Small cell lung cancer

The name of this type of common pathology according to the histological classification is explained by the small size of the cells, which are only twice as large as the blood cell. But, despite the part of the name “small”, the problems in patients with this type of disease arise very deep. The prognosis of small cell lung cancer (SCLC) directly depends on the methods of treating a tumor in the lungs, on when the diagnosis was made and what stage of development was detected, and is generally disappointing.

This malignant tumor is distinguished by its aggressive course - it spreads rapidly, forms metastases on other large organs that are distant from the focus.

The causes of MRL can be:

Nicotine addiction

Unfavorable ecology of the environment,

Severe lung disease (tuberculosis).

Symptoms of small cell lung cancer

In the early stages, small cell carcinoma does not make the patient aware of himself, and the symptoms are almost not observed. But as soon as a lung begins to form a tumor, the clinical manifestations become noticeable. They do not usually cause suspicion of cancer, as they are very similar to signs of other diseases of the respiratory organs.

The most common symptoms of SCLC include:

Pain in the chest,

Dry cough in the initial stages and cough with blood in the late,

Hoarse breathing, hoarseness when talking.

In cases where metastasis in myopathy has begun to develop on organs, clinical manifestations are added to the clinical manifestations:

Difficulty in swallowing food,

Hoarseness in the voice, etc.

To make a qualitative diagnosis of MRL at the initial stages, lung tomography and bone tissue scanning are necessary.

Treatment of small cell lung cancer

The most effective method of treating patients with SCR is chemotherapy, which serves as an independent method or in combination with radiation therapy or surgery on the lungs. In addition, it is possible to apply separately:

Surgical removal of a cancerous tumor, which is successfully carried out in the early stages,

Radiation therapy when it is impossible to apply surgical removal of a part of the affected organ.

Chemotherapy for small cell lung cancer in the early stages gives very good results. Its essence lies in the effect of certain drugs on cancer cells. Drugs kill cells, retard their growth and spread in the body.

Life expectancy for small cell lung cancer

Of all oncological diseases, MRL is distinguished by an aggressive course and an accelerated growth of metastases. If you do not start treatment in the early stages, the survival rate of patients is practically reduced to zero, i.e. no more than 2-3 months. Timely treatment can only prolong life several times with chemotherapy or radiation therapy.

It should be noted that this disease often affects men.

Education: He graduated from the residency in the "Russian Scientific Oncological Center named. N. N. Blokhin "and received a diploma in" Oncologist "

16 of the most harmful foods - proven by science

Is it true that you need to clean the body? Myths and proven facts!

In folk medicine, there are many recommendations and prescriptions for treating cancer using mainly the healing properties of plants. Plants that are used in traditional medicine to treat cancer can restrain the growth of tumors, destroy the affected cells and allow healthy cells to grow.

In the structure of cancer, this is one of the most common pathologies. The basis of lung cancer is malignant degeneration of the epithelium of the lung tissue and impaired air exchange. The disease is characterized by high mortality. The main risk group is smoking men aged 50-80 years. Feature of modern.

Breast cancer is the most common cancer in women. The relevance of the disease increased in the late seventies of the last century. The disease was characterized by a primary lesion of women over the age of fifty years.

Stomach cancer is a malignant degeneration of gastric epithelial cells. In the disease, 71-95% of cases are associated with the defeat of the stomach walls by the bacteria Helicobacter Pylori and are among the common cancers of people aged 50 to 70 years. In men, gastric cancer is diagnosed 10–20% more often than in women of the same age.

Cervical cancer (cervical cancer) is a virus-dependent oncologic disease. The primary tumor is a reborn glandular tissue (adenocarcinoma) or squamous cell carcinoma of the reproductive organ. Sick women from 15 to 70 years. Between the ages of 18 and 40, the disease is a significant cause of early death.

Skin cancer is a disease that gets its development from stratified squamous epithelium, which is a malignant tumor. Most often, it appears on open areas of the skin, the appearance of a tumor on the face is very high, the nose and forehead, as well as the corners of the eyes and ears are most susceptible. The body of such education "do not like" and are formed.

Intestinal cancer is a malignant degeneration of the glandular epithelium of the predominantly colon or rectum. In the first stages, flaccid symptoms that distract from the primary pathology and resemble a disorder of the gastrointestinal tract are characteristic. The leading radical treatment is surgical excision of the affected tissue.

