Targeted Radiation Therapy Improves Quality of Life Outcomes for Patients with Multiple Brain Metastases

In a Phase 3 randomized trial, Mass General Brigham researchers found that stereotactic radiation targeting individual tumors led to lower symptom burden, better cognitive outcomes, and better day-to-day function when compared with whole brain radiation.

Researchers from Mass General Brigham Cancer Institute have found that using a form of radiation therapy that targets individual tumors rather than whole brain radiation is more optimal for patients with tumors that have spread to the brain (called brain metastases), even if a larger number of tumors are present. The finding could help improve quality of life and cognitive function for many patients diagnosed with brain metastases each year in the United States and beyond. Results from this phase 3 randomized trial comparing patient outcomes have been published in JAMA.

“For patients with brain tumors, quality of life is so important. These results show that expanding the use of stereotactic radiation could minimize patients’ symptom burden and help preserve day-to-day functioning and cognitive abilities,” said lead author Ayal Aizer, MD, MHS, Director of Central Nervous System Radiation Oncology at Brigham and Women’s Hospital and Mass General Brigham Endowed Cancer Chair with Mass General Brigham Cancer Institute.

Previous studies have shown that, for patients with four or fewer brain tumors, stereotactic radiation—which uses focused beams of high-dose radiation to target individual tumors—improves cognitive function without jeopardizing long-term survival, when compared with whole brain radiation. However, patients with larger numbers of brain tumors typically receive whole brain radiation.

Recently, hippocampal-avoidance whole brain radiation, or whole brain radiation that avoids the small part of the brain that is vital to learning and memory, was shown to be better, from a cognitive standpoint, than whole brain radiation without hippocampal-avoidance.

To compare stereotactic radiation with hippocampal-avoidance whole brain radiation in patients with more than four tumors, researchers at Mass General Brigham Cancer Institute randomized 196 patients across four treatment centers to receive either stereotactic radiation or hippocampal-avoidance whole brain radiation. Patients enrolled in the study had between five and 20 brain metastases.

Researchers used a scoring system to assess the severity of symptoms experienced by patients with brain tumors as well as assess how these symptoms interfered with the patients’ daily lives. In patients receiving stereotactic radiation, scores improved six months after radiation, while in those receiving hippocampal-avoidance whole brain radiation, the scores worsened.

Patients managed with stereotactic radiation also displayed better performance status (overall functional capacity) and could remain more independent with everyday activities than those who received hippocampal-avoidance whole brain radiation. Most cognitive tests showed that patients who received stereotactic radiation performed better.

Median survival did not significantly differ between the two groups. New brain tumors were more common among those who received stereotactic radiation versus whole brain radiation (45% versus 24% at one year). However, most new metastases were treated with repeated stereotactic radiation or did not require treatment. In addition, only 3.2% of patients had a recurrence in a tumor treated with stereotactic radiation therapy, compared with 39.5% in patients who received hippocampal-avoidance whole brain radiation therapy.

Approximately 9% of patients in the stereotactic radiation group required subsequent whole brain radiation to treat new brain tumors that later emerged. In other words, stereotactic radiation often allowed patients to avoid whole brain radiation, rather than merely delaying it.

The authors note that limitations of the study include that it was not feasible to blind investigators regarding treatment assignment. In addition, high mortality rates among patients with multiple brain tumors could have impacted data analysis.

Authorship: In addition to Aizer, Mass General Brigham authors include Ivy Ricca, Marciana Johnson, Grant Benham, Beverly Spicer, Eileen Mann, Jennifer Nosker, Michael Parsons, Mallika L. Mendu, Diana D. Shi, Nayan Lamba, Daphne A. Haas-Kogan, Rifaquat Rahman, Fallon Chipidza, Monica Krishnan, Itai Pashtan, Luke Peng, Patrick Y. Wen, and Shyam Tanguturi. Additional authors include Kee-Young Shin, Paul Catalano, Kristin Roper, Jaroslaw Hepel, Brian Alexander, and Paul D. Brown.

Disclosures: Aizer reports research funding from Varian and NH TherAguix. Additional disclosures can be found in the paper.

Funding: This trial was supported by Varian, a Siemens Healthineers Company

Paper cited: Aizer AA et al. “Treatment for Brain Metastases with Stereotactic Radiation vs Hippocampal-Avoidance Whole Brain Radiation: A Randomized Clinical Trial” JAMA DOI: 10.1001/jama.2026.0076