bims-mesote 2026-08-30 papers

Issue of 2026–08–30
three papers selected by
Laura Mannarino, Humanitas Research

Cancers (Basel). 2026 Aug 14. pii: 2624. [Epub ahead of print]18(16):

Sex-Specific Patterns of Asbestos Exposure and Prognostic Biomarkers in Surgically Treated Pleural Mesothelioma: A Retrospective Cohort Study.

Nicolas Pinzon, Shubham Gulati, Andrew Del Re, Emanuela Taioli, Raja Flores, Andrea S Wolf, Stephanie Tuminello.

BACKGROUND/OBJECTIVES: Sex-based differences in asbestos exposure and tumor biology in pleural mesothelioma (PM) remain incompletely characterized. As an expert tertiary center, we sought to systematically characterize asbestos exposure by sex and assess biomarker prognostic relevance in surgically treated pleural mesothelioma.
METHODS: We conducted a retrospective, single-center cohort encompassing all patients who underwent surgical intervention for PM at our institution. Demographic characteristics, asbestos exposure history, tumor biomarker profiles, and survival outcomes were extracted from this database and supplemented by review of the electronic medical record. Sex differences in asbestos exposure and biomarker expression were assessed using Fisher's exact test on an available-case basis, while logistic regression was used to identify predictors of documented asbestos exposure. Overall survival was estimated using Kaplan-Meier analysis; independent associations between biomarkers and mortality were determined via multivariable Cox proportional hazards models adjusted for age, sex, and histological subtype.
RESULTS: Between 2015 and 2024, 106 patients (75% males) underwent surgical intervention for PM, with a median follow-up of 4.4 years. The mean age at surgery was 67.5 years (Standard Deviation [SD], 11). The cohort predominantly consisted of patients with epithelioid histology (n = 86, 81%), followed by biphasic (n = 16, 15%), and sarcomatoid (n = 4, 4%) subtypes. Thirty (28.3%) were alive at last follow-up. Median overall survival was 15.6 months (95% Confidence Interval [CI], 13.8-25.4 months), and 5-year survival was 17.8%. Of 92 patients with available exposure data, 66 (72%) had documented exposure histories. Although most of these exposures were occupational (46, 78%), a striking disparity was observed between occupational exposures in males vs. females (44 [86%] vs. 2 [25%]; n = 8 classifiable females; p < 0.001). Multivariable analysis demonstrated that male sex was associated with increased odds of asbestos exposure (Adjusted Odds Ratio [ORadj], 5.45; 95% Confidence Interval [CI], 1.90-16.35). PD-L1, Ki-67, or BAP1 expression were not associated with sex, age, or asbestos exposure. High Ki-67 (>15%) and PD-L1 (>15%) were associated with a four-fold and three-fold increased risk of mortality (Hazard Ratioadj [HRadj], 4.33 [95% CI, 1.85-10.13] and HRadj, 2.80 [95% CI, 1.39-5.64], respectively), whereas BAP1 loss was not (HRadj, 0.80; 95% CI, 0.45-1.44).
CONCLUSIONS: Our findings underscore the potential value of sex-sensitive screening protocols that more comprehensively assess non-occupational asbestos exposure pathways and offer additional evidence regarding the prognostic relevance of PD-L1, Ki-67, and BAP1 in surgical patients.

Keywords: BAP1; Ki-67; PD-L1; asbestos; exposure history; pleural mesothelioma; sex disparities; thoracic surgery

DOI: https://doi.org/10.3390/cancers18162624

Immunotargets Ther. 2026 ;15 585001

Prognostic Significance of Tumor-Cell VISTA Expression on Survival Outcomes in Nivolumab-Treated Pleural Mesothelioma: The HOT1901 Retrospective Multi-Institutional Study.

Hiroshi Yokouchi, Hiroshi Nishihara, Yoshiyuki Kenmotsu, Kosuke Tsuji, Takayuki Kishikawa, Hajime Kikuchi, Eisaku Miyauchi, Yutaro Nagano, Kenya Kanazawa, Jun Sugisaka, Takayuki Ohkuri, Satoshi Oizumi.

