bims-mesote 2022-01-16 papers

Issue of 2022–01–16
five papers selected by
Laura Mannarino, Humanitas Research

J Clin Med. 2021 Dec 22. pii: 33. [Epub ahead of print]11(1):

The Prognostic Value of 18F-FDG PET Imaging at Staging in Patients with Malignant Pleural Mesothelioma: A Literature Review.

Silvia Taralli, Romina Grazia Giancipoli, Carmelo Caldarella, Valentina Scolozzi, Sara Ricciardi, Giuseppe Cardillo, Maria Lucia Calcagni.

Malignant pleural mesothelioma (MPM) is an aggressive malignancy, frequently diagnosed at locally-advanced/metastatic stages. Due to a very poor prognosis and limited treatment options, the need to identify new prognostic markers represents a great clinical challenge. The prognostic role of metabolic information derived from Positron Emission Tomography (PET) with 18F-Fluoro-deoxy-glucose (18F-FDG) has been investigated in different MPM settings, however with no definitive consensus. In this comprehensive review, the prognostic value of FDG-PET imaging exclusively performed at staging in MPM patients was evaluated, conducting a literature search on PubMed/MEDLINE from 2010 to 2020. From the 19 selected studies, despite heterogeneity in several aspects, staging FDG-PET imaging emerges as a valuable prognostic biomarker, with higher tumor uptake predictive of worse prognosis, and with volumetric metabolic parameters like Metabolic Tumor Volume, (MTV) and Total Lesion Glycolisis (TLG) performing better than SUVmax. However, PET uptake parameters were not always confirmed as independent prognostic factors, especially in patients previously treated with pleurodesis and with a non-epithelioid histotype. Future prospective studies in larger and clinically homogeneous populations, and using more standardized methods of PET images analysis, are needed to further validate the value of staging FDG-PET in the prognostic MPM stratification, with a potential impact on better patient-tailored treatment planning, in the perspective of personalized medicine.

Keywords: 18F-FDG; PET/CT; mesothelioma; pleural; prognosis

DOI: https://doi.org/10.3390/jcm11010033

Front Oncol. 2021 ;11 784081

Biological Pathways Associated With the Development of Pulmonary Toxicities in Mesothelioma Patients Treated With Radical Hemithoracic Radiation Therapy: A Preliminary Study.

Sergio Crovella, Alberto Revelant, Elena Muraro, Ronald Rodrigues Moura, Lucas Brandão, Marco Trovò, Agostino Steffan, Paola Zacchi, Giuliano Zabucchi, Emilio Minatel, Violetta Borelli.

Radical hemithoracic radiotherapy (RHR), after lung-sparing surgery, has recently become a concrete therapeutic option for malignant pleural mesothelioma (MPM), an asbestos-related, highly aggressive tumor with increasing incidence and poor prognosis. Although the toxicity associated to this treatment has been reduced, it is still not negligible and must be considered when treating patients. Genetic factors appear to play a role determining radiotherapy toxicity. The aim of this study is the identification of biological pathways, retrieved through whole exome sequencing (WES), possibly associated to the development of lung adverse effects in MPM patients treated with RHR. The study included individuals with MPM, treated with lung-sparing surgery and chemotherapy, followed by RHR with curative intent, and followed up prospectively for development of pulmonary toxicity. Due to the strong impact of grade 3 pulmonary toxicities on the quality of life, compared with less serious adverse events, for genetic analyses, patients were divided into a none or tolerable pulmonary toxicity (NoSTox) group (grade ≤2) and a severe pulmonary toxicity (STox) group (grade = 3). Variant enrichment analysis allowed us to identify different pathway signatures characterizing NoSTox and Stox patients, allowing to formulate hypotheses on the protection from side effects derived from radiotherapy as well as factors predisposing to a worst response to the treatment. Our findings, being aware of the small number of patients analyzed, could be considered a starting point for the definition of a panel of pathways, possibly helpful in the management of MPM patients.

Keywords: mesothelioma; pulmonary toxicities; radical hemithoracic radiotherapy; thromboembolism; whole exome

DOI: https://doi.org/10.3389/fonc.2021.784081

Cancers (Basel). 2021 Dec 29. pii: 142. [Epub ahead of print]14(1):

A Trimodality, Four-Step Treatment including Chemotherapy, Pleurectomy/Decortication and Radiotherapy in Early-Stage Malignant Pleural Mesothelioma: A Single-Institution Retrospective Case Series Study.

Giovanni Vicidomini, Carminia Maria Della Corte, Antonio Noro, Raimondo Di Liello, Salvatore Cappabianca, Alfonso Fiorelli, Valerio Nardone, Gaetana Messina, Giuseppe Viscardi, Angelo Sangiovanni, Riccardo Monti, Marina Accardo, Floriana Morgillo, Fortunato Ciardiello, Renato Franco, Mario Santini.

BACKGROUND: Multimodality treatment is considered the best treatment strategy for malignant pleural mesothelioma (MPM). However, the ideal combination of them is still a matter of controversy. Here, we report a case series of MPM treated with a trimodality approach: induction chemotherapy (CT), pleurectomy/decortication (P/D), postoperative radiotherapy (RT) and post-operative CT.
METHODS: A retrospective case series of 17 MPM patients treated between 2013 and 2020 is presented. Patients had epithelial or mixed MPM diagnosed by video-assisted thoracoscopy and pathologic IMIG stage I or II disease. Treatment details and radiological data were collected. Induction therapy consisted of combination of cisplatin and pemetrexed, every 21 days for two cycles. P/D was performed 4-6 weeks after induction CT, post-operative RT 3-6 weeks after surgery, while post-operative CT was given 4-6 weeks after RT, with the same schedule of induction.
RESULTS: All patients showed objective response or stability of disease at the restaging following induction CT and underwent surgery by posterolateral thoracotomy. There were two cases of cardiac arrest as major intraoperative complication, both resolved by manual cardiac massage. Minor complications included one hemidiaphragm elevation, 1 anemia requiring blood transfusion, one wound infection, and two persistent air leaks. Median overall survival was 32.1 months, median progression free survival was 23.7 months.
CONCLUSIONS: These results suggest the feasibility of these trimodality treatment scheme for early stage MPM patients. Larger series and long-term prospective studies are needed to confirm the validity of this strategy.

