bims-mesote 2026-03-22 papers

Issue of 2026–03–22
six papers selected by
Laura Mannarino, Humanitas Research

J Thorac Oncol. 2026 Mar 13. pii: S1556-0864(26)00134-6. [Epub ahead of print] 103681

The International Association for the Study of Lung Cancer Pleural Mesothelioma Staging Project: Impact of Common Molecular Alterations and PD-L1 Expression on Overall Survival in a Select Cohort from the IASLC 9th Edition Staging Database.

Soo-Ryum Yang, Melissa Y Tjota, Emily Goren, Dorothy J Giroux, Francoise Galateau-Salle, Aliya N Husain, Hedy L Kindler, Michael W Drazer, Rania Aly, Joe Dycoco, Owen Mitchell, Kendra Lechtenberg, William D Travis, Valerie W Rusch, Ming Sound Tsao, Jennifer L Sauter.

INTRODUCTION: There is currently limited information on the prognostic association of molecular aberrations in pleural mesothelioma (PM). We examined the impact of common molecular alterations on overall survival (OS) in a 3-institution cohort from the IASLC 9th edition Staging Project as a pilot study to guide future data collection.
METHODS: Biomarker data included PD-L1 and BAP1 immunohistochemistry (IHC), and somatic genomic aberrations with putative functional impact (pathogenic) revealed by next generation sequencing (NGS). OS was calculated by Kaplan-Meier method and compared between groups by Cox proportional hazard regression. Models were compared using pseudo-R2 and Harrell's C-statistic.
RESULTS: Pathogenic alterations in BAP1 were most common (55.0%, 143/260), followed by CDKN2A (36.2%, 94/260), NF2 (23.8%, 62/260) and TP53 (18.1%, 47/260). Loss of BAP1 expression by IHC was detected in 260/452 (57.5%) cases. PD-L1 expression was positive (> 1% of tumor cells with membranous staining) in 89/200 (44.5%) cases. On univariate analysis, pathogenic alterations in CDKN2A, NF2 and TP53 were associated with worse OS (p<0.001); BAP1 alterations and loss of expression were associated with better OS (p=0.004 and <0.001, respectively); and PD-L1 expression was not associated with OS (p=0.645). Multivariable analyses confirmed OS associations (hazard ratios: CDKN2A, 2.12; NF2, 1.65; TP53, 1.74; BAP1 NGS, 0.58; BAP1 IHC, 0.58). While clinical covariates performed better than molecular alterations alone (C-statistic: 0.67 vs 0.65; R2: 25.3 vs 20.8), a model including BAP1 alterations plus any pathogenic alteration in CDKN2A, NF2, and TP53, along with clinical covariates best predicted survival (C-statistic: 0.70; R2: 37.0).
CONCLUSION: In this large PM cohort,CDKN2A, NF2, and TP53 alterations were associated with worse OS, while BAP1 alterations were associated with better prognosis, independent of clinical variables and histology. Modeling suggests that genomic alterations provide additional prognostic information beyond anatomic TNM and clinicopathologic features.

Keywords: Pleural mesothelioma; TNM; biomarkers; next generation sequencing; staging

DOI: https://doi.org/10.1016/j.jtho.2026.103681

Transl Oncol. 2026 Mar 18. pii: S1936-5233(26)00068-9. [Epub ahead of print]67 102731

Genomic landscape of pleural mesothelioma in Japanese patients: A comprehensive analysis using nationwide database.

