Lung cancer grade 3 small cell. What is small cell lung cancer

Instrumental methods for diagnosing small cell lung cancer (X-ray, CT, bronchoscopy, etc.) must be confirmed by the results of a biopsy of the tumor or lymph nodes, cytological analysis of pleural exudate. Surgical treatment of small cell lung cancer is advisable only in the early stages; the main role is given to polychemotherapy and radiation therapy.

Small cell lung cancer

Small cell lung cancer is one of the rapidly proliferating tumors with a high malignancy potential. In pulmonology, small cell lung cancer is much less common (15–20%) than non-small cell lung cancer (80–85%), but it is characterized by rapid development, seeding of the entire lung tissue, earlier and extensive metastasis. In the vast majority of cases, small cell lung cancer develops in patients who smoke, more often in men. The highest incidence is recorded in the age group. Almost always, the tumor begins to develop as a central lung cancer, but very soon metastasizes to the bronchopulmonary and mediastinal lymph nodes, as well as to distant organs (skeletal bones, liver, brain). Without special anticancer treatment, the median survival is no more than 3 months.

Causes of small cell lung cancer

The main and most significant cause of small cell lung cancer is tobacco smoking, and the main aggravating factors are the patient's age, nicotine addiction experience and the number of cigarettes smoked per day. In connection with the increasing prevalence of addiction among women in recent years, there has been a trend towards an increase in the incidence of small cell lung cancer among the fairer sex.

Other potentially significant risk factors include: hereditary burden of oncopathology, unfavorable ecology in the region of residence, harmful working conditions (contact with arsenic, nickel, chromium). The background against which lung cancer most often occurs can be tuberculosis of the respiratory organs, chronic obstructive pulmonary disease (COPD).

The problem of histogenesis of small cell lung cancer is currently considered from two positions - endodermal and neuroectodermal. Proponents of the first theory are inclined to the point of view that this type of tumor develops from the cells of the epithelial lining of the bronchi, which are similar in structure and biochemical properties to small cell carcinoma cells. Other researchers are of the opinion that the cells of the APUD system (diffuse neuroendocrine system) give rise to the development of small cell carcinoma. This hypothesis is confirmed by the presence of neurosecretory granules in tumor cells, as well as an increase in the secretion of biologically active substances and hormones (serotonin, ACTH, vasopressin, somatostatin, calcitonin, etc.) in small cell lung cancer.

Classification of small cell lung cancer

Staging of small cell carcinoma according to the international TNM system does not differ from that for other types of lung cancer. However, until now, a classification is relevant in oncology that distinguishes between localized (limited) and widespread stages of small cell lung cancer. The limited stage is characterized by a unilateral tumor lesion with an increase in hilar, mediastinal and supraclavicular lymph nodes. In the advanced stage, there is a transition of the tumor to the other half of the chest, cancerous pleurisy, metastases. About 60% of detected cases are in the advanced form (III-IV stage according to the TNM system).

In morphological terms, within small cell lung cancer, oat cell carcinoma, intermediate cell type cancer, and mixed (combined) oat cell carcinoma are distinguished. Oat cell carcinoma is microscopically represented by layers of small spindle-shaped cells (2 times larger than lymphocytes) with rounded or oval nuclei. Cancer from cells of the intermediate type is characterized by cells of a larger size (3 times more than lymphocytes) of a round, oblong or polygonal shape; cell nuclei have a clear structure. A combined histotype of a tumor is said to occur when the morphological features of oat cell carcinoma are combined with those of adenocarcinoma or squamous cell carcinoma.

Symptoms of small cell lung cancer

Usually the first sign of a tumor is a prolonged cough, which is often regarded as smoker's bronchitis. An alarming symptom is always the appearance of an admixture of blood in the sputum. Also characterized by chest pain, shortness of breath, loss of appetite, weight loss, progressive weakness. In some cases, small cell lung cancer clinically manifests with obstructive pneumonia caused by bronchus occlusion and atelectasis of a part of the lung, or exudative pleurisy.

In the later stages, when the mediastinum is involved in the process, a mediastinal compression syndrome develops, including dysphagia, hoarseness due to paralysis of the laryngeal nerve, signs of compression of the superior vena cava. Often there are various paraneoplastic syndromes: Cushing's syndrome, Lambert-Eaton's myasthenic syndrome, syndrome of inadequate secretion of antidiuretic hormone.

Small cell lung cancer is characterized by early and widespread metastasis to the intrathoracic lymph nodes, adrenal glands, liver, bones and brain. In this case, the symptoms correspond to the localization of metastases (hepatomegaly, jaundice, pain in the spine, headaches, bouts of loss of consciousness, etc.).

For a correct assessment of the degree of prevalence of the tumor process, clinical examination (examination, analysis of physical data) is supplemented by instrumental diagnostics, which is carried out in three stages. At the first stage, visualization of small cell lung cancer is achieved using radiation methods - chest X-ray, CT of the lungs, positron emission tomography.

The task of the second stage is the morphological confirmation of the diagnosis, for which bronchoscopy with biopsy, pleural puncture with exudate sampling, lymph node biopsy, and diagnostic thoracoscopy are performed. Subsequently, the obtained material is subjected to histological or cytological analysis. At the final stage, MSCT of the abdominal cavity, MRI of the brain, and skeletal scintigraphy allow to exclude distant metastasis.

Treatment and prognosis of small cell lung cancer

Accurate staging of small cell lung cancer determines the possibility of its surgical or therapeutic treatment, as well as predicting survival. Surgical treatment of small cell lung cancer is indicated only in the early stages (I-II). But even in this case, it is necessarily supplemented by several courses of postoperative polychemotherapy. With this scenario of patient management, the 5-year survival rate within this group does not exceed 40%.

The rest of patients with a localized form of small cell lung cancer are prescribed from 2 to 4 courses of treatment with cytostatics (cyclophosphamide, cisplatin, vincristine, doxorubicin, gemcitabine, etoposide, etc.) in monotherapy or combination therapy in combination with irradiation of the primary focus in the lung, lymph nodes root and mediastinum. When remission is achieved, prophylactic irradiation of the brain is additionally prescribed to reduce the risk of its metastatic lesion. Combination therapy can extend the life of patients with localized form of small cell lung cancer by an average of 1.5-2 years.

Patients with locally advanced stage of small cell lung cancer are shown to undergo 4-6 courses of polychemotherapy. With metastatic lesions of the brain, adrenal glands, bones, radiation therapy is used. Despite the sensitivity of the tumor to chemotherapy and radiotherapy, recurrences of small cell lung cancer are very frequent. In some cases, relapses of lung cancer are refractory to anticancer therapy - then the average survival usually does not exceed 3-4 months.

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Small cell lung cancer

One of the most common and intractable diseases among men is small cell lung cancer. At the initial stage, the disease is quite difficult to recognize, but with timely treatment, the chances of a favorable outcome are high.

Small cell lung cancer is one of the most malignant tumors according to the histological classification, which proceeds very aggressively and gives extensive metastases. This form of cancer makes up about 25% of other types of lung cancer and, if it is not detected at an early stage and properly treated, is fatal.

For the most part, this disease affects men, but recently there has been an increase in the incidence among women. Due to the absence of signs of the disease in the early stages, as well as the rapid growth of the tumor and the spread of metastases, in most patients the disease takes an advanced form and is difficult to cure.

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Causes

Smoking is the first and most important cause of lung cancer. The age of a person who smokes, the number of cigarettes per day, and the duration of the habit affect the likelihood of developing small cell lung cancer.

A good prevention is to give up cigarettes, which will significantly reduce the possibility of the disease, however, a person who has ever smoked will always be at risk.

Smokers are statistically 16 times more likely to get lung cancer than non-smokers and 32 times more likely to be diagnosed with lung cancer in those who started smoking in adolescence.

Nicotine addiction is not the only factor that can trigger the disease, so there is a possibility that non-smokers can also be among those with lung cancer.

Heredity is the second most important reason that increases the risk of the disease. The presence of a special gene in the blood increases the likelihood of getting small cell lung cancer, so there are fears that those people whose relatives suffered from this type of cancer may also get sick.

Ecology is the reason that has a significant impact on the development of lung cancer. Exhaust gases and industrial waste poison the air and enter the human lungs with it. Also at risk are people who have frequent contact with nickel, asbestos, arsenic or chromium due to their professional activities.

Severe lung disease is a prerequisite for the development of lung cancer. If a person has suffered from tuberculosis or chronic obstructive pulmonary disease during his life, this can cause the development of lung cancer.

Symptoms

Lung cancer, like most other organs, does not bother the patient at the initial stage and does not have pronounced symptoms. You can notice it with timely fluorography.

Depending on the stage of the disease, the following symptoms are distinguished:

• the most common symptom is a persistent cough. However, it is not the only accurate sign, since smokers (namely, they have a malignant tumor diagnosed more often than non-smokers) have a chronic cough even before the disease. At a later stage of cancer, the nature of the cough changes: it intensifies, is accompanied by pain and expectoration of bloody fluid.
• with small cell lung cancer, a person often experiences shortness of breath, which is associated with difficulty in the flow of air through the bronchi, which disrupts the proper functioning of the lung;
• at stages 2 and 3 of the course of the disease, sudden fevers or a periodic increase in temperature are not uncommon. Pneumonia, which smokers often suffer from, can also be one of the signs of lung cancer;
• systematic pain in the chest when coughing or trying to take a deep breath;
• bleeding of the lungs, which are caused by the germination of the tumor in the pulmonary vessels, is of great danger. This symptom indicates the neglect of the disease;
• when the tumor grows in size, it is able to depress neighboring organs, which can result in pain in the shoulders and limbs, swelling of the face and hands, difficulty swallowing, hoarseness in the voice, prolonged hiccups;
• at an advanced stage of cancer, the tumor seriously affects other organs, which further worsens the unfavorable picture. Metastases that have reached the liver can provoke jaundice, pain under the ribs, brain metastases lead to paralysis, loss of consciousness and disorders of the speech center of the brain, bone metastases cause pain and aches in them;

All of the above symptoms may be accompanied by sudden weight loss, loss of appetite, chronic weakness and fatigue.

Based on how intensely the symptoms manifest themselves and how timely a person seeks help from a doctor, one can make a forecast about the chances of his recovery.

Learn more about early stage lung cancer symptoms here.

Diagnostics

Adults, and especially smokers, should be periodically examined for lung cancer.

Diagnosis of a tumor in the lung consists of the following procedures:

1. Fluorography, which allows to detect any changes in the lungs. This procedure is carried out during a medical examination, after which the doctor prescribes other examinations that will help in making the correct diagnosis.
2. Clinical and biochemical analysis of blood.
3. Bronchoscopy is a diagnostic method in which the degree of lung damage is studied.
4. A biopsy is the surgical removal of a sample of a tumor to determine the type of tumor.
5. X-ray diagnostics, which includes X-ray examination, magnetic resonance imaging (MRI) and positive emission tomography (PET), which allow determining the location of tumor foci and clarifying the stage of the disease.

Video: About the early diagnosis of lung cancer

Treatment

The tactics of treating small cell lung cancer is developed based on the clinical picture of the disease and the general well-being of the patient.

There are three main ways to treat lung cancer, which are often used in combination:

1. surgical removal of the tumor;
2. radiation therapy;
3. chemotherapy.

Surgical removal of the tumor makes sense at an early stage of the disease. Its purpose is to remove the tumor or part of the affected lung. This method is not always possible in small cell lung cancer due to its rapid development and late detection, therefore, more radical methods are used for its treatment.

The possibility of surgery is also excluded if the tumor affects the trachea or neighboring organs. In such cases, immediately resort to chemotherapy and radiation therapy.

