bims-mesote 2021-01-17 papers

Issue of 2021–01–17
seven papers selected by
Laura Mannarino, Mario Negri Institute

Case Rep Oncol. 2020 Sep-Dec;13(3):13(3): 1483-1489

Exceptional Regression of Malignant Pleural Mesothelioma with Pembrolizumab Monotherapy.

Bernard F Hearon, Kyle N Redelman, Georges C Elhomsy, Dennis F Moore.

The lead author with clinical stage I malignant pleural mesothelioma, epithelioid type, highly programmed cell death ligand 1 (PD-L1) positive, and BAP1 negative, experienced a prompt and exceptionally favorable response to pembrolizumab monotherapy. After cessation of treatment due to immune-related endocrinopathies, complete metabolic response on interim PET/CT scan was achieved. Two years after initial diagnosis, unifocal tumor reactivation was addressed with successful pembrolizumab monotherapy rechallenge. Immunotherapy, typically not used as frontline treatment for malignant pleural mesothelioma, may provide an effective and durable response for some patients. Based on this single case study, epithelioid type tumors with strongly positive PD-L1 and BAP1-negative immunohistochemical markers may be well suited for treatment with immune checkpoint inhibitors such as pembrolizumab.

Keywords: Immune checkpoint inhibitor; Immune-related endocrinopathy; Malignant pleural mesothelioma regression; Pembrolizumab monotherapy; Programmed cell death ligand 1 expression; Therapeutic biomarkers

DOI: https://doi.org/10.1159/000512013

Cancer Res. 2021 Jan 14. pii: canres.3430.2020. [Epub ahead of print]

Roles of the BAP1 tumor suppressor in cell metabolism.

Anna Han, Timothy J Purwin, Andrew E Aplin.

BRCA1-associated protein 1 (BAP1) is emerging as an intensively studied cancer-associated gene. Germline mutations in BAP1 lead to a cancer syndrome, and somatic loss is found in several cancer types. BAP1 encodes a deubiquitinase enzyme, which plays key roles in cell cycle regulation, cell death, and differentiation. Recent studies have demonstrated that BAP1 is also involved in several aspects of cellular metabolism, including metabolic homeostasis, glucose utilization, control of ferroptosis, and stress response. A better knowledge of the metabolic roles of cancer-associated genes is important to understanding tumor initiation and progression, as well as highlighting potential therapeutic avenues. With this review, we summarize the current knowledge regarding BAP1-mediated regulation of metabolic activities that may support new strategies to treat BAP1-mutated cancers.

DOI: https://doi.org/10.1158/0008-5472.CAN-20-3430

Eur J Oncol Nurs. 2020 Dec 19. pii: S1462-3889(20)30169-1. [Epub ahead of print]50 101889

Living with mesothelioma: A qualitative study of the experiences of male military veterans in the UK.

Stephanie Ejegi-Memeh, Liz Darlison, Anne Moylan, Angela Tod, Virginia Sherborne, Clare Warnock, Bethany Hope Taylor.

PURPOSE: The UK has the highest incidence of mesothelioma in the world. Evidence in the United States suggests that mesothelioma may disproportionately affect military veterans. However, there has been no investigation of the experience of UK veterans living with mesothelioma. The Military Mesothelioma Experience Study (MiMES) aimed to understand the experience and health/support needs of British Armed Forces personnel/veterans with mesothelioma.
METHODS: Semi-structured interviews were conducted with 13 veterans living with mesothelioma, and nine family members of veterans living with mesothelioma. Participants were recruited via charities and asbestos support groups. Data were analysed using thematic analysis.
RESULTS: Participants' experiences are presented using three themes, i) exposure to asbestos and awareness of asbestos related diseases, ii) using military strategies to cope with mesothelioma and iii) preferences for information and support. MiMES indicates that the nature and range of UK military veterans' asbestos exposure is varied and not limited to high risk occupations. Participants' knowledge of asbestos and experience of mesothelioma influenced their experiences of diagnosis. Participants had coping strategies influenced by their military experiences. Assistance in navigating health and military systems was considered beneficial, especially if support was provided by professionals with knowledge or experience of the military. Attributes which may inhibit veterans from seeking professional support are discussed.
CONCLUSION: MiMES provides insight into how UK military veterans experience and cope with mesothelioma. Key implications focus on the role that Mesothelioma Nurse Specialists, Asbestos Support Groups and veterans groups play in providing acceptable support for UK veterans.

