Semin Respir Crit Care Med 2019; 40(03): 347-360
DOI: 10.1055/s-0039-1693406
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Malignant Mesothelioma: Has Anything Changed?

Roger Y. Kim
1   Division of Pulmonary, Allergy, and Critical Care, Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania
,
Daniel H. Sterman
2   Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, NYU School of Medicine, New York, New York
,
Andrew R. Haas
3   Section of Interventional Pulmonology and Thoracic Oncology, Division of Pulmonary, Allergy, and Critical Care, Department of Medicine, Perelman School of Medicine of the University of Pennsylvania, Philadelphia, Pennsylvania
› Author Affiliations
Further Information

Publication History

Publication Date:
16 September 2019 (online)

Abstract

Malignant pleural mesothelioma is a rare cancer associated with asbestos exposure and portends a dismal prognosis. Its worldwide incidence has been increasing, and treatment options are currently suboptimal and noncurative. However, since the turn of the century, several encouraging steps have been made toward improving outcomes for mesothelioma patients. An increased understanding of disease pathophysiology has led to more accurate diagnosis and staging, and the establishment of the standard of care first-line pemetrexed/platin doublet chemotherapy regimen in 2003 initially revolutionized treatment. While significant debate remains regarding the preferred approach to surgical and radiation therapy in the context of multimodal therapy, recent breakthroughs in immunotherapy offer hope for another paradigm shift in the near future. This review will summarize the current clinical approach to diagnosis, staging, and treatment of malignant pleural mesothelioma.

 
  • References

  • 1 Yap TA, Aerts JG, Popat S, Fennell DA. Novel insights into mesothelioma biology and implications for therapy. Nat Rev Cancer 2017; 17 (08) 475-488
  • 2 Mutsaers SE. The mesothelial cell. Int J Biochem Cell Biol 2004; 36 (01) 9-16
  • 3 Haas AR, Sterman DH. Malignant pleural mesothelioma: update on treatment options with a focus on novel therapies. Clin Chest Med 2013; 34 (01) 99-111
  • 4 Markowitz S. Asbestos-related lung cancer and malignant mesothelioma of the pleura: selected current issues. Semin Respir Crit Care Med 2015; 36 (03) 334-346
  • 5 Carbone M, Kratzke RA, Testa JR. The pathogenesis of mesothelioma. Semin Oncol 2002; 29 (01) 2-17
  • 6 Bianchi C, Bianchi T. Malignant mesothelioma: global incidence and relationship with asbestos. Ind Health 2007; 45 (03) 379-387
  • 7 Świątkowska B, Szeszenia-Dąbrowska N. Mesothelioma continues to increase even 40 years after exposure - evidence from long-term epidemiological observation. Lung Cancer 2017; 108: 121-125
  • 8 Choe N, Tanaka S, Kagan E. Asbestos fibers and interleukin-1 upregulate the formation of reactive nitrogen species in rat pleural mesothelial cells. Am J Respir Cell Mol Biol 1998; 19 (02) 226-236
  • 9 Pott F, Ziem U, Reiffer FJ, Huth F, Ernst H, Mohr U. Carcinogenicity studies on fibres, metal compounds, and some other dusts in rats. Exp Pathol 1987; 32 (03) 129-152
  • 10 Zanella CL, Posada J, Tritton TR, Mossman BT. Asbestos causes stimulation of the extracellular signal-regulated kinase 1 mitogen-activated protein kinase cascade after phosphorylation of the epidermal growth factor receptor. Cancer Res 1996; 56 (23) 5334-5338
  • 11 Carbone M, Ly BH, Dodson RF. , et al. Malignant mesothelioma: facts, myths, and hypotheses. J Cell Physiol 2012; 227 (01) 44-58
  • 12 Kindler HL, Ismaila N, Armato III SG. , et al. Treatment of malignant pleural mesothelioma: American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol 2018; 36 (13) 1343-1373
  • 13 Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018; 68 (06) 394-424
  • 14 Vogelzang NJ, Rusthoven JJ, Symanowski J. , et al. Phase III study of pemetrexed in combination with cisplatin versus cisplatin alone in patients with malignant pleural mesothelioma. J Clin Oncol 2003; 21 (14) 2636-2644
  • 15 Verma V, Ahern CA, Berlind CG. , et al. Survival by histologic subtype of malignant pleural mesothelioma and the impact of surgical resection on overall survival. Clin Lung Cancer 2018; 19 (06) e901-e912
