Spare the Hippocampus in Brain Radiotherapy, Preserve Memory

Nick Mulcahy

October 01, 2013

ATLANTA — A modified version of whole-brain radiotherapy (WBRT) might preserve memory function in cancer patients with brain metastases, according to a single-group study presented here at the American Society for Radiation Oncology (ASTRO) 55th Annual Meeting.

The mean decline in short-term memory function at 4 months was significantly better in patients who were treated with this new technique than in historic control subjects (7% vs 30%; P = .0003).

The memory test was the Hopkins Verbal Learning Test–Delayed Recall (HVLT–DR), and the 4-month measurement was the study's primary end point.

Loss of short-term memory function is a known casualty in some patients treated with WBRT, explained lead author Vinai Gondi, MD, a radiation oncologist from the University of Wisconsin School of Medicine and Public Health in Madison.

Dr. Gondi and a group of colleagues from the Radiation Therapy Oncology Group (RTOG) developed an approach to address the problem: hippocampal avoidance (HA)-WBRT. The hippocampus is the portion of the brain responsible for new memory formation, he explained to reporters at a press briefing.

The name is slightly misleading, he noted. "No, we do not spare the entire hippocampus," he told reporters.

Instead, the dose received by the entirety of the hippocampus did not exceed 10 Gy, and the maximum dose did not exceed 17 Gy. Overall, all patients received HA-WBRT to 30 Gy in 10 fractions.

The technique is a departure from traditional thinking about the treatment of brain metastases, said Dr. Gondi. The reason for irradiating the whole brain has been that, in addition to treating visible lesions, the therapy will treat "micromets" that are not perceivable with imaging. But radiation oncologists have been increasingly sensitive to the adverse effects of that approach, he explained.

The preservation of memory in cancer patients with brain metastases treated with radiotherapy is increasingly important because patients are living longer, said Colleen Lawton, MD, from the Medical College of Wisconsin in Milwaukee. She is president of ASTRO's board of directors, and was not involved with the study.

"Many of these patients will live years beyond the diagnosis of a brain metastasis and, therefore, quality of life is critical," she said in a premeeting interview with Medscape Medical News.

Quality-of-life assessments in this trial showed a more favorable profile for patients treated with HA-WBRT than for historic control subjects, Dr. Gondi reported.

Two treatment-related grade 3 adverse events were reported (fatigue, headache), but there were no treatment-related grade 4/5 events.

Benefit Continues at 6 Months

The multi-institutional phase 2 study, known as RTOG 0933, was conducted in the United States and Canada from 2011 to 2013. The investigators assessed a number of cognitive functions after radiotherapy in 113 adults who had a measurable brain metastasis outside a 5-mm margin around the hippocampus.

In addition to the delayed recall test, patients were assessed with the HVLT–Recall (HVLT–R) test and the HVLT–Immediate Recognition (HVLT–IR) test at baseline and at 2-, 4-, and 6-month intervals after treatment.

Of the 100 patients who were initially analyzable, 76% were categorized as recursive partitioning analysis prognostic class II. Notably, over the 6-month study period, the number of analyzable patients declined.

Six months after treatment, 29 analyzable patients had a 2% decline in HVLT-DR from baseline (95% confidence interval, −9.2% to −13.1%).

Because it is a novel technique, the investigators offered an educational program on the use of HA-WBRT before study enrolment began. With this, more than 80 RTOG-affiliated sites and 113 physicians became qualified to participate in the trial, said Dr. Gondi.

RTOG 0933 also included a "real-time" pretreatment "rapid review" of treatment plans prior to the start of therapy to ensure adherence to HA-WBRT.

The phase 2 study results were promising enough to warrant validation, Dr. Gondi reported.

Currently, a phase 3 trial, RTOG 1317, is comparing partial cranial radiation with and without sparing of the hippocampus in patients with nonsmall-cell lung cancer and brain metastases.

The study was supported by the RTOG and the National Cancer Institute. Some of the study coauthors report financial relationships with industry.

American Society for Radiation Oncology (ASTRO) 55th Annual Meeting: Abstract LBA1. Presented September 23, 2013.

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