Lung Cancer Symptoms and Diagnosis

Lung cancer ranks first among cancer-related deaths worldwide.
Lung cancer is the most common type of cancer in men, and it has also become frequent in women due to the rising rate of smoking.
Since lung cancer develops primarily due to smoking, the risk of lung cancer can be reduced and prevented if smoking is ceased.

It is our country's most common type of cancer and is usually centrally located.

Risk Factors for Lung Cancer

Smoking

Smoking is responsible for approximately 80-85% of lung cancer cases. It is more common in smokers, especially for squamous cell lung cancer and small cell lung cancer. There is a linear relationship between the number of cigarettes consumed daily, the duration of smoking, and the risk for lung cancer.

Genetic Factors

The incidence of lung cancer is slightly higher in individuals with a family history of lung cancer.

Occupational Exposure to Chemical Substances

Radiation Exposure

Some Prior Lung Diseases

The scar tissue in pulmonary tuberculosis, empyema, interstitial fibrosis, and other lung diseases with tissue destruction may form a basis for lung cancer. These patients are at high risk of adenocarcinoma than different lung cancer types.

Asbestos exposure, the most important known risk factor for mesothelioma (lung membrane cancer), also increases the risk of lung cancer.

Note: Especially people with a family history of cancer are at high risk with the addition of other threats. Smoking status plays a significant role in this kind of patient.

Classification of Lung Cancer by Cell Type

Small cell lung cancer: The incidence of small cell lung cancer among all lung cancers is approximately 15-20%.

Non-small cell lung cancers

Squamous cell carcinoma

The most common type in our country and is usually centrally located.

Adenocarcinoma

Adenocarcinoma of the Lung is the most common type in some countries. Its frequency has also started to increase in our country. It is generally located peripherally.
The course and treatment approach of small and non-small cell lung cancer is entirely different.

What are the symptoms of lung cancer?

Lung cancer symptoms can be examined in 2 groups, local signs and extrapulmonary symptoms:

  • Most of the patients are asymptomatic in the early period.
  • Cough: Although it is the most common symptom, patients do not go to the doctor with this complaint. Blood in the sputum may be a sign of cancer, and a doctor should be consulted.
  • Symptoms include expectoration, shortness of breath, spitting up blood, hoarseness, chest, shoulder, arm, or back pain, and wheezing.

Extrapulmonary manifestations of lung cancer

  • It may be due to the metastases of the tumor to other organs and some hormonal substances released from cancer.
  • The symptoms of metastasis are specific to the organ.
  • Widespread excruciating pain in bone metastases is joint.
  • In brain metastases, unconsciousness, seizures, loss of muscle strength, and visual disturbances may occur.

Diagnosis of Lung cancer

  • We are performing a detailed examination of patients who present to our clinic.
  • Chest X-ray serves as an essential diagnostic tool
  • Presentations such as tumors or infections caused by cancer, pleurisy (fluid accumulation), and atelectasis (lung collapse) may be detected.

Computed tomography of the thorax (Thorax CT) scanning is performed
If a tumor or other appearance associated with the cancer is detected in the chest X-ray, CT should be performed for further diagnosis.
CT also shows nodules that are not visible on chest X-rays.
After the standard chest X-ray and computed tomography examination, the regional spread of the disease can be estimated, and its localization is revealed. The physician can now decide which biopsy method will be required for a definitive lung cancer diagnosis.

Biopsy: A biopsy is performed to diagnose lung cancer and determine the cell type if cancer is suspected.
Bronchoscopy: it is preferred in lesions that are located centrally.
Trans Thoracic Needle Biopsy: In tumors located at the more extreme points of the lungs, a biopsy can be taken by entering the skin with a needle under ultrasonography or computed tomography guidance. Cells are aspirated.
Tru-cut biopsy: In tumors located at the more extreme points of the lungs, excisional biopsy is performed by entering through the skin under the guidance of computed tomography. These biopsies are much more valuable for genetic studies for smart drug treatments.
Navigational bronchoscopy and endobronchial ultrasonography; Due to technological developments in recent years, tumors located at the endpoints of the lung can also be reached with navigational bronchoscopy.

