Lung cancer is the most common cancer in the world and is the leading cause of cancer death, with 160,000 deaths in the U.S. annually. While there are more than a dozen different kinds of lung cancer there are two main types; non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), which together account for over 90% of all lung cancers. Malignant mesothelioma is a rare cancer that develops in the tissues that comprise the lining of the lung. Non-small cell lung cancer accounts for approximately 75% of these cancers and consists of squamous cell, adenocarcinoma and large cell types. Small cell lung cancer represents 20-25% of all lung cancers and is also referred to as “oat cell cancer”
Overall, lung cancer death rates dropped by 51% since 1990 among men and by 26% since 2002 among women. The risk of dying decreased 5% annually between 2013 and 2017 among men. This progress is largely attributed to breakthroughs with checkpoint inhibitors, and other precision cancer medicines.11
Lung cancer is characterized by the uncontrolled growth of abnormal cells in one or both of the lungs. The majority of lung cancers begin in the bronchial tubes that conduct air in and out of the lungs. Cancers of the lung are classified by how they appear under a microscope and by the unique cancer causing mutations or biomarkers they possess.
The detection of mutations or biomarkers is increasingly important for the management of lung cancer because specific precision cancer medicines or “targeted therapies” are now available in addition to chemotherapy and immunotherapy. Precision cancer medicine ared engineered to directly attack the cancer cells with specific abnormalities, leaving normal cells largely unharmed. As a result, patients newly diagnosed with lung cancer now receive molecular testing that guides their physicians in determining which therapies are more likely to boost the chances of survival while limiting the potential for adverse effects.
Signs and Symptoms of Lung Cancer
The most common symptoms of lung cancer are a persistent cough, shortness of breath and blood in the sputum.
- Persistent cough
- Shortness of breath
- Chest discomfort or pain
- Trouble breathing
- Wheezing
- Blood in sputum (mucus coughed up from the lungs)
- Hoarseness
- Loss of appetite
- Fatigue
- Difficulty swallowing
- Weigh loss
- Loss of appetite
Risk factors for Lung Cancer
Anything that increases your chance of getting a disease is called a risk factor. Having a risk factor does not mean that you will get lung cancer and not having risk factors doesn’t mean that you will not get cancer, it simply means that you are at greater risk than normal to develop the cancer.
Smoking is the major risk factor for lung cancer
Smoking of cigarettes, cigars, or pipes, now or in the past is the most important risk factor for developing lung cancer. The earlier in life a person starts smoking, the more often a person smokes, and the more years a person smokes, the greater the risk of developing lung cancer.
People between the ages of 55 and 79 years who have 30 pack years of tobacco exposure have the highest risk.11
Other Risk factors for lung cancer include the following:
- Lung Cancer Survivors (i.e. people who have been cured of a previous lung cancer)
- People with 20 pack years smoking exposure and another risk factor that places their risk for developing lung cancer at 5% over the next 5 years Other factors include
History of pneumonia.
A first degree relative that developed lung cancer before the age of 60.
Exposure to “secondhand” smoke (other individuals cigarette smoke)
Being exposed to radiation fromPrevious radiation therapy to the breast or chest
Diagnostic imaging tests like CT scans
Atomic bomb radiationRadon exposure in the home or workplace.
Exposure to asbestos, arsenic, soot or tar in the workplace
Older age is also a risk factor for most cancers. The chance of getting cancer increases as you get older.
Diagnosis & Tests for Lung Cancer
When lung cancer is diagnosed, the doctor must determine the type of cancer (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.
Confirming a diagnosis of lung cancer and the type of lung cancer requires a biopsy of the suspected cancer. A biopsy is the removal of a small piece of tissue for examination under a microscope and molecular testing and is obtained using one or more of the following procedures.
- 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. The focus of the staging evaluation is to determine if cancer is localized or metastatic. Metastatic disease is treated with systemic chemo-immunotherapy. Surgical resection however can be part of a curative treatment strategy if the cancer is localized.
The cancer’s stage is a key factor in determining the best treatment. Doctors will use the following imaging tests to help determine the stage of the cancer. In addition staging usually requires surgical evaluation of the mediastinum.
