Epidemiological Review of Recent Mesothelioma Developments

INTRODUCTION

In this feature article, we will provide a comprehensive update on innovation within mesothelioma epidemiology. Over the past few months, there has been a wide range of reports on studies which directly or indirectly apply to elements of mesothelioma development, detection and treatment.

Of course, this growing field of scientific research is relevant to occupational mesothelioma claims, where claimants will seek special damages from past employers (and their EL insurers) for life-preserving future care available on the private healthcare system. If medical advancements one day lead to identifying a potential cure, mesothelioma may no longer be considered as a fatal disease.

In recent years, there have been over 2,500 mesothelioma-related deaths annually and this trend is expected to continue until at least 2020, which further emphasises the importance of ongoing therapeutic trials and improving prognosis.

MESOTHELIOMA DETECTION

‘Breath Biopsy’ to Identify Early-Onset Cancer

This month, Cancer Research UK launched a 2-year clinical trial of the ‘Breath Biopsy’ device, which will detect volatile organic compounds (VOCs) exhaled by 1,500 oesophageal, stomach, prostate, kidney, bladder, liver and pancreatic cancer victims.[1] The introduction of this study is significant, as scientists target early diagnosis.

If the results of the clinical trial yield success, it is possible that a similar device will be produced to diagnose mesothelioma as a non-invasive, painless alternative to mesothelioma biomarkers. Mesothelioma advancement has been shown to affect patient survival.

Quicker Mesothelioma Blood Test

In Japan, a more effective blood test has been devised, with a view to diagnosing mesothelioma at an early stage.[2]

Currently, diagnosing mesothelioma can require a mixture of imaging scans, biopsies and blood tests.

However, in a new, faster method, called ‘CTC-Chip’, scientists have been able to detect circulating tumour cells (CTC), which are released when mesothelioma cells ‘land’ in a new location. ‘CTC-Chip’ is coated with an antibody against podoplanin, which is a common glycoprotein in the blood of pleural mesothelioma sufferers.

Common Mesothelioma Survival Factors Revealed

Scientists at the Mount Sinai Medical Center, New York, have published an article in the Carcinogenesis journal, which outlines the most significant characteristics for mesothelioma survival.[3] Information, relating to 16,000 mesothelioma patients, was taken from the National Cancer Institute database. Though men were more likely to develop mesothelioma, survival was better in patients who were:

  • Female;
  • Younger than 60;
  • Earning a higher income;
  • Not affected by existing health problems;
  • Diagnosed with an epithelial mesothelioma subtype;
  • In the early stages of cancer; and
  • Surgically operated on, or received medical treatment.

Having profiled the best-surviving patient as a young, healthy, affluent woman, it was identified that oestrogen could have tumour suppressing qualities. For this reason, the researchers have suggested that hormonal therapy could be added to treatment plans of mesothelioma patients with poor prognosis.

Contrary to study findings, the longest living mesothelioma patient is male and has survived the condition for more than 20 years. 

MESOTHELIOMA METASTASIS

Aggressive Mesothelioma Progression Shares Biological Similarities with Beneficial Growth and Repair Process

When humans heal and grow, it is made possible by a process known as epithelial-mesenchymal transition (EMT). This causes epithelial cells, which are fixed to a specific spot, to change their properties and become mesenchymal cells, which can migrate from one spot to another.

In a recent study, researchers at the Comprehensive Cancer Center (CCC) of MedUni Vienna and Vienna General Hospital recognised that aggressive malignant pleural mesothelioma cells share similar properties with mesenchymal cells.[4] What is more, they were able to detect the biological signals [fibroblast growth factors (FGF2) and epidermal growth factors (EGF)] responsible for causing tumour cells to inherit the characteristics of mesenchymal cells.

Lead author, Mir Ali Reza Hoda, suggested that:

‘Blockading these signals could therefore offer new approaches for treating certain aggressive forms of mesothelioma’.

Researchers Stop Malignant Cells from Growing and Spreading to Other Organs

Elsewhere, a group of biomedical engineers, at the University of Minnesota, has exposed the mechanism by which malignant cells move towards blood vessels and nearby tissue, publishing their findings in the Nature Communications journal.[5] Upon making this discovery, the researchers were able to develop an agent which stopped the cells from spreading (metastasising) to other areas of the body.

Typically, mesothelioma metastasis is described as a ‘localised spread’. Pleural mesothelioma cells tend to travel from the chest cavity lining into the immediate lung and then the neighbouring lung, followed by the adrenal glands, the kidneys and the liver. Peritoneal mesothelioma tends to spread to the lungs, the heart, the liver, the kidneys, the brain and bones.

