Kate O'Rourke

September 26, 2016

BOSTON — Postoperative stereotactic radiosurgery (SRS) after complete resection of brain metastases significantly improves local control compared with observation, according to a prospective, randomized controlled trial conducted at MD Anderson Cancer Center in Houston, Texas.

Researchers say the improved control is similar to that seen with whole-brain radiation (WBRT), which is a more toxic treatment.

"Postop radiosurgery appears to have a significant benefit in local control for management of completely resected brain metastases," said lead study author, Anita Mahajan, MD, Department of Radiation Oncology, MD Anderson Cancer Center.

She discussed the new study data here at a press briefing at the American Society for Radiation Oncology (ASTRO) 2016 Annual Meeting.

Surgical resection and WBRT independently have been shown to improve local control in patients with brain metastases, and surgical resection plus WBRT has been the standard of care for roughly the last 20 years (JAMA. 1998;280:1485-1489).

Postoperative WBRT, however, can cause alopecia, fatigue, and adverse cognitive outcomes.

Retrospective studies have shown that postoperative SRS may improve local control and allow delay or avoidance of WBRT.

"Retrospective studies suggest local control rates of 80% to 90% after postop SRS," said Dr Mahajan. "The advantage of stereotactic radiosurgery is it allows a highly conformal plan around an irregular target volume and the patient can be treated quickly after surgery with a single session treatment."

In the new study, Dr Mahajan and colleagues set out to evaluate SRS to the postoperative cavity in a prospective trial.

Between 2009 and 2015, the investigators enrolled patients with one to three brain metastases, with at least one metastasis that was completely resected, and randomly assigned them to observation of the surgical cavity or SRS of the remaining one to two metastases. The final analysis included 128 patients, and the median follow-up was 13 months.

The investigators identified a significant improvement in local control with SRS compared with observation at 6 months (83% vs 57%; P = .01) and 12 months (72% vs 45%; P = .01).

The median time to local progression in the observation group was 7.6 months and had not yet been reached in the SRS group. The rate of distant brain metastases was similar in the two group, with 43% of patients in the SRS group and 33% in the observation group remaining free of distant brain metastases (P = .29). Median overall survival (17 months) and time to whole-brain radiation were not different in the two groups.

"When we looked at the variables and local control, no significant differences were noted with prior GPA [graded prognostic assessment], the type of tumor, the number of brain metastases, or the type of resection," said Dr Mahajan. The initial tumor diameter, however, influenced local control (≤2.5 cm, 91%; 2.6 to 3.5 cm, 43%; >3.5 cm, 46%).

"Small tumors did appear to have a very high local control, despite the arm of randomization, and you wonder whether they could be managed with a single modality rather than both modalities. Since no toxicities were noted, larger tumors may benefit from a higher radiosurgery dose," said Dr Mahajan.

She also reported that the rate of leptomeningeal dissemination was similar between the two groups, and there were no treatment toxicities.

More Study Detail

Randomization had to occur within 30 days or surgery. Stratification before randomization included number of brain metastases (one vs two to three brain metastases), melanoma vs other cancers, and preoperative tumor size (<3 cm vs >3 cm). The maximum size of the postoperative cavity was 4 cm. Patient and tumor characteristics were well balanced in the two groups. Melanoma, lung cancer, and breast cancer were the most common indications.

The SRS target volume was the surgical cavity and a 1-mm margin, based on the MRI performed on the day of radiosurgery. The dose was volume dependent, with the lowest dose used being 12 Gy and the largest being 16 Gy. Distant brain metastases were defined as any new lesions separate from the surgical site, and they were managed at the physician's discretion. Patients remained on the study until local failure or the use of WBRT was needed.

"Ambiguous MRI findings were followed until they were deemed either reactive or progressive disease and then they were censored at the first day of detection," said Dr Mahajan.

In a discussion that followed the study's presentation, Vinai Gondi, MD, a radiation oncologist at Northwestern Medicine Cancer Center, Warrenville, Illinois, pointed out that the significant reduction in surgical bed relapse after SRS in the MD Anderson trial was similar to that seen with WBRT in the European Organisation for Research and Treatment of Cancer trial 22952-26001 (J Clin Oncol. 2011;29:134-141).

He said the data made him "question the role of surgical resection for brain metastases patients whose prognosis is limited to less than 6 months." SRS is a standard of care for brain metastases, he said.

Dr Mahajan and Dr Gondi have disclosed no relevant financial relationships.

American Society for Radiation Oncology (ASTRO) 2016 Annual Meeting. Abstract 3. Presented September 25, 2016.

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