Improving treatment of medulloblastoma
St. Jude Children's Research Hospital (ALSAC)
A recently completed international pilot study brings researchers closer to an international clinical trial aimed at improving guidelines for treatment of medulloblastoma, a common type of childhood brain cancer. A report on this study, from investigators at St. Jude Children's Research Hospital, appears in the March 15 issue of the Journal of Clinical Oncology (JCO).
The pilot study is the first to demonstrate that medulloblastoma samples can be rapidly delivered to a central research institution and analyzed. The findings confirmed that samples shipped from institutions in the United States and Australia can be analyzed at St. Jude for genetic abnormalities rapidly enough to provide physicians with information to guide their treatment decisions.
The study also demonstrated that by detecting the presence of a protein called ERBB2 in tumor samples, doctors might be able to predict which children with medulloblastoma will require more intensive treatment.
Radiation therapy can cause loss of some normal brain tissue, resulting in a decline in intellectual function and long-term problems with certain hormones, such as thyroid and growth hormones. Therefore, identifying patients who can safely undergo a milder course of treatment can help minimize these lasting effects of therapy.
Ultimately, guiding treatment using knowledge of tumor biology could increase survival rates while reducing the severity of toxic side-effects.
The study was led by Richard Gilbertson, MD, PhD, of St. Jude Department of Developmental Neurobiology, and Amar Gajjar, MD, in the department of Hematology/Oncology.
"This study paves the way to generate a comprehensive molecular fingerprint of the genetic abnormalities in medulloblastoma," Gilbertson said. "The information will allow us to provide new guidelines for the way we use existing treatments and help us to identify new therapies."
Gajjar elaborated on the need for new treatment guidelines.
"We clearly need new guidelines for judging how an individual child's tumor is going to behave," Gajjar said. "At present we know that 20 to 30 percent of patients thought to have a good chance of getting cured will actually turn out to be resistant to radiation and chemotherapy. We also can't reliably identify the unknown number of patients who are likely to be over-treated because their tumors are actually more sensitive to radiation than we realized."
International studies, to be conducted by the Children's Oncology Group (COG, US) and the International Society of Pediatric Oncology (SIOP, Europe) over the next several years, will prospectively evaluate the survival significance of molecular prognostic markers among children with medulloblastoma.
Other authors of the St. Jude study include Roberto Hernan, Mehmet Kocak, Christine Fuller, Youngsoo Lee, Peter J. McKinnon, Dana Wallace, and Larry Kun (St. Jude); and Ching Lau, Murali Chintagumpala, (Baylor) David Ashley (Royal Children's Hospital, Melbourne), and Steward Kellie (New Children's Hospital, Westmead)
This work was supported by the V-Foundation for Cancer Research, a Cancer Center (CORE) Support Grant and ALSAC.
For more information, or to contact St. Jude Children's Research Hospital (ALSAC), see their website at: www.stjude.org
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