Chemotherapy for small cell lung cancer can give good results if used in a timely manner. Its essence lies in taking special drugs that destroy tumor cells or significantly slow down their growth and reproduction.

The patient is prescribed the following drugs:

The drugs are taken at intervals of 3-6 weeks and for the onset of remission, at least 7 courses must be completed. Chemotherapy helps reduce the size of the tumor, but cannot guarantee complete recovery. However, she can prolong the life of a person even at the fourth stage of the disease.

Radiation therapy, or radiotherapy, is a method of treating cancer with gamma rays or x-rays to kill or slow down the growth of cancer cells.

It is used for an inoperable lung tumor, if the tumor affects the lymph nodes, or if it is not possible to perform an operation due to the unstable condition of the patient (for example, a serious illness of other internal organs).

In radiation therapy, the affected lung and all areas of metastasis are subject to radiation. For greater effectiveness, radiation therapy is combined with chemotherapy, if the patient is able to tolerate such combined treatment.

Palliative care is one of the possible options for helping a patient with lung cancer. It is applicable when all possible methods to stop the development of the tumor have failed, or when lung cancer is detected at a very late stage.

Palliative care is designed to ease the last days of the patient, provide him with psychological help and pain relief for severe symptoms of cancer. Methods of such treatment depend on the condition of the person and are purely individual for each.

There are various folk methods for the treatment of small cell lung cancer, which are popular in narrow circles. In no case should you rely on them and self-medicate.

Every minute is important for a successful outcome, and often people waste precious time in vain. At the slightest sign of lung cancer, you should immediately consult a doctor, otherwise a fatal outcome is inevitable.

The choice of a method of treating a patient is an important stage on which his future life depends. This method should take into account the stage of the disease and the psycho-physical condition of the patient.

The article will tell about what the radiation diagnosis of central lung cancer is.

You can learn more about the methods of treating peripheral lung cancer in this article.

How long do people live (life expectancy) with small cell lung cancer

Despite the transient course of small cell lung cancer, it is more sensitive to chemotherapy and radiotherapy compared to other forms of cancer, therefore, with timely treatment, the prognosis can be favorable.

The most favorable outcome is observed when cancer is detected at stages 1 and 2. Patients who start treatment on time can achieve complete remission. Their life expectancy already exceeds three years and the number of cured is about 80%.

At stages 3 and 4, the prognosis worsens significantly. With complex treatment, the patient's life can be extended by 4-5 years, and the percentage of survivors is only 10%. If untreated, the patient dies within 2 years from the date of diagnosis.

Lung cancer is one of the most common oncological diseases, which is very difficult to cure, but there are many ways to prevent its occurrence. First of all, it is necessary to cope with nicotine addiction, avoid contact with harmful substances and regularly undergo a medical examination.

Timely detection of small cell lung cancer in the early stages significantly increases the chances of defeating the disease.

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Do not self-medicate. Consult with your physician.

Small cell lung cancer

In the structure of oncological diseases, lung cancer is one of the most common pathologies. It is based on a malignant degeneration of the epithelium of the lung tissue, a violation of air exchange. The disease is characterized by high mortality. The main risk group is made up of older men who smoke. A feature of modern pathogenesis is a decrease in the age of primary diagnosis, an increase in the likelihood of lung cancer in women.

Small cell carcinoma is a malignant tumor that has the most aggressive course and widespread metastasis. This form accounts for about 20-25% of all types of lung cancer. Many scientific experts regard this type of tumor as a systemic disease, in the early stages of which, there are almost always metastases in the regional lymph nodes. Men suffer from this type of tumor most often, but the percentage of sick women is growing significantly. Almost all patients have a fairly severe form of cancer, this is due to the rapid growth of the tumor and widespread metastasis.

Causes of small cell lung cancer

In nature, there are many reasons for the development of a malignant neoplasm in the lungs, but there are the main ones that we encounter almost every day:

• smoking;
• exposure to radon;
• asbestosis of the lungs;
• viral damage;
• dust impact.

Clinical manifestations of small cell lung cancer

Symptoms of small cell lung cancer:

Fatigue and feeling weak

• a cough of a prolonged nature, or a newly appeared cough with changes in the patient's usual;
• lack of appetite;
• weight loss;
• general malaise, fatigue;
• shortness of breath, pain in the chest and lungs;
• voice change, hoarseness (dysphonia);
• pain in the spine with bones (occurs with bone metastases);
• epileptic seizures;
• lung cancer, stage 4 - there is a violation of speech and severe headaches appear.

Grades of small cell lung cancer

1. Stage 1 - the size of the tumor in diameter up to 3 cm, the tumor affected one lung. There is no metastasis.
2. Stage 2 - the size of the tumor in the lung is from 3 to 6 cm, blocks the bronchus and grows into the pleura, causing atelectasis;
3. Stage 3 - the tumor rapidly passes, its size has increased from 6 to 7 cm to neighboring organs, atelectasis of the entire lung occurs. Metastases in neighboring lymph nodes.
4. Stage 4 small cell lung cancer is characterized by the spread of malignant cells to distant organs of the human body, which in turn causes symptoms such as:

• headache;
• hoarseness or even loss of voice;
• general malaise;
• loss of appetite and a sharp decrease in weight;
• back pain, etc.

Diagnosis of small cell lung cancer

Despite all the clinical examinations, history taking and listening to the lungs, a qualitative diagnosis of the disease is also necessary, which is carried out using methods such as:

• skeletal scintigraphy;
• chest x-ray;
• detailed, clinical blood test;
• computed tomography (CT);
• liver function tests;
• magnetic resonance imaging (MRI)
• positron emission tomography (PET);
• sputum analysis (cytological examination to detect cancer cells);
• pleurocentesis (fluid collection from the chest cavity around the lungs);
• biopsy is the most common method of diagnosing a malignant neoplasm. It is carried out in the form of removal of a particle of a fragment of the affected tissue for further examination under a microscope.

There are several ways to perform a biopsy:

• bronchoscopy combined with biopsy;
• puncture biopsy is performed using CT;
• endoscopic ultrasound with biopsy;
• mediastinoscopy combined with biopsy;
• open lung biopsy;
• pleural biopsy;
• videothoracoscopy.

Treatment of small cell lung cancer

The most important place in the treatment of small cell lung cancer is chemotherapy. In the absence of appropriate treatment for lung cancer, the patient dies 5-18 weeks after diagnosis. To increase the mortality rate to 45 - 70 weeks, polychemotherapy helps. It is used both as an independent method of therapy, and in combination with surgery or radiation therapy.

The goal of this treatment is complete remission, which must be confirmed by bronchoscopic methods, biopsy and bronchoalveolar lavage. As a rule, the effectiveness of treatment is assessed after 6-12 weeks, after the start of therapy, also, according to these results, it is possible to assess the likelihood of a cure and the patient's life expectancy. The most favorable prognosis is in those patients who have achieved complete remission. This group includes all patients whose life expectancy exceeds 3 years. If the tumor has decreased by 50%, while there is no metastasis, it is possible to talk about partial remission. Life expectancy is correspondingly less than in the first group. With a tumor that is not amenable to treatment and active progression, the prognosis is unfavorable.

After determining the stage of the disease of lung cancer, it is necessary to assess the patient's state of health in terms of whether he is able to tolerate induction chemotherapy as part of a combination treatment. It is carried out in the absence of previous chemotherapy and radiation therapy, also while maintaining the patient's working capacity, there are no severe concomitant diseases, heart, liver failure, the function of the bone marrow PaO2 when breathing atmospheric air exceeds 50 mm Hg. Art. and no hypercapnia. But, it is also worth noting that mortality from induction chemotherapy is present and reaches 5%, which is comparable to mortality from radical surgical treatment.

If the state of health of the patient does not meet the specified norms and criteria, in order to avoid complications and severe side effects, the dose of anticancer drugs is reduced. An oncologist should conduct induction chemotherapy. Particular attention is required to the patient in the first 4 months. Infectious, hemorrhagic and other severe complications are also possible during the treatment.

Localized small cell lung cancer (SCLC) and its treatment

1. treatment efficiency 65-90%;
2. The 5-year survival rate is -10% and reaches 25% for patients who started treatment in good general health.

Chemotherapy (2-4 courses) in combination with radiation therapy in a total focal dose of Gy is fundamental in the treatment of a localized form of SCLC. It is considered correct to start radiation therapy against the background of chemotherapy during or after 1-2 courses. When observing remission, it is advisable to conduct brain irradiation in a total dose of 30 Gy, since SCLC is characterized by rapid and aggressive metastasis to the brain.

With a common form of SCLC, combined treatment is indicated, while irradiation is advisable to carry out in the presence of special indicators:

• the presence of metastasis in the bones;
• metastasis, brain;
• metastasis in the adrenal glands;
• metastasis in the lymph nodes, mediastinum with compression syndrome of the superior vena cava.

Note! With metastasis to the brain, treatment with a gamma knife is possible.

After conducting a statistical study, it was revealed that the effectiveness of chemotherapy in the treatment of advanced SCLC is about 70%, while in 20% of cases a complete remission is achieved, which gives survival rates close to those of patients with a localized form.

Chemotherapy

limited stage

At this stage, the tumor is located within one lung, and nearby lymph nodes may also be involved.

Applied methods of treatment:

• combined: chemo+radiotherapy followed by prophylactic cranial irradiation (PKO) in remission;
• chemotherapy with or without PCR, for patients who have impaired respiratory function;
• surgical resection with adjuvant therapy for stage 1 patients;
• combined use of chemotherapy and thoracic radiotherapy is the standard approach for patients with limited stage, small cell LC.

According to the statistics of clinical studies, combination treatment compared with chemotherapy without radiation therapy increases the 3-year survival prognosis by 5%. Drugs used: platinum and etoposide. Prognostic indicators for life expectancy - months and a forecast of 2-year survival of 50%.

Inefficient ways to increase forecast:

1. increasing the dose of drugs;
2. action of additional types of chemotherapy drugs.

The duration of the course of chemotherapy is not defined, but, nevertheless, the duration of the course should not exceed 6 months.

The question of radiotherapy: many studies show its benefits in the period 1-2 cycles of chemotherapy. The duration of the course of radiation therapy should not exceed days.

It is possible to use standard irradiation courses:

1. 1 time per day for 5 weeks;
2. 2 or more times a day for 3 weeks.

Hyperfractionated thoracic radiotherapy is considered preferable and contributes to a better prognosis.

Patients of older age (65-70 years) tolerate treatment much worse, the prognosis of treatment is much worse, as they respond quite poorly to radiochemotherapy, which in turn manifests itself in low efficiency and large complications. Currently, the optimal therapeutic approach for elderly patients with small cell LC has not been developed.

Patients who have achieved tumor remission are candidates for prophylactic cranial irradiation (PCR). The research results indicate a significant reduction in the risk of brain metastases, which without the use of PKO is 60%. RCC improves the prognosis of 3-year survival from 15% to 21%. Often, patients who survive non-small cell lung cancer have impairments in neurophysiological function, however, these impairments are not associated with the passage of PCC.

extensive stage

The spread of the tumor occurs outside the lung in which it originally appeared.

Standard methods of therapy:

• combined chemotherapy with or without prophylactic cranial irradiation;
• etoposide + cisplatin or etoposide + carboplatin is the most common approach, with proven efficacy. Other approaches have not yet shown significant benefits;
• cyclophosphamide + doxorubicin + etoposide;
• ifosfamide + cisplatin + etoposide;
• cisplatin + irinotecan;
• cyclophosphamide + doxorubicin + etoposide + vincristine;
• cyclophosphamide + etoposide + vincristine.

Irradiation is given for negative responses to chemotherapy, especially for metastases to the brain, spinal cord, or bones.

