Preop Stereotactic Radiotherapy Tied to Improved Brain Metastases Outcomes

By Marilynn Larkin

March 29, 2022

NEW YORK (Reuters Health) - In cancer patients with brain metastases, preoperative stereotactic radiotherapy (SRT) is associated with improved outcomes compared to no SRT, including a higher rate of necrosis and decreases in immunomodulatory cell populations, a small trial shows.

"Some of the findings, such as increased tumor necrosis, corroborated findings from preclinical studies and stereotactic radiosurgery (SRS) series outside of the brain, but some of the findings, such as the change in immunomodulatory cell populations, were interesting and require further study," Dr. Rupesh Kotecha of the Miami Cancer Institute, Baptist Health South Florida told Reuters Health by email.

Tumor samples from 22 patients (ages 35-80; two-thirds, women) who underwent dose-escalated pre-operative SRS/SRT and resection for brain metastases were included in the study, published in Scientific Reports. Samples were paired and compared with non-irradiated primary tumor samples.

Non-small cell lung cancer was the most common primary tumor (41%), followed by gynecologic malignancies (18%), breast cancer (14%), melanoma (9%), gastrointestinal (9%), and genitourinary (9%).

The median tumor diameter was 3.6 cm and the median gross tumor volume was 14.20 cm3.

Patients were given a median preoperative SRT dose of 18Gy in 1 fraction, with 3 receiving 27-30Gy in 3-5 fractions, followed by resection within a median interval of 67.8 h. The median duration from SRS/SRT to resection was 67.8 h.

As Dr. Kotecha noted, the rate of necrosis was significantly higher in irradiated than in non-irradiated primary tumors, and irradiated metastases demonstrated decreases in all immunomodulatory cell populations - CD3+, CD4+, CD8+ - compared to primary tumors.

The median follow-up was 12.3 months, and the 1-year freedom from local failure was 95%.

Dr. Kotecha said, "Our next steps are to continue to collect tissue samples from patients who undergo pre-operative SRT and perform advanced genomic and proteomic analysis. In parallel, we would also like to collect tissue samples from patients who undergo resection alone (without pre-operative radiotherapy) to help tease out differences from radiotherapy, and differences from brain metastasis biology compared to primary tumors."

Dr. John Suh, Chairman of Radiation Oncology at Cleveland Clinic, commented in an email to Reuters Health, "Given the small sample size of this study, the findings need further validation to determine the impact of the acute changes seen on histopathology and immune markers and the safety and efficacy of dose-escalated pre-operative SRT for (these) patients."

"Enrollment of patients into trials comparing (pre-operative and post-operative SRS and SRT) approaches is encouraged to determine optimal treatment strategies, "he said. "In addition, the use of dose-escalated pre-operative SRS and SRT should be performed as part of a clinical trial until more data is available."

Dr. Steve Braunstein, SRS Program Co-director University of California, San Francisco, also commented by email. "Longer term follow up of patients to characterize the risk of radiation necrosis will be important in the setting of dose-escalation, which can impact normal regional brain tissue. There are ongoing multi-institutional cooperative group efforts to further examine optimal patient selection, dosing and timing strategies for the use of preoperative radiosurgery."

"Notably," he added, "the logistics of preoperative radiosurgery can be complex, as urgent surgical decompression without delay may need to be prioritized in select cases."

SOURCE: Scientific Reports, online March 16, 2022.