Brain metastases

First reports revealing optimistic results in surgically treated patients who suffered from metastases in brain started to appear in 1933. However during the 80s of the last century, along with development of modern visual diagnostics technologies — computed tomography and magnetic resonance imaging — treatment of metastases in brain broadened its scope. In a period until the 80s of the last century only several studies reported possible efficiency of the surgical therapy, nevertheless the obtained results featured short average survival (up to 6 months) and high post-operative mortality (10-40%). Starting to use modern neurosurgical equipment since 90s of the last century, the post-operative mortality when treating metastases in brain does not exceed 3%.

The main goal of the surgical treatment is resection of all tumour tissues as much as possible and minimum resection of surrounding healthy tissue to obtain a “clear” border of resection. It can be achieved by using the available microneurosurgical equipment, surgical microscope and microneurosurgical instruments. A special care must be taken regarding blood vessels, located close to or crossing pathological tissues supplying the normal, functionally critical tissues.

Even though a surgery is the most invasive treatment method compared to others, it has certain advantages. Where no primary source of a brain metastasis is known, it allows obtaining histological diagnosis and it is very crucial for choosing further additional therapy, especially chemotherapy. A surgical evacuation allows quick decrease in secondary neurological complications, such as intracranial hypertension syndrome (determined by the mass effect of a metastasis and surrounding edema), secondary hydrocephalus or accumulation of cerebrospinal fluid and to prevent wedging of the brainstem.

Post-operative complications basically are neurological (paresis, aphasia, seizures etc.) and they can occur where a metastasis is localised or is positioned near a functionally critical area. Complications without neurological symptoms are also possible, for instance, post-operative hematoma, infected wound, deep vein thrombosis, pulmonary thromboembolism etc.

The main factors triggering them are patient's age > 50 years and weak functional condition of the patient. Contemporary neurosurgical equipment and adequate peri-operative treatment and care usually lower the post-operative complication risk, which stands at 5%-8%.

Before introduction of the whole-brain radiation therapy the survival rate of patients suffering from metastases in brain, starting from diagnosis to death was 1 to 2 months in clinical practice, and until 1954 there were no alternative therapies that could considerably improve the bad prognosis. 

For a long time whole-brain radiation therapy was the only option for treating metastases in brain. Its application improves patients' overall survival by few months, and it was believed that it prevents new metastases from forming, because it kills micrometastases not visible in CT and MRI scans. 

Regardless of improvements in conventional radiotherapy technologies providing increasingly better local and locally regional control of metastases, the average overall survival after the whole-brain radiation therapy as a monotherapy remains constant and is approximately 4-6 months. The long period of therapy is also a significant factor — it can last even up to 3 weeks. 

Role of the whole-brain radiation therapy (WBRT) in treating metastases in brain nowadays is not ambiguous, because it is related to high risk of brain tissue toxicity and consequent cognitive impairment (especially regarding memory and learning skills), as well as loss of autonomous functionality — an ability to function independently. It is a method of choice for patients with one or multiple metastases in brain where no surgical or radiosurgical treatment is an option.

Introduction of radiosurgery in neurooncology has considerably weakened the role of the whole-brain radiation therapy.

Radiosurgery procedure with CyberKnife can be a method of choice for small, hard-to-access metastases in brain. Several large-scale prospective studies have led to a conclusion that radiosurgery with CyberKnife is a method of choice for patients having up to four metastases in brain and it gives average overall survival between 8 and 16 months. Currently it is recognised as an efficient method for treating metastases in brain even where the primary tumour is not controlled. If metastases are treated with radiosurgery, patients’ quality of life can improve significantly. Better results can be achieved if the number of metastases does not exceed 1-4, and total volume capacity of 10 ml. In individual cases patients with more than 5 metastases in brain can be successfully treated, especially if they originate from “radioresistant” primary tumour, such as melanoma or renal cancer. Radiosurgery with CyberKnife is often used in combination with neurosurgery where the metastases cannot be removed fully during a surgery due to their location. In majority of cases radiosurgery ensures high local control of the tumour.

Radiosurgery is not efficient:

• If metastases are large (> 4 cm);
• If there are many metastases;
• If they have prominent mass effect;
• If a histological diagnosis is required.

Comparing treatment efficiency of radiosurgery with CyberKnife and neurosurgery, it was established during several studies that both methods have equal clinical efficiency, however therapy with CyberKnife is safe and non-invasive, performed on out-patient basis, which may be considered as alternative to surgical treatment under certain conditions.