A fairly positive response of 10-20% remission is given by cystplatin and etoposide. Clinical studies show the benefits of combination chemotherapy, which includes platinum. But despite this, cisplatin is often accompanied by severe side effects that can lead to serious consequences in patients suffering from cardiovascular diseases. Carboplatin is less toxic than cisplatin.

Note! The use of higher doses of chemotherapy drugs remains an open question.

For a limited stage, in case of a positive response to chemotherapy, an extensive stage of small cell lung cancer, prophylactic cranial irradiation is indicated. The risk of formation of metastases in the CNS within 1 year is reduced from 40% to 15%. There was no significant deterioration in health after PKO.

Patients diagnosed with advanced stage SCLC have a deteriorating health condition that complicates aggressive therapy. Conducted clinical studies have not revealed an improvement in survival prognosis with a decrease in drug doses or with the transition to monotherapy, but, nevertheless, the intensity in this case should be calculated from an individual assessment of the patient's health status.

Disease prognosis

As mentioned earlier, small cell lung cancer is one of the most aggressive forms of all cancers. What prognosis of the disease and how long patients live depends directly on the treatment of oncology in the lungs. A lot depends on the stage of the disease, and what type it belongs to. There are two main types of lung cancer - small cell and non-small cell.

SCLC, smokers are susceptible, it is less common, but spreads very quickly, forming metastases and capturing other organs. Is more sensitive to chemical and radiation therapy.

Small cell lung cancer, life expectancy in the absence of appropriate treatment, is from 6 to 18 weeks, and the survival rate reaches 50%. With appropriate therapy, life expectancy increases from 5 to 6 months. The worst prognosis is in patients with a 5-year illness. Approximately 5-10% of patients remain alive.

Informative video on the topic: Smoking and lung cancer

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Intercellular cancer

Small cell carcinoma is an extremely malignant tumor with an aggressive clinical course and widespread metastasis. This form accounts for 20-25% of all types of lung cancer. Some researchers regard it as a systemic disease, in which there are almost always metastases in regional and extrathoracic lymph nodes already in the initial stages. Among the patients, men predominate, but the percentage of affected women is increasing. The etiological connection of this cancer with smoking is emphasized. Due to the rapid growth of the tumor and widespread metastases, most patients have a severe form of the disease.

Symptoms

A new cough or a change in the patient's usual pattern of smoker cough.

Fatigue, lack of appetite.

Shortness of breath, chest pain.

Pain in the bones, spine (with metastases to the bone tissue).

An attack of epilepsy, headaches, weakness in the limbs, speech disorders are possible symptoms of brain metastases in stage 4 lung cancer./blockquote>

Forecast

Small cell lung cancer is one of the most aggressive forms. How long such patients live depends on the treatment. In the absence of therapy, death occurs in 2-4 months, and the survival rate reaches only 50 percent. With the use of treatment, the life expectancy of cancer patients can increase several times - up to 4-5. The prognosis is even worse after a 5-year period of the disease - only 5-10 percent of patients remain alive.

4 stage

Stage 4 small cell lung cancer is characterized by the spread of malignant cells to distant organs and systems, which causes symptoms such as:

headaches, etc.

Treatment

Chemotherapy plays an important role in the treatment of small cell lung cancer. In the absence of treatment, half of the patients die within 6-17 weeks after diagnosis. Polychemotherapy allows you to increase this indicator. It is used both as an independent method and in combination with surgery or radiation therapy.

The goal of treatment is to achieve complete remission, which must be confirmed by bronchoscopic methods, including biopsy and bronchoalveolar lavage. The effectiveness of treatment is assessed 6-12 weeks after its initiation. Based on these results, it is already possible to predict the likelihood of a cure and the life expectancy of the patient. The most favorable prognosis is for those patients who during this time managed to achieve complete remission. All patients whose life expectancy exceeds 3 years belong to this group. If the mass of the tumor has decreased by more than 50% and there are no metastases, they speak of partial remission. The life expectancy of such patients is less than in the first group. If the tumor does not respond to treatment or progresses, the prognosis is poor.

After the stage of the disease is determined (early or late, see "Lung Cancer: Stages of the Disease"), the general condition of the patient is assessed in order to find out whether he is able to tolerate induction chemotherapy (including as part of a combination treatment). It is carried out only if neither radiation therapy nor chemotherapy has been previously performed, if the patient is able to work, there are no serious concomitant diseases, heart, liver and kidney failure, bone marrow function is preserved, PaO2 when breathing atmospheric air exceeds 50 mm Hg . Art. and no hypercapnia. However, even in such patients, mortality during induction chemotherapy reaches 5%, which is comparable to mortality in radical surgical treatment.

If the patient's condition does not meet the specified criteria, in order to avoid severe side effects, the doses of anticancer drugs are reduced.

Induction chemotherapy should be performed by a specialist oncologist; special attention is required in the first 6. 12 weeks. In the process of treatment, infectious, hemorrhagic and other severe complications are possible.

Treatment of localized small cell lung cancer (SCLC)

The statistics of the treatment of this form of SCLC has good indicators:

the effectiveness of treatment is 65-90%;

tumor regression is observed in 45-75% of cases;

median survival reaches months;

2-year survival is 40-50%;

The 5-year survival rate is about 10%, while for patients who started treatment in good general condition, this figure is about 25%.

The basis for the treatment of a localized form of SCLC is chemotherapy (2-4 courses) according to one of the schemes indicated in the table in combination with radiation therapy of the primary focus, mediastinum and lung root in the total focal dose of Gy. It is advisable to start radiation therapy against the background of chemotherapy (during or after 1-2 courses). If the patient is in complete remission, it is also advisable to conduct brain irradiation in a total dose of 30 Gy, since SCLC is characterized by a high probability (about 70%) of brain metastasis.

Treatment for advanced small cell lung cancer (SCLC)

Patients with advanced MLR are treated with combined chemotherapy (see table), while irradiation is advisable only if there are special indications: with metastatic lesions of the bones, brain, adrenal glands, mediastinal lymph nodes with compression syndrome of the superior pudendal vein, etc.

With metastatic brain lesions, in some cases it is advisable to consider treatment with a gamma knife.

According to statistics, the effectiveness of chemotherapy in the treatment of advanced SCLC is about 70%, while in 20% of cases a complete regression is achieved, which gives survival rates close to patients with a localized form.

Chemotherapy

At this stage, the tumor is located within one lung, and nearby lymph nodes may also be involved. The following treatments are possible:

Combined chemo/radiotherapy followed by prophylactic cranial irradiation (PCR) in remission.

Chemotherapy with/without PCR for patients with impaired respiratory function.

Surgical resection with adjuvant therapy for stage I patients.

Combined chemotherapy and thoracic radiotherapy is the standard approach for patients with limited-stage small cell LC. According to statistics from various clinical studies, combination therapy compared with chemotherapy without radiation increases the 3-year survival prognosis by 5%. The most commonly used drugs are platinum and etoposide.

The average prognostic indicators are a life expectancy of a month and a forecast of a 2-year survival rate in the range of 40-50%. The following ways to improve the prognosis were ineffective: increasing the dose of drugs, the action of additional types of chemotherapy drugs. The optimal duration of the course has not been determined, but should not exceed 6 months.

The question of the optimal use of irradiation also remains open. Several clinical studies show the benefits of early radiotherapy (during cycles 1-2 of chemotherapy). The duration of the course of exposure should not exceed days. It is possible to use both the standard irradiation regimen (1 time per day for 5 weeks) and hyperfractionated (2 or more times a day for 3 weeks). Hyperfractionated thoracic radiotherapy is considered preferable and contributes to a better prognosis.

Age over 70 significantly worsens the prognosis of treatment. Elderly patients respond much worse to radiochemotherapy, which is manifested in low efficiency and complications. Currently, the optimal therapeutic approach for elderly patients with small cell LC has not been developed.

In rare cases, with good respiratory function and limited tumor process within the lung, surgical resection with or without subsequent adjuvant chemotherapy is possible.

Patients for whom it was possible to achieve remission of the tumor process are candidates for undergoing prophylactic cranial irradiation (PCR). The research results indicate a significant reduction in the risk of brain metastases, which without the use of PKO is 60%. RCC improves the prognosis of 3-year survival from 15% to 21%. Often, patients who survive non-small cell lung cancer have impaired neurophysiological function, but these disorders are not associated with the passage of PCC.

The tumor has spread beyond the lung in which it originally appeared. Standard treatment approaches include the following:

Combined chemotherapy with/without prophylactic cranial irradiation.

etoposide + cisplatin or etoposide + carboplatin is the most common approach and has been clinically proven to be effective. Other approaches have not yet shown a significant advantage.

cyclophosphamide + doxorubicin + etoposide

ifosfamide + cisplatin + etoposide

cyclophosphamide + doxorubicin + etoposide + vincristine

cyclophosphamide + etoposide + vincristine

Radiation therapy - used in case of a negative response to chemotherapy, especially with metastases in the brain, spinal cord or bones.

The standard approach (cystplatin and etoposide) gives a positive response in 60-70% of patients and leads to remission in 10-20%. Clinical studies testify to the benefits of combination chemotherapy, which includes platinum. However, cisplatin is often accompanied by severe side effects that can lead to serious consequences in patients suffering from cardiovascular diseases. Carboplatin is less toxic than cisplatin. The feasibility of using higher doses of chemotherapy drugs remains an open question.

As with limited stage, prophylactic cranial irradiation is indicated in case of a positive response to chemotherapy for advanced stage small cell lung cancer. The risk of formation of metastases in the CNS within 1 year is reduced from 40% to 15%. There was no significant deterioration in health after PKO.

Combined radiochemotherapy does not improve the prognosis compared to chemotherapy, but thoracic irradiation is reasonable for palliative therapy of distant metastases.

Often, patients diagnosed with advanced SCLC have a deteriorating health condition that complicates aggressive therapy. However, the conducted clinical studies have not revealed an improvement in the prognosis of survival with a decrease in doses of drugs or when switching to monotherapy. However, the intensity in this case should be calculated from an individual assessment of the patient's state of health.

Lifespan

How many live with lung cancer and how can you determine what life expectancy with lung cancer. It is not sad, but with such a terrifying diagnosis, patients without surgical intervention are always expected to die. About 90% percent of people die in the first 2 years of life, after the disease is diagnosed. But you should never give up. It all depends on at what stage the disease is detected in you and what type it belongs to. First of all, there are two main types of lung cancer - small cell and non-small cell.

Small cell, mainly smokers are susceptible, it is less common, but spreads very quickly, forming metastases and capturing other organs. It is more sensitive to chemical and radiation therapy.

How many live

The prognosis for lung cancer depends on many factors, but primarily on the type of disease. The most disappointing is small cell cancer. Within 2-4 months after the diagnosis, every second patient dies. The use of chemotherapy treatment increases life expectancy by 4-5 times. The prognosis for non-small cell cancer is better, but also leaves much to be desired. With timely treatment, the survival rate for 5 years is 25%. How long they live with lung cancer - there is no definite answer, life expectancy is affected by the size and location of the tumor, its histological structure, the presence of concomitant diseases, etc.

Among the variety of all known types of cancer, small cell lung cancer is one of the most common forms of cancer and, according to recent statistics, accounts for about 20% of all tumors affecting the lungs.

The danger of this type of cancer lies, first of all, in the fact that metastasis (the formation of secondary tumor nodes in organs and tissues) occurs quite rapidly, and not only the abdominal organs and lymph nodes are affected, but also the brain.

Small cell lung cancer equally often can be found in both the elderly and the young, but the age of 40-60 years can be considered the peak incidence. It is also worth noting that the vast majority of this disease affects men.

With late diagnosis, such a tumor is not treatable and, no matter how scary it sounds, leads to death. If the disease is detected in the early stages, the chances of recovery are quite high.

