- Screening for Lung Cancer
- Diagnosis – Lung cancer
- Tests for Lung Cancer
- Medical history and physical exam
- Imaging tests to look for lung cancer
- Tests to diagnose lung cancer
- Tests to find lung cancer spread in the chest
- Lung function tests
- Lab tests of biopsy and other samples
- Blood tests
- Blood Test to Identify Individuals for Lung Cancer Screening
- Blood Screening for Early-Stage Lung Cancer Possible
- Lung Cancer
- How to detect lung cancer: Symptoms
- How to detect lung cancer: Risk factors
- Does insurance cover early detection testing?
- New research suggests a simple blood test could improve the early detection of lung cancer
- A growing number of patients with advanced lung cancer could soon be offered a blood test instead of having to get a tumour sample for analysis.
Screening for Lung Cancer
Most lung cancers are first diagnosed based on symptoms. Symptoms of lung cancer are not very specific and generally reflect damage to the lungs’ ability to function normally. The most common symptoms are a worsening cough that will not go away, and chest discomfort. Other symptoms include shortness of breath, spitting up small amounts of blood, unexplained weight loss, back pain, loss of appetite, and a general fatigue.
Unlike mammography for breast cancer or colonoscopy for colon cancer, a widely accepted screening tool for early-stage lung cancer has not been available until recently. Regular chest X-rays are not reliable enough to find lung tumors in their earliest stages, when many doctors believe the tumors are at their smallest and most curable state.
Recent guidelines from the American Society of Clinical Oncologists suggests annual screening with low-dose computed tomography (LDCT) for smokers and former smokers at high risk for developing lung cancer. High risk factors include being between the age of 55 to 74, having smoked for 30 years or more, and either continuing to smoke or having quit within the past 15 years. At this time, yearly screening with LDCT is recommended for high-risk individuals after careful discussion with their physicians.
In addition to this screening procedure, there is current research looking into identifying less complicated and expensive ways to screen for lung cancer, including analyses of breath and saliva.
Once tests have been completed, it should be possible for doctors to know what stage your cancer is, what this means for your treatment and whether it’s possible to completely cure the cancer.
Non-small-cell lung cancer staging
Clinicians use a staging system for lung cancer called TNM, where:
- T describes the size of the tumour (cancerous tissue)
- N describes the spread of the cancer into lymph nodes
- M describes whether the cancer has spread to another area of the body such as the liver (metastasis)
There are 4 main stages for T:
T1 lung cancer means that the cancer is still inside the lung.
T1 is broken down into 3 sub-stages:
- T1a – the tumour is no wider than 1cm
- T1b – the tumour is between 1cm and 2cm wide
- T1c – the tumour between 2cm and 3cm wide
T2 is used to describe 3 possibilities:
- the tumour is between 3cm and 5cm wide, or
- the tumour has spread into the main airway or the inner lining of the chest wall, or
- the lung has collapsed or is blocked due to inflammation
T3 is used to describe 3 possibilities:
- the tumour is between 5cm and 7cm wide, or
- there is more than 1 tumour in the lung, or
- the tumour has spread into the chest wall, the phrenic nerve (a nerve close to the lungs), or the outer layer of the heart (pericardium)
T4 is used to describe a range of possibilities including:
- the tumour is wider than 7cm, or
- the tumour has spread into both sections of the lung (each lung is made up of 2 sections, known as lobes), or
- the tumour has spread into an area of the body near to the lung, such as the heart, the windpipe, the food pipe (oesophagus) or a major blood vessel
There are 3 main stages for N:
N1 is used to describe cancerous cells in the lymph nodes located inside the lung or in the area where the lungs connect to the airway (the hilum).
N2 is used to describe 2 possibilities:
- there are cancerous cells in the lymph nodes located in the centre of the chest on the same side as the affected lung, or
- there are cancerous cells in the lymph nodes underneath the windpipe
N3 is used to describe 3 possibilities:
- there are cancerous cells in the lymph nodes located on the chest wall on the other side of the affected lung, or
- there are cancerous cells in the lymph nodes above the collar bone, or
- there are cancerous cells in the lymph nodes at the top of the lung
There are 2 main stages for M:
- M0 – the cancer has not spread outside the lung to another part of the body
- M1 – the cancer has spread outside the lung to another part of the body
Small-cell lung cancer
Small-cell lung cancer is less common than non-small-cell lung cancer. The cancerous cells are smaller in size than the cells that cause non-small-cell lung cancer.
