NEWS | EPP Surgery Still Plays Important Role in Mesothelioma Treatment

The much-debated and extremely aggressive extrapleural pneumonectomy (EPP) surgery still should play a prominent role in the management of mesothelioma, according to a recent U.K. study.



The study reopened the simmering controversy over the value of the EPP by contradicting the conclusions of previous research that prompted some specialists to stop doing the surgery and others to dramatically reduce the number of procedures.

The EPP involves the removal of an entire lung, the lining surrounding the lung and heart, along with major parts of the diaphragm — all in a curative attempt to remove as much cancer as possible.

Critics of the EPP have argued the risks are not worth the rewards, and that the disease can be better managed in less aggressive ways. They point to the much-discussed Mesothelioma and Radical Surgery (MARS) trial completed in 2011, which cited 112 patients from 12 different hospitals throughout the U.K. The MARS conclusion was that benefits of the EPP were negligible, while quality of life was diminished.

"One more of those surgeries would be one too many," surgeon and researcher Tom Treasure, University College of London, told Asbestos.com shortly after the MARS trial. "That surgery can be stopped now without a loss."

Since the MARS trial, very few EPP surgeries have been done in the U.K. They are done more often in the U.S., although specialists are being much more selective with their surgical candidates.

Some Lobbying Against EPP

Robert Cameron, M.D., renowned thoracic surgeon at the Pacific Meso Center and the UCLA Medical Center, has lobbied vehemently against the EPP for many years, preferring the lung-sparing pleurectomy/decortication surgery.

Renowned specialist David Sugarbaker, M.D., who is leaving Brigham and Women's Hospital in Boston to start at a new mesothelioma program at the Baylor College of Medicine, continues to promote the benefits of the EPP.

"We have demonstrated improved short- and long-term outcomes with EPP in the present study," researchers wrote in the Journal of Thoracic and Cardiovascular Surgery (Jan. 15, 2014). "It is our contention that radical surgery, including EPP in the management of MPM [malignant pleural mesothelioma] should not be discouraged on the basis of a single controversial feasibility study (MARS trial)."

The study included 30 malignant pleural mesothelioma patients who had undergone EPP surgery at Castle Hill Hospital in the U.K. There were no in-hospital or under-30 day deaths. The long-term survival analysis included 35 percent living after three years and 31 percent more than four years.

Results Have Been Good

Two patients lived more than seven years. And two more were still alive after six years when the study data concluded in February 2013. The overall median survival was 20 months, but it increased to 47.5 months for patients who completed a trimodality treatment regimen that included chemotherapy and radiation.

Survival at six, 12 and 18 months was 80 percent, 65 percent and 55 percent, respectively. The survival in the MARS trial, for the same respective time periods, was 65 percent, 52 percent and 34 percent.

"The EPP has a definite role in the management of malignant pleural mesothelioma," Syed Qadri, a cardiothoracic surgeon at Castle Hill Hospital in the U.K., told Asbestos.com. "But it is not a procedure for every stage of disease, or every patient. It has shown encouraging results in selective groups of patients."

The researchers also pointed out that the operative mortality of EPP has decreased, from 31 percent in 1976 to 3.4 percent in 2011. Of the 30 patients who were part of the study, four died between 30-60 days after the surgery.

Surgery Patients Must Be Selected Well

The report emphasized certain characteristics that made EPP surgery considerably more effective. Prolonged survival was associated with epithelioid mesothelioma, a right-sided pneumonectomy, being younger than 65 and negative extrapleural lymph nodes.

In epithelioid mesothelioma, there was a 44 percent survival rate of three years or more. With the biphasic mesothelioma group, none survived 18 months. Those under 65 had a median survival rate of 27 months, compared to a 12-month survival rate for those over 65. The three-year survival was 41 percent for the younger group, but only 24 percent for the older group.

"The MARS trial definitely effected [negatively] the management of mesothelioma worldwide," Qadri said. "But we have [EPP] patients who still are alive after eight years. There are surgeons in the United States who believe in EPP, as well. We believe the EPP can be performed safely and effectively as part of a trimodality management."

SOURCE : http://www.asbestos.com/news/2014/03/13/epp-surgery-still-plays-important-role-in-mesothelioma-treatment/

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NEWS | Scientists ask for sufferers of the asbestos-related cancer mesothelioma to step forward to boost research

Scientists looking into possible treatments for the asbestos-related cancer mesothelioma are asking patients and their families to help steer future clinical research.



A survey has been launched aimed at better understanding the diagnosis, treatment and care of people with the disease, dubbed the “hidden killer” by the Health and Safety Executive.

