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Mesothelioma patients need to beware of low-volume centers that are less likely to follow mesothelioma treatment guidelines. That is the message from a new study based on data from the National Cancer Institute.
The study was run by doctors at Cedars-Sinai Medical Center in Los Angeles. It shows that treatment centers that do not see a lot of mesothelioma cases are less likely to follow the life-saving mesothelioma treatment guidelines.
Malignant pleural mesothelioma is a cancer that occurs on the membrane that surrounds the lungs. It is extremely rare and difficult to treat. Many hospitals and doctors never see more than a handful of cases.
Mesothelioma treatment guidelines are meant to help cancer doctors offer the best treatment options to their patients, even if they rarely treat mesothelioma.
The current guidelines say epithelioid mesothelioma patients should be offered a combination of surgery and chemotherapy. Adding a third treatment modality like radiation or immunotherapy improves survival even more.
Mesothelioma patients with sarcomatoid or biphasic mesothelioma should have chemotherapy.
But the new study suggests that too many smaller, non-academic hospitals are not following these mesothelioma treatment guidelines. Their patients may be paying the price.
Lower Compliance = Shorter Survival
The study is based on the cases of more than 3,400 mesothelioma patients. The patients received a mesothelioma diagnosis between 2004 and 2014.
Mesothelioma patients who have no treatment have a median survival estimate of 10.2 months. Those who have chemotherapy alone live for an estimated 15.4 months.
But those who receive combination treatment according to the mesothelioma treatment guidelines have a median survival of more than 21 months.
Researchers say the two top predictors of whether a center was following these guidelines were insurance status and facility type.
“In epithelial malignant pleural mesothelioma, a significant increase in overall survival was observed in surgery plus chemotherapy and trimodality,” observes lead researcher Fernando Espinoza-Mercado, MD.
Finding the RIght Mesothelioma Treatment Center
The bottom line for mesothelioma patients is to seek treatment in a larger, academic center, if at all possible. These centers have more experience with this rare cancer and are more likely to follow the current mesothelioma treatment guidelines.
“There is a suboptimal compliance with national guidelines for the treatment of MPM, particularly in low-volume non-academic settings,” concludes the new report. “Adherence to recommended surgery-based multimodal therapy is associated with an overall survival improvement.”
When it is not possible to travel to a higher-volume center, have a discussion with your physician about current mesothelioma treatment guidelines. This list of 7 questions for your oncologist can help you choose the best mesothelioma doctor for you.
New research out of Pennsylvania suggested that not all people with metastatic mesothelioma will live longer with chemotherapy.
Although chemotherapy is the primary treatment for malignant pleural mesothelioma, some types of metastatic mesothelioma appear to be less responsive than others.
In some cases, the researchers say best supportive care may be a better option for preserving a patient’s quality of life.
Three Mesothelioma Subtypes
There are three histological subtypes of malignant pleural mesothelioma. The categories are based on how the cells look under a microscope. Cell type appears to influence how aggressive they are as metastatic mesothelioma. Cell type also factors into mesothelioma prognosis.
Epithelioid mesothelioma is the most common cell type. Epithelioid cells tend to lack uniformity and may form small tubes or clusters. Epithelioid mesothelioma is usually more responsive to treatment than other subtypes, even after metastatic mesothelioma has occurred.
The non-eipthelioid subtypes are sarcomatoid and biphasic. Sarcomatoid cells are the least common but most aggressive mesothelioma subtype. Biphasic mesothelioma contains both epithelioid and sarcomatoid cells in the same tumor.
Assessing Treatment Options for Metastatic Mesothelioma
The new mesothelioma study was conducted at several top research centers including MD Anderson, University of Pennsylvania and Yale.
It included 4655 pleural mesothelioma patients from the National Cancer Database. Forty-one percent of the patients had metastatic mesothelioma. This means that mesothelioma cells have spread to other parts of their body.
People with metastatic mesothelioma are not good candidates for surgery. Chemotherapy is often the primary treatment for these patients. About half of the study subjects had chemotherapy and the other half received best supportive care.
“Chemotherapy was associated with higher overall survival in [metastatic mesothelioma] cases with unknown histology and [metastatic] epithelioid patients,” writes lead author Vivek Verma of the Radiation Oncology department at Pittsburgh’s Allegheny Health Network Cancer Institute.
But patients with metastatic mesothelioma of the sarcomatoid or biphasic subtype did not respond nearly as well. Chemotherapy led to longer survival in this group only if the cancer had not spread.
