Diagnosis & Tests

for Lung Cancer

When lung cancer is diagnosed, the doctor must determine the type (small cell or non small cell), the presence of biomarkers, and the extent of spread or stage of the cancer in order to determine the best treatment. Lung cancer may grow locally in the lungs or spread (metastasize) to other more distant sites in the body, including the lymph nodes, bones, and the brain. Determining the presence of a lung cancer and the type of lung cancer requires a biopsy to examine tissues from the lung. A biopsy is the removal of a small piece of tissue for examination under a microscope and is obtained using one or more of the following procedures.

Staging of Lung Cancer

Genomic or Biomarker Testing

Bronchoscopy: During a bronchoscopy, a surgeon inserts a bronchoscope (thin, lighted tube) through the nose or mouth into the trachea (windpipe) and bronchi (air passages that lead to the lung). Through this tube, the surgeon can examine the inside of the trachea, bronchi and lung and collect cells or small tissue samples.

Fine Needle Aspiration: During this procedure, a surgeon inserts a needle through the chest into the cancer to remove a tissue sample for examination under the microscope.

Thoracentesis: During a thoracentesis, a surgeon uses a needle to remove a sample of the fluid that surrounds the lungs in order to check for the presence of cancer cells.

Thoracotomy: A thoracotomy is a major operation, which involves opening the chest in order to diagnose lung cancer.

Sputum Cytology: Sputum cytology is a procedure used to examine mucus that is coughed up from the lungs or breathing tubes. The mucus is examined under a microscope in order to detect cancer cells.

Staging of Lung Cancer

In addition to diagnosing the type of lung cancer doctors also need to determine the stage or the extent of the spread of the cancer. A cancer’s stage is a key factor in determining the best treatment. This requires a number of additional tests.

Computed Tomography (CT) Scan: A CT scan is a technique for imaging body tissues and organs, during which X-ray transmissions are converted to detailed images, using a computer to synthesize X-ray data. A CT scan is conducted with a large machine positioned outside the body that can rotate to capture detailed images of the organs and tissues inside the body. This method is more sensitive and precise than an X-ray.

Magnetic Resonance Imaging (MRI): MRI uses a magnetic field rather than X-rays, and can often distinguish more accurately between healthy and diseased tissue. MRI gives better pictures of tumors located near bone than CT, does not use radiation as CT does, and provides pictures from various angles that enable doctors to construct a three-dimensional image of the tumor.

Mediastinoscopy A mediastinoscopy is a procedure that can indicate whether the cancer has spread to the lymph nodes in the chest. During a mediastinoscopy, a surgeon inserts a mediastinoscope (lighted tube) through a small incision in the neck while a patient is under general anesthesia. This mediastinoscope allows the surgeon to examine the center of the chest (mediastinum) and nearby lymph nodes, as well as remove a tissue sample.

Positron emission tomography (PET): Positron emission tomography (PET) scanning has been used to improve the detection of cancer in lymph nodes. One characteristic of living tissue is the metabolism of sugar. Prior to a PET scan, a substance containing a type of sugar attached to a radioactive isotope (a molecule that spontaneously emits radiation) is injected into the patient’s vein. The cancer cells “take up” the sugar and attached isotope, which emits positively charged, low energy radiation (positrons). The positrons react with electrons in the cancer cells, which creates the production of gamma rays. The gamma rays are then detected by the PET machine, which transforms the information into a picture. If no gamma rays are detected in the scanned area, it is unlikely that the mass in question contains living cancer cells.

Bone Scan: A bone scan is used to determine whether cancer has spread to the bones. Prior to a bone scan, a surgeon injects a small amount of radioactive substance into a vein. This substance travels through the bloodstream and collects in areas of abnormal bone growth. An instrument called a scanner measures the radioactivity levels in these areas and records them on x-ray film.