Sputum cytology.

Lung cancer treatment

Lung cancer treatment requires a multidisciplinary approach.

  • Pulmonary diseases
  • Thoracic surgery
  • Pathology
  • Radiology, Nuclear Medicine,
  • Oncology collaboration are required.

In lung cancer, different approaches can be applied according to the stage of the disease, location, and histopathologic examination. Each patient should be evaluated individually for an accurate decision on treatment methods. This way, the patient’s more precise treatment method is determined, and the chance of treatment success increases. All international treatment guidelines underline the need for a multidisciplinary approach in determining lung cancer treatment.

1. Lung Cancer Surgical Treatment

  • Since lung cancer spreads to distant organs and remains asymptomatic, we can only operate on 20-30% of patients.
  • A preoperative evaluation of the patient is done.
  • Pulmonary function tests of the patient are performed. If his pulmonary functions are sufficient, surgery is performed immediately.
  • If pulmonary function tests fail, the underlying disease is treated, and the test is repeated after the treatment. If the condition regresses, surgery is performed.
  • Perfusion scintigraphy can be done
  • 6-minute walking test
  • Cardiac evaluation (e.g., Echocardiography, angiography)
  • Smoking cessation is encouraged

Note: This evaluation aims to prepare the patient for surgical intervention, determine the possible risks, and prevent them.
Surgery is performed if the patient does not have distant metastases and no cancer spread in the lymph node.
During the operation, mediastinoscopy is performed, and lymph nodes are sampled and sent to the pathology laboratory for a frozen section procedure to make a rapid microscopic analysis. Pathologists report the result of the frozen section procedure while the operation is still ongoing; if cancer spreads in the lymph node, the surgery is terminated. If no cancer is distributed in the lymph nodes, the surgery continues.
The surgery can be performed in 2 ways:

Open surgery

The open method removes the cancerous lung lobe with an incision between the ribs.

Minimally invasive surgery (VATS)

Minimally invasive surgery is performed without opening the chest cavity, instead with a keyhole procedure by inserting a tiny video camera through small incisions. The surgeon operates from outside the chest. This procedure requires advanced surgeon experience. The aim is to reduce the risk of metastasis and recurrence.

Anatomical resections

(Described in detail in another section)

Segmentectomy

  • Requires slightly more experience in minimally invasive surgeries.
  • It is preferred if the tumor diameter is 2 cm or less.

Lobectomy

Only that lobe is removed if the tumor is located solitarily in one lobe.

Sleeve resections

To resect less lung tissue, the bronchi are sutured end to end. For example, when a whole lung needs to be removed, only one lobe is removed by sleeve resection, and the rest of the lung tissue is preserved.

Pneumonectomy

An entire lung is removed if the tumor mass is gross and involves both lobes.

Exception in operational criteria

Patients with lung cancer with metastasis do not generally undergo surgery. There are two exceptions to this.
Brain metastasis: If lung cancer has a single metastasis located in the brain, firstly brain surgery and then lung surgery can be performed (N2, if there is no cancer involvement in mediastinal lymph nodes)

Adrenal gland metastasis: If there is only one adrenal gland, surgery can be performed if there is no lymph node metastasis (N2).

2. Neo-adjuvant / Induction therapy (drug therapy) + Surgery

  • Depending on the characteristics of the tumor, surgery is preferred after chemotherapy ± radiotherapy in some patients, such as:
  • Pancoast tumors
  • N2 tumors, where mediastinal lymph nodes are involved.
  • In tumors that are in proximity to vital organs.
  • Surgery is performed 3-4 weeks after the last neoadjuvant chemotherapy course.

