Opinion statement
Malignant pleural mesothelioma (MPM) is a challenging disease to treat with median overall survival times ranging between 9-17 months for all stages of disease. Recent clinical trials have improved our understanding of the biology of MPM. However, survival results are still not ideal. For early-stage MPM, patients should be evaluated for trimodality therapy in an experienced cancer center. If treating off-protocol, MPM patients should receive a surgical staging evaluation. The decision to proceed with surgical resection also should be considered after an extensive and thorough pulmonary and cardiac evaluation. If deemed a good surgical candidate, patients should receive surgical resection (pleurectomy/decortication or extrapleural pneumonectomy), adjuvant radiation therapy (hemithoracic external beam or intensity modulated radiation therapy), and either neoadjuvant or adjuvant chemotherapy (cisplatin-pemetrexed for 4 cycles). The optimal precise sequence of the trimodality is unclear and should be decided upon by a multidisciplinary consensus for each individual patient. In general, clinical trial participation should be encouraged. Several trials are currently underway to examine intraoperative therapies, vaccines, immunotherapy additions, and novel radiation therapy techniques. Advances in the field of MPM are reliant on participation in clinical trials and identifying biomarkers that are predictive for response to systemic therapies and prognostic for survival benefit.
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Centers for Disease C. Prevention: Malignant mesothelioma mortality--United States, 1999-2005. MMWR Morb Mortal Wkly Rep. 2009;58:393–6.
Ahamad A, Stevens CW, Smythe WR, et al. Promising early local control of malignant pleural mesothelioma following postoperative intensity modulated radiotherapy (IMRT) to the chest. Cancer J. 2003;9:476–84.
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;21:2636–44.
Krug LM, Pass HI, Rusch VW, 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;27:3007–13.
Rintoul RC, Ritchie AJ, Edwards JG, 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. This study showed that video-assisted thoracoscopic partial pleurectomy did not improve survival over talc pleurodesis but may improve quality of life. VAT-PP should be reserved for patients who live beyond 6 months.
Rusch VW. Pleurectomy/decortication in the setting of multimodality treatment for diffuse malignant pleural mesothelioma. Semin Thorac Cardiovasc Surg. 1997;9:367–72.
Flores RM, Pass HI, Seshan VE, et al. Extrapleural pneumonectomy versus pleurectomy/decortication in the surgical management of malignant pleural mesothelioma: results in 663 patients. J Thorac Cardiovasc Surg. 2008;135:620-6–626 e1-3.
Martino D, Pass HI. Integration of multimodality approaches in the management of malignant pleural mesothelioma. Clin Lung Cancer. 2004;5:290–8.
Sugarbaker DJ, Jaklitsch MT, Bueno R, et al. Prevention, early detection, and management of complications after 328 consecutive extrapleural pneumonectomies. J Thorac Cardiovasc Surg. 2004;128:138–46.
Chang MY, Sugarbaker DJ. Extrapleural pneumonectomy for diffuse malignant pleural mesothelioma: techniques and complications. Thorac Surg Clin. 2004;14:523–30.
Rice DC, Stevens CW, Correa AM, et al. Outcomes after extrapleural pneumonectomy and intensity-modulated radiation therapy for malignant pleural mesothelioma. Ann Thorac Surg. 2007;84:1685–92. discussion 1692-3.
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;102:1–9.
Sugarbaker DJ, Flores RM, Jaklitsch MT, et al. Resection margins, extrapleural nodal status, and cell type determine postoperative long-term survival in trimodality therapy of malignant pleural mesothelioma: results in 183 patients. J Thorac Cardiovasc Surg. 1999;117:54–63. discussion 63-5.
de Perrot M, Feld R, Cho BC, et al. Trimodality therapy with induction chemotherapy followed by extrapleural pneumonectomy and adjuvant high-dose hemithoracic radiation for malignant pleural mesothelioma. J Clin Oncol. 2009;27:1413–8.
