bims-mesote 2021-08-08 papers

bims-mesote

Biomed News

on Mesothelioma

Issue of 2021–08–08
eleven papers selected by
Laura Mannarino, Humanitas Research

Phytochemicals in Malignant Pleural Mesothelioma Treatment-Review on the Current Trends of Therapies.
Malignant pleural mesothelioma showing rare morphology indistinguishable from myxofibrosarcoma concomitant with EGFR-mutated lung adenocarcinoma: A case report.
Intraoperative argon-plasma coagulation treatment for patients with malignant pleural mesothelioma.
Pleural mesothelioma in a circus worker.
Implementing CT tumor volume and CT pleural thickness into future staging systems for malignant pleural mesothelioma.
RRM1 and ERCC1 as biomarkers in patients with locally advanced and metastatic malignant pleural mesothelioma treated with continuous infusion of low-dose gemcitabine plus cisplatin.
The use of a next-generation sequencing-derived machine-learning risk-prediction model (OncoCast-MPM) for malignant pleural mesothelioma: a retrospective study.
Hyperthermic intrathoracic chemotherapy (HITHOC) should be included in the guidelines for malignant pleural mesothelioma.
Acute eosinophilic pneumonia after changing dosing schedule of nivolumab.
Evaluation of Deposition and Clearance of Asbestos (Detected by SEM-EDS) in Lungs of Deceased Subjects Environmentally and/or Occupationally Exposed in Broni (Pavia, Northern Italy).
Malignant peritoneal mesothelioma: correlation between CT imaging features and histologic subtypes.

Int J Mol Sci. 2021 Jul 31. pii: 8279. [Epub ahead of print]22(15):

Phytochemicals in Malignant Pleural Mesothelioma Treatment-Review on the Current Trends of Therapies.

Malgorzata Chmielewska-Kassassir, Lucyna A Wozniak.

  Malignant pleural mesothelioma (MPM) is a rare but highly aggressive tumor of pleura arising in response to asbestos fibers exposure. MPM is frequently diagnosed in the advanced stage of the disease and causes poor prognostic outcomes. From the clinical perspective, MPM is resistant to conventional treatment, thus challenging the therapeutic options. There is still demand for improvement and sensitization of MPM cells to therapy in light of intensive clinical studies on chemotherapeutic drugs, including immuno-modulatory and targeted therapies. One way is looking for natural sources, whole plants, and extracts whose ingredients, especially polyphenols, have potential anticancer properties. This comprehensive review summarizes the current studies on natural compounds and plant extracts in developing new treatment strategies for MPM.

Keywords:  MPM; chemotherapy; natural compounds; phytochemicals; polyphenols

DOI:  https://doi.org/10.3390/ijms22158279
Int J Surg Case Rep. 2021 Jul 27. pii: S2210-2612(21)00739-2. [Epub ahead of print]85 106237

Malignant pleural mesothelioma showing rare morphology indistinguishable from myxofibrosarcoma concomitant with EGFR-mutated lung adenocarcinoma: A case report.

Hiroko Onagi, Takuo Hayashi, Tsuyoshi Saito, Satsuki Kishikawa, Kazuya Takamochi, Kenji Suzuki.

   INTRODUCTION AND IMPORTANCE: Primary tumors of the pleura are rare, with malignant mesothelioma being the most common of these neoplasms. Pathological diagnosis of sarcomatoid mesothelioma can be more challenging than that of epithelioid malignant mesothelioma because of its similarities with true sarcomas and restricted or inconsistent expression of mesothelial markers in immunohistochemistry analysis.
PRESENTATION OF CASE: Here, we present an unusual case of malignant pleural mesothelioma concomitant with lung adenocarcinoma in a 72-year-old Japanese man, a smoker with no family history of cancer and asbestos exposure. Malignant pleural mesothelioma is composed of epithelial and spindle-shaped cells. Spindle-shaped cells with scant eosinophilic cytoplasm and hyperchromatic nuclei proliferated in abundant myxoid stroma containing thin-walled blood vessels, mimicking myxofibrosarcoma. The loss of BAP1 (BRCA1-associated protein 1) expression, as assessed by immunohistochemistry, and homozygous deletions of CDKN2A, detected using fluorescence in situ hybridization (FISH), were observed in both components. Targeted sequencing revealed that lung adenocarcinoma harbored EGFR mutations, whereas no mutations were detected in either component of biphasic mesothelioma.
DISCUSSION: Although alcian blue-stained mucins were detected in biphasic mesothelioma subsets, the clinicopathological significance of myxoid stroma in biphasic and sarcomatoid mesothelioma remains largely unknown.
CONCLUSION: Our case presented a unique morphology mimicking myxofibrosarcoma in a sarcomatoid component of biphasic mesothelioma; therefore, it raises a question on the clinicopathological significance of myxoid stroma in sarcomatous areas of biphasic and sarcomatoid mesothelioma.

