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Lung Cancer tests and diagnosis

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How is a tumour located
Confirmation of the tumour
How is the degree of tumour extension classified
Staging lung cancer

The first step is to analyse the associated symptoms and obtain all the relevant information on risk factors: such as smoking, occupation and family history. After the interview (anamnesis), the professional requests any additional tests necessary for the diagnosis and staging of the disease. Once diagnosed, the specialist evaluates the best treatment strategy, which is discussed in a multidisciplinary committee of specialists in pulmonology, radiology, nuclear medicine, anatomic pathology, medical oncology, radiation therapy, thoracic surgery, molecular biology and advanced lung cancer nursing practice.

How is a tumour located

The size and extent of the tumour can be seen from imaging tests. The specialist may request any of the following tests, some of which may require the prior administration of contrast or marker, but all are painless:

Chest scan or computed tomography (CT). This shows all the organs in the thorax and abdomen (lung, heart, large blood vessels, airways, chest wall, pleura, lymph nodes, liver and adrenal glands) in great detail.

Positron emission tomography (PET-CT). This technique provides other information to that provided by chest CT. Nowadays, it is considered essential to assess the degree of extension of the disease. Before the scan, a marker is administered, which is taken up with greater affinity by tumour cells. It scans the entire body to rule out any other tumours in the rest of the body, such as the bones or the brain.

Nuclear magnetic resonance (NMR) and head computed tomography (CT). This is requested as an additional test before the diagnosis of lung cancer to rule out any metastasis to the brain.

Confirmation of the tumour

If lung cancer is suspected, an imaging test (CT or PET-CT) must be performed. If the suspected diagnosis is confirmed, a tissue sample is obtained from the tumour and a biopsy is performed. From this, the pathologist determines the cell morphology and type of lung cancer. A tissue sample is also needed to complete the genetic study of the tumour.

The technique chosen for the biopsy depends on the location of the tumour:

Fibre-optic bronchoscopy. This test consists of inserting an endoscope through the nose or mouth to see a part of the interior of the pulmonary bronchi and, if a tumour is observed, to take a biopsy. This technique is performed under local anaesthesia.

Computerised tomography-guided lung needle biopsy (CT-LNB). If a bronchoscopy fails to make a diagnosis, a fine needle biopsy of the tumour can sometimes be taken through the chest. This is guided by CT under local anaesthesia.

Endobranchial ultrasound (EBUS) and/or endoscopic ultrasound (EUS). These are highly novel techniques for taking samples from the pulmonary lymph nodes by needle puncture. Both are performed using an endoscope inserted through the mouth to take samples from inside the bronchi (EBUS) or the oesophagus (EUS). These techniques are performed under general anaesthesia.

Surgery This is indicated only if a diagnosis cannot be obtained from the previous tests. It requires hospital admission and general anaesthesia.

How is the degree of tumour extension classified

The degree of tumour extension of lung cancer depend mainly on:

The size of the tumor.
How deeply the tumor has invaded nearby tissue, such as the chest wall.
Whether the lung cancer cells have spread to lymph nodes or other parts of the body.

Doctors quantify tumour extension using the TNM classification system. The TNM classification is used to define the appropriate treatment and predict disease evolution.

Staging lung cancer

The letters TNM are used to describe lung cancer staging:

The letter T refers to the tumour size (in centimetres) and its invasion of adjacent structures. There are four categories:
- T1 - tumours smaller than 3 cm.
- T2 - tumours of 3-5 cm.
- T3 - tumours of 5-7 cm.
- T4 - tumours larger than 7 cm or with invasion of contiguous structures, such as a major blood vessel, the mediastinum (rib cage), heart, vertebral bodies or oesophagus.

The letter N refers to the pulmonary lymph nodes. They are categorised as follows:
- N0 - no node is affected by the tumour.
- N1-N3 - lymph nodes invaded by tumour cells. They are further classified as follows, depending on the location of the affected lymph nodes:
  - N1 - ipsilateral hilar lymph nodes.
  - N2 - ipsilateral mediastinal or subcarinal nodes.
  - N3 - contralateral mediastinal or supraclavicular nodes.
The letter M refers to metastasis: M1 if there is metastasis or M0 if not. M1 is subdivided as follows:
- M1a - elsewhere within the thorax.
- M1b - a single area of cancer in an extrathoracic organ.
- M1c - multiple areas of cancer, affecting one or more organs other than the lung (e.g., bones, liver or brain).

Based on these aspects, lung cancer is grouped and classified into the following stages (TNM, 8th edition):

staging
IA	T1N0M0
IB	T2aN0M0
IIA	T2bN0M0
IIB	T1-2N1M0, T3N0M0
IIIA	T1-2N2M0, T3N1M0, T4N0-1M0
IIIB	T1-2N3M0, T3-4N2M0
IIIC	T3-4N3M0
IVA	Any T, N, and M1a with single or multiple intrathoracic metastasis (includes malignant pleural or pericardial effusion)
IVA	Any T, N, and M1b with single extrathoracic metastasis in a single organ
IVB	Any T, N, and M1c with multiple extrathoracic metastasis in one or more organs

Molecular Study of the Tumour

Once lung cancer has been diagnosed, a molecular study is needed to report the genetic properties of the tumour so appropriate, personalised treatment can be offered.

It must be emphasised that these genetic tumour alterations are NOT hereditary; that is, they are NOT germline or specific to the patient but rather somatic or specific to the tumour.

The genetic study is carried out on a sample of tumour tissue obtained in the biopsy or from the surgical specimen. In cases where there is not enough tumour material available, a liquid biopsy can be considered. A liquid biopsy consists of taking a blood sample from the patient where circulating DNA from the tumour is analysed.

Molecular analysis in lung cancer should consider the evaluation of several genes, among which are: PD-L1, EGFR, ALK, ROS1, RET, BRAF, NTRK, KRASG12C, METex14, EGFR and HER2 exon 20 insertions. This is why sequencing techniques are carried out in the laboratory: to obtain information from a large number of genes at the same time. The result of this analysis is crucial to be able to establish an individualised treatment strategy, also known as precision medicine.