Keywords: chemotherapy; mesothelioma; radiation therapy; statistics; surgery techniques; survival analysis

DOI: https://doi.org/10.3390/cancers14010142

Cancers (Basel). 2021 Dec 30. pii: 182. [Epub ahead of print]14(1):

Salvage Therapy for Relapsed Malignant Pleural Mesothelioma: A Systematic Review and Network Meta-Analysis.

Yu-Chen Tsai, Hsiao-Ling Chen, Tai-Huang Lee, Hsiu-Mei Chang, Kuan-Li Wu, Cheng-Hao Chuang, Yong-Chieh Chang, Yu-Kang Tu, Jen-Yu Hung, Chih-Jen Yang, Inn-Wen Chong.

Patients with malignant pleural mesothelioma (MPM) have very poor prognoses, and pemetrexed plus platinum is the standard first-line therapy. However, the second-line therapy for relapsed MPM remains controversial. A comprehensive search was performed to identify randomized controlled trials (RCTs) evaluating various second-line regimens in patients with relapsed MPM. Indirect comparisons of overall survival (OS) and progression-free survival (PFS) were performed using network meta-analysis. Surface under the cumulative ranking curve (SUCRA) values were used to rank the included treatments according to each outcome. Nivolumab alone or nivolumab plus ipilimumab provided significantly longer OS than placebo (hazard ratio (HR): 0.72, 95% confidence interval (CI): 0.55-0.94 for nivolumab alone; HR: 0.54, 95% CI: 0.31-0.92 for nivolumab plus ipilimumab). The best SUCRA ranking for OS was identified for nivolumab plus ipilimumab (SUCRA: 90.8%). Tremelimumab, vorinostat, nivolumab alone, chemotherapy (CTX), asparagine-glycine-arginine-human tumor necrosis factor plus CTX, and nivolumab plus ipilimumab all produced noticeable PFS benefits compared with placebo. Nivolumab plus ipilimumab had the best PFS ranking (SUCRA: 92.3%). Second-line treatment with nivolumab plus ipilimumab provided the OS and PFS outcomes for patients with relapsed MPM.

Keywords: NGR-hTNF; anetumab; chemotherapy; ipilimumab; malignant pleural mesothelioma (MPM); network meta-analysis; nivolumab; pembrolizumab; tremelimumab; vorinostat

DOI: https://doi.org/10.3390/cancers14010182

Medicine (Baltimore). 2022 Jan 07. 101(1): e28517

Diagnostic method for malignant pleural effusion distinguishing malignant mesothelioma from lung cancer using pleural carcinoembryonic antigen and hyaluronic acid levels.

Takeshi Saraya, Kosuke Ohkuma, Masachika Fujiwara, Haruyuki Ishii.

ABSTRACT: Malignant mesothelioma (MM) is difficult to diagnose because of the lack of parenchymal opacities, often revealing minimal or absent pleural thickening. Furthermore, pleural effusion has diverse differential diagnoses, including malignancies, infections, as well as collagen vascular and other benign diseases. In general practice, lung cancer (LC) is the most common malignancy causing pleural effusion; therefore, a simple method using pleural diagnostic markers to differentiate between LC and mesothelioma is crucial.We retrospectively reviewed the data of 530 adult patients diagnosed with pleural effusion between January 2010 and December 2020 in an outpatient or inpatient setting. Patients with pathologically diagnosed MM or LC with cytologically positive (class IV or V) pleural effusion were analyzed, and the characteristics of these 2 diseases were compared.During the study period, 27 patients diagnosed with MM and 100 patients diagnosed with LC were enrolled. Receiver operating characteristic curve analysis demonstrated that pleural carcinoembryonic antigen (CEA) and hyaluronic acid (HA) could discriminate MM from LC with an area under the curve of 0.925 (95% confidence interval [CI]: 0.879-0.972, P < .001) and 0.815 (95% CI: 0.686-0.943, P < .001), respectively. To diagnose MM, the accuracy of pleural HA >30,000 ng/mL revealed a sensitivity of 75.0%, specificity of 72.6%, and odds ratio of 7.94 (95% CI: 2.5-25.2, P = .001); pleural CEA <6.0 ng/mL revealed a sensitivity of 95.2%, specificity of 84.9%, smaller negative likelihood ratio of 0.06, and odds ratio of 112.5% (95% CI: 14.4-878.1, P < .001). Multiple logistic regression analysis revealed that these 2 parameters could discriminate MM from LC, with a hazard ratio of 23.6 (95% CI: 2.437-228.1, P = .006) and 252.3 (95% Cl: 16.4-3888.1, P < .001), respectively, and their combination had a high specificity of 98.3%.Pleural CEA (≥6.0 ng/mL) can rule out MM with a high degree of certainty, and the positive results for combination of pleural CEA <6.0 ng/mL and HA >30,000 ng/mL can confirm MM with high specificity, prior to cytological or pathological examinations.

DOI: https://doi.org/10.1097/MD.0000000000028517