scholarly journals PROGNOSTIC VALUES OF MIDKINE, SYNDECAN-1, HYALURONAN SYNTHASE-2, SESTRIN-1, LAMININ SUBUNIT ALPHA-4 AND FIBULIN-3 FOR MALIGNANT PLEURAL MESOTHELIOMA

2021 ◽  
Author(s):  
HAKAN AKGUN ◽  
Selma Metintas ◽  
Guntulu Ak ◽  
Secil Demirkol ◽  
Murat Isbilen ◽  
...  
Keyword(s):  
Survival Time ◽  
Malignant Pleural Mesothelioma ◽  
Multivariate Analyses ◽  
Ex Vivo ◽  
Relevant Literature ◽  
Good Prognosis ◽  
Hyaluronan Synthase ◽  
Pleural Mesothelioma ◽  
Analysis Tool ◽  
Hyaluronan Synthase 2

IntroductionThe prognosis of malignant pleural mesothelioma (MPM) is poor with a limited survival time. In this study, we aimed to examine expression levels of genes selected from relevant literature and to utilize in silico methods to determine genes whose expression could reflect the prognosis of the patients with MPM by ex-vivo validation experimentsMaterial and methodsThe study group consisted of 54 MPM patients treated by chemotherapy. Expression of 6 genes; midkine (MDK), syndecan 1 (SDC1), hyaluronan synthase 2 (HAS2), sestrin 1 (SESN1), laminin subunit alpha 4 (LAMA4), and fibulin 3 (FBLN3) were examined by qPCR in tumor tissues. SESN1 and LAMA4 were identified using an in house R-based script “Unsupervised Survival Analysis Tool." MDK, SDC1, HAS2, and FBLN3 were selected from current literature. We used two housekeeping genes; glucose-6-phosphate dehydrogenase and TATA-box binding protein as controls.ResultsOf the patients, 43 (79.6%) had epithelioid mesothelioma. The median survival for all patients was 10 (±1.2 SE) months (CI 95%; 7.7-12.3). In multivariate analyses, MDK (p=0.007), HAS2 (p=0.008) and SESN1 (p=0.014) expression were related with survival time in whole group. In epithelioid type MPM patients, MDK (p=0.014), FBLN3 (p=0.029), HAS2 (p=0.014) and SESN1 (p=0.045) expression was related with survival time by multivariate analyses.ConclusionsHigh HAS2 and SESN1 expressions and low MDK are potential biomarkers of good prognosis in MPM. High HAS2 and SESN1 expression and low MDK and FBLN3 can also be utilized as biomarkers of good prognosis for epithelioid MPM. Those results should be further investigated in sera, plasma, and pleural effusions

scholarly journals Patient-derived malignant pleural mesothelioma cell cultures: a tool to advance biomarker-driven treatments

Thorax ◽  
2020 ◽  
Vol 75 (11) ◽  
pp. 1004-1008 ◽  
Author(s):  
Nikolaos I Kanellakis ◽  
Rachelle Asciak ◽  
Megat Abd Hamid ◽  
Xuan Yao ◽  
Mark McCole ◽  
...  
Keyword(s):  
Cell Cultures ◽  
Malignant Pleural Mesothelioma ◽  
Poor Prognosis ◽  
Ex Vivo ◽  
Cytotoxic T Cells ◽  
Pleural Mesothelioma ◽  
Ex Vivo Model ◽  
High Throughput Drug Screening ◽  
Aggressive Cancer ◽  
Malignant Pleural Mesothelioma Cell

Malignant pleural mesothelioma (MPM) is an aggressive cancer, associated with poor prognosis. We assessed the feasibility of patient-derived cell cultures to serve as an ex vivo model of MPM. Patient-derived MPM cell cultures (n=16) exhibited stemness features and reflected intratumour and interpatient heterogeneity. A subset of the cells were subjected to high-throughput drug screening and coculture assays with cancer-specific cytotoxic T cells and showed diverse responses. Some of the biphasic MPM cells were capable of processing and presenting the neoantigen SSX-2 endogenously. In conclusion, patient-derived MPM cell cultures are a promising and faithful ex vivo model of MPM.

