Metastatic melanoma with brain damage

Metastatic melanoma is an oncological disease in which secondary tumors spread throughout the human body in a short period of time.

Intracerebral metastases are the most common tumors in the adult population, localized in the skull.  After the detection of this lesion, the survival statistics are as follows:

• without treatment for an average of 1 month;
• corticosteroid treatment – 2 months;
• after irradiation of the entire brain (OVGM) – 2-7 months;
• when using stereotactic radiosurgery – SRC) - 5.5-14 months;
• when using neurosurgery or radiosurgery in combination with OVGM – 6-15 months.

Referring to the survival statistics of patients with melanoma metastases in the brain, the overall survival is about 4-5 months (Fig. 1).

How often does melanoma metastasize to the brain?

With melanoma, the risk of spreading metastases to the brain is the highest among the most common oncological diseases.  Data on the occurrence of metastases in the brain among patients:

• 55-75% of patients will appear during the course of the disease;

• 6-43% of patients diagnosed with stage IV melanoma already have metastases in the brain;
• in 1/3 of patients with melanoma, neurological symptoms are present when metastases are detected in the brain;

Most often, melanoma metastases to the brain are manifested by hemorrhage into the tumor, and clinically manifested by a stroke-like condition. The peculiarities of intracerebral metastases of melanoma include their tendency to form multiple foci, hematogenous metastasis (Fig. 2). Melanoma is a tumor that is poorly sensitive to ionizing radiation.

How to treat patients?

To determine the tactics of treatment, a diagnosis of the state of the brain is performed. The patient is undergoing magnetic resonance imaging of the brain with contrast enhancement. This is the only way to see the true prevalence of the process in the brain (Fig. 3).

Methods of local control:

- Surgical treatment. It is indicated in the presence of perifocal edema with a mass effect, a rapid increase in neurological symptoms, the presence of hemorrhage in the tumor, the need for histological verification and the size of the focus more than 3 cm.

- Radiation therapy and radiosurgery. It is indicated in cases with multiple brain lesions.

At the same time, these criteria are not absolute and the choice of tactics is determined in each clinical case separately. And the issue of systemic therapy should always be considered.

In recent years, new classes of drugs – BRAF and MEK inhibitors, groups of targeted drugs, as well as anti-CTLA-4 and anti-PD-1/PD-L1 checkpoint inhibitors-have entered the practice of treating metastatic melanoma. The drugs are aimed at activating the immune system and the patient's own defenses. Activated cytotoxic T-lymphocytes have direct antitumor activity, which infiltrate the tumor tissue and cause its death.

The conducted studies demonstrate that the use of modern targeted drugs allows achieving objective responses to therapy in the treatment of metastatic melanoma. Experience from practice shows that patients with progressive melanoma in the brain are subject to treatment, and their survival is measured for years with the right selection of modern therapy.

Case study

The patient, over 60 years old, was diagnosed with stage IIA back skin melanoma in 2006, underwent surgical treatment and then 1 year of interferon therapy. After 7 years, the patient was marked by the progression of the disease – metastases of melanoma in the skin and lymph nodes. Their surgical removal was performed, a month later new metastases appeared, and then targeted therapy with a BRAF-inhibitor was prescribed. After 4 months, all the foci of metastasis disappeared. It was 2015, when BRAF-inhibitor therapy was just being introduced. And the therapy was canceled, which according to modern data was absolutely impossible to do. Which led to a natural result – the progression of the disease after 4 months, which was manifested by metastases to the brain. Neurosurgical and radiotherapy treatment was offered, which the patient refused, then the patient again received targeted therapy with a BRAF inhibitor until April 2016, and a partial reduction in the size of the tumors was achieved.

A further break of 3 months led to the progression of the disease – the continued growth of metastases in the brain and the appearance of new metastases in the main vessels between the head and the heart. Neurosurgical treatment was offered, which the patient refused. Then she was again offered stereotactic radiation therapy.

It was performed in September 2016 and targeted therapy with a BRAF inhibitor was also resumed. Against the background of treatment, the patient had a stabilization of the disease until July 2018. Then there was a continued growth of metastases in the brain, the appearance of metastases in the lymph nodes of the axillary region. The patient was prescribed immunotherapy with an anti-PD-1 inhibitor, which she receives from July 2018 to the present. During treatment, a reduction in the size of tumor foci was achieved, which was confirmed by control MRI of the brain with contrast enhancement and PET / CT of the whole body with 18-FDG, one of the controls is shown in Figure 4.

Thus, despite the statistical data, it was possible to achieve long-term survival of the patient, with the gradual use of modern methods of treatment.

Conclusion

1. Patients with metastases of melanoma in the brain in most cases are subject to treatment.
2. The choice of treatment strategy depends on the prevalence of metastases in the brain and the general condition of the patient.
3. Symptomatic metastases / metastases with a hemorrhage / diameter of more than 30 mm, at the first stage are subject to neurosurgical treatment.
4. Single / asymptomatic/up to 30 mm in diameter-at the first stage, they are subject to stereotactic radiosurgery.
5. Subsequent stages of treatment/multiple metastases-subject to drug treatment.

Conclusions

Patients with brain metastases are a group of patients with a poor clinical prognosis and a short life expectancy. The introduction of new modern methods of treatment into clinical practice can help to improve the survival rate of these patients. The accumulation of clinical experience will contribute to the optimization of approaches in the combined treatment of melanoma metastases in the brain.