Radiation Therapy in Mesothelioma

  • Jonas Willmann
  • Andreas RimnerEmail author
Living reference work entry


Malignant pleural mesothelioma (MPM) is a rare tumor, arising from cells of the parietal or visceral pleura, that is linked to exposure to asbestos. The prognosis for MPM patients is extremely poor. In MPM patients, early symptoms are few and unspecific, so presentation with extensive disease is common. Therefore, many patients can only be treated in a palliative intent. For those who present at an early, potentially resectable tumor stage, multimodality treatment has been employed to control the disease. However, due to the limited number of clinical trials, many of the therapeutic approaches to date lack strong evidence and are subject to controversies and changes. The best evidence available is for the use of platinum/pemetrexed-based chemotherapy, with most recent data showing a small additional survival advantage of adding bevacizumab. There has been an ongoing debate as to how radical surgery in MPM should be used and to what degree it can prolong survival without causing additional morbidity. Radiation therapy (RT) has been a third important element in most multimodality regimens to control the disease locally. The complex anatomy of the pleura and its proximity to vital organs at risk, especially the lung, pose distinct challenges to radiation oncologists. Novel techniques such as intensity-modulated radiation therapy (IMRT), volume modulated arc therapy (VMAT), or proton therapy are promising options to precisely deliver effective doses of radiation with minimized toxicities. The combination of these state of the art techniques with systemic therapies or immune checkpoint inhibitors is currently under investigation and might potentially yield more promising outcomes for future patients.


Malignant pleural mesothelioma Multimodality treatment Radical surgery Systemic therapy Radiation therapy 


  1. Allen AM, Czerminska M, Jänne PA, Sugarbaker DJ, Bueno R, Harris JR, et al. Fatal pneumonitis associated with intensity-modulated radiation therapy for mesothelioma. Int J Radiat Oncol Biol Phys. 2006;65(3):640–5.PubMedCrossRefPubMedCentralGoogle Scholar
  2. Alley EW, Lopez J, Santoro A, Morosky A, Saraf S, Piperdi B, 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(5):623–30.PubMedPubMedCentralCrossRefGoogle Scholar
  3. Arzt L, Quehenberger F, Halbwedl I, Mairinger T, Popper HH. BAP1 protein is a progression factor in malignant pleural mesothelioma. Pathol Oncol Res. 2014;20(1):145–51.PubMedCrossRefGoogle Scholar
  4. Ashton M, O’Rourke N, Macleod N, Chalmers A. 194 SYSTEMS-2: a randomised phase II trial of standard versus dose escalated radiotherapy in the treatment of pain in malignant pleural mesothelioma. Lung Cancer. 2016;91:S71.CrossRefGoogle Scholar
  5. Bernstein DM, Rogers RA, Sepulveda R, Donaldson K, Schuler D, Gaering S, et al. Quantification of the pathological response and fate in the lung and pleura of chrysotile in combination with fine particles compared to amosite-asbestos following short-term inhalation exposure. Inhal Toxicol. 2011;23(7):372–91.PubMedCrossRefGoogle Scholar
  6. Bott M, Brevet M, Taylor BS, Shimizu S, Ito T, Wang L, et al. The nuclear deubiquitinase BAP1 is commonly inactivated by somatic mutations and 3p21.1 losses in malignant pleural mesothelioma. Nat Genet. 2011;43(7):668–72.PubMedPubMedCentralCrossRefGoogle Scholar
