Spare the Hippocampus, Preserve the Memory in Whole Brain Irradiation

News October 01, 2013

ATLANTA (IMNG) – Sparing the hippocampus during whole brain irradiation can pay off in memory preservation for months to come, according to Dr. Vinai Gondi.

Adults with brain metastases who underwent whole brain radiation therapy (WBRT) with a conformal technique designed to minimize radiation dose to the hippocampus had a significantly smaller mean decline in verbal memory 4 months after treatment than did historical controls, reported Dr. Gondi, codirector of the Cadence Health Brain Tumor Center in Chicago and a coprincipal investigator in the Radiation Therapy Oncology Group Trial 0933.

“These phase II results are promising, and highlight the importance of the hippocampus as a radiosensitive structure central to memory toxicity,” Dr. Gondi said in a briefing prior to his presentation in a plenary session of the American Society for Radiation Oncology.

The hippocampus has been shown to play host to neural stem cells that are constantly differentiating into new neurons throughout adult life, a process important for maintaining memory function, he noted.

Previous studies have shown that cranial irradiation with WBRT is associated with a 4- to 6-month decline in memory function, as measured by the Hopkins Verbal Learning Test (HVLT) total recall and delayed recall items.

By using intensity modulated radiation therapy (IMRT) to shape the beam and largely spare the pocket of neural stem cells in the dentate gyrus portion of the hippocampus, the investigators hoped to avoid the decrements in memory function seen with earlier, less discriminating WBRT techniques, he said.

They enrolled 113 adults with brain metastases from various primary malignancies and assigned them to receive hippocampal-avoiding WBRT of 30 Gy delivered in 10 fractions. Radiation oncologists participating in the trial were trained in the technique, which involves careful identification of hippocampal landmarks and titration of the dose to minimize exposure of the hippocampus in general, and the dentate gyrus in particular. 

Under the protocol, the total radiation dose to the entire volume of the hippocampus can be no more than 10 Gy, and no single point in the hippocampus can receive more than 17 Gy.

Controls were patients in an earlier phase III clinical trial who underwent WBRT without hippocampal avoidance.

At 4 months, 100 patients treated with the hippocampal-sparing technique who were available for analysis had a 7% decline in the primary endpoint – delayed recall scores from baseline – compared with 30% for historical controls (P = .0003).

Among the 29 patients for whom 6-month data were available, the mean relative decline from baseline in delayed recall was 2% and in immediate recall was 0.7%. In contrast, there was a 3% increase in total recall scores.

The risk of metastasis to the hippocampus was 4.5% during follow-up, Dr. Gondi said.

The Radiation Oncology Therapy Group is currently developing a phase III trial of prophylactic cranial radiation with or without hippocampal avoidance for patients with small cell lung cancer.

The study demonstrates the value of improving and incorporating into practice newer radiation delivery technologies such as IMRT, said Dr. Bruce G. Haffty, a radiation oncologist at the Cancer Institute of New Jersey in New Brunswick, and ASTRO president-elect.

“It’s nice to have that technology available, and it’s now nice to see that we can use that technology to [reduce] memory loss and improve quality of life for our patients undergoing whole brain radiation therapy,” he said.

Dr. Haffty moderated the briefing, but was not involved in the study.

RTOG 0993 was supported by the National Cancer Institute. Dr. Gondi and Dr. Haffty reported having no relevant financial conflicts.