Causes of development

Small cell carcinoma of the lung occurs as a result of human exposure to such factors:

  • tobacco smoking
  • chronic inflammatory diseases of the lung tissue,
  • genetic predisposition
  • contact with industrial dust,
  • asbestosis,
  • lack of immune antitumor protection,
  • ionizing radiation.

Lung cancer occurs as a result of exposure to one or more harmful factors on the human body. The disease often develops in men over the age of 50 years. The main provocateur is the smoker’s experience: the bigger he is, the more likely he becomes ill with a malignant neoplasm of the lungs. As a result, a focus of atypical cells is formed, which very quickly grow and multiply, replacing healthy lung tissue. The more primitive cellular elements, the more malignant cancer proceeds.


On the morphological structure, there are such types of small cell lung cancer:

  • oat-cell with a predominance of spindle-like cells,
  • mixed incorporates squamous and oat-cell elements,
  • intermediate - cells of different forms.

Small cell carcinoma has an unfavorable prognosis, as it gives early and common metastases. Depending on the location of the tumor, such forms of a neoplasm can be distinguished:

  • Central cancer. The neoplasm grows in the bronchial lumen and is located behind the heart. Therefore, it is impossible to identify it on the radiograph. Characterized by severe symptoms with chest pain and hemoptysis.
  • Peripheral. Formed in the bronchioles and for a long time asymptomatic, but is clearly visible on the x-ray, where are determined:
    • germinating form that extends to nearby vessels and nerves,
    • cavitary - with the center of disintegration in the center.
  • Pneumonia-like cancer. The clinic is similar to inflammation of the lung tissue.
  • Atypical form. Due to the formation of secondary foci. The initial tumor has a small size and provokes the development of symptoms. There are such types of tumors, depending on the localization of metastases:
    • bone, which affects the spine and pelvis,
    • brainstorming with a stroke clinic,
    • hepatic, which is associated with liver damage and violation of the outflow of bile.
Back to table of contents

Main symptoms

Small-cell lung cancer triggers the development of such characteristic clinical signs in a patient:

  • prolonged cough
  • hemoptysis,
  • anorexia,
  • chest pressure
  • dyspnea,
  • voice change.

The increase in symptoms occurs over time. Initially, the disease proceeds without manifestations. After the formation of metastases, pain in the bones, jaundice of the skin and neurological manifestations are possible, which are associated with secondary foci in various organs. Most often, metastases affect the liver, bones of the spine and brain.

Stage of the disease

There are such stages of development of small cell lung cancer:

Back to table of contents

Diagnostic methods

Imaging techniques such as x-rays and MRI are shown for detecting small cell carcinoma. Pleurocentesis is also performed, which is a fluid intake from the pleural cavity. It is necessary to do a sputum analysis in which atypical cells can be detected. It is important to make a general and biochemical blood test. A lung biopsy or a tissue site is taken with a bronchoscopy, open or pleural puncture. After that, histological and cytological analysis of the sample with the characteristic of atypical cells is performed.

The small cell form is the most malignant among all types of lung cancer.

Pathology treatment

Lung cancer therapy depends on the stage at which the process was detected. With a limited neoplasm, the main method is an operation with the removal of a lobe, segment, or one lung. However, lung cancer is most often defined as inoperable due to the aggressive nature of the growth of the neoplasm. Therapy of small cell cancer consists in carrying out polychemotherapy using platinoids. After metastasis to distant organs, it is recommended to take a combination of several drugs. The most common among them are Etoposide, Cisplatin and Carboplatin. Still used remote radiation therapy, which is localized regionally. Irradiation is a method of palliative therapy that helps prolong the life of the patient. It is also important to conduct maintenance therapy with the use of painkillers and antiemetics.

Prediction for life

Treatment of small cell lung cancer is effective only in the initial stages of tumor development. Upon detection of a limited form of a neoplasm, the five-year survival rate is only 30%. In the case of the formation of secondary foci, the patient's life expectancy is no more than a year, an average of 10 months. Cancer recurrence is an unfavorable prognostic criterion and is not treatable.

First symptoms

Considering the preponderance of smokers among those who are sick, doctors admit that smoking is the main carcinogen causing this form of cancer. Also reasons not related to smoking, or factors relating to the patient’s lifestyle, are:

  • heavy ecological environment, work, implying contact with carcinogens,
  • chronic lung disease, turning into malignant tumors,
  • hereditary predisposition to the disease.