Jaklitsch MT, Grondin SC, Sugarbaker DJ. Treatment of malignant mesothelioma. World J Surg. 2001;25:210–7.
Treasure T, Lang-Lazdunski L, Waller D, 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;12:763–72. This United Kingdom trial randomized 50 MPM patients to extra-pleural pneumonectomy (EPP) or best supportive care. They reported no survival benefit to EPP, but had a high mortality rate in the EPP arm. In the USA, EPP is still considered to have a role in surgery for MPM.
Lang-Lazdunski L, Bille A, Lal R, et al. Pleurectomy/decortication is superior to extrapleural pneumonectomy in the multimodality management of patients with malignant pleural mesothelioma. J Thorac Oncol. 2012;7:737–43. This study supports the role of pleurectomy/decortication in MPM patients.
Treasure T, Sedrakyan A. Pleural mesothelioma: little evidence, still time to do trials. Lancet. 2004;364:1183–5.
Batirel HF, Metintas M, Caglar HB, et al. Trimodality treatment of malignant pleural mesothelioma. J Thorac Oncol. 2008;3:499–504.
Weder W, Stahel RA, Bernhard J, et al. Multicenter trial of neo-adjuvant chemotherapy followed by extrapleural pneumonectomy in malignant pleural mesothelioma. Ann Oncol. 2007;18:1196–202.
Weder W, Kestenholz P, Taverna C, et al. Neoadjuvant chemotherapy followed by extrapleural pneumonectomy in malignant pleural mesothelioma. J Clin Oncol. 2004;22:3451–7.
Flores RM, Krug LM, Rosenzweig KE, et al. Induction chemotherapy, extrapleural pneumonectomy, and postoperative high-dose radiotherapy for locally advanced malignant pleural mesothelioma: a phase II trial. J Thorac Oncol. 2006;1:289–95.
Rea F, Marulli G, Bortolotti L, et al. Induction chemotherapy, extrapleural pneumonectomy (EPP) and adjuvant hemi-thoracic radiation in malignant pleural mesothelioma (MPM): Feasibility and results. Lung Cancer. 2007;57:89–95.
Van Schil PE, Baas P, Gaafar R, et al. Trimodality therapy for malignant pleural mesothelioma: results from an EORTC phase II multicentre trial. Eur Respir J. 2010;36:1362–9.
Federico R, Adolfo F, Giuseppe M, et al. Phase II trial of neoadjuvant pemetrexed plus cisplatin followed by surgery and radiation in the treatment of pleural mesothelioma. BMC Cancer. 2013;13:22.
Tsao AS, He D, Saigal B, et al. Inhibition of c-Src expression and activation in malignant pleural mesothelioma tissues leads to apoptosis, cell cycle arrest, and decreased migration and invasion. Mol Cancer Ther. 2007;6:1962–72.
Mansfield A, Peikert T, Roden A, et al. Programmed cell death 1 ligand 1 expression and association with survival in mesothelioma. J Thorac Oncol. 2014;9:S7–S52.
Rusch VW, Figlin R, Godwin D, et al. Intrapleural cisplatin and cytarabine in the management of malignant pleural effusions: a Lung Cancer Study Group trial. J Clin Oncol. 1991;9:313–9.
Rusch V, Saltz L, Venkatraman E, et al. A phase II trial of pleurectomy/decortication followed by intrapleural and systemic chemotherapy for malignant pleural mesothelioma. J Clin Oncol. 1994;12:1156–63.
Colleoni M, Sartori F, Calabro F, et al. Surgery followed by intracavitary plus systemic chemotherapy in malignant pleural mesothelioma. Tumori. 1996;82:53–6.
Lee TT, Everett DL, Shu HK, et al. Radical pleurectomy/decortication and intraoperative radiotherapy followed by conformal radiation with or without chemotherapy for malignant pleural mesothelioma. J Thorac Cardiovasc Surg. 2002;124:1183–9.