Phase III Study of Pemetrexed in Combination With Cisplatin Versus Cisplatin Alone in Patients With Malignant Pleural Mesothelioma

2003 ◽  
Vol 21 (14) ◽  
pp. 2636-2644 ◽  
Author(s):  
Nicholas J. Vogelzang ◽  
James J. Rusthoven ◽  
James Symanowski ◽  
Claude Denham ◽  
E. Kaukel ◽  
...  
Keyword(s):  
Folic Acid ◽  
Survival Time ◽  
Median Survival ◽  
Malignant Pleural Mesothelioma ◽  
Median Survival Time ◽  
Response Rates ◽  
Phase Iii ◽  
Vitamin B ◽  
Pleural Mesothelioma ◽  
Time To Progression

Purpose: Patients with malignant pleural mesothelioma, a rapidly progressing malignancy with a median survival time of 6 to 9 months, have previously responded poorly to chemotherapy. We conducted a phase III trial to determine whether treatment with pemetrexed and cisplatin results in survival time superior to that achieved with cisplatin alone. Patients and Methods: Chemotherapy-naive patients who were not eligible for curative surgery were randomly assigned to receive pemetrexed 500 mg/m2 and cisplatin 75 mg/m2 on day 1, or cisplatin 75 mg/m2 on day 1. Both regimens were given intravenously every 21 days. Results: A total of 456 patients were assigned: 226 received pemetrexed and cisplatin, 222 received cisplatin alone, and eight never received therapy. Median survival time in the pemetrexed/cisplatin arm was 12.1 months versus 9.3 months in the control arm (P = .020, two-sided log-rank test). The hazard ratio for death of patients in the pemetrexed/cisplatin arm versus those in the control arm was 0.77. Median time to progression was significantly longer in the pemetrexed/cisplatin arm: 5.7 months versus 3.9 months (P = .001). Response rates were 41.3% in the pemetrexed/cisplatin arm versus 16.7% in the control arm (P < .0001). After 117 patients had enrolled, folic acid and vitamin B12 were added to reduce toxicity, resulting in a significant reduction in toxicities in the pemetrexed/cisplatin arm. Conclusion: Treatment with pemetrexed plus cisplatin and vitamin supplementation resulted in superior survival time, time to progression, and response rates compared with treatment with cisplatin alone in patients with malignant pleural mesothelioma. Addition of folic acid and vitamin B12 significantly reduced toxicity without adversely affecting survival time.

scholarly journals Genomics and Functional Genomics of Malignant Pleural Mesothelioma

2020 ◽  
Vol 21 (17) ◽  
pp. 6342 ◽  
Author(s):  
Ece Cakiroglu ◽  
Serif Senturk
Keyword(s):  
Functional Genomics ◽  
Malignant Pleural Mesothelioma ◽  
Relevant Literature ◽  
Functional Characterization ◽  
Surgical Techniques ◽  
Genetic Alterations ◽  
Treatment Modalities ◽  
Pleural Mesothelioma ◽  
Term Survival ◽  
Effective Treatments

Malignant pleural mesothelioma (MPM) is a rare, aggressive cancer of the mesothelial cells lining the pleural surface of the chest wall and lung. The etiology of MPM is strongly associated with prior exposure to asbestos fibers, and the median survival rate of the diagnosed patients is approximately one year. Despite the latest advancements in surgical techniques and systemic therapies, currently available treatment modalities of MPM fail to provide long-term survival. The increasing incidence of MPM highlights the need for finding effective treatments. Targeted therapies offer personalized treatments in many cancers. However, targeted therapy in MPM is not recommended by clinical guidelines mainly because of poor target definition. A better understanding of the molecular and cellular mechanisms and the predictors of poor clinical outcomes of MPM is required to identify novel targets and develop precise and effective treatments. Recent advances in the genomics and functional genomics fields have provided groundbreaking insights into the genomic and molecular profiles of MPM and enabled the functional characterization of the genetic alterations. This review provides a comprehensive overview of the relevant literature and highlights the potential of state-of-the-art genomics and functional genomics research to facilitate the development of novel diagnostics and therapeutic modalities in MPM.

