Measuring Mesothelioma Treatment Response with Biomarkers



2516827_blood testMalignant pleural mesothelioma is notoriously difficult to treat and doctors often have to try different treatment combinations to produce a response. But how can they know if a particular treatment strategy is working?
A team of researchers in Pisa, Italy suggest that three key biomarkers may be the answer. Soluble mesothelin-related peptides (SMRP), plasma osteopontin (pOPM) and vimentin have all been studied as potential diagnostic tools.
But University of Pisa scientists say these three key markers may also offer an efficient method for clinicians to track how well a mesothelioma tumor is responding to treatment. This could potentially improve mesothelioma outcomes by enabling doctors to change course if they are not seeing the hoped-for results.

Understanding Mesothelioma Biomarkers

Mesothelioma biomarkers are substances found in unusually high quantities in the blood, serum or lung fluid of mesothelioma patients. Because they are either not present in healthy people, or present at much lower levels, they can be valuable for making a mesothelioma diagnosis or for distinguishing pleural mesothelioma from other lung diseases.
The presence of SMRP in the blood indicates damage to mesothelial cells which line the membranes around the lungs. The test for SMRP called Mesomark has become a staple of mesothelioma management in recent years.
Plasma osteopontin is a protein that plays a role in inflammation, including the kind of inflammation caused by exposure to asbestos. Vimentin is another protein. It is expressed in the mesenchymal cells which give rise to all of the body’s connective tissues.

Biomarkers as Mesothelioma Treatment Monitors

To test the value of these three biomarkers as tools for measuring mesothelioma treatmentresponse, the researchers used 219 serum samples from 56 pleural mesothelioma patients.
By calculating the changes in levels of these biomarkers over time and comparing it to each patient’s clinical course, the doctors demonstrated how their levels fluctuated with mesothelioma treatment response.
“SMRP, pOPN, and vimentin showed statistically significant differences between the disease categories stable disease, partial response, and disease progression,” writes mesothelioma researcher Dr. Alessandra Bonotti.  
The analysis showed that these three markers were especially helpful in mesothelioma cases where there was either a partial response to treatment or where the tumor had progressed. “Their possible use in stable disease should be better investigated,” concludes Dr. Bonotti.
Source:
Bonotti, A, et al, “Serum mesothelin, osteopontin, and vimentin: useful markers for clinical monitoring of malignant pleural mesothelioma”, September 14, 2016, International Journal of Biological Markers, Epub ahead of print

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Mesothelioma Risk Among Seaman and Sailors Still Hard to Quantify


310188_Navy Ship smallThousands of people who worked aboard commercial ships may be at higher risk for developing malignant mesothelioma.
Unfortunately, although the mesothelioma risk for merchant seamen has been acknowledged since the 1970s, there is still little information on how high the risk may be.
That news comes from a new report on commercial seamen and mesothelioma published in the journal Inhalation Toxicology.

Mesothelioma Risk and Commercial Seamen

Seamen are thought to be more prone to pleural mesothelioma because of exposure toasbestos, a common but toxic mineral used primarily as an insulator in many ships built in the early part of the 20th century.
By the mid-1900s, cases of malignant mesothelioma had begun to arise in workers in asbestos product manufacturing and asbestos mining and milling industries.
But, according to David Dodge and Barbara Beck of the environmental and risk sciences consulting firm, Gradient, the danger of asbestos exposure on commercial ships was largely ignored for several more decades.
“We found that attention to the potential health risk of asbestos to merchant seamen began in the mid- to late- 1970s and early 1980s,” write Dodge and Beck.

Asbestos and Mesothelioma: Making the Connection

Although tests found the level of asbestos exposure during routine repairs aboard commercial ships was likely to be low, it was enough to send up red flags for people who worked on these ships.
“Responses to this evolving information served to warn seamen and the merchant shipping industry and led to increased precautions regarding asbestos exposure,” conclude Dodge and Beck.
As rates of lung cancer and pleural mesothelioma among merchant seamen began to climb in the 1990s, some researchers finally began to make a connection between shipboard asbestos exposure and cancer.