Chang MY, Sugarbaker DJ. Innovative therapies: intraoperative intracavitary chemotherapy. Thorac Surg Clin. 2004;14:549–56.
Rice TW, Adelstein DJ, Kirby TJ, et al. Aggressive multimodality therapy for malignant pleural mesothelioma. Ann Thorac Surg. 1994;58:24–9.
Lu C, Perez-Soler R, Piperdi B, et al. Phase II study of a liposome-entrapped cisplatin analog (L-NDDP) administered intrapleurally and pathologic response rates in patients with malignant pleural mesothelioma. J Clin Oncol. 2005;23:3495–501.
Richards WG, Zellos L, Bueno R, et al. Phase I to II study of pleurectomy/decortication and intraoperative intracavitary hyperthermic cisplatin lavage for mesothelioma. J Clin Oncol. 2006;24:1561–7.
van Ruth S, Baas P, Haas RL, et al. Cytoreductive surgery combined with intraoperative hyperthermic intrathoracic chemotherapy for stage I malignant pleural mesothelioma. Ann Surg Oncol. 2003;10:176–82.
Ratto GB, Civalleri D, Esposito M, et al. Pleural space perfusion with cisplatin in the multimodality treatment of malignant mesothelioma: a feasibility and pharmacokinetic study. J Thorac Cardiovasc Surg. 1999;117:759–65.
Sterman DH, Haas A, Moon E, et al. A trial of intrapleural adenoviral-mediated Interferon-alpha2b gene transfer for malignant pleural mesothelioma. Am J Respir Crit Care Med. 2011;184:1395–9.
Sterman DH, Recio A, Vachani A, et al. Long-term follow-up of patients with malignant pleural mesothelioma receiving high-dose adenovirus herpes simplex thymidine kinase/ganciclovir suicide gene therapy. Clin Cancer Res. 2005;11:7444–53.
Sterman DH. Gene therapy for malignant pleural mesothelioma. Hematol Oncol Clin N Am. 2005;19:1147–73. viii.
Sterman DH, Treat J, Litzky LA, et al. Adenovirus-mediated herpes simplex virus thymidine kinase/ganciclovir gene therapy in patients with localized malignancy: results of a phase I clinical trial in malignant mesothelioma. Hum Gene Ther. 1998;9:1083–92.
Sterman DH, Recio A, Carroll RG, et al. A phase I clinical trial of single-dose intrapleural IFN-beta gene transfer for malignant pleural mesothelioma and metastatic pleural effusions: high rate of antitumor immune responses. Clin Cancer Res. 2007;13:4456–66.
Lucchi M, Chella A, Melfi F, et al. A phase II study of intrapleural immuno-chemotherapy, pleurectomy/decortication, radiotherapy, systemic chemotherapy and long-term sub-cutaneous IL-2 in stage II-III malignant pleural mesothelioma. Eur J Cardiothorac Surg. 2007;31:529–33. discussion 533-4.
Astoul P, Picat-Joossen D, Viallat JR, et al. Intrapleural administration of interleukin-2 for the treatment of patients with malignant pleural mesothelioma: a Phase II study. Cancer. 1998;83:2099–104.
Boutin C, Viallat JR, Van Zandwijk N, et al. Activity of intrapleural recombinant gamma-interferon in malignant mesothelioma. Cancer. 1991;67:2033–7.
Goey SH, Eggermont AM, Punt CJ, et al. Intrapleural administration of interleukin 2 in pleural mesothelioma: a phase I-II study. Br J Cancer. 1995;72:1283–8.
Yajnik S, Rosenzweig KE, Mychalczak B, et al. Hemithoracic radiation after extrapleural pneumonectomy for malignant pleural mesothelioma. Int J Radiat Oncol Biol Phys. 2003;56:1319–26.
Baldini EH, Recht A, Strauss GM, et al. Patterns of failure after trimodality therapy for malignant pleural mesothelioma. Ann Thorac Surg. 1997;63:334–8.
