Limiting the amount of radiation absorbed in the hippocampal portion of the brain during whole-brain radiotherapy (WBRT) for brain metastases preserves memory function in patients for up to 6 months after treatment. This research was presented at the 55th annual meeting of the American Society for Radiation Oncology in Atlanta, Georgia.

The single-arm, phase II study was a multi-institutional, international clinical trial in the United States and Canada, conducted through the Radiation Therapy Oncology Group (RTOG). Researchers compared the study group to a historical control group of patients who had received WBRT without hippocampal avoidance in the PCI-P-120-9801 phase III trial.

This study enrolled 113 adult patients from 2011 through 2013 who had a measurable brain metastasis outside a 5-mm margin around the hippocampus. Of those patients, 100 were analyzable and 76% were categorized as recursive partitioning analysis class II. All patients received hippocampal avoidance whole-brain radiotherapy to 30 Gy in 10 fractions. In all analyzable patients, the dose received by the entirety of the hippocampus did not exceed 10 Gy, and the maximum dose did not exceed 17 Gy. Patients were assessed using the Hopkins Verbal Learning Test-Delayed Recall (HVLT-DR), the HVLT-Recall (HVLT-R) and the HVLT-Immediate Recognition (HVLT-IR) at baseline and post-treatment at 2-, 4- and 6-month intervals. The primary end point of the trial was the delayed recall at 4 months.

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Results showed that the 42 patients who were analyzable at 4 months postradiation therapy had a 7% decline in delayed recall from baseline to 4 months. This is statistically significant when compared to the historical control group (P=.0003), which demonstrated a 30% decline in delayed recall at 4 months. Six months after treatment, the 29 analyzable patients had a 2% decline in delayed recall from baseline.

“Radiotherapy to the brain is known to impact the memory function of cancer survivors,” said lead author Vinai Gondi, MD, co-director of the Cadence Brain Tumor Center and Associate Director of Research at the Cadence Proton Center in Warrenville, Illinois, and Clinical Assistant Professor at the University of Wisconsin School of Medicine and Public Health in Madison, Wisconsin. “A compartment of neural stem cells located in the hippocampus, sensitive to radiotherapy and important for memory function, is thought to be central to these effects.”

Gondi explained that the research team group developed advanced radiotherapy techniques that spare this hippocampal neural stem cell compartment from significant radiation doses. The study results were statistically better than historical data of whole-brain radiotherapy without hippocampal sparing and present a number of opportunities to introduce hippocampal sparing in other contexts of radiotherapy to the brain. Now, phase III trials are being developed to explore these other contexts and to validate these results.