Category: Featured News
IMPRINT May Lead to A “New Lung-Sparing Treatment Paradigm”
MesotheliomaHelp has recently reported on two studies showing the benefits of pleurectomy/decortication (P/D) over extrapleural pneumonectomy (EPP) for mesothelioma patients. Now, researchers report that following the surgery with chemotherapy and a novel radiation therapy is safe and resulted in a reduced rate of radiation pneumonitis.
Researchers from Memorial Sloan Kettering Cancer Center and MD Anderson tested a newly developed hemithoracic intensity-modulated pleural radiation therapy (IMPRINT) in a clinical trial of 27 mesothelioma patients who had undergone P/D and chemotherapy. The radiation therapy specifically targets the lining of the lung, where the mesothelioma cells are, and reduces the risk of damaging the lung itself.
The median progression-free survival and overall survival were 12.4 and 23.7 months, respectively. In addition, the two-year overall survival was 59% in patients with resectable tumors and was 25% in patients with unresectable tumors. Only eight patients developed radiation pneumonitis (grade 2 or 3) and all of them recovered after a dose of steroids.
“These results justify our next multicenter trial to explore the safety and feasibility of hemithoracic pleural intensity-modulated radiation therapy” in more medical centers with experience with this malignancy, the authors wrote, according to a June 21 article in Cancer Network.
Radiation therapy is one of the primary treatments for pleural mesothelioma, an asbestos-caused cancer of the lining of the lungs. However, due to the complex growth pattern of the mesothelioma cancer cells targeting just the diseased cells is difficult. Some oncologists shy away from it since radiation can sometimes be too damaging to surrounding organs, as well as causing damage to the lung (pneumonitis).
The researchers noted that the new technique using IMPRINT “has a significant learning curve, and thus should be exported to other centers slowly and carefully.”
P/D strips away the diseased membrane lining the lung and visible mesothelioma tumors, but spares the lung. The other surgical option for pleural mesothelioma patients is the EPP, a more radical procedure that involves removal of a lung, the diseased lining of the chest cavity and heart, and a portion of the diaphragm.
The researchers concluded that incorporating IMPRINT “with chemotherapy and P/D forms a new lung-sparing treatment paradigm for patients with locally advanced MPM [malignant pleural mesothelioma].”
Over 3,000 Americans are diagnosed with mesothelioma each year.
The study can be found in the Journal of Clinical Oncology.
To find out more about the clinical trial see ClinicalTrials.gov.
Researchers Report Activin A May Be A Significant Biomarker
Mesothelioma researchers have focused much of their efforts on developing targeted cancer treatments that center on getting to the specific gene or biomarker responsible for the disease. An alphabet soup of biomarkers, including Abcc10, VEGF, and PD-L1, that indicate mesothelioma, have been used to develop cancer treatments to fight the deadly disease. Now, researchers report that activin A is another biomarker that should be targeted when treating mesothelioma patients.
An international team of researchers, led by a group from the Comprehensive Cancer Center of Vienna, Austria, believe activin A, a biomarker that regulates cell growth and activates cell differentiation, could be a prognostic marker of mesothelioma, according to a June 8 article in the European Journal of Cancer. The researchers found that activin A was “significantly elevated in MPM [malignant pleural mesothelioma] patients.”
Pleural mesothelioma is an incurable, asbestos-caused cancer that attacks the pleural tissue surrounding the lung. The cancer is highly aggressive and is resistant to many cancer treatments making it a difficult disease to treat effectively. Biomarkers, or genetic indicators of the presence of disease, such as mesothelioma, can also be used to determine the severity of the disease, such as in a prognostic biomarker, and to assess the efficacy of a treatment. The findings by these researchers of the significance of activin A can guide medical professionals in the care of mesothelioma patients.
The highlights of the study, as noted by the authors who looked at data of 129 mesothelioma patients, include:
- Plasma activin A levels are increased in malignant pleural mesothelioma (MPM) patients.
- Increased levels associated with non-epithelioid morphology and high tumour volume.
- Plasma activin A level was an independent prognostic factor in MPM patients below 66 years of age with an epithelioid histology.
Research has shown that epithelioid mesothelioma is the most common type of mesothelioma, accounting for nearly 75 percent of all new cases. A study published in the September 2000 respiratory medicine journal Thorax determined that epithelioid mesothelioma patients had a better prognosis than those diagnosed with sarcomatoid or biphasic mesothelioma.