Asbestos Use in Ships

Asbestos, which was used throughout both commercial and naval vessels, is a naturally-occurring fibrous mineral. When it becomes airborne, the fibers can lodge in body tissues, causing irritation and inflammation that can eventually cause mesothelioma.
Toxicology experts now know that there is no safe level of exposure to asbestos. People who built both commercial and naval ships, sailed on them, repaired them, or decommissioned them, all face a potentially higher lifetime risk of pleural mesothelioma.
It can take decades for mesothelioma to develop but, once it does, it is extremely difficult to treat and there is no cure. An italian study published earlier this year found that the risk of malignant mesothelioma among shipyard workers remains high even thirty years after their jobs ended.
Even if they are unaware of specific instances of asbestos exposure, people who have worked aboard older commercial or military ships should be aware of the symptoms of mesotheliomaand should have regular medical exams.
Source:
Doge, DG and Beck, BD, Historical state of knowledge of the health risks of asbestos posed to seamen on merchant ships, November 10, 2016, Inhalation Toxicology, Epub ahead of print

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Multi-Modal Mesothelioma Treatment Leads to Three-Year Survival


There has been some encouraging news this month for patients suffering from an aggressive form of lung cancer called malignant pleural mesothelioma. New research suggests that, even in patients with advanced mesothelioma, long-term survival is possible with a strategic multi-modal approach.

The Research

The new mesothelioma study, conducted at several US medical centers and published in the Annals of Thoracic Surgery, analyzed the survival rates of 73 patients diagnosed with the epithelioid form of pleural mesotheliomabetween 2005 and 2013. All of the patients had been treated with a combination ofpleurectomy/decortication (PD) surgery and intraoperative photodynamic therapy (PDT).
PD surgery for malignant mesothelioma treatment involves removal of the diseased pleural membrane, portions of the diaphragm, and other at risk tissues. In contrast to the more radical EPP surgery, PD surgery leaves the lungs in place.
Photodynamic therapy requires that mesothelioma tumor cells be pre-treated with aphotosensitizing drug and then exposed to a light source on the end of an endoscope. The goal is to kill any residual mesothelioma cells that the surgeon may have missed.
Most of the mesothelioma patients (92%) analyzed for this study also underwent chemotherapy with pemetrexed (Alimta) after their surgery.

The Results

Although pleural mesothelioma typically carries a life expectancy of just 12 to 18 months, the median overall survival for patients receiving this PD/PDT therapy combination was more than twice that at nearly three years.
The news was even better for the 19 mesothelioma patients whose cancer had not spread to their lymph nodes; These patients had an overall median mesothelioma survival rate of 7.3 years.
“The role for lung-sparing surgery is unclear but this series demonstrates that it is an option, even for advanced cases,” writes study author Joseph S. Friedberg, MD, mesothelioma researcher at the University of Maryland Medical Center in Baltimore. “The overall survival of 7.3 years for the node negative subset of patients, still of advanced stage, is encouraging.”  
These node-negative patients experienced longer survival even though their mesothelioma tumors began growing again a median of 2.4 years after surgery. Dr. Friedberg says thisdisparity between tumor growth and survival may be related to the impact of the PDT, which is currently being studied as part of a randomized mesothelioma clinical trial.
Source:
Friedberg, JS, et al, “Extended Plearectomy-Decortication-based Treatment for Advanced Stage Epithelial Mesothelioma Yielding a Median Survival of Nearly Three Years”, November 4, 2016, The Annals of Thoracic Surgery, Epub ahead of print

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Study Finds Chemotherapy Maximizes Odds of Mesothelioma Survival



919316_chemo drugA large US study of mesothelioma patients confirms what other studies have suggested: Mesothelioma patients who havechemotherapy live longer than those who don’t, and multimodal therapy is the best way to improve overall mesothelioma survival.
The study utilized data from the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) database and included 1,625 Medicare patients with a diagnosis or eitherperitoneal or pleural mesothelioma.

Mesothelioma Treatment Patterns

Led by researchers at Wayne State University in Detroit, the study tracked mesothelioma treatment and survival data between January 2005 and December 2009 with follow-up through 2010.
The study included analysis of both the patient characteristics (like age, gender, and asbestos exposure) and the unique characteristics of their mesothelioma tumor (size, shape, subtype).
Changes were tracked over the course of various types of mesothelioma treatments in an effort to determine which characteristics, treatment patterns and chemotherapy regimens yielded the best mesothelioma survival.

