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New Perspectives in Thoracic Surgery for Malignant Pleural Mesothelioma

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Oncology".

Deadline for manuscript submissions: closed (31 October 2024) | Viewed by 4978

Special Issue Editor


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Guest Editor
Thoracic Surgery—Morelli Hospital, ASST Valtellina e Alto Lario, 23100 Sondalo, Italy
Interests: lung cancer; pulmonary metastasis; pleural mesothelioma; innovative surgical techniques; minimally invasive thoracic surgery; VATS; surgical oncology; respiration physiology
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Special Issue Information

Dear Colleagues,

Through the decades, mesothelioma surgery has been performed to diagnose disease, remove tumors (aggressive surgery such as extra-pleural pneumonectomy, or lung-sparing tumor-removing surgery, such as pleurectomy/decortication), or improve symptoms (palliative surgery). In a real-world multidisciplinary setting, many authors have reported that some long-term survivors benefit from surgery.

This Special Issue aims to understand what could happen in the future years, trying to foresee the trends in future  mesothelioma surgical treatments. We also would like to understand how to improve MDT, preoperative study, anesthesia, postoperative rehabilitation, palliation, and follow-up. Furthermore, is there a role for Artificial Intelligence in the treatment of mesothelioma? 

Simply put: should we leave surgery or could it still be somewhat useful? Which type of surgery, if any? It is widely recognized that a truly complete resection is not possible, and that neither an extrapleural pneumonectomy (EPP) nor a radical pleurectomy/decortication (P/D) can eradicate all residual microscopic tumour.

Recently, a strong debate has been going on following the IASLC presentation of the results of the MARS2 trial, which compared survival for two groups of pleural mesothelioma patients: one group had chemotherapy with surgery, and the other had chemo without surgery.

The MARS2 clinical study results were presented at the IASLC 2023 meeting, and the lead author, Dr.Lim, proposed eliminating surgery for patients affected by malignant pleural mesothelioma, so extending survival of 28%.

Dr. Lim stated: “Classifying this disease as [inoperable] from the outset would increase access to more effective systemic treatments to improve survival for patients with other stages of disease.”

However, the commentary of Dr. Ugalde Figueroa raised important questions about MARS2 data and analysis:

  • No true survival difference beetween the group: median survivals differed between the two groups, but not significantly.
  • Patient characteristics were unequal between groups: the surgery group had a higher percentage of patients with significant risk factors, possibly leading to an increase in postoperative unfavourable outcome.
  • The treating hospitals lacked experience: “Would the outcome be different in exclusively high-volume centers?”

We are solicitings clinical trials’ reports or projects, study designs, case series, technical “how-to-do-it” articles, narrative and systematic reviews, expert commentaries.

Dr. Paolo Scanagatta
Guest Editor

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Keywords

  • thoracic medicine
  • thoracic surgery
  • pleural mesothelioma
  • chemotherapy
  • oncology
  • thoracic anesthesia

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Published Papers (3 papers)