  • 16 Boutin C, Rey F. Thoracoscopy in pleural malignant mesothelioma: a prospective study of 188 consecutive patients. Part 1: diagnosis. Cancer 1993; 72 (02) 389-393
  • 17 Edmondstone WM. Investigation of pleural effusion: comparison between fibreoptic thoracoscopy, needle biopsy and cytology. Respir Med 1990; 84 (01) 23-26
  • 18 Pinelli V, Laroumagne S, Sakr L, Marchetti GP, Tassi GF, Astoul P. Pleural fluid cytological yield and visceral pleural invasion in patients with epithelioid malignant pleural mesothelioma. J Thorac Oncol 2012; 7 (03) 595-598
  • 19 Galbis JM, Mata M, Guijarro R, Esturi R, Figueroa S, Arnau A. Clinical-therapeutic management of thoracoscopy in pleural effusion: a groundbreaking technique in the twenty-first century. Clin Transl Oncol 2011; 13 (01) 57-60
  • 20 Grossebner MW, Arifi AA, Goddard M, Ritchie AJ. Mesothelioma--VATS biopsy and lung mobilization improves diagnosis and palliation. Eur J Cardiothorac Surg 1999; 16 (06) 619-623
  • 21 Maskell NA, Gleeson FV, Davies RJ. Standard pleural biopsy versus CT-guided cutting-needle biopsy for diagnosis of malignant disease in pleural effusions: a randomised controlled trial. Lancet 2003; 361 (9366): 1326-1330
  • 22 Agarwal PP, Seely JM, Matzinger FR. , et al. Pleural mesothelioma: sensitivity and incidence of needle track seeding after image-guided biopsy versus surgical biopsy. Radiology 2006; 241 (02) 589-594
  • 23 Ordóñez NG. Application of immunohistochemistry in the diagnosis of epithelioid mesothelioma: a review and update. Hum Pathol 2013; 44 (01) 1-19
  • 24 Husain AN, Colby T, Ordonez N. , et al; International Mesothelioma Interest Group. Guidelines for pathologic diagnosis of malignant mesothelioma: 2012 update of the consensus statement from the International Mesothelioma Interest Group. Arch Pathol Lab Med 2013; 137 (05) 647-667
  • 25 Wan C, Shen YC, Liu MQ. , et al. Diagnostic value of fluorescence in situ hybridization assay in malignant mesothelioma: a meta-analysis. Asian Pac J Cancer Prev 2012; 13 (09) 4745-4749
  • 26 Righi L, Duregon E, Vatrano S. , et al. BRCA1-associated protein 1 (BAP1) immunohistochemical expression as a diagnostic tool in malignant pleural mesothelioma classification: a large retrospective study. J Thorac Oncol 2016; 11 (11) 2006-2017
  • 27 Mansfield AS, Symanowski JT, Peikert T. Systematic review of response rates of sarcomatoid malignant pleural mesotheliomas in clinical trials. Lung Cancer 2014; 86 (02) 133-136
  • 28 Meyerhoff RR, Yang CF, Speicher PJ. , et al. Impact of mesothelioma histologic subtype on outcomes in the Surveillance, Epidemiology, and End Results database. J Surg Res 2015; 196 (01) 23-32
  • 29 Vigneswaran WT, Kircheva DY, Ananthanarayanan V. , et al. Amount of epithelioid differentiation is a predictor of survival in malignant pleural mesothelioma. Ann Thorac Surg 2017; 103 (03) 962-966
  • 30 Hollevoet K, Reitsma JB, Creaney J. , et al. Serum mesothelin for diagnosing malignant pleural mesothelioma: an individual patient data meta-analysis. J Clin Oncol 2012; 30 (13) 1541-1549
  • 31 Hollevoet K, Nackaerts K, Gosselin R. , et al. Soluble mesothelin, megakaryocyte potentiating factor, and osteopontin as markers of patient response and outcome in mesothelioma. J Thorac Oncol 2011; 6 (11) 1930-1937
  • 32 Pass HI, Goparaju C, Espin-Garcia O. , et al. Plasma biomarker enrichment of clinical prognostic indices in malignant pleural mesothelioma. J Thorac Oncol 2016; 11 (06) 900-909
  • 33 Creaney J, Robinson BWS. Malignant mesothelioma biomarkers: from discovery to use in clinical practice for diagnosis, monitoring, screening, and treatment. Chest 2017; 152 (01) 143-149
  • 34 Pass HI, Goparaju C. Fibulin-3 as a biomarker for pleural mesothelioma. N Engl J Med 2013; 368 (02) 190
  • 35 Creaney J, Dick IM, Meniawy TM. , et al. Comparison of fibulin-3 and mesothelin as markers in malignant mesothelioma. Thorax 2014; 69 (10) 895-902
  • 36 Kaya H, Demir M, Taylan M. , et al. Fibulin-3 as a diagnostic biomarker in patients with malignant mesothelioma. Asian Pac J Cancer Prev 2015; 16 (04) 1403-1407