These people are at risk. The recommendations of the doctors emphasize that it is important to monitor non-specific symptoms of lung cancer and to undergo prophylactic examinations to ensure the absence of a terrible disease.

Half of the disease goes away without recognizable symptoms, but then the cancer neoplasm quickly worsens the patient's condition. The first signs vary, depending on the site of the disease. They divide small cell carcinoma into central and peripheral, depending on the zone of formation of malignant cells.

Nonspecific symptoms

The first symptoms are not easy to catch, as the cough, indicating a disease of the respiratory system, is constantly observed in smokers: morning cough, tormenting smokers after waking up, indicates that the lungs are contaminated, and not the disease. And the difference between a smoker's cough and a symptom of the disease is not easy to feel. The same is typical for dyspnea and noisy breathing, familiar to smokers with many years of experience.

A sign indicating a pathology of the lungs is called a symptom of drumsticks — an increase in the end phalanges of the fingers. Dermatitis is possible. In the later stages, blood spurting is observed, evidence of a dangerous lung disease.

Gradually, there is evidence of a general depletion of the body: weight loss, body intoxication, fever.

Specific symptoms

In the early stages there are no specific symptoms, as well as non-specific ones. But when the first symptoms occur, among them are those that arouse serious suspicions about oncology, you need to contact a doctor if the signs of the disease go together:

  • Cough without sputum, smokers usually have sputum.
  • Husky voice for no apparent reason.
  • Sternum pain.
  • Weakness in the body.
  • Severe shortness of breath without exercise.

Only at the last stage, symptoms recognizable from the side develop: this damage to the lung tissue irreversibly affects breathing and oxygenation of the blood.

The patient does not want to eat or is unable to eat. The voice is barely audible or it is not (a variant of the disease with metastases affecting the larynx).

If metastases affect the veins, swelling of half of the face or neck is possible.

Manifestation of metastases, depending on the affected area of ​​the body, the patient develops: headache and obscure consciousness (metastases in the brain), pain in the bones, spine (metastases in the bone tissue).

Considering the large flow of patients providing histological and factual material for analysis, small cell lung cancer has been studied in detail and divided into stages. The basis of this division was the size of the original tumor, the presence of distant metastases and lymph nodes. Given the criteria, four stages are called, if there is a zero stage and two types of development of the disease in the third and second stages:

  • Stage 0. At the zero stage, which is sometimes isolated, a tumor appears in the lung tissues. If there is a danger that the tumor goes into a malignant cancer, it is immediately removed. The remaining organs, blood and lymph are not affected, and the cells in them are not modified.
  • Stage 1. In the first stage, a non-invasive formation is observed, no larger than three centimeters in size. Lymph nodes at this stage are not affected, and there is no hint of secondary foci of oncology. At the first stage, usually one lung is affected: the lesion of the left or right lung is visible at the examination. Rarely, cancer forms in both at once, but seizes them in later stages of the disease.
  • Stage 2. In the second stage, a different course of the disease is possible. In the first case, it does not affect the lymph, the nearest nodes are not dilated, and there is no metastasis. In the second case, oncology affects the nearest lymph nodes, they expand. The size of the neoplasm reaches a size of 3 centimeters and develops further.
  • Stage 3. In the third stage, the tumor mass is first held within the framework of the growing tumor, but later it does not spread out in breadth, but through the tissues that come in contact with it. The size of the tumor is arbitrary. In the third stage, the lymph nodes are precisely affected. Not only the bronchial nodes nearest to the tumor, but also the nodes of the mediastinum. There are no metastases in the third stage.
  • Stage 4. Metastases appear, distant foci of formation of various localization.They affect the characteristics of symptoms and the course of the disease, the severity of the patient's condition. In the fourth stage, the lymph nodes of the diaphragm are affected, as mentioned above: mediastinal node, bronchial nodes. The size of the tumor at the fourth stage does not play a role, the formation germinates into the adjacent tissues, capturing new areas, moving to the nearest organs.