External manifestations

Like many other serious diseases, up to a certain point it may not manifest itself at all. However, there are certain indirect signs that in the early stages may raise suspicions about the presence of this type of oncology. These include:

• lingering dry cough, and in the later stages - coughing up blood;
• wheezing, hoarse breathing;
• pain in the chest area;
• decreased appetite and sudden weight loss;
• deterioration of vision.

In the process of metastasis formation, the following are added to these signs:

• headache;
• a sore throat;
• pain in the spine;
• the skin may take on a slightly yellowish tint.

Diagnostics

With a complex manifestation of the above symptoms, you should immediately consult a doctor, since it is possible to diagnose lung cancer absolutely accurately only after special laboratory tests are carried out:

1. general and biochemical blood tests;
2. and a lung biopsy (the volume of lung damage is determined);
3. X-ray examinations of internal organs;
4. tomography (like an X-ray study, this type of diagnosis is designed to determine the stage of the disease, as well as the intensity of metastasis);
5. molecular genetic research.

How dangerous is small cell lung cancer?

For the successful treatment of this disease, timely diagnosis is extremely important. Disappointing statistics suggest that only 5% of cases are diagnosed before the disease affects the lymph nodes.

Metastases in this oncological disease spread to the liver, adrenal glands, lymph nodes, affect bone tissue and even the brain.

The risk group includes, first of all, smokers, because. Tobacco smoke contains a huge amount of carcinogens. In addition, many people have a hereditary predisposition to the formation of malignant tumors.

Possible complications and comorbidities in small cell lung cancer:

1. Inflammation of the lungs, bronchitis, pneumonia;
2. Pulmonary bleeding;
3. Cancer inflammation of the lymph nodes (as a result - shortness of breath, increased sweating);
4. oxygen deficiency;
5. Negative effects of chemotherapy and radiation on the body (damage to the nervous system, hair loss, disorders in the digestive tract, etc.)

The effectiveness of modern methods of treatment of small cell lung cancer

After all the necessary tests are passed, the studies are carried out and the diagnosis is confirmed, the doctor prescribes the most optimal method of treatment.

Surgery

Surgery is considered the most effective way to get rid of cancer. During the operation, the affected part of the lung is removed. However, this type of treatment justifies itself only at an early stage of the disease.

Chemotherapy

This type of treatment is prescribed for patients with a limited stage of lung cancer, when the process of metastasis has already affected other organs. Its essence lies in taking certain drugs in courses. Each course has a duration of 2 to 4 weeks. The number of prescribed courses is from 4 to 6. Small breaks are necessarily made between them.

Radiation therapy

Irradiation is most often carried out in combination with chemotherapy, but can be considered as a separate type of treatment. Radiation therapy is directly exposed to the foci of pathological formations - the tumor itself and the identified metastases. This method of cancer treatment is also used after the surgical removal of a malignant formation - to affect cancerous foci that could not be removed surgically. At an extensive stage, when the tumor has spread beyond one lung, radiation therapy is used to irradiate the brain, and also prevents intensive metastasis.

For prevention small cell lung cancer it is necessary to give up smoking, protect yourself from the influence of harmful environmental substances, monitor your health and take measures for the timely diagnosis of various diseases.

(Moscow, 2003)

N. I. Perevodchikova, M. B. Bychkov.

Small cell lung cancer (SCLC) is a peculiar form of lung cancer, which differs significantly in its biological characteristics from other forms, united by the term non-small cell lung cancer (NSCLC).

There is strong evidence that SCLC is associated with smoking. This confirms the changing frequency of this form of cancer.

Analysis of SEER data for 20 years (1978-1998) showed that, despite the annual increase in the number of patients with lung cancer, the percentage of patients with SCLC decreased from 17.4% in 1981 to 13.8% in 1998, which, according to appears to be related to the intense anti-smoking campaign in the US. Noteworthy is the relative, compared with 1978, reduction in the risk of death from SCLC, first recorded in 1989. In subsequent years, this trend continued, and in 1997 the risk of death from SCLC was 0.92 (95% Cl 0.89 - 0.95,<0,0001) по отношению к риску смерти в 1978 г., принятому за единицу. Эти достаточно скромные, но стойкие результаты отражают реальное улучшение результатов лечения больных МРЛ -крайне злокачественной, быстро растущей опухоли, без лечения приводящей к смерти в течение 2-4 месяцев с момента установления диагноза.

The biological features of SCLC determine the rapid growth and early generalization of the tumor, which at the same time has a high sensitivity to cytostatics and radiation therapy compared to NSCLC.

As a result of the intensive development of methods for the treatment of SCLC, the survival of patients receiving modern therapy has increased by 4-5 times compared to untreated patients, about 10% of the entire population of patients have no signs of the disease within 2 years after the end of treatment, 5-10% live more 5 years without signs of recurrence of the disease, i.e., they can be considered cured, although they are not guaranteed against the possibility of resumption of tumor growth (or the occurrence of NSCLC).

The diagnosis of SCLC is finally established by morphological examination and is built clinically on the basis of radiological data, in which the central location of the tumor is most often detected, often with atelectasis and pneumonia and early involvement of the lymph nodes of the root and mediastinum. Often, patients develop mediastinal syndrome - signs of compression of the superior vena cava, as well as metastatic lesions of the supraclavicular and less often other peripheral lymph nodes and symptoms associated with the generalization of the process (metastatic lesions of the liver, adrenal glands, bones, bone marrow, central nervous system).

About two-thirds of patients suffering from SCLC, already at the first visit, have signs of metastasis, 10% have metastases in the brain.

Neuroendocrine paraneoplastic syndromes are more common in SCLC than in other forms of lung cancer. Recent studies have made it possible to clarify a number of neuroendocrine characteristics of SCLC and identify markers that can be used to monitor the course of the process, but not for early diagnosis. cancer embryonic antigen (CEA).

The importance of "antioncogenes" (tumor suppressor genes) in the development of SCLC has been shown, and genetic factors that play a role in its occurrence have been identified.

A number of monoclonal antibodies to the surface antigens of small cell lung cancer cells have been isolated, but so far the possibilities of their practical application have been limited mainly to the identification of SCLC micrometastases in the bone marrow.

Staging and prognostic factors.

When diagnosing SCLC, the assessment of the prevalence of the process, which determines the choice of therapeutic tactics, is of particular importance. After morphological confirmation of the diagnosis (bronchoscopy with biopsy, transthoracic puncture, biopsy of metastatic nodes), CT of the chest and abdomen is performed, as well as CT or MRI of the brain with contrast and bone scanning.

Recently, there have been reports that positron emission tomography (PET) can further refine the stage of the process.

With the development of new diagnostic techniques, bone marrow puncture has largely lost its diagnostic value, which remains relevant only in the case of clinical signs of bone marrow involvement in the process.

In SCLC, as in other forms of lung cancer, staging is used according to the international TNM system, however, most patients with SCLC already have III-IV stages of the disease at the time of diagnosis, which is why the Veterans Administration Lung Cancer Study Group classification has not lost its significance so far, according to which distinguish between patients with localized SCLC (Limited Disease) and widespread SCLC (Extensive Disease).

In localized SCLC, the tumor lesion is limited to one hemithorax with involvement in the process of regional and contralateral lymph nodes of the mediastinal root and ipsilateral supraclavicular lymph nodes, when irradiation using a single field is technically possible.

Widespread SCLC is a process that goes beyond the localized. Ipsilateral lung metastases and the presence of tumor pleurisy indicates widespread SCRL.

The stage of the process that determines therapeutic options is the main prognostic factor in SCLC.

Surgical treatment is possible only in the early stages of SCLC - with a primary T1-2 tumor without regional metastases or with damage to the bronchopulmonary lymph nodes (N1-2).

However, one surgical treatment or a combination of surgery with radiation does not provide satisfactory long-term results. A statistically significant increase in life expectancy is achieved with the use of postoperative adjuvant combined chemotherapy (4 courses).

According to the summary data of modern literature, the five-year survival rate of operable SCLC patients who underwent combined chemotherapy or combined chemoradiotherapy in the postoperative period is about 39%.

A randomized study showed the advantage of surgery over radiation therapy as the first stage of complex treatment of technically operable patients with SCLC; five-year survival rate at stages I-II in the case of surgery with postoperative chemotherapy was 32.8%.

The feasibility of using neoadjuvant chemotherapy for localized SCLC, when patients underwent surgery after achieving the effect of induction therapy, continues to be studied. Despite the attractiveness of the idea, randomized trials have not yet made it possible to draw an unambiguous conclusion about the benefits of this approach.

Even in the early stages of SCLC, chemotherapy is an essential component of complex treatment.

In the later stages of the disease, the basis of therapeutic tactics is the use of combined chemotherapy, and in the case of localized SCLC, the expediency of combining chemotherapy with radiation therapy has been proven, and in advanced SCLC, the use of radiation therapy is possible only if indicated.

Patients with localized SCLC have a significantly better prognosis compared with patients with advanced SCLC.

The median survival of patients with localized SCLC when using combinations of chemotherapy and radiation therapy in the optimal mode is 16-24 months with a 40-50% two-year survival rate and a five-year survival rate of 5-10%. In a group of patients with localized SCLC who started treatment in good general condition, a five-year survival rate of up to 25% is possible. In patients with advanced SCLC, median survival may be 8–12 months, but long-term disease-free survival is extremely rare.

A favorable prognostic sign for SCLC, in addition to a localized process, is a good general condition (Perfomance Status) and, according to some reports, a female gender.

Other prognostic signs - age, histological subtype of the tumor and its genetic characteristics, the level of LDH in the blood serum are ambiguously regarded by various authors.

The response to induction therapy also makes it possible to predict the results of treatment: only the achievement of a complete clinical effect, i.e., complete regression of the tumor, allows us to count on a long relapse-free period up to a cure. There is evidence that patients with SCLC who continue to smoke during treatment have a worse survival rate compared to patients who quit smoking.

In the case of a recurrence of the disease, even after successful treatment of SCLC, it is usually not possible to achieve a cure.

Chemotherapy for SCLC.

Chemotherapy is the mainstay of treatment for patients with SCLC.

Classical cytostatics of the 70-80s, such as cyclophosphamide, ifosfamide, nitroso derivatives of CCNU and ACNU, methotrexate, doxorubicin, epirubicin, etoposide, vincristine, cisplatin and carboplatin, have antitumor activity in SCLC of the order of 20-50%. However, monochemotherapy is usually not effective enough, the resulting remissions are unstable, and the survival of patients who received chemotherapy with the drugs listed above does not exceed 3-5 months.

Accordingly, monochemotherapy has retained its significance only for a limited contingent of patients with SCLC, who, according to their general condition, are not subject to more intensive treatment.

Based on the combination of the most active drugs, combination chemotherapy regimens have been developed, which are widely used in SCLC.

Over the past decade, the combination of EP or EC (etoposide + cisplatin or carboplatin) has become the standard for the treatment of patients with SCLC, replacing the previously popular combinations CAV (cyclophosphamide + doxorubicin + vincristine), ACE (doxorubicin + cyclophosphamide + etoposide), CAM (cyclophosphamide + doxorubicin + methotrexate) and other combinations.

It has been proven that combinations of EP (etoposide + cisplatin) and EC (etoposide + carboplatin) have antitumor activity in advanced SCLC of the order of 61-78% (full effect in 10-32% of patients). Median survival is 7.3 to 11.1 months.

A randomized trial comparing the combination of cyclophosphamide, doxorubicin, and vincristine (CAV), etoposide with cisplatin (EP), and alternating CAV and EP showed similar overall efficacy of all three regimens (ER -61%, 51%, 60%) with no significant difference in time to progression (4.3, 4 and 5.2 months) and survival (median 8.6, 8.3 and 8.1 months), respectively. The inhibition of myelopoiesis was less pronounced with EP.

