Optimal treatment of brain metastases

Brain metastases (mets) are commonly regarded as ominous and are often associated with a very short survival interval. However, with contemporary treatment, these patients can survive for many years. For this reason, whole brain radiotherapy (WBRT), which used to be the most common therapy for metastatic disease in the brain, is rarely necessary. In fact, it should be avoided, if possible, due to associated cognitive decline and poor quality of life that follows.¹ WBRT is a consideration for leptomeningeal carcinomatosis or when there is a very large total volume of metastatic tumors. Some therapies (e.g., immune therapy, some targeted therapies) have brain activity, whereas very few chemotherapy drugs penetrate the brain. Response in the brain, however, is not predictable and often varies from patient to patient. When there is hope that an agent may have central nervous system benefit, careful observation and review of follow-up scans are needed in the event that other treatment is necessary.

From a radiation perspective, most metastatic tumors in the brain are best treated with focal radiosurgery, even when tumors are numerous. This is a paradigm shift from previous thinking that many mets require WBRT. For brain radiosurgery, strong evidence supports the superiority of Gamma Knife® radiosurgery over LINAC-based radiosurgery. Gamma Knife treatment utilizes 196 separate gamma frequency radiation sources housed in the Gamma Knife and aimed at the same point at the same time, providing extreme focus. This results in a huge sparing of radiation to the normal surrounding brain. Larson and colleagues have definitively shown that the volume of brain receiving a radiation dose of any isodose level below the treatment dose is 2.5-3 times the volume as administered with Gamma Knife treatment.²

The Northside Hospital Cancer Institute Gamma Knife Center is the busiest center in the state of Georgia, performing over 200 cases per year. Gamma Knife treatment is generally done with neurosurgery, radiation oncology and medical physics working together as a team. It is important to realize that there is an inverse relationship between the volume of a metastatic tumor in the brain and the response to radiation alone as treatment. Metastatic tumors that are greater than or equal to 2 cm in size only have about a 50% rate of control at only six months’ time with radiation alone.³ As such, if the patient’s survival is substantial and the location of the tumor is operable, it is best for the tumor to be excised. Furthermore, the tumor should be treated with radiosurgery preoperatively and then excised. This algorithm has the advantage of significantly reducing the risk of operative dissemination resulting in carcinomatous meningitis, and reduces the risk of radiation necrosis or adverse radiation reactions in the adjacent brain.⁴

Deep or other inoperable large metastatic tumors are sometimes best treated with “staged Gamma Knife radiosurgery.” In this technique, an initial Gamma Knife procedure is done at a reduced dose compared to single-fraction therapy. A second scan is then done a month or so later, and the new volume, often smaller, is then treated again in a second fraction. This has been found to be a very beneficial technique, and many providers have experienced the purported benefits in reducing toxicity and improving outcomes.⁵

In summary, patients with metastatic brain tumors treated optimally with contemporary techniques may have very long survival. Proof of this can be seen in a personally treated patient managed and followed for over 15 years since the initial diagnosis of multiple brain mets secondary to non-small cell lung carcinoma.

Figures:

The scans below show solitary melanoma metastasis at diagnosis in May 2020 on the left, and the most recent scan in December 2025 on the right. No recurrence in nearly five years and no new tumors.

The patient below had metastatic brain tumors from breast cancer. At diagnosis, multiple tumors were present, including three shown in the image on the left. The latest scan on the right, nearly five years later, shows no active brain tumors.

References: 

1. Masaaki Yamamoto et al., “Stereotactic Radiosurgery for Patients with Multiple Brain Metastases (JLGK0901): A Multi-Institutional Prospective Observational Study,” Lancet Oncology 15, no. 4 (2014): 387–95.
2. Lijun Ma et al., “Gamma Knife Surgery for Brain Metastases from Lung Cancer,” Journal of Neurosurgery 114, no. 6 (2011): 1580–84.
3. Eun Joo Lee et al., “Outcomes of Radiosurgery for Brain Metastases from Breast Cancer,” Journal of Neuro-Oncology 154 (2021): 25–34.
4. Raghu S. Prabhu et al., “Stereotactic Radiosurgery for Large Brain Metastases: Outcomes and Predictors,” International Journal of Radiation Oncology, Biology, Physics 111, no. 3 (2021): 764–72.
5. Cleveland Clinic, “Pioneering Staged Gamma Knife Therapy for Large Brain Metastases,” Consult QD, accessed May 12, 2025, https://consultqd.clevelandclinic.org/pioneering-staged-gamma-knife-therapy-large-brain-metastases.