Combination Of Asbestos And Cigarettes Together With Underlying Asbestosis Significantly Increases One’s Risk Of Developing Lung Cancer Later In Life

A recently released study sought to determine the extent to which the combination of asbestos exposure and cigarette smoking serves to act “synergistically” so as to multiply the odds that one will develop lung cancer, especially when the person has already developed asbestosis.

This study is the subject of “Asbestos, Asbestosis, Smoking and Lung Cancer: New Findings from the North American Insulator Cohort”, which was published online in April 2013 by the American Journal of Respiratory and Critical Care Medicine medical journal

An April 12, 2013 report found at the ScienceDaily web site, “Asbestos Exposure, Asbestosis, and Smoking Combined Greatly Increase Lung Cancer Risk”, does a good job of summarizing this asbestos lung cancer study, as well as adding some commentary from the lead author.

As for the findings, from the April 2013 ScienceDaily report:

Among non-smokers, asbestos exposure increased the rate of dying from lung cancer 5.2-fold, while the combination of smoking and asbestos exposure increased the death rate more than 28-fold. Asbestosis increased the risk of developing lung cancer among asbestos-exposed subjects in both smokers and non-smokers, with the death rate from lung cancer increasing 36.8-fold among asbestos-exposed smokers with asbestosis.

Among insulators who quit smoking, lung cancer morality dropped in the 10 years following smoking cessation from 177 deaths per 10,000 among current smokers to 90 per 10,000 among those who quit. Lung cancer rates among insulators who had stopped smoking more than 30 years earlier were similar to those among insulators who had never smoked.

And here’s how the lead author described this new study’s findings, overall:

“The interactions between asbestos exposure, asbestosis and smoking, and their influence on lung cancer risk are incompletely understood,” said lead author Steven B. Markowitz, MD DrPH, professor of occupational and environmental medicine at the School of Earth & Environmental Sciences at Queens College in New York. “In our study of a large cohort of asbestos-exposed insulators and more than 50,000 non-exposed controls, we found that each individual risk factor was associated with increased risk of developing lung cancer, while the combination of two risk factors further increased the risk and the combination of all three risk factors increased the risk of developing lung cancer almost 37-fold.”

“Our study provides strong evidence that asbestos exposure causes lung cancer through multiple mechanisms,” said Dr. Markowitz. “Importantly, we also show that quitting smoking greatly reduces the increased lung cancer risk seen in this population.”

We will continue to watch the medical journals for study articles that focus on asbestosis, lung cancer, and mesothelioma.


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Identification Of Gene Alterations in Asbestos-Related Cancers Like Non-Small Cell Lung Cancer Shows A Synergistic Effect Of Asbestos And Tobacco Smoke

An article published by the medical journal Mutagenesis in February 2013, “Differential mutation profiles and similar intronic TP53 polymorphisms in asbestos-related lung cancer and pleural mesothelioma” shows the synergistic effect between asbestos exposure and cigarette smoking.

As background,  lung cancer has been shown to be caused by both tobacco smoke and asbestos exposure, as well as other carcinogens. Exposure to both tobacco smoke and asbestos greatly enhances that risk so that the total risk is greater than adding the individual effects (a toxicology effect called synergism). If asbestos exposure increases your chance of getting cancer by 5 times and smoking increases your chance of getting cancer by 12 times, then being exposed to both of them can increase your chances by 60 to 100 times.

From the Absract for this February 2013 Mutagenesis article, which was based on a French study:

Given the interest in defining biomarkers of asbestos exposure and to provide insights into asbestos-related and cell-specific mechanisms of neoplasia, the identification of gene alterations in asbestos-related cancers can help to a better understanding of exposure risk. To understand the aetiology of asbestos-induced malignancies and to increase our knowledge of mesothelial carcinogenesis, we compared genetic alterations in relevant cancer genes between lung cancer, induced by asbestos and tobacco smoke, and malignant pleural mesothelioma (MPM), a cancer related to asbestos, but not to tobacco smoke…. While genetic changes in [non-small cell lung cancer (NSCLC)] are dominated by the effects of tobacco smoke, the increase of transversions in TP53 gene is consistent with a synergistic effect of asbestos. These results may help to define cell-dependent mechanisms of action of asbestos and identify susceptibility factors to asbestos.

