Brain metastases

Brain metastases are the most common tumors in the brain in adults, occurring in 10–15 out of 100,000 individuals annually. In 30-50% of cases, they are singular metastases. However, multiple brain metastases are often already present *. Primary tumors of brain metastases are mainly tumors in the lung, breast, skin, colon and kidney. Of these primary tumors, melanoma, the black skin cancer, has the highest tendency to metastasize to the brain *. In about 10% of cases, the primary tumor is unknown when a brain metastasis is first diagnosed, which means that the metastasis in the brain is the patient's first symptom.

Brain metastases are the most common cause of neurological complications in tumor diseases, which are no longer localized to one organ but affect the whole body *. About 10–15% of all patients with systemic tumor disease develop brain metastases *, *. 

If the metastases are located in eloquent brain areas or close to them, they often cause symptoms such as failures of the visual field, speech disorders, sensory disturbances or reductions in strength. However, depending on the location and number of brain metastases, the symptoms of brain metastases are varied. For example, if a metastasis blocks the drainage of cerebrospinal fluid, it can lead to a buildup with headaches, nausea and vomiting. Also common are first-ever epileptic seizures or headaches as the most common leading symptom *.

• Headaches 24%
• Disturbances of functions (e.g., paralysis, visual disturbances, speech disturbances) 20%
• Cognitive and behavioral changes 14%
• Epileptic seizures (focal or generalized) 12%
• Ataxia (disturbances of movement coordination) 7%

In contrast, the incidental discovery of brain metastases during cranial imaging, without patients having had prior symptoms, is relatively rate at only about 7%  *.

If a brain metastasis is detected by imaging without a known primary tumor, further imaging of the chest and abdomen is performed to find the primary tumor as soon as possible. If a metastasis to the meninges is suspected, a rare and serious complication of tumor diseases, a diagnosis can also be made by sampling cerebrospinal fluid from the spinal canal, as the tumor cells can often be detected here.

In the past, brain metastases were indicative of end-stage systemic tumor disease with only a few weeks of survival remaining *. In the mid-20th century, the establishment of whole-brain radiation and the use of steroids resulted in a significant improvement in the average survival time as well as the quality of life of patients *.

Until 1990, surgical removal (resection) of brain metastases was highly controversial. Then two scientific studies *, * were able to demonstrate the clear benefit of surgical removal of brain metastases with supporting data.

Nowadays, the treatment of brain metastases is always carried out in a multidisciplinary approach, in which surgical resection plays a very decisive role in the success of the therapy. At Inselspital, each individual patient is discussed within the framework of our interdisciplinary neuro-oncological tumor board. Neurosurgeons, neurologists, neuroradiologists, oncologists and radiation oncologists jointly determine the optimal therapy for each individual patient.

Especially if no information on the primary tumor is available, a tissue sample is crucial for further therapy, because depending on the tumor, the response to further treatment by radiotherapy can vary greatly. For example, metastases from renal cell carcinoma and from melanoma respond significantly worse to standard radiotherapy than metastases from small cell lung cell carcinoma *. Radiosurgery is therefore more successful in the former.

Assuming the tumor in the body is treated, under control, or cured, there are 3 major problem areas in the therapy of brain metastases:

• Brain metastases resistant to conventional standard radiation therapy (e.g., renal cell carcinoma, melanoma)
• Multiple brain metastases
• Local recurrences after surgery (approximately 30–40% in the literature).
• Subsequent metastases that were not visible at first (too small, or developed later, in 50% of patients

These constellations require different combinations of therapy methods.

Also in case of recurrent brain metastases, a new surgical resection is often possible *, *. This is especially true in young patients in good general condition. Especially radiotherapy and radiosurgery can be applied a maximum of two times. In surgery, only the proximity of the important functional areas determines the possibility of re-treatment. Again, a personalized approach according to patient and tumor type applies.

The current guidelines for the treatment of brain metastases were published by the European Association of Neuro-Oncology in 2017 and provide a foundation in the interdisciplinary treatment of brain metastases.

With neurosurgical operation and radiosurgery, procedures are available that enable effective treatment of local metastases. Whether patients can be cured depends mostly on whether the primary tumor can be controlled and cured and whether systemic spread of the cancer can be prevented. If these conditions are met, a patient with brain metastases can be cured.