Because cisplatin and carboplatin are equally effective in SCLC with better tolerability of carboplatin, combinations of etoposide with carboplatin (EC) and etoposide with cisplatin (EP) are used as interchangeable therapeutic regimens for SCLC.

The main reason for the popularity of the EP combination is that, having an equal antitumor activity with the CAV combination, it inhibits myelopoiesis to a lesser extent compared to other combinations, less limiting the possibilities of using radiation therapy - according to modern concepts, a mandatory component of localized SCLC therapy.

Most of the new regimens of modern chemotherapy are built on the basis of either adding a new drug to the combination of EP (or EC), or on the basis of replacing etoposide with a new drug. A similar approach is used for well-known drugs.

Thus, the pronounced antitumor activity of ifosfamide in SCLC served as the basis for the development of the ICE combination (ifosfamide + carboplatin + etoposide). This combination turned out to be highly effective, however, despite the pronounced antitumor effect, severe hematological complications served as obstacles to its widespread use in clinical practice.

at RONC im. N. N. Blokhin of the Russian Academy of Medical Sciences developed a combination of AVP (ACNU + etoposide + cisplatin), which has a pronounced antitumor activity in SCLC and, most importantly, is effective in brain and visceral metastases.

AVP combination (ACNU 3-2 mg/m 2 on day 1, etoposide 100 mg/m 2 on days 4, 5, 6, cisplatin 40 mg/m 2 on days 2 and 8 cycling every 6 weeks) has been used to treat 68 patients (15 with localized and 53 with advanced SCLC). The effectiveness of the combination was 64.7% with complete tumor regressions in 11.8% of patients and a median survival of 10.6 months. With SCLC metastases in the brain (29 evaluated patients), complete regression as a result of the use of the AVP combination was achieved in 15 (52% of patients), partial regression in three (10.3%) with a median time to progression of 5.5 months. Side effects of the AVP combination were myelosuppressive (leukopenia III-IV stage -54.5%, thrombocytopenia III-IV stage -74%) and were reversible.

New anticancer drugs.

In the nineties of the XX century, a number of new cytostatics with antitumor activity in SCLC came into practice. These include the taxanes (Taxol or paclitaxel, Taxotere or docetaxel), gemcitabine (Gemzar), the topoisomerase I inhibitors topotecan (Hycamtin) and irinotecan (Campto), and the vinca alkaloid Navelbine (vinorelbine). In Japan, a new anthracycline, Amrubicin, is being studied for SCLC.

In connection with the proven possibility of curing patients with localized SCLC using modern chemoradiotherapy, for ethical reasons, clinical trials of new anticancer drugs are carried out in patients with advanced SCLC, or in patients with localized SCLC in case of relapse of the disease.

Table 1
New drugs for advanced SCLC (I line of therapy) / according to Ettinger, 2001.

A drug		Number of b-ths (estimated)	Overall effect (%)	Median survival (months)
Taxotere
Topotecan
Irinotecan
Irinotecan
Vinorelbine
Gemcitabine
Amrubicin

Summary data on the antitumor activity of new anticancer drugs in SCLC are presented by Ettinger in a 2001 review. .

Information on the results of the use of new anticancer drugs in previously untreated patients with advanced SCLC (I-line chemotherapy) is included. Based on these new drugs, combinations have been developed that are undergoing phase II-III clinical trials.

Taxol (paclitaxel).

In the ECOG study, 36 previously untreated patients with advanced SCLC received Taxol at a dose of 250 mg/m 2 as a daily intravenous infusion once every 3 weeks. 34% had a partial effect, and the calculated median survival was 9.9 months. In 56% of patients, treatment was complicated by stage IV leukopenia, 1 patient died of sepsis.

In the NCTG study, 43 patients with SCLC received similar therapy under the protection of G-CSF. 37 patients were evaluated. The overall effectiveness of chemotherapy was 68%. Full effects were not recorded. Median survival was 6.6 months. Grade IV neutropenia complicated 19% of all chemotherapy courses.

With resistance to standard chemotherapy, Taxol at a dose of 175 mg/m 2 was effective in 29%, the median time to progression was 3.3 months. .

The pronounced antitumor activity of Taxol in SCLC served as the basis for the development of combination chemotherapy regimens with the inclusion of this drug.

The possibility of combined use in SCLC of combinations of Taxol and doxorubicin, Taxol and platinum derivatives, Taxol with topotecan, gemcitabine and other drugs has been studied and continues to be studied.

The feasibility of using Taxol in combination with platinum derivatives and etoposide is being most actively investigated.

In table. 2 presents his results. All patients with localized SCLC received additional radiation therapy of the primary focus and mediastinum simultaneously with the third and fourth cycles of chemotherapy. The effectiveness of the studied combinations was noted in case of severe toxicity of the combination of Taxol, carboplatin and topotecan.

table 2
Results of three therapeutic regimens including Taxol in SCLC. (Hainsworth, 2001) (30)

Therapeutic regimen	Number of patients II r/l		Overall Efficiency	Median survival (month)	Survival		Hematological complications
							Leukopenia III-IV Art.	Platelet singing	Death from sepsis
Taxol 135 mg/m2 Carboplatin AUC-5
Taxol 200 mg/m2 Carboplatin AUC-6 Etoposide 50/100mg x 10 days every 3 weeks
Taxol 100 mg/m2 Carboplatin AUC-5 Topotecan 0.75* mg/m 2 Zdn. every 3 weeks

p-distributed SCLC
l-localized SCRL

The multicenter randomized study CALGB9732 compared the efficacy and tolerability of combinations of α-etoposide 80 mg/m 2 days 1-3 and cisplatin 80 mg/m 2 1 day cycling every 3 weeks (Arm A) and the same combination supplemented with Taxol 175 mg/m 2 - 1 day and G-CSF 5 mcg / kg 8-18 days of each cycle (gr. B).

The experience of treating 587 patients with advanced SCLC who had not previously received chemotherapy showed that the survival of patients in the compared groups did not differ significantly:

In group A, the median survival was 9.84 months. (95% CI 8, 69 - 11.2) in group B 10, 33 months. (95% CI 9.64-11.1); 35.7% (95% CI 29.2-43.7) of patients in group A and 36.2% (95% CI 30-44.3) of patients in group B lived for more than a year. (drug-induced death) was higher in group B, which led the authors to conclude that the addition of Taxol to combinations of etoposide and cisplatin in the first line of chemotherapy for advanced SCLC increased toxicity without significantly improving treatment outcomes (Table 3).

Table H
Results of a Randomized Trial Evaluating the Efficacy of Adding Taxol to Etoposide/Cisplatin in 1-Line Chemotherapy for Advanced SCLC (Study CALGB9732)

	Number of patients	Survival		Toxicity > III Art.
		Median (months)		neutropenia	thrombocytopenia			neuro-toxicity	Lek. death
Etoposide 80 mg / m 2 1-3 days, cisplatin 80 mg / m 2 - 1 day. every 3 weeks x6		9,84 (8,69- 11,2)	35,7% (29,2-43,7)
Etoposide 80 mg / m 2 1-3 days, cisplatin 80 mg / m 2 - 1 day, Taxol 175 mg / m 2 1 day, G CSF 5 mcg / kg 4-18 days, every 3 weeks x6		10,33 (9,64-11,1)

From the analysis of the pooled data from the ongoing phase II-III clinical trials, it is clear that the inclusion of Taxol may increase the effectiveness of combination chemotherapy,

increasing, however, the toxicity of some combinations. Accordingly, the advisability of including Taxol in combination chemotherapy regimens for SCLC continues to be intensively studied.

Taxotere (doietaxel).

Taxotere (Docetaxel) entered clinical practice later than Taxol and, accordingly, later began to be studied in SCLC.

In a phase II clinical study in 47 previously untreated patients with advanced SCLC, Taxotere was shown to be 26% effective with a median survival of 9 months. Grade IV neutropenia complicated the treatment of 5% of patients. Febrile neutropenia was registered, one patient died of pneumonia.

The combination of Taxotere and cisplatin was studied as the first line of chemotherapy in patients with advanced SCLC in the Chemotherapy Department of the Russian Cancer Research Center. N. N. Blokhin RAMS.

Taxotere at a dose of 75 mg/m 2 and cisplatin 75 mg/m 2 were administered intravenously once every 3 weeks. Treatment was continued until progression or intolerable toxicity. In case of full effect, 2 cycles of consolidating therapy were additionally carried out.

Of the 22 patients to be evaluated, the full effect was registered in 2 patients (9%) and the partial effect in 11 (50%). The overall effectiveness was 59% (95% CI 48, 3-69.7%).

The median duration of response was 5.5 months, the median survival was 10.25 months. (95% Cl 9.2-10.3). 41% of patients survived 1 year (95% Cl 30.3-51.7%).

The main manifestation of toxicity was neutropenia (18.4% - stage III and 3.4% - stage IV), febrile neutropenia occurred in 3.4%, and there were no drug-induced deaths. Non-hematological toxicity was moderate and reversible.

Topoisomerase I inhibitors.

Among the drugs from the group of topomerase I inhibitors, topotecan and irinotecan are used for SCLC.

Topotecan (Hycamtin).

In the ECOG study, topotecan (Hycamtin) at a dose of 2 mg/m 2 was administered daily for 5 consecutive days every 3 weeks. In 19 out of 48 patients, a partial effect was achieved (effectiveness 39%), the median survival of patients was 10.0 months, 39% of patients survived one year. 92% of patients who did not receive CSF had grade III-IV neutropenia, grade III-IV thrombocytopenia. registered in 38% of patients. Three patients died from complications.

As a second-line chemotherapy, topotecan was effective in 24% of previously responding patients and in 5% of refractory patients.

Accordingly, a comparative study of topotecan and the combination of CAV was organized in 211 patients with SCLC who had previously responded to the first line of chemotherapy ("sensitive" relapse). In this randomized trial, topotecan 1.5 mg/m 2 was administered intravenously daily for five consecutive days every 3 weeks.

The results of topotecan did not differ significantly from the results of chemotherapy with the CAV combination. The overall effectiveness of topotecan was 24.3%, CAV - 18.3%, time to progression 13.3 and 12.3 weeks, median survival 25 and 24.7 weeks, respectively.

Stage IV neutropenia complicated topotecan therapy in 70.2% of patients, CAV therapy in 71% (febrile neutropenia in 28% and 26%, respectively). The advantage of topotecan was a significantly more pronounced symptomatic effect, which is why the US FDA recommended this drug as a second-line chemotherapy for SCLC.

Irinotecan (Campto, CPT-II).

Irinotecan (Campto, CPT-II) proved to have a fairly pronounced antitumor activity in SCLC.

In a small group of previously untreated patients with advanced SCLC, it was effective at 100 mg/m 2 weekly in 47-50%, although the median survival of these patients was only 6.8 months. .

In several studies, irinotecan has been used in patients with relapses after standard chemotherapy, with efficacy ranging from 16% to 47%.

The combination of irinotecan with cisplatin (cisplatin 60 mg/m 2 on day 1, irinotecan 60 mg/m 2 on days 1, 8, 15 cycling every 4 weeks, for a total of 4 cycles) was compared in a randomized trial with the standard combination of EP (cisplatin 80 mg / m 2 -1 day, etoposide 100 mg / m 2 days 1-3) in patients with previously untreated advanced SCLC. The combination with irinotecan (CP) was superior to the EP combination (84% vs. 68% overall efficacy, median survival 12.8 vs. 9.4 months, 2-year survival 19% vs. 5%, respectively).

