Brain Metastases in Diffuse Pleural Mesothelioma: Clinical, Histologic, and Molecular Correlates

Our plain-English summary of Brain Metastases in Diffuse Pleural Mesothelioma: Clinical, Histologic, and Molecular Correlates, by A. Ocejo, C. Wilhem, F.M. Bodd, et al (JTO Clinical and Research Reports, 2026).

The study

• Authors: A. Ocejo, C. Wilhem, F.M. Bodd, A. Arfe, M.G. Zauderer, A. Iqbal, J. Eng, Y. Yu, J.A. Budhu, J. Schefflein, R. Young, M.G. Kris, N.S. Moss, R. Bou-Nassif, C.B. Simone, P.S. Adusumilli, J.L. Sauter, M. Offin
• Journal: JTO Clinical and Research Reports
• Published: 2026;7(4):100968
• Read it: PubMed · Publisher · Free full text

Abstract

Introduction: Brain metastases (BrMs) are poorly studied and likely underreported in diffuse pleural mesothelioma (DPM), limiting understanding of risk factors associated with their development. We evaluated the genomic, histologic, and clinical landscapes of patients with DPM and BrMs.

Methods: We retrospectively reviewed all patients with a mesothelioma diagnosis treated at the Memorial Sloan Kettering Cancer Center between January 1, 2010, and May 1, 2025, with cross-sectional brain imaging. Clinicopathologic data and treatment outcomes were annotated for patients with BrMs.

Results: Among 194 patients with mesothelioma and brain imaging, 16 (8%) had BrMs. Half (n = 8) had tumors of epithelioid histology, 44% (n = 7) biphasic, and 6% (n = 1) sarcomatoid. Compared with our DPM cohort regardless of BrMs (n = 194) or a DPM cohort from The Cancer Genome Atlas (n = 74), patients with DPM and BrMs had a higher prevalence of LATS2 alterations (46% versus 7% versus 12%, respectively [p < 0.00001]). BrMs were typically (88%, n = 14) diagnosed after neurologic symptoms prompting imaging. Among patients with BrMs, the median overall survival from initial mesothelioma diagnosis was 35.4 (95% confidence interval, 19.3-not reached) months and 3.7 (95% confidence interval, 3.5-not reached) months from BrM diagnosis.

Conclusions: Our findings suggest that BrM develops relatively late in DPM, is more common than previously reported, and may be enriched in patients with LATS2 alterations. Prospective, multi-institutional studies with standardized brain imaging are needed to further characterize the incidence of BrMs in DPM and associated risk factors. Routine brain surveillance at diagnosis and with symptoms should be considered for patients with DPM.

© 2026 The Authors.

In plain English

This brief report retrospectively reviewed adults with diffuse pleural mesothelioma seen at Memorial Sloan Kettering Cancer Center from January 2010 to May 2025. Of 444 patients given systemic therapy, 194 had brain imaging, and 16 (8%) had brain metastases. Of these 16, 8 had epithelioid, 7 biphasic and 1 sarcomatoid tumors, and 5 (31%) reported occupational asbestos exposure. Fourteen (88%) were found after neurologic symptoms prompted imaging. Across all 16, the median time from mesothelioma diagnosis to brain metastases was 18.7 months. Among the 13 whose tumors were sequenced, 46% had LATS2 gene alterations. This compared with 7% of the center's cohort of 194 and 12% of a Cancer Genome Atlas cohort of 74. Median overall survival was 35.4 months (95% confidence interval 19.3 to not reached) from mesothelioma diagnosis and 3.7 months (3.5 to not reached) from brain metastasis diagnosis. The authors concluded that brain metastases develop relatively late, are more common than previously reported, and may be enriched in patients with LATS2 alterations. They noted the study was small, retrospective and reliant on symptom-driven imaging, so true incidence may be lower.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Single-institution retrospective analysis (published as a brief report) of medical records, imaging and tumor genetic testing
• Who was studied: Adults (18 or older) with pathologically confirmed diffuse pleural mesothelioma seen at Memorial Sloan Kettering Cancer Center, New York, from January 1, 2010, to May 1, 2025. Of 444 who received systemic therapy, 194 had brain imaging, and 16 of these had brain metastases.
• Exposure: Asbestos was not the exposure studied. The study examined clinical, histologic, molecular and treatment features of patients with brain metastases. Self-reported occupational asbestos exposure was recorded in 5 of the 16 patients with brain metastases (31%).
• Main results:
  • Among the 16 patients with brain metastases, 8 (50%) had epithelioid, 7 (44%) biphasic and 1 (6%) sarcomatoid tumors
  • 13 of the 16 patients with brain metastases (81%) underwent next-generation sequencing
  • LATS2 alterations were found in 46% of the sequenced patients with brain metastases. This compared with 7% of the institution's mesothelioma cohort regardless of brain metastases (n = 194) and 12% of a Cancer Genome Atlas mesothelioma cohort (n = 74), p less than 0.00001.
  • In 14 of the 16 patients (88%), brain metastases were diagnosed after neurologic symptoms prompted imaging
  • For all 16 patients with brain metastases, the median time from mesothelioma diagnosis to brain metastases was 18.7 months (range 0 to 44.1). This includes two patients whose brain metastases were found at initial diagnosis.
  • Among patients with brain metastases, median overall survival from initial mesothelioma diagnosis was 35.4 months (95% CI 19.3 to not reached). 11 of 16 (69%) died.
  • Median overall survival from brain metastasis diagnosis was 3.7 months (95% CI 3.5 to not reached)
  • Survival from brain metastasis diagnosis did not differ significantly by histology: the median was 4.7 months for epithelioid and 3.3 months for non-epithelioid tumors (log-rank p = 0.10)
  • 15 of the 16 patients (94%) received immune checkpoint blockade. Brain metastases were diagnosed during or after this treatment in 8 of these 15 (53%) and before it in 7 (47%).
• The authors' conclusion: The authors concluded that brain metastases develop relatively late in diffuse pleural mesothelioma, are more common than previously reported, and may be enriched in patients with LATS2 alterations. They called for prospective multi-institutional studies with standardized brain imaging. They also suggested screening brain imaging at diagnosis for patients with advanced disease or those being considered for surgery.
• Limitations the authors state:
  • The retrospective design, small sample size and single-center scope may affect generalizability
  • Lack of standardized neurologic assessments and reliance on symptom-based imaging may have missed subtle symptoms or asymptomatic disease
  • Because the cohort was enriched by imaging of symptomatic patients, the true incidence may be lower than observed
  • The 15-year study period introduces temporal confounding due to evolving systemic therapies
  • Paired molecular profiling of primary tumors and brain metastases was not uniformly available
  • Too few patients had leptomeningeal disease to draw conclusions about its prognosis compared with metastases in the brain tissue itself

Topics

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Mesothelioma, Memorial Sloan Kettering, Epithelioid, Histology, Biphasic Mesothelioma, Sarcomatoid, Median Overall Survival.

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