Small-cell lung cancer only has 2 possible stages:
- limited disease – the cancer has not spread beyond the lung
- extensive disease – the cancer has spread beyond the lung
Want to know more?
- Macmillan: lung cancer tests, treatments and side effects
- Cancer Research UK: lung cancer diagnosis
SATURDAY, June 2, 2018 (HealthDay News) — Genetic blood testing is showing potential as a means of catching some early stage cancers, researchers are reporting.
For example, a panel of three different genetic tests was able to detect early stage lung cancer about half of the time in people who’d already been diagnosed with the disease.
The tests also detected late-stage lung cancers about 9 out of 10 times, the researchers said.
The findings were reported Saturday at the American Society of Clinical Oncology’s annual meeting, in Chicago.
“This is proof of principle that broad genome-wide sequencing has the ability to find cancer, and sometimes early stage curable cancer,” said lead study author Dr. Geoffrey Oxnard. He’s an associate professor of medicine at the Dana-Farber Cancer Institute and Harvard Medical School, both in Boston.
“That creates an opportunity for further development as a cancer detection or screening assay,” he said.
Cancer survival rates soar when tumors are detected in their earliest stages, the researchers said in background notes. Having a blood test that can detect early cancers would save countless lives.
Tumors regularly shed DNA fragments that circulate in the bloodstream. These fragments, called cell-free DNA, are already analyzed to help cancer doctors choose targeted gene-based therapies for people with advanced lung cancer, the researchers said.
Oxnard and his colleagues want to take that a step further, by developing a test that uses cell-free DNA to catch cancers as early as possible.
Their overall effort, the Circulating Cell-Free Genome Atlas (CCGA) study, has enrolled more than 12,000 of a planned 15,000 participants across the United States and Canada.
The ASCO meeting report represents some of the first results from the larger study. In it, the researchers used genetic tests to analyze the blood of 127 people who had been diagnosed with lung cancer.
The three tests looked for both cancer mutations and changes in genetic function that can indicate cancer, the researchers said.
The tests detected early stage lung cancer between 38 and 51 percent of the time, and late-stage cancers between 87 and 89 percent of the time.
Tests for Lung Cancer
Some lung cancers can be found by screening, but most lung cancers are found because they are causing problems. The actual diagnosis of lung cancer is made by looking at a sample of lung cells in the lab. If you have possible signs or symptoms of lung cancer, see your doctor.
Medical history and physical exam
Your doctor will ask about your medical history to learn about your symptoms and possible risk factors. Your doctor will also examine you to look for signs of lung cancer or other health problems.
If the results of your history and physical exam suggest you might have lung cancer, more tests will be done. These could include imaging tests and/or biopsies of the lung.
Imaging tests to look for lung cancer
Imaging tests use x-rays, magnetic fields, sound waves, or radioactive substances to create pictures of the inside of your body. Imaging tests might be done for a number of reasons both before and after a diagnosis of lung cancer, including:
- To look at suspicious areas that might be cancer
- To learn how far cancer might have spread
- To help determine if treatment is working
- To look for possible signs of cancer coming back after treatment
A chest x-ray is often the first test your doctor will do to look for any abnormal areas in the lungs. If something suspicious is seen, your doctor may order more tests.
Computed tomography (CT) scan
A CT scan uses x-rays to make detailed cross-sectional images of your body. Instead of taking 1 or 2 pictures, like a regular x-ray, a CT scanner takes many pictures and a computer then combines them to show a slice of the part of your body being studied.
A CT scan is more likely to show lung tumors than routine chest x-rays. It can also show the size, shape, and position of any lung tumors and can help find enlarged lymph nodes that might contain cancer that has spread. This test can also be used to look for masses in the adrenal glands, liver, brain, and other organs that might be due to the lung cancer spread.
CT-guided needle biopsy: If a suspected area of cancer is deep within your body, a CT scan might be used to guide a biopsy needle into this area to get a tissue sample to check for cancer.
Magnetic resonance imaging (MRI) scan
Like CT scans, MRI scans show detailed images of soft tissues in the body. But MRI scans use radio waves and strong magnets instead of x-rays. MRI scans are most often used to look for possible spread of lung cancer to the brain or spinal cord.