Pleural mesothelioma (PM) is a rare and aggressive malignancy. The development of novel therapeutic strategies targeting PM remains an unmet clinical need. However, comprehensive genomic data from Asian populations, particularly from Japanese patients, are limited. This study aimed to elucidate the genomic landscape of PM in Japanese patients using the nationwide Center for Cancer Genomics and Advanced Therapeutics (C-CAT) genomic database. A total of 211 patients registered between June 2019 and March 2025 were analyzed. The most frequent genetic alterations were in BAP1, NF2, TP53, CDKN2A/B, and MTAP. The median tumor mutation burden (TMB) was 1.26, and no microsatellite instability-high patients were detected. The median overall survival (OS) after first-line treatment was 30.6 months. Patients treated with immune checkpoint inhibitors (ICIs) had a significantly better OS than those who did not receive ICIs. In univariate and multivariate analyses, TP53 alterations and high TMB (cutoff value of 1.6) were associated with poor prognosis. These results suggest that integrating clinical and genomic data can enhance prognostic stratification and contribute to the development of precision medicine for PM. This study provides the first large-scale genomic characterization of Japanese PM patients with C-CAT and highlights potential biomarkers for future therapeutic development.

Keywords: Cancer genomic medicine; Comprehensive cancer genomic profiling; Database analysis; Gene alterations; Mesothelioma

DOI: https://doi.org/10.1016/j.tranon.2026.102731

JCO Precis Oncol. 2026 Mar;10(3): e2501171

Diffuse Pleural Mesothelioma in Young (Age ≤50 Years) and Very Young (Age ≤35 Years) Patients: Clinical Characteristics, Genomics, and Survival.

Hely Ollila, Amina Tidjani, Jennifer L Sauter, Soo-Ryum Yang, Charles B Simone, Michael Offin, Prasad S Adusumilli.

PURPOSE: Although we typically consider diffuse pleural mesothelioma (DPM) as a disease of elderly males with a history of asbestos exposure, young individuals are also affected. Given the increasing incidence of cancer in young individuals, we investigated the characteristics and underlying biology of young patients with DPM.
METHODS: We identified patients with DPM age ≤50 years from Memorial Sloan Kettering Cancer Center (1990-2023). Clinicopathologic and genetic characteristics were compared between very young (≤35 years) and young (36-50 years) patients.
RESULTS: We identified 273 patients with DPM age ≤50 years; 39% were female, 40% had a history of self-reported occupational asbestos exposure (very young, 16% v young, 45%; P < .01), 16% had a personal history of cancer (very young, 7% v young, 18%; P = .07), and 70% had a family history of cancer (most commonly breast, lung, and colon). Most frequently altered somatic genes (51/273 tested; 46/51 positive) included BAP1 (22/47, 47%), NF2(18/47, 38%), CDKN2A/B (12/48, 25%), and TP53 (10/48, 21%). Very young patients had less somatic alterations in BAP1 (13% v 63%, P < .01) and a lower tumor mutational burden (0.9 v 1.8 mut/mB, P < .01); they were less frequently carriers of germline alterations (0% [0/8] v 43% [6/14], P = .05). Somatic alterations in CDKN2B were more frequent among females (females 42% v males 12%, P = .03).
CONCLUSION: Young patients with DPM have strong personal and family histories of cancer, and heterogeneous somatic and germline alterations, indicating divergent underlying biology. With the increasing prevalence of young adults with cancers, mesotheliomas, although uncommon, should be on the differential for patients even without asbestos exposure history in this age group.

DOI: https://doi.org/10.1200/PO-25-01171

Turk Gogus Kalp Damar Cerrahisi Derg. 2026 Mar 16.

Factors affecting prognosis in patients diagnosed with epithelioid pleural mesothelioma who underwent surgery.

Neslihan Akanil Fener, Nurcan Ünver, Halide Nur Ürer, Aysu Sinem Koç, Gülçehre Oğuztürk, Ekrem Cengiz Seyhan, Celal Buğra Sezen.