Researchers hope that patients, carers and clinicians will raise concerns about their experience and allow for the compilation of 10 aspects of mesothelioma which could benefit from research.

The survey is being carried out as part of a project by the Priority Setting Partnership which is funded by the National Institute for Health Research and the results are set to be published later this year.

“It is vital that we gather and listen to the views of as many people as possible so everyone knows the topics that are a priority for clinical research,” says Professor Dame Sally C. Davies, chief medical officer and chief scientific adviser at the Department of Health.

“Mesothelioma research has been identified as an important area and everyone needs to hear what patients, carers, families and healthcare professionals believe are the most important unanswered questions around the diagnosis, treatment and care of mesothelioma.”

Mesothelioma is a cancer of the membrane which covers the internal organs and it is currently incurable. Patients live, on average, for eight months following diagnosis. There is a direct link between the disease and the inhalation of asbestos fibres and it can take around 30 years for the effects to be seen.

The latest government figures show the disease caused 2,291 deaths in Britain in 2011 and the disease is set to reach its peak in 2016. Yet research funding is low. According to Lord Alton of Liverpool, the British Lung Foundation invested £1 million in 2011 but the government did not inject any funding.

The survey is being supported by a number of health organisations including the British Lung Foundation, Mesothelioma UK, The Mick Knighton Mesothelioma Research Fund, Asbestos Victims Support Groups Forum UK, The June Hancock Mesothelioma Research Fund, and Cumbria Asbestos-Related Disease Support.

Graham Sherlock-Brown, who has been diagnosed with mesothelioma, said: “It is essential that research money is put into finding ways to relieve the suffering caused by this aggressive disease.

“Progress in treatment is long overdue and mesothelioma victims deserve far better – very few survive past five years and mesothelioma will continue to claim victims as long as asbestos is present in the UK.

“That’s why I’m pleased to see the launch of this important survey, which gives patients and carers a much-needed voice.”

Asbestos was widely used in commercial buildings, homes and schools and was hailed for its strength and fire retardant properties.

Following a confirmed link between asbestos and mesothelioma, blue and brown asbestos was banned in the UK in 1985. White asbestos was banned in 1999 although it remains in many buildings to this day.

New cases of mesothelioma have increased fourfold since the 1980s. Asbestos exposure can also cause asbestosis, plural plaques, plural thickening and lung cancer.

The survey is available at www.psp.nihr.ac.uk/mesothelioma/survey

SOURCE : http://www.independent.co.uk/life-style/health-and-families/health-news/scientists-ask-for-sufferers-of-the-asbestosrelated-cancer-mesothelioma-to-step-forward-to-boost-research-9138990.html

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NEWS | Standard Chemotherapy Mix Still Best for Mesothelioma

Researchers at Japan’s Shizuoka Cancer Center and Juntendo University say the popular chemotherapy combination of cisplatin and Alimta (pemetrexed) should remain the gold standard for malignant pleural mesothelioma.


In a study published in Respiratory Investigations, the team, led by Takehito Shukuya, concluded that Alimta and the platinum-based drug cisplatin produced better long term results in mesothelioma patients than the combination of cisplatin and Gemzar (gemcitabine). Gemzar is a nucleoside analog that some studies have found to be a promising alternative to the more conventional Alimta-based mesothelioma treatment.

In a retrospective comparison study of the two treatment combinations, researchers examined the cases of 30 consecutive malignant pleural mesothelioma patients from July 2002 to December 2011. “We reviewed the medical charts of these patients and evaluated their characteristics as well as data regarding drug toxicity and antitumor efficacy,” Dr. Shukuya explains. Seventeen of the mesothelioma patients were treated with a combination of Alimta and cisplatin while the remaining 13 received cisplatin with Gemzar.

While 35% of the mesothelioma patients receiving Alimta saw a response to treatment, only 15% of the Gemzar group responded. The time it took for mesothelioma tumors to begin growing again after treatment was also significantly longer in patients on Alimta (median 215 days) than it was for those on Gemzar (median 142 days). Just as importantly, mesothelioma patients on Alimta had a median survival of more than a year and 7 months compared to about 10 months for those treated with the Gemzar combination.

Although both types of chemotherapy had the potential to cause serious side effects in the mesothelioma patients taking them, Alimta appeared to come out ahead of Gemzar in this area, too. The researchers report that both drug combinations caused thrombocytopenia, an abnormally low number of platelets, and neutropenia, a drop in neutrophil white blood cells, but that both problems were “more frequent and severe” with Gemzar treatment.

In the conclusion to their published summary, Dr. Shukuya and his colleagues write, “Cisplatin plus pemetrexed (Alimta) may be superior and should continue to be the standard front-line chemotherapeutic regimen for inoperable malignant pleural mesothelioma.”