Highlighting areas for future development, study author, Paolo Provenzano, stated his team would ‘like to find ways to suppress cancer cell movement while enhancing immune cell movement to fight the cancer’.

Pleural Lining Thickness Used to Stage Mesothelioma Patients

Japanese researchers have invented a new method of staging mesothelioma.[6] Staging can assist clinicians with future treatment planning and assessment of treatment success.

In 104 pleural mesothelioma patients, who all received chemotherapy prior to surgery, CT scanning was used to measure pleural lining thickness in three places:

  1. The upper chest.
  2. The mid-chest.
  3. The lower chest.

The researchers then produced two categorised values, on the basis of these thickness measurements:

  1. ‘Max’ – the thickest measurement.
  2. ‘Sum’ – the total of all three thickness measurements.

Both ‘max’ and ‘sum’ figures were associated with overall mesothelioma survival and recurrence-free survival. It was concluded that the ‘sum’ of pleural thickness values could be used to stage patients, as surgeons have to peel-back the pleural lining when they surgically operate.

MESOTHELIOMA TREATMENTS

Avelumab as a 2nd Line Treatment

In the growing field of immunotherapy research, we have regularly reported on clinical trials involving pembrolizumab, nivolumab, and ipilimumab.

Indeed, in edition 244 (here), we reported on the survival benefits of prescribing nivolumab in combination with ipilimumab. In the MAPS2 study, disease control rate was increased by 10% compared with patients who received nivolumab in isolation.

Avelumab (trade name Bavencio), is another available drug and it has been approved by the FDA to treat non-small cell lung cancer, stomach cancer and skin cancer.[7]

In the recent Phase I JAVELIN Solid Tumour Trial, conducted by the National Cancer Institute, 53 mesothelioma patients were monitored, all of whom had previously been treated with platinum and pemetrexed-based therapy.[8] The report remarked that:

‘Avelumab showed durable antitumor activity and disease control with an acceptable safety profile in a heavily pretreated cohort of patients with mesothelioma’.

43.8% of patients were still alive 12 months post-treatment and Avelumab has been recommended as a 2nd line option for those who do not respond to chemotherapy.                                        

Most Advantageous Treatment Order?

A group of healthcare professionals has identified that malignant mesothelioma is most effectively treated with surgery and chemotherapy. They have embarked on a new Phase II clinical trial, called EORTC 1205, which will follow early-stage pleural mesothelioma patients in Belgium, the Netherlands, Egypt and France, to assess whether chemotherapy should be administered before or after the completion of pleurectomy decortication, or extra pleural pneumonectomy surgery.[9]

Recent studies on this issue have found no definitive advantage either way. [10]

Chemotherapy prior to surgery has the benefit of shrinking a tumour, which theoretically increases the success of removing malignant material. This is the approach favoured in Europe. By contrast, chemotherapy post-surgery is can destroy any residual malignant tissue which is hidden from view, or is unresectable. In the US, this is the favoured approach.

The researchers consider that the conclusions on progression free survival (PFS), overall survival (OS), treatment-failure-free survival (TFFS), operative morbidity and mortality, toxicity and safety, drawn from EORTC 1205, will highlight the ‘most advantageous mesothelioma treatment’ order.

Post-Surgery Immunotherapy Spray as a Viable Alternative to Chemotherapy?

As a means to prevent cancerous tumour recurrence, or metastasis, scientists at UCLA have designed a biodegradable gel spray, containing immunotherapy-loaded calcium carbonate, for use after surgery.[11]

In mice with advanced melanoma, impressive survival results were observed. Tumour regrowth did not occur in the original site, nor in others. The spray also helped with wound healing.

It has been suggested that the spray could offer a genuine alternative to post-surgical chemotherapy.

Trial Underway for Chemotherapy Plus Vaccine Combination Therapy

Researchers at Cardiff University have published an article, in the OcoImmunology journal, which discussed the enhanced response of a novel cancer vaccine, ‘TroVax’, when taken in combination with chemotherapy.[12]

‘TroVax’ has already showed promise with renal, colorectal and prostate cancers. It is modified to target human protein 5T4, which are produced by malignant mesothelioma cells.

In the course of the Phase II trial, 27 patients received one injection of ‘TroVax’ two weeks prior to chemotherapy (permetrexed and cisplatin) beginning. Subsequent injections (up to 8) continued in regular intervals over a 6 month period.[13]

Tumours in 70% of patients stopped growing temporarily. The median length of time before re-growth was 7 months. What is more, 17% of patients’ mesothelioma tumours shrunk, with the addition of ‘TroVax’. As a result of beneficial responses to the combination therapy, lead researcher, Jason Lester stated:

‘In this phase II trial, TroVax with pemetrexed-cisplatin chemotherapy showed robust immune activity, acceptable safety and tolerability to warrant further investigation in a phase III setting’.

