bims-mesote 2025-07-06 papers

Issue of 2025–07–06
five papers selected by
Laura Mannarino, Humanitas Research

Lung Cancer. 2025 Jun 25. pii: S0169-5002(25)00531-8. [Epub ahead of print]206 108639

Long term side effects after volumetric modulated arc therapy to the pleura in patients with malignant pleural mesothelioma.

Vishruta Dumane, Juliana Runnels, Raja Flores, Andrea Wolf, Weijia Fu, Madhu Mazumdar, Thomas Marron, Jorge Gomez, Kenneth Rosenzweig.

PURPOSE: Lung-sparing pleurectomy/decortication (P/D) is the primary surgical approach for malignant pleural mesothelioma (MPM), and combining it with other therapies enhances patient outcomes.This report presents the extended follow-up results of MPM patients who underwent P/D and received volumetric modulated arc therapy (VMAT).
METHODS: From 2010 to 2021, 81 patients with biopsy-proven malignant pleural mesothelioma, all post-P/D with two intact lungs, were retrospectively analyzed. Some patients received either induction or post-radiation chemotherapy. The target volume was the entire hemithorax, excluding the ipsilateral lung, aiming for 50.4 Gy (1.8 Gy fractions), with a mean lung dose of <20 Gy. Kaplan-Meier analysis determined overall survival (OS) and progression-free survival (PFS). Pulmonary, cardiac, and gastrointestinal events (≥1 year follow-up) were scored using Common Terminology Criteria for Toxicity and Adverse Event Reporting version 5.0 (CTCAE V5.0).
RESULTS: Of the 81 patients, 45 (55.6 %) had ≥1 year of follow-up, median 2.2 years (26 months). Median OS was 14.2 months (95 % CI, 12.1-21) and PFS was 9.1 months (95 % CI, 7.7-12.5). The Kaplan-Meier OS rates were 60.5 % at 1 year, 33.3 % at 2 years; PFS rates were 40.7 % at 1 year, 19.8 % at 2 years. Seven patients (8.6 %) had grade 3 radiationpneumonitis, all resolving with care, and 1 patient experienced grade 3 pericarditis. No grade 3 gastrointestinal events occurred, and no grade 4 or 5 events were seen.
CONCLUSIONS: This study represents the largest retrospective cohort and longest follow-up to date assessing the safety of VMAT. Pleural VMAT proves safe, lacking unexpected long term severe side effects. Future research including treatment plan dose prediction, and advanced deployment techniques will aim to broaden mesothelioma radiotherapy delivery.

DOI: https://doi.org/10.1016/j.lungcan.2025.108639

Oxf Med Case Reports. 2025 Jun;2025(6): omaf082

Metastatic spread of pleural mesothelioma to the peritoneum and gallbladder presenting as recurrent acute cholecystitis.

Mina Fouad, Abed M Zaitoun, Dileep N Lobo.

Malignant pleural mesothelioma, a rare, aggressive cancer primarily associated with asbestos exposure, is characterised by poor prognosis and limited treatment options. Distant metastases are uncommon, and peritoneal involvement is rare, while metastasis to the gallbladder is extremely unusual. We report the case of a patient with malignant pleural mesothelioma undergoing immunotherapy with nivolumab and ipilimumab, who developed recurrent acute cholecystitis. Imaging revealed features of acute cholecystitis with gallstones. She eventually underwent a laparoscopic cholecystectomy because immunotherapy could not be continued in the presence of infection. Histopathological and immunohistochemical analysis confirmed metastatic epithelioid mesothelioma. The gallbladder metastasis was likely haematogenous or from peritoneal seeding, rather than direct spread. This case underscores the importance of a high index of suspicion when evaluating atypical presentations of mesothelioma, particularly in the context of immunotherapy.

Keywords: check-point inhibitors; cholecystectomy; cholecystitis; immunohistochemistry; immunotherapy; pleural mesothelioma

DOI: https://doi.org/10.1093/omcr/omaf082

Ann Thorac Surg. 2025 Jun 28. pii: S0003-4975(25)00565-X. [Epub ahead of print]

Prolonged Survival in Mesothelioma Patients without Surgical Resection: A National Cancer Database Analysis.

Peter L Zhan, Maureen E Canavan, Justin M Bader, Daniel J Boffa, Benjamin J Resio, Gavitt A Woodard.

