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Research on Clinical Treatment of Mesothelioma
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Research on Clinical Treatment of Mesothelioma

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Clinical Research of Cancer".

Deadline for manuscript submissions: 10 July 2025 | Viewed by 5032

Special Issue Editors

Dr. Giulia M. Stella

E-Mail Website
Guest Editor
1. Department of Internal Medicine and Medical Therapeutics, University of Pavia Medical School, 27100 Pavia, Italy
2. Unit of Respiratory System Diseases, Cardio-Thoracic and Vascular Department, IRCCS Fondazione Policlinico San Matteo, 27100 Pavia, Italy
Interests: thoracic cancers; personalized medicine; oncogenomics; metastatic process
Special Issues, Collections and Topics in MDPI journals
Dr. Walid Hadid

E-Mail Website
Guest Editor
Interventional Pulmonary Section, Community Health Network, Heart and Vascular Hospital, Community MD Anderson Cancer Center North, Indianapolis, IN, USA
Interests: lung cancer; pleural disease

Special Issue Information

Dear Colleagues,

Pleural mesothelioma (PM) is a rare and aggressive neoplasm that originates from the pleural mesothelium and whose onset is mainly linked to occupational and/or environmental exposure to asbestos. Conventional chemotherapy as well as targeted therapies have failed against disease progression and patients’ prognoses are still poor; in some instances, supportive care is the only therapeutic option. However, the advent of immunotherapy, the development of advanced cell therapy platforms, and the application of innovative technologies in cancer management have allowed some effective improvement in PM as well.

Thus, the aim of the present Special Issue is to recapitulate the current standard of care for this orphan cancer and to focus on novel and more promising approaches in PM screening, diagnosis, and treatment.

Dr. Giulia M. Stella
Dr. Walid Hadid
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • pleural mesothelioma
  • targeted therapy
  • local treatments
  • radiomics
  • genetic traits
  • occupational health
  • asbestos exposure

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Published Papers (6 papers)