The toxicity of the compared combinations was comparable: neutropenia more often complicated ER (92%) compared to the CP regimen (65%), diarrhea III-IV stage. occurred in 16% of patients treated with SR.

Also noteworthy is the report on the effectiveness of the combination of irinotecan with etoposide in patients with recurrent SCLC (overall efficacy 71%, time to progression 5 months).

Gemcitabine.

Gemcitabine (Gemzar) at a dose of 1000 mg/m 2 escalated to 1250 mg/m 2 weekly for 3x weeks, cycling every 4 weeks was used in 29 patients with advanced SCLC as 1st line chemotherapy. Overall efficacy was 27% with a median survival of 10 months. Gemcitabine was well tolerated.

The combination of cisplatin and gemcitabine used in 82 patients with advanced SCLC was effective in 56% of patients with a median survival of 9 months. .

Good tolerability and results comparable to standard regimens of gemcitabine in combination with carboplatin in SCLC served as the basis for the organization of a multicenter randomized study comparing the results of the combination of gemcitabine with carboplatin (GC) and the combination of EP (etoposide with cisplatin) in patients with SCLC with a poor prognosis. Patients with advanced SCLC and patients with localized SCLC with unfavorable prognostic factors were included - a total of 241 patients. Combination GP (gemcitabine 1200 mg/m 2 on days 1 and 8 + carboplatin AUC 5 on day 1 every 3 weeks, up to 6 cycles) was compared with combination EP (cisplatin 60 mg/m 2 on days 1 + etoposide 100 mg/m 2 per os 2 times a day 2 and 3 days every 3 weeks). Patients with localized SCLC who responded to chemotherapy received additional radiation therapy and prophylactic brain irradiation.

The efficacy of the GC combination was 58%, the EP combination was 63%, median survival was 8.1 and 8.2 months, respectively, with satisfactory chemotherapy tolerance.

Another randomized trial, which included 122 patients with SCLC, compared the results of using 2 combinations containing gemcitabine. The PEG combination included cisplatin 70 mg/m 2 on day 2, etoposide 50 mg/m 2 on days 1-3, gemcitabine 1000 mg/m 2 on days 1 and 8. The cycle was repeated every 3 weeks. The PG combination included cisplatin 70 mg/m 2 on day 2, gemcitabine 1200 mg/m 2 on days 1 and 8 every 3 weeks. The combination of PEG was effective in 69% of patients (complete effect in 24%, partial in 45%), the combination of PG in 70% (complete effect in 4% and partial in 66%).

The study of the possibility of improving the results of SCLC treatment by the use of new cytostatics is ongoing.

It is still difficult to unambiguously determine which of them will change the current options for treating this tumor, but the fact that the antitumor activity of taxanes, topoisomerase I inhibitors and gemcitabine has been proven allows us to hope for further improvement of modern therapeutic regimens for SCLC.

Molecularly targeted "targeted" therapy for SCLC.

A fundamentally new group of anticancer drugs are molecularly targeted, the so-called targeted (target-target, goal), drugs with a true selectivity of action. The results of molecular biology studies convincingly prove that the 2 main subtypes of lung cancer (SCLC and NSCLC) have both common and significantly different genetic characteristics. Due to the fact that SCLC cells, unlike NSCLC cells, do not express epidermal growth factor receptors (EGFR) and cyclooxygenase 2 (COX2), there is no reason to expect the possible effectiveness of such drugs as Iressa (ZD1839), Tarceva (OS1774) or Celecoxib, which are being intensively studied in NSCLC.

At the same time, up to 70% of SCLC cells express the Kit proto-oncogene encoding the CD117 tyrosine kinase receptor.

The tyrosine kinase inhibitor Kit Glivec (ST1571) is in clinical trials for SCLC.

The first results of the use of Glivec at a dose of 600 mg/m 2 orally daily as the only drug in previously untreated patients with advanced SCLC showed its good tolerability and the need to select patients depending on the presence of a molecular target (CD117) in the patient's tumor cells.

Tirapazamine, a hypoxic cytotoxin, and Exizulind, which affects apoptosis, are also being studied from this series of drugs. The expediency of using these drugs in combination with standard therapeutic regimens is being evaluated in order to improve the survival of patients.

Therapeutic tactics for SCLC

Therapeutic tactics in SCLC is determined primarily by the prevalence of the process and, accordingly, we specifically dwell on the issue of treating patients with localized, widespread and recurrent SCLC.

Some problems of a general nature are preliminary considered: intensification of doses of antitumor drugs, the feasibility of maintenance therapy, treatment of elderly patients and patients in a serious general condition.

Dose intensification in SCLC chemotherapy.

The issue of the advisability of intensifying chemotherapy doses in SCLC has been actively studied. In the 1980s, there was an idea that the effect was directly dependent on the intensity of chemotherapy. However, a number of randomized trials did not reveal a clear correlation between the survival of patients with SCLC and the intensity of chemotherapy, which was also confirmed by a meta-analysis of materials from 60 studies on this issue.

Arrigada et al. used a moderate initial intensification of the therapeutic regimen, comparing in a randomized study cyclophosphamide at a course dose of 1200 mg / m 2 + cisplatin 100 mg / m 2 and cyclophosphamide 900 mg / m 2 + cisplatin 80 mg / m 2 as 1 cycle of treatment (further therapeutic modes were the same). Among 55 patients who received higher doses of cytostatics, two-year survival was 43% compared with 26% for 50 patients who received lower doses. Apparently, it was the moderate intensification of induction therapy that turned out to be a favorable moment, which made it possible to obtain a pronounced effect without a significant increase in toxicity.

An attempt to increase the effectiveness of chemotherapy by intensifying therapeutic regimens using bone marrow autotransplantation, peripheral blood stem cells and the use of colony-stimulating factors (GM-CSF and G-CSF) showed that despite the fact that such approaches are fundamentally possible and it is possible to increase the percentage of remissions, the survival rate of patients cannot be significantly increased.

In the Chemotherapy Department of the Oncology Center of the Russian Academy of Medical Sciences, 19 patients with localized SCLC received therapy according to the CAM scheme in the form of 3 cycles with an interval of 14 days instead of 21 days. GM-CSF (leukomax) at a dose of 5 µg/kg was administered subcutaneously daily for 2-11 days of each cycle. When compared with the historical control group (25 patients with localized SCLC who received SAM without GM-CSF), it turned out that despite the intensification of the regimen by 33% (the dose of cyclophosphamide was increased from 500 mg/m 2 /week to 750 mg/m 2 /week , Adriamycin from 20 mg/m 2 /week to 30 mg/m 2 /week and Methotrexate from 10 mg/m 2 /week to 15 mg/m 2 /week) the results of treatment in both groups are identical.

A randomized trial showed that the use of GCSF (lenograstim) at a dose of 5 μg/kg per day in the intervals between VICE cycles (vincristine + ifosfamide + carboplatin + etoposide) can increase the intensity of chemotherapy and increase two-year survival, but at the same time, the toxicity of the intensified regimen increases significantly (out of 34 patients, 6 died from toxicosis).

Thus, despite ongoing research into early intensification of therapeutic regimens, there is no conclusive evidence for the benefit of this approach. The same applies to the so-called late intensification of therapy, when patients who have achieved remission after conventional induction chemotherapy are given high doses of cytostatics under the protection of bone marrow or stem cell autotransplantation.

In a study by Elias et al, patients with localized SCLC who achieved complete or significant partial remission after standard chemotherapy were treated with high-dose consolidation chemotherapy with bone marrow transplantation and radiation. After such intensive therapy, 15 of 19 patients had complete tumor regression, and the two-year survival rate reached 53%. The method of late intensification is the subject of clinical research and has not yet gone beyond the limits of clinical experiment.

supportive therapy.

The notion that long-term maintenance chemotherapy can improve long-term outcomes in patients with SCLC has been refuted by a number of randomized trials. There was no significant difference in the survival of patients who received long-term maintenance therapy and those who did not receive it. Some studies have shown an increase in time to progression, which, however, was achieved at the expense of a decrease in the quality of life of patients.

Modern SCLC therapy does not provide for the use of maintenance therapy, both with cytostatics and with the help of cytokines and immunomodulators.

Treatment of elderly patients with SCLC.

The possibility of treating elderly patients with SCLC is often questioned. However, the age of even more than 75 years cannot serve as a basis for refusing to treat patients with SCLC. In case of severe general condition and inability to use chemoradiotherapy, the treatment of such patients can begin with the use of oral etoposide or cyclophosphamide, followed, if the condition improves, by switching to standard chemotherapy EC (etoposide + carboplatin) or CAV (cyclophosphamide + doxorubicin + vincristine).

Modern possibilities of therapy of patients with localized SCLC.

The effectiveness of modern therapy in localized SCLC ranges from 65 to 90%, with complete tumor regression in 45-75% of patients and a median survival of 18-24 months. Patients who started treatment in good general condition (PS 0-1) and responded to induction therapy have a chance of a five-year relapse-free survival.

The combined use of combined chemotherapy and radiation therapy in localized forms of small cell lung cancer has received universal recognition, and the advantage of this approach has been proven in a number of randomized trials.

A meta-analysis of 13 randomized trials evaluating the role of chest radiation plus combination chemotherapy in localized SCLC (2140 patients) showed that the risk of death in patients receiving chemotherapy plus radiation was 0.86 (95% confidence interval 0.78 - 0.94) in relation to patients who received only chemotherapy, which corresponds to a 14% reduction in the risk of death. Three-year overall survival with the use of radiation therapy was better by 5.4 + 1.4%, which allowed us to confirm the conclusion that the inclusion of radiation significantly improves the results of treatment of patients with localized SCLC.

N. Murray et al. studied the question of the optimal timing of the inclusion of radiation therapy in patients with localized SCLC receiving alternating courses of combined CAV and EP chemotherapy. A total of 308 patients were randomized per group to receive 40 Gy in 15 fractions starting from the third week, concurrently with the first EP cycle, and to receive the same radiation dose during the last EP cycle, i.e. from week 15 of treatment. It turned out that although the percentage of complete remissions did not differ significantly, recurrence-free survival was significantly higher in the group receiving radiation therapy at an earlier time.

The optimal sequence of chemotherapy and radiation, as well as specific therapeutic regimens, are the subject of further research. In particular, a number of leading American and Japanese specialists prefer the use of a combination of cisplatin with etoposide, starting radiation simultaneously with the first or second cycle of chemotherapy, while at the ONC RAMS, radiation therapy at a total dose of 45-55 Gy is more often performed sequentially.

A study of the long-term results of liver treatment in 595 patients with inoperable SCLC who completed therapy at the ONC more than 10 years ago showed that the combination of combined chemotherapy with irradiation of the primary tumor, mediastinum, and supraclavicular lymph nodes increased the number of clinical complete remissions in patients with a localized process up to 64%. The median survival of these patients reached 16.8 months (in patients with complete tumor regression, the median survival is 21 months). 9% are alive without signs of disease for more than 5 years, that is, they can be considered cured.

The question of the optimal duration of chemotherapy in localized SCLC is not entirely clear, but there is no evidence of improved survival in patients treated for more than 6 months.

The following combination chemotherapy regimens have been tested and widely used:
EP - etoposide + cisplatin
EU - etoposide + carboplatin
CAV - cyclophosphamide + doxorubicin + vincristine

As mentioned above, the effectiveness of the EP and CAV regimens in SCLC is almost the same, however, the combination of etoposide with cisplatin, which inhibits hematopoiesis less, is more easily combined with radiation therapy.

There is no evidence of benefit from alternating courses of CP and CAV.

The feasibility of including taxanes, gemcitabine, topoisomerase I inhibitors, and targeted drugs in combination chemotherapy regimens continues to be studied.

