Acta Clinica Belgica International Journal of Clinical and Laboratory Medicine
ISSN: 1784-3286 (Print) 2295-3337 (Online) Journal homepage: http://www.tandfonline.com/loi/yacb20
PATHOLOGIC COMPLETE REMISSION OF MALIGNANT PLEURAL MESOTHELIOMA AFTER COMBINED MODALITY TREATMENT: A CASE REPORT K Moubax, V Van Damme, P Nafteux, M Van den Heuvel, E Verbeken, Y Lievens & K Nackaerts To cite this article: K Moubax, V Van Damme, P Nafteux, M Van den Heuvel, E Verbeken, Y Lievens & K Nackaerts (2013) PATHOLOGIC COMPLETE REMISSION OF MALIGNANT PLEURAL MESOTHELIOMA AFTER COMBINED MODALITY TREATMENT: A CASE REPORT, Acta Clinica Belgica, 68:5, 386-388 To link to this article: http://dx.doi.org/10.2143/ACB.3362
Published online: 06 May 2014.
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Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=yacb20 Download by: [FU Berlin]
Date: 28 November 2016, At: 14:47
386
PATHOLOGIC COMPLETE REMISSION OF MALIGNANT PLEURAL MESOTHELIOMA
Case Report
PATHOLOGIC COMPLETE REMISSION OF MALIGNANT PLEURAL MESOTHELIOMA AFTER COMBINED MODALITY TREATMENT: A CASE REPORT Moubax K1, Van Damme V2, Nafteux P3, Van den Heuvel M4, Verbeken E5, Lievens Y6, 7, Nackaerts K1 1
Department of Pulmonology, University Hospital Gasthuisberg, KU Leuven, Leuven, Department of Pulmonology, Hospital Sint-Andries, Tielt, 3Department of Thoracic Surgery, University Hospital Gasthuisberg, KU Leuven, Leuven, 4Department of Pulmonology, AZ Turnhout, Turnhout, 5Department of Pathology, University Hospital Sint-Rafaël, KU Leuven, Leuven, 6 Department of Radiation Oncology, University Hospital Gasthuisberg, KU Leuven, Leuven, 7 Department of Radiation Oncology, University Hospital Ghent, RU Ghent, Ghent 2
Correspondence and offprint requests to: Kristiaan Nackaerts, E-mail: [email protected]
ABSTRACT A 50-year-old patient with malignant pleural mesothelioma (epithelial subtype, clinically staged cT1bN0M0) underwent a combined modality treatment, including induction chemotherapy, followed by extrapleural pneumonectomy (EPP) and radical radiotherapy. After pathologic examination of the surgical specimen, a complete remission (pT0N0) was observed. The complete disappearance of solid tumour tissue after induction chemotherapy is a rarely observed and documented finding in the combined modality treatment of malignant pleural mesothelioma. The real prognostic value of the pathologic complete remission of a malignant pleural mesothelioma definitely needs to be further evaluated in a larger series of patients. Key words: mesothelioma, pleura, combined modality treatment, surgery
INTRODUCTION Malignant pleural mesothelioma (MPM) is a locally invasive tumour of the pleura, strongly associated with previous exposure to asbestos. The use of asbestos has been widespread in the late twentieth century, explaining the increasing incidence of MPM, which is predicted to peak in the next 10-20 years (1). The median
Acta Clinica Belgica, 2013; 68-5
survival time of MPM amounts to 4-12 months (2). In general, the role of single modality therapy for MPM with radiotherapy or surgery remains controversial while the survival of MPM patients can only modestly be prolonged with platin-pemetrexed combination chemotherapy. Consequently, combined modality treatment regimens have been developed and increasingly investigated. Here, we report a case of pathologic complete remission of MPM after surgical combined modality treatment.
