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.

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Source: Treatments to prolong life for mesothelioma patients closer


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New Paradigms in the Treatment of Mesothelioma and NSCLC: An Overview by Fred Hirsch

Dr. Haffizulla: Welcome to PracticeUpdate. I’m Dr. Farzanna Haffizulla. Joining me today is Dr. Fred Hirsch, CEO of the International Association for the Study of Lung Cancer, and Professor of Medicine at the University of Colorado in Denver. Dr. Hirsch, thank you, so much, for joining me.

Dr. Hirsch: Thank you, so much, for the invitation.

Dr. Haffizulla: You’re very welcome. Well, I want to first start off with talking about mesothelioma. Any latest advances or current treatments that have come to the forefront that have precipitated based on clinical trials recently?

Dr. Hirsch: Mesothelioma is an interesting disease where we unfortunately haven’t seen much progress, either, over a long time. Pemetrexed-platinum is a standard of care for mesothelioma, but what we have seen most recently is the introduction of immunotherapy also in this disease, and with very encouraging data. It is still very preliminary data, and certainly we need much more matured clinical trials, but already by now we can see a very clear encouraging signal with the PD-L1, PD-1 antibodies.

Dr. Haffizulla: Okay. Absolutely. Well, switching gears a little bit. I want to talk a little bit further on immunologic biomarkers, talking about neoantigen signatures and mutational load of tumors. Other than assessing or using this information to assess the severity of the disease, perhaps, or the risk of relapse and choice of agents that you would like to use in this particular patient, anything else you’d like to share on that home front?

Dr. Hirsch: Yeah, so that will probably be most related to non-small cell lung cancer. We have recently seen data in mesothelioma for follow-up on the mesothelioma stuff that mesothelioma has much less mutation burden than we see in small cell and non-small cell lung cancer, and that might be important when we are talking immunotherapy and promises, but we don’t know. We see encouraging results currently in mesothelioma with the new immune checkpoints. In non-small cell lung cancer there seems to be a relation between mutation burden and sensitivity to some of the checkpoint inhibitors, and that is interesting. On a personal level, I think we need to learn more about it because I don’t think all mutations are equal, and all mutations are not equally immunogenic, so we need to learn more about the mutation load, mutation types. Are we talking tumor heterogeneity? Are we talking trunk mutations? Are we talking branch mutations, so mutation load might be too broad in term in the future, but currently we actually see an association between mutation load and sensitivity to some of those immune checkpoints.

Source: New Paradigms in the Treatment of Mesothelioma and NSCLC: An Overview by Fred Hirsch


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Myxoid variant epithelioid pleural mesothelioma defines a favourable prognosis group: an analysis of 191 patients with pleural malignant mesothelioma

Malignant pleural mesothelioma shows marked cytoarchitectural diversity. The aim of the study was to evaluate how morphological phenotype impacted upon overall survival. 191 cases of malignant pleural mesothelioma with available follow-up were identified, examined and classified according to histological types. The epithelioid mesotheliomas were further subdivided according to morphological subtypes: myxoid, microcystic, tubulopapillary, solid epithelioid, micropapillary and pleomorphic; biphasic mesotheliomas were divided into epithelioid component dominant and sarcomatoid component dominant; pure sarcomatoid mesotheliomas were divided into not otherwise specified, leiomyoid, desmoplastic and heterologous. All cases were confirmed by two experienced observers. Myxoid variant malignant pleural epithelioid mesothelioma was observed to have a favourable overall survival compared with pleomorphic form (p=0.00008). Pleomorphic phenotype had the worst overall survival. Morphological phenotype is an important histological factor that should be included in pathology reports to convey potential favourable prognostic subgroups of patients with mesothelioma.

Source: Myxoid variant epithelioid pleural mesothelioma defines a favourable prognosis group: an analysis of 191 patients with pleural malignant mesothelioma


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Residual fibre lung burden among patients with pleural mesothelioma who have been occupationally exposed to asbestos

Objectives  To evaluate the lungs asbestos fibres concentration in participants with malignant pleural mesothelioma (MPM) who have been occupationally exposed.

Methods  The lung samples were obtained from pleuropneumonectomies or autopsies of 271 male MPMs. The lung samples were examined through scanning electron microscopy. Retrospective assessment was used to assess for asbestos exposure. This study includes 248 MPMs with an occupational exposure defined as either ‘definite’ or ‘probable’ or ‘possible’.