Patients with localized SCLC who achieve complete clinical remission have a 60% actuarial risk of developing brain metastases within 2-3 years from the start of treatment. The risk of developing brain metastases can be reduced by more than 50% when using prophylactic brain irradiation (PMB) at a total dose of 24 Gy. A meta-analysis of 7 randomized trials evaluating POM in patients in complete remission showed a reduction in the risk of brain damage, improvement in disease-free survival and overall survival of patients with SCLC. Three-year survival increased from 15% to 21% with prophylactic brain irradiation.

Principles of therapy for patients with advanced SCLC.

In patients with advanced SCLC, in whom combination chemotherapy is the main method of treatment, and irradiation is carried out only for special indications, the overall effectiveness of chemotherapy is 70%, but complete regression is achieved only in 20% of patients. At the same time, the survival rate of patients upon achieving complete tumor regression is significantly higher than in patients treated with a partial effect, and approaches the survival rate of patients with localized SCLC.

With SCLC metastases in the bone marrow, metastatic pleurisy, metastases in distant lymph nodes, combined chemotherapy is the method of choice. In case of metastatic lesions of the mediastinal lymph nodes with the syndrome of compression of the superior vena cava, it is advisable to use combined treatment (chemotherapy in combination with radiation therapy). With metastatic lesions of the bones, brain, adrenal glands, radiation therapy is the method of choice. With brain metastases, radiation therapy in SOD 30 Gy makes it possible to obtain a clinical effect in 70% of patients, and in half of them complete regression of the tumor is recorded according to CT data. Recently, data have appeared on the possibility of using systemic chemotherapy for SCLC metastases in the brain.

The experience of RONTS them. N. N. Blokhin of the Russian Academy of Medical Sciences for the treatment of 86 patients with CNS lesions showed that the use of combined chemotherapy can lead to complete regression of SCLC brain metastases in 28.2% and partial regression in 23%, and in combination with brain irradiation, the effect is achieved in 77.8% of patients with complete tumor regression in 48.2%. The problems of complex treatment of SCLC metastases in the brain are discussed in the article by Z. P. Mikhina et al. in this book.

Therapeutic tactics in recurrent SCLC.

Despite the high sensitivity to chemotherapy and radiotherapy, SCLC mostly recurs, and in such cases, the choice of therapeutic tactics (second-line chemotherapy) depends on the response to the first line of therapy, the time interval elapsed after its completion, and the nature of the spread of the tumor (localization of metastases) .

It is customary to distinguish between patients with sensitive relapse of SCLC who had a full or partial effect of first-line chemotherapy and progression of the tumor process no earlier than 3 months after the end of induction therapy, and patients with refractory relapse who progressed during induction therapy or less than 3 months after its completion. .

The prognosis for patients with recurrent SCLC is extremely unfavorable and there is no reason to expect a cure. It is especially unfavorable for patients with refractory relapse of SCLC, when the median survival after the detection of a relapse does not exceed 3-4 months.

With sensitive relapse, an attempt may be made to re-apply a therapeutic regimen that was effective in induction therapy.

For patients with refractory relapse, it is advisable to use antitumor drugs or their combinations that were not used during induction therapy.

The response to chemotherapy in relapsed SCLC depends on whether the relapse is sensitive or refractory.

Topotecan was effective in 24% of patients with sensitive and 5% of patients with resistant relapse.

The efficacy of irinotecan in sensitive relapsed SCLC was 35.3% (time to progression 3.4 months, median survival 5.9 months), in refractory relapse, the efficacy of irinotecan was 3.7% (time to progression 1.3 months). , median survival 2.8 months).

Taxol at a dose of 175 mg/m 2 with refractory relapse of SCLC was effective in 29% of patients with a median time to progression of 2 months. and a median survival of 3.3 months. .

A study of Taxotere in relapse) SCLC (without division into sensitive and refractory) showed its antitumor activity of 25-30%.

Gemcitabine in refractory recurrent SCLC was effective in 13% (median survival 4.25 months).

General principles of modern tactics for the treatment of patients with SCLC can be formulated as follows:

With operable tumors (T1-2 N1 Mo), surgery is possible followed by postoperative combined chemotherapy (4 courses).

The feasibility of using induction chemo- and chemoradiotherapy followed by surgery continues to be studied, but there is no conclusive evidence of the benefits of this approach.

For inoperable tumors (localized form), combined chemotherapy (4-6 cycles) is indicated in combination with irradiation of the tumor area of ​​the lung and mediastinum. Maintenance chemotherapy is inappropriate. In case of achieving complete clinical remission - prophylactic irradiation of the brain.

In the presence of distant metastases (a common form of SCLC), combined chemotherapy is used, radiation therapy is carried out according to special indications (metastases to the brain, bones, adrenal glands).

Currently, the possibility of curing about 30% of patients with SCLC in the early stages of the disease and 5-10% of patients with inoperable tumors has been convincingly proven.

The fact that in recent years a whole group of new anticancer drugs active in SCLC has appeared allows us to hope for further improvement in therapeutic regimens and, accordingly, improvement in treatment outcomes.

References for this article are provided.
Please, introduce yourself.

Lung cancer ranks first in terms of frequency of diagnosis among all cancers. The most aggressive form of lung cancer is small cell lung cancer, which is characterized by a latent course of the disease, early metastasis, and poor prognosis.

What is small cell lung cancer

Small cell carcinoma is a neoplasm of malignant origin, which is localized in the human respiratory apparatus. This neoplasm can initially be divided into two types - small cell carcinoma of the left and right lung. The name of this disease can be explained by the size of cellular structures, which have a small value exceeding the size of blood cells (erythrocytes) only 2 times.

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Small cell cancer is less common than non-small cell cancer (diagnosed in 80% of cases). Most often, this pathology is observed in smoking men aged 50-62 years. Due to the increase in the number of female smokers, the number of cases among women is also increasing.

The tumor almost always begins as a central cancer, this type is fleeting - it spreads very quickly, seeding the entire lung tissue, forming metastases in neighboring organs. This type of lung cancer is an intensively proliferating subspecies of tumors with a high potential for malignancy. Metastases affect not only the organs of the retroperitoneal space and lymph structures, but also the brain.

The basis of this type of oncology is the cancerous degeneration of the epithelium of the lung tissue, the violation of air exchange. This type of lung cancer is the most difficult to treat, it ends fatally in 85% of cases.

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Causes

The causes of tumor pathogenesis can be:

• smoking. This is the root cause of the beginning of the transformation of the structure of lung tissue cells;
• heredity (the presence in the history of a similar disease in relatives increases the risk of getting this disease);
• unfavorable ecology in the patient's area of ​​residence;
• previous severe lung diseases (asthma, chronic obstructive pulmonary disease, pulmonary tuberculosis, and other infectious diseases and pathological neoplasms);
• prolonged contact with carcinogens (arsenic, nickel, chromium). Contacting is possible both in places of residence and at the place of work;
• the impact on the body of radioactive ions (for example, it is possible during various man-made disasters);
• asbestosis of the lungs;
• dust impact;
• influence of radon.

Symptoms of the disease

At the initial stages of formation, small cell carcinoma is not expressed by specific symptoms, the symptoms can be disguised as other pathologies of the lung system. But with the further spread of small cell lung cancer, its rapid metastasis, the symptoms begin to be clearly traced and become noticeable.

In the early stages, this type of lung cancer can be suspected only by some indirect signs:

• cough (in the initial stages, dry and lingering, later acquiring a paroxysmal character and becoming hacking, with sputum and bloody secretions);
• pain in the chest area;
• mediastinal compression;
• causeless shortness of breath that occurs from time to time;
• weakness, general malaise;
• severe loss of appetite, sudden weight loss, cachexia;
• possibly reduced vision;
• there is hoarseness when breathing, hoarseness in the voice when talking (dysphonia).

With late diagnosis, metastases of this cancer spread and the clinical picture is supplemented by the following symptoms:

• intense headaches of a different nature (pulsating and pulling, localized in one place, to migraine-like tingling, which cover the entire head);
• pain localized in the area of ​​the entire back, often radiating to the projection of the spine, pain in the bones, aching joints (this is due to metastases to the bone tissue).

In the last stages, with the involvement of mediastinal tissues in the cancerous process, a mediastinal compression syndrome develops, consisting of:

• dysphagia (eating disorders, when it becomes difficult for the patient to swallow food or it is simply impossible);
• hoarseness of voice (appears with paralysis of the laryngeal nerve);
• abnormal swelling of the neck and face (usually unilateral, appears when the superior vena cava is compressed).

With metastases in the liver, icterus of the skin and the development of hepatomegaly are possible. Hyperthermic manifestations, paraneoplastic syndrome (Lambert-Eaton myasthenic syndrome, antidiuretic hormone secretory disorder syndrome, Cushingoid manifestations) may occur.

At stage 4, there is a violation of speech and headaches of high intensity, noisy breathing, dermatitis may appear, deformation of the fingers in the form of "drumsticks" is observed, symptoms of general intoxication, temperature increases, obstructive pneumonia, confused consciousness occurs.

Signs of pathology may vary depending on the location of the initial neoplasm.

Small cell carcinoma is usually central, less common peripheral. A primary tumor (as opposed to a secondary neoplasm) is detected extremely rarely by radiographic method.

Stages of the disease and types of cancer

The division of small cell carcinoma according to the TNM classification has no fundamental differences and consists in the following positions: T - shows the state of the primary neoplasm, N - the state of regional lymph nodes, M - the presence and absence of distant metastasis.

A clear division into stages helps to determine the methods of treating a neoplasm - surgical or therapeutic.

Stage 1 - the size of the tumor is within 3 cm, the tumor affects one lung, there are no metastases.

Stage 2 - the size of the neoplasm is 3-6 cm, it blocks the bronchus and penetrates the pleura, causing atelectasis;

Stage 3 - cancer quickly spreads to neighboring organs, the tumor grows up to 6-7 cm, there is atelectasis of the entire lung, there are metastases in neighboring lymph nodes.

Stage 4 - malignant cells are present in distant organs.

More than half of patients are diagnosed with stage 3 or 4, so this type of cancer is considered according to the criteria for two important categories: localized (limited) or advanced type of cancer:

• the localized form involves only one lung in the process (they share the right-sided and left-sided forms);
• a common variant (it is comparable to stages 3-4 according to the TNM system) occurs in 60-65% of cases. It covers the two parts of the chest together with the tumor process, with the addition of cancerous pleurisy and the rapid appearance of metastases.

According to histology, lung cancer is divided into the following types:

Squamous cell (epidermoid) cancer, which has subspecies:

• highly differentiated;
• moderately differentiated;
• undifferentiated.

small cell cancer It happens:

• oat cell, fine-grained, spindle cell;
• intermediate (intercellular);
• pleomorphic (multicellular).

Adenocarcinoma subdivided into:

• highly differentiated;
• moderately differentiated;
• poorly differentiated (low-differentiated);
• bronchoalveolar.

Large cell cancer has two subspecies:

• clear cell;
• giant cell.

mixed type cancer happens:

• adenocarcinoma and small cell;
• squamous and adenocarcinoma, etc.

The histological characteristics are rather conditional, since the clinical course may differ even in tumors with the same structure.

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Diagnosis of the disease

To make a diagnosis, various instrumental and laboratory studies are carried out, consisting of:

• chest x-ray;
• MRI, PET, computed tomography (CT);
• skeletal scintigraphy;
• analyzes of the functioning of the liver;
• blood test;
• sputum analysis (cytological examination to detect cancer cells);
• thoracentesis (fluid collection from the chest cavity near the lungs);
• measurements of IAP (intra-abdominal pressure);
• analysis for tumor markers;
• biopsies of neoplasms or nearby lymph nodes.