  • 37 Rusch VW. ; From the International Mesothelioma Interest Group. A proposed new international TNM staging system for malignant pleural mesothelioma. Chest 1995; 108 (04) 1122-1128
  • 38 Sobin LH, Gospodarowicz MK, Wittekind C. TNM Classification of Malignant Tumours. Hoboken, NJ: Wiley-Blackwell; 2010
  • 39 Berzenji L, Van Schil PE, Carp L. The eighth TNM classification for malignant pleural mesothelioma. Transl Lung Cancer Res 2018; 7 (05) 543-549
  • 40 Nowak AK, Chansky K, Rice DC. , et al; Staging and Prognostic Factors Committee, Advisory Boards and Participating Institutions. The IASLC Mesothelioma Staging Project: proposals for revisions of the T descriptors in the forthcoming eighth edition of the TNM Classification For Pleural Mesothelioma. J Thorac Oncol 2016; 11 (12) 2089-2099
  • 41 Rice D, Chansky K, Nowak A. , et al; Mesothelioma Domain of the IASLC Staging and Prognostic Factors Committee, Advisory Boards and Participating Institutions. The IASLC Mesothelioma Staging Project: proposals for revisions of the N descriptors in the forthcoming eighth edition of the TNM Classification for Pleural Mesothelioma. J Thorac Oncol 2016; 11 (12) 2100-2111
  • 42 Rusch VW, Chansky K, Kindler HL. , et al; IASLC Staging and Prognostic Factors Committee, Advisory Boards, and Participating Institutions. The IASLC Mesothelioma Staging Project: proposals for the M descriptors and for revision of the TNM stage groupings in the forthcoming (Eighth) edition of the TNM Classification for Mesothelioma. J Thorac Oncol 2016; 11 (12) 2112-2119
  • 43 Pass H, Giroux D, Kennedy C. , et al; IASLC Staging and Prognostic Factors Committee, Advisory Boards and Participating Institutions. The IASLC Mesothelioma Staging Project: improving staging of a rare disease through international participation. J Thorac Oncol 2016; 11 (12) 2082-2088
  • 44 Plathow C, Staab A, Schmaehl A. , et al. Computed tomography, positron emission tomography, positron emission tomography/computed tomography, and magnetic resonance imaging for staging of limited pleural mesothelioma: initial results. Invest Radiol 2008; 43 (10) 737-744
  • 45 Klabatsa A, Chicklore S, Barrington SF, Goh V, Lang-Lazdunski L, Cook GJ. The association of 18F-FDG PET/CT parameters with survival in malignant pleural mesothelioma. Eur J Nucl Med Mol Imaging 2014; 41 (02) 276-282
  • 46 Sharif S, Zahid I, Routledge T, Scarci M. Does positron emission tomography offer prognostic information in malignant pleural mesothelioma?. Interact Cardiovasc Thorac Surg 2011; 12 (05) 806-811
  • 47 Rice DC, Steliga MA, Stewart J. , et al. Endoscopic ultrasound-guided fine needle aspiration for staging of malignant pleural mesothelioma. Ann Thorac Surg 2009; 88 (03) 862-868 , discussion 868–869
  • 48 Kang B, Kim MA, Lee BY. , et al. Malignant pleural mesothelioma diagnosed by endobronchial ultrasound-guided transbronchial needle aspiration. Tuberc Respir Dis (Seoul) 2013; 74 (02) 74-78
  • 49 Alvarez JM, Hasani A, Segal A. , et al. Bilateral thoracoscopy, mediastinoscopy and laparoscopy, in addition to CT, MRI and PET imaging, are essential to correctly stage and treat patients with mesothelioma prior to trimodality therapy. ANZ J Surg 2009; 79 (10) 734-738
  • 50 Rice DC, Erasmus JJ, Stevens CW. , et al. Extended surgical staging for potentially resectable malignant pleural mesothelioma. Ann Thorac Surg 2005; 80 (06) 1988-1992 , discussion 1992–1993
  • 51 Armato III SG, Li P, Husain AN. , et al. Radiologic-pathologic correlation of mesothelioma tumor volume. Lung Cancer 2015; 87 (03) 278-282
  • 52 Liu F, Zhao B, Krug LM. , et al. Assessment of therapy responses and prediction of survival in malignant pleural mesothelioma through computer-aided volumetric measurement on computed tomography scans. J Thorac Oncol 2010; 5 (06) 879-884
  • 53 Gill RR, Richards WG, Yeap BY. , et al. Epithelial malignant pleural mesothelioma after extrapleural pneumonectomy: stratification of survival with CT-derived tumor volume. AJR Am J Roentgenol 2012; 198 (02) 359-363