Usually patients tolerate radiosurgery procedure well and it can be performed on out-patient basis or in a day hospital. Treatment complications are reported rarely and usually they are not severe. Most frequent side effects are nausea, vomiting and headache. They mostly disappear within 4-6 weeks. Delayed side effects are usually connected with a treatment result, manifesting 3-6 months after the radiosurgery treatment. Most common of them are edema, radiation necrosis (1-6% patients, out of whom not more than 4% require surgical removal of the necrotic process). In some cases seizures and neurological deficit may manifest in a subacute way, but usually — as a delayed complication. Higher risk of complications is possible in case of larger metastasis when WBRT together with radiosurgery is applied as therapy.

In order to achieve ultimate effect and to reduce a possibility of neglecting a very small-sized metastasis, it is important to use the most advanced diagnostic examinations to prepare the planning of the radiosurgery: 3 Tesla magnetic resonance imaging and at least 64 slice computed tomography scan, but when assessing the results, to perform tests repeatedly with the same equipment as previous one. Thus it is possible to avoid misinterpretation of facts of actual situation of a patient on the moment of control.

Chemotherapy plays a significant role in controlling a systemic disease, however it is not the basic therapy in case of metastases in brain. Chemotherapy medicines mainly do not penetrate brain cells due to hematoencephalic barrier. And the tumour metastasing in the brain has become resistant to chemotherapy, because previously it received an extensive chemotherapy treatment course to handle the underlying disease. Individual targeted therapy medicines can be used to treat metastases in brain, but their application depends directly on the type of the primary tumour.

Even though the radiosurgery with CyberKnife is very efficient method also in treating the metastatic tumours, including metastases in brain, however, it treats tumour nodules only locally, i.e. — they are destroyed in locations where the tumour is being treated, while those areas where no radiation is targeted mainly remain without therapeutic effect. For patients having a progressing tumour after the initial treatment, it is important not only to destroy the newly created tumour lesions — metastases — but also to determine after such local treatment whether there are circulating tumour cells in the blood with a potential to attach to other places of the body and create new metastases, as well as to determine what the genetic structure of the tumour is.

In the Radiosurgery Centre Sigulda we use cutting-edge technologies for testing a metastatic tumour's genome, offered by the tumour genome testing laboratory OncoDNA, located in the Institute of Pathology and Genetics of Belgium. A sample of piece of tumour's tissues, invaded lymph node or blood can be analysed to the tiniest detail in OncoDEEP, OncoTrace and OncoSTRAT&GO tests, thus allowing us understanding the genetic structure of the tumour.

Why is it necessary?

If we can find out what the tumour cells consist of and to what they react, we can administer medicines giving a palpable result, and avoid using those which should be used for similarly localised tumour, but in this particular case would not give any improvement or, even worse, would bring about only toxicity. Genetic testing of a tumour helps a skilled specialist to precisely choose next method of the systemic treatment — chemotherapy, targeted therapy or immunotherapy.

If you are diagnosed with a progressing illness or separate metastases have been found, apply for a consultation at a medical oncologist.

During the consultation it is possible to understand the current course of the illness as well as to receive a recommendation regarding the methods of testing the tumour's genome and to arrange further therapy on the basis of individually sampled cutting-edge chemotherapy and targeted therapy drugs.

If metastases in brain cause oedema in surrounding tissue, it is a common practice to prescribe medications to reduce cerebral oedema before and after a surgery or radiosurgery. Usually medications to treat oedema must be administered for a prolonged period, also after the treatment.

Treatment methods or a combination corresponding to each individual case is not a simple task. A common practice is to apply a combination of several methods, for example, neurosurgery with radiosurgery or whole-brain radiation therapy and chemotherapy. Combination of proper treatment options available allow extending survival rate and keeping the quality of life.

Final decision about choice of a method or their combination depends on clinical neurological situation of a patient, activity of the primary tumour, number and location of metastases.

Even though the major part of patients achieving local control die from the progressing illness outside the brain, the most frequent cause of death is recurring metastases and progressing symptoms of the central nervous system.

Potentially better results in radical treatment can be expected, if patient:

• Is under 65 years of age;
• Has good physically functional condition;
• Has one and easy-to-access metastasis in terms of a surgery, as well as stable / controlled underlying disease.

• Robotic radiosurgery with the CyberKnife® M6 system is an efficient and safe method based on clinical trials — known for more than 10 years;
• Radiosurgery with CyberKnife is a method of choice for patients with up to four metastases in brain;
• When treating metastases in brain with CyberKnife, no prolonged recovery and rehabilitation is required afterwards, side effects are usually milder than those brought about neurosurgery and largely can be controlled with a proper medical treatment.

