Your doctor will carry out a clinical respiratory examination. They will examine your chest and feel the lymph nodes in your neck. If there is a suspicion of lung cancer, they will arrange for an urgent imaging examination.
How is lung cancer diagnosed?
Different imaging techniques include:
- Chest X-ray: A chest X-ray is still the single most usefull for uncovering lung cancer. It often shows up as an unexplain or new shadow on the images.
- Computed tomography (CT or CAT scan):these special computer-assisted x-rays allow doctors to see exactly where a tumor is located in a lung as well as its relationship to other organs within the chest. It also helps in staging the cancer, which means determining if the cancer has spread to lymph nodes or other organs. An x-ray dye called contrast media may be injected into your blood to make structures inside your body show up better pictures.
- Magnetic resonance imaging (MRI):
- Positron emission tomography (PET): During a Pet Scan, a radioactive substance called a tracer is combined with a chemical substans such as glucose, and injected into the body. The tracer emit signals that are recorded by a special camera. These signals are converted into 3D images of the examined organ. The 3D images allow doctors to see the organ from any angle, which provides a clear view of any abnormalities.
Histopathology is the study of diseased cells and tissues using a microscope; it is carried out on a biopsy – a sample of cells or tissue that is taken from the tumor.
Techniques for obtaining a biopsy include:
- Bronchoscopy: A doctor or specially-trained nurse looks at the insides of the airways and lungs using a tube called a bronchoscope. It is carried out under local anaesthetic. During a bronchoscopy, the doctor or nurse will take samples of cells (biopsies) from the airways or lungs.
- CT-guided needle lung biopsy: If a biopsy is difficult to obtain with a bronchoscopy, your doctor may choose to obtain a biopsy during a CT In this procedure, you will have a local anaesthetic to numb the area. A thin needle is then inserted through your skin into your lung so that the doctor can remove a sample of cells from the tumor. The CT images are checked to ensure that the needle is in the right place.
- Endobronchial ultrasound-guided sampling (EBUS): This technique is used to confirm whether the cancer has spread to nearby lymph nodes, after radiological examinations have suggested that this might be the case. A bronchoscope, containing a small ultrasound probe, is passed through the trachea to see whether any nearby lymph nodes are larger than normal. The doctor can pass a needle along the bronchoscope to take biopsies from the tumor or the lymph nodes.
- Oesophageal ultrasound-guided sampling (EUS): Similar to EBUS, this technique is used to confirm whether the cancer has spread to nearby lymph nodes, after radiological examinations have suggested that this might be the case. However, unlike EBUS, the ultrasound probe is inserted through the oesophagus.
- Mediastinoscopy: This procedure is more invasive than EBUS/EUS but is recommended as an extra test if EBUS/EUS does not confirm that the cancer has spread to nearby lymph nodes. A mediastinoscopy is carried out under general anaesthetic and requires a short stay in hospital. A small cut is made in the skin at the base of your neck and a tube passed through the cut into your chest. A light and a camera attached to the tube allow the doctor to closely look at the middle of your chest – the mediastinum – for any abnormal lymph nodes, as these are the first areas that the cancer may spread to. Samples of tissue and lymph nodes can be taken for further examination.
Whereas histopathology is the laboratory examination of tissue or cells, cytology (or cytopathology) is the examination of cancerous cells spontaneously detached from the tumor.
- Bronchoscopy: Bronchial washings (in which a mild salt solution is washed over the surface of the airways)and the collection of secretions can be carried out during a bronchoscopy to look for the presence of cancerous cells.
- Thoracentesis/pleural drainage: Pleural effusion is an abnormal collection of fluid between the thin layers of tissue (pleura) that line the lung and the wall of the chest cavity. This fluid can be taken from the pleural cavity by thoracentesis or pleural drainage and examined in the laboratory for the presence of cancerous cells.
- Pericardiocentesis/pericardial drainage: Pericardial effusion is an abnormal collection of fluid between the heart and the sac that surrounds the heart (pericardium). This fluid can be taken from the pericardial cavity by pericardiocentesis or pericardial drainage and examined in the laboratory for the presence of cancerous cells. These techniques are carried out in the hospital, usually with the aid of ultrasound to help position the needle. You will be given a local anaesthetic and monitored closely for any complications afterwards.
Molecular diagnostics is a collection of techniques used to analyze biological markers in the genome and proteome – the individual’s genetic code and how their cells express their genes as proteins – by applying molecular biology to medical testing. The technique is used to diagnose and monitor disease, detect risk, and decide which therapies will work best for individual patients. By analyzing the specifics of the patient and their disease, molecular diagnostics offers the prospect of personalized approach and management for your condition.
Why test for genetic alterations? The cancer cells in the lungs can be tested for certain kinds of genetic alterations which, if found, can tell healthcare professionals even more about the cancer. Certain genetic alterations are linked with specific types of NSCLC. For example, if you have adenocarcinoma, your healthcare professional will most likely test the cells for two types of genetic alteration: Epidermal growth factor receptor (EGFR) and anaplastic lymphoma receptor tyrosine kinase (ALK) in this case . There are specific treatments available that target certain genetic alterations such as EGFR or ALK. Testing for genetic alterations may help a physician choose the most appropriate approach. To detect the ALK gene, doctors obtain a tumor sample via biopsy (a medical procedure that involves taking a small sample of tissue so that it can be examined under a microscope) or surgery and send it to a specialised lab for molecular testing and design a therapy for the patient.
