Pediatric Brain Tumors

An Overview from a Pediatric Perspective

Joseph L. Lasky III, M.D.
Assistant Professor of Pediatrics
David Geffen School of Medicine and Mattel Children’s Hospital at UCLA
Clinical Director
UCLA Pediatric Neuro-Oncology

Tumors of the brain and central nervous system are the most common solid tumor of children. Recent estimates place prevalence at 9.5 per 100,000 children in the United States, corresponding to an estimated 3,410 new cases of childhood brain tumors per year (according to recent data from the Central Brain Tumor Registry of the United States – CBTRUS). In fact, this rate appears to have been increasing over the last several decades, possibly due to better diagnostic techniques, although environmental causes are currently being investigated. Although the survival rates have improved dramatically for these tumors in the last four decades, the overall cure rates are still nowhere near the rates of other malignancies such as some forms of leukemia and lymphomas, where the cure rates approach 90%.  Taking all forms of brain tumors into account, survival for ages 0-19 years old at most approaches 65%, with many types having much less than 50% survival.

Current therapy for brain tumors involves using a combination of (and sometimes all) three modalities: surgery, chemotherapy, and radiation therapy. The types and intensity of treatment depend upon both the type of brain tumor and the grade or aggressiveness of the brain tumor. For example, the glioblastoma, or Grade 4 astrocytoma, is the most common adult malignant brain tumor but also occurs in children. Treatment for this tumor usually involves surgery first, and then combined radiation therapy and chemotherapy, followed by more chemotherapy for as long as one year in many cases.  In spite of this intensive treatment, less than 20% survival is still achieved. Therapy for low-grade brain tumors usually involves surgery alone, and with complete removal of the tumor, 90% survival rates can be achieved.

Indeed, in spite of poor outcomes for certain types of brain tumors, there are still many children (more than 26,000!) living with and surviving after brain tumors in the United States. However, although these survivors may have won the battle against the brain tumor, many still suffer from the long-term effects of therapy, most notably radiation therapy. Many of these children are left with memory, sleep, learning and many other cognitive problems that we are only beginning to learn how to diagnose and treat. Obviously new therapies must be investigated and old therapies must be adjusted so that toxic effects to these developing brains can be minimized or eliminated.  The “quantity” of life after cancer must be balanced with “quality” of life after cancer.

One of the exciting research projects taking place at UCLA, in a collaborative effort between adult and pediatric oncology, uses a brain tumor “vaccine” that attempts to harness the power of one’s own immune system to fight the tumor.  This method was developed for clinical use at UCLA by Dr. Linda Liau, a key leader in adult immunotherapy trials, and her lab. The procedure uses the patient’s own tumor, a piece of which is broken down and saved as a tumor “lysate” (no longer living tumor).  This lysate is then incubated with the patient’s own dendritic cells which are collected from the patient’s blood. Dendritic cells are the immune system’s “teacher” cells, that teach killer T-cells (or cytotoxic T-cells) which targets to attack. After the dendritic cells have engulfed the tumor proteins (from the lysate), they are then re-injected under the skin of the patient (usually on the arm) where they migrate to local lymph nodes and teach the cytotoxic T-cells to attack cells expressing those proteins, in this case the tumor cells. A Phase I toxicity trial has already been completed and published for adults with glioblastomas. The results were very encouraging, with basically no toxicity from the vaccine itself, and some patients displayed dramatic regression of these formerly highly resistant brain tumors! Dr. Liau has already moved onto performing a Phase II trial using this vaccine, expanding the trial to enroll many more patients.
         
We have already performed a set of vaccinations on one child successfully with no toxic effects from the vaccine. Our initial goal is to complete the toxicity and dose finding trial with pediatric patients, with a targeted accrual of 12 to 18 children with malignant brain tumors. We have already been communicating with other collaborating institutions around the United States, offering the opportunity of this novel therapy to their patients who have no other therapy left to work for them. Working with Dr. Liau and her colleagues has provided a truly unique opportunity to move forward with this project.  Additionally, Dr. Liau is already beginning to modify the protocol in various ways in order to optimize the response of the adult patients to the vaccine. As these developments are realized, they can be quickly incorporated into the treatment for children.
         
Along with providing innovative and less toxic therapies for children with brain tumors, we also work together with neurologists, neurosurgeons, psychiatry, child development specialists, school integration specialists, physical therapists, social work, and many other components of the pediatric neuro-oncology team to provide not just treatment for the patient, but care for the whole family. Caring for the child with a brain tumor can have just as many “side-effects” for the family and community as it does for the patient. These need to be recognized and remedied, as adequate healing for a child can only take place in an intact, loving environment.

Obviously, much work remains to be done, and unfortunately the federal government only has a finite amount of money and resources to allocate towards cutting-edge research. Furthermore, support for research benefiting children is an even smaller percentage of that total. Therefore, we rely on the enthusiasm, support, and generosity of individuals, organizations, and foundations to allow this important research to continue and more importantly allow us to support the families of children with these often devastating cancers. The Tug McGraw Foundation was formed “to support research that will improve their [children and adults with brain tumors] quality of life in the physical, social, spiritual, and cognitive areas.” Already, by founding the Tug McGraw Neuro-Oncology Quality of Life Research Center at Duke, the Foundation has made a huge difference in the lives of people living with brain tumors. Through the Tug McGraw Foundation’s future efforts, support for and generation of similar innovative ideas promises to continue.