Lung Cancer

Diagnostic Testing: Newer, Targeted Tests Assist in Precision Diagnosis

Advances in lung cancer diagnostic testing and therapies are guiding today’s treatment decisions. Accurately diagnosing the type of lung cancer and any genetic abnormalities that may be driving the cancer’s growth is necessary for developing the right treatment plan for your specific type. To do so, your medical team relies on various types of imaging tests, blood tests, biopsies and biomarker testing.

Imaging Tests

Imaging tests are often used early to diagnose lung cancer. These tests make detailed pictures of areas inside the body using different forms of energy, such as X-rays, ultrasound, radio waves and radioactive substances. One, or a combination of these tests, may be used to diagnose disease, plan treatment or find out how well a treatment is working. Some of the commonly used imaging tests for these purposes include the following.

Computed tomography (CT) produces three-dimensional, cross-sectional X-ray images, so it can provide more precise details than a standard X-ray. CT scans provide an excellent assessment of the size of lymph nodes; however, the size doesn’t always indicate whether the nodes are involved with cancer.

Positron emission tomography (PET) images are not as finely detailed as those from a CT scan, but they can provide helpful information, especially if the cancer has spread to other sites. PET is particularly useful if your doctor thinks cancer has spread beyond the lung but does not know where. It is also helpful in distinguishing cancerous lesions from benign (noncancerous) lesions.

Magnetic resonance imaging (MRI) may be done to look for metastasis in other parts of the body. It is most valuable for detecting it in the brain or spinal cord. A brain MRI is commonly done in the initial staging of lung cancer.

A bone scan determines whether lung cancer has spread to bone and is usually done only if a person has signs and symptoms of metastasis. A bone scan may not be needed if a PET is done because that will show if cancer has spread to bone.

With endobronchial ultrasound (EBUS), the doctor can examine areas in the space between the lungs (mediastinum), including lymph nodes. The doctor may choose to insert a biopsy needle through the bronchoscope to obtain a tissue sample for a pathologist to evaluate.

Biopsies

A biopsy is a procedure done to collect a sample of tissue or cells that will be examined under a microscope to see if cancer cells are present. Obtaining and analyzing a biopsy sample are crucial to diagnosing the type of lung cancer you may have, which will determine the type of treatment you may receive. A biopsy can be done by several methods, some of which are listed here.

A bronchoscopy allows your doctor to look inside the lungs and the large airways in the lungs (bronchi) for abnormal areas. The doctor will insert a bronchoscope (a thin tube-like instrument) through your nose or mouth into the trachea and lungs. The bronchoscope has a light and lens that let the doctor examine the inside of the trachea, bronchi and lungs. Tiny tools can be inserted into the bronchoscope to obtain samples of tissue or fluid to be analyzed. Other types of bronchoscopy your doctor may use include electromagnetic navigation bronchoscopy, navigational bronchoscopy, radial endobronchial ultrasound bronchoscopy and robotic bronchoscopy.

A core needle biopsy uses a needle inserted directly into the tumor to remove cells used to determine the type of lung cancer and for molecular testing. This biopsy provides a larger tissue sample than a fine-needle aspiration, which may be important for additional molecular and biomarker testing.

Fine-needle aspiration is a type of biopsy used to evaluate a possible lung tumor. In this test, cells are removed through a thin needle inserted directly into the tumor. The cells are examined under a microscope for signs of cancer. The doctor who performs this test may use ultrasound or CT to guide the placement of the needle. Ask your doctor if this biopsy will provide enough tissue for molecular testing.

Liquid biopsy for circulating tumor cells (CTC) is a minimally invasive procedure that is used to test a blood sample or pieces of DNA from the tumor cells. Pathologists use this test to look for genetic mutations in the blood to drive treatment decisions and to monitor any changes in the tumor’s DNA during treatment.

Mediastinoscopy is a surgical procedure to examine organs, tissues and lymph nodes between the lungs. The doctor can examine the area and remove tissue samples from lymph nodes. Mediastinotomy is a similar procedure that gives the doctor access to lymph nodes that cannot be reached by mediastinoscopy.

Thoracentesis removes fluid that has collected in the space around the lungs (pleural space). For this procedure, a needle will be inserted into the pleural space to draw out the fluid, which is then analyzed.

