Lung cancer represents the uncontrolled growth of abnormal cells in one or both lungs. It almost always begins in one lung, then spreads to lymph nodes or other tissues, including the other lung. Lung cancer can also metastasize throughout the body, spreading to the bones, brain, liver, or other organs. Because the lungs are large, cancer can grow for many years before it is detected. In fact, lung cancers can easily spread outside the lungs without causing any symptoms. Even when an underlying symptom, such as a persistent cough, occurs, it is often misunderstood as a cold, bronchitis, or allergy.
Most people who get lung cancer are smokers. However, not all smokers get cancer. In some cases, people who have never smoked also get lung cancer, which occurs when exposed to certain carcinogens in the workplace, such as asbestos, or radon gas, where the risk of developing lung cancer increases. Even when diagnosing lung cancer, it is essential to stop smoking if the person was a smoker. Smoking cessation will affect the effect of the therapy. There are more than a dozen different types of lung cancer. They differ in the type of cells found in tumors.
ETIOLOGY – causes
Cigarette smoking
Cigarette smoking is a direct cause of 90% of lung cancers in men and 79% of lung cancers in women. It is widely accepted as a major contributing factor to the increase in lung cancer incidence in this century.
Prospective cohort studies show that the risk of lung cancer in male smokers is 22 times higher than in non-smokers, and for female smokers, it is 12 times higher than in non-smokers. Cigarette smoke contains more than 4,000 chemical ingredients; at least 43 have been identified as carcinogens. Tobacco-induced carcinogenesis is a complex, multistage process. Accumulated DNA destruction in lung epithelial cells by exposure to inhaled carcinogens or their metabolites results in malignancy after a period of long latency.
Smoking cessation
With smoking cessation, a reduction in the risk of death from lung cancer than those who continue to smoke was observed within 5 years. The risk progressively decreases over time after smoking cessation. Even after 25 years or more, after smoking cessation, the risk of lung cancer among ex-smokers may be higher than the risk in individuals who have never smoked. However, it is understandably lower than those who continue to smoke.
Other factors
Although active tobacco smoking greatly increases the risk of lung cancer compared to the risk in non-smokers (the risk is lower in them), only 10% of smokers get lung cancer. At the same time, approximately 10% of lung cancers occur in people who have never smoked. Apart from active smoking, other factors also play a role in developing lung cancer.
Passive smoking
Prolonged inhalation of cigarette smoke from other people has been shown to increase lung cancer risk in non-smokers.
Air pollution, urban environment, and geographical location
The incidence of lung cancer and mortality rates are higher in industrialized countries and urban areas, which leads to the conclusion that air pollution contributes to the development of lung cancer.
Work environment factors
Exposure to specific work environment factors (carcinogens) by themselves or in combination with cigarette smoking can increase the risk of lung cancer. As with smoking, there is a long latency that can be up to 50 years between the first exposure to a carcinogen and lung cancer development. There is generally a relationship between the amount and duration of exposure about the risk of developing lung cancer. These carcinogens include asbestos fibers, arsenic, chromium, nickel, chloromethyl ethers, vinyl chloride, radon gas. These carcinogens may contribute to approximately 15% of lung cancers in men and 5% in women.
Scars and diffuse fibrosis
Peripheral cancers, especially subpleural adenocarcinomas and bronchoalveolar carcinomas, are often associated with focal scarring. Scars can result from bronchiectasis, heart attack, tuberculosis, or trauma. Earlier studies showed that 3 to 75 lung cancers developed on the scar.
Hereditary (hereditary) and socio-economic factors
Several studies have shown a link between a positive family history of lung cancer and an increased risk of developing lung cancer.
PULMONARY CARCINOMA CARCINOGENESIS
As is the case with other types of cancer, carcinogenesis of lung cancer is a multistage phenomenon. Carcinogens related to initiators directly produce irreversible DNA mutations in previously normal bronchial or other epithelial cells, thus initiating carcinogenesis. Further progression to the malignant phenotype occurs with continuous carcinogen damage, which refers to promoters that secondarily alter gene expression by affecting signal transduction. Tobacco smoke contains many known and suspected carcinogens, both initiators and promoters, which contribute to lung cancer development. Environmental and work environment factors may also be involved as carcinogens or cocarcinogens. Some mutations caused by carcinogens are biologically significant and contribute to the malignant phenotype’s development or progression. Mutations can modify oncogene protein products that regulate cell growth. Other mutations modify the protein products of tumor suppressor genes that inhibit cell growth. The result is a loss of cell growth control.
DIAGNOSIS
Diagnostic procedures can be divided into several groups:
- Procedures that bring the possibility of bronchial cancer to the working diagnosis in the first place and are carried out on the level of primary health care. Refer to the: anamnestic data about smoking habits, workplace, familial predisposition, appearance and characteristics of symptoms; then physical finding on the lungs, palpation of the cervical, supraclavicular, and axillary regions, liver, and spleen. Basic laboratory processing is also performed.