Results  The participants had finished working in asbestos exposure conditions more than 20?years ago (on average 26.1±11.0?years). The fibre burden resulted with a geometric mean equal to 2.0 (95% CI 1.6 to 2.4) million fibres per gram of dry lung tissue. The burden was higher among participants employed in asbestos textiles industry and in shipyards with insulation material, if compared with construction workers or non-asbestos textile workers or participants working in chemicals or as auto mechanics. 91.3% of MPMs had a detectable amount of amphibole fibres. A strong lung clearance capability was evident among workers exposed to chrysotile fibres. Owing to that, the 1997 Helsinki Criteria for occupational exposure were reached in <35% of cases among participant working in construction, in metallurgical industry, in chemical or textile industry and among those performing brake repair activities.

Conclusions  The MPM cases are now occurring in Italy in participants who ceased occupational asbestos exposure decades before the analysis. A large majority still shows a residual content of amphibole fibres, but given the lung clearance capability, attribution to occupational exposure cannot rely only on fibres detection.

Source: Residual fibre lung burden among patients with pleural mesothelioma who have been occupationally exposed to asbestos


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Systemically administered RNAi molecule sensitizes malignant pleural mesothelioma cells to pemetrexed therapy

Pemetrexed (PMX) is a key drug for the treatment of malignant pleural mesothelioma (MPM). However, its therapeutic efficacy is cruelly restricted in many clinical settings by the over-expression of thymidylate synthase (TS) gene. Recently, we emphasized the efficacy of locally administered shRNA designed against TS gene in enhancing the cytotoxic effect of PMX against orthotopically implanted MPM cells in tumor xenograft tumor model. In the present study, we investigated the efficacy of systemic, rather than local, delivery of TS RNAi molecule in sensitizing MPM cells to the cytotoxic effect of PMX. We here designed a PEG-coated TS shRNA lipoplex (PEG-coated TS shRNA-lipoplex) for systemic injection. PEG modifiaction efficiently delivered TS shRNA in the lipoplex to tumor tissue following intravenous administration as indicated by a significant suppression of TS expression level in tumor tissue. In addition, the combined treatment of PMX with systemic injection of PEG-coated TS shRNA-lipoplex exerted a potent antitumor activity against MSTO-211H xenograft mouse model, compared to a single treatment with either PMX or PEG-coated TS shRNA-lipoplex. Metastasis, or the spread, of mesothelioma plays an important role in the effectiveness of treatment options. The systemic, in addition to local, delivery of tumor targeted anti-TS RNAi system we propose in this study might be an effective option to extend the clinical utility of PMX in treating malignant mesothelioma.

Source: Systemically administered RNAi molecule sensitizes malignant pleural mesothelioma cells to pemetrexed therapy.


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Arginine Deprivation for Malignant Pleural Mesothelioma

Arginine deprivation is a novel anticancer strategy in argininosuccinate synthetase 1 (ASS1)–negative tumors. In a multicenter, phase II trial, immunohistochemistry identified 68 patients with ASS1 deficiency among 201 patients with malignant pleural mesothelioma (MPM). The ASS1-deficient patients were randomized in a 2:1 ratio to either best supportive care (BSC) or BSC plus intramuscular ADI-PEG20, a pegylated arginine deiminase that causes arginine deprivation, at 36.8 mg/m2 weekly (in 4-week cycles) for up to 6 months. Of the ADI-PEG20 recipients, 23% received six treatment cycles.

During a median follow-up of 38 months, no participants had partial or complete response. However, stable disease at 4 months (using modified Response Evaluation Criteria in Solid Tumors [RECIST]) was significantly more common with ADI-PEG20 than with BSC alone (52% vs. 22%). ADI-PEG20 also outperformed BSC alone significantly in median progression-free survival (PFS; 3.2 vs. 2.0 months; hazard ratio, 0.56) and nonsignificantly in median overall survival (11.5 vs. 11.1 months) and life expectancy (15.7 vs. 12.1 months). The most common ADI-PEG20 toxicities were grade 1–2 nonfebrile neutropenia, gastrointestinal events, injection-site reactions, and fatigue; grade 3 events, in 25% of ADI-PEG20 recipients, were anaphylaxis and serum sickness. The two treatment groups had similar quality of life (whether patient- or observer-reported).

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Source: Arginine Deprivation for Malignant Pleural Mesothelioma


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Scientists discover new option for treating malignant pleural mesothelioma

Researchers at the Comprehensive Cancer Center of MedUni Vienna and Vienna General Hospital have discovered a new option for treating malignant pleural mesothelioma. For the first time in the world, they were able to show in a preclinical study, both in the cell culture and in the animal model, that trabectedin, a chemotherapy drug that is already successfully used for other types of cancer, is also effective against malignant pleural mesothelioma. The active agent originally occurs in the Caribbean sea cucumber, a marine-dwelling tunicate. The study results were recently published in “Molecular Cancer Therapeutics”, the therapy-oriented journal of the American Association for Cancer Research (AACR). The initial interim results of a clinical study from Italy confirm these results and show that they are transferable to clinical practice.