Positron emission tomography (PET) scan
For a PET scan, a slightly radioactive form of sugar (known as FDG) is injected into the blood and collects mainly in cancer cells.
PET/CT scan: Often a PET scan is combined with a CT scan using a special machine that can do both at the same time. This lets the doctor compare areas of higher radioactivity on the PET scan with a more detailed picture on the CT scan. This is the type of PET scan most often used in patients with lung cancer.
PET/CT scans can be useful:
- If your doctor thinks the cancer might have spread but doesn’t know where. They can show spread of cancer to the liver, bones, adrenal glands, or some other organs. They are not as useful for looking at the brain or spinal cord.
- In diagnosing lung cancer, but their role in checking whether treatment is working is unproven. Most doctors do not recommend PET/CT scans for routine follow up of patients after lung cancer treatment.
For a bone scan, a small amount of low-level radioactive material is injected into the blood and collects mainly in abnormal areas of bone. A bone scan can help show if a cancer has spread to the bones. But this test isn’t needed very often because PET scans can usually show if cancer has spread to the bones.
Tests to diagnose lung cancer
Symptoms and the results of certain tests may strongly suggest that a person has lung cancer, but the actual diagnosis is made by looking at lung cells in the lab.
The cells can be taken from lung secretions (mucus you cough up from the lungs), fluid removed from the area around the lung (thoracentesis), or from a suspicious area using a needle or surgery (biopsy). The choice of which test(s) to use depends on the situation.
A sample of sputum (mucus you cough up from the lungs) is looked at in the lab to see if it has cancer cells. The best way to do this is to get early morning samples 3 days in a row. This test is more likely to help find cancers that start in the major airways of the lung, such as squamous cell lung cancers. It might not be as helpful for finding other types of lung cancer. If your doctor suspects lung cancer, further testing will be done even if no cancer cells are found in the sputum.
If fluid has collected around the lungs (called a pleural effusion), doctors can remove some of the fluid to find out if it is caused by cancer spreading to the lining of the lungs (pleura). The buildup might also be caused by other conditions, such as heart failure or an infection.
For a thoracentesis, the skin is numbed and a hollow needle is inserted between the ribs to drain the fluid. The fluid is checked in the lab for cancer cells. Other tests of the fluid are also sometimes useful in telling a malignant (cancerous) pleural effusion from one that is not.
If a malignant pleural effusion has been diagnosed and is causing trouble breathing, a thoracentesis may be repeated to remove more fluid which may help a person breathe better.
Doctors often use a hollow needle to get a small sample from a suspicious area (mass). An advantage of needle biopsies is that they don’t require a surgical incision. The drawback is that they remove only a small amount of tissue and in some cases, the amount of tissue removed might not be enough to both make a diagnosis and to perform more tests on the cancer cells that can help doctors choose anticancer drugs.
Fine needle aspiration (FNA) biopsy
The doctor uses a syringe with a very thin, hollow needle to withdraw (aspirate) cells and small fragments of tissue. A FNA biopsy may be done to check for cancer in the lymph nodes between the lungs.
Transtracheal FNA or transbronchial FNA is done by passing the needle through the wall of the trachea (windpipe) or bronchi (the large airways leading into the lungs) during bronchoscopy or endobronchial ultrasound (described below).
In some patients an FNA biopsy is done during an endoscopic esophageal ultrasound (described below) by passing the needle through the wall of the esophagus.
A larger needle is used to remove one or more small cores of tissue. Samples from core biopsies are often preferred because they are larger than FNA biopsies.
Transthoracic needle biopsy
If the suspected tumor is in the outer part of the lungs, the biopsy needle can be put through the skin on the chest wall. The area where the needle is to be inserted may be numbed with local anesthesia first. The doctor then guides the needle into the area while looking at the lungs with either fluoroscopy (which is like a x-ray) or CT scan.
A possible complication of this procedure is that air may leak out of the lung at the biopsy site and into the space between the lung and the chest wall. This is called a pneumothorax. It can cause part of the lung to collapse and sometimes trouble breathing. If the air leak is small, it often gets better without any treatment. Large air leaks are treated by inserting a chest tube (a small tube into the chest space) which sucks out the air over a day or two, after which it usually heals on its own.
Bronchoscopy can help the doctor find some tumors or blockages in the larger airways of the lungs, which can often be biopsied during the procedure.