Mesothelioma chemotherapy carries its own risks, including the risk of death. In cases where it is unlikely to help, this research suggests that best supportive care may be a better option.
The research team concludes that “careful patient selection in this population cannot be understated.”
A new National Cancer Institute study shines a light on some of the ways genes impact mesothelioma survival. It could have important implications for mesothelioma treatment.
The study was led by prominent mesothelioma researcher Raffit Hassan, MD. It focused on genetic mutations that may make certain mesothelioma patients more sensitive to chemotherapy.
Genes, Genotype, and Mesothelioma Treatment
A mesothelioma patient’s unique collection of genes, including genetic mutations, is known as their genotype.
Genes impact mesothelioma survival in a variety of ways. Tumor suppressor genes are supposed to help keep tumors from forming. People with mutations on these genes may be more likely to get malignant mesothelioma.
Other genes influence the cancer’s ability to “hide” from detection by the immune system. Some new treatments for mesothelioma focus on trying to offset the effects of these mutations.
DNA Repair Genes Impact Mesothelioma Survival
In the current mesothelioma study, Dr. Hassan and his colleagues analyzed how DNA repair genes impact mesothelioma survival.
DNA repair genes are supposed to help fix problems that can naturally crop up in the DNA during a cell’s life. Part of their job is to help keep tumors from forming in the first place.
But the new study shows that mesothelioma patients with mutations in these genes may also be more susceptible to chemotherapy. When chemotherapy damages DNA in these patients’ mesothelioma cells, the cells may not be able to recover.
As a result, it appears that these genes impact mesothelioma survival positively.
“Among 385 patients treated with platinum chemotherapy, median overall survival was significantly longer for patients with loss-of-function mutations in any of the targeted genes compared with patients with no such mutation,” writes Dr. Hassan.
The Effect of Genotype on Mesothelioma Prognosis
Apparently genes impact mesothelioma survival differently depending on what type of mesothelioma a patient has.
The study found that pleural mesothelioma patients with loss-of-function genetic mutations who had chemotherapy had a median survival of 7.9 years versus 2.4 year. Pleural mesothelioma affects the lining around the lungs. It is the most common type.
In contrast, There was no significant survival difference in peritoneal mesothelioma patients with or without these same loss-of-function mutations. Peritoneal mesothelioma impacts the lining around the abdomen. About a fifth of mesothelioma cases are this kind.
The researchers conclude: “Patients with pleural mesothelioma with inherited mutations in DNA repair and other tumor suppressor genes appear to particularly benefit from platinum chemotherapy compared with patients without inherited mutations.”
In general, chemotherapy for mesothelioma is only moderately effective. It typically extends survival by only a few months. Knowing ahead of time which patients are most likely to benefit could help in treatment planning.
Staging Helps Direct Surgery for Malignant Mesothelioma
Most mesothelioma patients receive chemotherapy. If the patient is healthy enough and the cancer has not spread, the patient may also have surgery for malignant mesothelioma.
Some patients have a lung removed along with their diseased pleural lining. Others have a more conservative type of surgery that leave the lungs in place.
One way doctors determine who would benefit from surgery for malignant mesothelioma is by examining cells from their lymph nodes. The more lymph nodes that contain mesothelioma cells, the more advanced the cancer is.
The new Canadian study focused on a minimally-invasive but precise way to check for cancer cells in the lymph nodes.
During EBUS-TBNA, the surgeon uses ultrasound to guide a biopsy needle into the space between the sternum and the spinal column.
Pleural mesothelioma tumors may shed cells into lymph nodes in this region. EBUS-TBNA removes some lymph node cells for testing.
It can take the place of a bigger, riskier procedure that involves placing a camera into the same area.
Using EBUS-TBNA to Plan Surgery for Malignant Mesothelioma
The new study looked back at the cases of 48 patients who had surgery for malignant mesothelioma. Patients were diagnosed between 2012 and 2014. More than 70 percent of the patients had epithelioid mesothelioma, the most common subtype.
EBUS-TBNA showed that 35 percent of the patients had Stage 2 or 3 mesothelioma. Although it was not very good at determining which patients definitely had mesothelioma, EBUS-TBNA was 100 percent accurate in ruling out the asbestos cancer.
Just as importantly, it helped show which patients were not good surgical candidates.
“EBUS-TBNA mediastinal lymph node staging prevented unnecessary surgery in 18.8% (9/48 patients) by detection of N2/N3 disease (8 patients) and metastatic secondary malignancy (1 patient),” writes lead author Kasia Czarnecka-Kujawa. “There were no EBUS-TBNA related complications.”