Lastly, we want you to know that there is evidence that quitting smoking will reduce the risk of lung cancer among people who have been exposed to asbestos dust, perhaps by as much as half after at least 5 years without smoking tobacco.


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Addition Of Thalidomide Maintenance To First-line Chemotherapy For Patients With Pleural Or Peritoneal Mesothelioma Did Not Help With Disease Progression

 

On April 12, 2013 The Lancet Oncology medical journal published early online this article, “Thalidomide versus active supportive care for maintenance in patients with malignant mesothelioma after first-line chemotherapy (NVALT 5): an open-label, multicentre, randomised phase 3 study”.

From the Abstract of this new medical study article concerning malignant mesothelioma disease progression:

Background
Standard chemotherapy does not lead to long-term survival in patients with malignant pleural mesothelioma. Malignant pleural mesothelioma is strongly dependent on vasculature with high vessel counts and high concentrations of serum vascular growth factors. Thalidomide has shown antiangiogenic activity, and we hypothesised that its use in the maintenance setting could improve outcomes.

Methods
In this open-label, multicentre, randomised phase 3 study, eligible patients had proven malignant pleural or peritoneal mesothelioma and had received a minimum of four cycles of first-line treatment containing at least pemetrexed, with or without cisplatin or carboplatin, and had not progressed on this treatment…. Thalidomide was given for a maximum of 1 year or until unacceptable toxicity….

Interpretation
No benefit was noted in time to progression with the addition of thalidomide maintenance to first-line chemotherapy. Different treatment strategies are needed to improve outcomes in patients with malignant mesothelioma.

This study involved 222 patients during the time period May 2004 to December 2009.

We will continue to watch for medical developments concerning mesothelioma treatments.


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Malignant Peritoneal Mesothelioma Treatment Options And Long-Term Survival Rates Are Examined In New Medical Study Article

Malignant peritoneal mesothelioma (MPM) is a primary cancer that arises diffusely from the mesothelial cells lining the peritoneum.

Cytoreduction surgery (CRS) with intraoperative or perioperative high-dose regional chemotherapy has been established as the preferred approach in selected patients.

Hyperthermic intraoperative peritoneal chemotherapy (HIPEC) is another treatment regimen for patients with peritoneal mesothelioma.

In this new medical study article, “Treatment Factors Associated With Long-Term Survival After Cytoreductive Surgery and Regional Chemotherapy for Patients With Malignant Peritoneal Mesothelioma”, we learn what factors affect survival rates for patients who underwent the CRS surgery and the HIPEC regimen.

From the Abstract:

Conclusion:  Operative CRS with HIPEC is associated with prolonged survival in patients with [malignant peritoneal mesothelioma (MPM)]. Factors associated with survival include age, complete or near complete gross tumor resection, histologic tumor grade, and HIPEC with cisplatin. Cisplatin (versus mitomycin-C) was independently associated with improved survival and demonstrates a salutary effect for HIPEC with cisplatin in the management of patients with [malignant peritoneal mesothelioma (MPM)].

“The median, actuarial overall survival was 38.4 months’, according to the authors of this article published online March 13, 2013 by the Surgery medical journal (Epub Ahead of Print).

When will continue to watch for new articles about mesothelioma survival and treatment options so that we can report significant findings to you here on Asbestos HUB.

If you know of any developments that we should be reporting on, please leave a Comment below or send me an email.


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How Is Localized Malignant Pleural Mesothelioma Different From The More Common Diffuse Form Of Mesothelioma

According to the World Health Organization (WHO), localized malignant mesothelioma of the pleura (LMM) is histologically identical to diffuse malignant mesothelioma but without any evidence of pleural spread, i.e., localized.

There is an impression that localized malignant mesothelioma of the pleura (LMM) may have a better outcome than the more common diffuse form of mesothelioma. Treatments for LLM include different combinations of surgery, chemotherapy, and radiotherapy.

