Why is early detection of Lung Cancer important?
Detection of cancer at its earlier stages is key to reducing cancer mortality. At an early stage, cancer is more likely to still be localized, not spread to other parts of the body yet, which makes treatment easier and more successful. People at high risk for lung cancer are recommended for annual screening with low dose computed tomography (LDCT) to find cancer at earlier stages when it can be successfully treated. The National Lung Cancer Screening Trial1 (NLCST) of more than 53,000 high-risk patients showed LDCT screening could lower mortality rates by 20% as compared to screening with traditional X-ray.
Why is CyPath® Lung important for early detection of lung cancer?
While widespread use of LDCT will help lower the death rate from lung cancer, the NLCST found that LDCT screening has a low positive predictive value of only 3.8%. That means that for every 100 people who were diagnosed by LDCT as positive for lung cancer, less than four of them actually had the disease. The low positive predictive value can lead to more expensive and riskier procedures to diagnose lung cancer. People may decide not to be screened because of the anxiety, cost and risk of a positive LDCT result that turns out to be incorrect.
A patient-friendly, accurate and reasonably priced test like CyPath® Lung offers significant benefits. The use of CyPath® Lung after a positive LDCT scan can increase the positive predictive value of screening, lowering the number of people who would otherwise have to undergo unnecessary and invasive procedures and providing physicians with greater confidence when follow-up is necessary.
How do CyPath® Lung’s trial results compare to other diagnostic methods?
Current diagnostic methods for lung cancer include PET scans, bronchoscopy and tissue biopsy. The table below compares the sensitivity and specificity of CyPath® Lung with tests and procedures currently used to diagnose lung cancer. CyPath® Lung compares favorably to these more invasive and expensive procedures.
*Specificity is a measure of how many times the test correctly indicates that a person who does not have the disease is negative. **Sensitivity is a measure of how many times the test correctly indicates that a person who does have the disease is positive.
Diagnostic Method Specificity* Sensitivity** CyPath Lung® 88% 82% Low Dose CT (LDCT)1 73.4% 93.8% FDG PET Scan2 82% 87% Bronchoscopy3 47% 88% Fine Needle Biopsy4 75.4% 90.4% Core Needle Biopsy4 88.6% 89.1%
What does CyPath® Lung detect in sputum?
CyPath® Lung reveals the lung environment by profiling cell populations in sputum. Certain cell populations can indicate that cancer is present in the lung. The test acquires information about sputum using a flow cytometer that individually scans and characterizes tens of millions of cells in minutes. CyPath® Lung labels a person’s sputum sample with fluorescent antibodies that uniquely identify different cell types and a fluorescent porphyrin called TCPP that preferentially binds to cancer cells and cancer-related cells. TCPP fluoresces a bright red color when attached to cancer cells that is visible when the sample is run through a flow cytometer. CyPath® Lung uses automated analysis that looks for cell populations in sputum that are predictive of cancer, one of which is the presence of cells that have taken up the proprietary TCPP porphyrin label.
Why is it important that this clinical study compare sputum from people at high risk for lung cancer with those who have the disease?
A diagnostic should be tested in the population in which it will be used. In the case of lung cancer, the relevant population is people at high risk for the disease. As LDCT screening shows, it is difficult to tell the difference between someone with cancer and someone at high risk without cancer. Smoking severely damages the lungs, leading to respiratory conditions that confound analysis and produce nodules that look like cancer on scans.
Many clinical studies of diagnostics on the market or in development compare cancer patients with healthy individuals, resulting in higher accuracy but lacking clinical relevance. The pathology of a healthy lung is very different from one with cancer, in contrast to the lungs of a high-risk individual without cancer that have endured the insult of smoking similar to patients with lung cancer. The CyPath® Lung trial compared these two very similar but difficult to distinguish cohorts – those at high risk with and without cancer – to provide meaningful results for clinical use.
Does this study build upon previous research?
The test validation of CyPath® Lung rests on a solid scientific foundation. Porphyrins have been known for decades to specifically concentrate in many types of cancer cells and cancer-associated cells such as macrophages, cells that clean debris from the tissues in the body. In addition, certain porphyrins are naturally fluorescent, with a distinct photon emission profile. Early research conducted at Los Alamos National Laboratory showed 100% accuracy in distinguishing lung cancer patients from healthy individuals by labeling sputum with the porphyrin TCPP. A later sputum cytology study5 published in 2015 showed that certain cells in sputum from lung cancer patients labeled by the porphyrin TCPP fluoresce a bright red color that can be measured under a microscope. In this trial, study participants were classified into cancer versus high-risk cohorts with 81% accuracy. Building on this scientific foundation, the current CyPath® Lung test still uses porphyrins but adds other markers to the analysis. In addition, the test is now performed on a flow cytometry platform which makes it possible to quickly analyze millions of cells in a single sputum sample.
What is novel about CyPath® Lung?
CyPath® Lung is the first non-invasive, accurate and well-balanced test for lung cancer, meaning that our test has high specificity and high sensitivity, compared to other tests that claim high sensitivity and very low specificity, or vice versa.