Alimta was developed by a Princeton scientist who claims to have conceived the idea while studying chemical compounds known as heterocyclic compounds in the iridescent wings of butterflies. It was approved as a first-line mesothelioma treatment in 2008. Both Alimta and Gemzar are marketed by Eli Lilly and Company.


Source:

Shukuya, T, “Comparison of cisplatin plus pemetrexed and cisplatin plus gemcitabine for the treatment of malignant pleural mesothelioma in Japanese patients”, March 2014, Respiratory Investigations, pp. 101-106. http://www.ncbi.nlm.nih.gov/pubmed/24636265
http://www.survivingmesothelioma.com/news/view.asp?ID=001588

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NEWS | Mesothelioma Surgery Debate: Experience is the Answer

A pair of researchers in the UK say a cancer center’s level of experience in dealing with mesothelioma may be the most important factor in achieving good surgical outcomes – not which surgery is chosen.


Their new meta-analysis is the latest in a long line of studies attempting to discern which type of mesothelioma surgery is best for patients in terms of survival and complications. The global medical community remains sharply divided over the risks and benefits of lung-sparing pleurectomy/decortication vs. lung-removing extrapleural pneumonectomy.

In the newest study, authors Sotiris and Sayonara Papaspyros analyzed the results of 16 separate studies comparing P/D to EPP in the treatment of mesothelioma. They found a median survival range from 8.1 to 32 months with P/D while the longest median survival after EPP was 46.9 months and the shortest was 6.9.

The rate of complications with each types of mesothelioma surgery was also mixed: Complication rates ranged from as low as 5.9% with P/D and 10% with EPP to as high as 55% with P/D and 82.6% with EPP. The highest median mortality for P/D among the studies was 9.8% while the highest with EPP was 12.5%. But there were some studies where no mesothelioma patients died from P/D while the lowest death rate found with EPP was 3.2%.

In an effort to summarize these conflicting findings, the authors conclude that either surgery is sometimes warranted that that clinical experience appears to have the biggest impact on outcomes. “This systematic review suggests that surgery in the context of trimodality therapy offers acceptable perioperative outcomes and long-term survival. Centers specializing in malignant pleural mesothelioma management have better results,” they write in ISRN Surgery.

Because of the usual shape and tricky location of mesothelioma tumors – spread across the thin pleural lining that surrounds the lungs – both types of mesothelioma surgeries are considered extremely challenging and it is usually not possible to remove all traces of mesothelioma. For this reason, most centers combine mesothelioma surgery with chemotherapy and radiation before and/or after the procedure.


Source:
Papaspyros, S and Papaspyros, S, “Surgical management of malignant pleural mesothelioma: Impact of surgery on survival and quality of life-relations to chemotherapy, radiotherapy, and alternative therapies”, February 2014, ISRN Surgery, http://www.hindawi.com/journals/isrn.surgery/2014/817203/
http://www.survivingmesothelioma.com/news/view.asp?ID=001589

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NEWS | Systemic stem cell therapy reduces malignant mesothelioma growth

Systemic delivery of stem cells expressing an apoptosis-inducing protein can successfully incorporate into malignant pleural mesothelioma (MPM) cells and subsequently induce their death, according to preclinical study findings.


While further validation is needed, the research opens up the possibility of using stem cell therapy to decrease tumour burden in this rare and largely untreatable type of lung cancer.

“Bone marrow-derived mesenchymal stem cells (MSCs) are attractive candidates as vectors for anticancer therapies for a variety of reasons,” say Sam Janes (University College London, UK) and colleagues who performed the study.

Indeed, in vitro studies have shown that MSCs migrate towards tumour cells and in vivo studies that they can then incorporate into a variety of cancer cell types. This is true in a variety of cancer cell types, including lung metastases. MSCs can also be delivered intravenously as well as intrapleurally.

“In this study, we show for the first time that MSCs expressing TRAIL (MSCTRAIL) induce apoptosis in MPM cells in vitro,” Janes and team report in Thorax. TRAIL, or tumour necrosis factor-related apoptosis-inducing ligand, is a transmembrane protein and an “exciting anticancer molecule”, the team explains.

Recombinant TRAIL has been tested in early clinical trials and shown promising results, but its short half-life of 32 minutes means that it would require multiple infusions to have any sustained therapeutic effect.

“MSCs home to and incorporate into tumours in vivo when delivered via both intrapleural and intravenous routes,” the team notes, so using these cells to deliver TRAIL is an interesting prospect for malignant mesothelioma, which is often too diffuse to surgically remove or does not respond well to chemotherapy.