3. Surgery + Adjuvant therapy

4. Chemotherapy + Radiation Therapy (Definite treatment, that is, Chemotherapy ± Radiotherapy): Surgery + Adjuvant treatment

Suppose the patient is inoperable and his cancer has metastasized. In that case, we consider the disease systemic rather than local, and the treatment consists of chemotherapy and radiotherapy combined.
Chemotherapy; It is a treatment course that activates the death of fast-growing cancer cells.

5. Radiation Therapy in Lung Cancer Treatment – Radiotherapy

Radiotherapy is also a treatment choice for lung cancer.

6. Smart Medicines (Target-Oriented Therapy)

Today, targeted therapy models that have fewer side effects than classical treatment methods in lung cancer remain up to date. Various lung cancer treatment methods have been developed in current studies to treat advanced lung cancer.

In the classical treatment model, a standard treatment approach is applied according to the histopathological type of cancer. Suppose the selected treatment method is incompatible with the determined cancer genetic structure. In that case, the patient can be unnecessarily exposed to the side effects, resulting in metastasis via blood or lymph, which is associated with shorter survival.

In targeted lung cancer treatment methods, personalized treatment is formed according to the genetic characteristics of the tumor cells.

While the drugs given in routine chemotherapy kill tumor cells, they also damage other cells of our body. These drugs are given intravenously. Side effects are common, for example, nausea, vomiting, homeostasis imbalance, and hair loss.
But smart or targeted drugs are only intended to kill the tumor cells and are taken orally.
The smart drugs available today are not effective in all types of cancer. Therefore, treating lung cancer may vary from person to person.
They are generally effective in a type of lung cancer called adenocarcinoma.

It is determined whether the drug will be beneficial by performing genetic analysis from the biopsy or the specimen from surgery.

These genetic markers are:

  • EGFR
  • ALK
  • ROS.1
  • C-MET
  • B-RAF

Approximately 7-10% of patients with lung adenocarcinoma can be treated with this treatment. Especially in non-smokers and female patients, the applicability rate of this treatment can reach up to 30%.

7. Immunotherapy (Target-Oriented Therapy)

  • In recent years, it has been one of the essential methods in advanced-stage (3B and 4th stages) lung cancers.
  • It is a treatment that affects the immune system.
  • It is a form of treatment that acts by re-establishing the healthy functioning cells of the damaged immune system.
  • With this method, patients can survive longer.
  • It is used in stage 3 patients who cannot undergo surgery after chemotherapy and radiotherapy.
  • In stage 4 patients, it can be used in combination with chemotherapy in the 1st line therapy or used alone and in combination with chemotherapy as a 2nd line therapy.
  • While the frequency of side effects related to this treatment is shallow, some can be very severe.
  • One of the most critical issues about immunotherapy is that it is not beneficial for all patients.

Note: As a result, we evaluate each patient's treatment individually, discuss them in the multidisciplinary oncology council, and decide accordingly.

Smart Drug Use and Immunotherapy in Lung Cancer

Smart Medicines (Target-Oriented Therapy)

Today, targeted therapy models with fewer side effects than classical treatment methods of lung cancer are up-to-date. Smart drugs are one of them.

Various molecular-level targeted cancer treatment methods are being developed in current studies to treat advanced lung cancer.

In the classical treatment model, we prefer a standard treatment approach according to the histopathological type of cancer. When the selected treatment method is incompatible with the determined cancer genetic structure, the patient can face side effects that can affect cancerous cells. The cancer spreads to the body via blood or lymph during the time before treatment, causing death before the expected time. In targeted therapy methods, personalized medicine treats according to the gene mutations detected by examining the cancer cell.

While the drugs of routine chemotherapy kill tumor cells, they also damage other cells of our body. Side effects are common, for example, nausea, vomiting, and hair loss. This type of treatment is intravenous.
But smart drugs or targeted drugs are only intended to kill tumor cells and are taken orally.
The smart drugs available today are effective only in a specific type of cancer.
They are generally effective in a type of lung cancer called adenocarcinoma. Drug effectivity is predicted by performing genetic studies from the biopsy or surgical specimen.
Analyzed genetic markers are as follows:

  • EGFR
  • ALK
  • ROS.1
  • C-MET
  • B-RAF

Approximately 7-10% of patients with lung adenocarcinoma benefit from this treatment. The applicability rate of the smart drug can reach up to 30%, especially in non-smokers and female patients.