CASE REPORT A 50-year-old man consulted because of dyspnoea, left chest pain, fever and malaise. His medical history revealed a deep vein thrombosis and surgery for varicose veins one year before. In spite of a treatment with amoxicillin-clavulanate, the fever reappeared and the chest pain persisted. Further imaging with positron emission tomography-computed tomography (PET-CT) scan confirmed the radiologically documented presence of a pleural effusion with an irregular thickened pleura and pleural calcifications on the left side (Figure 1A, B). During thoracoscopy, pleural thickening was observed and biopsied. A talc poudrage was also performed. Pathologic examination confirmed the presence of a malignant pleural mesothelioma of the epithelial subtype (Figure 1C). The staging was completed with a videomediastinoscopy and a laparoscopy, which were both negative. The final staging of this malignant pleural mesothelioma was cT1bN0M0. The patient started a combined modality treatment, including induction chemotherapy, followed by extrapleural
doi: 10.2143/ACB.3362
PATHOLOGIC COMPLETE REMISSION OF MALIGNANT PLEURAL MESOTHELIOMA
A B C
D E F Figure 1: Before induction chemotherapy: A. CT-scan: thickened, contrast-captating pleura and small amount of pleural fluid on the left side. B. PET-scan: increased FDG accumulation in the left pleura, physiological FDG accumulation in the heart; C. microscopic view of malignant pleural mesothelioma, epithelial subtype (haematoxylin and eosin 100×). After induction chemotherapy: D. CT-scan: slight decrease of pleural thickening and pleural fluid on the left side. E. PET-scan: visible but decreased FDG accumulation in the left pleura; F. microscopic view of scarred pleura with presence of scarred vessel and siderosis due to previous haemorrhagic necrosis (haematoxylin and eosin 50×).
neumonectomy and radical radiotherapy. Induction chemotherp apy consisted of 3 cycles of cisplatin 75 mg/m2 and pemetrexed 500 mg/m2, administered once every 21 days. Whole body PET-CT examination performed after induction chemotherapy showed a slight decrease in pleural thickness and 16F-fluorodeoxyglucose (FDG) uptake (Figure 1B, E). A left extrapleural pneumonectomy was performed without any postoperative complications. Macroscopically, no remaining tumour tissue was seen. Extensive sampling for histologic examination revealed scar tissue, but no residual tumour cells (Figure 1C, F). The final pathologic staging was pT0N0M0. Postoperative left hemithoracic radiotherapy was given to a dose of 54 Gy in 30 fractions of 1.8 Gy. Our patient survived for 73 months post-surgery without any documented relapse of his mesothelioma (6-monthly PET-CT evaluation). In the years following combined modality treatment, his physical condition became, however, increasingly impaired by chronic cardiac failure, for which he needed medical care. He died after a cardiac arrest.
DISCUSSION Traditionally, malignant pleural mesothelioma is regarded by the medical community as a non-curable disease with a
poor median survival of less than 12 months (1). This is largely due to the aggressive nature of MPM and its resistance to any single-treatment modality (1, 2). The majority of MPM patients are offered chemotherapy only. The combination treatment of cisplatin and pemetrexed has been demonstrated to significantly increase median survival, compared to single cisplatin treatment and is the only reimbursed chemotherapy regimen for MPM (1). Even after initial successful chemotherapy results, MPM will relapse but no further chemotherapy regimens have been registered yet. No molecular targeted treatments have to date been proven to impact significantly on the course of MPM disease. Therefore, combining different treatment modalities in MPM patients has been intensively investigated to improve prognosis. The combination of neoadjuvant chemotherapy, extrapleural pneumonectomy (EPP) and adjuvant pleural intensity-modulated radiation therapy (IMRT) appears to be a promising multi- or tri-modality treatment for selected MPM patients (3). This tri-modality treatment may not only result in a prolonged survival, but also may improve quality of life, as has been assessed in several, mostly retrospective or non-randomized prospective studies (2). The lack of large randomized clinical trials (RCT) and the relatively small number of selected MPM patients make it difficult for combined modality treatment (with EPP) to become generally accepted
Acta Clinica Belgica, 2013; 68-5
387
388
PATHOLOGIC COMPLETE REMISSION OF MALIGNANT PLEURAL MESOTHELIOMA