With around 90 new cases per year in Austria, malignant pleural mesothelioma is one of the rarer forms of cancer. However, it is on the increase. Malignant pleural mesothelioma is a very aggressive form of cancer that is associated with asbestos and is routinely treated with a combination of chemotherapy, surgery and radiotherapy. Since this particular type of tumour often develops resistance to chemotherapy and radiotherapy, the prognosis is very poor.

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Source: Scientists discover new option for treating malignant pleural mesothelioma

 


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Malignant mesothelioma of the pleura with desmoplastic histology: a case series and literature review

Abstract

Background

Desmoplastic malignant pleural mesothelioma (DMM) is rare histological subtype of diffuse malignant pleural mesothelioma (MPM), accounting for 5–10 % of cases. It has a poor prognosis, with direct invasion of the chest wall or lungs and distant metastases. Its pathological characteristics include dense collagen fibers in a storiform pattern. Its pretreatment pathological diagnosis is difficult, with fibrous pleuritis and reactive mesothelial hyperplasia as potential differential diagnoses.

Case presentation

We retrospectively reviewed the medical charts of patients with MPM from 1996 to 2012. Among 60 patients with MPM, four patients with the desmoplastic subtype were identified and their clinical characteristics, including asbestos exposure, treatment, and prognosis, were reviewed. All of the patients with DMM were men, with a median age of 69 years (range: 63–74 years). All four patients had been exposed to asbestos. The definitive diagnosis was made histologically and the International Mesothelioma Interest Group classification was advanced (III/IV: 2/3) in all four patients. Three patients were treated with chemotherapy (two with cisplatin/pemetrexed and one with cisplatin/gemcitabine) and one patient underwent surgery. The median survival time in the patients with DMM was 3.8 months (range: 0.9–11.5 months), compared with 10.5 months in patients with other subtypes of MPM in our institution.

Conclusions

DMM continues to have a poor prognosis. It is important to recognize this variant and distinguish it from pleural plaques, non-specific reactive pleural fibrosis, pleurisy, and other lung diseases.

Source: Malignant mesothelioma of the pleura with desmoplastic histology: a case series and literature review


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Asbestos-related cancer costs Canadians billions

A first-ever estimate of the toll of asbestos-related cancers on society pegs the cost of new cases at $1.7-billion per year in Canada, and notes that is likely an under-estimate.

The economic burden of lung cancer and mesothelioma from work-related asbestos exposure in Canada amounts to an average of $818,000 per case, according to a team led by health economist and senior scientist Dr. Emile Tompa at the Institute for Work & Health, a research organization, whose calculation includes costs related to health care and lost productivity and quality of life.

This is the first time a tally of these costs has been made public. Asbestos remains the top cause of occupational deaths in Canada: Workers’ compensation boards have accepted more than 5,700 claims since 1996. About 150,000 Canadian workers are exposed to asbestos in their workplaces, the research project Carex Canada estimates, among them construction workers and contractors, mechanics, shipbuilders and engineers. This country continues to allow exports and imports of asbestos, which rose to a six-year high last year. Dozens of other countries, including Australia and Britain, have banned it.

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Source: Asbestos-related cancer costs Canadians billions


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Mesothelioma Treatment Center at Baylor St. Luke’s launches clinical trial for cancer patients

The Baylor College of Medicine Mesothelioma Treatment Center at Baylor St. Luke’s Medical Center announced today that it has opened a new clinical trial that combines immunotherapy and surgery for the treatment of mesothelioma.

This is the first in-human study of neoadjuvant (before surgery) administration of a checkpoint inhibitor immunotherapy followed by surgical resection in patients with malignant pleural mesothelioma. The treatment focuses on the use of a preoperative boost to the immune system and cytoductive surgery with state-of-the art surgical techniques to combat the disease. The groundbreaking protocol will lay the foundation for multimodality therapy that includes using the patient’s own immune system in combination with surgical resection.

“We are very excited to be able to offer this trial to our patients. Much of our own data suggests that pleural mesothelioma may be a more immunogenic tumor than previously realized, and I predict that immunotherapy will rise to become a critical component of multimodality therapy for mesothelioma patients,” said Dr. Bryan Burt, assistant professor of surgery at Baylor College of Medicine and principal investigator of the trial. “This trial is one of the first of its kind in which immunotherapy is given before surgery, and from it, we expect to learn an enormous amount about this disease.”

Source: Mesothelioma Treatment Center at Baylor St. Luke’s launches clinical trial for cancer patients

 


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