bims-mesote 2024-09-15 papers

Issue of 2024–09–15
four papers selected by
Laura Mannarino, Humanitas Research

Heliyon. 2024 Aug 30. 10(16): e36306

Newest therapeutic strategies impacting on rarest thoracic malignancies: The clinical case report of biphasic pleural mesothelioma.

F Pellicioli, L Sala, F Colonese, E Belloni, M I Abbate, S Canova, A D'Agostino, D L Cortinovis.

A caucasian 62-year-old woman, diagnosed with biphasic pleural mesothelioma (PM) of II stage and BAP1 loss, was treated with therapies included in clinical trial and Early Access Programmes (EAP). During her clinical history, radiological images presented an unusual representation of the disease, with a pseudo progression discussed many times by several specialists. The patient's overall survival improved as a result of the multidisciplinary team and the availability of medicines outside of clinical practice.

Keywords: Case report; Clinical trial; Pleural mesothelioma

DOI: https://doi.org/10.1016/j.heliyon.2024.e36306

Front Oncol. 2024 ;14 1388829

Case report: complete response and long-term survival on third-line immunotherapy in patient with pleural mesothelioma.

Željka Jurić Čuljak, Snježana Tomić, Kristina Šitum, Tihana Boraska Jelavić.

Introduction: Pleural mesothelioma (PM) is a rare neoplasm with median survival time range from 8 to 14 months from diagnosis, and the 5-year survival rate less than 10%, indicating a poor prognosis. The standard treatment for unresectable PM for a long time has been polychemotherapy with pemetrexed and cisplatin for fit patients. Currently, the combination of the anti PD-1 inhibitor nivolumab and the anti-CTLA4 inhibitor ipilimumab has been recognized as the best possible frontline therapy (especially in the sarcomatoid or biphasic type) due to improved outcomes compared to the standard chemotherapy combination. There are still no established predictive biomarkers for any type of systemic therapy in this disease.
Case presentation: Patient who presented with cough and dyspnea has been diagnosed with advanced epithelioid type PM in May 2016. He was treated with three lines of therapy, including an antiangiogenic agent and immunotherapy with pembrolizumab in the third line. Immunotherapy with the PD-1 inhibitor pembrolizumab achieved a complete and prolonged response that transferred to long- term survival. Seven years from diagnosis, the patient is still alive. Histological findings showed an unusually immune-inflamed tumor microenvironment possibly leading to excellent response on immunotherapy.
Conclusions: The course of the disease in our patient points out that we need better predictive biomarkers to direct the treatment algorithm, as some of the patients, although chemorefractory to the best chemotherapy option, can sustain great benefit of second-line chemotherapy in combination with antiangiogenic agent, and especially immunotherapy, even in late lines of therapy.

Keywords: bevacizumab; case report; chemotherapy; immunotherapy; pembrolizumab; pleural mesothelioma

DOI: https://doi.org/10.3389/fonc.2024.1388829

J Imaging Inform Med. 2024 Sep 12.

Convolutional Neural Networks for Segmentation of Pleural Mesothelioma: Analysis of Probability Map Thresholds (CALGB 30901, Alliance).

Mena Shenouda, Eyjólfur Gudmundsson, Feng Li, Christopher M Straus, Hedy L Kindler, Arkadiusz Z Dudek, Thomas Stinchcombe, Xiaofei Wang, Adam Starkey, Samuel G Armato Iii.

The purpose of this study was to evaluate the impact of probability map threshold on pleural mesothelioma (PM) tumor delineations generated using a convolutional neural network (CNN). One hundred eighty-six CT scans from 48 PM patients were segmented by a VGG16/U-Net CNN. A radiologist modified the contours generated at a 0.5 probability threshold. Percent difference of tumor volume and overlap using the Dice Similarity Coefficient (DSC) were compared between the reference standard provided by the radiologist and CNN outputs for thresholds ranging from 0.001 to 0.9. CNN-derived contours consistently yielded smaller tumor volumes than radiologist contours. Reducing the probability threshold from 0.5 to 0.01 decreased the absolute percent volume difference, on average, from 42.93% to 26.60%. Median and mean DSC ranged from 0.57 to 0.59, with a peak at a threshold of 0.2; no distinct threshold was found for percent volume difference. The CNN exhibited deficiencies with specific disease presentations, such as severe pleural effusion or disease in the pleural fissure. No single output threshold in the CNN probability maps was optimal for both tumor volume and DSC. This study emphasized the importance of considering both figures of merit when evaluating deep learning-based tumor segmentations across probability thresholds. This work underscores the need to simultaneously assess tumor volume and spatial overlap when evaluating CNN performance. While automated segmentations may yield comparable tumor volumes to that of the reference standard, the spatial region delineated by the CNN at a specific threshold is equally important.

DOI: https://doi.org/10.1007/s10278-024-01092-z

Environ Pollut. 2024 Sep 10. pii: S0269-7491(24)01642-7. [Epub ahead of print] 124928

Integrated DNA Methylation Analysis of Peripheral Blood from Asbestos Exposed Populations and Patients with Malignant Mesothelioma Reveals Novel Methylation Driver Genes of Diagnostic and Prognostic Relevance.

Lingfang Feng, Tao Li, Biao Xu, Jing Huang, Hailing Xia, Zhaoqiang Jiang, Junfei Chen, Simiao Pan, Xing Zhang, Hua Jiang, Jianlin Lou.

Effective biomarkers are paramount importance for the early detection and prognosis prediction of malignant mesothelioma (MM) which mainly caused by asbestos exposure, and DNA methylation has been demonstrated to be a potentially powerful diagnostic tool. To elucidate the relationship between asbestos exposure and alterations in DNA methylation patterns, as well as the potential diagnostic and prognostic value of differentially methylated regions and CpG sites (DMRs/DMCs) in the progression of MM. The current study employed reduced representation bisulﬁte sequencing (RRBS) to examine the genome-wide DNA methylation profiles in the peripheral blood of individuals exposed to asbestos and those diagnosed with MM, in comparison to the controls, and DMRs/DMCs were subsequently validated by targeted bisulfite sequencing (TBS). Our results suggested that there were 12 DMRs/DMCs exhibiting a consistent change trend of DNA methylation in both RRBS and TBS results. Significant correlations were observed between DNA methylation levels of DMRs/DMCs and the duration of occupational asbestos exposure. The evaluation of the receiver operating characteristic (ROC) curve suggested that the DNA methylation status of FHIT, CCR12P and CDH15 may serve as diagnosis indicator in distinguishing MM patients from healthy controls and those exposed to asbestos. Our findings offer a foundation for the role of DNA methylation in the development of MM induced by asbestos exposure. The potential significance of FHIT, CCR12P and CDH15 DNA methylation alterations in the pathogenesis and advancement of MM disease suggests their potential as diagnostic and prognostic biomarkers.

Keywords: Asbestos exposure; Circulating biomarkers; DNA methylation; Epigenetics; Malignant mesotheliomas

DOI: https://doi.org/10.1016/j.envpol.2024.124928