bims-mesote 2025-08-10 papers

Issue of 2025–08–10
three papers selected by
Laura Mannarino, Humanitas Research

Muscles. 2024 Feb 08. 3(1): 48-59

Sarcopenia and Pleural Mesothelioma: The Current Knowledge.

Nikolaos D Karakousis, Konstantinos I Gourgoulianis, Nikolaos Papanas, Ourania S Kotsiou.

Pleural mesothelioma (PM) is a tumor related to adverse prognosis. The PM WHO classification has mainly identified three major subtypes of PM which are epithelioid, biphasic, and sarcomatoid. Sarcopenia is a medical issue related to a reduction in muscle mass and strength. It represents a major health issue globally because it is related to adverse effects such as hospitalization, increased length of stay, disability, increased morbidity and mortality and augmented health care expenditures. In this literature review, we attempted to examine the upcoming association between sarcopenia and PM. As recorded by the current literature, muscle loss in PM subjects was related to poorer survival and lower levels of activity. Subjects with PM had increased rates of pre-sarcopenia and malnutrition, while pre-sarcopenia was related to worse activity levels, and malnutrition was related to worse quality of life (QoL). Both tumor volume and sarcopenia were related to long-term mortality in surgically treated PM subjects, while sarcopenia was present both pre-operatively and post-operatively in these subjects. In addition, post-operative sarcopenic subjects showed a decreased 3-year overall survival (OS) in comparison with those who did not have sarcopenia, while pre-operative sarcopenia was importantly related to an increased rate of post-operative adverse outcomes. More studies are needed to validate these claims.

Keywords: low muscle mass; low muscle strength; lung disease; pleural mesothelioma; sarcopenia

DOI: https://doi.org/10.3390/muscles3010006

Nat Rev Dis Primers. 2025 Aug 07. 11(1): 56

Pleural mesothelioma.

Dean A Fennell, Yoshitaka Sekido, Paul Baas, Aliya N Husain, Alessandra Curioni-Fontecedro, Eric Lim, Isabelle Opitz, Charles B Simone, Fraser Brims, Martin Chi-Sang Wong.

Mesothelioma is a lethal cancer caused by exposure to asbestos, which arises predominantly in the pleural lining of the thoracic cavity or, less commonly, in the peritoneum, pericardium or tunica vaginalis. The incidence of mesothelioma increased globally during the late twentieth century, correlating with the use of asbestos, and it continues to rise in some regions. Asbestos tumorigenesis involves fibre persistence that leads to DNA damage mediated by chronic inflammation. The genomic landscape of mesothelioma is predominantly characterized by tumour suppressor alterations, most frequently occurring in BAP1, CDKN2A, CDKN2B, MTAP, NF2 and TP53. Patients with mesothelioma commonly present with fatigue, dyspnoea and/or cough caused by pleural effusion, pain and reduced appetite with weight loss. Imaging, cytology, histology and immunohistochemistry are used in diagnosis and support tumour staging. Genetic tests are relevant to reveal disease predispositions. Mesotheliomas are classified on the basis of histology into three distinct subtypes: epithelioid (the most common subtype with the best prognosis), biphasic and sarcomatoid (worst prognosis). Chemotherapy has been the standard of care for the past two decades but immune checkpoint inhibition targeting PD1 and CTLA4 is now considered to be the first-line treatment, showing improvement compared with chemotherapy. Few randomized trials have investigated the role of surgery and radiotherapy and none has found a clear benefit over systemic therapies. Mesothelioma is associated with considerable negative effects on quality of life in physical and emotional domains and also substantially affects patients' families and caregivers.

DOI: https://doi.org/10.1038/s41572-025-00640-3

Lung Cancer. 2025 Aug 05. pii: S0169-5002(25)00594-X. [Epub ahead of print]207 108702

First-line nivolumab plus ipilimumab in pleural mesothelioma: Efficacy and safety data from the real-world MesoNet study.

BACKGROUND: Despite the approval of nivolumab/ipilimumab, the prognosis of patients with pleural mesothelioma (PM) remains poor. Although this combination has shown improved survival in the landmark CheckMate (CM)-743 trial, evidence from real-world settings remains limited.
METHODS: In this retrospective, multicenter study, the outcome and safety data for 135 consecutive patients with first-line nivolumab/ipilimumab were evaluated among 1,575 adult patients with PM from 12 German cancer centers. Radiologic response and progression were analyzed according to the revised modified RECIST criteria.
RESULTS: The median overall survival (OS) was 13.1 months for the unselected real-world cohort, and 15.5 months for CM-743-eligible patients (16.7 months for the non-epithelioid and 10 months for the epithelioid subtypes). Patients who experienced partial responses to nivolumab/ipilimumab had significantly longer survival than those without (24 months vs. 10.3 months; p = 0.00026). 37 % of patients experienced immune-related adverse events (irAEs), among whom 58 % had grade 3/4 toxicity. IrAEs of any grade were associated with longer survival (17.3 months vs. 11.7 months for patients without irAEs; p = 0.022). Furthermore, grade 1/2 irAEs were associated with even better outcomes when compared to grade 3/4 toxicities (22.7 months vs. 16.7 months median OS) and absence of toxicity (p < 0.0167 for trend).
CONCLUSIONS: Overall survival with first-line nivolumab/ipilimumab in the real-world setting is comparable to the CM-743 results among trial-eligible patients, especially with non-epithelioid tumors, but shorter for the unselected cohort. IrAEs, in particular those of low-grade, were associated with better outcomes. In the absence of predictive biomarkers and with few therapeutic options available, both dual checkpoint blockade and platinum-pemetrexed chemotherapy remain viable first-line regimens.

Keywords: Epithelioid; First-line; Immunotherapy; Mesothelioma; Retrospective cohort

DOI: https://doi.org/10.1016/j.lungcan.2025.108702