in treatment guidelines of MPM (1, 3). In 2011, the results of the Mesothelioma and Radical Surgery randomised feasibility study (MARS trial) were published (4). After registering 122 patients, only 50 MPM patients were randomised between EPP or no EPP. No survival advantage for the EPP surgery group was noted and also no differences in quality of life between both study groups were observed. Although these data were obtained in a limited group of patients, it was nevertheless concluded that radical surgery with EPP within trimodality treatment of MPM had no benefit to offer and could even possibly harm patients. As a reaction to the MARS paper, a statement of the International Mesothelioma Interest Group was published after their Congress Meeting in Boston in 2012 (5). A multidisciplinary panel of experts stated that the treatment of all solid tumours, also including MPM, is dependent on macroscopic complete resection and treatment of micrometastatic disease. The role of surgery, either EPP or lungsparing pleurectomy/decortication (P/D), was discussed. After pointing in detail to all shortcomings of the MARS trial results, they stated that surgery, whether P/D or EPP, with the goal of obtaining a macroscopic complete resection should be performed in the multimodality approach of MPM. This statement was based on multiple large, mainly non-randomised and often retrospective institutional series of surgical combined modality treatment for MPM. The type of surgery will depend on clinical factors and on individual surgical judgement and expertise (6). EPP, as in our patient, has been performed and accepted by many as a feasible treatment option in wellselected patients (1). This procedure involves en bloc resection of the parietal and visceral pleura, lung, ipsilateral hemidiaphragm and ipsilateral pericardium. However, there remains some concern about the morbidity, mortality and the efficacy of this major surgical procedure (1, 2). Debulking of the pleura by P/D, which implies resection of the parietal and visceral pleura, pericardium and diaphragm (if needed), while leaving the lung intact, is another surgical option (3). Recently, an analysis of 667 patients (in a non-randomised, multi-institutional study) showed that patients who underwent EPP generally had a poorer survival compared to P/D (7). However, because this was a retrospective analysis, selection bias may have played a role in the observed survival differences. Another problem observed with tri-modality treatment is the high proportion of MPM patients not being able to complete all 3 treatment modalities (1, 2). This all illustrates the importance of a careful patient selection at diagnosis. First, because there are case reports describing MPM patients, as in our case, who are in complete remission after multimodality treatment and therefore may survive longer (8, 9). Second, because patients who survive at least three years postoperatively, have a fifty procent chance of surviving also beyond 5 years (10). In order to improve the results of combined modality therapy, patient selection should ideally be further refined. The currently accepted MPM staging systems have not consistently stratified the survival of patients with MPM (10). This is why Sugarbaker et al. investigated, in a retrospective study of 636 patients, several additional factors that could play a role in determining outcome (10). They found that patients who survived longer than three years after surgery for MPM
Acta Clinica Belgica, 2013; 68-5
(when compared to less than three years survivors), were relatively younger and relatively more frequent of female gender. They had also more tumours of epithelial histologic subtype (less of the sarcomatoid or mixed type) and were more likely to have normal preoperative counts for white blood cells, haemoglobin and platelets (10). The longest median survival (more than seven years) was experienced by women under the median age of 56 (10). Our MPM patient was also a younger patient (50 years at diagnosis) and his tumour was of the epithelial subtype. Because of the relative rarity of MPM, its aggressive nature and the lack of useful predictive and prognostic biomarkers there remains a multitude of challenges in the randomization process between P/D and EPP. Until now, no large RCT examining combined modality with EPP versus P/D has been performed (1, 2). In conclusion, trimodality treatment with neoadjuvant chemotherapy, surgery and adjuvant radiotherapy may be advantageous for some MPM patients by increasing the median survival and may sometimes even lead not only to a macroscopic but occasionally also to a complete pathologic remission in few patients. The real prognostic value of pathologic complete remission after combined modality treatment of MPM definitely needs to be further evaluated in a larger series of patients (9). Elaborating how exactly to preselect MPM patients for better ‘personalising’ their surgical modality will finally be the key research question in future clinical management trials of malignant pleural mesothelioma.