Background: Nivolumab is used as a second-line treatment for pleural mesothelioma (PM); however, predictive or prognostic biomarkers remain unclear. We aimed to identify factors associated with survival in nivolumab-treated PM patients.
Methods: This retrospective, multi-institutional cohort study included patients with PM who received nivolumab monotherapy as a second-line or later treatment at 18 hospitals in Japan. We evaluated associations of progression-free survival (PFS) and overall survival (OS) with baseline clinical variables, protein expression in tumor tissue specimens obtained before first-line therapy by immunohistochemical (IHC), and tumor mutational and copy-number profiles detected by next-generation sequencing (NGS).
Results: Fifty-five patients were enrolled, with evaluable IHC in 42 and NGS in 33. V-domain immunoglobulin suppressor of T-cell activation (VISTA) expression was classified as high or low using a cutoff of 10% VISTA-positive tumor cells. High VISTA expression (n=35) was significantly associated with improved PFS and OS compared with low expression (n=7) (PFS: median, 5.1 vs 2.4 months, p = 0.001; OS: median, 12.8 vs 4.3 months, p = 0.007). Multivariate analysis confirmed high VISTA expression as an independent predictor of prolonged PFS and OS (PFS: hazard ratio [HR] 0.14, p < 0.001; OS: HR 0.38, p = 0.044).
Conclusion: Low tumor-cell VISTA expression was associated with poorer outcomes following nivolumab treatment; however, independent validation in prospective studies with a comparator arm is required before VISTA expression can be used to guide treatment selection. These findings support further investigation of biomarkers for combination strategies such as nivolumab-ipilimumab or chemoimmunotherapy in PM.

Keywords: VISTA; immunohistochemical staining; mesothelioma; next-generation sequencing; survival

DOI: https://doi.org/10.2147/ITT.S585001

Cureus. 2026 Jul;18(7): e113313

First-Line Nivolumab Plus Ipilimumab in Inoperable Epithelioid Malignant Pleural Mesothelioma: Real-World Experience From an Indian Tertiary Care Center.

Avi Shah, Ankit Agarwal, Vishva Rajpuria, Shiv Ghodasara, Jagdish Swami, Vibhav Kanth, Hiren Dangar, Ashish Jakhetiya.

Background Malignant pleural mesothelioma (MPM) is a highly aggressive, rare malignancy with poor prognosis. Standard frontline treatments have traditionally relied on platinum-based chemotherapy doublets, which offer limited long-term survival benefit. This study evaluates the efficacy, clinical-demographic profile, and safety of first-line dual checkpoint inhibition using nivolumab and ipilimumab in patients with inoperable MPM within an Indian tertiary care setting. Materials and methods A retrospective study was conducted from January 2021 to August 2023 at a single tertiary care center in India. Fifteen patients aged ≥ 18 years with histologically confirmed, previously untreated, metastatic/inoperable epithelioid MPM and an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-2 were included. Patients received nivolumab (240 mg intravenously every two weeks) combined with ipilimumab (1 mg/kg intravenously every six weeks) until disease progression or unacceptable toxicity. Response assessments were performed using positron emission tomography (PET) scans at three months using modified RECIST criteria. The primary objective of this study was to evaluate the real-world overall survival (OS), including median OS and one-year OS and safety profile. Secondary objectives included the assessment of objective response rate (ORR) at first reassessment using modified RECIST criteria and the characterization of the clinical-demographic landscape of this population and toxicity profile. Results The cohort consisted of 15 patients (median age: 65 years, range: 40-76), comprising eight males (54%) and seven females (46%). The median number of administered treatment cycles was seven for nivolumab (range: 2-26) and three for ipilimumab (range: 1-10). At the three-month evaluation, nine patients (60%) achieved a partial response, maintaining a stable response through the 12-month follow-up. Six patients (40%) experienced disease progression after the initial assessment, experiencing an OS of less than nine months. At the 12-month endpoint, the one-year OS rate was 60%, with nine patients alive and continuing immunotherapy. Treatment-related adverse events (TRAEs) occurred in 12 patients (80%), with Grade 3 or 4 TRAEs reported in four patients (26%). The most common all-grade TRAEs were diarrhea (26%), hypothyroidism/thyroiditis (20%), and rash (13%). Grade 3/4 toxicities included hepatitis (6%) and severe diarrhea (13%). Conclusion First-line treatment with combined nivolumab and ipilimumab demonstrates promising clinical efficacy, durable responses, and a manageable safety profile in Indian patients presenting with inoperable epithelioid MPM. These real-world outcomes align closely with global clinical trial benchmarks, supporting a chemotherapy-free dual-immunotherapy strategy. Larger prospective randomized trials are needed to validate these findings within the regional population.

Keywords: dual immune checkpoint inhibitors; malignant pleural mesothelioma (mpm); real world data; safety and efficacy; unresectable pleural mesothelioma

DOI: https://doi.org/10.7759/cureus.113313