Tests to find lung cancer spread in the chest
If lung cancer has been found, it’s often important to know if it has spread to the lymph nodes in the space between the lungs (mediastinum) or other nearby areas. This can affect a person’s treatment options. Several types of tests can be used to look for this cancer spread.
An endobronchial ultrasound can be used to see the lymph nodes and other structures in the area between the lungs if biopsies need to be taken in those areas.
Endoscopic esophageal ultrasound
An endoscopic esophageal ultrasound goes down into the esophagus where it can show the nearby lymph nodes which may contain lung cancer cells. Biopsies of the abnormal lymph nodes can be taken at the same time as the procedure.
Mediastinoscopy and mediastinotomy
These procedures may be done to look more directly at and get samples from the structures in the mediastinum (the area between the lungs). The main difference between the two is in the location and size of the incision.
A mediastinoscopy is a procedure that uses a lighted tube inserted behind the sternum (breast bone) and in front of the windpipe to look at and take tissue samples from the lymph nodes along the windpipe and the major bronchial tube areas. If some lymph nodes can’t be reached by mediastinoscopy, a mediastinotomy may be done so the surgeon can directly remove the biopsy sample. For this procedure, a slightly larger incision (usually about 2 inches long) between the left second and third ribs next to the breast bone is needed.
Thoracoscopy can be done to find out if cancer has spread to the spaces between the lungs and the chest wall, or to the linings of these spaces. It can also be used to sample tumors on the outer parts of the lungs as well as nearby lymph nodes and fluid, and to assess whether a tumor is growing into nearby tissues or organs. This procedure is not often done just to diagnose lung cancer, unless other tests such as needle biopsies are unable to get enough samples for the diagnosis. Thoracoscopy can also be used as part of the treatment to remove part of a lung in some early-stage lung cancers. This type of operation, known as video-assisted thoracic surgery (VATS), is described in Surgery for Non-Small Cell Lung Cancer.
Lung function tests
Lung (or pulmonary) function tests (PFTs) are often done after lung cancer is diagnosed to see how well your lungs are working. This is especially important if surgery might be an option in treating the cancer. Surgery to remove lung cancer may mean removing part or all of a lung, so it’s important to know how well your lungs are working beforehand. Some people with poor lung function (like those with lung damage from smoking) don’t have enough undamaged lung to withstand removing even part of a lung. These tests can give the surgeon an idea of whether surgery is a good option, and if so, how much lung can safely be removed.
There are different types of PFTs, but they all basically have you breathe in and out through a tube that is connected to a machine that measures airflow.
Sometimes PFTs are coupled with a test called an arterial blood gas. In this test, blood is removed from an artery (instead of from a vein, like most other blood tests) so the amount of oxygen and carbon dioxide can be measured.
Lab tests of biopsy and other samples
Samples that have been collected during biopsies or other tests are sent to a pathology lab. A pathologist, a doctor who uses lab tests to diagnose diseases such as cancer, will look at the samples and may do other special tests to help better classify the cancer. (Cancers from other organs also can spread to the lungs. It’s very important to find out where the cancer started, because treatment is different depending on the type of cancer.)
The results of these tests are described in a pathology report, which is usually available within a week. If you have any questions about your pathology results or any diagnostic tests, talk to your doctor. If needed, you can get a second opinion of your pathology report by having your tissue samples sent to a pathologist at another lab.
For more information, see Understanding Your Pathology Report.
Molecular tests for gene changes
In some cases, especially for non-small cell lung cancer (NSCLC), doctors may look for specific gene changes in the cancer cells that could mean certain targeted drugs might help treat the cancer.
- EGFR is a protein that appears in high amounts on the surface of 10% to 20% of NSCLC cells and helps them grow. Some drugs that target EGFR can be used to treat NSCLC with changes in the EGFR gene, which are more common in certain groups, such as non-smokers, women, and Asians. But these drugs don’t seem to be as helpful in patients whose cancer cells have changes in the KRAS gene. Doctors now test NSCLC cells for changes in genes such as EGFR and KRAS to determine if these newer treatments are likely to be helpful.
- About 5% of NSCLCs have a change in the ALK gene. This change is most often seen in non-smokers (or light smokers) who have the adenocarcinoma subtype of NSCLC. Doctors may test cancers for changes in the ALK gene to see if drugs that target this change may help them.
- About 1% to 2% of NSCLCs have a rearrangement in the ROS1 gene, which might make the tumor respond to certain targeted drugs. A similar percentage have a rearrangement in the RET gene. Certain drugs that target cells with RET gene changes might be options for treating these tumors.
