White matter is the part of the brain composed of nerves that are covered in a pearly-white sheath. Much of the cerebral cortex, where high level thinking occurs, is made of white matter.
The study demonstrates that this damage, called white matter lesions (WMLs), can be mistaken for recurrent cancer, prompting physicians to treat the patient aggressively--and needlessly--with more radiation and chemotherapy.
"Irradiation and high-dose chemotherapy are treatments we want to use as sparingly as possible," said Amar Gajjar, M.D., member of Hematology-Oncology and director of Neuro-oncology at St. Jude. "This new information represents an important caution sign for physicians who otherwise might assume that WMLs are actually tumors that need further treatment."
Gajjar is senior author of the JCO report, which is the first to describe both the finding and the actual incidence of early-onset WMLs--that is, how frequently these lesions occur in patients with medulloblastoma or PNET who have been treated with radiation and high-dose chemotherapy following surgery. The study is also the first to note the impact of such changes in white matter on intellectual outcome in children with brain tumors. Specifically, the study found that the presence of WMLs is associated with a decline in neurocognitive, or intellectual, function.
"In the vast majority of children, the changes seen on MRI scans after treatment are WMLs and not cancer," says Maryam Fouladi, M.D., assistant member of St. Jude Hematology-Oncology and lead author of the report. "Physicians can follow up these initial findings with repeat MRI scans to determine whether the WMLs disappear. If they do disappear, then it wasn't cancer and didn't require treatment. But even though these changes tend to be only temporary, some children with these changes tends to develop permanent neurologic problems, such as difficulty swallowing."
The team followed 127 patients for up to 13 months after the start of treatment for brain cancer. During this time 22 of these patients developed WMLs following treatment for brain cancer. The WMLs disappeared in 16 patients (73 percent) within 23.5 months after being detected. In two patients the WMLs remained after 19 and 31 months, respectively. Two other patients developed cancer again while still showing evidence of WMLs. In the remaining patients the WML led to tissue breakdown. Patients with WMLs experienced a significant decline in estimated IQ and math scores.
The researchers concluded that, in patients with medulloblastoma or PNET who had been treated with irradiation and high-dose radiation, WMLs are usually short-lived and do not cause symptoms. However, these WMLs can mimic the early stages of tumor recurrence, and thus make it difficult for physicians to accurately diagnose the return of cancer.
Other authors of this report are Fred Laningham, James W. Langston, Larry E. Kun and Raymond K. Mulhern (St. Jude); Murali Chintagumpala, Charles W. McCluggage, Shaio Woo and Kevin Krull (Texas Children's Hospital/Baylor College of Medicine, Houston); David Ashley (Royal Children's Hospital, Melbourne, Australia); and Stewart J. Kellie (Children's Hospital at Westmead, Sydney, Australia).
This work was supported in part by the Center of Research Excellence and ALSAC.
St. Jude Children's Research Hospital
St. Jude Children's Research Hospital is internationally recognized for its pioneering work in finding cures and saving children with cancer and other catastrophic diseases. Founded by late entertainer Danny Thomas and based in Memphis, Tennessee, St. Jude freely shares its discoveries with scientific and medical communities around the world. No family ever pays for treatments not covered by insurance, and families without insurance are never asked to pay. St. Jude is financially supported by ALSAC, its fundraising organization. For more information, please visit www.stjude.org.
Journal
Journal of Clinical Oncology