Lung cancer
- davorkust
- Jun 29
- 7 min read
Updated: Jun 30
Introduction and incidence
The lungs are a pair of organs in the chest, and their main function is to filter the air we breathe, extracting oxygen and releasing it into the blood, and taking carbon dioxide from the blood and releasing it from the body through exhalation. The left lung is divided into two lobes, and the right is slightly larger (the left side of the chest is partly occupied by the heart) and is divided into three lobes. Lung cancer is one of the most common malignant diseases in the world, and is considered one of the easiest to prevent. According to data from the Cancer Registry for 2017, lung cancer is the second most common cancer in men in Croatia, accounting for 17% of all new cancer cases that year, while it was third in women with 9%. It has been noticeable over time in Croatia and the world that the proportion of female patients has increased, due to the increase in the number of female smokers, while lung cancer was previously a disease predominantly affecting men.
There are two main types of lung cancer: small cell lung cancer, and all others, collectively called non-small cell lung cancer. The second type is significantly more common, and can be further divided into squamous cell carcinoma (squamous cell cancer), adenocarcinoma, large cell carcinoma, and some rare subtypes. The frequency of individual types is shown in Figure 1.
Risk factors
The main risk factor for the development of lung cancer is smoking, and the vast majority of cases of this disease could be completely prevented without any other methods by simply quitting smoking. Smoking is a risk factor for all subtypes of lung cancer, and the largest proportion of non-smoker cancers is adenocarcinoma (although the largest proportion is still caused by smoking). The risk exists with smoking cigarettes, cigars, and pipes, and is higher the longer and more a person smokes. Passive smoking is also dangerous. Additional risk factors include occupational exposure (in the workplace) to asbestos, arsenic, chromium, beryllium, nickel, soot or tar, exposure to radon, radiation from diagnostic or therapeutic procedures to the chest area, air pollution, and a family history of lung cancer.
Signs and Symptoms
Although there are some differences, the symptoms of all subtypes of lung cancer are similar. They may include chest discomfort or pain, a cough that does not stop or gets worse over time, difficulty breathing, wheezing, blood in the sputum, hoarseness, loss of appetite, weight loss for no apparent reason, constant fatigue, difficulty swallowing, swelling in the face or neck veins. Be sure to consult a doctor if you notice any symptoms that do not go away over time.
Diagnosis
The basis is a detailed examination of the patient and taking a thorough medical history. Usually the first examination is a chest X-ray, but it is definitely recommended to have a chest CT scan, which provides a much more precise image and the ability to detect much smaller changes in the lung parenchyma. Sputum (sputum) can be analyzed under a microscope for the presence of tumor cells. Thoracentesis, on the other hand, refers to the removal of fluid accumulated between the lungs and the pleura with a thin needle if said fluid is present, and after removal, it can also be examined for the possible presence of tumor cells. In any case, if the test results indicate the presence of lung cancer, in most cases it will be necessary to perform a biopsy (tissue sample taking) to confirm the diagnosis. The above can be done in several ways: transthoracic biopsy (taking a sample through the skin, often with the use of endoscopic ultrasound or CT to more precisely locate the suspected lesion), bronchoscopy (insertion of a thin, long, flexible tube through the nose or mouth through the trachea into the lungs; the device has a tool at the tip for taking a tissue sample), and less often, a surgical approach can be used (thoracoscopy, mediastinoscopy, thoracotomy, etc.). In addition to confirming the disease, the tissue sample is additionally tested for the presence of certain genetic mutations, which is important in the later decision on treatment. Among other tests, it is recommended to perform a CT scan of the abdomen to evaluate the possible spread of the disease, and the tumor marker CYFRA21-1, as well as other tests depending on the specific situation/indication. You can read more about the diagnosis of malignant diseases in general in a separate article.
In January 2020, the Ministry of Health presented the National Lung Cancer Screening Program. This is the 4th national cancer early detection program in Croatia, after breast, colon and cervical cancer. We can boast that Croatia is the first country in the EU to introduce such a program, which aims to reduce lung cancer mortality by 20% in the next 5 to 10 years. The program aims to include people between the ages of 50 and 75 who are active smokers or have stopped smoking 15 years ago, and have smoked at least a pack of cigarettes per day for a period of at least 30 years.