- About 5% of NSCLCs have changes in the BRAF gene. Certain drugs that target cells with BRAF gene changes might be an option for treating these tumors.
These molecular tests can be done on tissue taken during a biopsy or surgery for lung cancer. If the biopsy sample is too small and all the molecular tests cannot be done, the testing may also be done on blood that is taken from a vein just like a regular blood draw. This blood contains the DNA from dead tumor cells found in the bloodstream of people with advanced lung cancer. Obtaining the tumor DNA through a blood draw is sometimes called a “liquid biopsy” and can have advantages over a standard needle biopsy, which can carry risks like a pneumothorax (lung collapse) and shortness of breath.
Blood tests are not used to diagnose lung cancer, but they can help to get a sense of a person’s overall health. For example, they can be used to help determine if a person is healthy enough to have surgery.
A complete blood count (CBC) looks at whether your blood has normal numbers of different types of blood cells. For example, it can show if you are anemic (have a low number of red blood cells), if you could have trouble with bleeding (due to a low number of blood platelets), or if you are at increased risk for infections (because of a low number of white blood cells). This test could be repeated regularly during treatment, as many cancer drugs can affect blood-forming cells of the bone marrow.
Blood chemistry tests can help find abnormalities in some of your organs, such as the liver or kidneys. For example, if cancer has spread to the bones, it might cause higher than normal levels of calcium and alkaline phosphatase.
Blood Test to Identify Individuals for Lung Cancer Screening
A relatively simple blood test could refine current lung cancer screening eligibility criteria and help identify more high-risk individuals for low-dose CT (LDCT), according to an international research group.
The blood test measures levels of four circulating proteins. The measures are then used to calculate a lung cancer risk score.
A blinded external validation study found that this test discriminated more accurately between future cases of lung cancer and control cases than a traditional smoking history–based risk model and current US screening criteria.
The US Preventive Services Task Force (USPSTF) currently recommends LDCT screening for lung cancer in ever-smokers with a 30 pack-year history who have not smoked for up to 15 years, the researchers note. However, individuals eligible for screening represent fewer than 50% of incident lung cancer cases.
“Biomarker-based risk profiling has the potential to improve eligibility criteria for lung cancer screening,” say the researchers, from the University of Texas MD Anderson Cancer Center, Houston, and the International Agency for Research on Cancer (IARC), Lyons, France.
“There is an urgent need to improve lung cancer risk assessment because current screening criteria miss a large proportion of cases,” the study authors write. “This study provided a proof of principle in showing that a panel of circulating protein biomarkers may improve lung cancer risk assessment and may be used to define eligibility for computed tomography screening.”
A report on their collaborative study, which was part of the Integrative Analysis of Lung Cancer Etiology and Risk (INTEGRAL) Consortium for Early Detection of Lung Cancer, was published online July 12 in JAMA Oncology.
The biomarker-based risk assessment tool consists of a panel of four proteins: cancer antigen 125; carcinoembryonic antigen; cytokeratin-19 fragment; and the precursor of surfactant protein B.
The researchers developed it using prediagnostic blood samples from US patients at high risk for lung cancer. These included 108 ever-smoking patients for whom lung cancer had been diagnosed within 1 year after blood collection, and 216 smoking-matched control patients from the Carotene and Retinol Efficacy Trial (CARET) cohort.
To validate the tool, absolute risk estimates were used for 63 ever-smoking patients for whom lung cancer had been diagnosed within 1 year after blood collection. These patients were matched with 90 control patients from the European Prospective Investigation Into Cancer and Nutrition (EPIC) study and the Northern Sweden Health and Disease Study (NSHDS). Mean age of the patients was 58 years; 69% were men.
The researchers then combined the biomarker score with data on smoking exposure. Using this integrated risk prediction model, they identified 40 of the 63 incident lung cancer cases, or 63% of future lung cancer cases, for LDCT screening. This corresponded to a sensitivity of 0.63.
By comparison, 26 of 62 incident lung cancer cases, or 42% of future lung cancer cases, were identified for LDCT screening using the USPSTF eligibility criteria. This corresponded to a sensitivity of 0.42.
“We feel that these results represent an important stepping stone in improving lung cancer screening using biomarkers,” Mattias Johansson, PhD, of the IARC, who is a principal study investigator, told Medscape Medical News.
