bims-mesote 2026-08-23 papers

Issue of 2026–08–23
five papers selected by
Laura Mannarino, Humanitas Research

J Natl Compr Canc Netw. 2026 Aug;pii: e267059. [Epub ahead of print]24(8):

Current Surgical Perspectives for Pleural Mesothelioma.

Simon Esteva, Fereidoun Abtin, Gregory A Fishbein, Robert B Cameron, Bryan M Burt, Jane Yanagawa.

This review summarizes the current NCCN recommendations for the surgical management of pleural mesothelioma, highlighting the clinical trials and retrospective analyses that have shaped current practice and informed guideline recommendations. Advances in systemic therapy, surgical technique, and radiation therapy have shifted management toward multidisciplinary care. Contemporary treatment paradigms emphasize the importance of histology, stage, performance status, and institutional expertise when considering surgical intervention. Surgery can still be considered part of the multimodality treatment strategy in carefully selected patients, despite recent evidence suggesting its possible lack of benefit. Further investigation is required to improve patient stratification, refine multimodal regimens, and develop novel therapeutic approaches. This review aims to provide a contemporary framework for understanding the current role of surgery within the broader management of pleural mesothelioma.

DOI: https://doi.org/10.6004/jnccn.2026.7059

Discov Oncol. 2026 Jul 25. pii: 1226. [Epub ahead of print]17(1):

Identification of disulfidptosis-related molecular subtypes in pleural mesothelioma demonstrates a correlation with the immune infiltration, prognosis and therapy efficacy.

Jing Ding, Xuefeng Huang, Wenxiu Yao, Tongyu Lin.

BACKGROUND: Pleural mesothelioma (PM) is a rare and aggressive malignancy with increasing incidence, high mortality, and limited treatment options. Disulfidptosis, a newly identified form of regulated cell death, may play an important role in cancer, but its relevance in PM remains unclear.
METHODS: Transcriptomic and clinical data of PM were obtained from public databases. PM was classified into molecular subtypes based on disulfidptosis-related genes (DRGs). We then compared prognosis, tumor microenvironment, metabolic features, predicted response to immune checkpoint blockade, and chemotherapy sensitivity between subtypes. In addition, a prognostic signature was established, and key genes were identified using random survival forest analysis.
RESULTS: Two novel DRG-defined molecular subtypes were identified in PM. The DRGs-high subtype (Cluster 2) was associated with significantly worse overall survival, an immunosuppressive microenvironment dominated by M2 macrophages, and a lower predicted likelihood of response to immune checkpoint blockade. In contrast, the DRGs-low subtype (Cluster 1) showed metabolic reprogramming toward glycolysis and fatty acid oxidation, increased NK cell infiltration, and reduced sensitivity to chemotherapy. An 11-gene prognostic signature demonstrated predictive performance, with an AUC of 0.95 for 5-year survival (95%CI 0.881-1.013). Random survival forest analysis identified LMNB2 and CDCA2 as key genes, both of which were highly expressed in tumor tissues.
CONCLUSIONS: PM can be classified into two DRG-defined molecular subtypes with distinct prognostic, immune, and metabolic features. These findings provide insights into PM heterogeneity and may support future studies on therapeutic stratification. The prognostic signature remains exploratory and requires validation in independent external cohorts before clinical application.

Keywords: Disulfidptosis; Molecular subtypes; Pleural mesothelioma; Prognostic signature; Tumor microenvironment

DOI: https://doi.org/10.1007/s12672-026-05557-1

Int J Radiat Oncol Biol Phys. 2026 Aug 20. pii: S0360-3016(26)04151-9. [Epub ahead of print]

Proton Therapy for Hemithoracic Pleural Irradiation: A Step toward Safer Radiation Treatment.

Drishti Panse, Ii Charles B Simone, Annemarie Shepherd, Nitin Ohri, Narek Shaverdian, Jana Fox, Haibo Lin, Siyu Yang, Minglei Kang, Zhiqiang Han, Andy Shim, Kenneth Rosenzweig, Robert M Samstein, Stanislav Lazarev.