The researchers conclude that the EBUS-TBNA “may impact significantly management of patients with malignant pleural mesothelioma” by detecting metastatic cancer.
Preventing surgery for malignant mesothelioma when it is unlikely to help can prevent surgery-related complications and deaths.
Czarnecka-Kujawa, K, et al, “Endobronchial ultrasound-guided transbronchial needle aspiration mediastinal lymph node staging in malignant pleural mesothelioma”, February 2019, Journal of Thoracic Disease, pp. 602-612, http://jtd.amegroups.com/article/view/26697/20060
A combination mesothelioma therapy that showed promise in early trials is finally being studied on a larger scale.
The power-packed chemo-immuno-gene therapy known as TR002 has the potential to change the outlook for thousands of malignant mesothelioma patients.
A small trial of the combination mesothelioma therapy in 2016 produced “significantly higher” mesothelioma survival rates than most patients are told to expect.
Drug company Trizell announced last month that the combination will now be tested on 300 patients at sites in the US, Europe, Australia and Russia.
Combination Mesothelioma Therapy Starts with Gene Therapy
TR002 is an investigational gene therapy for mesothelioma patients who have failed first-line chemotherapy.
This combination mesothelioma therapy is based on the human interferon-alpha 2b gene. The gene is delivered to mesothelioma patients via a virus that is altered to serve as a carrier or “vector”.
Once the drug-carrying virus is delivered into the pleural cavity (around the lungs), the virus breaks down and the gene can do its work.
Interferon alpha-2b is a protein the body uses to fight cancer. This first step of the combination mesothelioma therapy turns cells into interferon alpha-2b producing machines. This enhances the body’s ability to fight mesothelioma.
Chemotherapy is Second Part of Treatment
After mesothelioma patients receive the TR002 portion of the combination mesothelioma therapy, they have a two-week “break”. Patients will then have chemotherapy with gemcitabine.
A previous Phase 2 study of this combination mesothelioma therapy took place at the Abramson Cancer Center. That trial included 40 mesothelioma patients with unresectable pleural mesothelioma. Some had never had any chemotherapy and some were having chemotherapy for the second time.
The overall disease control rate with the combination mesothelioma therapy was 87.5 percent. Patients who were having chemotherapy for the second time survived nearly twice as long as is normally expected (17 vs. 9 months).
“The results that we noted in our previous study showed significant prolongation of life expectancy and particularly so for about 25 percent of these refractory patients who have gone on to live two and in some cases three years and more,” says Daniel H. Sterman, MD.
Dr. Sterman is Director of the Multidisciplinary Pulmonary Oncology Program at NYU Langone Health. He and Dr. Steven Albelda of Pennsylvania’s Perelman School of Medicine pioneered the new treatment.
The new trial of the combination mesothelioma therapy will enroll 300 mesothelioma patients who have failed first-line chemotherapy.
Sterman, DH, et al, “Pilot and feasibility trial of immuno-gene therapy of malignant mesothelioma using intrapleural delivery of adenovirus-interferon-alpha combined with chemotherapy”, March 11, 2016, Clinical Cancer Research, Epub ahead of print
The group conducted a study using a large US government database of information on pleural mesothelioma survival and treatment.
They used the data to create a visual representation of pleural mesothelioma survival called a nomogram. Testing of the nomogram showed it was more accurate at predicting survival in patients who have mesothelioma surgery than the tool doctors normally use.
Pleural Mesothelioma Survival and TNM
The most popular method for “staging” cancer is called the TNM staging system. TNM stands for tumor node metastasis.
With TNM, the further a cancer has spread in the body, the higher the stage number. Some studies have linked higher TNM stage with poor pleural mesothelioma survival.
But the Chinese team says TNM does not go far enough. Their extensive study of the factors that impact pleural mesothelioma survival after surgery found “no significant association” between TNM stage and survival.
Instead, the researchers say their new nomogram can predict pleural mesothelioma survival in surgery patients with far greater accuracy.
Using SEER, the Chinese team identified the top factors in pleural mesothelioma survival after surgery. These included things like age, gender, subtype, stage, chemotherapy, and type of mesothelioma surgery.
They used the data to create the nomogram. Then they validated the nomogram in a separate group of 312 mesothelioma surgery patients.
“A calibration plot for the nomogram for predicting one‐year and three‐year survival indicated that the nomogram has high predictive accuracy in the validation cohort,” writes lead researcher Minglei Zhuo.
What Factors Impact Pleural Mesothelioma Survival?
The results of the Chinese analysis of pleural mesothelioma survival were in line with prior research.