Johansson said the research will continue to further evaluate these and other risk biomarkers in larger international cohorts. “In Europe, we would like to see implementation studies that evaluate the practical and financial implications of using such a biomarker test for lung cancer screening,” he said.
He added that a clinical test based on these results is “still a few years away.”
In a statement issued by the IARC, Paul Brennan, PhD, head of the section of genetics at the IARC, who is one of the study’s principal investigators, said this is “the first study to systematically demonstrate that a panel of protein markers can improve the identification of future lung cancer cases.”
The results also suggest that the integrated risk prediction model could be used to reduce a greater number of false positive screening results than the current smoking model (17% vs 5%, respectively) without affecting the test’s ability to predict future lung cancer cases. “These improvements in sensitivity and specificity were consistently observed across each evaluated stratum,” the study authors say.
In addition, the study showed that the sensitivity of the integrated risk prediction model was more modest in cases diagnosed up to 2 years after blood draw when compared to the smoking model. This suggests that “an annual biomarker test may be necessary in a screening program,” the investigators point out.
The population that would benefit most from a biomarker test prior to LDCT screening still needs to be identified, they add.
The study was funded by the National Cancer Institute and the National Cancer Institute Early Detection Research Network, Fondation ARC Pour la Recherche Sur le Cancer and INCa, the MD Anderson Lung Cancer Moon Shot Program, the Lyda Hill Foundation, the Canary Foundation, the LUNGevity Foundation, and the S. Rubenstein Family Foundation. The study authors have disclosed no relevant financial relationships.
JAMA Oncol. Published online July 12, 2018. Abstract
Blood Screening for Early-Stage Lung Cancer Possible
It is possible to detect early-stage lung cancer by sequencing circulating cell-free tumor DNA (cfDNA), suggest preliminary findings from the Circulating Cell-Free Genome Atlas (CCGA) study (abstract LBA8501), presented at the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting, held June 1–5 in Chicago.
The initial results show that early-stage lung cancer can be detecting using genome sequencing of blood samples, reported lead study author Geoffrey R. Oxnard, MD, of Dana Farber Cancer Institute and Harvard Medical School in Boston.
“These are promising early results, and next steps are to further optimize the assays and validate results in a larger group of people,” Oxnard said. “Assays detected lung cancer across stages, histologies, and populations.”
So-called “liquid biopsies” are already in use for patients with advanced lung cancer, to help identify targeted therapy options.
But lung cancer survival rates are significantly improved with early diagnosis.
Low-dose computed tomography (LDCT) is the current gold standard for lung cancer screening, but few high-risk people undergo LDCT exams, in part because of a relatively high rate of false-positive results which can prompt unnecessary invasive procedures. Genomic testing of plasma cfDNA might prove to be a simpler screening test for lung cancer and could detect targetable tumor gene signatures, Oxnard noted. “There is an unmet need globally for early detection tests for lung cancer that can be easily implemented by healthcare systems,” he said.
To date, the CCGA study authors have enrolled 12,292 of 15,000 intended participants, Oxnard reported. Seventy percent of the enrolled participants have cancer diagnoses.
Their preplanned preliminary analysis of 2,800 patient plasma samples were used for a “training” set from 1,733 patients with clinically evaluable cancers—127 of whom have lung cancers. And a second “test” set of 980 clinically evaluable patients’ samples (including 47 lung cancers) were also included in the analysis. Findings for the 127 patients with stage I–IV lung cancer were reported.
Three genomic assays were used to detect lung cancer cfDNA: targeted sequencing of somatic mutations, including single nucleotide polymorphisms, or SNPs, and INDEL mutations; whole-genome sequencing to detect tumor-gene copy number aberrations; and whole-genome bisulfite sequencing (WGBS) of cfDNA to detect epigenetic abnormalities.
Comparable “signals” of lung cancer were detected using all three assays and were more pronounced with more advanced stages of lung cancer, Oxnard reported. The findings show that cfDNA sequencing holds promise as a lung cancer screening tool with low false-positive rates.
WGBS testing detected 41% of stage I, II, and IIIA lung tumors, and 89% of late-stage (IIIB–IV) lung cancers. Whole-genome sequencing detected 38% of early-stage lung cancers and 87% of late-stage cases. Targeted sequencing detected 51% of early-stage and 89% of late-stage lung tumors.
