Stereotactic Radiosurgery for 15 or More Brain Metastases?

Stereotactic radiosurgery (SRS) directs high-dose radiation directly at a tumor to kill cancer cells while minimizing injury to surrounding healthy tissue. It is an advanced radiotherapy technique. No actual surgery is performed; the name reflects radiation's surgery-like destruction of the tumor. Particularly for small or medium-sized tumors, this approach minimizes discomfort, shortens treatment and speeds recovery. In sensitive organs such as the brain, SRS is especially favored when surgery is unsuitable or high-risk.

Brain metastases occur when cancer cells spread to the brain from elsewhere in the body. This indicates advanced cancer and generally requires a more aggressive approach. Even when cancer elsewhere is controlled, brain metastases can substantially affect quality of life and cause serious neurological impairment.

Improved imaging and more effective treatments mean patients with advanced cancer live longer, increasing the risk of brain metastases. SRS has therefore become an increasingly important option for controlling them. When effective, it may preserve quality of life and neurological function for longer. Compared with broader treatment such as whole-brain radiation therapy (WBRT), it may have fewer adverse cognitive effects, helping patients maintain everyday life as normally as possible.

A Surprising Study

New findings suggest that SRS may be feasible, safe and effective in patients with 15 or more brain metastases, offering an appropriate alternative to WBRT alone.

In particular, patients with 15 or more brain metastases treated with SRS were reported to have much better cognitive outcomes and similar survival compared with WBRT.

More specifically, SRS-treated patients experienced less radiation necrosis, and most assessed patients had stable or improved cognitive function.

Radiation necrosis is cell death and tissue damage in the treated area caused by radiotherapy. It generally occurs in high-dose regions and can be mistaken for cancer progression.

A Retrospective Analysis With Important Findings

This article extends existing treatment boundaries by showing that SRS can be successfully delivered in real-world settings to patients with 15 or more brain metastases.

The study was published online on 12 April 2024 in Radiation Oncology Advances.

Brain metastases are increasingly common in cancer, directly related to better imaging and treatments that control primary tumors and prolong survival. SRS is already accepted and proven effective for one to four brain metastases. Recent evidence also suggests effectiveness with more than five, and that total tumor volume may matter more than lesion count.

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

Study Details

To assess whether patients with 15 or more brain metastases could benefit, researchers reviewed outcomes in 118 patients treated with linear accelerator-based SRS.

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

The most common primary tumor was lung cancer (48%), followed by melanoma (21%) and breast cancer (15%). Median lesions treated per session numbered 20, ranging from 15 to 94, and median total tumor volume was 7 cc. Most patients (82%) received fractionated SRS totaling 24 Gy in three fractions.

At SRS, 19% had previously received WBRT and 24% had previously undergone SRS.

Results

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

The "relatively low" necrosis rate suggests that this approach "would be safe."

An important secondary outcome was assessed using serial Patient-Reported Outcomes Measurement Information System (PROMIS)-8 short-form scores.

During six months of follow-up, scores remained stable in 20 of 31 patients (64.5%) and improved in five (16%). The remaining six had declines exceeding five points; two were attributed to progression, one to radiation necrosis, one to salvage WBRT and another to lurbinectedin. At final follow-up, 47% had scores above 35, a notable finding given the normal general-population mean of 50.

Local control was achieved in 97.6%. Cumulative distant intracranial failure was 46%. Median overall survival for the full cohort was 5.8 months, and almost 30% were alive at 12 months.

Patients without prior brain radiotherapy survived longer than previously irradiated patients: median survival was 7.4 versus 4.6 months (P = 0.034). Overall survival from brain metastasis diagnosis was 11.3 months; in radiotherapy-naive patients, it was 9.2 months.

The authors identified limitations including the retrospective design, heterogeneous population and small number of patients with objective cognitive data. The study therefore proposes a new approach rather than changing current practice.

Regardless of survival duration, being able to interact with one's surroundings and function independently matters greatly to patients, families and caregivers. It is a critical part of improving quality of life and making life more meaningful.