Small cell lung cancer: what it is, symptoms, treatment, prognosis

What is small cell lung cancer?

Small cell lung cancer (MRL) - aggressive form lung cancer. It is characterized by the rapid, uncontrolled growth of certain cells in the lungs. Eventually, a tumor forms and the cancer can spread (metastasize) to other parts of the body. The main risk factor is tobacco use; almost all affected people smoke or have previously smoked. Symptoms can vary from one person to another, and rarely any symptoms occur in the early stages of the disease.

Typically, SCLC is divided into two main stages: stage-limited disease, which is potentially curable in about 20-25% of patients, and advanced stage disease, which is more difficult to cure. Patients are often treated with chemotherapy and radiation therapy. Surgery may be recommended for a small group of people with very early stage cancer.

Small cell lung cancer is characterized as neuroendocrine carcinoma because cancer cells have characteristics of nerve cells and endocrine (hormone-secreting) cells. Endocrine tissue is a specialized tissue containing hormone-secreting cells. These hormones have many functions in the body.

Signs and symptoms

The signs and symptoms of small cell lung cancer can vary from one person to the next. The specific signs depend on many factors, including the exact location and size of the tumor, the degree of tumor invasion in nearby tissues or organs, and whether the disease has remained localized or has spread to other areas of the body (metastasized). In the early stages of the disease, there may be no symptoms (asymptomatic) or only mild symptoms. As the tumor grows, more signs and symptoms appear.

Common symptoms include:

• persistent cough;
• chest painthat is aggravated by coughing, laughing, or taking a deep breath;
• shortness of breath (dyspnea);
• hemoptysis (blood in sputum);
• a hoarse, hoarse voice.

Some people may develop loss of appetite, unintentional weight loss, fatigue, and recurrent episodes of lung infections such as pneumonia or bronchitis.

When SCLC spreads (metastasizes), the most commonly affected lymph nodes, the brain, liver, adrenal glands, bones and bone marrow. The symptoms that develop will vary depending on the specific area (s) affected and the extent of the disease. Symptoms may include:

• bone pain due to spread to bones;
• yellowing of the eyes, skin, and mucous membranes (jaundice) as a result of cancer spreading to the liver;
• headaches, dizziness, double vision, cramps or feeling of numbness or tingling in the hands, fingers, feet, and legs if cancer has spread to the brain;
• small formations on the skin when the tumor spreads to the skin or lymph nodes.

Patients with SCLC can also develop paraneoplastic syndromes. These syndromes are rare diseases that are caused either by abnormal hormone production or by an abnormal response of the immune system to cancer. It is believed that white blood cells (leukocytes), which usually help protect the body from bacteria, viruses, and other foreign invaders, can mistake to attack healthy tissue, causing various neurological problems such as weakness, loss of sensation, imbalance or confusion consciousness. The common paraneoplastic syndrome in SCLC is called inappropriate antidiuretic hormone secretion syndrome. This syndrome is characterized by an overproduction of antidiuretic hormone that causes people retain water and reduce salt (sodium) levels in the body, which can cause fatigue, lethargy, and confusion consciousness.

Causes and risk factors

Small cell lung cancer is primarily caused by cancer-causing chemicals (carcinogens) found in tobacco smoke. These carcinogens cause damage to DNA (deoxyribonucleic acid; genes) in cells, leading to cancer. However, the exact reason why normal cells become cancerous is unknown. Most likely, several factors, including genetic and environmental, play a role in the development of SCLC in certain individuals. Current research shows that abnormalities in the DNA, which is the carrier of the body's genetic code, underlie malignant cell transformation.

In SCLC, genetic changes can affect oncogenes or tumor suppressor genes. These gene changes are acquired throughout life; they are not inherited. They are acquired due to exposure to environmental factors such as smoking, or occur accidentally for no known reason (spontaneously). These gene changes are altered or incomplete versions of common genes that normally regulate cell growth and division. An altered oncogene promotes uncontrolled growth (cancer). Tumor suppressor genes usually restrict or stop cell growth. When tumor suppressor genes change (mutate), cells can multiply rapidly (proliferate), causing cancer. When a normal gene is present, they seem to prevent the development of cancer.

