Lung cancer and brain metastasis

According to Professor Rafal Dziadziuszko, head of the Department of Oncology and Radiotherapy at the Medical University of Gdansk, ALK+ lung cancer is diagnosed in about 5 percent of patients in Poland These are often younger people, patients are usually 35-55 years old at the time of diagnosis and are at an important point in their professional and family lives. They are often people with young children, in the midst of intense professional development. Meanwhile, they are suddenly confronted with an illness that forces them to redefine their activities in all fields of life.

The clinical course of the disease is characteristic and often different from most courses of other lung cancers.

- It is an aggressive cancer with a high incidence of pleural fluid and metastasis to the central nervous system, liver, bone and lymph nodes. Symptoms associated with the course of the disease are often due to distant metastases. These include bone pain, headaches or shortness of breath resulting from pleural fluid, also requiring drainage of the pleural cavity," explains Professor Rafal Dziadziuszko.

The diagnostic standard for assessing the severity of the disease and the presence of metastases in the central nervous system is computed tomography and magnetic resonance imaging of the brain. The examination is performed at the beginning of treatment and at the onset of characteristic symptoms.

Until a decade ago, the diagnosis meant a verdict, as patients survived only about a year. Since Japanese scientists described the discovery in 2007 of the ALK gene rearrangement and the resulting biological mechanism associated with disease progression, there have been at least five effective drugs that are now available in Poland. These are ALK inhibitors, which were first introduced into clinical practice in Poland about 10 years ago.

- From the point of view of both the course of the disease and the results of treatment, today the fate of these patients is significantly different. The survival period is many years, and I also have patients I have been treating since we gained access to drugs. Patients are often able to enjoy normal functioning thanks to them. Most often, they return to work and to a normal life. What's more, treatment is provided in an outpatient setting. It is often the case that during those few years my patients have been in the hospital only once, at the time of the disease diagnosis, or not at all," points out Prof. Dziadziuszko.

The latest drugs are third-generation ALK inhibitors, such as lorlatinib. They offer greater treatment options compared to older therapies, primarily by improving penetration into the central nervous system, which is a "special concern" site for the disease. This is because it is the location where metastasis often occurs. For the body, on the other hand, it is a kind of control tower. If a problem arises in this area, the situation significantly affects the patient's functioning. New-generation drugs are the result of the efforts of researchers over the past decade to create and introduce drugs with the best possible safety profile, with good penetration into the CNS.

- In Poland, third-generation inhibitors are drugs that are reserved for treating failures after older inhibitors. First-generation drugs are practically no longer used, due to suboptimal penetration into the brain. We try to use these new drugs as early as possible, according to the principle of "the best drug as early as possible." Undoubtedly, this has an impact on the fate of patients," points out the head of the Department of Oncology and Radiotherapy at the Medical University of Gdansk.

- Both second- and third-generation inhibitors are recommended for first-line treatment, so that the protective effect on the brain is as strong as possible and the time to disease progression is as long as possible. The treatment of drug choice is, of course, individual and depends on the patient's other diseases, the professor adds.

Patients and doctors also need better access to molecular diagnostics so that ALK gene rearrangement determination is at the highest possible level and carried out as soon as possible in every patient diagnosed with non-small cell lung cancer. Early diagnosis and rapid implementation of the most advanced therapies will avoid the appearance of CNS metastases.

- Classically, patients with brain metastases were treated locally, i.e. with precise irradiation only to the metastatic area, and later were treated systemically. Today we know that this direction should be changed. For effective systemic drugs, we reserve radiation for later. Radiation therapy is completely safe for the patient, and if it can be delayed with effective systemic treatment that also protects the disease elsewhere, it should be done," believes Prof. Rafal Dziadziuszko.