Small cell lung cancer is divided not only into stages, but also into types of disease. They indicate further development and, therefore, the necessary treatment. This classification is based on the speed of development of a malignant formation:

  • Carcinoma with small cell type. This malignant type of disease is more difficult to treat, it is more aggressive. The treatment will be chemotherapy, using at the same time several drugs.
  • Small cell carcinoma of the combined type. A disease with a more favorable prognosis than the previous one. The name was chosen because it combines the symptoms of squamous and large cell carcinoma, adding to this a unique histological picture.

There is another classification, based on the cytological principle, describing the types of malignant cells formed during the oncological process in the lungs. The clinical picture will vary, as will the prognosis for the patient. Then the cancer is subdivided into:

  • Oat-cell form, cellular amorphism causes the affected cells to take a certain shape.
  • Spindle cell type of neoplasm.
  • Fine-grained type.
  • Intermediate stage (intercellular type of cancer, when there is no predominance of well-defined cells, this is an undifferentiated type of disease).
  • Pleomorphic (multicellular cancer, describing the proximity of different types of cells within the same neoplasm).

Before treatment, a complete diagnosis is carried out, showing the localization of oncology, the shape of the tumor, the degree of development of the disease, the presence of metastases, and the damage to organs adjacent to oncology. It is determined how well they function and how dangerous the disease is for them in the near future. Various methods are used for diagnosis: first of all, it is fluorography, blood tests (the patient’s microscopic blood sample will show a characteristic picture of cancer in the blood), tests for cancer markers, biopsy with further analysis of the material collected, MRI, which most accurately visualizes the course of the disease. And when the overall picture is determined, an accurate diagnosis is made and a prognosis is made, the doctors build the treatment that is most suitable for the patient, taking into account the individual picture of the disease.

The main tools for the treatment of small cell carcinoma are called chemotherapy, radiation therapy, and surgical intervention. In the course of treatment, the methods are combined and help to achieve the best results for the patient.

Chemotherapy is used to prepare for surgery, as it is able to limit the tumor, keeping it within certain limits. Chemotherapy is used as a separate method of treatment, it reduces the size of the tumor, preventing it from developing and seizing new tissues.

Radiation therapy has been learned to use, directing radiation only to the affected cells, affecting and irradiating healthy tissues to a minimum. It kills malignant, modified cells, significantly slowing the development of the oncological process.

In addition to treatment methods, there is a diet that helps to improve the patient’s condition, as the menu contains substances that the patient needs to fight the disease. The diet for small cell lung cancer includes:

  • Proteins, destroyed by chemotherapy and radiation therapy. The lack of substances affects the general state of health and the speed of recovery processes, in particular, cell regeneration. So the diet includes meat, poultry and fish.
  • Light proteins are especially relevant if the patient suffers from anorexia, if he becomes sick or tears from drugs administered during chemotherapy. Yogurts, milk, eggs are perceived by the body more easily.

The diet of the patient completely excludes alcoholic beverages and caffeine, weakening the body, which is in serious condition from illness or treatment.

But diet is an auxiliary method for recovery, not the main one. Some believe that only a selection of diets can be cured, but the opinion is wrong. The disease will progress. Let us turn to the description of medical methods of intervention in the development of the oncological process.

Early treatment

If a patient is diagnosed with the first or second stage of small cell lung cancer, then the most effective treatment will be surgery, which involves the removal of a malignant tumor along with part of the lung. It happens that you need to remove the entire organ, if there are several formations or they have captured most of the lung area. Then the recovery period will be long, but the patient will remain alive.

Combine surgery with chemotherapy, necessary to limit the growth of the tumor and to designate its limits. After surgery, chemotherapy is also prescribed to rule out relapses. Irradiation is also applied. All methods of combating neoplasm and the spread of infected cells are used, because there is a great chance to destroy a malignant tumor or achieve a period of complete remission, which undoubtedly is a victory over a life-threatening disease.

In addition to drugs and the method of treatment, a diet, a special diet, an exercise regime, and everything that helps the body recover will be prescribed.

Late treatment

From the third stage, the formation becomes inoperable, therefore the main treatment method cannot be applied. The main method is polychemotherapy - treatment with different drugs at the same time. They are selected individually for the patient in order not to cause harm to the body, but to hit the malignant cells as efficiently as possible. At the same time apply and radiation therapy. These are the only methods that can keep the cancer in the previous framework. Achieving remission - stopping the development of the disease and improving the patient's condition - a victory over the disease at this stage. In this state, it is necessary to carry out preventive irradiation of the brain, since metastasis to it has serious consequences for the whole organism.