- Standard chest radiogram. It reveals the size, shape, and location of the tumor. However, they cannot tell us if it is cancer.
- Cytological analysis of sputum is a microscopic examination of cells in the cough. This analysis can detect lung cancer that was not found on a standard breast radiogram. A positive finding of malignant cells in the sputum is described in 60% of cases. By taking a cough correctly, repeating the samples 3-5 times, a positive finding is obtained in about 80% of cases. The more peripheral the localization of cancer, if the bronchus is obstructed and therefore difficult to cough, the less likely it is to verify the sputum’s malignancy. However, even a positive finding of malignant cells in the cough does not show the tumor’s localization and spread, so accompanying tests are usually needed.
- Conchological processing with biopsy is required when cancer is suspected (forceps biopsy, brush biopsy, transbronchial lung biopsy), transthoracic lung biopsy, or biopsy after thoracotomy, and puncture of enlarged supraclavicular, cervical, axillary, and other lymph nodes. The pathohistological microscopic analysis will reveal whether these are cancer cells and, if so, which cell type. A biopsy can pinpoint the type of lung cancer, so these tests are critical in diagnosing cancer and assessing the best therapy.
- CT (computed tomography) I MRI (magnetic resonance) of the chest are more sophisticated methods to obtain a three-dimensional tumor image. Because CT and MRI can show lungs, lymph nodes, or other parts of the body with much greater accuracy than a standard chest radiograph. They can accurately determine whether cancer has spread from the lungs to other parts of the chest or body.
- If lung cancer is diagnosed, the person may undergo SCI (scintigraphy) of the bones to see if the lung cancer had spread. Thus, bone abnormalities can be observed, and it can be distinguished whether they are caused by some other disease (e.g., arthritis) or lung cancer. Other methods (abdominal ultrasound, possibly CT of the brain) are also performed to confirm or rule out the malignancy propagation. It should be emphasized that these methods verify macrometastases and that the issue of micrometastases, especially in the microcellular type of cancer, remains open.
- Diagnostic procedures assess the cardiorespiratory, hematopoietic, renal, hepatic, and other systems for selection and application of therapeutic procedures.
PULMONARY CANCER PROGNOSIS
Overall survival from lung cancer is about 10%. The disease’s stage based on the TNM system is incomparably the most important factor in determining the survival of patients with lung cancer. The International Lung Cancer Staging System, used by the American Cancer Committee and the International Union Against Cancer, provides a reproducible method for documenting the anatomical spread of T-based lung cancer (primary tumor size and invasiveness), N (nodal metastasis), and M ( presence or absence of distant metastases) system. The stage is based on the TNM classification, and patients in the same group of disease stages have a similar prognosis and therapeutic choice of drugs. In general, the higher the stage (or T, N, or M individually), the worse the prognosis.
TNM classification can be clinical, based on clinical or radiological findings, or pathological, based on examining the resection material by a pathologist. The TNM classification criteria are the same for both clinical and pathological staging.
INTERNATIONAL TNM CLASSIFICATION OF PULMONARY CANCER (1997) 1.2
In the assessment of anatomical enlargement, lymph node involvement, and the presence of distant metastases, we use the TNM classification:
Primary tumor
T0 – No visible primary tumor
TX – The primary tumor cannot be identified. The tumor is proven by the presence of malignant cells in the sputum or bronchial lavage but is not seen radiologically or bronchoscopically.
TIS – Cancer in situ
T1 – Tumor smaller than 3 cm in largest diameter, surrounded by lungs or visceral pleura, without bronchoscopically visible invasion proximal to the lobar bronchus (i.e., not in the main bronchus).
T2 – Tumor of any of the following sizes or extensions:
- More than 3 cm in maximum diameter
- Involves the main bronchus; 2.2 cm distal to the carina
- It affects the visceral pleura
- It is associated with atelectasis or obstructive pneumonitis that spreads to the hilar region but does not affect the lungs themselves.
T3 – A tumor of any size that directly affects any of the following structures: chest wall, diaphragm, mediastinal pleura, parietal pericardium; or a tumor in the main bronchus less than 2 cm away from the carina but not affecting the carina; or associated atelectasis or obstructive pneumonitis of the affected lung.
T4 – Tumor of any size involving the following: mediastinum, heart, large blood vessels, trachea, esophagus, vertebrae, carina; or a tumor with a malignant pleural or pericardial effusion, or with a satellite tumor nodule (s) within the ipsilateral lobe of the lung with a primary tumor.
Lymph node capture
N0 – No metastases in regional lymph nodes.
N1 – Metastases in ipsilateral peribronchial and/or ipsilateral hilar lymph nodes and intrapulmonary lymph nodes affected by direct spread of the primary tumor.
