in the U.S. will be diagnosed with medulloblastoma, making it the most common malignant brain tumor in children. (8) Although medulloblastoma occurs in adults, the tumor is 10 times more common in children. (9) In most patients, the tumor is discovered before they are old enough to drive. The cancer begins in a region of the brain called the posterior fossa, a small space at the back of the skull near the brainstem, which controls vital functions like breathing; and the cerebellum, which is responsible for movement, balance and coordination. The first symptoms are typically headaches and morning vomiting that worsens with time. This aggressive cancer often spreads to other parts of the brain and spine.
While news that your child has a malignant brain tumor remains a life-altering, frightening event, there is renewed reason for hope.
St. Jude has begun an ambitious multi-center, international clinical trial called SJMB12 that builds on recent scientific and clinical research advances to create an even more tailored approach to medulloblastoma treatment. To guide treatment, we are using both clinical risk factors -- like whether the surgeon was able to remove the entire tumor, the appearance of the tumor under the microscope and if the tumor has spread to other parts of the brain -- and molecular risk factors, like a patient's tumor molecular subtype. We are using this combined approach to risk assessment, a first in North America, to match patients with the radiation dose, mix of chemotherapy agents or novel therapies targeting specific subtypes that we believe offers the best hope for a long, rewarding life.
The goal is to cure more children and adolescents with the disease as well as to improve their quality of life during treatment and beyond. We are even testing to see if incorporating aerobic exercise and computer games into cancer treatment will ease side effects like fatigue and sleep disturbances or help preserve memory and cognitive functioning, including attention span.
With that in mind, I called the emergency department doctor on that recent Saturday night. We talked about how the family might proceed. Within 48 hours, our neurosurgeon had removed the child's tumor and confirmed the diagnosis. It was the first step in this child's battle against a life-threatening disease. I am optimistic for this child and others newly diagnosed with medulloblastoma. I am excited because medulloblastoma treatment has entered a new era -- in which clinical care and laboratory advances combine to benefit not only this patient, but also others worldwide.
This blog post is part of a series produced by The Huffington Post and St. Jude Children's Research Hospital in recognition of National Childhood Cancer Awareness Month. For more information about St. Jude, click here.
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