“Our findings suggest that the measurement of circulating activin A may support the histological classification of MPM and at the same time help to identify epithelioid MPM patients with poor prognosis,” concluded the researchers.
Results of the study can be found in the June 8 issue of the European Journal of Cancer.
Researchers Report the EGFR Gene Found in Mesothelioma Silences Tumor Suppression Leading to Uncontrolled Growth
The epidermal growth factor receptor (EGFR) gene has been the focus of researchers for finding new, effective treatments for both lung cancer and mesothelioma patients. The gene, that is overexpressed in more than 50% of pleural mesothelioma patients, and in approximately 15% of lung cancer patients, is one of the primary targets for bringing personalized care to the cancer patients. Now, researchers report they understand just how the gene impacts cancer growth.
Researchers from Yale are referring to the EGFR gene as the “silencer” gene, because, they say, it “silences genes that typically suppress tumors.” The team, led by Narendra Wajapayee, assistant professor of pathology and a member of Yale Cancer Center, report in a June 23 press release, that this critical finding “may lead to the development of more effective, individualized treatment for patients with lung cancer and other cancer types.”
Wajapayee and the team found that EGFR negatively regulated the TET1 protein, important for controlling gene expression and required to suppress tumors, allowing the cancer cells continue to grow and divide.
“EGFR can target multiple unrelated tumor suppressor genes in different cancer types using a common mechanism,” said Wajapayee.
Approximately 2,500 to 3,000 Americans are diagnosed with mesothelioma, an asbestos-caused cancer, each year. Most people diagnosed with mesothelioma are retired workers and veterans who were exposed to asbestos in a workplace or during military service decades ago. The most common form of the cancer is malignant pleural mesothelioma, affecting the lining of the lungs. Disease symptoms can take between 15 and 60 years to appear.
Mesothelioma often resists standard treatments and can build up a resistance to the powerful chemotherapy drugs used to attack the aggressive cancer. Although even targeted EGFR inhibitors can eventually become ineffective, personalized cancer treatment targeted to the unique characteristics of the patient optimizes the potential for success of the treatment.
“The finding informs the future direction of research and treatment of patients who don’t respond or develop resistance to drugs that inhibit EGFR,” said Wajapayee . “It will also help determine how effective cancer therapies will be against different EGFR mutations.”
The results of the study can be found in the June 23 issue of Cell Reports.
Sources:
- Researchers from Yale
http://news.yale.edu/2016/06/23/silencer-study-reveals-how-cancer-gene-promotes-tumor-growth - Cell Reports
http://www.cell.com/cell-reports/fulltext/S2211-1247(16)30700-8
Liquid Biopsies Continue March Towards Use as Diagnostic Tool
MesotheliomaHelp has reported several times over the last year about the promising cancer detection process referred to as a “liquid biopsy.” By using a blood test, as opposed to conducting a traditional biopsy requiring a painful process to remove tissue, researchers report they can detect a specific mutation in a specific cancer to drive treatment. Now, researchers report they are one step closer to developing a blood test that can detect nearly any mutation in cancer.
In a June 6 press release, Guardant Health, along with Samsung Medical Center (Sungkyunkwan University School of Medicine, Korea), reports success with the NEXT-2 clinical trial of 200 advanced cancer patients. The study that used liquid biopsy to test the feasibility of using it “as the sole diagnostic tool” to guide oncologists in matching patients to therapies for multiple cancers, “demonstrated high actionability in matching patients to targeted therapies, as well as statistically significant response rates in lung (88%) and gastric (60%) cancers.”
“The results we have seen have been outstanding, and have certainly exceeded our expectations,” said Dr. Jeeyun Lee at Samsung Medical Center, the primary investigator on the study.
The NEXT-2 trial used the Guardant360 technology – the first and only liquid biopsy that covers all 70 guideline-recommended biomarkers in a single test, according to Guardant. Next up for Guardant is to refine their technology to show that it can effectively spot previously undetected cancers in high-risk patients, such as smokers. Potentially, this technology can be used in other high-risk patients like those previously exposed to asbestos, to detect mesothelioma.
In addition, in a June 4 article in Time, Guardant reported encouraging results from a study of 15,000 patients who were tested with Guardant360. The team was able to identify cancer mutations in over two-thirds of the patients where existing treatments are available. When compared with a traditional tissue biopsy, the blood tests were 98% accurate.