In general, people who are older, men, and those with a non-epithelial mesothelioma subtype do not live as long after pleural mesothelioma surgery.
But the goal of the nomogram is to allow for much more individualized treatment planning. Doctors can plot each mesothelioma patient’s unique characteristics on the nomogram to come up with a far more accurate predictor of their own mesothelioma prognosis
“These results improve our understanding of resected malignant pleural mesothelioma lesions and provide a reliable tool for predicting patient overall survival,” concludes Dr. Zhuo.
The research team plans to create a separate nomogram for predicting pleural mesothelioma survival in people who do not have surgery.
Chinese researchers say soluble mesothelin-related peptides (SMRP) in lung fluid is still one of the best biomarkers for mesothelioma, even if it sometimes produces false positives..
SMRP has been studied extensively as a way to help diagnose mesothelioma. The most popular test to check levels of SMRPs in the body is a blood test called MESOMARK. In recent years, other biomarkers for mesothelioma have also emerged.
But SMRPs are not just in the blood. A new meta-analysis of SMRPs from pleural effusions finds that they have a valuable place among top biomarkers for mesothelioma.
Biomarkers for Mesothelioma: SMRPs and Others
Malignant mesothelioma is a type of cancer that starts on the membranes around the lungs, heart or abdomen. SMRPs are produced by the breakdown of proteins in these membranes.
When SMRPs are released by cells in the pleural membrane, some can end up in lung fluid. People with mesothelioma tend to develop excess fluid around their lungs called pleural effusions (PE),
The amount of SMRPs in pleural effusions appears to correlate with the extent of malignant mesothelioma in the body. This is why SMRPs are one of the key biomarkers for mesothelioma.
Some other biomarkers for mesothelioma include osteopontin, fibulin-3 (FBLN3), neutrophil to lymphocyte ratio, c-MET expression, and ki-67 ratios. FBLN3 is most often used for mesothelioma prognosis rather than diagnosis.
Meta-Analysis of Biomarkers for Mesothelioma
A meta-analysis is a study of studies. The current meta-analysis comes from researchers at Capital Medical University in Beijing. Their aim was to evaluate the value of PE-SMRPs among biomarkers for mesothelioma on a larger scale than any single study.
Their meta-analysis included thirteen other studies on SMRP in PE. The studies Included 759 cases of malignant pleural mesothelioma and 1,061 cases of malignant pleural effusion that was not caused by mesothelioma. Another 1,539 cases of pleural effusions had benign causes.
The researchers found that testing SMRPs in pleural effusions diagnosed mesothelioma correctly about 70 percent of the time. The true positive rate is called sensitivity.
The same test was better at ruling out mesothelioma. Testing for SMRPs from pleural effusions correctly ruled out malignant mesothelioma about 90 percent of the time.
“Although the sensitivity of SMRPs was low, PE-SMRPs can be a good indicator of the existence of malignant pleural mesothelioma,” conclude the researchers.
Biomarkers for Mesothelioma are Only Part of the Diagnostic Picture
Not all types of mesothelioma produce high levels of SMRPs. Sarcomatoid mesothelioma produces much less than other types, so SMRP testing may not detect it.
This is one reason that biomarkers for mesothelioma are not the only tool doctors use to diagnose asbestos cancer.
Mesothelioma diagnosis usually also involves imaging studies and histochemical testing of tumor cells. A thorough work history, including any history of asbestos exposure is also important.
About 2,500 Americans receive a mesothelioma diagnosis every year.
The older a mesothelioma patient is, the less likely he or she may be to receive mesothelioma chemotherapy. A new study says many older mesothelioma sufferers may be paying the price in shorter lifespans.
Chemotherapy with pemetrexed (Alimta) and cisplatin is the gold standard for mesothelioma treatment. Many studies have linked it with longer mesothelioma survival.
But an Australian study suggests that not enough older people are receiving mesothelioma chemotherapy.
In fact, the older they are, the less likely they are to have chemotherapy for their mesothelioma. As a result, their chances of dying from malignant mesothelioma are higher.
Mesothelioma Chemotherapy is Standard of Care
Malignant mesothelioma is a hard-to-treat cancer with a poor prognosis. Mesothelioma chemotherapy is the primary way oncologists try to help extend survival.
Most patients undergo other treatments along with mesothelioma chemotherapy. These might include surgery, intrapleural chemotherapy, radiation, or immunotherapy.
But there is one group of mesothelioma patients who are not getting the benefits of mesothelioma chemotherapy as often as they could be. Others may be receiving chemotherapy when it could do more harm than good.
