Radiation’s Link to Higher Mortality Underscored by Largest-Ever Study of Pediatric Low-Grade Glioma Patients

The first comprehensive, large-scale study of the long-term survival of children treated for low-grade gliomas, the most common pediatric brain tumor, revealed that nearly 90% are alive 20 years later and that few die from the cancer as adults. However, children who received radiation as part of their treatment had significantly lower long-term survival rates than children who were not radiated.

Researchers from Dana-Farber/Boston Children’s Cancer and Blood Disorders Center (Boston, MA, USA) reported that these findings remain regardless of whether surgeons could effectively remove a child’s whole tumor or only part of it, suggesting that the radiation itself may clarify the disparity.

The findings were published online January 30, 2014, in the journal Pediatric Blood and Cancer. Delivery of radiation to children’s developing brains has been linked to a number of adverse long-term effects, including cognitive development and endocrine function. While a number of major hospitals, including Dana-Farber/Boston Children’s, have almost eliminated radiation in treating low-grade gliomas, the level to which other institutions employ radiation varies, according to the study’s senior author, Peter Manley, MD, of the Brain Tumor Center at Dana-Farber/Boston Children’s Hospital (Boston, MA, USA).

“We found for the first time that once you survive your childhood with a low-grade glioma, you are not likely to die of that tumor as an adult,” Dr. Manley said. “This is incredibly encouraging for patients and families. However, we also found some things that we are currently doing to treat low-grade gliomas, such as radiation, are increasing the rate of death later, so that as an adult you won’t die of the tumor, but you may die from the treatment.”

The data did not allow researchers to determine the precise process fueling the link between radiation treatment and reduced long-term survival (e.g., second cancers, other radiation-induced toxicities). However, because of the excellent overall long-term survival findings among the patients evaluated, the investigators believe that clinicians treating children for a pediatric low-grade glioma should make reducing long-term toxicity risk one of their first concerns.

“We strongly recommend treatments that are less likely to cause long-term effects and second cancers,” Dr. Manley said. “According to our analysis, radiation was the most common factor linked to differences in mortality among long-term survivors. There are multiple options available today for treating children with these tumors. We should exhaust all those before considering the use of radiation.”

Low-grade gliomas—a type of non-malignant, usually nonaggressive tumors that includes pilocytic astrocytomas, diffuse astrocytomas, and mixed gliomas—account for about 30% of all childhood brain tumors. Treatment typically consists of surgery and chemotherapy. Radiation, once a major part of therapy for these gliomas, has been not as popular since the mid-1990s, as it has for other childhood cancers such as Hodgkin’s lymphoma and germ cell tumors.

To better understand survival factors among this population, Dr. Manley, lead author Pratiti Bandopadhayay, MBBS, PhD, from Dana-Farber/Boston Children’s Hospital (Boston, MA, USA), and their collaborators analyzed Surveillance, Epidemiology, and End Results (SEER) data from the US National Cancer Institute (Bethesda, MD, USA) on more than 4,000 patients diagnosed with pediatric low-grade gliomas between 1973 and 2008. Eighteen percent of the patients in the cohort received radiation as part of their treatment.

The overall prognosis for children with low-grade gliomas is quite favorable, with 5- and 10-year survival rates approaching 90%. However, up to now, the long-term survival—20 years and beyond —of adult survivors has never been comprehensively studied. Manley and his colleagues found little drop-off in survival at 20 years post-treatment, with almost 90% of pediatric survivors still alive.

Other factors that affected survival included tumor location (cerebellum or not), tumor type (pilocytic or not), aggressiveness of the tumor (grade 1 vs. grade 2), year of diagnosis (before or after 1990) and age at diagnosis (< 2 years old). In the team's multivariate analysis, these other factors all had less effect on long-term survival than radiation.

“There is an impression that children diagnosed with anything more aggressive than a grade 1 tumor do poorly in the long term,” said Dr. Manley. “However, we found, regardless of whether the diagnosis is grade 1 or grade 2, children with low-grade gliomas still do well.”

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Dana-Farber/Boston Children’s Cancer and Blood Disorders Center