False-positive findings were rare. Fewer than 1% of noncancer patient samples yielded a consistent “cancer-like” signal, Oxnard reported. Much more research is needed before the tests are ready for clinical use, however.
More than half (54%) of somatic mutations detected were from patient leukocytes rather than DNA shed into the bloodstream by lung tumors. Such mutational “noise” accumulates as a natural part of the aging process and must be reliably differentiated from tumor cfDNA, Oxnard cautioned. “White blood cell–derived mutations and copy number variations are a significant source of potential false-positives that must be accounted for to obtain high specificity,” he explained.
“We’re one step closer to being able to detect early lung cancer from a simple blood test,” commented ASCO Expert David Graham, MD, of the Levine Cancer Institute, Charlotte, North Carolina.
The study was funded by GRAIL, Inc.
Sources Used in Current Review
2018 review performed by Imad Tarhoni, MD, PhD Candidate, Department of Cell and Molecular Medicine, Rush University Medical Center.
(2014) Department of Health and Human Services. Executive Summary. The Health Consequences of Smoking—50 Years of Progress: A Report of the Surgeon General. Available online at www.surgeongeneral.gov/library/reports/50-years-of-progress/exec-summary.pdf. Accessed Sept 15, 2018.
(2017) Lung Cancer Screening. National Comprehensive Cancer Center Network Guidelines for Patients. Available online at www.nccn.org/patients/guidelines/lung_screening. Accessed Sept 15, 2018.
(2018) Lung Cancer – Non-Small Cell Lung Cancer. National Comprehensive Cancer Network Guidelines for Patients. Available online at www.nccn.org/patients/guidelines/lung-nsclc. Accessed Sept 15, 2018.
(Feb 03, 2017) UPtoDate.com. Available online through https://www.uptodate.com. Accessed on 10/3/2018.
(December 2013) U.S. Preventive Services Task Force. Final Recommendations, Lung Cancer: Screening. Available online at https://www.uspreventiveservicestaskforce.org/Page/Document/RecommendationStatementFinal/lung-cancer-screening. Accessed December 2018.
Sources Used in Previous Reviews
(Updated 2012 April 17). Lung Cancer and the Environment. Centers for Disease Control and Prevention . Available online at http://ephtracking.cdc.gov/showCancerLcEnv.action. Accessed July 2013.
How to detect lung cancer: Symptoms
How to detect lung cancer: Risk factors
There are many factors that might put you at risk for lung cancer. Many people believe that smoking alone causes lung cancer. But, increasingly, people who have never smoked or who quit smoking many years ago are being diagnosed with lung cancer.
If you have any of the following lung cancer risk factors, you should see your doctor to determine if you need further screening for cancer.
- Exposure to second-hand smoke
- Exposure to radon gas
- Exposure to asbestos
- Exposure to other carcinogens
- Air pollution
- Arsenic in drinking water
- Previous radiation to lungs
- Personal or family history of lung cancer
Does insurance cover early detection testing?
Studies over the last 15 years using early detection screening such as spiral CT have been shown to reduce lung cancer deaths by 16% to 20%. The U.S. Preventive Services Task Force now recommends annual computed tomography (CT) screening for people who meet specific criteria. This non-invasive diagnostic test is covered by Medicare and most insurance companies.
If you answered YES to these 3 questions, you meet the criteria:
New research suggests a simple blood test could improve the early detection of lung cancer
Lung CA seen on CXR. Credit: James Heilman, MD/Wikipedia
New research led by scientists at the Medical Research Council (MRC) Toxicology Unit suggests that by analysing levels of DNA in the blood, the early detection of lung cancer could be improved.
The study, published in the journal Disease Models and Mechanisms, found that in preliminary tests using mice, a blood test could measure the circulating levels of DNA in the blood which cancer cells shed as they grow and multiply, and could even predict the presence of tumours in the lungs before they became cancerous.
Lung cancer is the number one cause of cancer-related death around the world, partly due to the difficulties in detecting the disease at an early stage. By the time lung cancer is diagnosed, it has often spread to other parts of the body making it much more difficult to treat, which is why improved diagnosis at an earlier stage is key to beating the disease.
The scientists at the MRC Toxicology Unit, part of the University of Cambridge, alongside scientists at the University of Leicester, used mice with a mutation in a gene called KRAS to model the pre-cancerous stages of lung cancer. The researchers took regular computed tomography (CT) scans to monitor the development of small pre-cancerous lung tumours in the mice. To determine whether circulating DNA could be used to detect the tumours before they became malignant, blood samples were taken along with the CT scans at different time intervals.
