New research confirms need for lung cancer testing
Different kinds of lung cancer behave in different ways, suggesting they are fundamentally different diseases. According to a University of Colorado Cancer Center study published in Cancer, the official journal of the American Cancer Society, different subgroups of non-small cell lung cancer (NSCLC) show distinct patterns of spread in the body.
The study looked at 209 patients diagnosed with stage IV non-small cell lung cancer separated into four different molecular subgroups using testing performed by the University of Colorado Molecular Correlates Laboratory (CMOCO): those with epidermal growth factor receptor (EGFR) mutations, v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations, anaplastic lymphoma receptor tyrosine kinase (ALK) gene rearrangements or a group without any of these abnormalities.
ALK positive lung cancer was strongly associated with cancers that spread to the linings around the heart and lungs (pericardial and pleural disease). Patients with ALK positive NSCLC were also predisposed to develop liver metastases as were those with an EGFR mutation when the different subgroups were compared.
“In the last few years we have been able to separate lung cancer into different molecular subtypes to help improve outcomes from specific targeted therapies. This study really confirms that these molecular subtypes are manifesting as different diseases in patients,” said Robert Doebele, MD, PhD, lead author of the study and CU Cancer Center investigator.
Another University of Colorado study published in the same edition of Cancer drills down on how some of these different molecular subtypes of lung cancer are detected in the first place. Specifically, the study examined the companion diagnostic test for detecting the ALK positive lung cancer cases, called a fluorescence in situ hybridization (FISH) test. This test is used to select patients for treatment with crizotinib, an ALK inhibitor drug. Now University of Colorado researchers have solved an unanswered question as to why patients who respond to crizotinib only appear to have the ALK change in a fraction of the cells in their cancers.
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.
By looking in detail at the genetic changes present in the cancer cells they came to two major conclusions. First- cell counts below 100 percent in ALK positive tumors reflect the fact the assay misses a proportion of cells and not that the cells are truly missing the ALK change.
Second, the ALK change happens early in the development of the cancer and is likely to be a fundamental driver of the cancer’s growth. The study was conducted by D. Ross Camidge, MD, PhD, the director of the lung cancer clinical program at the CU Cancer Center and University of Colorado Hospital and Marileila Varella Garcia, PhD, professor of medicine, medical oncology and pathology at University of Colorado School of Medicine.
Further tests you may have
If the first tests suggest that you have lung cancer, your specialist may want to do some of the further tests described below, to confirm the diagnosis and to see if the cancer has spread to any other part of the body. This process is called staging and may take some time. The results will help you and your doctor decide on the best treatment.
Sometimes these tests may be done again, during and after treatment, to check on your progress.
MRI scan - uses magnetic fields to build up a series of cross-sectional pictures of the body
Mediastinoscopy - a procedure done under a general anaesthetic, where the doctor can look inside your chest at the area behind the breast bone
Thoracoscopy - similar to a mediastinoscopy, but to look at a different part of your chest
Lung biopsy - some cells are removed from the abnormal area and examined under a microscope
Endobronchial ultrasound scan, endoscopic ultrasound scan and abdominal ultrasound scan - these procedures use sound waves to look at internal organs
Isotope bone scan - a scan to check for abnormalities in the bones
Lung function tests - breathing tests to check how well your lungs are working
“Knowing that ALK changes are driving the cancer and that they are not actually missing from a significant proportion of the cancer reinforces our understanding of ALK positive lung cancer. It now makes sense why targeting these changes is going to affect a very large proportion of the tumor and explains the dramatic clinical responses seen with crizotinib.”
“In order to treat any disease successfully, you have to know what you are really treating,” said Camidge.” “It is only by understanding lung cancer better that we can hope to improve outcomes in the long term.”
###
Both studies were funded by the University of Colorado Lung specialized Program of Research Excellence.
The CU Cancer Center’s Thoracic Oncology Program is world renowned for its pioneering treatment of lung cancer. The program includes a multidisciplinary team of specialists and subspecialists working together to establish the best treatment plan for each patient. Advanced molecular profiling of a patient’s tumor, combined with an extensive array of standard and experimental treatments available through clinical trials has lead to major advances in patient outcomes in the last few years. The program’s one-year survival rates for advanced lung cancer consistently run twice as high as the national average. The survival rates at five years run four times higher than the national average.
CU Cancer Center is the lead site for the national Lung Cancer Mutation Consortium, the collaboration of 14 of the nation’s elite lung cancer programs. The consortium is profiling ten different molecular abnormalities in lung cancer and pairing them with specific experimental treatments over the next few years.
Please consider supporting the Lung Cancer Colorado Fund. This unique fund is overseen by the physicians and scientists and supports all aspects of the Center’s and University of Colorado Hospital’s combined fight against lung cancer.
For an appointment with a University of Colorado physician, please call Tiffany Caudill, intake coordinator for the lung cancer program at 720-848-0392 or email .(JavaScript must be enabled to view this email address). To request physician interviews, please call Erika Matich at 303-524-2780 or email .(JavaScript must be enabled to view this email address).
###
Erika Matich
.(JavaScript must be enabled to view this email address)
303-524-2780
University of Colorado Denver