Tracking Treatment Results

Of the 1,625 mesothelioma patients who were eligible for inclusion in the study, the median age at diagnosis was 78. Thirty percent of patients had mesothelioma surgery as part of their treatment strategy and 45 percent had chemotherapy.
The chemotherapy regimen prescribed most often nationwide for mesothelioma treatment was a combination of pemetrexed (Alimta) and cisplatin or carboplatin. Sixty-seven percent of the mesothelioma patients who received chemotherapy had this combination. The same combination or a drug call gemcitabine was most often used for second-line chemotherapy treatment.
Overall mesothelioma survival among the study subjects was a median of 7 months for those who received chemotherapy with those who received second-line chemotherapy living for amedian of a year.

Chemotherapy Impacts Survival More Than Surgery

While the survival odds for mesothelioma remain grim, the research team concluded that chemotherapy still offered the best chance at a longer life. Their data suggests that it matters even more than surgery.
“Irrespective of surgical resection, mesothelioma patients receiving some form ofchemotherapy survived longer than patients who did not, with an additional survival benefitamong those patients receiving multimodal treatment,” writes Jennifer Lynn Beebe-Dimmer of Wayne State University Medical School.
The study was presented at the annual meeting of the American Society of Clinical Oncology last year and appears in a recent issue of Clinical Epidemiology.
Source:
Beebe-DImmer, JL, et al, “Mesothelioma in the United States: a Surveillance, Epidemiology, and End Results (SEER)-Medicare Investigation of treatment patterns and overall survival”, October 26, 2016, Clinical Epidemiology, eCollection

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Platelet Count May be an Effective Tool for Mesothelioma Prognosis


2105823_blood test5high platelet count may not bode well for people battlingmalignant pleural mesothelioma.
New evidence suggests that people who have a high concentration of platelets in their blood prior to the start of mesothelioma treatment have shorter overall survival than those with normal platelet counts.
The news comes from a Chinese meta-analysis including more than 3,600 mesothelioma patients.

Platelets and Health

Smaller than either red or white blood cells, platelets are the components in blood that facilitateclotting. The normal range for platelet counts is 150,000 to 400,000 platelets per microliter (mcL).
When an unusually high concentration of platelets is caused by a secondary problem (such as cancer-related inflammation), it is known as thrombocytosis. By itself, thrombocytosis usually does not cause symptoms and requires a blood test to diagnose.

Platelet Count for Mesothelioma Prognosis

Researchers with First Affiliated Hospital of Fujian Medical University in Fujian, China analyzed 18 different published studies on the relationship between thrombocytosis and mesothelioma survival. The analysis included mesothelioma studies conducted through April 2016 and published in one of four large online databases.
Although there was significant variability between the studies, a clear correlation was found between platelet counts before the start of treatment and mesothelioma treatment  response.
“In conclusion, high pretreatment platelet count resulted in poor overall survival in malignant mesothelioma. Therefore, platelet count could be an adequate and useful factor of prognosis for malignant mesothelioma,” writes Dr. Y. Zhuo of the Thoracic Surgery Department.

A Simple Prognostic Tool

Mesothelioma is rare and difficult to treat. Only about 2,500 people are diagnosed with mesothelioma in the US each year, but the majority of those face a life expectancy of a year or less.
But certain factors can impact outcomes and are valuable for treatment planning, which typically involves a combination of multiple therapies. Because it is fast and easy to measure with a blood draw, platelet count may offer a simple prognostic tool to assist in the mesotheliomatreatment planning process.

Another New Tool for Mesothelioma Prognosis

Platelet count is just one possibility for helping doctors predict mesothelioma prognosis. Earlier this year, an international team of scientists conducted a study suggesting that the protein complex Activin A may be another prognostic indicator in malignant mesothelioma. 
That study included an analysis of plasma samples from 129 mesothelioma patients at four different European institutions. The results showws that the mesothelioma patients had significantly higher levels of Activin A in their bodies than did the healthy controls.
The mesothelioma patients with the lowest Activin A levels had the highest survival levels. Like platelet count, Activin A can be measured with a blood draw.
Source:
Zhuo, Y, et al, “Pretreatment thrombocytosis as a significant prognostic factor in malignant mesothelioma: a meta-analysis”, November 16, 2016, Platelets, Epub ahead of print

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