bims-mesote 2021-12-12 papers

bims-mesote

Biomed News

on Mesothelioma

Issue of 2021–12–12
seven papers selected by
Laura Mannarino, Humanitas Research

Early Response to Chemotherapy in Malignant Pleural Mesothelioma Evaluated Using Diffusion-Weighted Magnetic Resonance Imaging: Initial Observations.
Induction Chemotherapy Followed by Pleurectomy Decortication and Hyperthermic Intraoperative Chemotherapy (HITHOC) for Early-Stage Epitheliod Malignant Pleural Mesothelioma-A Prospective Report.
Bioinformatic Analysis of Potential Biomarker for hsa-miR-196b-5p in Mesothelioma.
Correlation of MET-Receptor Overexpression with MET Gene Amplification and Patient Outcome in Malignant Mesothelioma.
Malignant Pleural Mesothelioma: new guidelines make us stronger for defeating this disease.
The highlights of the 15th international conference of the international mesothelioma interest group - Do molecular concepts challenge the traditional approach to pathological mesothelioma diagnosis?
Intrapleural Hyaluronidase in Viscous Malignant Mesothelioma Pleural Effusion.

JTO Clin Res Rep. 2021 Dec;2(12): 100253

Early Response to Chemotherapy in Malignant Pleural Mesothelioma Evaluated Using Diffusion-Weighted Magnetic Resonance Imaging: Initial Observations.

Sebastian Curcean, Lin Cheng, Simona Picchia, Nina Tunariu, David Collins, Matthew Blackledge, Sanjay Popat, Mary O'Brien, Anna Minchom, Martin O Leach, Dow-Mu Koh.

   Introduction: We compared the magnetic resonance imaging total tumor volume (TTV) and median apparent diffusion coefficient (ADC) of malignant pleural mesothelioma (MPM) before and at 4 weeks after chemotherapy, to evaluate whether these are potential early markers of treatment response.
Methods: Diffusion-weighted magnetic resonance imaging was performed in 23 patients with MPM before and after 4 weeks of chemotherapy. The TTV was measured by semiautomatic segmentation (GrowCut) and transferred onto ADC maps to record the median ADC. Test-retest repeatability of TTV and ADC was evaluated in eight patients. TTV and median ADC changes were compared between responders and nonresponders, defined using modified Response Evaluation Criteria In Solid Tumors on computed tomography (CT) at 12 weeks after treatment. TTV and median ADC were also correlated with CT size measurement and disease survival.
Results: The test-retest 95% limits of agreement for TTV were -13.9% to 16.2% and for median ADC -1.2% to 3.3%. A significant increase in median ADC in responders was observed at 4 weeks after treatment (p = 0.02). Correlation was found between CT tumor size change at 12 weeks and median ADC changes at 4 weeks post-treatment (r = -0.560, p = 0.006). An increase in median ADC greater than 5.1% at 4 weeks has 100% sensitivity and 90% specificity for responders (area under the curve = 0.933, p < 0.001). There was also moderate correlation between median tumor ADC at baseline and overall survival (r = 0.45, p = 0.03).
Conclusions: Diffusion-weighted magnetic resonance imaging measurements of TTV and median ADC in MPM have good measurement repeatability. Increase in ADC at 4 weeks post-treatment has the potential to be an early response biomarker.

Keywords:  Biomarker; Diffusion-weighted imaging; Malignant mesothelioma; Modified RECIST; Treatment response

DOI:  https://doi.org/10.1016/j.jtocrr.2021.100253
J Clin Med. 2021 Nov 26. pii: 5542. [Epub ahead of print]10(23):

Induction Chemotherapy Followed by Pleurectomy Decortication and Hyperthermic Intraoperative Chemotherapy (HITHOC) for Early-Stage Epitheliod Malignant Pleural Mesothelioma-A Prospective Report.

Stefano Bongiolatti, Francesca Mazzoni, Ottavia Salimbene, Enrico Caliman, Carlo Ammatuna, Camilla E Comin, Lorenzo Antonuzzo, Luca Voltolini.