Keywords:  Biphasic subtype; Homozygous deletions of p16; Malignant mesothelioma; Myxofibrosarcoma

DOI:  https://doi.org/10.1016/j.ijscr.2021.106237
Mol Clin Oncol. 2021 Sep;15(3): 188

Intraoperative argon-plasma coagulation treatment for patients with malignant pleural mesothelioma.

Akira Iyoda, Yoko Azuma, Takashi Sakai, Satoshi Koezuka, Hajime Otsuka, Naobumi Tochigi, Kazutoshi Isobe, Atsushi Sano.

  Malignant pleural mesothelioma (MPM) is often associated with asbestos exposure and carries an extremely poor prognosis. The present study assessed the effectiveness of argon plasma coagulation (APC) treatment in patients with MPM who underwent radical pleural decortication (PD). The clinical data from 11 patients who underwent radical PD treated with APC at Toho University Omori Medical Center from July 2015 to March 2020 were retrospectively analyzed. Clinical features, local recurrence, and clinical prognoses were evaluated. The median overall survival was 18.5 months, and the 1- and 2-year overall survival rates were 71.6 and 43.0%, respectively. One patient survived 5 years but had recurrent tumors. The median disease-free survival was 11.1 months. The 1- and 2-year disease-free survival rates were 49.9 and 12.5%, respectively. Three patients had no recurrences, two of whom were followed continuously (39.6 and 10.2 months). The present study revealed that APC treatment for MPM might be associated with good survival and prognosis. APC as an additional intraoperative treatment for patients with MPM may be further investigated with larger multi-center clinical trials to support its efficacy.

Keywords:  argon plasma coagulation; decortication; mesothelioma

DOI:  https://doi.org/10.3892/mco.2021.2350
J Occup Health. 2021 Jan;63(1): e12250

Pleural mesothelioma in a circus worker.

Carolina Mensi, Carolina Zellino, Marco Polonioli, Barbara Dallari, Angela Cecilia Pesatori, Luciano Riboldi, Dario Consonni.

   OBJECTIVES: To describe an unusual occupational asbestos exposure in a patient with mesothelioma.
METHODS: Since 2000, the Lombardy Mesothelioma Registry (LMR) collects cases of malignant mesothelioma (MM) occurring among people residing in the Lombardy Region, North-West Italy, with a population of 10 million inhabitants. For each case, clinical records and asbestos exposure are collected. Each case is then classified in agreement with the guidelines of the National Mesothelioma Registry.
RESULTS: We identified a male (86 years old), former smoker, who had been working for 53 years as a circus truck driver and tamer of lions and tigers. The first circumstance of exposure was the use of an asbestos tape that wrapped around the hoop in the feline jumping show with a flaming hoop. The second one was the presence of insulating panels protecting the engine placed inside the trucks.
CONCLUSION: A new MM case with an occupational etiology has been found in the public entertainment, an occupational sector not usually considered at risk for the presence of asbestos.

Keywords:  asbestos; circus; mesothelioma; occupational exposure; public entertainment

DOI:  https://doi.org/10.1002/1348-9585.12250
Cancer Imaging. 2021 Aug 03. 21(1): 48

Implementing CT tumor volume and CT pleural thickness into future staging systems for malignant pleural mesothelioma.

Olivia Lauk, Miriam Patella, Thomas Neuer, Bianca Battilana, Thomas Frauenfelder, Thi Dan Linh Nguyen-Kim, Walter Weder, Claudio Caviezel, Sven Hillinger, Ilhan Inci, Isabelle Opitz.