Analyzing Chemotherapy Use Among Mesothelioma Patients
Australia was once a major global producer of asbestos and now has one of the highest per capita rates of asbestos cancer in the world.
Researchers with Australia’s Asbestos DIseases Research Institute in Sydney conducted the new study. It included 910 mesothelioma patients. Forty-one percent of the patients were younger than 70. Forty percent were between 70 and 80. The final 19 percent were over 80.
The study found that the median overall mesothelioma survival rate in these patients decreased as they got older, as did chemotherapy use.
Mesothelioma Chemotherapy and Survival
Only 66 percent of patients under 70 received mesothelioma chemotherapy. That group had a median survival of 13.5 months. The rate of chemotherapy dropped to just 35 percent in mesothelioma patients between 70 and 80. Survival in this group was 9.5 months.
Among mesothelioma patients over 80, only 8 percent received chemotherapy. Their median overall survival was just 7.1 months.
“A Kaplan Meier analysis revealed that there was a significant survival advantage for patients under 70 and 70 to 80 years receiving chemotherapy, but not for patients over 80 years,” writes author Anthony Linton.
Patients under 70 who did receive chemotherapy had a survival rate of 16.8 months. Patients in the same age group who did not have mesothelioma chemotherapy had a median survival of just 7 months.
A similar difference was observed in the 70 to 80 year old group. With mesothelioma chemotherapy, those patients lived for a median of 13.9 months. Without it, survival dropped to just 5.8 months. Patients over 80 did not live longer with chemotherapy.
The authors do not explore why there is a difference in chemotherapy use in older patients. They conclude that more study is needed to determine whether the current treatment guidelines are relevant for the oldest mesothelioma patients.
A UK study says prophylactic radiation of the chest wall is unlikely to prevent pleural mesothelioma metastasis.
Pleural mesothelioma is an aggressive cancer caused by asbestos. Tumors start on the lining around the lungs and can spread to the lungs and other organs. Pleural mesothelioma is the most common type of asbestos cancer.
Doctors sometimes use procedures that pierce the chest wall to help diagnose mesothelioma or to deal with mesothelioma side effects. Sometimes, new mesothelioma tumors can form along the instrument tracts or in the spot where the chest wall was pierced. When tumors spread it is known as mesothelioma metastasis.
Some evidence suggests that radiating the chest wall after a procedure might prevent mesothelioma metastasis in that area. But a three-year mesothelioma research study appears to refute the idea.
Preventing Pleural Mesothelioma Metastasis
Malignant pleural mesothelioma is a rare cancer but it is also fast-growing. Mesothelioma metastasis to other parts of the chest is common. These metastatic tumors can impact the lungs and other organs.
As mesothelioma spreads in the chest, fluid can collect around the lungs, causing breathing problems and chest pain. Doctors may pierce the chest wall with an instrument to drain off the fluid. Collecting cells for mesothelioma biopsy may also require a chest wall puncture
Mesothelioma metastasis along the instrument tract or on the chest wall can be a serious problem. In some centers, doctors have tried to prevent this by routinely irradiating these areas.
Radiation kills cancer cells by disrupting their DNA so they cannot replicate. But it is also risky because it can damage healthy cells, too.
The goal of the new study was to determine whether chest wall radiation to prevent mesothelioma metastasis is worth the risk.
The Risk of Prophylactic Radiation
Between 2012 and 2015, 375 mesothelioma patients at 54 UK hospitals took part in the study. They all had procedures that required doctors to insert an instrument through the chest wall.
Half of the patients received chest wall radiation afterward and half did not.
“No significant difference was seen in the incidence of chest wall metastases (CWM) at 6 months between the prophylactic radiotherapy and no radiotherapy groups,” reports lead investigator Neil Bayman, MD.
Even though there was no difference in the amount of mesothelioma metastasis in the chest, there were problems.
More than 62 percent of irradiated patients developed radiation dermatitis. Radiation dermatitis can cause red, itchy, rough skin. In its most severe form, radiation dermatitis can cause painful, broken skin that is prone to infection.
After analyzing the results, the researchers conclude, “There is no role for the routine use of prophylactic irradiation to chest wall procedure sites in patients with malignant pleural mesothelioma.”
Bayman, N, et al, “Prophylactic Irradiation of Tracts in Patients With Malignant Pleural Mesothelioma: An Open-Label, Multicenter, Phase III Randomized Trial”, March 2019, Journal of Clinical Oncology, https://ascopubs.org/doi/10.1200/JCO.18.01678