SEOM clinical guidelines for the treatment of malignant pleural mesothelioma (2020)

AbstractMesothelioma is a rare and aggressive tumour with dismal prognosis arising in the pleura and associated with asbestos exposure. Its incidence is on the rise worldwide. In selected patients with early-stage MPM, a maximal surgical cytoreduction in combination with additional antitumour treatment may be considered in selected patients assessed by a multidisciplinary tumor board. In patients with unresectable or advanced MPM, chemotherapy with platinum plus pemetrexed is the standard of care. Currently, no standard salvage therapy has been approved yet, but second-line chemotherapy with vinorelbine or gemcitabine is commonly used. Novel therapeutic approaches based on dual immunotherapy or chemotherapy plus immunotherapy demonstrated promising survival benefit and will probably be incorporated in the future.

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Malignant Mesothelioma: Has Anything Changed?

Seminars in Respiratory and Critical Care Medicine ◽

10.1055/s-0039-1693406 ◽

2019 ◽

Vol 40 (03) ◽

pp. 347-360 ◽

Cited By ~ 5

Author(s):

Roger Y. Kim ◽

Daniel H. Sterman ◽

Andrew R. Haas

Keyword(s):

Malignant Pleural Mesothelioma ◽

Multimodal Therapy ◽

Asbestos Exposure ◽

Treatment Options ◽

Standard Of Care ◽

Turn Of The Century ◽

Clinical Approach ◽

Pleural Mesothelioma ◽

Dismal Prognosis ◽

Near Future

AbstractMalignant pleural mesothelioma is a rare cancer associated with asbestos exposure and portends a dismal prognosis. Its worldwide incidence has been increasing, and treatment options are currently suboptimal and noncurative. However, since the turn of the century, several encouraging steps have been made toward improving outcomes for mesothelioma patients. An increased understanding of disease pathophysiology has led to more accurate diagnosis and staging, and the establishment of the standard of care first-line pemetrexed/platin doublet chemotherapy regimen in 2003 initially revolutionized treatment. While significant debate remains regarding the preferred approach to surgical and radiation therapy in the context of multimodal therapy, recent breakthroughs in immunotherapy offer hope for another paradigm shift in the near future. This review will summarize the current clinical approach to diagnosis, staging, and treatment of malignant pleural mesothelioma.

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Local Therapies and Modulation of Tumor Surrounding Stroma in Malignant Pleural Mesothelioma: A Translational Approach

International Journal of Molecular Sciences ◽

10.3390/ijms22169014 ◽

2021 ◽

Vol 22 (16) ◽

pp. 9014

Author(s):

Daniela Lisini ◽

Sara Lettieri ◽

Sara Nava ◽

Giulia Accordino ◽

Simona Frigerio ◽

...

Keyword(s):

Malignant Pleural Mesothelioma ◽

Asbestos Exposure ◽

Local Drug Delivery ◽

Pleural Mesothelioma ◽

Therapeutic Approaches ◽

Cell Therapies ◽

Complex Interactions ◽

Biologic Effects ◽

Drug Doses ◽

Lower Drug

Malignant Pleural Mesothelioma (MPM) is a rare and aggressive neoplasm of the pleural mesothelium, mainly associated with asbestos exposure and still lacking effective therapies. Modern targeted biological strategies that have revolutionized the therapy of other solid tumors have not had success so far in the MPM. Combination immunotherapy might achieve better results over chemotherapy alone, but there is still a need for more effective therapeutic approaches. Based on the peculiar disease features of MPM, several strategies for local therapeutic delivery have been developed over the past years. The common rationale of these approaches is: (i) to reduce the risk of drug inactivation before reaching the target tumor cells; (ii) to increase the concentration of active drugs in the tumor micro-environment and their bioavailability; (iii) to reduce toxic effects on normal, non-transformed cells, because of much lower drug doses than those used for systemic chemotherapy. The complex interactions between drugs and the local immune-inflammatory micro-environment modulate the subsequent clinical response. In this perspective, the main interest is currently addressed to the development of local drug delivery platforms, both cell therapy and engineered nanotools. We here propose a review aimed at deep investigation of the biologic effects of the current local therapies for MPM, including cell therapies, and the mechanisms of interaction with the tumor micro-environment.

