Worse Neuropsychological, Socioeconomic Outcomes in Adult Survivors of Pediatric Low-Grade Glioma

By Will Boggs MD

July 03, 2019

NEW YORK (Reuters Health) - Compared with their siblings, adult survivors of pediatric low-grade glioma have lower neuropsychological scores and socioeconomic status, especially if their treatment included radiotherapy, according to findings from the Childhood Cancer Survivor Study (CCSS).

"The most surprising finding was how closely the risk-gradient in these survivors, now decades from treatment, mirrors that found soon after treatment," said Dr. M. Douglas Ris from Baylor College of Medicine and Texas Children's Hospital, in Houston.

"Measures of central tendency, like mean IQ, remain in the 'average range,' but the curve for survivors is clearly shifted in the negative direction. There is also more variability or dispersion of scores in the survivors than in the sibling comparison group," he told Reuters Health by email.

About 75% of children diagnosed with a central nervous system tumor will become five-year survivors. Little is known about the long-term outcomes of patients with low-grade tumors, who typically receive less toxic treatments than those with the most aggressive and malignant tumors.

Dr. Ris and colleagues used data from survivors of pediatric low-grade gliomas (n=181) participating in the CCSS and a sibling comparison group (n=105) to investigate neuropsychological and socioeconomic outcomes in adults who had been treated with (n=96) and without (n=85) radiation.

In adjusted models, siblings had higher mean scores than survivors treated with surgery plus radiotherapy or surgery only across all neuropsychological outcomes, the researchers report in Cancer, online June 24.

Older age at diagnosis was associated with significantly higher neuropsychological scores in most domains.

In a subset analysis of survivors who received surgery and radiation, those with chemotherapy scored significantly lower than survivors who received surgery and radiotherapy without chemotherapy on most neuropsychological measures.

In multivariable models, surgery plus radiotherapy was associated with a 7.7-fold increased risk (P<0.001) of having an occupation score in the lowest sibling quartile, and surgery-only was associated with a 2.8-fold increased risk (P=0.007), compared with siblings.

Surgery plus radiation therapy, but not surgery alone, was associated with a significantly increased risk of an annual income below $20,000 and with a significantly increased risk for an educational level lower than a bachelor's degree.

Younger age at diagnosis was associated with lower occupation scores and lower educational level, such that a five-year increase in the age at diagnosis conferred a 50% reduction in the odds of a lower occupation score or in the odds of an educational level less than a bachelor's degree.

"Adult health care systems need to understand the life-long legacy of pediatric brain tumors, even those considered 'benign' that are treated with less toxic treatments," Dr. Ris said. "Our study demonstrates that commonly used indices of neurocognitive outcome, like IQ, are associated with broader neuropsychological deficits, such as memory, executive functions, and motor functions. More importantly, they are also associated with real-life outcomes, such as educational and occupational attainment."

"It is also important to keep in mind, though, that the story of survivors is not simply one of risk, but also of resilience," he said. "Despite their early history of a life-threatening disease, survivors persist in overcoming obstacles throughout life and may even excel."

Dr. Danny Indelicato of the University of Florida College of Medicine, in Gainesville, who recently described the late effects after radiation therapy for low-grade glioma, told Reuters Health by email, "While new chemotherapy is promising, radiation remains the most effective tool in treating a child with an unresectable low-grade glioma. But this article highlights important consequences of treatment in patients who become long-term survivors. Therefore, we must continue to investigate new radiation technology and techniques that minimize the irradiation of normal brain tissue."

"We also must devote more resources in diagnosing and supporting the growing number of brain-tumor survivors," said Dr. Indelicato, who was not involved in the new work. "As the late Dr. Giulio D'Angio said, 'Cure is not enough.'"

"These patients were treated with radiation 40 years ago," Dr. Indelicato said. "Fortunately, over the last 4 decades, there have been dramatic improvements in radiotherapy that have reduced unnecessary radiation exposure in the developing brain. This has translated into improved neurocognitive outcomes."

He added, "Children should undergo formal neurocognitive testing on a regular basis until they finish formal education. As adults, they should be screened for cognitive dysfunction by their primary-care providers or, even better, in one of the brain-tumor-survivorship clinics throughout the United States."

SOURCE: https://bit.ly/2KFkC08

Cancer 2019.

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