  • 54 Gill RR, Naidich DP, Mitchell A. , et al; Malignant Mesothelioma Volumetric CT Study Group. North American multicenter volumetric CT study for clinical staging of malignant pleural mesothelioma: feasibility and logistics of setting up a quantitative imaging study. J Thorac Oncol 2016; 11 (08) 1335-1344
  • 55 Byrne MJ, Nowak AK. Modified RECIST criteria for assessment of response in malignant pleural mesothelioma. Ann Oncol 2004; 15 (02) 257-260
  • 56 Armato III SG, Nowak AK. Revised modified response evaluation criteria in solid tumors for assessment of response in malignant pleural mesothelioma (version 1.1). J Thorac Oncol 2018; 13 (07) 1012-1021
  • 57 Haas AR, Sterman DH, Musani AI. Malignant pleural effusions: management options with consideration of coding, billing, and a decision approach. Chest 2007; 132 (03) 1036-1041
  • 58 Lee YCG, Fysh ETH. Indwelling pleural catheter: changing the paradigm of malignant effusion management. J Thorac Oncol 2011; 6 (04) 655-657
  • 59 Pien GW, Gant MJ, Washam CL, Sterman DH. Use of an implantable pleural catheter for trapped lung syndrome in patients with malignant pleural effusion. Chest 2001; 119 (06) 1641-1646
  • 60 Davies HE, Mishra EK, Kahan BC. , et al. Effect of an indwelling pleural catheter vs chest tube and talc pleurodesis for relieving dyspnea in patients with malignant pleural effusion: the TIME2 randomized controlled trial. JAMA 2012; 307 (22) 2383-2389
  • 61 Argento AC, Schembri F. The evolving role of the indwelling tunneled pleural catheter. A means to an end. Am J Respir Crit Care Med 2017; 195 (08) 976-978
  • 62 Rintoul RC, Ritchie AJ, Edwards JG. , et al; MesoVATS Collaborators. Efficacy and cost of video-assisted thoracoscopic partial pleurectomy versus talc pleurodesis in patients with malignant pleural mesothelioma (MesoVATS): an open-label, randomised, controlled trial. Lancet 2014; 384 (9948): 1118-1127
  • 63 Yanagawa J, Rusch V. Surgical management of malignant pleural mesothelioma. Thorac Surg Clin 2013; 23 (01) 73-87 , vi
  • 64 Rice D, Rusch V, Pass H. , et al; International Association for the Study of Lung Cancer International Staging Committee and the International Mesothelioma Interest Group. Recommendations for uniform definitions of surgical techniques for malignant pleural mesothelioma: a consensus report of the International Association for the Study of Lung Cancer International Staging Committee and the International Mesothelioma Interest Group. J Thorac Oncol 2011; 6 (08) 1304-1312
  • 65 Batirel HF, Metintas M, Caglar HB. , et al. Adoption of pleurectomy and decortication for malignant mesothelioma leads to similar survival as extrapleural pneumonectomy. J Thorac Cardiovasc Surg 2016; 151 (02) 478-484
  • 66 Flores RM. Pleurectomy decortication for mesothelioma: the procedure of choice when possible. J Thorac Cardiovasc Surg 2016; 151 (02) 310-312
  • 67 Lauk O, Hoda MA, de Perrot M. , et al. Extrapleural pneumonectomy after induction chemotherapy: perioperative outcome in 251 mesothelioma patients from three high-volume institutions. Ann Thorac Surg 2014; 98 (05) 1748-1754
  • 68 Mollberg NM, Vigneswaran Y, Kindler HL. , et al. Quality of life after radical pleurectomy decortication for malignant pleural mesothelioma. Ann Thorac Surg 2012; 94 (04) 1086-1092
  • 69 Rena O, Casadio C. Extrapleural pneumonectomy for early stage malignant pleural mesothelioma: a harmful procedure. Lung Cancer 2012; 77 (01) 151-155
  • 70 Spaggiari L, Marulli G, Bovolato P. , et al. Extrapleural pneumonectomy for malignant mesothelioma: an Italian multicenter retrospective study. Ann Thorac Surg 2014; 97 (06) 1859-1865
  • 71 Sugarbaker DJ, Richards WG, Bueno R. Extrapleural pneumonectomy in the treatment of epithelioid malignant pleural mesothelioma: novel prognostic implications of combined N1 and N2 nodal involvement based on experience in 529 patients. Ann Surg 2014; 260 (04) 577-580 , discussion 580–582
  • 72 Sugarbaker DJ, Wolf AS, Chirieac LR. , et al. Clinical and pathological features of three-year survivors of malignant pleural mesothelioma following extrapleural pneumonectomy. Eur J Cardiothorac Surg 2011; 40 (02) 298-303
  • 73 van Gerwen M, Wolf A, Liu B, Flores R, Taioli E. Short-term outcomes of pleurectomy decortication and extrapleural pneumonectomy in mesothelioma. J Surg Oncol 2018; 118 (07) 1178-1187