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How I treat malignant pleural mesothelioma

ESMO Open ◽

10.1136/esmoopen-2019-000669 ◽

2020 ◽

Vol 4 (Suppl 2) ◽

pp. e000669 ◽

Cited By ~ 3

Author(s):

Giuseppe Viscardi ◽

Raimondo Di Liello ◽

Floriana Morgillo

Keyword(s):

Clinical Trials ◽

Malignant Pleural Mesothelioma ◽

Advanced Disease ◽

Asbestos Exposure ◽

Pleural Mesothelioma ◽

Second Line ◽

Multimodal Approach ◽

Disease Focus ◽

Established Treatment ◽

Line Chemotherapy

Malignant pleural mesothelioma is a rare and aggressive malignancy mostly associated with occupational asbestos exposure. Prognosis is poor and only highly selected patients may benefit from aggressive surgical management, also as part of a multimodal approach. In advanced disease, the combination of pemetrexed and platinum remains the only established treatment, while efficacy evidence of second line chemotherapy is lacking. Thus, a deeper knowledge of biology of the disease and more effective treatments are urgently needed. Refer to specialised centres with multidisciplinary expertise is mandatory, as well as inclusion of patients in clinical trials is advisable whenever possible. In all stages of disease focus on symptoms control is paramount.

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Novel malignant-mesothelioma-associated antigens (Gene-X and THBS-2) in the diagnosis of malignant pleural mesothelioma (MPM).

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.10585 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. 10585-10585

Author(s):

Fumihiro Tanaka ◽

Yoshiki Shigematsu ◽

Takeshi Hanagiri ◽

Hidetaka Uramoto ◽

Tomoko So ◽

...

Keyword(s):

Antibody Titer ◽

Malignant Pleural Mesothelioma ◽

Early Stage ◽

Asbestos Exposure ◽

Serum Antibody ◽

Diagnostic Value ◽

Pleural Mesothelioma ◽

Roc Curve Analysis ◽

Antibody Titers ◽

Serum Antibody Titer

10585 Background: Malignant pleural mesothelioma (MPM) is a highly aggressive malignant tumor of the pleura associated with asbestos exposure, and its diagnosis is usually difficult at early stage. We identified novel mesothelioma-related antigens, Gene-X and thrombospondin-2 (THBS-2), recognized by tumor-infiltrating B cells (Cancer Sci 2009), but the clinical significance in the diagnosis of MPM remains unclear. Methods: A total of 120 patients, who presented with a suspicion of MPM and received pleural biopsy, were reviewed; 97 patients were finally diagnosed with MPM and 27 were with non-malignant diseases (NM). The antibody-titers against Gene-X and THBS-2 in the sera were measured by ELISA method. Results: The serum antibody-titer against THBS-2 was significantly higher in MPM patients than in NM (P<0.01), but there was no difference in the serum antibody-titer against Gene-X (Table). The receiver operating characteristic (ROC) curve analysis showed a significant diagnostic value of serum antibody-titer against THBS-2 with the area-under curve of 0.886 (95% CI, 0.797 - 0.975; P<0.001) in discrimination of MPM from NM diseases; the sensitivity and specificity, when the cut-off value was 0.08, were 72.2% and 95.5%, respectively. Conclusions: The serum antibody-titer against THBS-2 can be a useful non-invasive marker in the diagnosis of MPM. [Table: see text]

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Patients over 65 with early breast cancer and preference for intraoperative radiation despite no survival benefit.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e12612 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e12612-e12612

Author(s):

Annie Tang ◽

Jason F. Kelly ◽

Elizabeth Cureton ◽

Veronica Shim

Keyword(s):

