Oncological Frontiers in the Treatment of Malignant Pleural Mesothelioma

Vita, Emanuele; Stefani, Alessio; Salvatore, Mariantonietta Di; Chiappetta, Marco; Lococo, Filippo; Margaritora, Stefano; Bria, Emilio

doi:10.3390/jcm10112290

Cited by 7 publications

(9 citation statements)

References 66 publications

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“…MPM usually affects patients from the fifth to seventh decades, and it develops in males in 70–80% of cases ( 5 ). No efficacious treatment has been yet developed for MPM with the standard therapy consisting of the combination of chemotherapy and surgery in clinically fit patients ( 6 ). However, individuals with MPM have a very poor prognosis resulting in a 5-year survival rate of about 10% with a median overall survival (OS) of 8.3 months ( 7 , 8 ).…”

Section: Introductionmentioning

confidence: 99%

The genetic susceptibility in the development of malignant pleural mesothelioma: somatic and germline variants, clinicopathological features and implication in practical medical/surgical care: a narrative review

Congedo,

West,

Evangelista

et al. 2024

J Thorac Dis

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Background and Objective Malignant pleural mesothelioma (MPM) is a very aggressive primary tumor of the pleura whose main risk factor is exposure to asbestos. However, only a minority of exposed people develops MPM and the incidence of MPM cases without an apparent association with asbestos exposure has been increasing in recent years, suggesting that genetic predisposing factors may play a crucial role. In addition, several studies reported familial cases of MPM, suggesting that heredity may be an important and underestimated feature in MPM development. Several candidate genes have been associated with a predisposition to MPM and most of them play a role in DNA repair mechanisms: overall, approximately 20% of MPM cases may be related to genetic predisposition. A particular category of patients with high susceptibility to MPM is represented by carriers of pathogenic variants in the BAP1 gene. Germline variants in BAP1 predispose to the development of MPM following an autosomal dominant pattern of inheritance in the familial cases. MPMs in these patients are significantly less aggressive, and patients require a multidisciplinary approach that involves genetic counseling, medical genetics, pathology, surgical, medical, and radiation oncology expertise. In the present narrative review, we presented a comprehensive overview of genetic susceptibility in the development of MPM. Methods The narrative review is based on a selective literature carried out in PubMed in 2023. Inclusion criteria were original articles in English language, and clinical trials (randomized, prospective, or retrospective). Key Content and Findings We summarized the somatic and germline variants and the differences in terms of clinicopathological features and prognosis between gene-related MPM (GR-MPM) and asbestos-related MPM (AR-MPM). We also discussed the indications for screening, genetic testing, and surveillance of patients with BAP1 germline variants. Conclusions In this narrative review, we have emphasized that the BAP1 gene’s harmful germline variations are inherited in an autosomal dominant manner in familial cases. MPMs in individuals with these variations are less severe, and their medical care necessitates a collaborative effort. Additionally, we have outlined the current therapeutic prospects for MPM, including the possibility of gene-specific therapy, which is currently promising but still requires clinical validation.

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Section: Introductionmentioning

confidence: 99%

The genetic susceptibility in the development of malignant pleural mesothelioma: somatic and germline variants, clinicopathological features and implication in practical medical/surgical care: a narrative review

Congedo,

West,

Evangelista

et al. 2024

J Thorac Dis

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“…Biological targeted therapy for MPM is not recommended because of the lack of known oncogenic driver alterations (7). Clinical studies of MPM immunotherapy has underwent a transition from relapse to second-line, monotherapy to combination, and now seemed promising in some phase II clinical studies (8). Based on these trials, the NCCN guidelines (2018) recommend nivolumab ± ipilimumab or pembrolizumab as subsequent systemic therapy (9).…”

Section: Introductionmentioning

confidence: 99%

Cost-effectiveness of nivolumab plus ipilimumab as first-line treatment for American patients with unresectable malignant pleural mesothelioma