Guide to lung cancer molecular testing
The College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology convened an expert panel to develop an evidence-based guideline to help define the key questions and literature search terms, review abstracts and full articles, and draft recommendations.
The purpose of the guideline is to set the standards for the molecular analysis of lung cancers in order to guide targeted therapy treatment decisions based on the molecular results. The guideline mentions testing only for advanced stage patients.
The 2013 guideline was largely reaffirmed with updated recommendations to allow testing of cytology samples, require improved assay sensitivity, and recommend against the use of immunohistochemistry for EGFR testing. Key new recommendations include ROS1 testing for all adenocarcinoma patients; the inclusion of additional genes ( ERBB2, MET, BRAF, KRAS, and RET) for laboratories that perform next-generation sequencing panels; immunohistochemistry as an alternative to fluorescence in situ hybridization for ALK and/or ROS1 testing; use of 5% sensitivity assays for EGFR T790M mutations in patients with secondary resistance to EGFR inhibitors; and the use of cell-free DNA to “rule in” targetable mutations when tissue is limited or hard to obtain.
The liquid biopsy for advanced NSCLC – new frontiers in LC management
Components of tumors, which are shed into the circulation, i.e., circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), or extracellular vesicles, are increasingly being used for monitoring tumor genomes. Liquid biopsy is the innovative solution to cancer detection and treatment. While liquid biopsies are revolutionizing oncology, they are not yet ready to entirely replace their competition, solid tissue biopsies.
A liquid biopsy looks for signs of cancer in a person’s bodily fluid – most often blood, but also urine, saliva, etc. The most significant benefit of using this procedure is that they can be easily accessed and collecting them is generally quick and “non-invasive,” causing relatively little pain or discomfort. This procedure is based on the analysis of circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), or tumor-derived extracellular vesicles, which have been shed from tumors and their metastatic sites into the blood.
According to IASLC, one of the hallmarks of NSCLC is represented by the expanding array of effective targeted therapies with activity in specific molecular subsets of this disease. Since acquired resistance to targeted inhibitors is nearly universal, development of next-generation agents able to overcome common resistance mechanisms has been a vital key of experimental and therapeutic research. To this point it should be noted, though, that the liquid biopsy is still far from replacing the tumor biopsy, which remains a cornerstone of the patient’s diagnosis – including, of course, the histology of NSCLC and the molecular characterization whenever liquid biopsy-based approaches fail to give a positive result. Nonetheless we strongly believe that with the growing relevance of molecular testing in every field of cancer, physicians dealing with cancer have developed confidence in the liquid biopsy technologies. In our opinion this is aided through the conformity and the accuracy of the pathologists’ reports and through the creation of a specific board that takes care of considering the molecular identity of the patient’s tumor in a multidisciplinary team. 1
One of the keys in this discovery process is not only to find the cancer cell or find the mutated DNA fragment circulating in the blood, but also to find out whether that particular person’s cancer is going to be a problem. To me, that’s going to be an even bigger challenge, consider dr. Len Lichtenfeld, deputy chief medical officer of the American Cancer Society.
- IASLC Statement Paper: Liquid Biopsy for Advanced Non-Small Cell Lung Cancer (NSCLC), Components of tumors, which are shed into the circulation, i.e., circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), or extracellular vesicles, are increasingly being used for monitoring tumor genomes.
Understanding liquid biopsy
Blood plasma of cancer patients contains DNA fragments that originate from the tumour. Cancer is a disease of the genome, characterized by and caused by variable patterns of genomic alterations. Cancer is difficult to treat because every cancer is different, and can further evolve over time and in response to treatment. Current methods for monitoring cancer dynamics are limited: protein markers and imaging estimate tumour burden, but can’t assess genomic status.
One potential way to improve early cancer detection is through liquid biopsy, which looks for signs of cancer in blood or other bodily fluids. This approach is already used in some cases to get information about a tumour that has already been diagnosed, but research is progressing to a point where the technology may be able to be applied to early cancer detection or even screening. This procedure is based on the analysis of circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), or tumor-derived extracellular vesicles.
As cancer cells die, they release fragments of their genetic material into the blood, which is known as circulating tumour DNA (ctDNA). These bits of cancer DNA can be detected by specialized equipment and alert researchers to cancer’s presence.
As a tumour grows, it releases whole cells that enter the bloodstream and travel around the body. These cells, called circulating tumour cells (CTCs) can be detected in a blood sample and indicate that cancer is present.
Cells commonly pinch off a part of themselves, creating a bubble-like structure called an exosome. Exosomes have a variety of biological uses, including communication between cells and transporting waste from cells. When a cancer cell pinches off an exosome, it contains fluid from the cell, along with genetic material and proteins. While most cells, healthy or unhealthy, secrete exosomes, researchers have found that cancer cells tend to release far more.
Source: Schorey JS, Cheng Y, Singh PP, Smith VL. (2014) Exosomes and other extracellular vesicles in host-pathogen interactions. EMBO Rep
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