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German scientists say a protein could help doctors distinguish mesothelioma from other conditions.
Malignant mesothelioma is a cancer that grows on the membranes around organs. These membranes are called mesothelial membranes.
But other conditions can also grow on mesothelial membranes. One of those conditions is adenomatoid tumors.
Adenomatoid tumors are benign but, even under the microscope, their cells can look a lot like malignant mesothelioma.
Now, a group of pathologists in Germany say the BAP1 protein can tell these two conditions apart. If doctors can distinguish mesothelioma from other conditions early enough, mesothelioma patients may have better outcomes.
BAP1 Loss and Mesothelioma
BAP1 is a protein encoded by the BAP1 gene. BAP1 is one of the proteins that helps keep normal cells from turning into cancer cells.
When the BAP1 gene is missing or has an error on it, a person’s body does not produce BAP1 protein. Doctors refer to this as BAP1 loss.
BAP1 loss can put a person at risk for certain kinds of cancer. Malignant mesothelioma is one cancer that is more common in people with BAP1 loss. If people with BAP1 loss are exposed to asbestos, they are even more likely to get this rare cancer.
In the early days, it can be very hard to distinguish mesothelioma from other conditions, which can delay treatment.
Using BAP1 to Distinguish Mesothelioma from Other Conditions
In a new published article, a team of doctors in Germany say BAP1 may be the key to distinguish mesothelioma from other conditions.
They studied the BAP1 levels in 264 cases of malignant mesothelioma and 42 cases of adenomatoid tumors.
Fifty-six percent of malignant mesothelioma cases showed BAP1 loss. It was most common among people with epithelioid mesothelioma. Even the four mesothelioma samples that were most similar to adenomatoid tumors had BAP1 loss.
In contrast, none of the 42 adenomatoid tumors showed BAP1 loss. The German researchers say this shows the potential value of BAP1 to distinguish mesothelioma from other conditions.
They believe that it might even be helpful for earlier mesothelioma diagnosis.
“Surface components of malignant mesothelioma of the pleura showed concordant loss as the invasive tumor suggesting a potential role for BAP1 loss for recognizing so-called early mesothelioma,” concludes the report summary.
Mesothelioma is an extremely rare but aggressive cancer for which there is no cure. Very few of the estimated 2,500 Americans diagnosed with mesothelioma each year live longer than a year.
Erber, R, et al, “BAP1 Loss is a Useful Adjunct to Distinguish Malignant Mesothelioma Including the Adenomatoid-like Variant From Benign Adenomatoid Tumors”, January 11, 2019, Applied Immunohistochemistry and Molecular Morphology, Epub ahead of print, https://www.ncbi.nlm.nih.gov/pubmed/30640754
Researchers in Toronto say machine learning could help doctors diagnose mesothelioma earlier.
Molecular geneticists at the University of Toronto teamed up with cancer and heart doctors to conduct the new research.
The team collected data from hundreds of suspected mesothelioma cases and ran it through different statistical analysis programs. The goal was to see which one was best at determining who had pleural mesothelioma and who did not.
The results revealed some important information – both about the machine learning tools and about how doctors might diagnose mesothelioma earlier, even without them.
Why Doctors Need to Diagnose Mesothelioma Earlier
Mesothelioma is almost always caused by asbestos exposure. In the first few years of the disease, there may be no mesothelioma symptoms.
When patients do develop mesothelioma symptoms like chest pain and shortness of breath, it can mean that the disease is in an advanced stage.
Mesothelioma diagnosis usually involves a number of tests. Patients may have imaging scans, blood tests, and a biopsy. By the time mesothelioma is finally diagnosed, it may already be too late for treatment to help.
Right now, only a small percentage of mesothelioma patients live beyond 18 months. If doctors could find a way to diagnose mesothelioma earlier, it could improve the odds of surviving it.
How Machine Learning Could Help
Machine learning is the process by which artificial intelligence can “learn” to get better at analyzing data, by analyzing a lot of it. There are many different kinds of machine learning algorithms and they all work a little differently.
To see which one might help diagnose mesothelioma earlier, the Toronto researchers used data from the health records of 324 Turkish people. The people were all exposed to asbestos and had mesothelioma symptoms.
After testing five different types of machine learning tools, they concluded that one called “random forest” was the most effective. It was able to quickly and accurately identify the people who ended up having mesothelioma.
“Our results show that machine learning can predict diagnoses of patients having mesothelioma symptoms with high accuracy, sensitivity, and specificity in a few minutes,” concludes lead researcher Davide Chicco.