BACKGROUND: The MARS 2 trial demonstrated no survival benefit from cytoreductive surgery over chemotherapy alone in resectable pleural mesothelioma. Using the National Cancer Database (NCDB), we investigated the necessity of surgery for long-term mesothelioma survival.
METHODS: The NCDB was queried for all adult patients diagnosed with malignant pleural mesothelioma between 2010 and 2018. Kaplan-Meier analysis compared survival across patient cohorts by treatment, including those receiving chemotherapy who declined or forewent a recommended surgery. Survival outcomes were compared to those who underwent chemotherapy and surgery, with and without propensity score matching.
RESULTS: Of 21,768 included patients, 9.4% (2,045) survived ≥5 years. Among them, 1,227 had underwent surgery, and 708 did not receive any surgical intervention. Multivariable logistic regression modeling identified young age, treatment at an academic center, chemotherapy, epithelioid histology, and clinical stage I disease as characteristics associated with improved survival among non-surgically treated patients. In propensity-matched cohorts, patients receiving chemotherapy and refusing surgery (n=116) had nearly identical 5-year OS rates (16.4%; median OS 22.9 months; IQR 10.8-38.2) as those receiving chemotherapy and surgery (n=232; 16.4% 5y OS; median OS 21.9 months; IQR 11.6-50.9; p=0.77).
CONCLUSIONS: NCDB data align with the randomized MARS 2 findings, showing that long-term survival without curative intent surgical resection is possible for some patients with mesothelioma. Notably, over 16% of chemotherapy-treated patients who declined surgery survived ≥5 years after diagnosis. Methods to identify patients who are most likely to achieve long-term survival based on clinical or biologic features are needed to refine prognostication and guide treatment.

Keywords: MARS2; extrapleural pneumonectomy; malignant pleural mesothelioma; pleurectomy decortication; survival

DOI: https://doi.org/10.1016/j.athoracsur.2025.06.015

J Thorac Oncol. 2025 Jun 27. pii: S1556-0864(25)00808-1. [Epub ahead of print]

Clinical and Pathologic Phenotyping of mesotheliomas developing in carriers of Germline BAP1 Mutations.

Michele Carbone, Michael Minaai, Muaiad Kittaneh, Thomas Krausz, Markku M Miettinen, Qiang Pan Hammarström, Lennart Hammarström, Hassan Abolhassani, Ian Pagano, Ronghui Xu, Flavia Novelli, Giovanni Gaudino, Sandra Pastorino, Kavita Y Sarin, Robert T Ripley, Harvey I Pass, David S Schrump, Haining Yang.

INTRODUCTION: Mesothelioma is frequent among carriers of inactivating heterozygous germline BAP1 mutations (BAP1+/-). We studied whether the natural history and the pathology of mesotheliomas in BAP1+/- carriers differed from sporadic, not-genetically related, mesotheliomas.
METHODS: During 1999-2024, we studied 47 families carrying BAP1+/- transmitted in a Mendelian fashion. We characterized these mutations, collected family history, clinical records, prepared family pedigrees and diagnosed their mesotheliomas.
RESULTS: We identified 34 different germline inactivating mutations. Among 238 BAP1+/- carriers aged 27-81, 84 were diagnosed with mesothelioma (35%), 1/84 had evidence of asbestos exposure. No mesothelioma was recorded among 123 siblings/relatives who did not inherit BAP1+/- p<0.0001. The 84 BAP1+/- patients developed mesothelioma at a relatively young age; 45.2% developed multiple cancers. BAP1+/- patients had a florid, diffuse mesothelial hyperplasia often present in both pleural cavities, peritoneum and pericardium. Thoracoscopy and laparoscopy showed several multi-cavity ∼1-3 mm whitish flat lesions, imaging was usually negative for cancer. Histology revealed epithelioid cells lacking BAP1 nuclear staining arranged in tubulo-papillary and trabecular architectures, focally invading sub-mesothelial adipose tissue. These findings may lead to the diagnosis of stage IV metastatic mesothelioma. However, we found that these tumors remain indolent for years and, at this early stage, patients do not require aggressive therapy. We refer to these tumors as "Low-grade-germline-mutant-BAP1-associated-mesotheliomas, L-BAM" to distinguish them from aggressive, therapy-resistant, sporadic mesotheliomas. For the 1/3 of patients who develop lesions visible by imaging, surgery and/or chemotherapy leads to survival of several years, some were cured. Deep invasion by mesothelioma cells with a solid architecture is rare: these cases have poor survival.
CONCLUSIONS: Compared to sporadic mesotheliomas, mesotheliomas developing in BAP1+/- carriers are a different disease, biologically, histologically and clinically: these patients require a tailored clinical approach.

Keywords: BAP1; Diagnosis; Mesothelioma; Prognosis

DOI: https://doi.org/10.1016/j.jtho.2025.06.020