PMC Symposium Highlights New Mesothelioma Research, Clinical Trials
UCLA and the Pacific Mesothelioma Center (PMC) hosted the 8th International Symposium on Malignant Pleural Mesothelioma at UCLA’s Meyer and Renee Luskin Conference Center on the last weekend of September 2018.
The conference saw doctors from around the world showcase new findings related to pleural mesothelioma. Doctors and practitioners from Scotland, France, Australia, Japan, Belgium and the United States presented studies.
Their presentations reported on new methods that could potentially be used to diagnose and treat mesothelioma in the future.
Why New Ways are Needed
However, these methods are not 100% effective and current treatments cannot cure patients. Most people are diagnosed with mesothelioma after it has spread to other areas of the body. In some cases, patients may also suffer health complications from the side effects of existing treatments.
“In general, we have a hard time overall doing better than somewhere around 18-19 months in terms of patient survival,” said Dr. Robert Cameron, scientific advisor for the PMC.
As a result, many new diagnosis and treatment methods are being tested in clinical trials. New measures such as immunotherapy, breath compound analysis and other measures may hold the key to improving patient survival.
Immunotherapy: A New Hope for Mesothelioma Treatment
Studies about the benefits of immunotherapy were an important part of this year’s conference. Immunotherapy allows doctors to harness the body’s immune system to fight tumors.
When your body is sick, cells are developed by your immune system to fight the infection. However, some cancer cells can suppress the body’s immune response.
Immunotherapy allows the body to enhance the production of anti-tumor cells that can overpower the cancer cells.
Since immunotherapy is still being studied, it has not been widely used outside of these trials. It is not always effective, but fortunately, many different forms of immunotherapy are being studied.
Modified Measles Virus to Improve Immune Response
Nicolas Boisergault from France’s CRCINA Cancer Research Center unveiled studies that used an oncolytic measles virus to infect and kill mesothelioma cells. An oncolytic virus infects and kills tumor cells without harming healthy cells.
By harnessing a weakened version of the measles virus and infecting it with the delta c protein, scientists could cause rapid tumor death and improve the body’s immune response.
A weakened form of the measles disease is currently used to vaccinate children.
Immunotherapy and T-Cells
Multiple presentations emphasized how protein-focused drugs could harness the immune system to fight cancer cells. PhD candidate Wesley Wilson stated that the successes or failures of treatments like surgery and chemotherapy are governed by the immune system.
Some of these therapies centered on the body’s production of T cells. T cells are produced by the immune system to attack diseases. Normally, your body produces different proteins and chemicals to regulate the T cell response.
Mesothelioma cells can evade T cells, allowing tumors to grow. Fortunately, immunotherapy can stop this by targeting certain proteins.
- PD-1 and PD-L1 immunotherapy: PD-1 is a protein found on T cells. PD-1 acts as an inhibitor for your body’s T cells to regulate them. However, cancer cells are equipped with a similar protein called PD-L1. Cancer cells can connect to T cells using these proteins and escape detection. PD-1 and PD-L1 immunotherapy can block this connection, allowing T cells to do their job and kill the cancerous cells.
- CTLA 4 antibodies: CTLA 4 is a protein generated on the surfaces of T cells to stop them from going crazy and attacking healthy cells. CTLA antibodies allow the immune response to continue. While these drugs alone had mixed results in clinical trials, they have shown promise in combination with other treatments. For example, Dr. Mikihio Kohno noted that combining CTLA-4 blocking drugs with radiotherapy improved local tumor control and allowed the body to attack other tumors in distant areas.
Dr. Robert Cameron explained how the immune system reacts to certain drugs and surgery.
Current surgeries such as extrapleural pneumonectomy (EPP) and pleurectomy with decortication (P/D) give doctors better access to tumors. However, there is no way to completely remove all the cancer cells.
Cameron and his team analyzed the effects of old immune-drug studies and new surgeries.
When analyzing old data, they found that patients given immunological agents:
- Responded well when given short-term doses
- Lived longer when the agents were given alongside surgery
However, surgeries alone presented challenges. In minor surgeries, there was not a big immune response. In major surgeries, there were high levels of proteins that suppressed the immune system.
“I think this is some really helpful information because it tells us what’s normally happening after surgery—which is, almost everything that’s happening is not amenable to the immune system, at least the cellular immune system,” Cameron said.
Cameron suggested that combining certain drugs with surgery could improve the immune system response.
New Mesothelioma Diagnosis Methods May Be Safer, Cheaper
Outside of studies that looked at immune-based treatments for mesothelioma, doctors and researchers also studied new ways to detect and diagnose the condition.
As with treatment methods, current mesothelioma diagnosis methods are not always accurate and can sometimes weaken patients. Most of them are also very expensive.
Fortunately, upcoming methods could help diagnose mesothelioma without these problems.
Dr. Kevin LaMote reported on how compounds in the breath could be used to diagnose mesothelioma. Current studies suggest that certain compounds in the breath can distinguish between people with mesothelioma and those who have been exposed to asbestos.
“Once these [compounds] are known, we will try to build specific sensors so that just a patient can breathe into a machine or a small sensor device and where a yes or no answer will hopefully come out,” LaMote said.
The goal of the breath test would be to replace the need for CT scans or biopsies, which can be invasive and expensive. Follow-up studies are being conducted to externally validate their findings.
“It will not diagnose on its own, but I see it as an add-on tool in the diagnostic work,” LaMote said.
Dr. Kevin G. Blyth of the Scottish Mesothelioma Service noted that MRI scans may be a useful tool to diagnose mesothelioma.
According to Blyth, current scans such as CTs or ultrasounds cannot effectively differentiate mesothelioma from benign diseases in some cases. Blyth studied how perfusion MRI could be used to better distinguish between the two.
Perfusion MRI enhances the natural imaging contrast of a standard MRI procedure. MRIs have helped Blyth and others better see loculation and effusion in patients.
Based on data pulled from a substudy, Blyth illustrated that perfusion MRI scans were more than 90% sensitive and outperformed expert opinions based on just CT or MRI scans.
From this, Blyth and his team studied how perfusion MRI scans could be used to determine the volume of a mesothelioma tumor—something that is notoriously hard given the disease’s nature.
“Meso has an incredibly complex tumor shape,” Blyth said. “It’s a rind around a lung.”
Blyth and his team created contour masks (computer-assisted images) of mesothelioma-affected areas. Then, they tuned into the actual tumor based on signal intensity data from the perfusion MRI study. A more intense signal would indicate where a tumor is located.
The volume-based study showed that this method could be used to measure patient survival based on the size of the tumors. Additionally, this method was better at predicting survival when compared to CT-based staging scans.
The Future of Mesothelioma Research
Mesothelioma is a complex disease, and there are no simple answers when it comes to treatment. However, as doctors and researchers have shown, new studies may present better ways to diagnose, manage and treat this rare form of cancer.
The PMC is a division of the Pacific Heart, Lung & Blood Institute (PHLBI). 10 of the presentations and several question-and-answer sessions are available online on the PHBLI’s YouTube channel.
Outside of PMC’s symposium, there are many other conferences that take place around the world each year. With each new year comes new data and potential treatments—the building blocks of a cure.