There are many different oncogenes or tumor suppressor genes that are associated with small cell lung cancer. Two tumor suppressor genes that have been associated with many SCLC patients are TP53, which has been linked to many types of cancer, and the gene RB1which is associated with retinoblastoma and other types of carcinomas. Gene TP53 changed in 75% of the SCLC, and the gene RB1 changed in 90% of the IRL.

There are several risk factors associated with SCLC. Anything that increases the risk of developing a disease is a risk factor. Having a risk factor does not mean that a person will necessarily develop the disease, and people without risk factors can still develop the disease. The main risk factor for SCLC is smoking, and more than 95% of cases are current or former smokers. Heavy smokers are especially at risk for SCLC. Chronic exposure to secondhand smoke also increases the risk of lung cancer. Other environmental hazards are less common but include exposure to chloromethyl ethers, which are used in chemical production, asbestos or radon. Radon is a colorless, odorless, radioactive gas. It appears naturally in the environment when uranium is decomposed in soil or rock.

Affected populations

The incidence of small cell lung cancer has declined over the past two decades, which most researchers associate with a reduction in smoking in some countries. Lung carcinomas, as a group, are the second most common form of cancer. SCLC accounts for about 10-15% of people with lung cancer. According to the International Agency for Research on Cancer, about 1 million new cases of lung cancer, and 60% of cancer patients die as a result of this diseases. Almost everyone who develops SCLC has smoked in the past. The disease is extremely rare in people who have never smoked.

Diagnostics

The diagnosis of small cell lung cancer is based on the identification of characteristic symptoms, a detailed history of the patient, careful clinical evaluation, and various specialized tests. SCLC is an aggressive cancer, and in people who may be affected, the cancer has already spread after the diagnosis.

- Analyzes and imaging studies.

A plain x-ray (X-ray) of the chest may show a tumor or lump in the lungs. If a mass is found, more specialized imaging techniques can be used to determine if cancer is present, the extent of the disease, and whether the cancer has spread to other areas. Such imaging techniques can include computed tomography (CT), positron emission tomography (PET), and magnetic resonance imaging (MRI). During computed tomography uses a computer and X-rays to create cross-sectional images of the inside of the body. Computed tomography of the chest can show small tumors that are not found on a plain x-ray, and can also show if the tumor has spread to nearby lymph nodes. Computed tomography scans of other areas of the body can show if cancer has spread (metastasized) to certain areas.

Another advanced imaging technique known as positron emission tomography (PET scan) can also be used. During a PET scan radioactive sugar is introduced into the body. This sugar will accumulate in those parts of the body where the need for energy is higher. Tumors require a lot of energy to grow and spread and absorb radioactive sugar. When scanned, areas that absorb radioactive sugar, including small cell lung cancer, may appear as bright spots in the images. PET scans are often used to show if SCLC has spread to other parts of the body. For example, a PET scan can determine if cancer has spread to the bone. Previously, this required a bone scan, but when a PET scan is used, a bone scan is no longer required. Nowadays, PET scans are almost always performed in conjunction with computed tomography (PET / CT).

During a bone scan, a relatively harmless radioactive dye is injected into the blood, which is absorbed by abnormal areas of the bone. A special camera that can detect the dye in the bones is used to create an image of the skeleton to determine if the tumor has spread to other areas of the body.

Magnetic resonance imaging (MRI) uses a magnetic field and radio waves to produce cross-sectional images of selected organs and tissues of the body. An MRI of the brain may be done to determine if the cancer has spread to the brain.

To determine a specific type of carcinoma, a portion of the tumor (biopsy) must be obtained from the lungs or other area of ​​the body. To obtain a sample of the tumor, doctors usually recommend a bronchoscopy or a needle biopsy. During a bronchoscopy, a doctor inserts a bronchoscope through the mouth into the victim's lungs to obtain a tissue sample for analysis (biopsy). Fine needle aspiration - another type of biopsy. It includes a thinner hollow needle that is inserted into the tumor to remove tissue. The needle is attached to a syringe that is used to extract (aspirate) a sample of tissue and fluid from a mass or tumor.