Two Symptoms May Also Boost Efforts to Diagnose Mesothelioma Earlier
Another important fact to come out of the study are the two features that point to mesothelioma more than all the others.
The Random Forest tool showed that lung side and platelet count could be used to diagnose mesothelioma earlier.
The researchers say even doctors who do not have access to artificial intelligence could be pretty confident in making a mesothelioma diagnosis based largely on these factors.
“The importance of pleural plaques in lung sides and blood platelets in mesothelioma diagnosis indicates that physicians should focus on these two features when reading records of patients with mesothelioma symptoms,” concludes. Dr. Chicco.
Chicco, D, et al, “Computational prediction of diagnosis and feature selection on mesothelioma patient health records”, 2019, PLoS One, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0208737
To test their idea, researchers started with mRNA molecules that tell cells to produce luciferase. Luciferase is a bioluminescent or glowing protein. The goal was to make it easy to see which cells took the information and ran with it.
Next, the team mixed the mRNA into a formula that the mice could breathe in. The mixture was designed to linger in the lungs so that the mRNA could do its job.
When the team checked the mice 24 hours later, the lung cells were producing luciferase, just as they had hoped. The mRNA had been evenly distributed through all five lobes of the lungs.
Just as importantly, there was no glowing tissue outside of the lungs.
The Future of Inhalable Mesothelioma Treatment
Other scientists have also experimented with the possibility of an inhalable mesothelioma treatment.
Last Fall, Swiss scientists tested an experimental therapy containing resveratrol. Resveratrol is the powerful cancer-fighting compound concentrated in red wine.
In that study, asbestos-exposed mice that inhaled the resveratrol either never developed mesothelioma tumors or had smaller tumors.
Pleural mesothelioma is usually caused by inhalation of asbestos fibers. It is most common in people who have worked around asbestos in their job.
People with recurrent mesothelioma may get another chance at treatment with the immunotherapy drug avelumab.
Malignant mesothelioma is highly resistant to standard cancer therapies. That means that the asbestos cancer usually comes back, or recurs, even after treatment.
The most common treatment for mesothelioma is chemotherapy with Alimta. Alimta is the only drug approved specifically for mesothelioma. Patients with recurrent mesothelioma often have several rounds of chemotherapy with Alimta.
Now a new study suggests that some cases of recurrent mesothelioma that stop responding to Alimta may respond to avelumab.
Considering Avelumab for Recurrent Mesothelioma
Bavencio is the brand name for avelumab. It is a type of immunotherapy drug called a monoclonal antibody. Bavencio targets a protein called programmed death-ligand 1 (PD-L1).
PD-L1 helps mesothelioma cells “hide” from the immune system.
The FDA originally approved Bavencio to treat non-small-cell lung cancer. It has since been approved to treat stomach cancer and a certain kind of skin cancer, too.
The National Cancer Institute ran the new study on Bavencio for mesothelioma. It included patients with recurrent mesothelioma from 25 sites in three countries. They were all diagnosed between September 2014 and July 2015.
Fifty-three patients received Bavencio. Thirty-eight percent of them already had three or more other kinds of mesothelioma treatments.
They got 10 mg/kg of Bavencio every two weeks until their mesothelioma came back or until they got too sick to continue.
Avelumab Deemed Safe and Effective as Second-Line Treatment
Researchers monitored the recurrent mesothelioma patients in this study for a median of two years.
Sixty-seven percent of patients responded well to Bavencio. In one patient, the drug wiped out their mesothelioma tumor. Four other patients saw their tumors shrink.
For fifty-eight percent, their recurrent mesothelioma stopped growing. It took a median of four months for mesothelioma tumors to start growing again after treatment with Bavencio.
Forty-three percent of patients were still alive a year after treatment.
Only 8 patients had a serious side effect either from the treatment or from its impact on their immune system. There were no treatment-related deaths.
“Avelumab showed durable antitumor activity and disease control with an acceptable safety profile in a heavily pretreated cohort of patients with mesothelioma,” concludes the report.
About 3,000 people contract mesothelioma in the US each year. Most do not live longer than a year.
Researchers at the University of Pittsburgh have named what they say are the top six mesothelioma survival factors.
According to their new study, patients with one or more of these factors tend to have better mesothelioma treatment outcomes and live longer.
Malignant mesothelioma – also called asbestos cancer – is one of the deadliest forms of cancer. It starts on internal membranes and spreads quickly. There is no cure and the disease is very hard to slow down. Many mesothelioma patients die within 12 to 18 months.
But there are cases of much longer mesothelioma survival. Some patients have even lived for decades after mesothelioma treatment.