   OBJECTIVES: Tumor thickness and tumor volume measured by computed tomography (CT) were suggested as valuable prognosticator for patients' survival diagnosed with malignant pleural mesothelioma (MPM). The purpose was to assess the accuracy of CT scan based preoperatively measured tumor volume and thickness compared to actual tumor weight of resected MPM specimen and pathologically assessed tumor thickness, as well as an analysis of their impact on overall survival (OS).
METHODS: Between 09/2013-08/2018, 74 patients were treated with induction chemotherapy followed by (extended) pleurectomy/decortication ((E)PD). In 53 patients, correlations were made between CT-measured volume and -tumor thickness (cTV and cTT) and actual tumor weight (pTW) based on the available values. Further cTV and pT/IMIG stage were correlated using Pearson correlation. Overall survival (OS) was calculated with Kaplan Meier analysis and tested with log rank test. For correlation with OS Kaplan-Meier curves were made and log rank test was performed for all measurements dichotomized at the median.
RESULTS: Median pathological tumor volume (pTV) and pTW were 530 ml [130 ml - 1000 ml] and 485 mg [95 g - 982 g] respectively. Median (IQR) cTV was 77.2 ml (35.0-238.0), median cTT was 9.0 mm (6.2-13.7). Significant association was found between cTV and pTV (R = 0.47, p < 0.001) and between cTT and IMIG stage (p = 0,001) at univariate analysis. Multivariate regression analysis revealed, that only cTV correlates with pTV. Median follow-up time was 36.3 months with 30 patients dead at the time of the analysis. Median OS was 23.7 months. 1-year and 3-year survival were 90 and 26% respectively and only the cTV remained statistically associated with OS.
CONCLUSION: Preoperatively assessed CT tumor volume and actual tumor volume showed a significant correlation. CT tumor volume may predict pathological tumor volume as a reflection of tumor burden, which supports the integration of CT tumor volume into future staging systems.

Keywords:  Computed tomography tumor volume; Macroscopic complete resection; Malignant pleural mesothelioma; Pathological tumor weight; Pleurectomy/decortication

DOI:  https://doi.org/10.1186/s40644-021-00415-5
BMC Cancer. 2021 Aug 05. 21(1): 892

RRM1 and ERCC1 as biomarkers in patients with locally advanced and metastatic malignant pleural mesothelioma treated with continuous infusion of low-dose gemcitabine plus cisplatin.

Wendy Muñoz-Montaño, Sae Muñiz-Hernández, Alejandro Avilés-Salas, Rodrigo Catalán, Luis Lara-Mejía, Suraj Samtani-Bassarmal, Andres F Cardona, Jorge Mendoza-Desión, Daniel Hernández-Cueto, Altagracia Maldonado, Guillermina Baay-Guzmán, Sara Huerta-Yepes, Oscar Arrieta.

   BACKGROUND: Malignant Pleural Mesothelioma (MPM) is a rare but aggressive neoplasia that usually presents at advanced stages. Even though some advances have been achieved in the management of patients with MPM, this malignancy continuous to impose a deleterious prognosis for affected patients (12-18 months as median survival, and 5-10% 5-year survival rate), accordingly, the recognition of biomarkers that allow us to select the most appropriate therapy are necessary.
METHODS: Immunohistochemistry semi-quantitative analysis was performed to evaluate four different biomarkers (ERCC1, RRM1, RRM2, and hENT-1) with the intent to explore if any of them was useful to predict response to treatment with continuous infusion gemcitabine plus cisplatin. Tissue biopsies from patients with locally advanced or metastatic MPM were analyzed to quantitatively asses the aforementioned biomarkers. Every included patient received treatment with low-dose gemcitabine (250 mg/m2) in a 6-h continuous infusion plus cisplatin 35 mg/m2 on days 1 and 8 every 3 weeks as first-line therapy.
RESULTS: From the 70 eligible patients, the mean and standard deviation (SD) for ERCC1, RRM1, RRM2 and hENT-1 were 286,178.3 (± 219, 019.8); 104,647.1 (± 65, 773.4); 4536.5 (± 5, 521.3); and 2458.7 (± 4, 983.4), respectively. Patients with high expression of RRM1 had an increased median PFS compared with those with lower expression (9.5 vs 4.8 months, p = < 0.001). Furthermore, high expression of RRM1 and ERCC1 were associated with an increased median OS compared with their lower expression counterparts; [(23.1 vs 7.2 months for RRM1 p = < 0.001) and (17.4 vs 9.8 months for ERCC1 p = 0.018)].
CONCLUSIONS: ERCC1 and RRM1 are useful biomarkers that predict better survival outcomes in patients with advanced MPM treated with continuous infusion of gemcitabine plus cisplatin.