  7. Bueno R, Stawiski EW, Goldstein LD, Durinck S, De Rienzo A, Modrusan Z, et al. Comprehensive genomic analysis of malignant pleural mesothelioma identifies recurrent mutations, gene fusions and splicing alterations. Nat Genet. 2016;48(4):407–16.PubMedCrossRefPubMedCentralGoogle Scholar
  8. Cedrés S, Ponce-Aix S, Zugazagoitia J, Sansano I, Enguita A, Navarro-Mendivil A, et al. Analysis of expression of programmed cell death 1 ligand 1 (PD-L1) in malignant pleural mesothelioma (MPM). PLoS One. 2015;10(3):1–12.CrossRefGoogle Scholar
  9. Ceresoli GL, Zucali PA, Gianoncelli L, Lorenzi E, Santoro A. Second-line treatment for malignant pleural mesothelioma. Cancer Treat Rev. 2010;36:24–32.PubMedCrossRefPubMedCentralGoogle Scholar
  10. Chance WW, Rice DC, Allen PK, Tsao AS, Fontanilla HP, Liao Z, et al. Hemithoracic intensity modulated radiation therapy after pleurectomy/decortication for malignant pleural mesothelioma: toxicity, patterns of failure, and a matched survival analysis. Int J Radiat Oncol Biol Phys. 2015;91(1):149–56.PubMedCrossRefPubMedCentralGoogle Scholar
  11. Cigognetti M, Lonardi S, Fisogni S, Balzarini P, Pellegrini V, Tironi A, et al. BAP1 (BRCA1-associated protein 1) is a highly specific marker for differentiating mesothelioma from reactive mesothelial proliferations. Mod Pathol. 2015;28(8):1043–57.PubMedCrossRefPubMedCentralGoogle Scholar
  12. Clive AO, Taylor H, Dobson L, Wilson P, de Winton E, Panakis N, 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(8):1094–104.PubMedPubMedCentralCrossRefGoogle Scholar
  13. Curran D, Sahmoud T, Therasse P, van Meerbeeck J, Postmus PE, Giaccone G. Prognostic factors in patients with pleural mesothelioma: the European Organization for Research and Treatment of Cancer experience. J Clin Oncol. 1998;16(1):145–52.PubMedCrossRefPubMedCentralGoogle Scholar
  14. De Bruin ML, Burgers JA, Baas P, van’t Veer MB, Noordijk EM, Louwman MWJ, et al. Malignant mesothelioma after radiation treatment for Hodgkin lymphoma. Blood. 2009;113(16):3679–81.PubMedCrossRefPubMedCentralGoogle Scholar
  15. de Perrot M, Feld R, Leighl NB, Hope A, Waddell TK, Keshavjee S, et al. Accelerated hemithoracic radiation followed by extrapleural pneumonectomy for malignant pleural mesothelioma. J Thorac Cardiovasc Surg. 2016;151(2):468–75.PubMedCrossRefPubMedCentralGoogle Scholar
  16. de Perrot M, Dong Z, Bradbury P, Patsios D, Keshavjee S, Leighl NB, et al. Impact of tumour thickness on survival after radical radiation and surgery in malignant pleural mesothelioma. Eur Respir J. 2017;49(3):1601428.PubMedCrossRefPubMedCentralGoogle Scholar
  17. Dumane VA, Rimner A, Yorke ED, Rosenzweig KE. Volumetric-modulated arc therapy for malignant pleural mesothelioma. Appl Radiat Oncol. 2016;2(December):28–37.Google Scholar
  18. Feigen M, Lee ST, Lawford C, Churcher K, Zupan E, Scott AM, et al. Establishing locoregional control of malignant pleural mesothelioma using high-dose radiotherapy and 18F-FDG PET/CT scan correlation. J Med Imaging Radiat Oncol. 2011;55(3):320–32.PubMedCrossRefPubMedCentralGoogle Scholar
  19. Flores RM, Pass HI, Seshan VE, Dycoco J, Zakowski M, Carbone M, et al. Extrapleural pneumonectomy versus pleurectomy/ decortication in the surgical management of malignant pleural mesothelioma: results in 663 patients. J Thorac Cardiovasc Surg. 2008;135(3):620.PubMedCrossRefGoogle Scholar
  20. Fodor A, Fiorino C, Dell’Oca I, Broggi S, Pasetti M, Cattaneo GM, et al. PET-guided dose escalation tomotherapy in malignant pleural mesothelioma. Strahlenther Onkol. 2011;187(11):736–43. Urban and Vogel.PubMedCrossRefGoogle Scholar
