Brain metastasis occurs when cancer cells from another part of the body spread to the brain. In the past, whole-brain radiation was generally considered when multiple metastases were present in the brain. Today, in selected patients, multiple metastases can be targeted individually with Gamma Knife radiosurgery.
The number of metastases alone is not what matters. The treatment decision is made by considering together the total volume, size, and location of the metastases, as well as the patient’s overall condition and whether the cancer in other parts of the body is under control.
How Many Metastases Can Be Treated with Gamma Knife?
There is no single numerical answer to this question that applies to everyone.
In the large prospective JLGK0901 study, stereotactic radiosurgery outcomes in selected patients with 5–10 brain metastases were shown not to be worse in terms of overall survival than in patients with 2–4 metastases [1]. This study played an important role in questioning rigid limits based solely on the number of metastases.
Current guidelines strongly support stereotactic radiosurgery for 1–4 metastases. In addition, this treatment may be considered for 5–10 metastases in selected patients with good overall condition [2,3]. European guidelines specifically identify a total metastasis volume of approximately less than 15 mL as an important criterion in this group [3].
Gamma Knife may also be used in some patients with more than ten lesions. However, the evidence in this area is based largely on retrospective studies. Therefore, the decision must be individualized [4].
What Is More Important Than the Number?
The presence of 10 very small metastases in one patient may represent a more suitable situation for Gamma Knife than the presence of a single but very large metastasis in another patient.
The following factors are particularly considered in treatment planning:
- Total volume of the metastases
- Diameter of the largest lesion
- Proximity of the lesions to sensitive structures such as the brainstem or visual pathways
- Edema and mass effect in the brain
- The patient’s neurological symptoms
- Overall health status
- Control of the cancer outside the brain
- Whether regular MRI follow-up is possible
Therefore, the question “How many metastases are there?” is important; however, it does not by itself determine the treatment decision.
Can Large Metastases Also Be Treated with Gamma Knife?
Small metastases can generally be treated in a single session. With larger metastases, however, delivering a high dose in a single session may increase the risk of radiation injury.
In this situation, several options may be considered:
- Delivering treatment over several days
- First removing the large mass surgically, followed by radiosurgery to the surgical cavity
- Selecting other radiation therapy methods according to the patient’s condition
Surgery may be more appropriate, particularly for large metastases that cause significant mass effect, severe edema, or rapid neurological deterioration.
Why Might Gamma Knife Be Preferred Instead of Whole-Brain Radiation?
Gamma Knife aims to limit the radiation dose received by healthy brain tissue while delivering a high dose to metastases.
One important advantage of this approach is that it may reduce the risk of impairment in memory and other cognitive functions that may be associated with whole-brain radiation. However, Gamma Knife targets only the metastases visible at the time of treatment; it does not prevent new metastases from developing elsewhere in the brain in the future.
Therefore, regular contrast-enhanced brain MRI examinations are necessary after treatment.
Can Gamma Knife Be Repeated If New Metastases Develop?
Yes. If the patient’s overall condition and the number, volume, and location of the new lesions are appropriate, Gamma Knife can be performed again later.
However, if numerous new metastases develop within a short period, the total tumor burden increases, or leptomeningeal spread is present, whole-brain radiation or systemic treatments may be more appropriate.
Is Gamma Knife Suitable for Every Patient?
No.
Gamma Knife alone may not be sufficient in the presence of very large lesions, severe brain compression, uncontrolled widespread systemic disease, very extensive brain involvement, or leptomeningeal metastasis.
The treatment decision should be made through a joint evaluation by specialists in neurosurgery, radiation oncology, and medical oncology.
Conclusion
The presence of multiple metastases in the brain does not mean that Gamma Knife treatment cannot be performed.
Today, decisions are based not only on the number of metastases but also on the total tumor volume, the size and location of the lesions, the patient’s overall condition, and systemic control of the cancer.
In appropriately selected patients, 5–10, and sometimes more, brain metastases can be treated with Gamma Knife. However, the safe and appropriate limit differs for each patient.
References
- 1. Yamamoto M, Serizawa T, Shuto T, et al. Stereotactic radiosurgery for patients with multiple brain metastases: a multi-institutional prospective observational study (JLGK0901). Lancet Oncology. 2014;15:387–395. doi:10.1016/S1470-2045(14)70061-0.
- 2. Vogelbaum MA, Brown PD, Messersmith H, et al. Treatment for brain metastases: ASCO-SNO-ASTRO guideline. Journal of Clinical Oncology. 2022;40:492–516. doi:10.1200/JCO.21.02314.
- 3. Le Rhun E, Guckenberger M, Smits M, et al. EANO–ESMO clinical practice guidelines for diagnosis, treatment and follow-up of patients with brain metastasis from solid tumours. Annals of Oncology. 2021;32:1332–1347. doi:10.1016/j.annonc.2021.07.016.
- 4. Yamamoto M, Kawabe T, Sato Y, et al. Stereotactic radiosurgery for patients with 10 or more brain metastases. Progress in Neurological Surgery. 2019;34:110–124. doi:10.1159/000493056.