Breast Cancer ◽

Overall Survival ◽

Survival Benefit ◽

Chart Review ◽

Radiation Treatment ◽

Early Stage ◽

Tumor Board ◽

Endocrine Treatment ◽

Intraoperative Radiation ◽

Positive Breast Cancer

e12612 Background: Patients over 65 years of age with early-stage hormone receptor (HR)-positive breast cancer have many radiation treatment options based on the PRIME II and CALGB 9343. Our study aims to evaluate treatment preference of patients over 65 years of age when intraoperative radiation therapy (IORT) is offered. Methods: A retrospective chart review was conducted among patients over 65 years old diagnosed with early-stage HR-positive breast cancer during 2016-2019 in a single breast program in a large integrated healthcare system. At our institution, every breast cancer patient is reviewed at a weekly multi-disciplinary breast conference for IORT eligibility and tracked prospectively. All patients in this study met with breast surgeons and radiation oncologists prior to their locoregional treatment decisions. We identified patients who were offered IORT as an option. The tumor board discussion, treatment team recommendation, and the final patient decision for radiation were obtained from the chart review. Demographics including age, race, hormone therapy, and co-morbidities (Charlson Comorbidity Index) were collected. Logistic regression analysis was used to evaluate if any factors were associated with patients’ radiation treatment choice. Results: Among 225 patients who were over 65 with early endocrine responsive breast cancer, 63 patients met the IORT guideline (28%). Their ages ranged from 65-86 with a mean of 70.4 years. 74.6% of patients chose IORT compared with 14.3% who opted for whole breast radiation. Only 4.8% of patients chose to omit radiation after breast-conserving surgery, and 6.3% chose mastectomy. Patients who chose IORT was also more likely to take endocrine treatment (OR 4.76 CI 1.42-16.0, p = 0.01). Age, race, and co-morbidities were not associated with preference for IORT (OR 0.95 p = 0.34, OR 1.09 p 0.92, and OR 1.15 p = 0.53, respectively). Conclusions: Early-stage breast cancer patients over age 65 with HR-positive disease overwhelmingly desired radiation treatment even after being counseled that it does not confer an overall survival benefit. IORT was strongly preferred over whole breast radiation. This finding indicates that these women choose to maximize their local cancer control, regardless of its impact on overall survival, and prefer the convenience of single fraction, integrated radiation delivery. Further studies need to be completed on patient reported outcomes in this study population.

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Redefining mesothelioma types as a continuum uncovers the immune and vascular systems as key players in the diagnosis and prognosis of this disease

10.1101/334326 ◽

2018 ◽

Author(s):

Nicolas Alcala ◽

Christophe Caux ◽

Nicolas Girard ◽

J.D. McKay ◽

Francoise Galateau-Salle ◽

...

Keyword(s):

Malignant Pleural Mesothelioma ◽

Checkpoint Inhibitors ◽

Asbestos Exposure ◽

Continuous Model ◽

Therapeutic Options ◽

Molecular Profile ◽

Pleural Mesothelioma ◽

Therapeutic Approaches ◽

Aggressive Disease ◽

Key Players

SummaryMalignant Pleural Mesothelioma (MPM) is an aggressive disease related to asbestos exposure, which incidence is expected to increase in the future, and with no effective therapeutic options. We have performed unsupervised analyses of publicly available RNAseq data for 297 MPM. We found that the molecular profile and the prognosis of this disease is better explained by a continuous model rather than by the current WHO classification into the epitheloid, biphasic and sarcomatoid histological types. The main source of variation of this continuum was explained by the immune and vascular pathways, with strong differences in the expression of pro-angiogenic genes and immune checkpoint inhibitors across samples. These data may inform future classifications of MPM and may also guide personalised therapeutic approaches for this disease.SignificanceMalignant Pleural Mesothelioma (MPM) is an aggressive disease with no effective therapeutic options. Unsupervised transcriptomic analyses of 297 MPM unveiled the vascular and the immune systems as key players in the prognosis of this disease, and identified potential therapeutic approaches for this disease targeting these pathways.

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Malignant Pleural Mesothelioma: Genetic and Microenviromental Heterogeneity as an Unexpected Reading Frame and Therapeutic Challenge

Cancers ◽

10.3390/cancers12051186 ◽

2020 ◽

Vol 12 (5) ◽

pp. 1186 ◽

Cited By ~ 2

Author(s):

David Michael Abbott ◽

Chandra Bortolotto ◽

Silvia Benvenuti ◽

Andrea Lancia ◽

Andrea Riccardo Filippi ◽

...

Keyword(s):

Malignant Pleural Mesothelioma ◽

Current Knowledge ◽

Asbestos Exposure ◽

Progressive Increase ◽

Pleural Mesothelioma ◽

Therapeutic Approaches ◽

Reading Frame ◽

Inflammatory Microenvironment ◽

One Year ◽

Global Population

Mesothelioma is a malignancy of serosal membranes including the peritoneum, pleura, pericardium and the tunica vaginalis of the testes. Malignant mesothelioma (MM) is a rare disease with a global incidence in countries like Italy of about 1.15 per 100,000 inhabitants. Malignant Pleural Mesothelioma (MPM) is the most common form of mesothelioma, accounting for approximately 80% of disease. Although rare in the global population, mesothelioma is linked to industrial pollutants and mineral fiber exposure, with approximately 80% of cases linked to asbestos. Due to the persistent asbestos exposure in many countries, a worldwide progressive increase in MPM incidence is expected for the current and coming years. The tumor grows in a loco-regional pattern, spreading from the parietal to the visceral pleura and invading the surrounding structures that induce the clinical picture of pleural effusion, pain and dyspnea. Distant spreading and metastasis are rarely observed, and most patients die from the burden of the primary tumor. Currently, there are no effective treatments for MPM, and the prognosis is invariably poor. Some studies average the prognosis to be roughly one-year after diagnosis. The uniquely poor mutational landscape which characterizes MPM appears to derive from a selective pressure operated by the environment; thus, inflammation and immune response emerge as key players in driving MPM progression and represent promising therapeutic targets. Here we recapitulate current knowledge on MPM with focus on the emerging network between genetic asset and inflammatory microenvironment which characterize the disease as amenable target for novel therapeutic approaches.