The team found that the mice developing cancerous lung tumours had higher levels of circulating DNA compared with healthy mice, and that the levels of DNA released by the cancerous tumours into the blood of the mice correlated with the size of the tumours seen on the CT scans. The circulating DNA was then analysed for the presence of the precise KRAS mutation that caused the tumours to develop. The researchers found that, significantly, in later stages of tumour development where tumours were still pre-cancerous, the KRAS mutation could still be detected in circulating DNA.
“This observation is exciting because it suggests that tumour-causing mutations may be detectable in circulating DNA from patients with early-stage cancers or with pre-cancerous tumours”, says Dr. Miguel Martins, a programme leader at the MRC Toxicology Unit and lead author of the study.
Regarding the importance of follow-up studies, he believes that “Similar studies should now be conducted using mice bearing pre-cancerous lesions in other tissues. This will give us a better idea of whether circulating DNA has potential use for early cancer detection in patients.”
Dr. Mariana Delfino-Machin, Programme Manager for Cancer at the MRC, which funded the research, added “This is a really promising piece of early-stage research. Lung cancer is incredibly difficult to diagnose at the stage where it can be successfully treated, leading to a poor rate of survival. Developing early detection strategies to improve survival rates is key, and if this can be achieved using only a blood sample it would greatly benefit patients and the NHS. We look forward to the results of the next stages of this research.”
Gut stem cells offer clues for preventing tumours in inherited bowel cancer More information: ‘Early detection of pre-malignant lesions in a KRASG12D-driven mouse lung cancer model by monitoring circulating-free DNA’ by Martins et al, Disease Models and Mechanisms, dmm.biologists.org/content/12/2/dmm036863 Journal information: Disease Models and Mechanisms Provided by Medical Research Council Citation: New research suggests a simple blood test could improve the early detection of lung cancer (2019, February 12) retrieved 2 February 2020 from https://medicalxpress.com/news/2019-02-simple-blood-early-lung-cancer.html This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no part may be reproduced without the written permission. The content is provided for information purposes only.
A growing number of patients with advanced lung cancer could soon be offered a blood test instead of having to get a tumour sample for analysis.
New data from the BFAST trial presented at the ESMO Congress 2019 have shown that the test can be used successfully to identify complex DNA mutations in the cells of patients with non-small cell lung cancer (NSCLC) suitable for the latest targeted medicines. The test could help to help to decide the best treatment for patients.
The technique detects tiny pieces of tumour DNA that are shed from cancer cells into the blood.
Study author Dr Shirish Gadgeel, Rogel Cancer Center, University of Michigan, USA, said: “One of the biggest recent changes in treatment of NSCLC has been our ability to identify targetable genetic mutations that drive progression of the disease, but it is a major challenge to get a suitable tumour sample for analysis.
“We showed that liquid biopsy could be used to detect a complex type of driver mutation, called ALK, in patients with NSCLC. These then responded at least as well to targeted therapy as in previous studies using conventional biopsy techniques.”
In the BFAST analysis, over 2,000 patients with untreated NSCLC had blood tests using state-of-the-art technology to check for multiple driver genetic mutations. Approximately 1 in 20 were found to have tumour DNA showing a rearrangement in the ALK gene.
In patients treated with alectinib, a cancer treatment that targets the ALK mutation, over three quarters showed no signs of disease progression in the subsequent 12 months.
Gadgeel said: “Liquid biopsy identified a similar proportion of patients with ALK mutations to that typically seen with traditional biopsy and the results with alectinib compared well with those seen in a pivotal study of this treatment.”
Commenting on the results of the study, Professor Alberto Bardelli, Department of Oncology, University of Turin, Italy, said: “Rearrangement in the ALK gene described in the BFAST study is typically difficult to detect so it is an important advance to have shown that it can be detected in the blood and used to guide ALK inhibitor treatment which has then been demonstrated to be effective in patients with this mutation.
He added: “It is encouraging to see that increasing numbers of patients with lung cancer can benefit from liquid biopsy to identify their disease mutation instead of tissue samples.
“At present the technology is quite expensive but as it becomes more widely used, the cost is likely to come down so that testing becomes more affordable and available in daily practice.”