The Significance of Short Latency in Mesothelioma for Attribution of Causation: Report of a Case with Predisposing Germline Mutations and Review of the Literature

Klebe, Sonja; Hocking, Ashleigh; Soeberg, Matthew; Leigh, James

doi:10.3390/ijerph182413310

Cited by 4 publications

(2 citation statements)

References 57 publications

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“…presentation. [1][2][3] MPM patients have a poor prognosis: 5-year survival rates of 5%-10% are reported with standard chemotherapy. 4 5 Addition of bevacizumab to firstline chemotherapy improved overall survival (OS) by approximately 2 months with manageable adverse events (AEs), while tumor-treating fields (TTF, non-invasive delivery of alternating electric fields to tumors) in combination with platinum-based chemotherapy demonstrated activity in a phase 2 study of epithelioid MPM and was approved by the US Food and Drug Administration.…”

Section: Open Accessmentioning

confidence: 99%

ONCOS-102 plus pemetrexed and platinum chemotherapy in malignant pleural mesothelioma: a randomized phase 2 study investigating clinical outcomes and the tumor microenvironment

Ponce,

Cedrés,

Ricordel

et al. 2023

J Immunother Cancer

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BackgroundONCOS-102, an oncolytic adenovirus expressing granulocyte-macrophage colony-stimulating factor, can alter the tumor microenvironment to an immunostimulatory state. Combining ONCOS-102 with standard-of-care chemotherapy for malignant pleural mesothelioma (MPM) may improve treatment outcomes.MethodsIn this open-label, randomized study, patients with unresectable MPM received intratumoral ONCOS-102 (3×1011virus particles on days 1, 4, 8, 36, 78, and 120) and pemetrexed plus cisplatin/carboplatin (from day 22), or pemetrexed plus cisplatin/carboplatin alone. The primary endpoint was safety. Overall survival (OS), progression-free survival, objective response rate, and tumor immunologic activation (baseline and day 36 biopsies) were also assessed.ResultsIn total, 31 patients (safety lead-in: n=6, randomized: n=25) were enrolled. Anemia (15.0% and 27.3%) and neutropenia (40.0% and 45.5%) were the most frequent grade ≥3 adverse events (AEs) in the ONCOS-102 (n=20) and chemotherapy-alone (n=11) cohorts. No patients discontinued ONCOS-102 due to AEs. No statistically significant difference in efficacy endpoints was observed. There was a numerical improvement in OS (30-month OS rate 34.1% vs 0; median OS 20.3 vs 13.5 months) with ONCOS-102 versus chemotherapy alone in chemotherapy-naïve patients (n=17). By day 36, ONCOS-102 was associated with increased T-cell infiltration and immune-related gene expression that was not observed in the control cohort. Substantial immune activation in the tumor microenvironment was associated with survival at month 18 in the ONCOS-102 cohort.ConclusionsONCOS-102 plus pemetrexed and cisplatin/carboplatin was well tolerated by patients with MPM. In injected tumors, ONCOS-102 promoted a proinflammatory environment, including T-cell infiltration, which showed association with survival at month 18.

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Section: Open Accessmentioning

confidence: 99%

ONCOS-102 plus pemetrexed and platinum chemotherapy in malignant pleural mesothelioma: a randomized phase 2 study investigating clinical outcomes and the tumor microenvironment

Ponce,

Cedrés,

Ricordel

et al. 2023

J Immunother Cancer

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“…that a combination of inherited mutations and asbestos fibres may induce MM with shorter latencies, following short-term exposure or exposure to relatively low doses of asbestos (Klebe et al, 2021).…”

Section: Mesothelioma Overviewmentioning

confidence: 95%

A multimodal approach to identify asbestos and characterise clinically relevant mesothelioma biomarkers

Voloacă¹

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Malignant mesothelioma (MM) is an aggressive cancer of the mesothelium, with long latency and poor overall survival (OS), associated with occupational and environmental exposure to asbestos and other mineral fibres (MF). Considering that early diagnosis has been linked to an improvement in prognosis and treatment response, there is an urgent need for reliable MM biomarkers. Additionally, current asbestos identification techniques lack sensitivity and fail to detect shorter fibres or fibre fragments. Accurately identifying MF within MM samples is not only essential in aiding early diagnosis, but it also plays a key role in linking this diagnosis to asbestos exposure, which has high implications in legal, social, and political matters. The aim of the current project is to (1) develop MM cellular models suitable for laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) imaging, (2) identify various MF based on their metal content within MM in vitro models as well as patient samples using a combination of LA-ICP-MS and LA-ICP-time of flight (TOF)MS instrumentation, (3) investigate the MM metallome in human tissue samples using LA-ICP-MS elemental mapping, and (4) characterise a panel of emerging MM biomarkers using a multi-modal approach. For the first time, this study has developed an asbestos detection technique using LA-ICP-MS imaging to identify MF within MM samples. High-resolution and high-speed analysis suggests that LA-ICP-MS imaging has the potential to be ultimately integrated in the clinical workflow to aid the identification of patients at an earlier and more treatable stage to improve survival outcomes. Moreover, the selected panel of biomarkers was characterised in cellular models, whilst novel biomarkers were tentatively identified using matrix assisted laser desorption ionisation (MALDI)-MS imaging of tissue microarrays, setting the basis for vital future investigations, and ultimately supporting MM biomarker discovery, early diagnosis, and improved prognosis.

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Targeting DNA Damage Response Deficiency in Thoracic Cancers

Bzura,

Spicer,

Dulloo

et al. 2024

Drugs

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The Significance of Short Latency in Mesothelioma for Attribution of Causation: Report of a Case with Predisposing Germline Mutations and Review of the Literature

Cited by 4 publications

References 57 publications

ONCOS-102 plus pemetrexed and platinum chemotherapy in malignant pleural mesothelioma: a randomized phase 2 study investigating clinical outcomes and the tumor microenvironment

ONCOS-102 plus pemetrexed and platinum chemotherapy in malignant pleural mesothelioma: a randomized phase 2 study investigating clinical outcomes and the tumor microenvironment

A multimodal approach to identify asbestos and characterise clinically relevant mesothelioma biomarkers

Targeting DNA Damage Response Deficiency in Thoracic Cancers

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