N2 – Metastases to ipsilateral mediastinal and/or subcarinal lymph nodes.
N3 – Metastases to contralateral mediastinal, contralateral hilar, ipsilateral or contralateral scapular, or supraclavicular lymph nodes.
Metastases
M0 – No visible distant metastases.
M1 – There are distant metastases.
STAGES OF PULMONARY CANCER
Before choosing the best treatment, it is necessary first to evaluate the stage of lung cancer. Stages of lung cancer refer to whether cancer has spread to the lungs and/or other organs. Surgical treatment, chemotherapy, and radiation therapy can be used to treat lung cancer, but whether to use them individually or in combination is determined by how advanced the cancer is.
There are 4 stages of lung cancer:
Stage I: The cancer was localized only in the lungs and did not spread to the lymph nodes. Surgical removal of the tumor is recommended, which is successful for most patients. (While this sounds encouraging, unfortunately, most people are not diagnosed with cancer at this stage, as the symptoms are often not severe enough to suspect cancer).
Stage II: Cancer has spread to neighboring lymph nodes. Depending on the lymph nodes’ size on chest CT, additional tests may be recommended, such as mediastinoscopy to perform a lymph node biopsy. Mediastinoscopy can determine whether lymph nodes are affected by cancer or are enlarged only due to cancer inflammation. If this procedure shows only minimal traces of cancer in these lymph nodes, surgical removal of the main tumor with concomitant irradiation and/or chemotherapy of the lymph nodes is recommended.
Stage III: Cancer has spread to lymph nodes in the lungs. Stage III has two “types”:
If it’s a solitary tumor mass, that’s stage III-A. Most doctors will recommend starting treatment for stage III-A with chemotherapy or a combination of chemotherapy with radiation therapy. Then, depending on this treatment’s success, the remaining tumor can be removed surgically.
This combination of chemotherapy with surgical treatment or irradiation offers the best treatment options. If cancer in the chest has spread to more than one area, it is called stage III-B.
Most doctors do not recommend surgical treatment for stage III-B. The combination of chemotherapy and irradiation is usually of the greatest benefit.
Stage IV: This is the most advanced stage of lung cancer. Cancer has spread to the body’s distant parts – to the liver, bones, brain, or some other organ. Most doctors agree that stage IV chemotherapy is the most effective treatment.
TNM CLASSIFICATION AND STAGES:
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STAGE 0
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TIS
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N0
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M0
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STAGE I
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T1 |
N0
N0 |
M0
M0 |
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STAGE II
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T1 |
N1
N1 |
M0
M0 |
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STAGE III A
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T1 |
N2
N2 N0 N1 N2 |
M0
M0 M0 M0 M0 |
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STAGE III B
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ANY T
T4 |
N3
ANY N |
M0
M0 |
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STAGE IV
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ANY T
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ANY N
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M1
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After selecting patients according to the histological type and extent of the disease, the general condition of the patient, i.e., “performance status,” is assessed. This estimate is subject to a subjective factor, so we use classification according to Karnofsky :
| 100% | without symptoms of the disease |
| 80-90% | capable of doing easier jobs |
| 60-70% | less than 50% of the time, it is bedridden |
| 40-50% | more than 50% of the time, it is bedridden |
| 20-30% | the patient is constantly in bed |
THERAPY
Lung cancers are potentially curable by surgical resection in the early stages. In general, stages I, II, and IIIA of non-small cell carcinomas, as well as microcellular carcinomas in some cases, are treated by surgical resection. Microcellular carcinomas are usually present at an advanced stage and, as they occasionally respond to chemotherapy and radiation, are usually treated in these ways.
Patients with more advanced stages of non-small cell carcinoma, or who are not otherwise for surgical treatment, may be treated with chemotherapy and radiation with generally poorer results.
A significant factor for the poor prognosis of lung cancer is that most patients are already present with an advanced stage when diagnosed. In one large study, out of nearly 2,000 patients, about 64% of patients had advanced local spread or distant metastases, while only 29.4% had localized disease and 6.6% only regional metastases. (3) In recent studies of 1198 patients for whom the stage was known, 60% had distant metastases, 26% regional metastases, and only 15% localized disease. (4)
Of those with an apparently early stage of the disease, assuming they are treated with surgical resection, approximately half of the patients will die from lung cancer. This group of patients is of particular interest since identifying biological markers is used to determine probable disease progression, which can be used to identify patients for more aggressive therapeutic measures or therapeutic studies.
Several studies have shown that cell type and degree of differentiation affect prognosis. Cell types associated with a poorer prognosis are usually present at an advanced stage, reflecting their more aggressive behavior. When the stage is taken into account, many studies have failed to show a significant difference in survival between different cell types.
