In the two largest clinical studies ever conducted on the molecular genetics of lung cancer, an international team led by scientists at the University of California, San Francisco (UCSF) has demonstrated that an available molecular test can predict the likelihood of death from early-stage lung cancer more accurately than conventional methods. The work may eventually help improve the odds of survival for hundreds of thousands of patients each year.
Reported this week in The Lancet (Jan. 27, 2012), the two studies demonstrated how the test, which measures the activity of fourteen genes in cancerous tissue, improves the accuracy of prognosis. This in turn could guide treatments for patients with the most common form of the disease, non-squamous non-small cell lung cancer.
The two independent clinical trials included one blinded study involving the analysis of tissue samples from 433 people with early-stage lung cancer in northern California and another study involving 1,006 people with early-stage lung cancer in China. In both trials, the team showed that the test could accurately predict whether the odds of death within five years of surgery to remove a lung cancer were low, intermediate, or high.
“It’s quite exciting,” said David Jablons, MD, the Ada Distinguished Professor in Thoracic Oncology and leader of the Thoracic Oncology Program at the Helen Diller Family Comprehensive Cancer Center at UCSF. “This has the potential to help hundreds of thousands of people every year survive longer.” Jablons co-led the study with Michael Mann, MD, a UCSF Associate Professor of Cardiothoracic Surgery.
Today, doctors assess early-stage lung cancers by their size, location and microscopic appearance. This information, known as staging, is then used to guide the use of additional treatment following surgery. If doctors could more precisely gauge prognosis, more people who might benefit from additional therapy could receive it immediately after surgery, before any residual cancer has had a chance to grow.
Evidence from other studies suggests that chemotherapy given in early-stage lung cancer helps thwart recurrence when there is evidence of lymph node involvement. Such involvement increases the risk of other, undetectable metastasis.
Tests to diagnose lung cancer
If there’s reason to think that you may have lung cancer, your doctor can order a number of tests to look for cancerous cells and to rule out other conditions. In order to diagnose lung cancer, your doctor may recommend:
Imaging tests. An X-ray image of your lungs may reveal an abnormal mass or nodule. A CT scan can reveal small lesions in your lungs that might not be detected on an X-ray.
Sputum cytology. If you have a cough and are producing sputum, looking at the sputum under the microscope can sometimes reveal the presence of lung cancer cells.
Tissue sample (biopsy). A sample of abnormal cells may be removed in a procedure called a biopsy. Your doctor can perform a biopsy in a number of ways, including bronchoscopy, in which your doctor examines abnormal areas of your lungs using a lighted tube that’s passed down your throat and into your lungs; mediastinoscopy, in which an incision is made at the base of your neck and surgical tools are inserted behind your breastbone to take tissue samples from lymph nodes; and needle biopsy, in which your doctor uses X-ray or CT images to guide a needle through your chest wall and into the lung tissue to collect suspicious cells. A biopsy sample may also be taken from lymph nodes or other areas where cancer has spread, such as your liver.
The scientists plan to design a large clinical trial that would seek to confirm that using the algorithm to guide therapy helps people with lung cancer survive longer.
The study conducted in China is the first major clinical trial result to emerge from the China Clinical Trials Consortium (CCTC), a collaboration between hospitals and universities across mainland China that was founded with the help of leaders from the UCSF Thoracic Oncology Program to confront the epidemic of lung cancer in China.
“The CCTC represents a revolutionary new collaborative approach to clinical research among Chinese and Western experts,” said Mann. “It is fitting that this body’s first major effort may support a molecular personalization of lung cancer care, and yield one of the first examples that fundamental tumor biology reaches across ethnic lines and can be used to try to improve outcomes for a large percentage of patients.”
Problems with Lung Cancer Prognosis
Lung cancer is the most common cause of cancer death in both the United States and the world. More people die from the disease each year than from breast, colon and prostate cancers combined. It claims more than 150,000 American lives annually and accounts for some 1.4 million deaths around the world. About 85 percent of Americans with all types of lung cancer die within five years of diagnosis.
Most cases result from exposure to cigarette smoke, but other causes include exposure to asbestos, chemicals, environmental factors and genetic susceptibility.