  21. Geltner C, Errhalt P, Baumgartner B, Ambrosch G, Machan B, Eckmayr J, et al. Management of malignant pleural mesothelioma – part 1: epidemiology, diagnosis, and staging: consensus of the Austrian Mesothelioma Interest Group (AMIG). Wien Klin Wochenschr. 2016;128(17–18):611–7.PubMedPubMedCentralCrossRefGoogle Scholar
  22. Gill RR. Imaging of mesothelioma. In: Tannapfel A, editor. Recent results in cancer research: malignanant mesothelioma. Springer: Berlin/Heidelberg; 2011. p. 27–43.Google Scholar
  23. Guo G, Chmielecki J, Goparaju C, Heguy A, Dolgalev I, Carbone M, et al. Whole-exome sequencing reveals frequent genetic alterations in BAP1, NF2, CDKN2A, and CUL1 in malignant pleural mesothelioma. Cancer Res. 2015;75(2):264–9.PubMedCrossRefPubMedCentralGoogle Scholar
  24. Gupta V, Mychalczak B, Krug L, Flores R, Bains M, Rusch VW, et al. Hemithoracic radiation therapy after pleurectomy/decortication for malignant pleural mesothelioma. Int J Radiat Oncol Biol Phys. 2005;63(4):1045–52.PubMedCrossRefPubMedCentralGoogle Scholar
  25. Henderson DW, Reid G, Kao SC, van Zandwijk N, Klebe S. Challenges and controversies in the diagnosis of mesothelioma: part 1. Cytology-only diagnosis, biopsies, immunohistochemistry, discrimination between mesothelioma and reactive mesothelial hyperplasia, and biomarkers. J Clin Pathol. 2013;66(10):847–53.PubMedCrossRefPubMedCentralGoogle Scholar
  26. Herndon JE, Green MR, Chahinian AP, Corson JM, Suzuki Y, Vogelzang NJ. Factors predictive of survival among 337 patients with mesothelioma treated between 1984 and 1994 by the Cancer and Leukemia Group B. Chest. 1998;113(3):723–31.PubMedCrossRefGoogle Scholar
  27. Hoang CD. Surgical controversies in mesothelioma: MesoVATS addresses the role of surgical debulking. Transl Lung Cancer Res. 2016;5(1):82–4.PubMedPubMedCentralGoogle Scholar
  28. Jassem J, Ramlau R, Santoro A, Schuette W, Chemaissani A, Hong S, et al. Phase III trial of pemetrexed plus best supportive care compared with best supportive care in previously treated patients with advanced malignant pleural mesothelioma. J Clin Oncol. 2008;26(10):1698–704.PubMedCrossRefGoogle Scholar
  29. Kishan AU, Cameron RB, Wang PC, Alexander S, Qi SX, Low DA, et al. Tomotherapy improves local control and changes failure patterns in locally advanced malignant pleural mesothelioma. Pract Radiat Oncol. 2015;5(6):366–73.PubMedCrossRefGoogle Scholar
  30. Krayenbuehl J, Oertel S, Davis JB, Ciernik IF. Combined photon and electron three-dimensional conformal versus intensity-modulated radiotherapy with integrated boost for adjuvant treatment of malignant pleural mesothelioma after pleuropneumonectomy. Int J Radiat Oncol Biol Phys. 2007;69(5):1593–9.PubMedCrossRefGoogle Scholar
  31. Krayenbuehl J, Hartmann M, Lomax AJ, Kloeck S, Hug EB, Ciernik IF. Proton therapy for malignant pleural mesothelioma after extrapleural pleuropneumonectomy. Int J Radiat Oncol Biol Phys. 2010;78(2):628–34.PubMedCrossRefGoogle Scholar
  32. Kristensen CA, Nøttrup TJ, Berthelsen AK, Kjær-Kristoffersen F, Ravn J, Sørensen JB, et al. Pulmonary toxicity following IMRT after extrapleural pneumonectomy for malignant pleural mesothelioma. Radiother Oncol. 2009;92(1):96–9.PubMedCrossRefGoogle Scholar