Phase II study of amrubicin for previously treated patients with malignant pleural mesothelioma.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e21095-e21095
Author(s):  
Kazumasa Akagi ◽  
Takaya Ikeda ◽  
Katsumi Nakatomi ◽  
Hirokazu Taniguchi ◽  
Midori Shimada ◽  
...  
Keyword(s):  
Survival Time ◽  
Phase Ii ◽  
Malignant Pleural Mesothelioma ◽  
Phase Ii Study ◽  
Performance Status ◽  
Pleural Mesothelioma ◽  
Line Treatment ◽  
Second Line ◽  
Previously Treated Patients ◽  
Previously Treated

e21095 Background: Malignant pleural mesothelioma (MPM) is a rare disease with few effective treatments and poor prognosis. Although pemetrexed (PEM) and cisplatin for the first-line treatment, and nivolumab for the second-line are considered as the standard treatment for patients with unresectable disease, these effects are still limited. There are no other effective agents for second-line treatment, although PEM-based regimens, vinorelbine, gemcitabine are recommended by some guidelines. Novel therapeutic strategies for the treatment of MPM are urgently required. Amrubicin (AMR) is a chemically synthesized anthracycline-based anticancer drug that inhibits cell growth by stabilizing the cleavable complex via topoisomerase II. The same anthracycline; adriamycin was one of the key drugs for MPM prior to the appearance of PEM, but its efficacy against MPM has not been revealed. Thus, we planned a phase II study of AMR therapy for previously treated MPM. Methods: Eligibility criteria were previously treated patients with unresectable MPM, performance status 0-2, age≦75, and adequate hematological, hepatic and renal function. Patients were treated with injections of AMR 35 mg/m2 on days 1, 2, and 3. The treatments were repeated every 3-4 weeks. The primary endpoint was the response rate (RR), the secondary endpoints were safety, progression-free survival time (PFS), overall survival time (OS). Results: Although the number of target cases was 32 cases, case registration was delayed and evaluation was performed with 10 cases enrolled. Patients' characteristics were as follows: male/female = 9/1; performance status 0/1/2 = 0/10/0; median age (range) = 67 (49-73); histology epithelial/sarcomatoid/mixed = 4/3/3; stage (IMIG) I/II/III/IV/postoperative recurrence = 0/1/4/4/1. RR was 10.0% (1/10), median PFS was 1.6 months and median OS was 6.6 months. Disease control rate was 50.0% (5/10). Adverse events of Grade 3 or 4 were neutropenia 60.0% (6/10), thrombocytopenia 10.0% (1/10), anemia 10.0% (1/10), febrile neutropenia 10.0% (1/10), and pneumonia 10.0% (1/10). Conclusions: This study demonstrated that AMR therapy for previously treated MPM was tolerable. The efficacy was limited, but may be effective in some cases. Clinical trial information: UMIN000006381 .

scholarly journals Malignant Pleural Mesothelioma Nodal Status: Where Are We at?