Virotherapy Can Be Improved with Immune-Stimulating Strategy

Virotherapy uses a modified virus to target cancer cells. However, an issue with modified viruses is that they can block the body’s natural immune response to malignant mesothelioma, which is to release white blood cells called T lymphocytes (CTLs).

To combat this issue, University of Hong Kong researchers have published a research paper, which suggests that virotherapy techniques should be combined with an immune-stimulating strategy, as it ‘results in the induction of potent antitumor CTLs that not only eradicate established mesothelioma but also prevent the second tumor challenge’.[14]

In theory, therefore, this new strategy would better prepare the body for relapse after fighting the first wave of mesothelioma and reduce the risk of tumours re-forming.

In fact, the approach already exists. In the Biomedicine journal, biologists in Minnesota showcased the benefits of viroimmunotherapy, where Keytruda was used to stimulate the immune system and saw evidence of improved survival.

Peritoneal Mesothelioma Patients Receive New T-Cell Therapy

The National Cancer Institute is funding development of a new treatment method, called CAR T-cell therapy, which could be rolled out for mesothelioma and lung cancer patients.[15] This therapy is already revolutionising the treatment of blood and bone marrow cancers.

Participants, invited to take part in the study, will have peritoneal mesothelioma and a life expectancy of more than 3 months.

T-cells are a type of white blood cell which cause the immune system to attack cancer cells. CAR T-cell therapy involves:

  1. Extracting patient T-cells.
  2. Fine-tuning instructions to attack asbestos-related tumours.
  3. Returning CAR-cells to the local site where the tumour resides.[16]

In the first project, undertaken by the University of Pennsylvania, CAR T-cells will be programmed to attack mesothelin protein (trial 1), located on most mesothelioma tumours, as well as the fibroblast activation protein, which is part of the tumour support system (trial 2).

In a related project, University of Pennsylvania researchers will seek to combine CAR T-cell therapy with other types of therapy.

The study is scheduled to continue until the end of 2020.

Permetrexed Nanoparticles Target Pleural Mesothelioma in New Study

What happens when you load gold nanoparticles with permetrexed chemotherapy?

In a recent study of malignant pleural mesothelioma patients (MPM), researchers sought to use the unique elemental qualities of gold nanoparticles (GNP) to target tumorous cells. Such qualities include:

  • Specific targeting of malignant cells, with increased intracellular drug accumulation
  • Reduced systemic toxicity, and,
  • In the case of MPM, direct treatment administration into the pleural space.[17]

Results showed that using gold nanoparticles as a drug delivery system yielded improved uptake of permetrexed:

‘The innovative use of specifically targeted GNPs opens the perspective of local intrapleural administration to avoid normal cell toxicity and enhance chemotherapy efficacy’.

Apatinib as a 3rd Line Mesothelioma Treatment

Despite the fact that there is currently no approved 2nd line therapy for pleural mesothelioma, Chinese researchers have been developing a drug, called Apatinib, which could be used as a 3rd line treatment.[18]

The drug is being administered to a 58-year-old patient with advanced epithelioid mesothelioma, who received a chemotherapy combination of pemetrexed (trade name Alimta) and cisplatin (1st line) and a different combination of gemcitabine (trade name Gemzar) and cisplatin (2nd line), both without success.

Even though the chemotherapy combination treatments were ineffective, Apatinib achieved a 5-month progression-free survival. As such, the research team explained, in the Medicine journal:

‘Apatinib may be a potential therapeutic drug for malignant pleural mesothelioma, particularly as a third-line treatment in cases resistant to chemotherapeutic options’.

Surgery Should Not Be the Default Option for Pericardial Mesothelioma Victims

Surgery is the most common treatment method for pericardial mesothelioma, which is the rarest form of asbestos-induced mesothelioma. Having investigated 103 cases, however, doctors at the University of Texas arrived at the conclusion that chemotherapy may be a better option.[19] Writing in the Clinical Lung Cancer journal, the authors noted:

‘Surgery did not provide a statistically significant survival benefit ... A survival benefit was noted in those who received chemotherapy ... specifically chemotherapy with a platinum agent with or without pemetrexed’.

