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BOSTON -- In patients with resected brain metastases, postoperative radiosurgery of the surgical cavity should be considered a standard of care and a less toxic alternative to whole brain radiotherapy (WBRT), two studies reported here found.

Results from an international phase III trial showed that stereotactic radiosurgery (SRS) provided equivalent overall survival to WBRT -- the current standard of care for patients following resection -- but left patients with significantly better cognitive function and quality of life for up to 6 months.

There was no statistically significant difference in survival between treatment groups, with a median overall survival of 11.5 months following SRS and 11.8 months following WBRT (P=0.65), , of the Mayo Clinic in Rochester, MN, reported here at the annual meeting of the .

However, patients treated with SRS experienced significantly longer survival without cognitive decline. The median cognitive deterioration-free survival (CDFS) was 3.2 months for patients given SRS versus 2.8 months for those who received WBRT (HR 2.0; P<0.0001).

At 6 months, 53.8% of patients who received SRS experienced a decline in cognitive function versus 85.7% of patients treated with WBRT (P=0.0006). They had significantly less deterioration in immediate recall (17.3% versus 47.9%, respectively; P<0.0001), delayed recall (27.5% versus 62.5%; P<0.0001), and processing speed (17.3% versus 37.5%; P=0.03).

"Our multi-institutional, randomized trial is the first to demonstrate clearly the efficacy of SRS compared to WBRT in a post-operative setting," Brown told delegates. "Our results confirm that radiosurgery to the surgical cavity is a viable treatment option to improve local control with less impact on cognitive function and quality of life compared to WBRT."

Brown added, "Whole brain RT has no survival benefit and it does have significant toxicity. I just want to emphasize that."

Despite the lack of clinical data on the efficacy of SRS in this setting, the technology is widely used to reduce or avoid the effects of WBRT on cognitive function, he acknowledged. SRS makes it possible to conserve healthy brain tissue by delivering a single fraction of precise, high-dose radiation to the surgical cavity, Brown noted, adding: "We're talking millimeters."

WBRT can delay systemic therapy and requires patients to be hospitalized for 2-3 weeks, he pointed out. "Radiosurgery has the advantage of being a one-day session."

"I want to congratulate you and your group and your patients," said , from Western University in London, Ontario, Canada, who moderated the session. "This will help me better inform my patients about the trade-offs involved regarding the decision about SRS of the cavity versus whole brain radiotherapy."

For the study, 194 patients seen at cancer centers across the U.S. and Canada were enrolled from 2011 to 2015. Median age was 61 years. Eligibility criteria included one to four brain metastases with a diameter of less than 5 cm; 77% of study participants had a single metastasis from a primary tumor in the lung. Median follow-up was 15.6 months.

Following resection of a single lesion, patients were randomized to SRS or WBRT. All unresected metastases were treated with SRS, regardless of treatment arm.

Patients who received WBRT experienced higher overall intracranial tumor control at 6 and 12 months than those who received SRS (90.0% and 78.6% versus 74.0% and 54.7%, respectively; P<0.0001). However, there was no clinically significant difference in median surgical bed relapse-free survival between treatment arms, the study showed.

At three months, SRS patients had a better overall quality of life with a mean change from baseline of -1.5 versus -7.0 for patients treated with WBRT (P=0.03). They also had significantly better scores in physical wellbeing (-6.4 versus -20.2; P=0.002).

At six months, patients who underwent SRS continued to experience significantly less deterioration of physical wellbeing than who received WBRT (-3.2 versus -15.1, respectively; P=0.016).

Skip Post-Op RT for Small Tumors?

A separate but parallel study comparing post-operative SRS to the surgical cavity with observation in patients with resected brain metastases was presented by , of MD Anderson Cancer Center in Houston.

The prospective, randomized, single-center trial demonstrated that radiosurgery to the surgical bed significantly reduced local recurrence of the resected tumor compared to observation alone. There were no improvements seen in overall survival or in the rates of distant brain metastases (DBMs) between patients who received SRS and those who were observed, Mahajan told attendees.

"Our research shows that radiosurgery in this patient cohort does reduce the incidence of local recurrence, although the findings for overall brain control, overall survival and time until whole brain radiation therapy limit our ability to conclude an obvious clinical benefit," said Mahajan.

For the study, 128 patients with one to three brain metastases were enrolled from October 2009 to October 2015. Sixty-three were assigned to SRS of the surgical cavity (or cavities in the case of multiple resections) and 65 to observation alone. Median age was 59 years.

At 6 months following SRS, local control rates were 83% compared with 57% for the observation group. At 12 months, there was a significant benefit in local control seen in patients who received SRS compared to those who were observed (72% versus 45%; HR 0.46; P=0.01). "This benefit has continued over 2 years," Mahajan said.

Local recurrence appeared to be influenced by lesion size. Tumors that were smaller (2.5 cm or less) had a very low recurrence rate despite the intervention. "When we pooled the two groups, they actually had a 90% control rate after complete resection," noted Mahajan. "It appears that smaller tumors may not need post-operative radiosurgery after resection."

Lesions that were 2.6-3.5 cm in diameter had a control rate of 43% while lesions larger than 3.5 cm had a 46% control rate.

Local recurrence was not significantly affected by the number of brain metastases, histology (melanoma or other) or prognosis, said Mahajan.

Like Brown, Mahajan acknowledged the lack of clinical evidence on the efficacy of post-operative SRS. "While oncology teams see the potential of radiosurgery, its novelty means that we have limited prospective evidence of its efficacy."

That could change soon, pointed out Rodrigues. "Put together, these trials confirm that SRS is a viable option in the management of these patients," he said.

Twelve months after SRS, 58% of patients had developed DBMs, compared to 67% who received observation (HR 0.79; P=0.29). This was not statistically significant, Mahajan pointed out. Both groups had a median overall survival of 17 months (HR 1.22; P=0.37).

In the SRS group, 24 patients went on to receive WBRT within an average of 16.1 months whereas 30 of 67 patients in the observation group went on to WBRT within 15.2 months on average (HR 0.8; P=0.42).

Mahajan said the researchers are now looking at how best to identify which patients will benefit from different treatments.