2021 ◽  
Vol 10 (21) ◽  
pp. 5177
Author(s):  
Sara Ricciardi ◽  
Francesco Carleo ◽  
Massimo O. Jaus ◽  
Marco Di Martino ◽  
Luigi Carbone ◽  
...  
Keyword(s):  
Lymph Node ◽  
Malignant Pleural Mesothelioma ◽  
Relevant Literature ◽  
Prospective Trial ◽  
High Volume ◽  
Lymph Node Status ◽  
Lymph Node Staging ◽  
Pleural Mesothelioma ◽  
Node Positive ◽  
Pre Treatment

Due to the lack of both prospective trial and high-volume retrospective studies, the management of clinical N+ malignant pleural mesothelioma (MPM) patients remains highly debated. Node positive patients show poor survival compared with node-negative ones; thus, lymph node staging appears crucial in determining treatment strategy. Notwithstanding the improvement in pre-treatment staging and the update on lymph node classification in the 8th edition of TNM, several open controversies remain on N parameter. How should we stage suspected N+ patients? How should we treat node positive patients? Which is the definition of a “resectable patient”? Is the site or the number the main prognostic factor for node positive patients? The aim of our narrative review is to analyse the existing relevant literature on lymph node status in MPM.

scholarly journals Comparison of VATS Pleurectomy/Decortication Surgery plus Hyperthermic Intrathoracic Chemotherapy with VATS talc pleurodesis for the treatment of Malignant Pleural Mesothelioma: a randomized pilot study

2021 ◽  
Author(s):  
Marcello Migliore ◽  
Maria Fiore ◽  
Rosario Tumino ◽  
Tommaso Filippini ◽  
Marco Nardini ◽  
...  
Keyword(s):  
Survival Time ◽  
Malignant Pleural Mesothelioma ◽  
Cox Regression ◽  
Pilot Trial ◽  
Primary Objective ◽  
Pleural Mesothelioma ◽  
Talc Pleurodesis ◽  
Cox Regression Analysis ◽  
Group A ◽  
Group B

Introduction No previous study provides compelling evidence to convince surgeons to opt for one procedure over another for the treatment of Malignant Pleural Mesothelioma (MPM). Hyperthermic intrathoracic chemotherapy (HITHOC) adjunct to surgery for MPM has no definite role. The primary objective of this randomized pilot trial was to evaluate the feasibility for future large studies. Method The study design was a prospective randomized three-centric pilot trial (ISRCTN12709516). We recruited patients diagnosed with MPM and prospectively assigned them to two groups: Group A Video Assisted Thoracic Surgery (VATS) talc pleurodesis or Group B VATS P/D plus HITHOC. The main outcome measures were description of study feasibility. We collected socio-demographic and clinical patients information. Data of Kaplan-Meier survival analysis and Cox regression analysis are presented. Results From November-2011 to July-2017 24 males and 3 females, with a median age of 68-years were enrolled (recruitment rate 5 patients/year). Preoperative stage was I-II, and 18 had epithelioid type. 14 patients were in the Group A. Operative mortality was 0. Follow-up ranged from 6 to 80 months. The median overall survival time started to diverge at 20 months. In Group A, it was 19 months (95% CI:12-25) and in Group B, it was 28 months (95% CI:0-56). Survival rate for the epithelioid type was 15 months (0-34) in groups A. and 45 months (0-107) in the Group B with an HR 0.77 (95% CI:0.28-2.2). Conclusion These findings suggest that VATS P/D plus HITHOC may improve survival time in MPM patients undergoing surgical treatment and support the need for a larger multicenter randomized clinical trial.

scholarly journals Current evidence and future perspectives of immune-checkpoint inhibitors in unresectable malignant pleural mesothelioma

2020 ◽  
Vol 8 (1) ◽  
pp. e000461 ◽  
Author(s):  
Katsuyuki Hotta ◽  
Nobukazu Fujimoto
Keyword(s):  
Malignant Pleural Mesothelioma ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Relevant Literature ◽  
Predictive Biomarkers ◽  
Current Evidence ◽  
Pleural Mesothelioma ◽  
First Line ◽  
Platinum Based Chemotherapy