This issue was explored in this November 2012 medical journal article, “What is the survival after surgery for localized malignant pleural mesothelioma?”. From the Abstract:

In order to advise our patients on prognosis, we studied the duration of survival after surgical resection of [localized malignant mesothelioma of the pleura (LMM)]. A total of 150 papers were found, of which 16 represented the best evidence to answer the question…. Some report median survival (range: 11.6–36 months) and others disease-free survival (range: 0 months to 11 years). Median survival to the longest follow-up was 29 months when calculated by pooling data from informative papers using the Kaplan–Meier method. Our review suggests that survival in [localized malignant mesothelioma of the pleura (LMM)] is longer than that generally quoted for the more common diffuse form of malignant mesothelioma. Hence, aggressive treatment of LMM may be reasonable in appropriate patients.

We will continue to monitor the medical journals for reports concerning mesothelioma treatments and survival times.

Increased Risk Of Pleural Mesothelioma Where There Was Asbestos Exposure Together With Mineral Wool And/Or Silica Exposure, Also (i.e., Co-exposure)

The medical journal American Journal of Respiratory and Critical Care Medicine published this article early online on March 7, 2013:   “Pleural Mesothelioma and Occupational Co-exposure to Asbestos, Mineral Wool and Silica”.

From the Abstract for this new medical journal article about mesothelioma:

Rationale: Occupational co-exposure to asbestos and other fibers or particles could modify the carcinogenicity of asbestos with regard to pleural mesothelioma.

Objectives: To estimate associations between pleural mesothelioma and occupational mineral wool [(MW)] and silica exposure and to study the impact of occupational co-exposure on the risk of pleural mesothelioma….

Conclusion: Our results are in favour of an increased risk of pleural mesothelioma for subjects exposed to both asbestos and [mineral wool (MW)] or asbestos and silica.

This March 2013 article was based on a French pooled case-control study.

We will continue to monitor the literature for medical developments concerning mesothelioma (“meso”).


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Making the Diagnosis of Mesothelioma: Leslie Litzky, MD, Pathologist (Video)

Leslie Litzky, MD, discusses the pathology behind the diagnosis of malignant mesothelioma at the 2012 Focus on Mesothelioma Conference.

Her clear and concise explanation is addressed to mesothelioma patients as well as their family so that they can better understand the diagnostic testing process.

(10:51 video on YouTube)


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Mesothelioma Medical Update: February 2013: Two New Experimental Mesothelioma Treatment Drugs

In February 2013 we learned of two mesothelioma drugs under development for possible future use as treatment alternatives.

First, from a February 12, 2013 report published online by FierceDrugDelivery, “Genelux, Sloan-Kettering test delivery of mesothelioma drug”, we were introduced to GL-ONC1, which might also eventully be used at the diagnosis stage.

From that article about GL-ONC1 for mesothelioma:

California-based Genelux is helming a first-in-man trial of its new mesothelioma treatment at Memorial Sloan-Kettering Cancer Center in New York.

The center has begun injecting the drug, GL-ONC1, into the cavity surrounding the lungs to treat the rare and aggressive form of cancer called mesothelioma, which can occur as a result of exposure to asbestos. Patients suffering from mesothelioma may experience a buildup of fluid around the lungs, and the dose of GL-ONC1 is designed to temper those symptoms. It marks the first time the drug will be delivered in such a way.

GL-ONC1, according to the company, is both a treatment and a diagnostic–a genetically modified vaccinia virus, it produces a green fluorescent protein that can be tracked within the patient to determine the expression of the disease.

Next, we refer you to a drug company press release issued in February 2013, “Verastem Files for Orphan Disease Status for VS-6063 in Mesothelioma”:

Verastem is seeking orphan drug designation in the US and the EU for the use of VS-6063 in mesothelioma. VS-6063 is anticipated to enter a potentially pivotal study in mesothelioma midyear 2013….

VS-6063 is an oral small molecule inhibitor of focal adhesion kinase (FAK), which is a critical pathway for cancer stem cells. VS-6063 was well-tolerated and demonstrated signs of clinical activity in a Phase 1 study in advanced solid tumors. VS-6063 is currently in a Phase 1/2 study in patients with advanced ovarian cancer, where VS-6063 is being tested in combination with paclitaxel.