During videothoracoscopy, a thin tube with a built-in camera (thoracoscope) is inserted into the chest through a small surgical incision, which allows the doctor to examine the lungs and obtain tissue samples. This is usually a formal surgical procedure performed in an operating room or similar setting, and general anesthesia with a temporary breathing tube may be required.

Sometimes doctors may prescribe mediastinoscopyto assess whether the cancer has spread to the lymph nodes in the middle chest. This involves making a small incision in the upper sternum, a thin bone that runs down the center of your chest. A small, thin tube called a mediastinoscope runs behind the sternum along the trachea so doctors can view and take samples of mediastinal tissue, i.e. the area between the lungs in the central chest region cells.

- Staging.

The most commonly used staging (classification) system for small cell lung cancer (SCLC) is the VALG classification system. Veterans Administration Lung Group). This system basically divides the disease into two categories - limited stage SCLC and large stage SCLC. Stage limited means the cancer is confined to one side of the chest and can be treated within a single radiation field or port. A radiation field or port is an area of ​​the body where radiation is directed to kill cancer cells. If the cancer is localized in a small area, it can be treated within a single radiation field or port.

The extensive stage is when the cancer has spread beyond one side of the chest. The primary purpose of staging an SCLC is to determine if the cancer has spread to other organs.

The International Association for the Study of Lung Cancer has suggested that doctors adopt a different staging system called the TNM classification system (from the English. The Tumor, Node, Metastasis - tumor, node, metastasis), which is a general cancer classification system developed by the American Joint Committee on Cancer. This system is based on the extent of the tumor (T), the spread of the cancer to the lymph nodes (N) and to what extent, and whether the cancer has spread (metastasized) to other areas of the body (M). This is a more complex staging system.

Standard treatments

Therapeutic management of patients with small cell lung cancer may require the coordinated efforts of a team of medical professionals, such as physicians specializing in diagnosis and drug treatment of cancer (medical oncologists), doctors who specialize in the treatment of cancer with radiation (radiation oncologists), doctors who specialize in on the study of tissues and cells to identify the disease and determine which disease is present (pathologists), doctors who specialize in interpreting X-rays imaging (radiologists), surgeons who specialize in removing cancers by surgery (oncologists), doctors who specialize in diagnosing and treating lung diseases (pulmonologists); cancer nurses (cancer nurses), psychiatrists, nutritionists, and other health professionals.

Psychosocial support is also important for the entire family. Some organizations provide support and information about lung cancer or lung diseases. Patients with SCLC who are still smokers are strongly advised to quit smoking. The importance of quitting smoking cannot be overstated.

Specific therapeutic procedures and interventions can vary depending on many factors, such as:

• stage of the disease;
• the size of the tumor;
• whether the cancer has spread (metastasized) and to which organs it has spread;
• the presence or absence of certain symptoms;
• the age and general health of the patient;
• and / or other elements.

Decisions regarding the use of certain drug regimens and / or other treatments must be made doctors and other members of the medical team after careful consultation with the patient, based on the characteristics of his situations; carefully discussing the potential benefits and risks, including possible side and long-term effects; patient preferences; and other relevant factors.

—​ Limited disease.

In rare cases, people with limited stage small cell lung cancer who have a small tumor that is not has spread to nearby lymph nodes (early stage or stage 1 SCLC), can sometimes be treated with surgery removal of the tumor. However, in most people, the tumor is not localized and, since it is usually a fast-growing cancer, it is often it metastasizes at least to nearby lymph nodes or other areas of the chest.

Most patients with limited stage SCLC are treated simultaneously with chemotherapy and radiation therapy. Chemotherapy Is the use of certain drugs to kill or stop the growth of cancer cells. Cancer cells grow and divide rapidly, making them susceptible to chemotherapy drugs. Various drug combinations can be used; this is called the chemotherapy regimen. The most common chemotherapy regimen used for SCLC is the combination of etoposide with cisplatin or carboplatin. This can be called platinum-based chemotherapy because carboplatin and cisplatin are platinum-containing compounds. Carboplatin generally causes fewer and less serious side effects than cisplatin. SCLC is very sensitive to chemotherapy, and sometimes the improvement can be rapid and significant. However, cancer often recurs and may become resistant to chemotherapy regimens that have been successful in the past.

