Clinical Safety and Activity of Pembrolizumab in Patients With Malignant Pleural Mesothelioma

BACKGROUND  Malignant pleural mesothelioma is a highly aggressive cancer with poor prognosis and few treatment options following progression on platinum-containing chemotherapy. We assessed the safety and efficacy of pembrolizumab (an anti-programmed cell death receptor 1 [PD-1] antibody) in advanced solid tumours expressing programmed cell death ligand 1 (PD-L1) and report here on the interim analysis of the malignant pleural mesothelioma cohort.

METHODS  Previously treated patients with PD-L1-positive malignant pleural mesothelioma were enrolled from 13 centres in six countries. Patients received pembrolizumab (10 mg/kg every 2 weeks) for up to 2 years or until confirmed progression or unacceptable toxicity….

FINDINGS  As of June 20, 2016, 25 patients received pembrolizumab. 16 (64%) patients reported a treatment-related adverse event; the most common adverse event were fatigue (six [24%]), nausea (six [24%]), and arthralgia (five [20%])….

INTERPRETATION  Pembrolizumab appears to be well tolerated and might confer anti-tumour activity in patients with PD-L1-positive malignant pleural mesothelioma. Response durability and efficacy in this patient population warrants further investigation.

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Source: Clinical Safety and Activity of Pembrolizumab in Patients With Malignant Pleural Mesothelioma


 Mesothelioma, Asbestos, and Legal Compensation: Basic Facts

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Asbestos exposure is still making people sick

Researchers at the US Centers for Disease Control and Prevention are struggling to understand why younger populations continue to suffer asbestos-related medical issues despite efforts to reduce exposure from the toxic mineral.

According to a report released by the CDC on Thursday, numbers of deaths related to malignant mesothelioma increased from 2,479 in 1999 to 2,597 in 2015.

The largest increase was seen in those over 85 years old, but younger populations continue to be affected.

In those 16 years, 16,914 of the deaths were among people 75 to 84 years old. In the same period, 682 people between the ages of 25 and 44 died of mesothelioma-related problems.

“Although deaths among persons aged less than 35 years are of concern, we do not have information to understand potential causes,” said Dr. Jacek Mazurek, lead author of the CDC report.

Source: Asbestos exposure is still making people sick


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Arizona High Court to Rule on Liability in Asbestos Take Home Exposure Case

The Arizona Supreme Court has agreed to consider whether employers can be held liable to somebody who contracted cancer from asbestos brought home on a parent’s work clothes.

The case stems from the 2014 death of Dr. Ernest Quiroz, whose 2013 negligence lawsuit contends he was exposed to asbestos on his father’s work clothes.

The facts as outlined in the appeal indicate he lived with his father from 1952 to 1966, during the time his father worked at Reynolds Metal Co. Dr. Quiroz lived in California until 1976 and in Michigan until his death in 2014. The suit alleges Dr. Quiroz contracted mesothelioma as a result of the exposure to his father’s work clothes.

The suit argues that Reynolds Metal Co. was legally obligated to avoid creating hazardous conditions that would injure people off its property.

Reynolds won a pretrial ruling by a trial judge, and the Court of Appeals upheld it.

The Court of Appeals said potential drawbacks of recognizing what’s called a duty of care in so-called “take-home exposure” cases outweigh potential benefits, partly by opening the door to liability claims involving an array of hazardous materials.

Source: Arizona High Court to Rule on Liability in Asbestos Take Home Exposure Case

 


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Patient-Derived Xenograft Establishment from Human Malignant Pleural Mesothelioma

Purpose: Malignant pleural mesothelioma (MPM) is a rare but aggressive disease with few therapeutic options. The tumor–stromal interface is important in MPM, but this is lost in cell lines, the main model used for preclinical studies. We sought to characterize MPM patient-derived xenografts (PDX) to determine their suitability as preclinical models and whether tumors that engraft reflect a more aggressive biological phenotype.

Experimental Design: Fresh tumors were harvested from extrapleural pneumonectomy, decortication, or biopsy samples of 50 MPM patients and implanted subcutaneously into immunodeficient mice and serially passaged for up to five generations. We correlated selected mesothelioma biomarkers between PDX and patient tumors, and PDX establishment with the clinical pathologic features of the patients, including their survival. DNA of nine PDXs was profiled using the OncoScan FFPE Express platform. Ten PDXs were treated with cisplatin and pemetrexed.

Results: A PDX was formed in 20 of 50 (40%) tumors implanted. Histologically, PDX models closely resembled the parent tumor. PDX models formed despite preoperative chemotherapy and radiotherapy. In multivariable analysis, patients whose tumors formed a PDX had significantly poorer survival when the model was adjusted for preoperative treatment (HR, 2.46; 95% confidence interval, 1.1–5.52; P = 0.028). Among 10 models treated with cisplatin, seven demonstrated growth inhibition. Genomic abnormalities seen in nine PDX models were similar to that previously reported.

Conclusions: Patients whose tumors form PDX models have poorer clinical outcomes. MPM PDX tumors closely resemble the genotype and phenotype of parent tumors, making them valuable models for preclinical studies.

Source: Patient-Derived Xenograft Establishment from Human Malignant Pleural Mesothelioma


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Diagnostic and Prognostic Biomarkers in the Rational Assessment of Mesothelioma (DIAPHRAGM) study: protocol of a prospective, multicentre, observational study

Malignant pleural mesothelioma (MPM) is an asbestos-related cancer, which is difficult to diagnose. Thoracoscopy is frequently required but is not widely available. An accurate, non-invasive diagnostic biomarker would allow early specialist referral, limit diagnostic delays and maximise clinical trial access. Current markers offer insufficient sensitivity and are not routinely used. The SOMAmer proteomic classifier and fibulin-3 have recently demonstrated sensitivity and specificity exceeding 90% in retrospective studies. DIAPHRAGM (Diagnostic and Prognostic Biomarkers in the Rational Assessment of Mesothelioma) is a suitably powered, multicentre, prospective observational study designed to determine whether these markers provide clinically useful diagnostic and prognostic information.