Palliative Care Makes No Difference to Health-Related Quality of Life in Mesothelioma Patients

A study, involving 174 malignant mesothelioma patients in the UK and Australia, has found that those who were not referred for palliative care in the early stages of treatment had similar levels of depression and anxiety to patients who were, i.e. there was no noticeable benefit until the later stages of the disease.[20] As such, the study authors concluded:

‘There is no role for routine referral to specialist palliative care (SPC) soon after diagnosis of malignant pleural mesothelioma for patients who are cared for in centres with good access to SPC when required’.

OTHER CANCER TREATMENTS

New Cancer Drug, MCY-M11

The National Cancer Institute at the National Institute of Health has begun a Phase I trial of a new peritoneal mesothelioma and ovarian cancer drug, MCY-M11, in partnership with Washington University, St. Louis.[21]

We previously reported, in edition 256 of BC Disease News (here) that there had been initial success in laboratory testing and clinicians are hoping to see replicated results in human testing.

Even though clinical trials of MCY-M11 are still in their infancy, we will continue to follow-up on the progress of the drug with great interest.

Changing Prescription Opioids Benefits Cancer Patients

Opioids are often prescribed to cancer patients for pain relief, but debilitating side-effects of ineffective prescriptions is common, as no one person responds to opioids in the same way. However, An Italian study, involving 498 cancer patients, has observed the outcomes of switching opioids.[22] Around 25% of the patients observed had cancer of the lungs or pleura, including pleural mesothelioma.

Each patient was treated with either morphine, oxycodone, fentanyl or buprenorphine. Of the patients who switched to a different opioid, 51.4% reported significantly improved pain reduction, while 43.5% reported better control of side-effects.

The results of this Italian research may increase uptake of the practice, which has previously been limited because of the high burden of toxic reactions.

Sugar Supplement Slows Rate of Tumour Growth

Joint research, conducted by Cancer Research UK and Worldwide Cancer Research, has led researchers to believe that a sugar supplement, mannose, which naturally occurs in cranberries, may benefit cancer survival.[23]

In the Nature journal, study authors reported that tumours in mice with cancer were reduced in size when mannose was taken as a supplement. Mannose also enhanced the success of chemotherapy (cisplatin and doxorubicin) and prolonged survival.

Kevin Ryan, Professor at the Cancer Research UK Beatson Institute explained that mannose interferes with glucose and limits cancer cell absorption of sugar:

‘Tumours need a lot of glucose to grow, so limiting the amount they can use should slow cancer progression’.

Adding mannose to treatment plans could potentially benefit pleural and peritoneal mesothelioma patient survival.

 

[1] Alex Strauss ‘New Study Could Lead to a Mesothelioma Breath Test’ (3 January 2019 Surviving Mesothelioma) <https://survivingmesothelioma.com/mesothelioma-breath-test/> accessed 23 January 2019.

[2] Alex Strauss, ‘Japanese Discovery Could Lead to New Mesothelioma Blood Test’ (1 December 2018 Surviving Mesothelioma) <https://survivingmesothelioma.com/new-mesothelioma-blood-test/> accessed 24 January 2019.

[3] Alex Strauss, ‘Who Survives Mesothelioma and Why?’ (19 January 2019 Surviving Mesothelioma) <https://survivingmesothelioma.com/survives-mesothelioma/> accessed 23 January 2019.

[4] Terri Oppenheimer, ‘Researchers Discover What Drives The Spread of the Most Type of Malignant Mesothelioma’ (24 December 2018 Mesothelioma.net) <https://mesothelioma.net/mesothelioma-news/researchers-discover-what-drives-the-spread-of-the-most-type-of-malignant-mesothelioma/> accessed 23 January 2019.

[5] Terri Oppenheimer, ‘Cancer Discovery May Help Slow Mesothelioma Metastases’ (30 November 2018 Mesothelioma.net) <https://mesothelioma.net/mesothelioma-news/cancer-discovery-may-help-slow-mesothelioma-metastases/> accessed 23 January 2019.

[6] Alex Strauss, ‘Mesothelioma Staging May be Easier with New Approach’ (23 December 2018 Surviving Mesothelioma) <https://survivingmesothelioma.com/mesothelioma-staging-new-approach/> accessed 24 January 2019. 

[7] Alex Strauss, ‘Avelumab May Offer a Second-Line Option for Recurrent Mesothelioma’ (8 January 2019 Surviving Mesothelioma) <https://survivingmesothelioma.com/recurrent-mesothelioma-avelumab-treatment/> accessed 25 January 2019.

[8] ‘Avelumab Safe, Active in Previously Treated, Unresectable Mesothelioma’ (Oncology Learning Network) <https://www.oncnet.com/news/avelumab-safe-active-previously-treated-unresectable-mesothelioma> accessed 25 January 2019.