  Malignant pleural mesothelioma (MPM) is an aggressive disease with poor prognosis and the current treatment for early-stage MPM is based on a multimodality therapy regimen involving platinum-based chemotherapy preceding or following surgery. To enhance the cytoreductive role of surgery, some peri- or intra-operative intracavitary treatments have been developed, such as hyperthermic chemotherapy, but long-term results are weak. The aim of this study was to report the post-operative results and mid-term outcomes of our multimodal intention-to-treat pathway, including induction chemotherapy, followed by surgery and Hyperthermic Intraoperative THOracic Chemotherapy (HITHOC) in the treatment of early-stage epithelioid MPM. Since 2017, stage I or II epithelioid MPM patients have been inserted in a surgery-based multimodal approach comprising platinum-based induction chemotherapy, followed by pleurectomy and decortication (P/D) and HITHOC with cisplatin. The Kaplan-Meier method was used to estimate overall survival (OS), disease-free survival (DFS) and progression-free survival (PFS). During the study period, n = 65 patients affected by MPM were evaluated by our institutional Multidisciplinary Tumour Board; n = 12 patients with stage I-II who had no progression after induction chemotherapy underwent P/D and HITHOC. Post-operative mortality was 0, and complications developed in n = 7 (58.3%) patients. The median estimated OS was 31 months with a 1-year and 3-year OS of 100% and 55%, respectively. The median PFS was 26 months with 92% of a 1-year PFS, whereas DFS was 19 months with a 1-year DFS rate of 83%. The multimodal treatment of early-stage epithelioid MPM, including induction chemotherapy followed by P/D and HITHOC, was well tolerated and feasible with promising mid-term oncological results.

Keywords:  disease-free survival; epithelioid malignant pleural mesothelioma; hyperthermic intraoperative thoracic chemotherapy; overall survival; pleurectomy and decortication; progression-free survival

DOI:  https://doi.org/10.3390/jcm10235542
Genet Test Mol Biomarkers. 2021 Dec 07.

Bioinformatic Analysis of Potential Biomarker for hsa-miR-196b-5p in Mesothelioma.

Eun Jung Sohn.

  Purpose: Malignant pleural mesothelioma is a rare neoplasia with a poor prognosis, and the majority of patients have advanced disease at the time of presentation. Exposure to asbestos is the most important risk factor for malignant pleural mesothelioma. Materials and Methods: To determine the cytotoxicity of geldanamycin in mesothelioma H28 cells, the MTT assay was used. To determine changes in microRNA (miRNA) expression in geldanamycin-treated H28 cells, miRNA microarray analysis was performed. To determine the function of miR-196b-5p, we performed Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of miR-196b-5p targets predicted by miRwalk. Results: Our data showed that geldanamycin treatment reduced H28 cell viability in a dose-dependent manner. MicroRNA array showed that expression of hsa-miR-196b-5p was downregulated in geldanamycin-treated H28 cells. Geldanamycin regulated miRNAs with roles in processes such as aging, angiogenesis, apoptosis, cell cycle, cell differentiation, cell proliferation, DNA repair, and secretion. Survival analysis showed that low expression of hsa-miR-196b-5p was significantly associated with a better outcome in mesothelioma patients. Expression of miR-196b-5p was also significantly associated with the developmental stages of mesothelioma. To narrow down the target genes of miR-196b-5p, we determined the overlap between the predicted target genes of miR-196b-5p and downregulated mRNAs in ovarian cancer based on the Gene Expression Omnibus dataset GSE12345. PDE1A, LAMA4, and PAPPA were identified as both miR-196b-5p targets and downregulated genes in GSE12345 and were thus considered targets of miR-196b-5p. Gene-miRNA expression correlation analysis showed that PDE1A, LAMA4, and PAPPA expression was negatively correlated with miR-196b-5p expression. Conclusions: We suggest that geldanamycin is potentially useful as an anticancer effect for the treatment of mesothelioma via regulating miR-196b-5p. Furthermore, miR-196b-5p may be a potential biomarker for mesothelioma.

Keywords:  geldanamycin; mesothelioma; microRNA

DOI:  https://doi.org/10.1089/gtmb.2021.0147
Int J Mol Sci. 2021 Nov 28. pii: 12868. [Epub ahead of print]22(23):

Correlation of MET-Receptor Overexpression with MET Gene Amplification and Patient Outcome in Malignant Mesothelioma.

Eric Santoni-Rugiu, Maya Jeje Schuang Lü, Jan Nyrop Jakobsen, Linea Cecilie Melchior, Jesper Ravn, Jens Benn Sørensen.

  Thanks to clinically newly introduced inhibitors of the mesenchymal-epithelial transition (MET) receptor tyrosine-kinase, MET-gene copy number gain/amplification (MET-GCNG/GA) and increased expression of the MET protein are considered very promising therapeutic targets in lung cancer and other malignancies. However, to which extent these MET alterations occur in malignant mesothelioma (MM) remains unclear. Thus, we investigated by well-established immunohistochemistry and fluorescence in situ hybridization methods, the frequency of these alterations in specimens from 155 consecutive MMs of different subtypes obtained from pleural or peritoneal biopsies and pleurectomies. Thirty-three benign reactive mesothelial proliferations (RMPs) were used as controls. MET-protein upregulation was observed in 35% of all MM-cases, though restricted to predominantly epithelioid MMs. We detected low-/intermediate-level MET-GCNG/GA in 22.2% of MET-overexpressing MMs (7.8% of whole MM-cohort) and no MET-GCNG/GA in the other 77.8%, suggesting other upregulating mechanisms. In contrast, 100% of RMPs exhibited no MET-upregulation or MET-GCNG/-GA. Neither MET exon 14 skipping mutations nor MET-fusions were detected as mechanisms of MET overexpression in MM using RNA next-generation sequencing. Finally, in two cohorts of 30 MM patients with or without MET overexpression (MET-positive/-negative) that were matched for several variables and received the same standard chemotherapy, the MET-positive cases showed a significantly lower response rate, but no significant difference in progression-free or overall survival. Our results imply that MET overexpression occurs in a substantial fraction of predominantly epithelioid MMs, but correlates poorly with MET-amplification status, and may impact the likelihood of response to mesothelioma standard chemotherapy. The predictive significance of MET-IHC and -FISH for possible MET-targeted therapy of MM remains to be elucidated.