Genomic or Biomarker Testing-Precision Cancer Medicine

The purpose of precision cancer medicine is to define the genomic alterations in the cancers DNA that are driving that specific cancer. Cancer used to be diagnosed solely by a visual microscopic examination of tumor tissue and all patients received the same chemotherapy. Precision cancer medicine utilizes molecular diagnostic & genomic testing, including DNA sequencing, to identify cancer-driving abnormalities in a cancer’s genome. Once a genetic abnormality is identified, a specific targeted therapy can be designed to attack a specific mutation or other cancer-related change in the DNA programming of the cancer cells. Precision cancer medicine uses targeted drugs and immunotherapies engineered to directly attack the cancer cells with specific abnormalities, leaving normal cells largely unharmed.

By testing an individual’s lung cancer for specific unique biomarkers doctors can offer the most personalized treatment approach utilizing precision medicines.

Lung Cancer Biomarkers

PD-1: PD-1 is a protein that inhibits certain types of immune responses, allowing cancer cells to evade an attack by certain immune cells. Drugs that block the PD-1 pathway enhance the ability of the immune system to fight cancer and are referred to as checkpoint inhibitors for their ability to help the immune system recognize and attack cancer. Overall two thirds of lung cancer patients have some expression of PD-1, and one third are “high expressers” meaning over 50% of the tested tumor expresses PD-1.1,2

Epidermal growth factor receptor (EGFR): The EGFR pathway is a normal biologic pathway found in healthy cells. It is involved in regular cellular division and growth. However, certain mutations within the EGFR gene can lead to an overactive EGFR pathway, leading to the development and/or spread of cancer. These cancers are referred to as EGFR-positive, and there are several FDA-approved medications to block the activity of EGFR and slow cancer growth for EGFR-positive cancers. EGFR mutations are most common in individuals who never smoked, woman, people of Asian ethnicity, and those with a type of lung cancer known as adenocarcinoma.3,4

ALK+ Lung Cancer: Approximately 5% of all NSCLC have an identified mutation referred to as the anaplastic lymphoma kinase (ALK) mutation. The ALK mutation is responsible for initiating and promoting cancer growth. Individuals with ALK+ lung cancer tend to be non-smokers or former light smokers; younger, and are a type of NSCLC referred to as adenocarcinoma (based upon the cells affected); and respond worse to standard chemotherapy regimens than patients who do not have the ALK mutation.5

ROS-1+ Lung Cancer: The ROS-1 mutation is an uncommon mutation found in only 1% of individuals with NSCLC. Research has indicated that the ROS-1 mutation plays a role in the development and progression of some lung cancers, and patient characteristics are similar to those who have ALK+ NSCLC.6

Next: Screening & Prevention of Lung Cancer

Next: Management of Non Small Cell Lung Cancer

Next: Management of Small Cell Lung Cancer

References


1 KEYTRUDA (pembrolizumab) demonstrates superior progression-free and overall survival compared to chemotherapy as first line treatment in patients with advanced non-small cell lung cancer. [Press release.] http://www.mercknewsroom.com/news-release/oncology-newsroom/mercks-keytruda%C2%A0pembrolizumab-demonstrates-superior-progression-free- Accessed June 21, 2016.

2 Borghaei H, Paz-Ares L, Horn L, et al. Nivolumab versus Docetaxel in Advanced Nonsquamous Non–Small-Cell Lung Cancer. New England Journal of Medicine. 2015; 373:1627-1639.

3 OSI Pharmaceuticals. FDA Approves Tarceva as a Maintenance Therapy for Advanced Non-small Cell Lung Cancer. Available at: http://investor.osip.com/releasedetail.cfm?ReleaseID=460783. Accessed April 19, 2010.

4 Zhou C, Wu Y-L, Chen G et al. Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer (OPTIMAL, CTONG-0802): A multicentre, open-label, randomized, phase 3 study. Lancet Oncology. Early online publication July 22, 2011.

5 Shaw AT, Kim DW, Mehra R, et al: Ceritinib in ALK-rearranged non–small-cell lung cancer. New England Journal of Medicine. 2014; 370: 1189-1197.

6 United States Food and Drug Administration (FDA). FDA expands use of Xalkori to treat rare form of advanced non-small cell lung cancer. Available at: http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm490329.htm. Accessed March 11, 2016.