Radiation therapy It is usually used in combination with chemotherapy (chemoradiotherapy) to treat patients with limited stage SCLC. Radiation therapy uses powerful X-rays to directly destroy cancer cells. Radiation therapy is directed at the chest (thoracic radiation therapy) to the underlying tumor of the lung and to the lymph nodes where the cancer has spread.

Patients who have successfully completed chemotherapy and chest radiation therapy may also receive preventive radiation therapy to the brain, called prophylactic brain radiation brain. Because SCLC is an aggressive cancer and can spread to the brain, radiation prophylaxis used to kill any microscopic cancer cells that may have reached the head brain. Prophylactic brain irradiation is usually given to people who have a good response to initial therapy and who are healthy enough to receive treatment.

About 25% of people with limited stage SCLC can be cured with chemotherapy and radiation therapy.

— Extensive disease.

Treatment for advanced small cell lung cancer is primarily platinum-based chemotherapy, similar to that used for limited stages of the disease. Sometimes, instead of using etoposide with cisplatin or carboplatin, doctors may use a medicine called irinotecan.

The combination of irinotecan with platinum is more effective in the Japanese; in Europeans, etoposide appears to be just as effective and is associated with less serious side effects. It has recently been shown that the addition of an immunotherapy drug called atezolizumab, which boosts the immune system to fight cancer, to a standard regimen of carboplatin plus etoposide improves outcome in some advanced stage patients MRL. However, this combination of drugs has not been approved by the US Food and Drug Administration (FDA).

Although the advanced stage of the disease is incurable, most patients experience a decrease in cancer size, improvement in symptoms, and prolongation of life with chemotherapy. The goals of treatment are to improve symptoms, maintain quality of life, and prolong life. In some situations, after chemotherapy, chest irradiation is recommended for patients with extensive SCLC. Because of the high risk of SCLC spreading to the brain, frequent brain MRI scans are generally recommended.

—​ Relapse.

Although small cell lung cancer is very sensitive to initial chemotherapy, the carcinoma often comes back (relapses). When cancer comes back, it is usually more resistant to previously effective chemotherapy regimens. You can try different chemotherapy regimens, but they are usually not as effective. When cancer comes back, it can be very aggressive. The only second-line drug approved for the treatment of SCLC in the United States is the chemotherapy drug topotecan. Some drugs, other drugs available, do have the ability to reduce or slow down the progression of carcinoma, but the results are generally disappointing. New drugs are currently being investigated in clinical trials for second-line therapy for individuals with SCLC.

In 2017, the FDA approved nivolumab (Opdivo®) for the treatment of SCLC patients in whom cancer has spread (metastasized) and who were previously treated with two types of therapy, including chemotherapy. Nivolumab is a form of immunotherapy. Immunotherapy is the most recent addition to cancer therapy. Nivolumab is designed to use the body's immune system to fight cancer.

—​ Supportive therapy.

Patients may require supportive therapy. Many patients with SCLC have a significant decrease in lung function and need treatment to help breathing. This may include drugs called bronchodilators, which widen the airways of the lungs, or supplemental oxygen therapy.

—​ Clinical trials.

Individuals with the disease are encouraged to explore the possibility of participating in clinical trials. Participation in a clinical trial can give the patient access to new treatments. This decision should be made after careful consultation with the individual oncologist and the entire medical team.

Forecast

The overall 5-year survival rate for patients with small cell lung cancer is 6%. It is important to note that survival depends on several factors, including the stage of the disease. For people with localized SCLC, which means the cancer has not spread outside the lungs, the overall 5-year survival rate is 27%. For regional SCLC, which means that the cancer has spread outside the lung to nearby areas, the 5-year survival rate is 16%. If the carcinoma has spread to a distant part of the body, the 5-year survival rate is 3%. However, some people with advanced lung cancer can live for many years after diagnosis.