In addition to the brain, the first danger is waiting for all organs that actively supply blood: the liver, kidneys and bone tissues. They become brittle and, in severe cases, break easily. Then the patient is immobilized due to multiple bone fractures.

If remission is not achieved, the tumor continues to grow, affecting new tissues and organs, undergoes symptomatic treatment, most often associated with painkillers. Palliative therapy can improve the patient’s quality of life with fatal injuries. As a result, there is an improvement in the emotional and psychological state, which is the main goal of this kind of therapy. Patients receive professional help from psychologists. They work with the perception of the fear of death, helping the patient not to panic, worsening his own condition and weakening the body with constant stress. With the right treatment in the late stages, a comfortable life with small cell lung cancer in the late stages is possible. Treatment and prophylactic irradiation of the brain prolongs life by two years.

Both in the later and in the early stages of the disease, self-treatment is impossible and even dangerous. With the diagnosis of small cell lung cancer, even taking vitamins can worsen the condition. People who use folk methods or try to get rid of the disease, eliminating the symptoms, lose time, worsening their chances of recovery. The earlier the patient turns to professional doctors, the greater the chances of a long and comfortable life.

Treatment or lack of medical care strongly influences the prognosis of the disease. If the patient does not receive treatment, he burns three to four months after the pathology enters the last stage, when distant metastases begin to appear, which are formed in organs that are well supplied with blood.

If a patient goes through complex therapy, the period of remission and a stable period increases significantly: if the disease is diagnosed in the initial stages, then the probability that the patient will live for five years is 80% of cases. If the second stage of small cell lung cancer is diagnosed, the probability drops to 60%, most patients live with a diagnosis of less than five years. If the patient turned in the late stages of the disease, the prognosis becomes extremely disappointing, because only 5-10% of patients were able to cross the five-year survival limit with lung cancer.

There are a lot of factors that indirectly affect the patient's life span: not the last is considered the age, general health, psychological and psychiatric condition of the patient, the presence of concomitant or other chronic diseases.


Lung cancer is a serious medical and social problem, in developed countries it is the most common malignant tumor and is the most common cause of death from cancer pathology. According to the International Agency for the Study of Cancer, about 1 million new cases of lung cancer are reported every year in the world, and 60% of cancer patients die as a result of this disease.

In Russia, lung cancer also takes the 1st place among oncological diseases and its share in this pathology is 12%; in 15% of cases, lung cancer was diagnosed in deceased cancer patients. Men suffer from lung cancer much more often, every 4th malignant tumor in men is lung cancer, in women it is only every 12th. According to 2000 data, lung cancer caused the death of 32% of men, and 7.2% of women who had any malignant neoplasms.


The main causes of any cancer include carcinogens (such as tobacco smoke), ionizing radiation, and viral infection. Their effect causes cumulative changes in DNA in the lining tissue of the bronchi of the lung (bronchial epithelium). The more tissue is damaged, the higher the risk of developing cancer.


According to the medical classification refers to stage 4.

According to the histological picture of the studied tissues (morphological classification), the following are distinguished:

  • small cell (IRL),
  • non-small cell or large cell (NSCLC),
  • adenocarcinoma (a tumor affects the glandular tissue of the lung),
  • mixed type (lesion of large areas of the lung with a soft tumor),
  • squamous.

In turn, MRL is divided according to the shape of tumor cells: pleomorphic, oat-cell, spindle-cell.

Among the main reasons contributing to the emergence of the disease, called smoking.

Among others, there are:

  • work in production, where there are toxic and harmful substances,
  • unfavorable ecological living conditions,
  • hereditary factors, propensity for cancer,
  • lung cancer can be triggered by other lung tissue diseases,
  • complications after severe forms of infectious diseases.

The causes of the genesis (development) are studied by oncologists. Scientists identify lung tissue cells that are transformed into cancer cells.

There are several fundamental theories and research studies. Given the complexity of biochemical processes and the variety of forms of SCLC, each has practical confirmation.

Symptoms and manifestations of MRL

Small cell lung cancer is dangerous because the early stages are mild, but the disease develops quickly. Often, the first symptoms appear when a sufficiently large area is affected and metastases begin to appear. Therefore, prophylactic examinations and x-rays can prevent the development of the disease.