Immunotherapy

It is one of the most critical options in advanced stage (Stages 3B and 4) lung cancers in recent years. It is a treatment that affects the patient's immune system. It acts by re-establishing the healthy functioning of the damaged immune system. With this method, patients can survive longer.
It benefits stage 3 patients who cannot undergo surgery after chemotherapy and radiotherapy treatment.
In stage 4 patients, it can be used in combination with chemotherapy in the 1st line therapy or alone as a 2nd line therapy.

While the frequency of the side effect rate related to this treatment is low, some side effects can be very severe.
One of the most critical issues about immunotherapy is that it is not beneficial for every patient.
In our country, this treatment method is not covered within the scope of health insurance.

Note:As a result, we evaluate each patient's treatment individually, discuss them in the multidisciplinary oncology council, and decide accordingly.

How Is Staging In Lung Cancer?

Staging in lung cancer is critical in terms of the course of the disease and the determination of the treatment method.
1. Small cell lung cancer, there are two stages localized and diffuse stage;
Localized phase; In small-cell lung cancer, the disease is limited to one side of the chest without spreading to the opposite lung or other organs.

Diffuse stage; In small-cell lung cancer, the disease has metastasized to organs other than the lung or the opposite lung.

Treatment is different in localized and diffuse stages of small-cell lung cancer, and we stage the using the following:

  • Brain CT or brain MRI
  • Upper abdomen CT
  • PET-CT

2. Since surgery is the most effective treatment in the early stages of non-small cell lung cancer, staging is critical.

Lung cancer is staged according to the TNM system.
T is used to define many features, such as tumor size, the relationship of the tumor with neighboring tissues and organs, and the bronchoscopic appearance of cancer.
N defines the presence or absence of metastases in the tumor's regional or distant lymph nodes.
M is associated with distant organ metastases, and there is no metastasis in M0 cases.

Staging with non-invasive methods in lung cancer (Imaging methods)

  • Computed Tomography
  • Brain MRI
  • USG
  • PET-CT: Detects metastasis. It can not detect brain metastasis. It should be kept in mind that PET uptake is weak or absent in some cancer types.

Non-invasive methods of staging in lung cancer

Minimally invasive methods

Minimal invazif yöntemler

  • Bronchoscopy
  • EBUS ; Endobronchial ultrasonography
  • EUS: Endoscopic ultrasonography

Invasive methods

  • Bronchoscopy
  • Video-assisted mediastinoscopy
  • Thoracoscopy (VATS)
  • Mediastinotomy
  • Supraclavicular biopsy
  • Pleural fluid biopsy

Note: The main point to be considered here is that a biopsy should be performed in lymph nodes with PET-CT involvement or in places where there is a possibility of cancer. PET-CT positivity can also be detected in non-cancer diseases such as tuberculosis, other infectious diseases, and sarcoidosis, which are common in our country.
Deciding without a biopsy may lead to the wrong treatment regimen. N2 (mediastinal lymph nodes), that is, it is necessary to biopsy large lymph nodes with PET involvement on the trachea. The least harmful method to the lymph nodes is chosen.
The first choice for the patient is endobronchial ultrasonography (EBUS) or Endoesophageal ultrasonography (EUS). Endobronchial ultrasonography is a safe and outpatient bronchoscopic method that does not require hospitalization. With this method, the probability of accurate lung cancer staging is over 85-90%. If there is no success, more invasive procedures such as video mediastinoscopy or thoracoscopy (VATS), surgical staging methods, are preferred. Surgical staging methods are performed under general anesthesia, and a vast number of sampling is done.

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