Keywords:  Biomarkers; ERCC1; Immunohistochemistry; Mesothelioma; RRM1

DOI:  https://doi.org/10.1186/s12885-021-08287-5
Lancet Digit Health. 2021 Jul 28. pii: S2589-7500(21)00104-7. [Epub ahead of print]

The use of a next-generation sequencing-derived machine-learning risk-prediction model (OncoCast-MPM) for malignant pleural mesothelioma: a retrospective study.

Marjorie G Zauderer, Axel Martin, Jacklynn Egger, Hira Rizvi, Michael Offin, Andreas Rimner, Prasad S Adusumilli, Valerie W Rusch, Mark G Kris, Jennifer L Sauter, Marc Ladanyi, Ronglai Shen.

BACKGROUND: Current risk stratification for patients with malignant pleural mesothelioma based on disease stage and histology is inadequate. For some individuals with early-stage epithelioid tumours, a good prognosis by current guidelines can progress rapidly; for others with advanced sarcomatoid cancers, a poor prognosis can progress slowly. Therefore, we aimed to develop and validate a machine-learning tool-known as OncoCast-MPM-that could create a model for patient prognosis.
METHODS: We did a retrospective study looking at malignant pleural mesothelioma tumours using next-generation sequencing from the Memorial Sloan Kettering Cancer Center-Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT). We collected clinical, pathological, and routine next-generation sequencing data from consecutive patients with malignant pleural mesothelioma treated at the Memorial Sloan Kettering Cancer Center (New York, NY, USA), as well as the MSK-IMPACT data. Together, these data comprised the MSK-IMPACT cohort. Using OncoCast-MPM, an open-source, web-accessible, machine-learning risk-prediction model, we integrated available data to create risk scores that stratified patients into low-risk and high-risk groups. Risk stratification of the MSK-IMPACT cohort was then validated using publicly available malignant pleural mesothelioma data from The Cancer Genome Atlas (ie, the TCGA cohort).
FINDINGS: Between Feb 15, 2014, and Jan 28, 2019, we collected MSK-IMPACT data from the tumour tissue of 194 patients in the MSK-IMPACT cohort. The median overall survival was higher in the low-risk group than in the high-risk group as determined by OncoCast-MPM (30·8 months [95% CI 22·7-36·2] vs 13·9 months [10·7-18·0]; hazard ratio [HR] 3·0 [95% CI 2·0-4·5]; p<0·0001). No single factor or gene alteration drove risk differentiation. OncoCast-MPM was validated against the TCGA cohort, which consisted of 74 patients. The median overall survival was higher in the low-risk group than in the high-risk group (23·6 months [95% CI 15·1-28·4] vs 13·6 months [9·8-17·9]; HR 2·3 [95% CI 1·3-3·8]; p=0·0019). Although stage-based risk stratification was unable to differentiate survival among risk groups at 3 years in the MSK-IMPACT cohort (31% for early-stage disease vs 30% for advanced-stage disease; p=0·90), the OncoCast-MPM-derived 3-year survival was significantly higher in the low-risk group than in the high-risk group (40% vs 7%; p=0·0052).
INTERPRETATION: OncoCast-MPM generated accurate, individual patient-level risk assessment scores. After prospective validation with the TCGA cohort, OncoCast-MPM might offer new opportunities for enhanced risk stratification of patients with malignant pleural mesothelioma in clinical trials and drug development.
FUNDING: US National Institutes of Health/National Cancer Institute.

DOI: https://doi.org/10.1016/S2589-7500(21)00104-7
Ann Transl Med. 2021 Jun;9(11): 960

Hyperthermic intrathoracic chemotherapy (HITHOC) should be included in the guidelines for malignant pleural mesothelioma.

Marcello Migliore, Michael Ried, Laureano Molins, Marco Lucchi, Marcello Ambrogi, Tamas F Molnar, Hans-Stefan Hofmann.

DOI: https://doi.org/10.21037/atm-20-7247
Jpn J Clin Oncol. 2021 Aug 03. pii: hyab130. [Epub ahead of print]

Acute eosinophilic pneumonia after changing dosing schedule of nivolumab.

Kanako Shinada, Shuji Murakami, Hideyasu Sugimoto, Haruhiro Saito.