Expected therapeutic results are based on quantitative clinical research and qualitative clinical research; efficiency is proven in patient surveillance for more than 10 years.

In 87-95% of cases where metastases in brain are treated with CyberKnife, a tumour is expected to stop growing or disappear over next 3 to 6 months after the treatment.

On the basis of several studies on application of CyberKnife in treating metastases in brain, the average expected survival is 8 to 16 months. Individual results depend on several factors:

• Patient’s age;
• Functional and physical condition;
• Number of detected metastases;
• Underlying disease.

Currently it is recognised as an efficient method for treating metastases in brain even where the primary tumour is not controlled. If metastases are treated with radiosurgery, patients’ quality of life can improve significantly.

• If metastases in head have been detected where they already have serious side effects, robotic radiosurgery can be combined with a microsurgery thus reducing the mass effect on other parts of the brain surgically;
• If during a neurosurgery separate larger metastases have been removed, smaller ones can be destroyed with CyberKnife.

Beams from several hundred angles with a precision of a millimetre are targeted on the tumour nodule. It allows linear accelerator of the radiosurgery system CyberKnife® M6 to precisely target the affected tissue while minimising exposure to nearby tissues.

Treatment of metastases in brain with CyberKnife is a painless procedure and requires no post-operative recovery or rehabilitation and it almost does not influence the quality of life.

A patient may lay and breathe freely during the robotic radiosurgery. The device spots even the slightest patient movements and adjusts accordingly. For safety reasons the patient has a light thermoplastic mask during the procedure, and usually it does not cause unpleasant sensations and claustrophobia. Unlike other radiosurgery methods, such as Gammaknife, a patient does not require a stereotactic frame or tight fixation mask, commonly used in other radiosurgery systems.

Radiosurgery with CyberKnife is a treatment on out-patient basis. After the procedure you can go home the same day and no hospital stay is required unless you feel good.

Majority of our patients are satisfied with their choice and an opportunity to finish their tasks.
Radiosurgery with CyberKnife makes patients feel better, because it destroys the tumour's metastases in a comfortable and efficient way, not affecting the quality of life.

Unpredictability of real costs related to the disease can actually make your budget vulnerable:

• Waiting in a queue for the whole-brain radiation therapy and weeks of treatment may interfere with the routine schedule of yours and your relatives;
• Neurosurgery can be related to hardly predictable post-operative care and rehabilitation costs, which are not routinely covered from the state budget,
• Unclear picture of doctor's fee,
• These are issues raising the stress level and leading to anxiety in already complicated period of disease.

We have tried to elaborate our service price list to make costs of diagnostics and therapy transparent and predictable.

However, if you have any question about possible costs, please ask our customer consultants.

View our service price list.

Uncontrolled cell growth, dividing and growth outside the cells they originate from, are the main characteristics of cancer, however severity of this disease lies in fact that it can invade other tissues and organs.

Cancer cells may spread locally (directly) by moving to closest nearby healthy tissue. Cancer may spread also regionally (distally), for example, spreading in nearby lymph nodes, tissues or organs, and cells may travel to distant parts of the body, for example, brain, spine, lungs, kidneys and other organs.

Spread of cancer cells from their primary source to other part of the body is called a metastatic process. Metastases are cancer cells that break away from the initial or primary tumour and enter the bloodstream or lymphatic system from where they travel to other organs or parts of the body, spread and start to divide creating a new tumour nodule.

Cancer of this kind is called a metastatic cancer. But also where several (multiple) metastases are found, the cancer can be treated efficiently and does not necessarily mean a death sentence.

Cancer may spread to almost any part of the body, however it has a tendency to invade certain organs, characteristic to that type of tumour. The most common sites where metastases found are lymph nodes, bones, brain, spine, kidneys and lungs.
Usually the new (metastatic) tumour nodule grow from the same cells as the primary tumour of the same cancer. For example, if a breast cancer spreads to lungs, the cancer cells detected in lungs are cells of the breast cancer rather than cells of the lung cancer. Tumour of that type is called a metastatic breast cancer with a metastasis in lungs rather than the lung cancer.
Recent studies show that metastases can be polymorphous or have varied cell structure, therefore they react differently on the prescribed treatment.