  33. Krug LM, Pass HI, Rusch VW, Kindler HL, Sugarbaker DJ, Rosenzweig KE, et al. Multicenter phase II trial of neoadjuvant pemetrexed plus cisplatin followed by extrapleural pneumonectomy and radiation for malignant pleural mesothelioma. J Clin Oncol. 2009;27(18):3007–13.PubMedPubMedCentralCrossRefGoogle Scholar
  34. Krug LM, Kindler HL, Calvert H, Manegold C, Tsao AS, Fennell D, 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(4):447–56.PubMedCrossRefPubMedCentralGoogle Scholar
  35. Landreville S, Agapova OA, Matatall KA, Kneass ZT, Onken MD, Lee RS, et al. Histone deacetylase inhibitors induce growth arrest and differentiation in uveal melanoma. Clin Cancer Res. 2012;18(2):408–16.PubMedCrossRefPubMedCentralGoogle Scholar
  36. Larson T, Melnikova N, Davis SI, Jamison P. Incidence and descriptive epidemiology of mesothelioma in the United States, 1999–2002. Int J Occup Environ Health. 2007;13(4):398–403.PubMedCrossRefGoogle Scholar
  37. Levy A, Chargari C, Cheminant M, Simon N, Bourgier C, Deutsch E, et al. Radiation therapy and immunotherapy: implications for a combined cancer treatment. Crit Rev Oncol Hematol. 2013;85(3):278–87.PubMedCrossRefPubMedCentralGoogle Scholar
  38. Lo Iacono M, Monica V, Righi L, Grosso F, Libener R, Vatrano S, et al. Targeted next-generation sequencing of cancer genes in advanced stage malignant pleural mesothelioma: a retrospective study. J Thorac Oncol. 2015;10(3):492–9.PubMedCrossRefPubMedCentralGoogle Scholar
  39. Ludgate CM. Optimizing cancer treatments to induce an acute immune response: radiation Abscopal effects, PAMPs, and DAMPs. Clin Cancer Res. 2012;18(17):4522–5.PubMedCrossRefPubMedCentralGoogle Scholar
  40. 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(2):133–8.PubMedCrossRefPubMedCentralGoogle Scholar
  41. MacLeod N, Kelly C, Stobo J, McMahon L, Taggart D, Fallon M, et al. Pain in malignant pleural mesothelioma: a prospective characterization study. Pain Med. 2016;17(11):2119–2126.PubMedCrossRefPubMedCentralGoogle Scholar
  42. Mansfield AS, Roden AC, Peikert T, Sheinin YM, Harrington SM, Krco CJ, et al. B7-H1 expression in malignant pleural mesothelioma is associated with sarcomatoid histology and poor prognosis. J Thorac Oncol. 2014;9(7):1036–40.PubMedPubMedCentralCrossRefGoogle Scholar
  43. May RJ, Dao T, Pinilla-Ibarz J, Korontsvit T, Zakhaleva V, Zhang RH, et al. Peptide epitopes from the Wilms’ tumor 1 oncoprotein stimulate CD4 + and CD8+ T cells that recognize and kill human malignant mesothelioma tumor cells. Clin Cancer Res. 2007;13(15):4547–55.PubMedCrossRefPubMedCentralGoogle Scholar
  44. Miles EF, Larrier NA, Kelsey CR, Hubbs JL, Ma J, Yoo S, et al. Intensity-modulated radiotherapy for resected mesothelioma: the Duke experience. Int J Radiat Oncol Biol Phys. 2008;71(4):1143–50.PubMedCrossRefGoogle Scholar
  45. Minatel E, Trovo M, Polesel J, Rumeileh IA, Baresic T, Bearz A, et al. Tomotherapy after pleurectomy/decortication or biopsy for malignant pleural mesothelioma allows the delivery of high dose of radiation in patients with intact lung. J Thorac Oncol. 2012;7(12):1862–6.PubMedCrossRefGoogle Scholar
  46. Minatel E, Trovo M, Polesel J, Baresic T, Bearz A, Franchin G, et al. Radical pleurectomy/decortication followed by high dose of radiation therapy for malignant pleural mesothelioma. Final results with long-term follow-up. Lung Cancer. 2014;83(1):78–82.PubMedCrossRefGoogle Scholar
  47. Nelson DB, Rice DC, Niu J, Atay S, Vaporciyan AA, Antonoff M, et al. Long-term survival outcomes of cancer-directed surgery for malignant pleural mesothelioma: propensity score matching analysis. J Clin Oncol. 2017;35(29):3354–62.PubMedCrossRefPubMedCentralGoogle Scholar