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Research

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10 pages, 194 KiB  
Communication
Why the MARS2 Trial Does Not Mean the End of All Mesothelioma Surgery
by David Waller, Rocco Bilancia, Luigi Ventura, Sara Tenconi, Laura Socci and Andrea Bille
Cancers 2025, 17(5), 724; https://doi.org/10.3390/cancers17050724 - 21 Feb 2025
Viewed by 215
Abstract
Background/Objectives: The published report of the MARS2 trial suggested that the addition of extended pleurectomy/decortication to chemotherapy for pleural mesothelioma was harmful. Thus, the report goes on, all disease should be considered as unresectable and no further mesothelioma surgery for survival benefit should [...] Read more.
Background/Objectives: The published report of the MARS2 trial suggested that the addition of extended pleurectomy/decortication to chemotherapy for pleural mesothelioma was harmful. Thus, the report goes on, all disease should be considered as unresectable and no further mesothelioma surgery for survival benefit should be considered. This statement has changed clinical practice in the UK; however, the design of the MARS2 trial has several limitations which should prevent its conclusions being over interpreted. These limitations include the following: the inclusion of too many patients who would fall outside contemporary selection criteria including age, co-morbidity and histology; the unnecessary resection of too much tissue, particularly the diaphragm, and operating on patients too late in the disease process due to less than rigorous staging. Methods: We retrospectively analysed the selection and outcome of data of 79 of the 158 (50%) patients who underwent surgery in the surgical arm of the MARS2 study who were operated by the authors in four of the five trial surgical centres. We revised the clinical staging of these patients by applying the criteria in the forthcoming 9th TNM edition including the measurement of pleural thickness. Results: Based on reported guidelines, the selection for surgery was reset as stage I or II epithelioid PM. We found that 52 (66%) of these patients (group A) would not have been considered for surgery using contemporary selection criteria for the following reasons: non-epithelioid PM in 5; cT/4 in 35; cT2N1 in 10 and 2 cT2N0 (pN1), which would have been detected on preoperative mediastinal biopsy. Of the 27 (34%) trial patients fulfilling current criteria (group B), 12 were cT1N0, 1 was cT1N1, 6 were cT1N0pN1 and 8 were cT2N0, all with epithelioid PM. The median survival of group B was 32 (1–72) months, which was significantly higher than in group A: 8.5 (1–55) months, p < 0.0005 (Mann–Whitney). Conclusions: As contemporary selection criteria were not applied in MARS2, its conclusions cannot be universally applied to all those with PM. Together with the favourable postoperative survival in this selected group, we suggest that there is still scope for a further trial of surgery in early-stage epithelioid mesothelioma. Full article
(This article belongs to the Special Issue Research on Clinical Treatment of Mesothelioma)
11 pages, 658 KiB  
Article
Paradoxical Improvement in Malignant Pleural Mesothelioma Outcomes Following Delayed Treatment Initiation
by Ashwin Kulshrestha, Emanuela Taioli, Andrea Wolf, Raja Flores and Stephanie Tuminello
Cancers 2024, 16(22), 3755; https://doi.org/10.3390/cancers16223755 - 7 Nov 2024
Viewed by 1126
Abstract
Background/Objectives: Time to treatment initiation (TTI) has been identified as a predictor of survival in many cancers, but its impact on malignant pleural mesothelioma (MPM) is unknown. This study investigates factors influencing TTI in MPM and its association with overall survival. Methods: The [...] Read more.
Background/Objectives: Time to treatment initiation (TTI) has been identified as a predictor of survival in many cancers, but its impact on malignant pleural mesothelioma (MPM) is unknown. This study investigates factors influencing TTI in MPM and its association with overall survival. Methods: The Surveillance, Epidemiology, and End Results (SEER) database was used to obtain data for MPM patients in the United States. TTI was defined as the number of days from diagnosis to initiation of first treatment, and delayed TTI was defined as exceeding the median TTI. Χ2 tests and t-tests compared sociodemographic and clinical differences between early and delayed TTI groups, while Kaplan–Meier and Cox proportional hazards models evaluated relationships between prognostic factors, TTI, and survival. Results: Among 4879 MPM patients, the median TTI was 39 days. Median survival was 10 months among early TTI patients and 13 months among delayed TTI patients. Patients with epithelioid histology were more likely to have delayed TTI, as were patients who received combination therapy or were diagnosed more recently (p < 0.0001). Adjusting for covariates, delayed TTI status remained associated with better survival (HR 0.79, 95% CI: 0.74–0.84). Conclusions: This study presents an important insight into the management of MPM, demonstrating that delayed time to treatment initiation is positively associated with improved overall survival, contrary to findings in most cancers. This finding underscores the importance of comprehensive, multidisciplinary care, as delays due to robust staging evaluations and patient travel to high-volume centers of excellence likely contribute to delays in treatment. Taken together, these results suggest that clinicians should prioritize personalized treatment planning and collaborative care over a push to rapidly initiate treatment to optimize patient outcomes in MPM. Full article
(This article belongs to the Special Issue Research on Clinical Treatment of Mesothelioma)
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10 pages, 1413 KiB  
Article
Impact of T Cell Ratios on Survival in Pleural Mesothelioma: Insights from Tumor Microenvironment Analysis
by Laura V. Klotz, Andreas Weigert, Florian Eichhorn, Michael Allgäuer, Thomas Muley, Rajiv Shah, Rajkumar Savai, Martin E. Eichhorn and Hauke Winter
Cancers 2024, 16(19), 3418; https://doi.org/10.3390/cancers16193418 - 8 Oct 2024
Viewed by 1130
Abstract
Background: Immunotherapy has significantly improved overall survival in patients with pleural mesothelioma, yet this benefit does not extend to those with the epithelioid subtype. Tumor growth is believed to be influenced by the immune response. This study aimed to analyze the tumor microenvironment [...] Read more.
Background: Immunotherapy has significantly improved overall survival in patients with pleural mesothelioma, yet this benefit does not extend to those with the epithelioid subtype. Tumor growth is believed to be influenced by the immune response. This study aimed to analyze the tumor microenvironment to gain a better understanding of its influence on tumor growth. Methods: The tumor immune cell infiltration of 188 patients with pleural mesothelioma was characterized by multiplex immunofluorescence staining for CD3+ cells (CD3+), CD4+ cells (CD3+/CD4+), CD8+ cells (CD3+/CD8+), Treg (CD3+/CD4+/CD8-/CD163-/Foxp3+), PD1 cells (PD1+), and T helper cells (CD3+/CD4+/CD8-/CD163-/FoxP3-). The distribution of specific immune cells was correlated with clinical parameters. Results: A total of 188 patients with pleural mesothelioma (135 epithelioid, 9 sarcomatoid, 44 biphasic subtypes) were analyzed. The median age was 64.8 years. Overall survival was significantly longer in the epithelioid subtype than in the non-epithelioid subtype (p = 0.016). The presence of PD-L1 expression had a negative effect on overall survival (p = 0.041). A high ratio of CD4+ cells to regulatory T cells was associated with a significantly longer overall survival of more than 12 months (p = 0.015). The ratio of CD4+ cells to regulatory T cells retained its significant effect on overall survival in the multivariate analysis. Conclusions: Distinct differences in the T cell immune infiltrates in mesothelioma are strongly associated with overall survival. The tumor microenvironment could therefore serve as a source of prognostic biomarkers. Full article
(This article belongs to the Special Issue Research on Clinical Treatment of Mesothelioma)
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Review