Keywords:  MET; fluorescence in situ hybridization; gene amplification; immunohistochemistry; malignant mesothelioma; overexpression; patient outcome

DOI:  https://doi.org/10.3390/ijms222312868
Ann Oncol. 2021 Dec 06. pii: S0923-7534(21)04850-X. [Epub ahead of print]

Malignant Pleural Mesothelioma: new guidelines make us stronger for defeating this disease.

J Remon, L E L Hendriks, P Bironzo.

DOI: https://doi.org/10.1016/j.annonc.2021.11.019
Lung Cancer. 2021 Nov 06. pii: S0169-5002(21)00590-0. [Epub ahead of print]163 1-6

The highlights of the 15th international conference of the international mesothelioma interest group - Do molecular concepts challenge the traditional approach to pathological mesothelioma diagnosis?

Sonja Klebe, Francoise Galateau Salle, Rossella Bruno, Luka Brcic, Heather I Chen-Yost, Marie-Claude Jaurand.

  Pathology plays an important role in diagnosing mesothelioma since radiological and clinical findings alone cannot distinguish mesothelioma reliably from its many mimics. The long-held gold standard for pathological diagnosis requires a tissue biopsy that, in addition to mesothelial phenotype, demonstrates invasion, but this is challenged by the WHO recognition of mesothelioma in situ (MIS) and concurrent acknowledgement of all mesotheliomas as malignant. Tumor sampling and ancillary techniques are of paramount importance for diagnosis of MIS. Standardisation of these techniques, cut-off points and terminology, and an updated staging system are urgently required. These clinically relevant issues and the impact of new developments were illustrated at the pathology session of 15th meeting of the International Mesothelioma Interest Group. It was reported that combination of losses in p16 nuclear expression, with cut-off ≤ 1%, and cytoplasmic MTAP with cut-off ≥ 30% demonstrated increased specificity (96%) and high sensitivity (86%) for CDKN2A HD detection. Otherwise, the combination of p16 IHC and CDKN2A HD may improve prognosis. The potential usefulness of pleural effusions for early diagnosis was demonstrated in a retrospective study investigating pleural effusions had been diagnosed as benign prior to mesothelioma diagnosis. Alterations of BAP1 (IHC) and CDKN2A (FISH) were detectable 2 or more years prior diagnosis. Moreover, analysis of gene expression profiles in cytology samples by principal component analysis discriminated reactive hyperpasia from epitheliod mesothelioma. Early diagnosis, including cytology diagnosis, is being acyively investigated. Since no treatment recommendations exist for MIS, pathologists recognise the need for international collaborations to fully characterise this rare entity. Clear communication with the clinical teams is required to ensure optimum patient care. The data reported in this meeting are encouraging and open avenues for further work that will allow even earlier diagnosis and better characterisation of mesothelioma progression, based on changes in gene expression, including epigenetic changes.

Keywords:  Early diagnosis; Fluorescence in situ hybridisation (FISH); Loss of heterozygosis (LOH); Mesothelioma; Mesothelioma in situ; Molecular markers

DOI:  https://doi.org/10.1016/j.lungcan.2021.10.019
Chest. 2021 Dec;pii: S0012-3692(21)01365-9. [Epub ahead of print]160(6): e609-e611

Intrapleural Hyaluronidase in Viscous Malignant Mesothelioma Pleural Effusion.

Chuan T Foo, Anna Paterson, Adam Duckworth, Jurgen Herre.

  Malignant pleural effusion is common in mesothelioma. We report a case of viscous recurrent malignant mesothelioma pleural effusion. The viscosity was due to the presence of hyaluronic acid and resulted in prolonged drainage time. The use of intrapleural hyaluronidase significantly reduced fluid viscosity and drainage duration. No adverse reactions were noted. This novel case highlights the feasibility and safety of the use of intrapleural hyaluronidase in the management of hyaluronic acid-rich viscous malignant pleural effusion.

Keywords:  hyaluronic acid; hyaluronidase; malignant pleural effusion; mesothelioma; viscous pleural effusion

DOI:  https://doi.org/10.1016/j.chest.2021.07.031