There are several ways to do a biopsy, using:

• bronchoscopy;
• endoscopic ultrasound;
• mediastinoscopy.

Also perform:

• pleural biopsy;
• open lung biopsy;
• videothoracoscopy.

Treatment of small cell lung cancer

The main methods of treatment of this cancer are: polychemotherapy and radio irradiation. Surgical intervention makes sense to carry out only in the early stages.

Therapy for lung cancer is also carried out by other methods of treatment:

• immunotherapy
• brachytherapy;
• photodynamic therapy;
• targeted therapy;
• laser coagulation;
• radiofrequency ablation;
• cryodestruction;
• chemoembolization;
• radioembolization;
• biotherapy.

Each of these methods may be applicable in the treatment of lung cancer.

The goal of therapy for small cell lung cancer is to achieve absolute remission, which is confirmed by biopsy, bronchial examination (bronchoscopy), bronchoalveolar lavage. The effectiveness of treatment can be assessed after 6-12 weeks from the start of therapy, and then a life expectancy forecast can be made.

The most effective way to treat lung cancer is chemotherapy, which is carried out as an independent method of treatment, and as an addition to radiation exposure. Women are more sensitive to treatment.

Chemotherapy is used only when neither chemotherapy nor radiation therapy has been performed before, there are no concomitant serious diseases, heart and liver failure, and bone marrow potential is within the normal range. If the patient's condition does not meet these indicators, the dosage of chemotherapy drugs is reduced in order to avoid severe side effects.

Chemotherapy for small cell cancer is effective at any stage - at the initial stages it can prevent the spread of metastases, at the last it helps to alleviate the course of the disease and prolong the life of the patient. To suppress tumor angiogenesis, Avastin is also used, which affects this process of tumor development by binding to the VEGF protein.

A limited form of neoplasm of the lung (right or left) needs a small number (2-4) of chemotherapy courses. Cytostatic drugs are commonly used: Doxorubicin, Cyclophosphamide, Gemcitabine, Cisplatin, Etoposide, Vincristine and others. Cytostatics are used as monotherapy or in combination with irradiation of the primary tumor site. In remission, radioirradiation of the brain is additionally performed to reduce the risk of metastatic seeding.

Combination therapy for a limited form of small cell cancer offers a chance to extend life up to 2 years. With a common form of lung cancer, the number of chemotherapy courses increases to 4-6. In the presence of metastases in nearby and distant organs (adrenal glands, skeletal system, brain, and others), chemotherapy is carried out accompanied by radiotherapy.

Drug (palliative) treatment is more often used to maintain the vital activity of already affected organs and alleviate the patient's condition. This type of treatment is supportive. Preparations of various pharmacological groups are used:

• pain medications (including narcotic drugs),
• anti-inflammatory drugs;
• antibiotic substances to prevent infection and exacerbate the disease;
• drugs to protect the liver ("Essentiale");
• means for supplying oxygen to cell structures ("Pantogam", "Glycine") - in case of damage to brain cells;
• lowering the temperature ("Nimesulide", "Paracetamol", "Ibuprofen") with hyperthermia.

Surgical intervention for small cell carcinoma is carried out at stages 1-2 and must be accompanied by a course of postoperative polychemotherapy. With excision of malignant tissues of the organ, life expectancy increases. If this lung cancer is determined in the last stages with the coverage of the cancerous process of other organs, surgical treatment is not performed due to the increased risk of death during the operation. In addition to the classic method of tumor removal, sparing surgery using a CyberKnife can be used.

Treatment of localized small cell carcinoma and prognosis

With the treatment of this form of cancer, the prognosis is as follows:

• tumor regression occurs in 45-75% of cases;
• the effectiveness of therapy - 65-90%;
• 2-year survival - 40-50%;
• The 5-year survival threshold is 10-25% for patients who start treatment in good general health.

The main method of treating a localized form of this cancer is chemotherapy (2-4 courses) in conjunction with radiation therapy. Radiation therapy is performed on the background of chemotherapy or after the patient has received several courses of chemotherapy. During remission, brain irradiation is performed, since this type of cancer has a tendency to quickly and aggressively metastasize to the brain.

Applied therapy regimens:

• combined: chemotherapy and radiation therapy with prophylactic cranial irradiation (PKO) in the presence of remission;
• chemotherapy with or without PCO, for patients with impaired respiratory function;
• surgical resection in conjunction with adjuvant therapy for patients at stage 1;
• combined use of chemotherapy and thoracic radiotherapy - used for patients with a limited stage.

How to treat a common form of small cell cancer

With a common form, combined treatment is carried out, it makes sense to carry out irradiation with the following indicators:

• ongoing process of metastasis in the adrenal glands;
• bone metastases;
• metastasis in the lymph nodes, mediastinum with compression syndrome of the superior vena cava;
• metastases in the brain.

Applied methods of therapy:

• combination chemotherapy with or without cranial radiation;
• "Ifosfamide" along with "Cisplatin" and "Etoposide";
• "Cisplatin" + "Irinotecan";
• a combination of "Etoposide", "Cisplatin" and "Carboplatin";
• "Cyclophosphamide" along with "Doxorubicin", "Etoposide" and "Vincristine";
• a combination of "Doxorubicin" with "Cyclophosphamide" and "Etoposide";
• "Cyclophosphamide" in combination with "Etoposide" and "Vincristine".

Irradiation is used when chemotherapy is not effective, especially for metastases to the spinal cord, brain, or bones.

A combination of "Cisplatin" and "Etoposide" gives a good effect. Although "Cisplatin" often has severe side effects, leading to serious consequences in those with cardiovascular disease. Carboplatin is not as toxic as Cisplatin.

Nutrition in lung cancer, as in other types of oncology, should be sparing and nutritious, it is mandatory to follow a diet, diet and give up bad habits.

The use of folk remedies is possible as an addition to the main treatment and only with the permission of the attending physician. Refusal of the main treatment in favor of traditional medicine can lead to a deterioration in the patient's condition and the transience of the disease, followed by death.

It is useful to drink decoctions of medicinal herbs at the stages of remission, as well as to reduce pain syndromes during the main treatment, informing the doctor.

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How long do people live with small cell lung cancer?

With timely diagnosis and treatment, there is a chance of recovery.

Transient disease gives about 8-16 weeks of life (after which the patient dies) in case of refusal of treatment or insensitivity to it.

All patients who crossed the 3-year life expectancy threshold belong to the complete remission group, their survival rate can reach 70-92% of the total number of this disease.

If the size of the neoplasm after treatment has decreased by half or more from the original size, then this indicates a partial remission, and the life expectancy of these patients is two times less than the previous one.

Only 5-11% of all patients overcome the five-year survival threshold.

The overall life expectancy depends on:

• timely diagnosis;
• stage of the detected disease;
• high-quality complex treatment;
• postoperative (or after a course of polychemotherapy) observation;
• the general health of the patient.

With combined treatment in stages I and II, the chances of crossing the 5-year threshold are about 40%.

At later stages, with combination therapy, life expectancy increases by an average of two years.

In patients with a localized tumor (not an early stage, but without distant metastasis) using complex therapy, a two-year survival rate of about 65-75%, about 5-10% of patients can overcome the 5-year threshold, with good health, the chances of surviving up to 5 years increased in 25% of patients.

In the case of advanced type 4 lung cancer, the survival rate is usually up to 1 year. The prognosis for an absolute cure (without recurrence) is unlikely.

Small cell lung cancer is a malignant neoplasm that develops as a result of pathological changes in the cells of the mucous membrane of the respiratory tract. The disease is dangerous because it develops very quickly, already in the initial stages it can metastasize to the lymph nodes. The disease occurs more often in men than in women. At the same time, smokers are most susceptible to its occurrence.

As in any other cases, there are 4 stages of small-cell lung cancer pathology. Let's consider them in more detail:

1 stage	the tumor is small, localized in one segment of the organ, no metastasis
Stage 2 SCLC	the prognosis is quite comforting, although the size of the neoplasm is much larger, can reach 6 cm. Single metastases are observed. Their location is regional lymph nodes.
Stage 3 SCLC	the prognosis depends on the characteristics of the particular case. The tumor can exceed 6 cm in size. It spreads to neighboring segments. Metastases are more distant, but are within regional lymph nodes
Stage 4 SCLC	the prognosis is not as encouraging as in previous cases. The neoplasm goes beyond the organ. There is extensive metastasis

Of course, the success of treatment, as with any cancer, will depend on the timeliness of its detection.

Important! Statistics show that small cell makes up 25% of all existing varieties of this disease. If metastasis is observed, in most cases it affects 90% of the thoracic lymph nodes. Slightly less will be the share of the liver, adrenal glands, bones and brain.

Clinical picture

The situation is aggravated by the fact that the symptoms of small cell lung cancer at the initial stage are practically not noticeable. They can often be confused with a common cold, because a person will experience a cough, hoarseness, and difficulty breathing. But, when the disease becomes more serious, the clinical picture becomes brighter. A person will notice signs such as:

• a worsening cough that does not go away after taking conventional antitussive drugs;
• pain in the chest area that occurs systematically, increasing its intensity over time;
• hoarseness of voice;
• impurities of blood in sputum;
• shortness of breath even in the absence of physical exertion;
• loss of appetite, and accordingly, weight;
• chronic fatigue, drowsiness;
• difficulty in swallowing.

These symptoms should prompt immediate medical attention. Only timely diagnosis and effective therapy will help improve the prognosis for SCLC.

Diagnosis and features of treatment

Important! Most often, SCLC is diagnosed in people aged 40-60 years. At the same time, the proportion of men is 93%, and women suffer from this form of oncology only in 7% of the total number of cases.

High-precision diagnostics performed by experienced specialists is the key to successful getting rid of the disease. It will allow you to confirm the presence of oncology, as well as determine exactly what kind of it you have to deal with. It is possible that we are talking about non-small cell lung cancer, which is considered a less aggressive type of disease, allows you to make more comforting predictions.

The main diagnostic methods should be:

1. laboratory blood tests;
2. sputum analysis;
3. chest x-ray;
4. body CT;

Important! A lung biopsy is mandatory, followed by examination of the material. It allows you to more accurately determine the features of the neoplasm and its nature. A biopsy may be performed during bronchoscopy.

This is a standard list of studies that a patient must undergo. It can be supplemented with other diagnostic procedures if necessary.

If we talk about the treatment of small cell lung cancer, then its main method remains surgical intervention, as in other types of oncology. It is carried out in two ways - open and minimally invasive. The latter is more preferable, because it is considered less traumatic, has fewer contraindications, and is characterized by high accuracy. Such operations are performed through small incisions on the patient's body, controlled by special video cameras that display the image on the monitor.

Given the fact that the type of oncology in question progresses very quickly, often being detected already at the stage of metastasis, doctors will use chemotherapy or radiation therapy as additional methods of treating SCLC. At the same time, irradiation or therapy with anticancer drugs can be carried out before surgery, with the aim of stopping tumor growth, destroying cancer cells, and are often performed after surgery - here they are needed to consolidate the result and prevent relapse.

Additional therapies can be used in combination. This way you can achieve more significant results. Sometimes doctors resort to polychemotherapy, combining several drugs. Everything will depend on the stage of the disease, the characteristics of the state of health of a particular patient. Radiation therapy for SCLC can be either internal or external, depending on the size of the tumor and the extent of metastases.

As for the question - how many people live with SCLC, it is difficult to give an unambiguous answer here. Everything will depend on the stage of the disease. But, given the fact that pathology is often detected already in the presence of metastasis, the main factors determining life expectancy will be: the number of metastases and their location; professionalism of attending physicians; the accuracy of the equipment used.

In any case, even with the last stage of the disease, there is a chance to extend the life of the patient by 6-12 months, significantly alleviating the symptoms.