  • 74 Treasure T, Lang-Lazdunski L, Waller D. , et al; MARS trialists. Extra-pleural pneumonectomy versus no extra-pleural pneumonectomy for patients with malignant pleural mesothelioma: clinical outcomes of the Mesothelioma and Radical Surgery (MARS) randomised feasibility study. Lancet Oncol 2011; 12 (08) 763-772
  • 75 Sharif S, Zahid I, Routledge T, Scarci M. Extrapleural pneumonectomy or supportive care: treatment of malignant pleural mesothelioma?. Interact Cardiovasc Thorac Surg 2011; 12 (06) 1040-1045
  • 76 Bovolato P, Casadio C, Billè A. , et al. Does surgery improve survival of patients with malignant pleural mesothelioma?: a multicenter retrospective analysis of 1365 consecutive patients. J Thorac Oncol 2014; 9 (03) 390-396
  • 77 Batirel HF, Metintas M, Caglar HB. , et al. Macroscopic complete resection is not associated with improved survival in patients with malignant pleural mesothelioma. J Thorac Cardiovasc Surg 2018; 155 (06) 2724-2733
  • 78 Cao C, Tian D, Park J, Allan J, Pataky KA, Yan TD. A systematic review and meta-analysis of surgical treatments for malignant pleural mesothelioma. Lung Cancer 2014; 83 (02) 240-245
  • 79 Maasilta P. Deterioration in lung function following hemithorax irradiation for pleural mesothelioma. Int J Radiat Oncol Biol Phys 1991; 20 (03) 433-438
  • 80 Baldini EH, Recht A, Strauss GM. , et al. Patterns of failure after trimodality therapy for malignant pleural mesothelioma. Ann Thorac Surg 1997; 63 (02) 334-338
  • 81 Rusch VW, Rosenzweig K, Venkatraman E. , et al. A phase II trial of surgical resection and adjuvant high-dose hemithoracic radiation for malignant pleural mesothelioma. J Thorac Cardiovasc Surg 2001; 122 (04) 788-795
  • 82 Gupta V, Mychalczak B, Krug L. , et al. Hemithoracic radiation therapy after pleurectomy/decortication for malignant pleural mesothelioma. Int J Radiat Oncol Biol Phys 2005; 63 (04) 1045-1052
  • 83 Stahel RA, Riesterer O, Xyrafas A. , et al. Neoadjuvant chemotherapy and extrapleural pneumonectomy of malignant pleural mesothelioma with or without hemithoracic radiotherapy (SAKK 17/04): a randomised, international, multicentre phase 2 trial. Lancet Oncol 2015; 16 (16) 1651-1658
  • 84 Cho BC, Feld R, Leighl N. , et al. A feasibility study evaluating surgery for mesothelioma after radiation therapy: the “SMART” approach for resectable malignant pleural mesothelioma. J Thorac Oncol 2014; 9 (03) 397-402
  • 85 de Perrot M, Feld R, Leighl NB. , et al. Accelerated hemithoracic radiation followed by extrapleural pneumonectomy for malignant pleural mesothelioma. J Thorac Cardiovasc Surg 2016; 151 (02) 468-473
  • 86 Rimner A, Zauderer MG, Gomez DR. , et al. Phase II study of hemithoracic Intensity-Modulated Pleural Radiation Therapy (IMPRINT) as part of lung-sparing multimodality therapy in patients with malignant pleural mesothelioma. J Clin Oncol 2016; 34 (23) 2761-2768
  • 87 Pan HY, Jiang S, Sutton J. , et al. Early experience with intensity modulated proton therapy for lung-intact mesothelioma: a case series. Pract Radiat Oncol 2015; 5 (04) e345-e353
  • 88 Badiyan SN, Molitoris JK, Zhu M, Glass E, Diwanji T, Simone II CB. Proton beam therapy for malignant pleural mesothelioma. Transl Lung Cancer Res 2018; 7 (02) 189-198
  • 89 Boutin C, Rey F, Viallat JR. Prevention of malignant seeding after invasive diagnostic procedures in patients with pleural mesothelioma. A randomized trial of local radiotherapy. Chest 1995; 108 (03) 754-758
  • 90 Bydder S, Phillips M, Joseph DJ. , et al. A randomised trial of single-dose radiotherapy to prevent procedure tract metastasis by malignant mesothelioma. Br J Cancer 2004; 91 (01) 9-10
  • 91 O'Rourke N, Garcia JC, Paul J, Lawless C, McMenemin R, Hill J. A randomised controlled trial of intervention site radiotherapy in malignant pleural mesothelioma. Radiother Oncol 2007; 84 (01) 18-22
  • 92 Clive AO, Taylor H, Dobson L. , et al. Prophylactic radiotherapy for the prevention of procedure-tract metastases after surgical and large-bore pleural procedures in malignant pleural mesothelioma (SMART): a multicentre, open-label, phase 3, randomised controlled trial. Lancet Oncol 2016; 17 (08) 1094-1104
