The first long-term outcome study of low-grade gliomas in children shows that 87% of patients are still alive 20 years after their diagnosis, but that outcomes are significantly inferior in those treated with radiation therapy.
The study was published online January 30 in Pediatric Blood & Cancer.
The results show 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," senior author Peter Manley, MD, a pediatric neuro-oncologist at the Brain Tumor Center of Dana-Farber/Boston Children's Cancer and Blood Disorders Center, said in a statement.
"This is incredibly encouraging for patients and families.... In adults, these tumors tend to transform into more aggressive tumors," he told Medscape Medical News.
"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," Dr. Manley is quoted as saying in a press release issued by his institution about this study.
Dr. Manley and colleagues acknowledge that the analysis does not show a causal relation between radiation therapy and increased mortality. They note that the observed association might be explained by "a combination of both selection bias (i.e., children with harder-to-control disease are more likely to have received radiation) and radiation-induced mortality, such as the increased risk of secondary malignancy and vasculopathy."
An expert not involved in the study agrees. The tumors that had been treated with radiation were likely to have been more aggressive and have a worse prognosis, said David Sandberg, MD, codirector of the pediatric brain tumor program at the University of Texas M.D. Anderson Cancer Center in Houston.
"Therapeutic strategies should be designed to provide tumor control while avoiding those that can cause irreversible long-term toxicity...as patients can be expected to survive long into adulthood," Dr. Manley and colleagues conclude.
"Radiation is still an effective treatment for low-grade gliomas," Dr. Manley told Medscape Medical News. "Knowing that the outcomes for these patients are so good, we would recommend using therapies that minimize the long-term toxicities associated with certain treatments, and radiation has long-term effects of stroke, secondary malignancy, and cognitive delay."
Dr. Sandberg told Medscape Medical News that although he agrees with this general notion, the study results should be interpreted with caution.
"This study does not provide any compelling evidence to suggest that radiation therapy actually caused an increased risk of cancer-specific death," he emphasized. "While radiation therapy is avoided whenever possible in patients with low-grade gliomas, it is an important tool with risks that are almost certainly outweighed by benefits in a subset of patients."
Retrospective Analysis of SEER Data
Dr. Manley and colleagues identified 4040 children diagnosed with grade I or II glioma in the Surveillance, Epidemiology, and End Results (SEER) database from 1973 to 2008. The median age at diagnosis was 9 years.
Histologic groupings included pilocytic astrocytoma, diffuse astrocytoma, astrocytoma not otherwise specified, glioma not otherwise specified, mixed glioma, and unique astrocytoma variants.
Overall cancer-specific survival at 20 years was 87%, which is similar to previously reported 5- and 10-year rates.
In the study cohort, 18% of patients had received radiation as part of their treatment. On multivariate analysis, radiation was found to increase the risk for death from the tumor, compared with no radiation (hazard ratio [HR], 3.9; P < .0001).
Children who did not have cerebellar disease had an increased risk for disease-related death (HR, 2.3; P< 0.0001), as did those who had nonpilocytic astrocytoma histology (HR, 2.2; P < .0001).
There was no significant difference in overall survival between patients who received a gross total surgical resection and those who had residual disease, regardless of radiation status.
Radiation "Almost Eliminated"
Dana-Farber/Boston Children's and a number of other institutions have "almost eliminated" radiation therapy for low-grade gliomas in children because of their own observations about the detrimental effects of radiation, Dr. Manley reported.
"There were a number of neuro-oncologists who had a lot of experience following these patients long-term who felt this to be true, but there were no data to support this opinion. Now there are," he said.
But Dr. Sandberg emphasized that there are subtleties the study authors did not address.
"Almost every major hospital, M.D. Anderson included, uses radiation therapy only in a minority of patients with low-grade gliomas," Dr. Sandberg explained. "There is near universal agreement that low-grade gliomas in locations amenable to surgical resection should be removed completely and patients should be observed without radiation or other adjuvant therapy. In the event of recurrence or progression of lesions not amenable to surgical resection, both chemotherapy and radiation therapy can delay progression in selected patients."
However, he emphasized that "not all low-grade gliomas are the same. For example, a pilocytic astrocytoma in a cerebellar hemisphere can be removed surgically with no radiation or adjuvant therapy of any type. The recurrence rate for this tumor will be very low. The same pathology located in the optic pathways and hypothalamus (an optic chiasmatic/hypothalamic glioma) usually cannot be completely resected without causing blindness and/or severe endocrinopathy. If such a tumor progresses, chemotherapy is typically the first line of treatment. However, chemotherapy often fails for low-grade gliomas, and radiation therapy is very effective in some such patients in preventing further progression and saving vision. I am quite certain that radiation therapy is used in such patients at Dana-Farber and all other major treatment centers."
This study was supported by the Stop & Shop Family Pediatric Brain Tumor Program, the Andrysiak Fund for LGG, the Pediatric Low-Grade Astrocytoma Foundation, Friends of Dana-Farber, the Nuovo-Soldati Foundation, the Philippe Foundation, and the St. Baldrick's Foundation. Dr. Manley and Dr. Sandberg have disclosed no relevant financial relationships.
Pediatr Blood Cancer. Published online January 30, 2014. Abstract
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Cite this: Excellent Survival in Pediatric Gliomas, But Worse After Radiation - Medscape - Feb 06, 2014.