[9] ‘Study Seeks to Determine Most Advantageous Mesothelioma Treatment Order’ (17 January 2019 Mesothelioma.net) <https://mesothelioma.net/mesothelioma-news/study-seeks-to-determine-most-advantageous-mesothelioma-treatment-order/> accessed 23 January 2019.

[10] Tim Povtak, ‘Debate Continues on When Best to Use Mesothelioma Chemotherapy’ (3 January 2019 Asbestos.com) <https://www.asbestos.com/news/2019/01/03/chemotherapy-mesothelioma-debate/> accessed 24 January 2019. 

[11] Alex Strauss, ‘Survival After Mesothelioma Surgery Could Rise with Immunotherapy Spray’ (December 10 2018 Surviving Mesothelioma) <https://survivingmesothelioma.com/survival-after-mesothelioma-surgery/> accessed 25 January 2019.

[12] Tim Povtak, ‘Vaccine and Chemotherapy Combo Shows Promise for Mesothelioma’ (22 January 2019 Asbestos.com) <https://www.asbestos.com/news/2019/01/22/vaccine-chemotherapy-mesothelioma-treatment/> accessed 25 January 2019.

[13] Alex Strauss, ‘Chemotherapy for Mesothelioma May Work Better with TroVax’ (30 December 2018 Surviving Mesothelioma) <https://survivingmesothelioma.com/chemotherapy-mesothelioma-trovax/> accessed 25 January 2019.

[14] Alex Strauss, Virotherapy for Mesothelioma Can Be More Effective’ (15 December 2018 Surviving Mesothelioma) <https://survivingmesothelioma.com/virotherapy-mesothelioma/> accessed 24 January 2019.

[15] Tim Povtak, ‘Abramson Developing CAR T-Cell Therapy for Mesothelioma’ (20 November 2018 Asbestos.com) <https://www.asbestos.com/news/2018/11/20/car-t-therapy-grant-mesothelioma/> accessed 24 January 2019.

[16] Terri, Oppenheimer, ‘New Approach Being Tested on Peritoneal Mesothelioma Patients’ (26 January 2018 Mesothelioma.net) <https://mesothelioma.net/mesothelioma-news/new-approach-being-tested-on-peritoneal-mesothelioma-patients/> accessed 24 January 2019.

[17] Cova E et. al, Pemetrexed-loaded nanoparticles targeted to malignant pleural mesothelioma cells: an in vitro study, International Journal of Nanomedicine 2019:14 773–785 <https://www.dovepress.com/pemetrexed-loaded-nanoparticles-targeted-to-malignant-pleural-mesothel-peer-reviewed-article-IJN> accessed 25 January 2019.

[18] Alex Strauss, ‘When Chemotherapy Fails: Apatinib May Offer Third-Line Option for Mesothelioma Patients’ (12 November 2018 Surviving Mesothelioma) <https://survivingmesothelioma.com/when-chemotherapy-fails-apatinib-may-offer-third-line-option-for-mesothelioma-patients/> accessed 25 January 2019.

[19] Alex Strauss, Treatment for Pericardial Mesothelioma: Chemotherapy is Best’ (1 January 2019 Surviving Mesothelioma) <https://survivingmesothelioma.com/chemotherapy-treatment-pericardial-mesothelioma/> accessed 25 January 2019.

[20] Alex Strauss, ‘Palliative Care for Mesothelioma: Earlier is Not Necessarily Better’ (22 January 2019 Surviving Mesothelioma) <https://survivingmesothelioma.com/palliative-care-mesothelioma-earlier/> accessed 23 January 2019.

[21] Terri Oppenheimer, ‘Clinical Testing of Anti-Tumor Mesothelioma Drug Begins (14 November 2018 Mesothelioma.net) <https://mesothelioma.net/mesothelioma-news/clinical-testing-of-anti-tumor-mesothelioma-drug-begins/> accessed 24 January 2019.

[22] Tim Povtak, ‘Study Shows Cancer Patients Can Benefit from Opioid Switching’ (26 November 2018 Mesothelioma.com) <https://www.asbestos.com/news/2018/11/26/mesothelioma-opioid-switching/> accessed 24 January 2019.

[23] Alex Strauss, ‘Study Suggests Sugar Supplement Could Slow Growth of Mesothelioma’ (23 November 2018 Surviving Mesothelioma) <https://survivingmesothelioma.com/sugar-supplement-may-slow-cancer-growth/> accessed 24 January 2019.