Researchers focused on 888 cases of peritoneal mesothelioma or pleural mesothelioma. Patients were diagnosed between 1990 and 2017.
Pleural mesothelioma grows on the lining around the lungs and is hardest to treat. Peritoneal mesothelioma grows on the lining around the abdomen. It makes up about a fifth of all mesothelioma cases.
Identifying Survival Factors
The median overall survival rate of the mesothelioma patients in the study was 15 months. Pleural mesothelioma patients had a median survival of 14 months. The median survival among the peritoneal mesothelioma patients was 31 months.
When the researchers analyzed the cases, they found six top factors associated with longer survival:
45 or younger
Epithelioid mesothelioma subtype
Stage 1 cancer (very little spread)
Treated with both surgery and chemotherapy
Combined Treatment Impacts Mesothelioma Survival
Doctors already knew that peritoneal mesothelioma patients usually live longer than people with pleural mesothelioma.
But one of the most important discoveries from the new study is that peritoneal mesothelioma patients lived longest with a combination of surgery and chemotherapy.
According to the findings, these patients lived as much as 23 months longer than other patients when they had both kinds of treatment.
But the study also contained some sobering news: Overall mesothelioma survival has not changed for many years, even with more advanced treatments.
Amin, W, et al, “Factors influencing malignant mesothelioma survival: a retrospective review of the National Mesothelioma Virtual Bank cohort”, December 19, 2018
A large new study now underway may eventually make it possible to create a mesothelioma breath test.
Cancer Research UK has launched a two-year clinical trial of the Breath Biopsy. The Breath Biopsy is a device that detects molecules exhaled by people with cancer.
The Need for Early Mesothelioma Detection
Malignant mesothelioma is one of the deadliest types of cancer. Most people who get mesothelioma have been exposed to asbestos. By the time they receive a diagnosis, many mesothelioma patients have advanced disease.
Late diagnosis is one of the main reasons people with mesothelioma often die within a year. When mesothelioma cancer is in an advanced stage, it is less likely to respond to treatment.
Scientists around the world are searching for ways to diagnose mesothelioma earlier. Tests for cancer biomarkers in the blood and lung fluid do not work well for early mesothelioma.
The UK scientists hope that a mesothelioma breath test will be a better alternative.
Device Picks up Cancer “Signature”
Cancer causes biochemical changes in the body. These biochemical changes produce volatile organic compounds (VOCs) that a person exhales.
The theory is that different types of cancer produce different combinations of VOCs.
The Breath Biopsy measures these VOCs to see what type of cancer produced them. A mesothelioma breath test should have a unique breath “signature”.
Cancer Research UK is recruiting up to 1,500 people in Cambridge to study the technology. Some of the study participants will be cancer patients and some will be healthy people.
Study subjects will breathe into the device for ten minutes. The device collects and stores the VOCs for later analysis in a lab.
People with suspected stomach or esophagus cancer will try the test first. Then other types of cancer patients will test it. The researchers will compare the VOCs of different kinds of cancers to look for patterns.
“We urgently need to develop new tools, like this breath test, which could help to detect and diagnose cancer earlier,” lead investigator Rebecca Fitzgerald said in a statement. “Through this clinical trial we hope to find signatures in breath needed to detect cancers earlier.”
Advantages of a Mesothelioma Breath Test
One big advantage of a mesothelioma breath test is that it is simple and painless. Researchers say people may be more likely to have a test when there is no needle or scalpel involved.
A mesothelioma breath test would also be quick and cheap. The company that developed the Breath Biopsy is hoping that many doctors will want to use it.
“The concept of providing a whole-body snapshot in a completely non-invasive way is very powerful and could reduce harm by sparing patients from more invasive tests that they don’t need,” said Billy Boyle, CEO of Owlstone Medical, the UK company that makes the test.
If it works the way it is supposed to, the Breath Biopsy could be used along with existing tests to detect mesothelioma earlier.
“Is a breath test key to detecting cancer?”, January 3, 2019, BBC News online, https://www.bbc.com/news/health-46746552
Von Radowitz, John, “Breath test that could revolutionise cancer diagnosis to be trialled in Britain”, January 3, 2019, The Independent, https://www.independent.co.uk/news/health/cancer-breath-test-breathalyser-molecules-liver-prostate-kidney-bladder-pancreatic-a8708861.html
Some of the nation’s top cancer researchers say chemotherapy is the best treatment for pericardial mesothelioma. Even surgery does not extend survival as well as chemotherapy.
Doctors at the University of Texas reached that conclusion after studying more than 100 cases of pericardial mesothelioma.