  48. Neumann V, Loseke S, Nowak D, Herth FJ, Tannapfel A. Malignant pleural mesothelioma: incidence, etiology, diagnosis, treatment, and occupational health. Dtsch Arztebl Int. 2013;110(18):319–26.PubMedPubMedCentralGoogle Scholar
  49. Ngamwong Y, Tangamornsuksan W, Lohitnavy O, Chaiyakunapruk N, Scholfield CN, Reisfeld B, et al. Additive synergism between asbestos and smoking in lung cancer risk: a systematic review and meta-analysis. PLoS One. 2015;10:e0135798.PubMedPubMedCentralCrossRefGoogle Scholar
  50. Pan HY, Jiang S, Sutton J, Liao Z, Chance WW, Frank SJ, et al. Early experience with intensity modulated proton therapy for lung-intact mesothelioma: a case series. Pract Radiat Oncol. 2015;5(4):e345–53.PubMedCrossRefPubMedCentralGoogle Scholar
  51. Pass HI, Kranda K, Temeck BK, Feuerstein I, Steinberg SM. Surgically debulked malignant pleural mesothelioma: results and prognostic factors. Ann Surg Oncol. 1997;4(3):215–22.PubMedCrossRefPubMedCentralGoogle Scholar
  52. Patel PR, Yoo S, Broadwater G, Marks LB, Miles EF, D’Amico TA, et al. Effect of increasing experience on dosimetric and clinical outcomes in the management of malignant pleural mesothelioma with intensity-modulated radiation therapy. Int J Radiat Oncol Biol Phys. 2012;83(1):362–8.PubMedCrossRefPubMedCentralGoogle Scholar
  53. Pehlivan B, Topkan E, Onal C, Nursal GN, Yuksel O, Dolek Y, et al. Comparison of CT and integrated PET-CT based radiation therapy planning in patients with malignant pleural mesothelioma. Radiat Oncol (Lond). 2009;4:35.CrossRefGoogle Scholar
  54. Rea F, Marulli G, Bortolotti L, Breda C, Favaretto AG, Loreggian L, et al. Induction chemotherapy, extrapleural pneumonectomy (EPP) and adjuvant hemi-thoracic radiation in malignant pleural mesothelioma (MPM): feasibility and results. Lung Cancer. 2007;57(1):89–95.PubMedCrossRefPubMedCentralGoogle Scholar
  55. Rena O, Casadio C. Extrapleural pneumonectomy for early stage malignant pleural mesothelioma: a harmful procedure. Lung Cancer. 2012;77(1):151–5.PubMedCrossRefPubMedCentralGoogle Scholar
  56. Rice D. Standardizing surgical treatment in malignant pleural mesothelioma. Ann Cardiothorac Surg. 2012;1(4):497–501.PubMedPubMedCentralGoogle Scholar
  57. Rice DC, Smythe WR, Liao Z, Guerrero T, Chang JY, McAleer MF, et al. Dose-dependent pulmonary toxicity after postoperative intensity-modulated radiotherapy for malignant pleural mesothelioma. Int J Radiat Oncol Biol Phys. 2007a;69(2):350–7.PubMedCrossRefPubMedCentralGoogle Scholar
  58. Rice DC, Stevens CW, Correa AM, Vaporciyan AA, Tsao A, Forster KM, et al. Outcomes after extrapleural pneumonectomy and intensity-modulated radiation therapy for malignant pleural mesothelioma. Ann Thorac Surg. 2007b;84(5):1685–93.PubMedCrossRefPubMedCentralGoogle Scholar
  59. Rimner A, Spratt DE, Zauderer MG, Rosenzweig KE, Wu AJ, Foster A, et al. Failure patterns after hemithoracic pleural intensity modulated radiation therapy for malignant pleural mesothelioma. Int J Radiat Oncol Biol Phys. 2014;90(2):394–401.PubMedPubMedCentralCrossRefGoogle Scholar
  60. Rimner A, Simone CB 2nd, Zauderer MG, Cengel KA, Rusch VW. Hemithoracic radiotherapy for mesothelioma: lack of benefit or lack of statistical power? Lancet Oncol. 2016a;17(2):e44–5.CrossRefGoogle Scholar
  61. Rimner A, Zauderer MG, Gomez DR, Adusumilli PS, Parhar PK, Wu AJ, 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. 2016b;34(23):2761–8.PubMedPubMedCentralCrossRefGoogle Scholar