Tang

et al. 2022

Front. Public Health

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BackgroundThe treatment paradigm of unresectable malignant pleural mesothelioma (MPM) has changed in recent years. Checkmate 743 demonstrate that nivolumab plus ipilimumab showed good clinical benefits compared with chemotherapy in the treatment of MPM. The study is aim to evaluate the cost-effectiveness of Nivolumab plus ipilimumab vs. platinum plus chemotherapy for the first-line treatment of unresectable MPM.MethodsA Markov model was developed to compare the cost and quality-adjusted life-year (QALY) of nivolumab plus ipilimumab and chemotherapy over a 10-year time horizon. Clinical efficacy and safety data were extracted from the CheckMate 743 trials. Health state utilities were obtained from published literature. Costs were collected from an US payer perspective. One-way and probabilistic sensitivity analyses were conducted to explore the impact of uncertainties on the cost-effectiveness's results.ResultsIn the base case analysis, the incremental healthcare costs and QALYs for Nivolumab plus Ipilimumab vs. chemotherapy are $196,604.22 and 0.53, respectively, resulting an incremental cost-effectiveness ratio (ICER) of $372,414.28/QALYs for the model cohort of patients with locally advanced or metastatic MPM. However, Probabilistic sensitivity analysis showed that there was no probability that Nivolumab plus ipilimumab was cost-effective within the fluctuation range of other model parameters in first-line in unresectable MPM. The results of one-way sensitivity analysis showed that the cost of Nivolumab was the most sensitive parameter.ConclusionsThe ICER of Nivolumab plus ipilimumab is above the theoretical willingness-to-pay threshold in the U.S, which suggests that first-line nivolumab plus ipilimumab for unresectable MPM may be not a cost-effective choice.

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“…The major risk factors for MM are asbestos exposure and viral infection (e.g., Simian Virus 40, SV40). The most common histological subtypes are the epithelioid (60–80%), the sarcomatoid (20%), and the biphasic ( Vita et al, 2021 ). The outcome of MM is closely cell type-dependent—for instance, epithelioid MM is less aggressive, even though long-term outcomes are still poor.…”

Section: Introductionmentioning

confidence: 99%

“…The outcome of MM is closely cell type-dependent—for instance, epithelioid MM is less aggressive, even though long-term outcomes are still poor. The standard MM treatment is currently based on a multimodal approach, including induction AC (platin and pemetrexed), surgical resection, and sometimes RT, which is generally offered to patients with pleural MM, to young patients with a good Eastern Cooperative Oncology Group (ECOG) ( Martin, 2021 ) performance status (PS), to patients with localized disease and to those with the epithelioid subtype ( Vita et al, 2021 ). The clinical role of second-line AC for progressive or relapsed disease is still undefined, as no post-progression validated treatment has emerged.…”

Section: Introductionmentioning

confidence: 99%

Improved Survival and Quality of Life Through an Integrative, Multidisciplinary Oncological Approach: Pathophysiological Analysis of Four Clinical Cancer Cases and Review of the Literature

Berretta

Morra²,

Taibi

et al. 2022

Front. Pharmacol.

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Objectives: According to the National Cancer Institute, the integrative medicine (IM) approach to medical care combines standard medicine with complementary and alternative medicine practices that have proved safe and effective.Methods: We describe the clinical cases of four patients with malignant pleural mesothelioma (MPM), diffuse malignant peritoneal mesothelioma (DMPM), intrahepatic cholangiocarcinoma, and breast cancer (BC) who received supportive treatment (ST) according to an IM approach after the failure of standard cancer treatments or the appearance of serious adverse events caused by antiblastic chemotherapy. The critical role of complementary drugs in reducing the side effects of cancer treatments and normalizing the white cell count is especially apparent in the case of the patient with metastatic BC, who experienced prolonged neutropenia.Results: The IM approach was well-tolerated and had no adverse side effects. It improved the quality of life (QoL) of all patients and in two cases extended overall survival.Conclusion: The extended clinical and instrumental response to IM of the patients with malignant mesothelioma and the improved health-related QoL and good tolerance of the ST demonstrated in all cases support the value of this approach in patients whose cancer therapies have failed but who show a good performance status. Our data require confirmation in a well-designed prospective clinical trial.

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Oncological Frontiers in the Treatment of Malignant Pleural Mesothelioma

Cited by 7 publications

References 66 publications

The genetic susceptibility in the development of malignant pleural mesothelioma: somatic and germline variants, clinicopathological features and implication in practical medical/surgical care: a narrative review

The genetic susceptibility in the development of malignant pleural mesothelioma: somatic and germline variants, clinicopathological features and implication in practical medical/surgical care: a narrative review

Cost-effectiveness of nivolumab plus ipilimumab as first-line treatment for American patients with unresectable malignant pleural mesothelioma

Improved Survival and Quality of Life Through an Integrative, Multidisciplinary Oncological Approach: Pathophysiological Analysis of Four Clinical Cancer Cases and Review of the Literature

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