Thoracoscopy looks for cancer that has spread to the spaces between the lungs and the chest wall. If the doctor notices a suspicious area, he or she can remove the tissue for examination.

Video-assisted thoracoscopic surgery (VATS) uses a thoracoscope (a thin tube-like instrument with a camera on the end) to examine the lung and chest wall and to remove some lung cancer tumors.

Other Tests

Testing for biomarkers (tumor markers) is key in the shift toward personalized medicine, also referred to as precision medicine. It targets a patient’s specific tumor type based on the presence of genetic alterations.

Additional tests may be needed to accurately diagnose the lung cancer. These tests look at blood, tissue and mucus and include the following.

A complete blood count (CBC) measures the number of red blood cells, white blood cells and platelets. Your blood counts may be abnormal – too low or too high – because of cancer, effects of treatment (can lower counts) or another health problem.

Immunohistochemistry uses antibodies to test for certain antigens (markers) in a tissue sample. It may be used to determine the difference between lung cancer types.

With sputum cytology, a sample of your sputum is examined under a microscope to see if cancer cells are present. Sputum is the mucus coughed up from the windpipe (trachea) and bronchi (large airways).

Monitoring Tests

Your doctor may use some of the following tests to monitor how the cancer is responding to treatment.

A body plethysmograph test measures how much air your lungs can hold and the amount of air left in your lungs after you exhale.

A gas diffusion test measures how much oxygen is traveling into your lungs from your blood.

A high-altitude simulation test (HAST) measures if your heart and lungs will be able to withstand traveling in an airplane or to a city or country with a high altitude.

A pulmonary function test (PFT) measures how well your lungs work by how much air they can hold and how quickly air is moved into and out of them. It also measures how much oxygen is used and how much carbon dioxide is given off during breathing. A pulmonary function test can be used to diagnose a lung disease and to see how well treatment for the disease is working.

Pulse oximetry measures the level of oxygen in your blood. If oxygen is too low, your doctor may prescribe extra oxygen for you.

Spirometry measures how much air and how fast you can breathe. This test is given to determine if you are a candidate for lung surgery or radiation therapy.

Questions to Ask Your Medical Team

  • Which diagnostic and staging tests do you recommend for me?
  • How should I prepare for these tests?
  • Will I need more than one test?
  • Will any of the procedures be painful?
  • Will my biopsy specimen be large enough for multiple biomarker tests?
  • Which tests will be run?
  • If a biomarker test is positive, how will that affect my treatment options?
  • Will I need to be sedated?
  • Has cancer spread beyond my lungs?
  • How will we know if the cancer is responding to treatment?

 

National Guidelines Recommend Testing for Gene Abnormalities

Doctors are increasingly relying on molecular and biomarker testing results to treat lung cancer. Treatment options can now be targeted to the subtype and molecular abnormalities that may be present. A pathologist will examine the biopsy tissue for specific biomarkers, which are substances such as genes or molecules that can be measured in the blood, plasma, urine, cerebrospinal fluid or other body fluids or tissues. They are produced by cancer cells or other cells of the body in response to cancer. Biomarkers are also known as tumor markers or biological markers.

Most molecular testing for lung cancer looks for epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) fusions, for which several targeted therapies have been developed. Researchers have identified other biomarkers that are involved in some types of lung cancers. As a result, national guidelines recommend the following genes be tested if lung cancer is suspected: ALK, BRAF, EGFR, MET, ERBB2 (HER2), NTRK, RET and ROS1.

Today, next-generation sequencing (NGS) is used to test these genes. This technique is capable of processing multiple DNA sequences simultaneously with more speed and accuracy. NGS can be done on both tumor tissue and blood and at present can detect abnormalities associated with specific therapies.

Because immunotherapy options are now available to treat some types of lung cancer, your doctor may also test you for PD-L1, which is a biomarker that helps determine if you would be a good candidate for this treatment.

Before you undergo a biopsy, ask your doctor if you will be tested for any or all of these genes. If so, a larger biopsy sample may be needed than if the doctor is only testing for EGFR and ALK. Asking in advance may prevent the need to re-biopsy tissue in order to obtain a second sample to test.

Additional Resources

 

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