The researchers used a variety of methods to show that MSCTRAIL could kill MPM cells in vitro and then home in on, and kill, tumour cells in animal model of malignant mesothelioma. Dual fluorescence and bioluminescent imaging were used to track the movement of the stem cells.

While both intrapleural and intravenous delivery of the stem cells was able to decrease the tumour burden in mice, intravenous administration appeared to have a greater effect. MSCTRAIL also resulted in a greater level of cell death when compared with treatment with recombinant TRAIL in vitro.

“The therapeutic effect seen with intravenous delivery could be related to greater engraftment of MSCs within the tumour and is an important finding when considering the future therapeutic role of MSCTRAIL therapy in the clinic,” the researchers conclude.

Source

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NEWS | The Impact of Asbestos Use Worldwide

Although the danger of asbestos was acknowledged decades ago, and although the mineral is entirely or mostly banned in most industrialized nations, the world is still feelings the effects of asbestos use. According to the World Health Organization (WHO), deaths from asbestos-related disease worldwide increased from 90,000 in 2006 to 107,000 in 2010. These are deaths from lung cancer, mesothelioma and asbestosis caused by asbestos exposure, mostly in the workplace. As many as one in three deaths from occupational cancer may be caused by asbestos WHO says. Several thousand more deaths annually can be attributed to exposure to asbestos in the home.


WHO also estimated that about 125 million people around the world are still being exposed to asbestos at work each year. Many of these workers are in developing countries with little or no safety regulation to protect them.

The world’s production of asbestos is decreasing, slowly. In 2012 an estimated 2 million tons of asbestos was produced, but this is about half the production level of 1977. The number of asbestos-producing countries also has decreased. Only four countries account for 90 percent of the world’s production — Russia, China, Brazil and Kazakhstan. Russia is by far the primary source of the world’s asbestos; in 2012 one million tons of asbestos came from Russia alone.

Russia’s prodigious asbestos production raised concerns about the recent Winter Olympics in Sochi. Was asbestos used to construct the Olympic village and sports facilities? Russia’s own building codes forbid its use, but whether building codes are enforced is an open question. And Russian officials have been evasive when questioned directly about asbestos in Sochi.

Not long ago, Canada would have been on that short list of top producers as well. Canada was a major supplier of the world’s asbestos, even after its use was restricted in Canada. Most of Canada’s asbestos was exported to developing countries such as Bangladesh, India and Indonesia. The last two asbestos mines in Canada stopped production in 2011, however, and there was little political will to provide loans to re-open them. In 2012, the government of Canada announced it would no longer oppose international efforts to list asbestos as a hazardous substance under the Rotterdam Convention, a multilateral treaty that is intended to protect people in developing countries from imported hazardous substances.

Canada is not alone. In the past 35 years, a number of other countries have ceased to export asbestos. And at this time, 54 countries have either entirely or partly banned asbestos. So, along with the reduction of asbestos producers, there are also many fewer asbestos consumers. In 2012 China and India alone accounted for more than half of the world’s consumption of asbestos.

Asbestos mining and most—not all—industrial uses of asbestos have stopped in the United States. But the U.S. still exports and imports asbestos. According to the United States Geological Survey (USGS), in 2012 the U.S. exported and re-exported $26.4 million of asbestos-containing products such as brake linings. Most of these products went to Mexico, South Korea, Canada, the United Kingdom and Venezuela. The “re-exported” products were made outside the United States.

Also in 2012 the United States imported 1,610 tons of chrysotile asbestos, the USGS says, all from Brazil. Exactly how this asbestos is being used is not explained in USGS reports. Records say the United States imported $8.61 million of products containing asbestos in 2011, although the USGS isn’t sure if all of those products were correctly labeled.

Because of the long incubation period of asbestos-related cancer — 40 years between exposure and diagnosis is not unheard of — incidents of disease continue for a long time after asbestos use is discontinued. For example, although Italy banned asbestos in 1992, approximately 1,000 Italians die each year of mesothelioma and another 1,000 of other asbestos-related disease. Many of these deaths cluster around what were once asbestos manufacturing plants, shipyards, and other facilities that processed asbestos. The government has responded by launching a national asbestos project to investigate causes, increase public awareness and improve diagnosis and treatment.

Currently the highest rates of reported mesothelioma are in Australia, the United States, the United Kingdom, and the Netherlands. Cases may be underreported in developing countries, of course.

In short, the devastating effects of asbestos exposure will continue to be felt for a long time to come, although decades from now we can expect to see most of the world’s cases of asbestos-related disease in the developing nations using it so recklessly now.

SOURCE

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