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Stereotactic radiosurgery appears to be feasible, safe, and effective for patients with 15 or more brain metastases and may be a viable alternative to whole brain radiation therapy (WBRT) alone in this population, new findings suggested. 

Overall, patients with 15 or more brain metastases who received stereotactic radiosurgery demonstrated "excellent subjective cognitive outcomes" and "comparable survival outcomes compared with contemporary studies evaluating WBRT in this population," the study authors reported.

More specifically, few patients who received stereotactic radiosurgery experienced radiation necrosis of any grade and most patients evaluated showed stable or improved cognitive function.

Eric Chang, MD, who was not involved in the research, called the retrospective study "important." "This paper further pushes the envelope and shows that [stereotactic radiosurgery] can be done in real practice for patients with 15-plus brain metastases," said Chang, chair of the Department of Radiation Oncology, Keck School of Medicine of University of Southern California, Los Angeles. 

The study was published online earlier this month in Advances in Radiation Oncology. 

Brain metastases are becoming more common in patients with cancer. The growing incidence of brain metastases is driven, in part, by advances in imaging and cancer therapies that have allowed patients to live longer with controlled primary tumors.

The use of stereotactic radiosurgery alone has been established for patients with one to four brain metastases. Recent evidence suggests stereotactic radiosurgery is also effective for patients with more than five brain metastases and that total tumor volume, not the number of metastases, may dictate outcomes for patients.

However, most patients with 15 or more brain metastases continue to receive WBRT, despite poor neurocognitive outcomes and impaired quality of life.

To determine whether patients with 15 or more brain metastases can benefit from stereotactic radiosurgery, the study authors reviewed outcomes for 118 patients who received linear accelerator-based stereotactic radiosurgery to treat their brain metastases. 

The primary trial endpoint was grade ≥ 3 radiation necrosis, secondary endpoints included neurocognitive decline of ≥ 5 points, local control, intracranial progression-free survival, and overall survival.

The most common primary tumors were lung (48%), followed by melanoma (21%) and breast (15%). The median number of lesions treated per course was 20 and ranged from 15 to 94. Median total tumor volume per patient was 7 cc. Most patients (82%) received fractionated stereotactic radiosurgery at a dose of 24 Gy in three fractions. 

At the time of stereotactic radiosurgery, 19% patients had received prior WBRT and 24% had received prior stereotactic radiosurgery. 

The primary endpoint of grade ≥ 3 radiation necrosis occurred in four patients (3.2%), and the rate of any grade radiation necrosis was 15.3%. 

The "relatively low" rate of radiation necrosis suggests that this treatment approach "would be safe," said Jonathan Knisely, MD, radiation oncologist at Weill Cornell Medicine Brain and Spine Center, New York City, who did not participate in the study. 

Cognitive outcomes — a key secondary endpoint — was evaluated using serial Patient-Reported Outcome Measurement Information System (PROMIS)-8 short-form scores. 

Among 31 patients with 6 months of data, PROMIS scores were stable in 20 patients (64.5%) and improved in five patients (16%). The remaining six patients demonstrated a decline of more than five points on PROMIS. Two of these patients had tumor progression, one had radiation necrosis, another had salvage WBRT, and a third declined on lurbinectedin. At the last follow up, 47% patients had a PROMIS score > 35 (a normal score is 50, on average, in the general population).

Overall, 97.6% of patients demonstrated local control. The cumulative incidence of distant intracranial failure was 46%. The median overall survival in the entire cohort was 5.8 months, with almost 30% of patients alive at 12 months. 

Patients with no history of prior brain radiotherapy survived longer than those with prior brain radiotherapy (median survival, 7.4 months vs 4.6 months; P = .034). When estimating survival from the date patients were diagnosed with brain metastases, median overall survival was 11.3 months overall and 9.2 months for radiotherapy naïve patients. 

Rates of 1-year freedom from neurological death (84%), leptomeningeal disease (94.6%), and salvage WBRT (84%) were high.

The authors noted the limitations of their analysis include the retrospective design and a heterogenous patient population, as well as a limited number of patients with objective cognitive data available for analysis. 

Chang and Knisely also noted that only a small cohort of patients in the study were assessed with the PROMIS tool. 

"Because this is a retrospective study, it is not practice-changing yet," said Chang. It's "more practice-suggesting."

However, "the ability to interact with one’s environment and to function independently is important for every patient and for every patient’s family and caregivers," said Knisely, "whether or not any given patient may have durable survival." 

The study had no specific funding. Raval, Chang, and Knisely had no relevant disclosures.