Microcellular carcinoma is generally associated with the worst prognosis. It is most likely to be detected in more advanced stages (83.9% of stage III microcellular carcinomas versus 65.1% of adenocarcinomas, 57% of large cell carcinomas, and 56.9% of squamous cell carcinomas). (3)
Squamous cell carcinoma is more likely to be present at an early stage than other cell types and has longer survival in some slightly but not all studies. The longer survival seen in Pancoast tumors, ranging from 23% three-year survival to 31-34% five-year survival in various studies, apparently refers to the high percentage of squamous cell carcinomas. (6,7)
Solitary peripheral bronchioalveolar carcinomas have better five-year survival than other types, from 23 to 100% in different studies. 4)
Thus, it is first necessary to determine the stage of lung cancer to apply the most effective form of treatment. Each cancer case is different, so the treatment may differ from what will be mentioned.
Stage I
Recommended treatment: surgical removal of the tumor.
Stage II
Recommended treatment: surgical removal of tumors and lymph nodes, concomitant irradiation, and/or chemotherapy.
If it is the stage I or stage II lung cancer, surgical removal of the cancer is still essential. Recovery will vary from person to person, depending on age, health, or other factors.
Stage III
Stage III-A: Recommended treatment: chemotherapy and irradiation to shrink the tumor, followed by surgical treatment to remove the remaining tumor.
Stage III-B: Recommended treatment: a combination of chemotherapy and irradiation therapy to shrink the tumor.
Stage IV
Recommended treatment: a combination of chemotherapeutics and finding the most effective ones.
SURGERY
In the stage, I or stage II lung cancer, surgical removal of cancer with possible lymph nodes possible removal is still essential. Recovery will vary from person to person, depending on age, health, or other factors.
Chemo and irradiation therapy
Chemotherapy
is usually a combination of drugs used over several weeks or months, depending on the general health condition, the type of lung cancer, and its prevalence in the body. Chemotherapy can be used to slow the growth of cancer, prevent it from spreading, reduce the symptoms caused by cancer, or eliminate all cancer cells from the body. Even when chemotherapy cannot cure cancer, it can help a better and longer life.
Irradiation therapy
is used to reduce or stop tumor growth. In fact, radiation “kills” tumor cells. In some cases, radiation is used to shrink the tumor before surgically removing it. It can also be used after surgical treatment to destroy the remaining cancer cells. Irradiation and chemotherapy are often used in conjunction with surgery. The overall treatment regimen will depend on the total amount of radiation required as determined by the radiotherapist. This amount is divided into “daily doses” that are considered effective in an individual case, with the least damage to the body’s normal cells. Radiation treatment usually lasts a few weeks, followed by a rest period of a few weeks, before the next cycle begins.
Side effects of radiation and chemotherapy
The side effects of chemotherapy or radiation vary from person to person, just as lung cancer symptoms will vary. Some people have only a few side effects, or none at all; other people have many of them. The two basic things that will have the greatest impact on side effects are therapeutic doses and how the body reacts to them.
Unfortunately, some of the side effects of cancer therapy are difficult to control. When chemotherapy or irradiation is used to destroy cancer cells, some healthy cells and tissues can also be affected. However, there are ways to reduce many of the side effects of treatment.
Side effects of chemotherapy
Chemotherapy can lead to one or more of the following side effects:
- nausea and vomiting
- fatigue and anemia
- temperature and infection
- hair loss
Because chemotherapeutics work on rapidly dividing cancer cells, they will also damage healthy rapidly dividing blood cells, including:
- infection-fighting cells (leukocytes)
- blood-clotting cells (platelets)
- cells that carry oxygen to all parts of the body (erythrocytes)
- hair root cells (resulting in hair loss)
- cells lining the digestive tract (resulting in nausea or vomiting)
These chemotherapy-related symptoms will usually disappear gradually during recovery or after stopping treatment.
Side effects of radiation
Side effects of radiation include:
- skin irritation and hair loss in the treatment area
- fatigue that usually increases during the treatment itself
- dry, sore throat, and difficulty swallowing
- pain and numbness in the shoulder and chest muscles
- nausea (not typical)
It is important to note that the skin during irradiation treatment is prone to become very tender and sensitive. It may become red or dark, and hair in the area may fall out. It is necessary to be very careful and wash it with lukewarm water and mild soap. Do not use powder, creams, or other ointments on the area during the treatment and for a few weeks after the end of the treatment.
PREVENTION
Avoidance of risk factors in particular:
Smoking cessation
Smoking cessation reduces the risk of dying from lung cancer compared to those who continue to smoke.
The risk progressively decreases over time after smoking cessation. Even after 25 years or more, after smoking cessation, the risk of lung cancer among ex-smokers may be higher than the risk in individuals who have never smoked. However, it is understandably lower than those who continue to smoke.
Avoidance of air pollution
Avoidance of known carcinogens
Healthy and balanced diet