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17 pages, 691 KiB  
Review
Recent Advances in Mesothelioma Treatment: Immunotherapy, Advanced Cell Therapy, and Other Innovative Therapeutic Modalities
by Ratoe Suraya, Tatsuya Nagano and Motoko Tachihara
Cancers 2025, 17(4), 694; https://doi.org/10.3390/cancers17040694 - 18 Feb 2025
Viewed by 162
Abstract
Mesothelioma is a highly malignant condition arising from the pleura and peritoneum that is closely related to asbestos exposure. The prognosis for this condition has traditionally been poor due to the difficulty physicians have faced in diagnosing and treating this disease, even in [...] Read more.
Mesothelioma is a highly malignant condition arising from the pleura and peritoneum that is closely related to asbestos exposure. The prognosis for this condition has traditionally been poor due to the difficulty physicians have faced in diagnosing and treating this disease, even in its early phase. Fortunately, recent advances in both the molecular understanding of the development of this disease and innovative and novel treatment modalities have accelerated the discovery of new ways to treat mesothelioma. In this review, we first summarize the mechanism of mesothelioma pathophysiology and then relate it to emerging treatment modalities. These include immunotherapy or immune checkpoint inhibitors (ICIs), molecular targeted therapies, and cell-based therapies (such as CAR-T cells or dendritic cells). The scientific basis for the utilization of these treatment modalities, alongside the current clinical evidence for each option, will be explored in detail later on. The hope is that this review can elucidate how these emerging therapeutic options work clinically to help accelerate further developments in novel mesothelioma treatment modalities. Full article
(This article belongs to the Special Issue Research on Clinical Treatment of Mesothelioma)
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Other