Ahamad A, Stevens CW, Smythe WR, et al. Intensity-modulated radiation therapy: a novel approach to the management of malignant pleural mesothelioma. Int J Radiat Oncol Biol Phys. 2003;55:768–75.
Gomez DR, Hong DS, Allen PK, et al. Patterns of failure, toxicity, and survival after extrapleural pneumonectomy and hemithoracic intensity-modulated radiation therapy for malignant pleural mesothelioma. J Thorac Oncol. 2013;8:238–45. A review of the patterns of failure post-EPP and IMRT.
Miles EF, Larrier NA, Kelsey CR, et al. Intensity-modulated radiotherapy for resected mesothelioma: the Duke experience. Int J Radiat Oncol Biol Phys. 2008;71:1143–50.
Allen AM, Czerminska M, Janne PA, et al. Fatal pneumonitis associated with intensity-modulated radiation therapy for mesothelioma. Int J Radiat Oncol Biol Phys. 2006;65:640–5.
Komaki R, Liao Z, Liu H, et al: Fatal pneumonitis associated with intensity-modulated radiation therapy for mesothelioma: in regard to Allen et al. (Int J Radiat Oncol Biol Phys 2006;65:640-645). Int J Radiat Oncol Biol Phys 66:1595-6; author reply 1596, 2006
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;63:1045–52.
Rosenzweig KE, Zauderer MG, Laser B, et al. Pleural intensity-modulated radiotherapy for malignant pleural mesothelioma. Int J Radiat Oncol Biol Phys. 2012;83:1278–83. Reports on the use of intensity-modulated radiotherapy (IMRT) in MPM patients post-resection.
Rimner A, Spratt DE, Zauderer MG, et al: Failure Patterns After Hemithoracic Pleural Intensity Modulated Radiation Therapy for Malignant Pleural Mesothelioma. Int J Radiat Oncol Biol Phys, 2014
Feigen M, Lee ST, Lawford C, et al. Establishing locoregional control of malignant pleural mesothelioma using high-dose radiotherapy and (18) F-FDG PET/CT scan correlation. J Med Imaging Radiat Oncol. 2011;55:320–32.
Minatel E, Trovo M, Polesel J, 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;83:78–82.
Chance WW, Rice DC, Allen P, et al: Postoperative hemithoracic intensity-modulated radiation therapy (IMRT) with an optional integrated boost for malignant pleural mesothelioma: toxicity, patterns of failure, and a matched survival analysis. ASTRO abstract, 2014.
Willner J, Jost A, Baier K, et al. A little to a lot or a lot to a little? An analysis of pneumonitis risk from dose-volume histogram parameters of the lung in patients with lung cancer treated with 3-D conformal radiotherapy. Strahlenther Onkol. 2003;179:548–56.
Chang JY, Komaki R, Wen HY, et al. Toxicity and patterns of failure of adaptive/ablative proton therapy for early-stage, medically inoperable non-small cell lung cancer. Int J Radiat Oncol Biol Phys. 2011;80:1350–7.
Chang JY, Komaki R, Lu C, et al. Phase 2 study of high-dose proton therapy with concurrent chemotherapy for unresectable stage III nonsmall cell lung cancer. Cancer. 2011;117:4707–13.
Chang JY, Cox JD. Improving radiation conformality in the treatment of non-small cell lung cancer. Semin Radiat Oncol. 2010;20:171–7.
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Daniel Gomez declares that he has no conflict of interest.
Anne Tsao is on the advisory board for Genentech, Roche, Lilly, Medimmune, Astellas, and Boeringer Ingelheim and has received grants from Medimmune.
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Gomez, D., Tsao, A.S. Local and Systemic Therapies for Malignant Pleural Mesothelioma. Curr. Treat. Options in Oncol. 15, 683–699 (2014). https://doi.org/10.1007/s11864-014-0314-4
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DOI: https://doi.org/10.1007/s11864-014-0314-4