Whole-Brain Radiation Preserved Neurocognitive Function

ATLANTA — Whole-brain radiation therapy can preserve neurocognitive function in patients with brain metastases, according to a 135-patient study presented at the annual meeting of the American Society of Clinical Oncology.

Dr. Jing Li reported that patients lived longer and had better neurocognitive function if their tumors shrank more than 45% during the 2 months after whole-brain radiation therapy (WBRT).

These “good responders” scored better on all eight neurocognitive tests used in the study, compared with “poor responders” with less than 45% tumor shrinkage at the 2-month mark. The effects were statistically significant over the course of the study on tests of executive function and fine motor coordination.

The effects were most dramatic in a small group of 7–9 long-term survivors who demonstrated cognitive improvement when tested 15 months after receiving WBRT.

Magnetic resonance imaging at 4 months showed that brain tumors had shrunk 80% on average from baseline by then in patients who would survive 15 months.

“Neurocognitive function is stable or improving over time in long-term survivors,” said Dr. Li of the University of Wisconsin at Madison. “It appears that the adverse impact of tumor growth on neurocognitive function is greater than that of whole brain radiation therapy. Therefore, improving response is a worthy aim in this patient population.”

Although WBRT is used to reduce neurologic symptoms caused by brain metastases, she said the treatment's effects on neurocognitive skills have up to now gone “largely unstudied.” The lack of data was attributable, she suggested, to inadequate assessment tools and the poor prognosis (4–6 months median survival) in the 10%–30% of cancer patients who develop brain metastases.

For this study, Dr. Li and her colleagues selected 135 of 208 patients in the control arm of a prospective, randomized, multicenter trial that compared WBRT alone with WBRT with motexafin gadolinium enhancement. Only those who survived until the first follow-up magnetic resonance image was taken 2 months later were eligible for the neurocognitive study. All neurocognitive participants had received 30 Gy of radiation in 10 fractions without motexafin gadolinium.

The investigators determined that median tumor shrinkage was 45% at two months for the entire population. They classified patients as good or poor responders based on their relationship to the median.

To determine changes in neurocognitive function, the researchers administered eight tests that had been validated in another pilot study and could be completed within 30 minutes.

The eight tests covered three neurocognitive domains: memory, executive function (decision-making capacity), and fine motor coordination.

Poor responders had a shorter time to neurocognitive deterioration on all eight tests, compared with the good responders, according to Dr. Li. She said this difference was statistically significant on two pegboard tests used to measure fine motor coordination (287 vs. 380 days and 291 vs. 401 days) and the Trail B test of executive function (331 vs. 462 days).

In a discussion of Dr. Li's presentation, Dr. Jeff A. Sloan suggested the differences might have been statistically significant on all eight tests had the investigators chosen a less stringent definition of neurocognitive deterioration. The criterion used was a decline of two standard deviations from baseline on two consecutive measurements or on the last follow-up visit before death.

“Two standard deviations is a huge change, a profound change,” Dr. Sloan of the Mayo Clinic in Rochester, Minn., said, praising the study for its rigor. “… [T]he bar was set so high, it is not surprising that only three of these eight [findings] were significant.”

ATLANTA — Whole-brain radiation therapy can preserve neurocognitive function in patients with brain metastases, according to a 135-patient study presented at the annual meeting of the American Society of Clinical Oncology.

Dr. Jing Li reported that patients lived longer and had better neurocognitive function if their tumors shrank more than 45% during the 2 months after whole-brain radiation therapy (WBRT).

These “good responders” scored better on all eight neurocognitive tests used in the study, compared with “poor responders” with less than 45% tumor shrinkage at the 2-month mark. The effects were statistically significant over the course of the study on tests of executive function and fine motor coordination.

The effects were most dramatic in a small group of 7–9 long-term survivors who demonstrated cognitive improvement when tested 15 months after receiving WBRT.

Magnetic resonance imaging at 4 months showed that brain tumors had shrunk 80% on average from baseline by then in patients who would survive 15 months.

“Neurocognitive function is stable or improving over time in long-term survivors,” said Dr. Li of the University of Wisconsin at Madison. “It appears that the adverse impact of tumor growth on neurocognitive function is greater than that of whole brain radiation therapy. Therefore, improving response is a worthy aim in this patient population.”

Although WBRT is used to reduce neurologic symptoms caused by brain metastases, she said the treatment's effects on neurocognitive skills have up to now gone “largely unstudied.” The lack of data was attributable, she suggested, to inadequate assessment tools and the poor prognosis (4–6 months median survival) in the 10%–30% of cancer patients who develop brain metastases.