Jump to: Research, Review

11 pages, 1989 KiB  
Systematic Review
A Meta-Analysis of First-Line Treatments for Unresectable Pleural Mesothelioma: Indirect Comparisons from Reconstructed Individual Patient Data of Six Randomized Controlled Trials
by Andrea Messori, Sabrina Trippoli, Eugenia Piragine, Sara Veneziano and Vincenzo Calderone
Cancers 2025, 17(3), 503; https://doi.org/10.3390/cancers17030503 - 3 Feb 2025
Viewed by 528
Abstract
Background: In unresectable pleural mesothelioma, pemetrexed+cisplatin as first line is considered the standard of care, but novel treatments have been recently proposed. Methods: Our objective was to compare, albeit indirectly, the results of randomized controlled trials on overall survival (OS). The IPDfromKM method [...] Read more.
Background: In unresectable pleural mesothelioma, pemetrexed+cisplatin as first line is considered the standard of care, but novel treatments have been recently proposed. Methods: Our objective was to compare, albeit indirectly, the results of randomized controlled trials on overall survival (OS). The IPDfromKM method was employed for reconstruct individual patient data (IPD) from the graphs of Kaplan–Meier curves. Cox statistics was run to estimate hazard ratios (HRs). Results: After a literature search on Medline (via PubMed) and Scopus databases, six randomized controlled trials were identified in which five new treatments (nivolumab plus ipilimumab, bevacizumab plus pemetrexed plus cisplatin, chemotherapy plus pembrolizumab, ONCOS-102 plus pemetrexed plus cisplatin/carboplatin and cediranib plus pemetrexed+cisplatin with maintenance with cediranib) were evaluated. In five trials, pemetrexed plus cisplatin was the standard of care given to the control arms. Nivolumab plus ipilimumab, bevacizumab plus pemetrexed plus cisplatin and chemotherapy plus pembrolizumab showed a significantly better OS compared with controls. ONCOS-102 plus pemetrexed plus cisplatin/carboplatin did not significantly improve OS. In contrast, OS worsened with cisplatin alone and with cediranib plus pemetrexed+cisplatin with maintenance with cediranib. Discussion: Our analysis indicates that, in patients with unresectable pleural mesothelioma, three of the five novel treatments provided a significant survival benefit compared with the standard of care. Further research is needed to confirm the OS benefit found in our analysis with some treatments, whereas cisplatin alone and cediranib plus pemetrexed+cisplatin with maintenance with cediranib do not seem to deserve further research. Full article
(This article belongs to the Special Issue Research on Clinical Treatment of Mesothelioma)
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13 pages, 1484 KiB  
Study Protocol
Phase I Clinical Trial on Pleural Mesothelioma Using Neoadjuvant Local Administration of Paclitaxel-Loaded Mesenchymal Stromal Cells (PACLIMES Trial): Study Rationale and Design
by Giulia Maria Stella, Daniela Lisini, Paolo Pedrazzoli, Giulia Galli, Chandra Bortolotto, Giulio Melloni, Gioacchino D’Ambrosio, Catherine Klersy, Amelia Grosso, Francesca Paino, Stefano Tomaselli, Laura Saracino, Giulio Alessandri, Augusto Pessina, Elena Grignani, Vittorio Rosti, Angelo Guido Corsico, Patrizia Comoli and Francesco Agustoni
Cancers 2024, 16(19), 3391; https://doi.org/10.3390/cancers16193391 - 4 Oct 2024
Viewed by 1233
Abstract
Background and rationale. Pleural mesothelioma (PM) is a rare and aggressive neoplasm that originates from the pleural mesothelium and whose onset is mainly linked to exposure to asbestos, which cannot be attacked with truly effective therapies with consequent poor prognosis. The rationale of [...] Read more.
Background and rationale. Pleural mesothelioma (PM) is a rare and aggressive neoplasm that originates from the pleural mesothelium and whose onset is mainly linked to exposure to asbestos, which cannot be attacked with truly effective therapies with consequent poor prognosis. The rationale of this study is based on the use of mesenchymal stromal cells (MSCs) as a vehicle for chemotherapy drugs to be injected directly into the pathological site, such as the pleural cavity. Study design. The study involves the use of a conventional chemotherapeutic drug, Paclitaxel (PTX), which is widely used in the treatment of different types of solid tumors, including PM, although some limitations are related to pharmacokinetic aspects. The use of PTX-loaded MSCs to treat PM should provide several potential advantages over the systemically administered drug as reduced toxicity and increased concentration of active drug in the tumor-surrounding context. The PACLIMES trial explores the safety and toxicity of the local administration of Paclimes in chemonaive patients, candidates for pleurectomy. The secondary objective is to find the effective Paclimes dose for subsequent phase II studies and to observe and record the antitumor activity. Future direction. The experimental pre-clinical background and rationale are discussed as well. Full article
(This article belongs to the Special Issue Research on Clinical Treatment of Mesothelioma)
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