Metastases in brain is the most frequently occurring type of intracranial tumours (24-45% of cancer patients), they are found even more often than primary brain tumours. Metastases in brain are mainly spreading from respiratory organ tumours, melanoma or breast tumour. As the control of underlying disease improves and neuroradiological examinations become more available, the number of such patients is expected to grow in future. Approximately 80% of metastases in brain localise in cerebral hemispheres, 15% — in cerebellum, 5% — in brainstem. Modern treatment of metastases in brain means a combination of different treatment methods and its goal is to extend survival and improve the quality of life of patient to an extent possible.

Metastases in brain are most frequently occurring type of intracranial tumours. Metastases in brain account for 45% of all CNS tumours.

Most often metastases in brain originate from:

• Lung and bronchial tumours (48%);
• Breast cancer (15%);
• Melanoma (10%);
• Genitourinary system tumours (~9%);
• Osteosarcoma (~9%);
• Head and neck tumours (6%);
• Gastrointestinal system tumours (3%);
• Lymphomas (1%).
• When treating primary tumours in body, 10-40% of patients have metastases in brain detected during their lifetime.

Even though approximately 80% of patients are diagnosed with metastases in brain in case of already known primary tumour, sometimes cancer metastases in brain are diagnosed concurrently with the primary disease or even before the primary tumour is identified. In up to 10% of cases the metastases allow identifying the primary tumour. There are cases when the primary tumour cannot be found.

If a metastasis in brain is a single lesion and is not a part of a metastatic process, it is called a solitary metastasis (metastasis in brain)

Where there are two to three metastases, they are called ogliometastases, but four and more metastases are called multiple metastases.

A single or solitary metastasis is most common in case of a primary breast cancer, colorectal cancer and renal cell carcinoma, whereas lung cancer and especially melanoma usually make several metastases in brain.

Patients diagnosed with metastases in head have worse prognosis both in terms of expected survival and lowering of quality of life.

If no proper treatment is applied since the moment the metastases are detected in head, patients usually die in few months’ time.

Prognosis of average survival for patients with several metastases is worse (2.3-7.1 months) and depend on the type of tumour, number of metastases, position in the brain and size).

Metastases in brain may be asymptomatic or cause no prominent manifestations. However, most frequent symptoms are those encouraging to look for the source of a problem, and eventually leading to finding of metastases.

Most frequent manifestations of metastases in brain:

• Headache;
• Nausea, vomiting;
• Seizures;
• Paresis or palsy (full or partial loss of senses, sensitivity or movements);
• Communication and cognitive disorders (speech disorders, memory and judgement disorders).

Complications often have a negative impact on the patient's quality of life creating functional restrictions, limiting involvement in social events and triggering changes in personality. In order to reduce the risk of potential complications and improve survival prognosis and quality of life, early diagnostics of metastases in brain is crucial.

Metastases are most often found where a patient notices various neurological, communication and/or cognitive disorders. It is a common practice to refer patients with such symptoms to a computed tomography (CT) scan to exclude stroke or haemorrhage finding in the brain. If a CT scan raises suspicions about a metastatic process, it is advisable to perform high quality magnetic resonance imaging (MRI) scan. If the MRI scan is performed properly, it is possible to detect tumour lesions of 2-5 mm in size in the brain, however most commonly tumours exceeding 5 mm in diameter are found.

Comparing results of CT and MRI with a contrast agent, it has been established that the CT scan reveals one metastasis in patients, whereas the MRI scan reveals several metastases in brain.

Metastases in brain are easy to visualise with MRI (with a contrast agent), however, if the situation is not clear, other diagnostic methods can be recommended: computed tomography, positron emission tomography or angiography. If visual diagnostics do not show a convincing result, a biopsy can be performed by professional team of neurosurgeons.

Different types of primary cancer have varied tendency to create metastases in brain. Metastases in brain are mainly created by lung cancer as well as breast cancer, melanoma, colorectal cancer and renal cell cancer. Melanoma, a relatively seldom occurring tumour (accounts for approximately 1% of all tumours detected) is highly inclined to metastasise in the brain. It must be noted that melanomas, which are localised in neck and head area, has the strongest capacity to metastasise in brain, if compared to other possible localisations of primary melanomas.

Care and treatment of patients suffering from metastases in brain are usually related to additional financial burden on the patient and his or her relatives. Therefore early diagnosing of metastases in brain is crucial. Timely diagnostics allows using radiosurgery to treat metastases thus reducing potential risk of complications and improving survival prognosis and quality of life.

If you are not sure whether your disease (cancer) can progress and create metastases, do not hesitate to call our consultants or apply for a consultation at our specialists.