For this study, Dr. Li and her colleagues selected 135 of 208 patients in the control arm of a prospective, randomized, multicenter trial that compared WBRT alone with WBRT with motexafin gadolinium enhancement. Only those who survived until the first follow-up magnetic resonance image was taken 2 months later were eligible for the neurocognitive study. All neurocognitive participants had received 30 Gy of radiation in 10 fractions without motexafin gadolinium.

The investigators determined that median tumor shrinkage was 45% at two months for the entire population. They classified patients as good or poor responders based on their relationship to the median.

To determine changes in neurocognitive function, the researchers administered eight tests that had been validated in another pilot study and could be completed within 30 minutes.

The eight tests covered three neurocognitive domains: memory, executive function (decision-making capacity), and fine motor coordination.

Poor responders had a shorter time to neurocognitive deterioration on all eight tests, compared with the good responders, according to Dr. Li. She said this difference was statistically significant on two pegboard tests used to measure fine motor coordination (287 vs. 380 days and 291 vs. 401 days) and the Trail B test of executive function (331 vs. 462 days).

In a discussion of Dr. Li's presentation, Dr. Jeff A. Sloan suggested the differences might have been statistically significant on all eight tests had the investigators chosen a less stringent definition of neurocognitive deterioration. The criterion used was a decline of two standard deviations from baseline on two consecutive measurements or on the last follow-up visit before death.

“Two standard deviations is a huge change, a profound change,” Dr. Sloan of the Mayo Clinic in Rochester, Minn., said, praising the study for its rigor. “… [T]he bar was set so high, it is not surprising that only three of these eight [findings] were significant.”

ATLANTA — Whole-brain radiation therapy can preserve neurocognitive function in patients with brain metastases, according to a 135-patient study presented at the annual meeting of the American Society of Clinical Oncology.

Dr. Jing Li reported that patients lived longer and had better neurocognitive function if their tumors shrank more than 45% during the 2 months after whole-brain radiation therapy (WBRT).

These “good responders” scored better on all eight neurocognitive tests used in the study, compared with “poor responders” with less than 45% tumor shrinkage at the 2-month mark. The effects were statistically significant over the course of the study on tests of executive function and fine motor coordination.

The effects were most dramatic in a small group of 7–9 long-term survivors who demonstrated cognitive improvement when tested 15 months after receiving WBRT.

Magnetic resonance imaging at 4 months showed that brain tumors had shrunk 80% on average from baseline by then in patients who would survive 15 months.

“Neurocognitive function is stable or improving over time in long-term survivors,” said Dr. Li of the University of Wisconsin at Madison. “It appears that the adverse impact of tumor growth on neurocognitive function is greater than that of whole brain radiation therapy. Therefore, improving response is a worthy aim in this patient population.”

Although WBRT is used to reduce neurologic symptoms caused by brain metastases, she said the treatment's effects on neurocognitive skills have up to now gone “largely unstudied.” The lack of data was attributable, she suggested, to inadequate assessment tools and the poor prognosis (4–6 months median survival) in the 10%–30% of cancer patients who develop brain metastases.

For this study, Dr. Li and her colleagues selected 135 of 208 patients in the control arm of a prospective, randomized, multicenter trial that compared WBRT alone with WBRT with motexafin gadolinium enhancement. Only those who survived until the first follow-up magnetic resonance image was taken 2 months later were eligible for the neurocognitive study. All neurocognitive participants had received 30 Gy of radiation in 10 fractions without motexafin gadolinium.

The investigators determined that median tumor shrinkage was 45% at two months for the entire population. They classified patients as good or poor responders based on their relationship to the median.

To determine changes in neurocognitive function, the researchers administered eight tests that had been validated in another pilot study and could be completed within 30 minutes.

The eight tests covered three neurocognitive domains: memory, executive function (decision-making capacity), and fine motor coordination.

Poor responders had a shorter time to neurocognitive deterioration on all eight tests, compared with the good responders, according to Dr. Li. She said this difference was statistically significant on two pegboard tests used to measure fine motor coordination (287 vs. 380 days and 291 vs. 401 days) and the Trail B test of executive function (331 vs. 462 days).

In a discussion of Dr. Li's presentation, Dr. Jeff A. Sloan suggested the differences might have been statistically significant on all eight tests had the investigators chosen a less stringent definition of neurocognitive deterioration. The criterion used was a decline of two standard deviations from baseline on two consecutive measurements or on the last follow-up visit before death.

“Two standard deviations is a huge change, a profound change,” Dr. Sloan of the Mayo Clinic in Rochester, Minn., said, praising the study for its rigor. “… [T]he bar was set so high, it is not surprising that only three of these eight [findings] were significant.”