  62. Rintoul RC, Ritchie AJ, Edwards JG, Waller DA, Coonar AS, Bennett M, et al. 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):1118–27.PubMedCrossRefPubMedCentralGoogle Scholar
  63. Røe OD, Stella GM. Malignant pleural mesothelioma: history, controversy and future of a manmade epidemic. Eur Respir Rev. 2015;24(135):115–31.PubMedCrossRefPubMedCentralGoogle Scholar
  64. Rosenzweig KE, Zauderer MG, Laser B, Krug LM, Yorke E, Sima CS, et al. Pleural intensity-modulated radiotherapy for malignant pleural mesothelioma. Int J Radiat Oncol Biol Phys. 2012;83(4):1278–83.PubMedPubMedCentralCrossRefGoogle Scholar
  65. Rusch VW, Piantadosi S, Holmes EC. The role of extrapleural pneumonectomy in malignant pleural mesothelioma. A Lung Cancer Study Group trial. J Thorac Cardiovasc Surg. 1991;102(1):1–9.PubMedGoogle Scholar
  66. Rusch VW, Rosenzweig K, Venkatraman E, Leon L, Raben A, Harrison L, et al. A phase II trial of surgical resection and adjuvant highdose hemithoracic radiation for malignant pleural mesothelioma. J Thorac Cardiovasc Surg. 2001;122(4):788–95.PubMedCrossRefGoogle Scholar
  67. Rusch V, Baldini EH, Bueno R, De Perrot M, Flores R, Hasegawa S, et al. The role of surgical cytoreduction in the treatment of malignant pleural mesothelioma: meeting summary of the International Mesothelioma Interest Group Congress, September 11–14, 2012, Boston, Mass. J Thorac Cardiovasc Surg. 2013;145:909–10.PubMedCrossRefPubMedCentralGoogle Scholar
  68. Rusch VW, Rimner A, Krug LM. The challenge of malignant pleural mesothelioma: new directions. J Thorac Oncol. 2014;9(3):271–2.PubMedCrossRefPubMedCentralGoogle Scholar
  69. Rusch VW, Gill R, Mitchell A, Naidich D, Rice DC, Pass HI, et al. A multicenter study of volumetric computed tomography for staging malignant pleural mesothelioma. Ann Thorac Surg. 2016a;102(4):1059–66.PubMedPubMedCentralCrossRefGoogle Scholar
  70. Rusch VW, Rimner A, Adusumilli PS. SMART or simply bold? J Thorac Cardiovasc Surg. 2016b;151(2):476–7.PubMedCrossRefPubMedCentralGoogle Scholar
  71. Scherpereel A, Astoul P, Baas P, Berghmans T, Clayson H, De Vuyst P, et al. Guidelines of the European Respiratory Society and the European Society of Thoracic Surgeons for the management of malignant pleural mesothelioma. Eur Respir J. 2010;35:479–95.PubMedCrossRefPubMedCentralGoogle Scholar
  72. Sedrakyan A, Treasure T, Browne J, Krumholz H, Sharpin C, van der Meulen J. Pharmacologic prophylaxis for postoperative atrial tachyarrhythmia in general thoracic surgery: evidence from randomized clinical trials. J Thorac Cardiovasc Surg. 2005;129(5):997–1005.PubMedCrossRefPubMedCentralGoogle Scholar
  73. Shaikh F, Zauderer MG, von Reibnitz D, Wu AJ, Yorke ED, Foster A, et al. Improved outcomes with modern lung-sparing trimodality therapy in patients with malignant pleural mesothelioma. J Thorac Oncol. 2017;12(6):993–1000.PubMedPubMedCentralCrossRefGoogle Scholar
  74. Stahel RA, Riesterer O, Xyrafas A, Opitz I, Beyeler M, Ochsenbein 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):1651–8.PubMedCrossRefPubMedCentralGoogle Scholar
  75. Taioli E, Wolf AS, Flores RM. Meta-analysis of survival after pleurectomy decortication versus extrapleural pneumonectomy in mesothelioma. Ann Thorac Surg. 2015;99(2):472–80.PubMedCrossRefPubMedCentralGoogle Scholar
  76. Testa JR, Cheung M, Pei J, Below JE, Tan Y, Sementino E, et al. Germline BAP1 mutations predispose to malignant mesothelioma. Nat Genet. 2011;43(10):1022–5.PubMedPubMedCentralCrossRefGoogle Scholar