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Virtual Clinical and Precision Medicine Tumor Boards: A Cloud-based Platform-mediated Implementation of Multidisciplinary Reviews among Oncology Centers in the Covid-19 Era. (Preprint)

10.2196/preprints.26220 ◽

2020 ◽

Author(s):

Livio Blasi ◽

Roberto Bordonaro ◽

Vincenzo Serretta ◽

Dario Piazza ◽

Alberto Firenze ◽

...

Keyword(s):

Decision Making ◽

Health Professionals ◽

Clinical Pathways ◽

Prospective Trial ◽

Banking System ◽

Outcome Data ◽

Tumor Board ◽

Time Saving ◽

Tumor Boards ◽

Multidisciplinary Tumor Board

BACKGROUND Multidisciplinary tumor boards play a pivotal role in the patients -centered clinical management and in the decision-making process to provide best evidence -based, diagnostic and therapeutic care to cancer patients. Among the barriers to achieve an efficient multidisciplinary tumor board, lack of time and geographical distance play a major role. Therefore the elaboration of an efficient virtual multidisciplinary tumor board (VMTB) is a key-point to reach a successful oncology team and implement a network among health professionals and institutions. This need is stronger than ever in a Covid-19 pandemic scenario. OBJECTIVE This paper presents a research protocol for an observational study focused on exploring the structuring process and the implementation of a multi-institutional VMTB in Sicily. Other endpoints include analysis of cooperation between participants, adherence to guidelines, patients’ outcomes, and patients satisfaction METHODS This protocol encompasses a pragmatic, observational, multicenter, non-interventional, prospective trial. The study's programmed duration is five years, with a half-yearly analysis of the primary and secondary objectives' measurements. Oncology care health-professionals from various oncology subspecialties at oncology departments in multiple hospitals (academic and general hospitals as well as tertiary centers and community hospitals) are involved in a non-hierarchic fashion. VMTB employ an innovative, virtual, cloud-based platform to share anonymized medical data which are discussed via a videoconferencing system both satisfying security criteria and HIPAA compliance. RESULTS The protocol is part of a larger research project on communication and multidisciplinary collaboration in oncology units and departments spread in the Sicily region in Italy. Results of this study will particularly focus on the organization of VMTB involving oncology units present in different hospitals spread in the area and create a network to allow best patients care pathways and a hub and spoke relationship. Results will also include data concerning organization skills and pitfalls, barriers, efficiency, number and type con clinical cases, and customers’ satisfaction. CONCLUSIONS VMTB represents a unique opportunity to optimize patient’s management in a patient centered approach. An efficient virtualization and data banking system is potentially time-saving, a source for outcome data, and a detector of possible holes in the hull of clinical pathways. The observations and results from this VMTB study may hopefully useful to design nonclinical and organizational interventions that enhance multidisciplinary decision-making in oncology.

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Current and Future Treatments for Classic Galactosemia

Journal of Personalized Medicine ◽

10.3390/jpm11020075 ◽

2021 ◽

Vol 11 (2) ◽

pp. 75 ◽

Cited By ~ 1

Author(s):

Britt Delnoy ◽

Ana I. Coelho ◽

Maria Estela Rubio-Gozalbo

Keyword(s):

Standard Of Care ◽

Type I ◽

Therapeutic Approaches ◽

Restricted Diet ◽

Galactose Metabolism ◽

Galt Activity ◽

Classic Galactosemia ◽

Pathogenic Factors ◽

Future Treatments ◽

Novel Therapeutic

Type I (classic) galactosemia, galactose 1-phosphate uridylyltransferase (GALT)-deficiency is a hereditary disorder of galactose metabolism. The current therapeutic standard of care, a galactose-restricted diet, is effective in treating neonatal complications but is inadequate in preventing burdensome complications. The development of several animal models of classic galactosemia that (partly) mimic the biochemical and clinical phenotypes and the resolution of the crystal structure of GALT have provided important insights; however, precise pathophysiology remains to be elucidated. Novel therapeutic approaches currently being explored focus on several of the pathogenic factors that have been described, aiming to (i) restore GALT activity, (ii) influence the cascade of events and (iii) address the clinical picture. This review attempts to provide an overview on the latest advancements in therapy approaches.

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