Platinum-based chemotherapy is commonly used as the standard first-line treatment for unresectable malignant pleural mesothelioma (MPM). However, in recent times, immune-checkpoint inhibitors (ICIs) have led to a paradigm shift. Herein, we review relevant literature and ongoing trials of ICIs used as both first-line and salvage therapies. Specifically, in the Japanese single-arm, phase II trial, the MERIT trial, nivolumab, an antiprogrammed cell death 1 (PD-1) antibody showed favorable efficacy when used as a salvage therapy. Currently, multiple ICI monotherapy or combination therapy trials have been conducted, which could provide further evidence. Among available ICIs, the anti-PD-1 antibody is promising for unresectable MPM, despite the limited efficacy of anti-CTLA4 monotherapy. Ongoing studies will further confirm the potential efficacy of ICIs for MPM, as observed across other malignancies. It is also crucial to identify any clinically useful predictive biomarkers that could reveal ICIs with maximal effects in MPM.

Methodology for lognormal modelling of malignant pleural mesothelioma survival time distributions: a study of 5580 case histories from Europe and USA

2004 ◽  
Vol 49 (17) ◽  
pp. 3991-4004 ◽  
Author(s):  
Richard F Mould ◽  
Michael Lahanas ◽  
Bernard Asselain ◽  
David Brewster ◽  
Sjaak A Burgers ◽  
...  
Keyword(s):  
Survival Time ◽  
Malignant Pleural Mesothelioma ◽  
Pleural Mesothelioma ◽  
Case Histories

Liposomal doxorubicin and cisplatin as first-line chemotherapy in unresectable malignant pleural mesothelioma: A phase II study

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e13507-e13507
Author(s):  
O. Arrieta ◽  
L. A. Medina ◽  
E. Guzmán ◽  
M. A. Rios Trejo ◽  
D. Mendoza ◽  
...  
Keyword(s):  
Malignant Pleural Mesothelioma ◽  
Liposomal Doxorubicin ◽  
Tumor Tissue ◽  
Good Prognosis ◽  
Phase Iii ◽  
Stage Iii ◽  
Pleural Mesothelioma ◽  
Highly Active ◽  
Initial Injection

e13507 Background: Malignant pleural mesothelioma (MPM) is a poor prognosis neoplasm. Its worldwide incidence is rising but until recently chemotherapy has not been shown to be effective in its treatment. The combination of cisplatin and pemetrexed is the approved “standard” treatment in unresectable MPM. Liposomal doxorubicin (LD) consists of pegylated phospholipid- vesicles that encapsulate doxorubicin conferring minimal capture from the reticulo-endothelial system resulting in a greater serum half- life, an enhanced liposome deposition in the tumor and a lower degree of toxicity. We evaluated the combination of LD and Cisplatin (Cis) in chemonaive patients with unresectable MPM. Methods: From September 2006 to October 2008, consecutive patients with stage III / IV MPM were included to receive LD 40 mg/m2 and Cis 60 mg/m2 every 21 days for a maximum of 4 cycles. Imaging studies were performed prior and after 2 cycles to assess response. Gamma camera images (GCI) of Tc-99m-labeled LD were acquired to evaluate LD accumulation in measurable tumor tissue. Patients gave written informed consent. Results: Twenty seven patients were included, 81.5% were stage III and 18.5% were IV. According to EORTC prognostic factors, 33.3% and 66.7% had poor and good prognosis, respectively. Median age was 59.2 years (33–80). Median follow-up was of 5.2 ± 0.8 months. Median survival has not been reached. The 2-year overall survival was 52.5% ± 14.2. Median time to progression was 5.0 ± 1.1 months (CI 95%, 2.7–7.3). Overall response was 45.5%, stable disease 36.4% and progression of 18.2%. GCI showed good accumulation and retention (60%) of the labeled LD in tumor tissue at 4 h after the initial injection. There were no toxic deaths. Conclusions: Cis+LD is a highly active regimen in MPM with comparable results to the most active regimens so far reported. A phase III trial is warranted to confirm these findings. No significant financial relationships to disclose.

Sign in / Sign up

Export Citation Format

Share Document