CyPath® Lung assesses the lung environment by characterizing cell populations in sputum, using antibody staining of cells similar to the flow cytometry analysis of blood for lymphomas and other blood-related cancers. CyPath® Lung uniquely incorporates the porphyrin TCPP to identify cancer and cancer-related populations in sputum and delivers an automated analysis to physician in minutes.
Exfoliated cells in sputum have long been of interest for lung cancer diagnosis. Traditional slide-based sputum cytology, which looks at only a fraction of the entire sputum sample, has been shown to detect lung cancer in 60% to 82% of cases6.
Sputum bathes the lungs, coming into direct contact with a possible tumor that sheds cancerous and cancer-related cells, making sputum an excellent sample for cancer detection.
Sputum can be collected easily at home, either spontaneously or with assist from a non-invasive, hand-held airway clearing device that helps people expel the sample into a collection cup.
How is the sputum sample collected?
A physician orders CyPath® Lung and gives the patient a sputum collection kit to take home. The test also can be shipped directly to the patient’s home. The kit includes one test collection cup; a pre-addressed, overnight envelope for returning the samples; patient instruction booklet; and a small cold pack to be placed in the freezer during the three-day collection period. Patients collect a sputum sample at home every day for three consecutive days, storing each sample in the same collection cup. Sputum is expelled and collected by coughing into the collection cup. The patient stores the collection cup in a cool, dark place or in a refrigerator between collections.
On the third day of collection, the patient places the collection cup containing the sputum sample back into the kit box for return by overnight mail to the laboratory. The patient adds the frozen cold pack to the kit box that contains his or her sputum sample prior to sending it to the laboratory for analysis.
Can the test be used for more types of cancer and lung diseases?
bioAffinity Technologies plans to develop additional cancer diagnostics using its flow cytometry platform. The Company also plans to develop tests related to the health of the lung, including diagnostics for asthma and COPD. Additional research and development are required to bring these tests to market.
What is the next step for clinical trials?
Several clinical trials are planned including the following:
- CyPath® Lung Pivotal Clinical Trial is a prospective, multi-site trial enrolling approximately 2,000 high-risk patients at 20 collection sites over a two-year period that will establish sensitivity and specificity in distinguishing high-risk individuals with cancer from those who are cancer-free but have a suspicious lung nodule revealed by LDCT screening.
- Pivotal Clinical Trial Combining LDCT with CyPath® Lung is a prospective, multi-site trial enrolling approximately 2,000 high-risk patients over a two-year period to establish sensitivity and specificity of combined testing for participants with suspicious nodules revealed by LDCT who are subsequently tested by CyPath® Lung.
- Clinical Utility Trial of CyPath® Lung is a prospective, multi-site trial to determine how physicians currently manage patients with suspicious lung nodules and how the results of combined testing including CyPath® Lung will change clinical decision-making.
What's the difference between CyPath® Lung and liquid biopsies?
Most liquid biopsies are used after a tissue biopsy has confirmed a diagnosis to identify specific gene mutations in the tumor cells. This information helps inform therapeutic choices by giving physicians the opportunity to select drugs that target the cellular pathways that are affected by the gene mutations. CyPath® Lung detects lung cancer prior to confirmatory tests.
Some liquid biopsies seek to find cancer earlier. So far, diagnostic liquid biopsies for early lung cancer show high sensitivity and very low specificity, or vice versa. Low sensitivity means a test misses the majority of cancers for which it is testing, leading to high false negatives. Low specificity means the test misses the majority of people who do not have cancer, instead calling them positive, leading to many unnecessary follow-up tests. CyPath® Lung is different, showing both high specificity and sensitivity in testing for lung cancer.
CyPath® Lung reveals the lung environment by profiling cell populations in sputum, i.e., whole cells, to detect the disease. Liquid biopsies most often analyze blood samples. Although some identify whole cells as well (so-called circulating tumor cells), most liquid biopsies look for genetic fragments of cancer cells in blood.
Sputum is much more concentrated with cancer-related cells/material than blood, providing a better sample to analyze for lung cancer.
Several companies are developing “pan-cancer” blood tests (liquid biopsies), meaning that one blood draw could be used to detect one or more of 10 to 20 cancers. This approach limits the search for specific mutations, which is especially problematic for lung cancer since lung cancer is known to be associated with many different types of mutations.
CyPath® Lung is reasonably priced. Liquid biopsies can be expensive, costing more than 10 times the price of CyPath® Lung.
Sputum travels well. A three-day sample overnighted to the laboratory exhibits high viability, with on average more than 60% of cells arriving alive for processing. In comparison, blood can be especially vulnerable to handling and processing problems. DNA, RNA and proteins tend to degrade quickly when processed inappropriately. Degradation of test targets is a particular concern when the targets are rare, as is the case with early-stage cancers.
Does insurance cover CyPath® Lung testing?
CyPath® Lung is billed as basic flow cytometry testing.
For more information on billing, click here.