Keywords: Asbestos; Lived experience; Mesothelioma; Military; Qualitative; Veterans

DOI: https://doi.org/10.1016/j.ejon.2020.101889

Curr Treat Options Oncol. 2021 Jan 12. 22(2): 14

A Review of Pharmacologic Management in the Treatment of Mesothelioma.

Eric P Borrelli, Conor G McGladrigan.

OPINION STATEMENT: Mesothelioma is a rare and severe form of cancer that is associated with asbestos exposure. Approximately 2500 Americans die annually from this condition with a median survival of 1 year. The latency period of this disease ranges anywhere from 20 to 70 years, with shorter latency periods associated with a higher exposure intensity to asbestos. Therefore, cases of mesothelioma are expected in the coming decades. This highlights the need for clinicians to understand the pharmacologic regimens available for treating this rare, yet serious malignancy. With multiple treatment regimens available in the treatment of this condition, clinicians should take an evidence-based approach and consider the totality of evidence and safety information while considering the best patient-centered approach for treatment. This article provides a review of current pharmacologic treatment options available for mesothelioma and goes into detail about the recommended medication regimens and dosages and the available evidence of efficacy, effectiveness, and/or safety and estimates the annual cost of treatment for these medications on the U.S. healthcare system per patient. A brief introduction is provided for several promising agents currently under investigation for mesothelioma as well.

Keywords: Asbestos; Cost; Mesothelioma; Pharmaceuticals; Treatment guidelines

DOI: https://doi.org/10.1007/s11864-020-00807-y

Lancet Oncol. 2021 Jan 12. pii: S1470-2045(20)30606-9. [Epub ahead of print]

Surgery for malignant pleural mesothelioma after radiotherapy (SMART): final results from a single-centre, phase 2 trial.

B C John Cho, Laura Donahoe, Penelope A Bradbury, Natasha Leighl, Shaf Keshavjee, Andrew Hope, Prodipto Pal, Michael Cabanero, Kasia Czarnecka, Karen McRae, Ming-Sound Tsao, Marc de Perrot.

BACKGROUND: A novel approach for managing malignant pleural mesothelioma, surgery for mesothelioma after radiotherapy (SMART), consisting of a short accelerated course of high-dose, hemithoracic, intensity modulated radiotherapy (IMRT) followed by extrapleural pneumonectomy was developed. The aim of this study was to evaluate the clinical feasibility of the SMART protocol.
METHODS: In this single-centre, phase 2 trial, patients aged 18 years or older with an Eastern Cooperative Oncology Group performance status of 0-2, with histologically proven, resectable, cT1-3N0M0 disease who had previously untreated malignant pleural mesothelioma were eligible for inclusion. Patients received 25 Gy in five daily fractions over 1 week to the entire ipsilateral hemithorax with a concomitant 5 Gy boost to high risk areas followed by extrapleural pneumonectomy within 1 week. Adjuvant chemotherapy was offered to patients with ypN+ disease on final pathology. The primary endpoint was feasibility, which was defined as the number of patients with 30-day perioperative treatment-related death (grade 5 events) or morbidity (grade 3 or 4 events). A key secondary endpoint was cumulative incidence of distant recurrence. The final analysis was done on an intention-to-treat basis (including all eligible patients). This trial is registered with ClinicalTrials.gov, NCT00797719.
FINDINGS: Between Nov 1, 2008, and Oct 31, 2019, 102 patients were enrolled onto the trial and 96 eligible patients were treated with SMART on protocol and included in the analysis. Extrapleural pneumonectomy was done at a median of 5 days (range 2-12) after completing IMRT. 47 (49%) patients had 30-day perioperative grade 3-4 events and one (1%) patient died within 30 days perioperatively (grade 5 event; pneumonia). After a median follow-up of 46·8 months (IQR 13·4-61·2), the 5-year cumulative incidence of distant recurrence was 62 (63·3% [95% CI 52·3-74·4]). The most common first sites of recurrence were the contralateral chest (33 [46%] of 72 patients) and the peritoneal cavity (32 [44%]).
INTERPRETATION: Results from this study suggest that extrapleural pneumonectomy after radiotherapy can be done with good early and long-term results. However, minimising grade 4 events on the protocol is technically demanding and might affect survival beyond the post-operative period.
FUNDING: Princess Margaret Hospital Foundation Mesothelioma Research Fund.

DOI: https://doi.org/10.1016/S1470-2045(20)30606-9