Reasons that indicate that the examination and consultation of a doctor is necessary:

  1. If smoking is accompanied by coughing (smoker's bronchitis) and seizures become more frequent, this is an excuse to get tested.
  2. Frequent respiratory infections, turning into bronchitis.
  3. There was shortness of breath, which was not observed previously. There may be a characteristic whistle and noise when breathing (stridor).
  4. The above symptoms are accompanied by weight loss and increased fatigue and weakness.
  5. On the origin and development of the disease can indicate sputum with blood.

In case of a possible appearance of metastasis and their penetration into other organs, the following symptoms are possible:

  • pain in the bones and back (penetration into the bone tissue),
  • Strong headache. Disorders characteristic of stroke (impaired coordination, blurred vision, seizures, numbness of the extremities) may indicate that metastases penetrate the head.

Stages of development and stage

It is easier to cure small cell lung cancer at an early stage. Treatment is prescribed immediately after the results of the examination. The nature of medical treatment depends on the results of the examination and the stage of the disease.

The stage of cancer is classified according to the size of the area affected by the tumor and the spread of metastases.

  1. Oncological neoplasm up to 3 centimeters. The pleura and lymph nodes are not affected.
  2. Oncological neoplasm up to 3 centimeters. Metastases of the lymph nodes and bronchi are affected.
  3. Oncological tumors of various sizes. The organs of the thoracic cavity and nearby lymph nodes are affected.
  4. The defeat of the whole organism in the form of metastasis penetration into remote areas of the body.

Most often, patients are treated in the first and second stages, which significantly increases the chances of healing.


Given the seriousness of the disease and its rapid dynamics, conduct a comprehensive survey.


Tissue examination, (morphological diagnosis):

  • using an endoscope, examine the lung tissue and bronchi (bronchoscopy),
  • lung puncture,
  • examination of tissues for the presence of cancer cells (biopsy).

Examination using medical equipment for localization, tumor size, metastasis spread:

  • CT scan,
  • Magnetic resonance imaging,
  • positron emission tomography.

The doctor analyzes the data, conducts examination of the patient. Considered age and general condition. Based on the information collected, a course of treatment is prescribed.

Treatment methods

With common characteristic signs of the course of the disease, the condition of the body of each person individually. The specialist selects the course based on a combination of factors. There are several techniques that are used to combat the SCLC.

Small cell lung cancer treatment:

  • Surgical removal of the tumor. The operation can have a positive effect on stages 1 and 2. In addition, other courses of treatment are prescribed to prevent recurrences and metastasis. There are different types of resection (removal) of lung tissue. Perhaps removing the entire lung, or individual sections.
  • Drug treatment with special drugs cytostatics. Chemotherapy. Most often, the treatment takes place in a hospital, in order to monitor the dynamics. The form of medication (pills or intravenous injections) are approved by the attending physician. The main goal is the remission of the disease, that is, the suspension of development. Chemotherapy is conducted intermittently. In combination, drugs are taken that neutralize the side effects of cytostatics and restore immunity.
  • After a course of chemotherapy or during it, radiation therapy (radiotherapy) is prescribed. In radiation therapy, beam ionizing radiation is used, locally acting on the tumor cells of the neoplasm. Cancer cells are more susceptible to radiation than healthy ones. As a result, the tumor cell structure is destroyed, and it dies. The development of a tumor and metastasis is suspended, as the process of development and division stops. The main disadvantage of the method is that affecting the affected areas affects healthy tissue. But a new generation of linear accelerators with 3D visualization has appeared. Initially, the body is scanned, then the affected areas are marked, and only then is the irradiation performed.

The combination of these basic methods suspends the course of the disease and provides an opportunity for the development of positive dynamics. Modern equipment and new drugs give a person hope that pulmonary cancer can be cured.

Treatment statistics

IRL belongs to the group of severe oncological diseases.

On average, not more than ten percent of patients experience the five-year threshold. With early diagnosis and effective treatment, the survival rate after five years is 15-17 percent. Compared to cancer of other organs, this is the lowest survival statistics.

But medicine is developing rapidly, which gives hope. The main thing to remember is that the disease retreats first of all before those who believe in it.

Watch the video: Small cell lung cancer may respond to combination of immunotherapy and targeted therapy (December 2019).