OBJECTIVES: Malignant pleural mesothelioma (MPM), thymic malignancies with pleural metastases, and thoracic soft tissue sarcoma (STS) with pleural or chest wall involvement are typically aggressive malignancies requiring multimodal therapy. Hemithoracic pleural irradiation has historically been delivered using photon-based intensity-modulated pleural radiation therapy (IMPRINT). Proton-based IMPRINT may reduce dose to critical structures, and mitigate toxicity, however clinical data remains limited. This study evaluates dosimetric parameters and toxicities following intensity-modulated proton therapy (IMPT)-based IMPRINT.
METHODS: We retrospectively analyzed patients with MPM, thymic malignancies, and STS with pleural metastases treated with pencil beam scanning, IMPT-based IMPRINT at a single institution between December 2019 and September 2025, receiving ≥45 Gy. Dosimetric parameters and acute (≤6 months) and late toxicities were assessed using Common Terminology Criteria for Adverse Events v5.0.
RESULTS: Thirty-one consecutive patients were included, with a median age of 50 years. 48% had MPM, 39% had thymic malignancies, and 13% had STS. 97% had ECOG of 0-1. The median pleural dose was 50.4 Gy in 28 fractions, with a boost to 59.4 Gy delivered via simultaneous integrated boost (n=10) or sequential boost (n=3). Median clinical target volume was 2,127 cm³ with V95% of 98%. Median mean total lung dose was 15.3 Gy, contralateral mean lung dose was 0.3 Gy, V5Gy of 1.2 % and V20Gy of 0.03%. Median dose to heart was 14.2 Gy, liver was 16.9 Gy, esophagus was 20.6 Gy, and spinal cord Dmax was 39.3 Gy. At a median follow-up duration of 13.8 months, eight patients (26%) developed grade ≥2 pneumonitis, two of which were grade 3 pneumonitis (6%). No other acute or late grade ≥3 events occurred.
CONCLUSION: In the largest proton cohort of hemithoracic irradiation reported, IMPT-based IMPRINT demonstrated dosimetric advantages and favorable tolerability across a heterogeneous population. IMPT-based IMPRINT is feasible and well tolerated for pleural malignancies.

DOI: https://doi.org/10.1016/j.ijrobp.2026.07.058

Cureus. 2026 Jul;18(7): e112768

Haemophagocytic Lymphohistiocytosis Following Ipilimumab and Nivolumab in Malignant Pleural Mesothelioma: A Case Report.

Cho May Than, Maung Moe, Ye Win, Kyaw Maung.

Haemophagocytic lymphohistiocytosis (HLH) is a rare but potentially fatal hyperinflammatory syndrome caused by dysregulated immune activation. With the increasing use of immune checkpoint inhibitors (ICIs), HLH has emerged as an uncommon but serious immune-related adverse event. An 84-year-old woman with malignant pleural mesothelioma developed fever, rigours, collapse, confusion, worsening cytopenias, cholestatic liver dysfunction, marked hyperferritinaemia, hypertriglyceridaemia, and hypofibrinogenaemia after treatment with ipilimumab and nivolumab. Extensive microbiological investigations were negative. She fulfilled five HLH-2004 diagnostic criteria, supporting a diagnosis of probable ICI-associated HLH. Dexamethasone was started, with rapid clinical and biochemical improvement. This case highlights the importance of recognising HLH as a rare but life-threatening complication of checkpoint inhibitor therapy and supports early corticosteroid treatment, once infection has been reasonably excluded.

Keywords: checkpoint inhibitor; haemophagocytic lymphohistiocytosis; hlh; immune-related adverse event; immunotherapy; ipilimumab; mesothelioma; nivolumab

DOI: https://doi.org/10.7759/cureus.112768

J Natl Compr Canc Netw. 2026 Aug;pii: e260038. [Epub ahead of print]24(8):

Mesothelioma: Pleural, Version 3.2026, NCCN Clinical Practice Guidelines In Oncology.

Mesothelioma is a rare cancer that originates from the mesothelial surfaces of certain sites within the body. Pleural mesothelioma is the most common type and represents approximately 85% of mesotheliomas. The NCCN Guidelines for Mesothelioma: Pleural provide recommendations for evaluation and treatment in patients with pleural mesothelioma. The NCCN Guidelines will continue to be updated annually based on available clinical evidence and panel consensus.

DOI: https://doi.org/10.6004/jnccn.2026.0038