  • 93 Bayman N, Appel W, Ashcroft L. , et al. PRophylactic Irradiation of Tracts in Patients With Malignant Pleural Mesothelioma: An Open-Label, Multicenter, Phase III Randomized Trial. J Clinic Oncol 37 (14) 1200-1208
  • 94 Macleod N, Price A, O'Rourke N, Fallon M, Laird B. Radiotherapy for the treatment of pain in malignant pleural mesothelioma: a systematic review. Lung Cancer 2014; 83 (02) 133-138
  • 95 MacLeod N, Chalmers A, O'Rourke N. , et al. Is Radiotherapy useful for treating pain in mesothelioma?: a phase II trial. J Thorac Oncol 2015; 10 (06) 944-950
  • 96 Ashton M, O'Rourke N, Macleod N. , et al. SYSTEMS-2: a randomised phase II study of radiotherapy dose escalation for pain control in malignant pleural mesothelioma. Clin Transl Radiat Oncol 2017; 8: 45-49
  • 97 Sterman DH, Albelda SM. Advances in the diagnosis, evaluation, and management of malignant pleural mesothelioma. Respirology 2005; 10 (03) 266-283
  • 98 van Meerbeeck JP, Gaafar R, Manegold C. , et al; European Organisation for Research and Treatment of Cancer Lung Cancer Group; National Cancer Institute of Canada. Randomized phase III study of cisplatin with or without raltitrexed in patients with malignant pleural mesothelioma: an intergroup study of the European Organisation for Research and Treatment of Cancer Lung Cancer Group and the National Cancer Institute of Canada. J Clin Oncol 2005; 23 (28) 6881-6889
  • 99 Castagneto B, Botta M, Aitini E. , et al. Phase II study of pemetrexed in combination with carboplatin in patients with malignant pleural mesothelioma (MPM). Ann Oncol 2008; 19 (02) 370-373
  • 100 Ceresoli GL, Zucali PA, Favaretto AG. , et al. Phase II study of pemetrexed plus carboplatin in malignant pleural mesothelioma. J Clin Oncol 2006; 24 (09) 1443-1448
  • 101 Ceresoli GL, Castagneto B, Zucali PA. , et al. Pemetrexed plus carboplatin in elderly patients with malignant pleural mesothelioma: combined analysis of two phase II trials. Br J Cancer 2008; 99 (01) 51-56
  • 102 Ceresoli GL, Zucali PA, Mencoboni M. , et al. Phase II study of pemetrexed and carboplatin plus bevacizumab as first-line therapy in malignant pleural mesothelioma. Br J Cancer 2013; 109 (03) 552-558
  • 103 Zalcman G, Mazieres J, Margery J. , et al; French Cooperative Thoracic Intergroup (IFCT). Bevacizumab for newly diagnosed pleural mesothelioma in the Mesothelioma Avastin Cisplatin Pemetrexed Study (MAPS): a randomised, controlled, open-label, phase 3 trial. Lancet 2016; 387 (10026): 1405-1414
  • 104 Zucali PA, Simonelli M, Michetti G. , et al. Second-line chemotherapy in malignant pleural mesothelioma: results of a retrospective multicenter survey. Lung Cancer 2012; 75 (03) 360-367
  • 105 Bearz A, Talamini R, Rossoni G. , et al. Re-challenge with pemetrexed in advanced mesothelioma: a multi-institutional experience. BMC Res Notes 2012; 5: 482
  • 106 Zucali PA, Perrino M, Lorenzi E. , et al. Vinorelbine in pemetrexed-pretreated patients with malignant pleural mesothelioma. Lung Cancer 2014; 84 (03) 265-270
  • 107 Zauderer MG, Kass SL, Woo K, Sima CS, Ginsberg MS, Krug LM. Vinorelbine and gemcitabine as second- or third-line therapy for malignant pleural mesothelioma. Lung Cancer 2014; 84 (03) 271-274
  • 108 Scherpereel A, Wallyn F, Albelda SM, Munck C. Novel therapies for malignant pleural mesothelioma. Lancet Oncol 2018; 19 (03) e161-e172
  • 109 Buikhuisen WA, Scharpfenecker M, Griffioen AW, Korse CM, van Tinteren H, Baas P. A randomized phase II study adding axitinib to pemetrexed-cisplatin in patients with malignant pleural mesothelioma: a single-center trial combining clinical and translational outcomes. J Thorac Oncol 2016; 11 (05) 758-768
  • 110 Papa S, Popat S, Shah R. , et al. Phase 2 study of sorafenib in malignant mesothelioma previously treated with platinum-containing chemotherapy. J Thorac Oncol 2013; 8 (06) 783-787
  • 111 Dubey S, Jänne PA, Krug L. , et al. A phase II study of sorafenib in malignant mesothelioma: results of Cancer and Leukemia Group B 30307. J Thorac Oncol 2010; 5 (10) 1655-1661