- 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.
- 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.
- Positron emission tomography (PET): PET scanning has been used to improve the detection of cancer in lymph nodes and a combined PET/CT is often used to evaluate lung cancers. 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 that are 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.
Clinical staging without surgical evaluation of the Mediastinum is often inaccurate; studies have shown that clinical staging under stages a third of patients and suggests cancer is present when in not in ~15% of patients.13
Staging The Mediastinum
The mediastinum is the space behind the breastbone (sternum) in the middle of the chest, between the 2 lungs. It contains: Lymph nodes. The heart and its great vessels.
Determining the presence of cancer in the mediastinum is essential for NSCLC treatment planning. Incorrectly staged patients may undergo unnecessary surgery, not be offered systemic treatment that could prolong their survival or be unnecessarily exposed to the side effects of chemo-immunotherapy that offers no benefit.
In addition to PET/CT scanning physical examination of the mediastinum is required to arrive at the correct stage of NSCLC. There are two ways to evaluate the mediastinum.
- During a mediastinoscopy, a surgeon makes a small incision in the neck while a patient is under general anesthesia. Next, a thin scope, called a mediastinoscope, is inserted through the opening to provide access to the lungs and surrounding lymph nodes. This mediastinoscope allows the surgeon to examine the center of the chest (mediastinum) and nearby lymph nodes, as well as remove a tissue sample.
- Endobronchial ultrasound (EBUS) is a minimally invasive procedure used to evaluate the mediastinum that allows physicians to perform a technique known as transbronchial needle aspiration (TBNA) to obtain tissue or fluid samples from the lungs and surrounding lymph nodes without conventional surgery.
Benefits of EBUS
- Provides real-time imaging of the surface of the airways, blood vessels, lungs, and lymph nodes
- The improved images allow the physician to easily view difficult-to-reach areas and to access more, and smaller, lymph nodes for biopsy.
- The accuracy and speed of EBUS allows rapid onsite pathologic evaluation in the operating room.
- EBUS is performed under moderate sedation or general anesthesia
- Patients recover quickly and can usually go home the same day
Genomic or Biomarker Testing-Precision Cancer Medicine
Molecular diagnostic genomic testing, including DNA sequencing, is performed to identify lung cancer growth driving abnormalities in a cancer’s genome and biomarkers that can guide treatment with precision cancer medicines 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. All newly diagnosed patients should be tested for PD-1, ALK, EGFR and ROS before beginning treatment.
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 inhibitor immunotherapy 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-1.2,3
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 specific precision cancer medicines are available for treatment. 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.4,5
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 mutation6
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.7
- Treatment of Non Small Cell Lung Cancer
- Treatment of Small Cell Lung Cancer
- Malignant Mesothelioma
- Solitary Pulmonary Nodules and Granulomas
References
- American Cancer Society. Cancer Facts & Figures 2017.
- Non-Small Cell Lung Cancer Treatment (PDQ®)–Patient Version.
- 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.] mercknewsroom.com/news-release/oncology-newsroom/mercks-keytruda%C2%A0pembrolizumab-demonstrates-superior-progression-free- Accessed June 21, 2016.
- 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.
- OSI Pharmaceuticals. FDA Approves Tarceva as a Maintenance Therapy for Advanced Non-small Cell Lung Cancer. Available at: investor.osip.com/releasedetail.cfm?ReleaseID=460783. Accessed April 19, 2010.
- 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, 2011.8. 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.
- United States Food and Drug Administration (FDA). FDA expands use of Xalkori to treat rare form of advanced non-small cell lung cancer. Available here. Accessed March 11, 2016.
- Lung Cancer Prevention (PDQ®)–Patient Version
- The National Lung Screening Trial Research Team. Reduced lung-cancer mortality with low-dose computed tomographic screening. New England Journal of Medicine. 2011;365:395-409.
- NCCN press release. NCCN announces new addition to library of guidelines: NCCN guidelines for lung cancer screening. November 9, 2011.
- Lung Cancer Risk Assessment Tool
- Cancer mortality continues steady decline, driven by progress against lung cancer.
- Journal of Thoracic, Cardiovascular surgery: 2009; 137;13-9.