  77. Tischoff I, Neid M, Neumann V, Tannapfel A. Pathohistological Diagnosis and Differential Diagnosis. In: Tannapfel A, (ed). Malignant Mesothelioma (Recent Results in Cancer Research). Berlin Heidelberg: Springer; 2011. p. 57–78.CrossRefGoogle Scholar
  78. Treasure T, Lang-Lazdunski L, Waller D, Bliss JM, Tan C, Entwisle J, et al. 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(8):763–72.PubMedPubMedCentralCrossRefGoogle Scholar
  79. Van Meerbeeck JP, Gaafar R, Manegold C, Van Klaveren RJ, Van Marck EA, Vincent M, et al. 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. J Clin Oncol. 2005;23(28):6881–9.PubMedCrossRefPubMedCentralGoogle Scholar
  80. Vogelzang NJ, Rusthoven JJ, Symanowski J, Denham C, Kaukel E, Ruffie P, 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):2636–44.PubMedCrossRefPubMedCentralGoogle Scholar
  81. Wagner JC, Sleggs CA, Marchand P. Diffuse pleural mesothelioma and asbestos exposure in the North Western Cape Province. Br J Ind Med. 1960;17(4):260–71.PubMedPubMedCentralGoogle Scholar
  82. Walters J, Maskell NA. Biopsy techniques for the diagnosis of mesothelioma. In: Tannapfel A, (ed) Malignant Mesothelioma (Recent Results in Cancer Research). Berlin Heidelberg: Springer; 2011. p. 45–55.CrossRefGoogle Scholar
  83. Weder W, Stahel RA, Baas P, Dafni U, De Perrot M, McCaughan BC, et al. The MARS feasibility trial: conclusions not supported by data. Lancet Oncol. 2011;12(12):1093–4.PubMedCrossRefGoogle Scholar
  84. Wolf AS, Flores RM. Current treatment of mesothelioma: extrapleural pneumonectomy versus pleurectomy/decortication. Thorac Surg Clin. 2016;26(3):359–75.PubMedCrossRefGoogle Scholar
  85. Xu J, Kadariya Y, Cheung M, Pei J, Tlarchek J, Sementino E, et al. Germline Mutation of Bap1 Accelerates Development of Asbestos-Induced Malignant Mesothelioma Jinfei. Cancer Res. 2014;6(244):1–16.Google Scholar
  86. Yajnik S, Rosenzweig KE, Mychalczak B, Krug L, Flores R, Hong L, et al. Hemithoracic radiation after extrapleural pneumonectomy for malignant pleural mesothelioma. Int J Radiat Oncol Biol Phys. 2003;56(5):1319–26.PubMedCrossRefPubMedCentralGoogle Scholar
  87. Zalcman G, Mazieres J, Margery J, Greillier L, Audigier-Valette C, Moro-Sibilot D, et al. 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):1405–14.PubMedCrossRefPubMedCentralGoogle Scholar
  88. Zauderer MG, Krug LM. Novel therapies in phase II and III trials for malignant pleural mesothelioma. J Natl Compr Cancer Netw. 2012;10(1):42–7.CrossRefGoogle Scholar
  89. 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(3):271–4.PubMedPubMedCentralCrossRefGoogle Scholar
  90. Zauderer MG, Tsao AS, Dao T, Panageas KS, Lai WV, Rimner A, et al. A randomized phase II trial of adjuvant galinpepimut-S, WT-1 analog peptide vaccine, after multimodality therapy for patients with malignant pleural mesothelioma. Clin Cancer Res. 2017; clincanres.2169.2017.Google Scholar
  91. Zucali PA, Simonelli M, Michetti G, Tiseo M, Ceresoli GL, Collovà E, et al. Second-line chemotherapy in malignant pleural mesothelioma: results of a retrospective multicenter survey. Lung Cancer. 2012;75(3):360–7.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of Radiation OncologyUniversity Hospital ZurichZurichSwitzerland
  2. 2.Department of Radiation OncologyMemorial Sloan-Kettering Cancer Center New YorkNew YorkUSA

Personalised recommendations