Surgery is still the most common treatment for pericardial mesothelioma. But the new research suggests that chemotherapy may be better.
In the study, chemotherapy and cancer spread were the only factors that seemed to impact mesothelioma survival.
What is Pericardial Mesothelioma?
Malignant mesothelioma tumors grow on the linings around internal organs.
The most common type is pleural mesothelioma which grows near the lungs. Peritoneal mesothelioma on the abdominal lining is the second most common type.
Pericardial mesothelioma grows on the lining around the heart. It is the rarest type of mesothelioma. Fewer than one percent of all diagnosed mesothelioma cases are pericardial.
Malignant mesothelioma is usually caused by exposure to asbestos. Average survival among people with the pericardial type is six to ten months.
Beyond that, doctors do not know very much about this rare malignancy.
Studying Treatment for Pericardial Mesothelioma
Very few people contract pericardial mesothelioma. To study it, the Texas researchers had to look far back in the medical literature.
Between 2000 and 2016, they found 103 people who received treatment for pericardial mesothelioma.
The median age at diagnosis was 55. The median overall survival for these mesothelioma patients was six months.
Researchers compared men and women, asbestos exposure levels, radiation history, and mesothelioma subtypes. They also looked at each patient’s prescribed treatment for pericardial mesothelioma.
Chemotherapy for Mesothelioma Has Greatest Survival Benefit
Besides cancer spread, the study showed that only one factor had an impact on mesothelioma survival.
“A survival benefit was noted in those who received chemotherapy (median survival, 13 months vs. 0.5 months),” writes lead author and internist Elizabeth McGehee, MD. “In multivariate analysis, only the receipt of chemotherapy was associated with improved survival.”
Pericardial mesothelioma patients who received chemotherapy had a median survival of 13 months. That compares to a median of two weeks in patients who did not have chemotherapy.
Patients did best when the treatment for pericardial mesothelioma included a platinum drug. Common platinum drugs include cisplatin and carboplatin. The addition of Alimta did not appear to make a difference.
Malignant mesothelioma is one of the rarest cancers and one of the hardest cancers to treat. Although there is no cure for mesothelioma yet, Ginsburg and Kraus show that patients are not powerless.
The National Cancer Institute recommends exercise to fight obesity, which has been linked to increased risk of 13 different cancers. Regular exercise may reduce the risk for colon cancer by 24 percent and breast cancer by 12 percent.
A number of other studies have focused on cancer-fighting compounds in fruit and vegetables, mushrooms, wine, herbs, and spices.
Exercise and a healthy diet may also help reduce mesothelioma treatment-related side effects.
Most malignant mesothelioma patients will have chemotherapy. The most common type of chemotherapy is by infusion. Each session takes several hours.
Every mesothelioma patient undergoing chemotherapy faces the possibility of kidney damage. That possibility can even limit how much medicine doctors can use.
But a new Dutch study finds that faster mesothelioma chemotherapy may be as safe for the kidneys as standard chemotherapy.
Analyzing Faster Mesothelioma Chemotherapy
The study included 230 lung cancer patients who had chemotherapy. Some of the study subjects had non-small cell lung cancer. Some had small-cell lung cancer. And some had pleural mesothelioma, the most aggressive lung-related cancer.
About half of the patients had regular chemotherapy with cisplatin. Cisplatin is a platinum-based drug usually given along with Alimta for mesothelioma patients.
It took three hours for the patients in the “regular chemotherapy” group to complete a session.
A second group got faster mesothelioma chemotherapy in just one hour. The Dutch doctors looked for acute kidney injury (AKI) in both groups. They also watched for a decrease in eGFR, a measure of kidney function.
“There was no significant difference in renal function between rapid infusion of cisplatin and regular infusion of cisplatin,” writes researcher Eveline S Mense, PharmD, in the Journal of Clinical Pharmacy and Therapeutics.
Chemotherapy for Malignant Mesothelioma
Chemotherapy is currently the most effective way to treat pleural mesothelioma. Mesothelioma patients get the best results with a combination of mesothelioma and surgery. But even patients who are not candidates for surgery can usually have chemotherapy.
Some patients also benefit from emerging mesothelioma treatments like targeted radiation and immunotherapy.
While chemotherapy can be effective, it can also be inconvenient, especially if a patient lives far away from the infusion center.
The Dutch team says faster mesothelioma chemotherapy could make treatment easier on patients.
They conclude, “A 1-hour infusion of cisplatin is a safe and feasible method, which may potentially shorten duration of hospital admittance and enable treating patients in the outpatient setting.”