Keywords:  bronchoalveolar lavage; eosinophilic pneumonia; immune checkpoint inhibitor; malignant pleural mesothelioma; nivolumab

DOI:  https://doi.org/10.1093/jjco/hyab130
Front Public Health. 2021 ;9 678040

Evaluation of Deposition and Clearance of Asbestos (Detected by SEM-EDS) in Lungs of Deceased Subjects Environmentally and/or Occupationally Exposed in Broni (Pavia, Northern Italy).

Silvia D Visonà, Silvana Capella, Sofia Bodini, Paola Borrelli, Simona Villani, Eleonora Crespi, Claudio Colosio, Carlo Previderè, Elena Belluso.

  Biodurability is one of the main determinants of asbestos hazardousness for human health. Very little is known about the actual persistence of asbestos in lungs and its clearance, nor about differences in this regard between the different mineralogical types of asbestos. The aim of the present study was to evaluate the amount, the dimensional characteristics and the mineralogic kinds of asbestos in lungs (measured using SEM-EDS) of a series of 72 deceased subjects who were certainly exposed to asbestos (mainly crocidolite and chrysotile) during their life. Moreover, we investigated possible correlations between the lung burden of asbestos (in general and considering each asbestos type), as well as their dimension (length, width, and l/w ratio) and the duration of exposure, the latency- in case of malignant mesothelioma (MM), the survival and the time since the end of exposure. In 62.5% of subjects, asbestos burden in lungs was lower that the threshold considered demonstrative for occupational exposure. In 29.1% of cases no asbestos was found. Chrysotile was practically not detected. The mean length of asbestos fibers and the length to width ratio were significantly related to the duration of exposure to asbestos. No other statistically significant correlations were found between the amount and dimensional characteristics of asbestos (nor with the relative amount of each asbestos type) and the other chronological variables considered. In conclusion, it was pointed out that chrysotile can be completely removed from human lungs in <8 years and, instead, amphiboles persist much more time. The present results suggest, as well, that the finding of no asbestos in lungs cannot rule out the attribution of MM to asbestos (in particular, chrysotile) inhaled in an occupational setting. This point is of crucial importance from a legal point of view.

Keywords:  SEM-EDS; asbestos; asbestos clearance; chrysotile; lung fiber burden; malignant mesothelioma

DOI:  https://doi.org/10.3389/fpubh.2021.678040
Abdom Radiol (NY). 2021 Aug 03.

Malignant peritoneal mesothelioma: correlation between CT imaging features and histologic subtypes.

Isha D Atre, Gaurav V Watane, Mukesh G Harisinghani.

   PURPOSE: To identify correlation between CT imaging features and histologic subtypes of Malignant Peritoneal Mesothelioma (MPM).
METHODS: This was a retrospective single-center study of 51 consecutive patients with the diagnosis of Malignant Peritoneal Mesothelioma (MPM). The tumors were classified into pure epithelioid type and those with sarcomatoid component (pure sarcomatoid and biphasic type). Imaging features of these subtypes were compared for extent and type of peritoneal thickening, omental thickening, abdominal visceral infiltration, abdominal wall infiltration, and loco-regional and distant metastases. Fisher's Exact test was used to correlate the association of imaging features with histology types followed by multivariate analysis using logistic regression test.
RESULTS: 32 males and 19 females with a median age of 63 years (range 35-86 years) were included in the study. 41/51 (80%) were epithelioid histology type and 10/51 (20%) had sarcomatoid component (3 pure sarcomatoid type, 7 biphasic type). Abdominal visceral infiltration was seen more commonly in cases of MPM with sarcomatoid component (p = 0.001). Sarcomatoid type also had a frequent association with metastases (p = 0.001) and discrete masses (p = 0.01). Epithelioid type was commonly associated with ascites (p = 0.04). On multivariate analysis, most significant correlation was identified between the sarcomatoid type and imaging features of metastases (p = 0.001) and visceral infiltration (p = 0.019).
CONCLUSION: Sarcomatoid type of MPM showed significant correlation with more aggressive imaging features of metastases and visceral infiltration as compared to epithelioid type.

Keywords:  Epithelioid; Malignant peritoneal mesothelioma; Mesothelioma; Peritoneum; Sarcomatoid

DOI:  https://doi.org/10.1007/s00261-021-03231-4