Stage of the disease
Lung cancer, like other malignant diseases, is divided into 4 stages.
In stage I, the tumor is confined to the lungs and is up to 4 cm in size.
In stage II, the tumor is up to 7 cm in size, or up to 5 cm if lymph nodes on the same side of the chest as the primary lung tumor are also affected.
In stage III, lymph nodes on the same side of the lung are affected, and nodes on both sides of the chest and above the collarbone may also be affected, and the tumor can be any size. Surrounding structures such as the esophagus, trachea, or heart may also be affected.
In stage IV, the disease has spread to the lungs (lung metastases from the primary lung tumor), tumor cells have been found in the fluid around the lungs or heart, or distant metastases are present in organs of the body (e.g., liver, bones, brain).
Treatment
Stage I. Treatment options include surgery (wedge resection, segmental resection, and lobectomy are some of the possible procedures; as a rule, part of the affected lung is removed), radiotherapy (including stereotactic radiotherapy, and is used in patients who are not candidates for surgical treatment for any reason or refuse surgery)
Stage II. Treatment options for stage I can be used in stage II, but in some patients it will be necessary to remove the entire lung by surgery. Also, in some patients, chemotherapy treatment will be required in addition to surgery (before or after surgery).
Stage III. This stage of the disease includes patients with very diverse disease spread in relation to surrounding structures, and therefore treatment needs to be adapted to the specific situation. Possible options include various combinations of surgery, radiotherapy, and chemotherapy. Most patients will receive multiple treatment options, in combination or separately. In some patients, immunotherapy with durvalumab can be applied as maintenance therapy after chemotherapy and radiotherapy. Patients who are not in a good enough general condition for such intensive treatment will be agreed to an individualized protocol which, for example, may include only radiotherapy.
Stage IV. In case of extended disease, it is necessary to apply systemic treatment, and the choice of therapy depends to a large extent on the previously detected mutations in the tissue sample of the previous biopsy. If the patient's tumor shows one of the analyzed mutations, therapy directly aimed at that mutation can be applied. Potential mutations of the EGFR gene (receptor for epidermal growth factor - some of the drugs used when the mutation is present are osimertinib, gefitinib, erlotinib, afatinib), ALK (so-called anaplastic lymphoma kinase - possible therapies are alectinib, crizotinib, ceritinib, brigatinib and lorlatinib), BRAF (possible therapy with BRAF and MEK inhibitors such as dabrafenib and trametinib), ROS1 (possible therapy with crizotinib and entrectinib). NTRK inhibitors such as larotrectinib are also in use. Some targeted drugs can be used with chemotherapy regardless of the mutation finding, such as bevacizumab, cetuximab and necitumumab. In addition, the presence of the PD-L1 protein is analyzed, which is important for the possible use of immunotherapy (for example, nivolumab, pembrolizumab and atezolizumab) - depending on the higher or lower expression of PD-L1, immunotherapy can be used alone or in combination with chemotherapy. For patients who are not candidates for targeted therapy or immunotherapy, the treatment of choice is chemotherapy. In some patients, treatment can be started with polychemotherapy (several cytostatics at once), and then continued with maintenance therapy (one cytostatic). It is important to note that one of the options is also participation in appropriate clinical trials.
Additional interesting facts
What is the CYFRA21-1 tumor marker and should I do it?
CYFRA21-1 is one of a series of tumor markers used in oncology. It is actually a fragment of a protein called cytokeratin 19. Cytokeratins are substances that are important structural proteins of human cells. As such, cytokeratins are not soluble in serum/blood, unlike their fragments that are, so CYFRA21-1 can be measured in the blood. What is interesting about cytokeratin 19 (and therefore its fragment CYFRA21-1) is that although it is found in many tissues in the body, it particularly accumulates in the lungs, especially in active malignant disease in the lungs. As a result, the concentration of the CYFRA21-1 marker in the blood can also increase. The aforementioned marker is not generally used as a method of detecting lung cancer, but it can be a good indicator of the effectiveness of treatment if the values fall during therapy (and vice versa), and to this extent it is a useful tumor marker that, along with imaging diagnostics, can provide the doctor with reliable information about the activity of the disease itself.
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