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Research

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11 pages, 853 KiB  
Article
Dose-Dependent Concentration and Penetration Depth of Cisplatin in Human Lung Tissue During Hyperthermic Exposure
by Christopher Larisch, Till Markowiak, Martin Ignaz Schauer, Svitlana Golovchenko, Patrick J. Bednarski, Karolina Mueller, Christian Großer, Hans-Stefan Hofmann and Michael Ried
J. Clin. Med. 2025, 14(3), 983; https://doi.org/10.3390/jcm14030983 - 4 Feb 2025
Viewed by 693
Abstract
Background: Hyperthermic intrathoracic chemotherapy (HITOC) is an additive treatment option after surgical cytoreduction of pleural malignancies. Despite growing clinical experience and studies evaluating its feasibility, postoperative morbidity and mortality, as well as the effect on survival, there is still only little known [...] Read more.
Background: Hyperthermic intrathoracic chemotherapy (HITOC) is an additive treatment option after surgical cytoreduction of pleural malignancies. Despite growing clinical experience and studies evaluating its feasibility, postoperative morbidity and mortality, as well as the effect on survival, there is still only little known about the local effects of HITOC on the lung parenchyma and tumour cells. The objective of this in vitro study was to evaluate the dose-dependent concentration and penetration depth of cisplatin in human lung tissue. Methods: In total, 40 patients were enrolled for elective lung resection, and wedge samples were taken to the laboratory. The visceral pleura was removed, and the decorticated lung tissue was incubated in cisplatin solutions of different concentrations (0.05, 0.075, and 0.1 mg/mL) at 42 °C over 60 min. Afterwards, platinum amounts in the lung tissue samples were measured using atomic absorption spectroscopy. Results: A strong decline of the cisplatin concentration was found until a depth of 3.5 mm, followed by a mild decline until a depth of 7.5 mm. In a depth of 0.5 mm, there was only a significant difference between 0.05 and 0.1 mg/mL (p = 0.03, Cohen’s d = 0.43). In a depth of 1.5 mm, there was an overall significant difference in cisplatin concentration dependent on dose (p = 0.027). In deeper tissue layers, no significant difference in cisplatin concentrations in the tissue was found. Conclusions: A dose-dependent increase of the cisplatin concentration was found for superficial tissue layers. This emphasises the relevance of sufficiently high intrathoracic concentrations of the chemotherapeutic agent. This study confirms that cisplatin penetrates lung tissue in therapeutically effective concentrations. Full article
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15 pages, 2386 KiB  
Article
Prognostic Value of PD-L1, BAP-1 and ILK in Pleural Mesothelioma
by Oliver Illini, Michal Benej, Anna Sophie Lang-Stöberl, Hannah Fabikan, Luka Brcic, Florian Sucher, Dagmar Krenbek, Tibor Krajc, Christoph Weinlinger, Maximilian J. Hochmair, Arschang Valipour, Thomas Klikovits and Stefan Watzka
J. Clin. Med. 2024, 13(23), 7322; https://doi.org/10.3390/jcm13237322 - 2 Dec 2024
Viewed by 1094
Abstract
Background: Pleural mesothelioma (PM) is a rare type of cancer with poor prognosis. Prognostic and predictive biomarkers could improve treatment strategies in these patients. Programmed death ligand 1 (PD-L1), integrin-linked kinase (ILK) and breast cancer gene 1-associated protein (BAP-1) have been proposed [...] Read more.
Background: Pleural mesothelioma (PM) is a rare type of cancer with poor prognosis. Prognostic and predictive biomarkers could improve treatment strategies in these patients. Programmed death ligand 1 (PD-L1), integrin-linked kinase (ILK) and breast cancer gene 1-associated protein (BAP-1) have been proposed to predict outcomes in PM, but existing data are limited and controversial. Design and Methods: This single-center, retrospective study analyzed data on expression patterns and the prognostic role of PD-L1, ILK and BAP-1 in consecutive patients diagnosed with PM. Results: Of all patients (n = 52) included, more than half showed a positive PD-L1 expression (52% TPS ≥ 1%, 65% CPS ≥ 1), 69% showed a BAP-1 loss and 80% an ILK ≥ 50%. Positive PD-L1 expression was more frequent in the non-epithelioid subtype (p = 0.045). ILK intensity (p = 0.032) and positive PD-L1 (p = 0.034) were associated with more advanced tumor stages. The median overall survival (OS) was 16.9 (95% CI 13.1–25.2) months. Multimodality therapy (MMT) including surgery and early stage were independent prognostic factors for longer OS (MMT: HR 0.347, 95% CI 0.13–0.90, p = 0.029; advanced stage: HR 4.989; 95% CI 1.64–15.13, p = 0.005). Patients with an expression of PD-L1 TPS ≥ 1% or BAP-1 positivity showed numerically worse survival with a median OS of 15.3 (11.5; 24.4) vs. 20.0 (11.2; 34.9) and 11.3 (5.6; 31.0) vs. 20.0 (15.2; 28.1) months, respectively. Furthermore, PD-L1 was associated with worse survival in patients receiving MMT (PD-L1 TPS ≥ 1%: 15.8 (12.1–25.4) vs. 31.3 (17.4–95.4) p = 0.053). ILK expression ≥50% did not influence survival. The combinations of CPS ≥ 1% with BAP-1 positivity or ILK expression ≥50% were associated with worse survival (p = 0.045, p = 0.019). Conclusions: In this real-world analysis, expressions of PD-L1 and BAP-1 were associated with worse survival in patients with PM. ILK showed no prognostic value. Further studies with larger cohorts are needed to identify prognostic and predictive biomarkers facilitating optimized individual treatment decision in this rare type of cancer. Full article
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Review

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11 pages, 241 KiB  
Review
Malignant Pleural Mesothelioma: A Comprehensive Review
by Molly Jain, Morgan Kay Crites, Patricia Rich and Bharat Bajantri
J. Clin. Med. 2024, 13(19), 5837; https://doi.org/10.3390/jcm13195837 - 30 Sep 2024
Cited by 6 | Viewed by 2791
Abstract
Mesotheliomas are hyperplastic tumors that envelop the serosal membranes that safeguard the body’s external surfaces. Although certain instances may exhibit indolent characteristics, a significant number of tumors demonstrate rapid progression and a poor prognosis. Mesotheliomas are typically categorized as benign or malignant, with [...] Read more.
Mesotheliomas are hyperplastic tumors that envelop the serosal membranes that safeguard the body’s external surfaces. Although certain instances may exhibit indolent characteristics, a significant number of tumors demonstrate rapid progression and a poor prognosis. Mesotheliomas are typically categorized as benign or malignant, with malignant mesothelioma being more frequently linked to asbestos exposure. Malignant pleural mesothelioma (MPM) predominantly impacts males and often emerges in the late 50 s or beyond, characterized by a median age of early 70 s among patients exposed to asbestos lasting from 2 to 4 decades. Respiratory exposure to asbestos particles leads to the development of malignant mesothelioma, characterized by recurrent inflammation, disruption of cell division, activation of proto-oncogenes, and generation of free radicals. In pleural mesothelioma, BAP1, CDKN2A, and NF are the most often mutated genes. Accurate diagnosis and assessment usually require the use of chest computed tomography (CT) scans, magnetic resonance imaging (MRI), and positron emission tomography (PET). Radiation therapy, immunotherapy, chemotherapy, and surgery are some of the treatment options that are currently available. This systematic review provides a comprehensive analysis of the latest research, biomarkers, evaluation, and management strategies for malignant pleural mesothelioma. Full article
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