bims-mesote 2025-02-02 papers

Issue of 2025–02–02
three papers selected by
Laura Mannarino, Humanitas Research

Eur J Surg Oncol. 2025 Jan 21. pii: S0748-7983(25)00056-3. [Epub ahead of print] 109628

Cytoreductive surgery in diffuse pleural mesothelioma. What have we learnt from MARS2, EORTC-L1205 and other recent studies?

Loïc Lang-Lazdunski.

Cytoreductive surgery remains controversial in pleural mesothelioma. The MARS2 trial suggested that extended pleurectomy decortication following neoadjuvant chemotherapy was associated with no survival benefit, more serious adverse events and poorer quality of life than systemic chemotherapy alone in patients with resectable pleural mesothelioma. However, patient selection, chemotherapy scheme, high surgical mortality (9 %) and poor outcomes in the surgical cohort have been raised by mesothelioma experts as potential issues in MARS2. The EORTC-L1205trial reported high morbidity, but low surgical mortality (1.7 %) and more favourable outcomes, suggesting that well-selected patients could benefit from extended pleurectomy decortication and systemic chemotherapy. Other recently-published studies show that cytoreductive surgery remains a valuable option in well-selected patients offering median survivals of 34-38 months, when the best systemic options combining chemotherapy agents, anti-angiogenics or immune checkpoint inhibitors offer median survivals of 18-24 months. Careful patient selection is essential to avoid futile or detrimental surgery and there is evidence that preservation of the diaphragm is associated with lower morbidity and mortality, better long-term outcomes.

Keywords: Chemotherapy; Immunotherapy; Pleural mesothelioma; Pleurectomy decortication; Surgery

DOI: https://doi.org/10.1016/j.ejso.2025.109628

Medicina (Kaunas). 2025 Jan 16. pii: 144. [Epub ahead of print]61(1):

The Effect of Systemic Inflammation and Clinicopathologic Features on Survival in Malignant Pleural Mesothelioma: A Multicenter Analysis.

Background and Objectives: Malignant pleural mesothelioma (MPM) is a rare and aggressive malignancy with a poor prognosis. Identifying reliable prognostic factors is crucial for risk stratification and optimizing treatment strategies. This study aimed to evaluate the impact of clinicopathologic factors and systemic inflammatory markers on survival outcomes in patients with MPM. Materials and Methods: This retrospective, multicenter study included 217 patients diagnosed with MPM between January 2009 and March 2024. Data on age, gender, histology, disease stage, treatment modalities, and inflammatory markers such as the neutrophil-to-lymphocyte ratio (NLR) and C-reactive protein/albumin ratio (CAR) were collected. Survival outcomes were analyzed using Kaplan-Meier methods, and prognostic factors were evaluated using Cox regression analysis. Results: CAR was identified as an independent prognostic factor for both overall survival (OS) and progression-free survival (PFS). Patients with CAR < 0.98 had significantly longer OS (87.0 months vs. 14.0 months, p < 0.001) and PFS (17.61 months vs. 8.96 months, p = 0.010). While NLR was significant in univariate analysis (OS: 25.0 months for NLR < 2.58 vs. 21.0 months for NLR ≥ 2.58, p = 0.040), it did not retain significance in the multivariate model (p = 0.180). Epithelioid histology and early-stage disease were strongly associated with improved survival outcomes (OS: 32.0 vs. 11.0 months for epithelioid vs. non-epithelioid histology, p < 0.001; 32.0 vs. 12.0 months for early-stage vs. metastatic disease, p < 0.001). Conclusions: CAR is a strong independent prognostic factor in MPM, reflecting systemic inflammation and nutritional status. Epithelioid histology and early-stage disease are associated with significantly longer survival, underscoring the critical role of early detection in improving patient outcomes.

Keywords: C-reactive protein/albumin ratio (CAR); epithelioid histology; malignant pleural mesothelioma; neutrophil/lymphocyte ratio (NLR); survival

DOI: https://doi.org/10.3390/medicina61010144

Cancers (Basel). 2025 Jan 14. pii: 252. [Epub ahead of print]17(2):

Analysis of TERT mRNA Levels and Clinicopathological Features in Patients with Peritoneal Mesothelioma.

Antonio d'Amati, Gabriella Serio, Andrea Quaranta, Luigi Vimercati, Michelina De Giorgis, Loredana Lorusso, Mariella Errede, Vito Longo, Andrea Marzullo, Domenico Ribatti, Tiziana Annese.

BACKGROUND/OBJECTIVES: Telomerase reverse transcriptase (TERT) is the catalytic subunit of the telomerase enzyme responsible for telomere length maintenance and is an important cancer hallmark. Our study aimed to clarify the mRNA expression of TERT in peritoneal mesothelioma (PeM), and to explore the relationship between its expression and the clinicopathological parameters and prognosis of patients with PeM.
METHODS: In a cohort of 13 MpeM patients, we evaluated histotype, nuclear grade, mitotic count, necrosis, inflammation, Ki67, BAP1, MTAP and p16 expression by immunohistochemistry, p16/CDKN2A status by FISH and TERT mRNA expression by RNAscope.
RESULTS: Our results showed several statistical correlations between TERT mRNA-score and other investigated features: (i) a poor positive correlation with BAP1 score (r = 0.06340; p ≤ 0.0001); (ii) a moderate positive correlation with p16 FISH del homo (r = 0.6340; p ≤ 0.0001); (iii) a fair negative correlation with p16 FISH del hetero (r = -0.3965; p ≤ 0.0001); a negative poor correlation with MTAP (r = -0.2443; p ≤ 0.0001); and (iv) a negative fair correlation with inflammatory infiltrate (r = -0.5407; p = 0.0233). Moreover, patients survive for a significantly longer time if they have a low mitotic index adjusted (2-4 mitotic figures per 2 mm2) (p ≤ 0.0001), are male (p = 0.0152), lose BAP1 (p = 0.0152), are p16 positive and present no deletion or heterozygous for p16 (p ≤ 0.01).
CONCLUSIONS: TERT is highly expressed in PeM, but it is not one of the crucial factors in evaluating the prognosis of patients. Nevertheless, the results validate the prognostic significance of the mitotic index, BAP1 loss and p16/CDKN2A status.

Keywords: BAP1; MTAP; RNAscope; TERT mRNA; inflammatory infiltrate; malignant peritoneal mesothelioma; p16

DOI: https://doi.org/10.3390/cancers17020252