On June 1, the U.S. Food and Drug Administration announced approval of the first liquid biopsy test to detect the EGFR mutation in lung cancer patients. The cobas EGFR Mutation Test v2, is a companion diagnostic for the cancer drug Tarceva (erlotinib), an EGFR tyrosine kinase inhibitor used to treat lung cancer and mesothelioma.
The FDA notes that tumor DNA actually sheds from a tumor into the bloodstream, allowing a liquid biopsy, or blood test, to be used to detect cancer mutations. Currently, there are no effective non-invasive methods for early detection or treatment monitoring for either lung cancer or mesothelioma. However, a blood test can be used for both detection, treatment monitoring as well as for identifying the appropriate treatment protocol.
“Approvals of liquid biopsy tests make it possible to deliver highly individualized health care for patients,” said Alberto Gutierrez, Ph.D., director of the Office of In Vitro Diagnostics and Radiological Health in the FDA’s Center for Devices and Radiological Health. “Liquid biopsies also have the potential to allow physicians to identify patients whose tumors have specific mutations in the least invasive way possible.”
“This is a great day for patients,” said Helmy Eltoukhy, co-founder and CEO of Guardant Health. “With the evidence that liquid biopsies are both concordant with tissue, and useful for treating, clinicians have a tool for genotyping that doesn’t bring with it the cost and potential harm of repeat invasive biopsies.”
Sources:
- Guardant Health
http://www.prnewswire.com/news-releases/first-prospective-clinical-utility-trial-using-comprehensive-liquid-biopsy-to-guide-metastatic-cancer-patients-to-molecularly-matched-therapies-demonstrates-comparable-results-to-tissue-based-testing-300279906.html - U.S. Food and Drug Administration
http://www.mercknewsroom.com/news-release/oncology-newsroom/merck-announces-fda-acceptance-review-mk-3475-biologics-license-appli - (June 4 article in) Time
http://time.com/4357037/blood-test-cancer
Finding Cause of Cancer Metastasis May Lead to New Treatments
MesotheliomaHelp has reported on a variety of studies recently where researchers have delved into the reason for metastasis in cancer. Many of the findings focused on cancer pathways. Now, in a new study, researchers report a pair of molecules may be the reason cancers grow unchecked. For aggressive cancers like mesothelioma that elude treatments, this finding could lead to a new treatment that ends cancer growth.
Researchers from Queen Mary University of London’s Barts Cancer Institute of England, led by Dr Stéphanie Kermorgant, report that they focused their research on understanding how cancer cells can continue to thrive after they break away from the primary tumor – when they are most vulnerable. They knew that integrins, or proteins on the cell surface, use ‘outside-in’ and ‘inside-out’ signaling to anchor cancer cells in place. But, using lung and breast cancer cell cultures from zebrafish and mice, they discovered that once the cancer cells began their metastasis process and were floating the integrins started using ‘inside-in’ signaling, or signaling from within the cell.
“Metastasis is currently incurable and remains one of the key targets of cancer research,” said Dr. Kermorgant. “Our research advances the knowledge of how two key molecules communicate and work together to help cancer cells survive during metastasis.”
They found that the beta-1 and c-Met proteins pair up, and migrate into the floating cancer cell to an area that is typically reserved for signaling cell death. Instead, in the case of floating cancer cells, the proteins’ “inside-in” signaling actually guides the rest of the cells to resist death.
Pleural mesothelioma, a cancer of the lining of the lungs caused by past asbestos exposure, is one cancer that is highly aggressive and spreads quickly to other sites. Survival is typically one year after diagnosis. Research shows that metastasis is the cause of nearly 90 percent of cancer deaths, making it critically important that researchers fully understand how to stop metastasis to increase survival in mesothelioma patients.
The QMUL researchers report that current research for integrins focuses on trying to prevent the anchor from failing, or keeping the cells attached in place and not migrating. However, they plan to prevent the integrin from getting inside the cells in the first place, thus, leading “to the design of better therapies against metastasis and more effective treatment combinations that could prevent and slow both tumour growth and spread.”
“We hope that our support of this exciting research will one day lead to better treatments that can prevent the spread of cancer,” said Dr. Susie Gray, Research and Communications Officer at Rosetree Trust, one of the organizations that provided funding for the research.
2,500 to 3,000 people are diagnosed with mesothelioma each year in the U.S. Mesothelioma takes decades to appear after exposure, but then advances rapidly.
The results of the study can be found in the June 23 issue of Nature Communications.
Photo Credit: Barts Cancer Institute, QMUL
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