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Source: Diagnostic and Prognostic Biomarkers in the Rational Assessment of Mesothelioma (DIAPHRAGM) study: protocol of a prospective, multicentre, observational study


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Lung-sparing surgery may boost mesothelioma survival

Surgery that preserves the lung, when combined with other therapies, appears to extend the lives of people with a subtype of the rare and deadly cancer mesothelioma, a new study suggests.

Tracking 73 patients with advanced malignant pleural mesothelioma—which affects the lungs’ protective lining in the chest cavity—researchers found that those treated with lung-sparing had an average survival of nearly three years. A subset of those patients survived longer than seven years.

Mesothelioma patients treated with chemotherapy alone, which is standard care, live an average of 12 to 18 months, the researchers said.

Study participants received lung-sparing surgeries and another treatment called photodynamic therapy that uses light to kill cancer cells. Ninety-two percent of the group also received chemotherapy.

The study volunteers achieved far longer survival times, said study author Dr. Joseph Friedberg.

“When you take the [entire] lung out, it’s a significant compromise in quality of life,” said Friedberg. He’s director of the University of Maryland Medical Center’s Mesothelioma and Thoracic Oncology Treatment and Research Center in Baltimore.

“For all intents and purposes, this [lung-sparing surgical approach] is the largest palliative operation known to man, since chances of curing mesothelioma are vanishingly small,” said Friedberg. He completed the research while at his previous post at the University of Pennsylvania.

“Plus, most of these patients are elderly, so preserving quality of life was really the goal,” he added.

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Source: Lung-sparing surgery may boost mesothelioma survival


 

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Asbestos-related cancer won’t be overcome anytime soon, doctors say

New methods are giving doctors a better handle on diagnosing and treating asbestos-related cancers, but no cures are on the horizon.

“I think it would be overly optimistic to say it’s going to be cured. I mean we can always dream,” said oncologist Dr. Christopher Lee, an expert on mesothelioma.

Paul Demers, a senior scientist in prevention at the Occupational Cancer Research Centre in Toronto, said one of the difficulties in diagnosing mesothelioma is the long latency period — the period between exposure and the development of symptoms — which can sometimes be up to 40 years.

When asbestos fibres are inhaled or ingested, they become trapped in the pleural lining of the lungs. Over time, thousands of tiny fibres cause scarring in the tissue.

New equipment like the CyTOF instrument allows doctors to detect asbestos earlier and with more precision, which could facilitate more effective treatments for asbestos victims.

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Source: Asbestos-related cancer won’t be overcome anytime soon, doctors say


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Malignant Mesothelioma in a Motor Vehicle Mechanic

Case reports remain an important source of data in the debate over the carcinogenic effect of asbestos-containing automotive friction products. This report documents a case of pleural mesothelioma accompanied by asbestos bodies in the lung tissue of a career auto mechanic with no other known sources of exposure. Previously unreported historical and contemporary exposure data are also discussed in the context of providing additional support for the proposition that work with asbestos-containing automotive products presents a risk of significant exposure. While there remains a body of negative epidemiology that fails to find an increased risk of disease among auto workers, those data must be approached with caution. Many of those studies have drawn technical criticisms, which are beyond the scope of this report, but they remain a key part of the legal defense mounted by defendant-companies who are involved in asbestos-related litigation. This ongoing debate provides the context for the continued relevance of case reports such as this one, as well as the presentation of new and previously unpublished exposure data.

Source: Malignant Mesothelioma in a Motor Vehicle Mechanic


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Deadly Remnants of Asbestos in Italy (photos slideshow)

Although Italy joined asbestos-producing nations in banning the carcinogenic material at the end of the 20th century, thousands of people working in factories and living in public housing had already been exposed. In other words, as the Italian photographer Cinzia Canneri explained, the damage had been done by the 1980s.

Ms. Canneri said it could take up to 30 years after exposure for diseases like asbestosis or mesothelioma to develop. As a result, large numbers of people in the last decade have begun to suffer in Italy and more are expected to — with few legal or medical protections.

“They have not been recognized as victims,” Ms. Canneri said through an interpreter. “They want to speak and be heard.

”To help them, Ms. Canneri spent the last two years closely following asbestos victims, documenting their daily lives and struggles as they deal with new diseases, mourn deceased family members, visit doctors and contemplate whether or not time is running out on their health.

[Article continues at original source]

Source: Deadly Remnants of Asbestos in Italy (photos slideshow)


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Treatments to prolong life for mesothelioma patients closer

Researchers have uncovered a strange way that asbestos-related tumours grow, which could pave the way towards better treatments.

The scientists at Adelaide’s Flinders University have found that malignant mesothelioma tumours are able to transform into blood vessels, promoting their own growth.

Associate Professor Sonja Klebe said the behaviour was unusual.

“Instead of waiting for the outside of the tissue to grow blood vessels in, the tumour cells themselves branch out, growing blood vessels that reach out into surrounding tissues, tapping into the native vasculature,” she said.

Existing tumour treatments target blood vessels that grow into the cancer, and not the other way around.

“So I think a future approach would involve treating both of these types of vessels to more or less starve the tumour of blood supply,” Associate Professor Klebe said.

[Article continues at original source]

Source: Treatments to prolong life for mesothelioma patients closer


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