  • 112 Grosso F, Steele N, Novello S. , et al. Nintedanib plus pemetrexed/cisplatin in patients with malignant pleural mesothelioma: phase II results from the randomized, placebo-controlled LUME-Meso trial. J Clin Oncol 2017; 35 (31) 3591-3600
  • 113 Tsao AS, Moon J, Wistuba II. , et al. Phase I trial of cediranib in combination with cisplatin and pemetrexed in chemonaive patients with unresectable malignant pleural mesothelioma (SWOG S0905). J Thorac Oncol 2017; 12 (08) 1299-1308
  • 114 Tsao AS, Miao J, Wistuba II. , et al. SWOG S0905: a randomized phase II study of cediranib versus placebo in combination with cisplatin and pemetrexed in chemonaive patients with malignant pleural mesothelioma. J Clin Oncol 2018; 36: 8514
  • 115 Scherpereel A, Berghmans T, Lafitte JJ. , et al; European Lung Cancer Working Party (ELCWP). Valproate-doxorubicin: promising therapy for progressing mesothelioma. A phase II study. Eur Respir J 2011; 37 (01) 129-135
  • 116 Krug LM, Kindler HL, Calvert H. , et al. Vorinostat in patients with advanced malignant pleural mesothelioma who have progressed on previous chemotherapy (VANTAGE-014): a phase 3, double-blind, randomised, placebo-controlled trial. Lancet Oncol 2015; 16 (04) 447-456
  • 117 Soria JC, Gan HK, Blagden SP. , et al. A phase I, pharmacokinetic and pharmacodynamic study of GSK2256098, a focal adhesion kinase inhibitor, in patients with advanced solid tumors. Ann Oncol 2016; 27 (12) 2268-2274
  • 118 Fennell DA, Baas P, Taylor P. , et al. Maintenance defactinib versus placebo after first-line chemotherapy in patients with merlin-stratified pleural mesothelioma: COMMAND-a double-blind, randomized, phase II study. J Clin Oncol 2019; 37 (10) 790-798
  • 119 Szlosarek PW, Steele JP, Nolan L. , et al. Arginine deprivation with pegylated arginine deiminase in patients with argininosuccinate synthetase 1-deficient malignant pleural mesothelioma: a randomized clinical trial. JAMA Oncol 2017; 3 (01) 58-66
  • 120 Beddowes E, Spicer J, Chan PY. , et al. Phase 1 dose-escalation study of pegylated arginine deiminase, cisplatin, and pemetrexed in patients with argininosuccinate synthetase 1-deficient thoracic cancers. J Clin Oncol 2017; 35 (16) 1778-1785
  • 121 Phillips M, Szyszko T, Hall P. , et al. Expansion study of ADI-PEG 20, pemetrexed and cisplatin in patients with ASS1-deficient malignant pleural mesothelioma (TRAP). J Clin Oncol 2017; 35: 8553
  • 122 Lievense LA, Sterman DH, Cornelissen R, Aerts JG. Checkpoint blockade in lung cancer and mesothelioma. Am J Respir Crit Care Med 2017; 196 (03) 274-282
  • 123 Brahmer J, Reckamp KL, Baas P. , et al. Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer. N Engl J Med 2015; 373 (02) 123-135
  • 124 Garon EB, Rizvi NA, Hui R. , et al; KEYNOTE-001 Investigators. Pembrolizumab for the treatment of non-small-cell lung cancer. N Engl J Med 2015; 372 (21) 2018-2028
  • 125 Astoul P, Roca E, Galateau-Salle F, Scherpereel A. Malignant pleural mesothelioma: from the bench to the bedside. Respiration 2012; 83 (06) 481-493
  • 126 Mansfield AS, Roden AC, Peikert T. , et al. B7-H1 expression in malignant pleural mesothelioma is associated with sarcomatoid histology and poor prognosis. J Thorac Oncol 2014; 9 (07) 1036-1040
  • 127 Calabrò L, Morra A, Fonsatti E. , et al. Tremelimumab for patients with chemotherapy-resistant advanced malignant mesothelioma: an open-label, single-arm, phase 2 trial. Lancet Oncol 2013; 14 (11) 1104-1111
  • 128 Maio M, Scherpereel A, Calabrò L. , et al. Tremelimumab as second-line or third-line treatment in relapsed malignant mesothelioma (DETERMINE): a multicentre, international, randomised, double-blind, placebo-controlled phase 2b trial. Lancet Oncol 2017; 18 (09) 1261-1273
  • 129 Alley EW, Lopez J, Santoro A. , et al. Clinical safety and activity of pembrolizumab in patients with malignant pleural mesothelioma (KEYNOTE-028): preliminary results from a non-randomised, open-label, phase 1b trial. Lancet Oncol 2017; 18 (05) 623-630
  • 130 Quispel-Janssen J, Zago G, Schouten R. , et al. OA13.01 A phase II study of nivolumab in malignant pleural mesothelioma (NivoMes): with translational research (TR) biopies. J Thorac Oncol 2017; 12: S292-S293