We will continue to watch for new possible mesothelioma treatments as the year goes on and let you know about those here on Asbestos HUB.


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French Medical Study Suggests An Increased Risk Of Pleural Mesothelioma Associated With Pleural Plaques

On January 25, 2013 the Journal of the National Cancer Institute published online this article “Pleural Plaques and the Risk of Pleural Mesothelioma”, which reported on a recent French medical study concerning asbestos exposure and mesothelioma.

From the Abtsract for this new medical journal article:

Background  The association between pleural plaques and pleural mesothelioma remains controversial. The present study was designed to examine the association between pleural plaques on computed tomography (CT) scan and the risk of pleural mesothelioma in a follow-up study of asbestos-exposed workers….

Conclusion  The presence of pleural plaques may be an independent risk factor for pleural mesothelioma.

We will continue to monitor the medical literature for developments relevant to asbestos-mesothelioma cases.


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The Stanford School Of Medicine Approach To Malignant Pleural Mesothelioma Cases

Malignant Pleural Mesothelioma (MPM) is a rare and aggressive form of cancer that is associated with exposure to asbestos in the remote past.

Generally, mesothelioma (sometimes called “meso”, for short) has a long latency period meaning that is usually not diagnosed until 15 to 50 years after the initial asbestos exposure.

The three major subtypes of malignant pleural mesothelioma (MPM) are:

  1. Epithelial MPM is the most common form and makes up about 60% of all cases.
  2. Sarcomatoid MPM comprises about 10% of all cases and these tumors display a somewhat more aggressive behavior.
  3. The remainder of cases are comprised of the Mixed, or Biphasic variant of MPM that contains elements of both Epithelial and Sarcomatoid MPM.

From the Malignant Pleural Mesothelioma page on the Stanford School of Medicine website we get the following information about the staging of mesothelioma diagnoses:

Generally, Stage I MPM represents early disease with low tumor burden, Stage II MPM represents more locally advanced disease with a greater tumor burden, Stage III MPM represents locally advanced disease with significant invasion of surrounding structures or spread to mediastinal lymph nodes, and Stage IV MPM represents a technically unresectable tumor, or spread to the abdomen or other side of the chest.

Next, we get this overview of what is called “The Stanford Approach to Malignant Pleural Mesothelioma”:

Diagnosis:  We routinely perform minimally invasive VATS [(video-assisted thoracic surgery)] procedures to obtain an adequate tissue biopsy for diagnosis. If adequate tissue has already been obtained at another institution, we will arrange review by our Stanford pathology team.

Staging:  Chest CT [(computed tomograpy)] and PET scans [(an imaging technique that highlights tumors)] are utilized to evaluate the distribution of disease, and this is sometimes supplemented with MRI. We recommend and perform cervical mediastinoscopy to evaluate potential spread to mediastinal lymph nodes (N2 disease), and this can often be performed at the same time as the VATS biopsy.

Treatment:  Whenever possible, we believe in a surgery-based multi-modality treatment program for MPM:

  • For Stage I-III disease without the presence of disease in the mediastinal lymph nodes (N2 negative), we recommend surgical resection (either P/D [(Pleurectomy & Decortication)] or EPP [(Extrapleural Pneumonectomy)], depending upon extent of disease and patient health status) and adjuvant (postoperative) chemotherapy and possibly radiation. When the character of the tumor is resectable by P/D, this is our favored approach. However, when significant invasion of the lung is present, EPP is recommended in sufficiently healthy patients.

  • For patients in whom N2 disease is present, our treatment pathway entails preoperative chemotherapy, still possibly followed by surgical resection, and potential adjuvant radiotherapy.

  • For patients with Stage IV disease or those not medically fit for surgery, we generally recommend chemotherapy, with or without state-of-the-art radiotherapy, and aggressive control of symptoms.

As a final note, we point out that at the Stanford School of Medicine you will find a highly regarded surgeon, Bryan Burt, M.D., who has extensive experience with diagnosing and treating mesothelioma.


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