Background: To examine how pathological variables affect prognosis in patients undergoing surgery for epithelioid pleural mesothelioma (PM).
Methods: The study examined 64 patients treated surgery for PM between January 2007 and October 2019, retrospectively. Clinicopathological variables including age, surgical procedure, tumor stage, and detailed histopathological features (nuclear atypia, mitotic count, necrosis, nuclear grading, and tumor grade) were evaluated. Overall survival was analyzed using Kaplan-Meier and Cox proportional hazards regression models. To avoid multicollinearity among interrelated pathological parameters, two separate multivariate Cox models were constructed.
Results: The 5-year survival rate was 8 percent, compared to 62 percent in the first year. Individuals 65 and older had no 5-year survival, whereas patients 65 and younger had a rate of 11 percent (p=0.046). In comparison to groups with mild and moderately high mitotic scores, those with a high mitotic score (p=0.019) had significantly lower median survival and 5-year survival rates. Variables (p<0.15) included in the univariate survival analysis were patients who 65 years and older, type of operation, mitosis, necrosis, tumor stage, nuclear grading, and grade of mesotheliomas. In multivariate analysis, high nuclear grade (Model 1: Hazard ratio [HR]=2.48, 95% confidence interval [CI]: 1.09-5.62, p=0.030) and high tumor grade (Model 2: HR=2.36, 95% CI: 1.05-5.31, p=0.037) were independently associated with worse overall survival.
Conclusion: Pathological grading, represented by either nuclear grade or tumor grade, is the strongest independent prognostic factor for survival in patients with epithelioid PM.

Keywords: Epithelioid pleural mesothelioma; grade; survival

DOI: https://doi.org/10.4274/tjtcs.2026.28506

Ann Surg Oncol. 2026 Mar 16.

Cytoreductive Surgery With or Without HITHOC for Pleural Mesothelioma: A Meta-analysis of Survival and Perioperative Outcomes.

Lucas Monteiro Delgado, Rachid Eduardo Noleto da Nobrega Oliveira, Guilherme Franceschini Machado, Luiza Soares Guerra, Cauã de Toledo Corrêa, Mario Claudio Ghefter, Paulo Manuel-Pêgo Fernandes, Marcello Migliore, Ricardo Mingarini Terra, Paula Duarte D'Ambrosio.

BACKGROUND: Pleural mesothelioma (PM) is a rare and aggressive malignancy with limited overall survival (OS) despite multimodal therapy. Cytoreductive surgery is the standard of care for selected patients. However, locoregional recurrence remains common. Hyperthermic intrathoracic chemotherapy (HITHOC) has been proposed as an adjunct to enhance local disease control.
METHODS: A systematic review and meta-analysis were performed according to PRISMA guidelines and registered in PROSPERO (CRD420251132268). This study searched PubMed, Embase, and Cochrane Library up to 18 July 2025. Pooled hazard ratios (HRs), odds ratios (ORs), and mean differences (MDs) were calculated using random-effects models. Individual patient data (IPD) were reconstructed to generate Kaplan-Meier curves.
RESULTS: Six studies comprising 1060 patients were included. Of these patients, 490 (46.2%) received HITHOC and 570 (53.8%) underwent surgery without HITHOC. Overall survival analysis showed a significant survival benefit for HITHOC (HR, 0.82; 95% confidence interval [CI] 0.71-0.94). The median OS was 21.3 months (95% CI, 19.2-24.9 months) in the HITHOC group versus 18.8 months (95% CI, 17.5-20.9 months) in the non-HITHOC group. No statistically significant differences were found for 30-day mortality (OR, 0.53; 95% CI, 0.16-1.05), 90-day mortality (OR, 0.49; 95% CI, 0.24-1.01), bronchopleural fistula/empyema (OR, 0.55; 95% CI, 0.07-4.12), arrhythmia (OR, 1.17; 95% CI, 0.45-3.06), or hospital length of stay (MD, 0.38 days; 95% CI, -4.61 to 5.37 days).
CONCLUSION: For patients undergoing cytoreductive surgery for pleural mesothelioma, HITHOC is associated with a significant improvement in OS without increased early postoperative risk. These findings support the use of HITHOC in specialized centers with appropriate surgical expertise and patient selection.

Keywords: Cytoreductive surgery; HITHOC; Hyperthermic intrathoracic chemotherapy; Mesothelioma; Meta-analysis; Survival

DOI: https://doi.org/10.1245/s10434-026-19376-9