  • 131 Calabrò L, Morra A, Giannarelli D. , et al. Tremelimumab combined with durvalumab in patients with mesothelioma (NIBIT-MESO-1): an open-label, non-randomised, phase 2 study. Lancet Respir Med 2018; 6 (06) 451-460
  • 132 Disselhorst MJ, Quispel-Janssen J, Lalezari F. , et al. Ipilimumab and nivolumab in the treatment of recurrent malignant pleural mesothelioma (INITIATE): results of a prospective, single-arm, phase 2 trial. Lancet Respir Med 2019; 7 (03) 260-270
  • 133 Scherpereel A, Mazieres J, Greillier L. , et al; French Cooperative Thoracic Intergroup. Nivolumab or nivolumab plus ipilimumab in patients with relapsed malignant pleural mesothelioma (IFCT-1501 MAPS2): a multicentre, open-label, randomised, non-comparative, phase 2 trial. Lancet Oncol 2019; 20 (02) 239-253
  • 134 Zalcman G, Peters S, Mansfield AS. , et al. Checkmate 743: a phase 3, randomized, open-label trial of nivolumab (nivo) plus ipilimumab (ipi) vs pemetrexed plus cisplatin or carboplatin as first-line therapy in unresectable pleural mesothelioma. J Clin Oncol 2017; 35: TPS8581
  • 135 Kelly RJ, Sharon E, Pastan I, Hassan R. Mesothelin-targeted agents in clinical trials and in preclinical development. Mol Cancer Ther 2012; 11 (03) 517-525
  • 136 Hassan R, Kindler HL, Jahan T. , et al. Phase II clinical trial of amatuximab, a chimeric antimesothelin antibody with pemetrexed and cisplatin in advanced unresectable pleural mesothelioma. Clin Cancer Res 2014; 20 (23) 5927-5936
  • 137 Le DT, Brockstedt DG, Nir-Paz R. , et al. A live-attenuated Listeria vaccine (ANZ-100) and a live-attenuated Listeria vaccine expressing mesothelin (CRS-207) for advanced cancers: phase I studies of safety and immune induction. Clin Cancer Res 2012; 18 (03) 858-868
  • 138 Jahan T, Hassan R, Alley E. , et al. 208O_PR: CRS-207 with chemotherapy (chemo) in malignant pleural mesothelioma (MPM): results from a phase 1b trial. J Thorac Oncol 2016; 11: S156
  • 139 Beatty GL, Haas AR, Maus MV. , et al. Mesothelin-specific chimeric antigen receptor mRNA-engineered T cells induce anti-tumor activity in solid malignancies. Cancer Immunol Res 2014; 2 (02) 112-120
  • 140 Ordóñez NG. The immunohistochemical diagnosis of mesothelioma: a comparative study of epithelioid mesothelioma and lung adenocarcinoma. Am J Surg Pathol 2003; 27 (08) 1031-1051
  • 141 Krug LM, Dao T, Brown AB. , et al. WT1 peptide vaccinations induce CD4 and CD8 T cell immune responses in patients with mesothelioma and non-small cell lung cancer. Cancer Immunol Immunother 2010; 59 (10) 1467-1479
  • 142 Zauderer MG, Tsao AS, Dao T. , et al. A randomized phase II Trial of adjuvant galinpepimut-S, WT-1 analogue peptide vaccine, after multimodality therapy for patients with malignant pleural mesothelioma. Clin Cancer Res 2017; 23 (24) 7483-7489
  • 143 Hegmans JP, Veltman JD, Lambers ME. , et al. Consolidative dendritic cell-based immunotherapy elicits cytotoxicity against malignant mesothelioma. Am J Respir Crit Care Med 2010; 181 (12) 1383-1390
  • 144 Cornelissen R, Hegmans JP, Maat AP. , et al. Extended tumor control after dendritic cell vaccination with low-dose cyclophosphamide as adjuvant treatment in patients with malignant pleural mesothelioma. Am J Respir Crit Care Med 2016; 193 (09) 1023-1031
  • 145 Sterman DH, Recio A, Carroll RG. , et al. A phase I clinical trial of single-dose intrapleural IFN-β gene transfer for malignant pleural mesothelioma and metastatic pleural effusions: high rate of antitumor immune responses. Clin Cancer Res 2007; 13 (15, Pt 1): 4456-4466
  • 146 Sterman DH, Recio A, Haas AR. , et al. A phase I trial of repeated intrapleural adenoviral-mediated interferon-β gene transfer for mesothelioma and metastatic pleural effusions. Mol Ther 2010; 18 (04) 852-860
  • 147 Sterman DH, Haas A, Moon E. , et al. A trial of intrapleural adenoviral-mediated Interferon-α2b gene transfer for malignant pleural mesothelioma. Am J Respir Crit Care Med 2011; 184 (12) 1395-1399
  • 148 Sterman DH, Alley E, Stevenson JP. , et al. Pilot and feasibility trial evaluating immuno-gene therapy of malignant mesothelioma using intrapleural delivery of adenovirus-IFNα combined with chemotherapy. Clin Cancer Res 2016; 22 (15) 3791-3800