CONFLICT OF INTEREST: None. REFERENCES 1. Scherpereel A, Astoul P, Baas P, et al. Guidelines for the European Respiratory Society and the European Society of Thoracic Surgeons for the management of malignant pleural mesothelioma. Eur Respir J 2010; 35: 479-495. 2. Cao CQ, Yan TD, Bannon PG, McCaughan BC. A systematic review of extrapleural pneumonectomy for malignant pleural mesothelioma. J Thorac Oncol 2010; 5: 1692-1703. 3. Zauderer MG, Krug LM. The evaluation of multimodality therapy for malignant pleural mesothelioma. Curr Treat Options Oncol 2011; 12(2): 163-172. 4. 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) randomized feasibility study. Lancet Oncol 2011; 12(8): 763-772. 5. Rusch V, Baldini EH, Bueno R, 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: 909-910. 6. Baas P. Primum non nocere? Does this also apply to mesothelioma? Lung Cancer 2012; 77(1): 1. 7. 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(3): 620-626. 8. Takanen S, Resuli B, Graziano V, et al. Complete response and long-term survival in malignant pleural mesothelioma: case report. Anticancer Research 2012; 32: 1485-1488. 9. Bech C, Sörensen JB. Chemotherapy induced pathologic complete response in malignant pleural mesothelioma. A review and case report. J Thoracic Oncol 2010; 5(5): 735-740. 10. Sugarbaker DJ, Wolf SA, 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(2): 298-303.
ISSN: 1784-3286 (Print) 2295-3337 (Online) Journal homepage: http://www.tandfonline.com/loi/yacb20
PATHOLOGIC COMPLETE REMISSION OF MALIGNANT PLEURAL MESOTHELIOMA AFTER COMBINED MODALITY TREATMENT: A CASE REPORT K Moubax, V Van Damme, P Nafteux, M Van den Heuvel, E Verbeken, Y Lievens & K Nackaerts To cite this article: K Moubax, V Van Damme, P Nafteux, M Van den Heuvel, E Verbeken, Y Lievens & K Nackaerts (2013) PATHOLOGIC COMPLETE REMISSION OF MALIGNANT PLEURAL MESOTHELIOMA AFTER COMBINED MODALITY TREATMENT: A CASE REPORT, Acta Clinica Belgica, 68:5, 386-388 To link to this article: http://dx.doi.org/10.2143/ACB.3362
Published online: 06 May 2014.
Submit your article to this journal
Article views: 12
View related articles
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=yacb20 Download by: [FU Berlin]
Date: 28 November 2016, At: 14:47
386
PATHOLOGIC COMPLETE REMISSION OF MALIGNANT PLEURAL MESOTHELIOMA
Case Report
PATHOLOGIC COMPLETE REMISSION OF MALIGNANT PLEURAL MESOTHELIOMA AFTER COMBINED MODALITY TREATMENT: A CASE REPORT Moubax K1, Van Damme V2, Nafteux P3, Van den Heuvel M4, Verbeken E5, Lievens Y6, 7, Nackaerts K1 1
Department of Pulmonology, University Hospital Gasthuisberg, KU Leuven, Leuven, Department of Pulmonology, Hospital Sint-Andries, Tielt, 3Department of Thoracic Surgery, University Hospital Gasthuisberg, KU Leuven, Leuven, 4Department of Pulmonology, AZ Turnhout, Turnhout, 5Department of Pathology, University Hospital Sint-Rafaël, KU Leuven, Leuven, 6 Department of Radiation Oncology, University Hospital Gasthuisberg, KU Leuven, Leuven, 7 Department of Radiation Oncology, University Hospital Ghent, RU Ghent, Ghent 2
Correspondence and offprint requests to: Kristiaan Nackaerts, E-mail: [email protected]
ABSTRACT A 50-year-old patient with malignant pleural mesothelioma (epithelial subtype, clinically staged cT1bN0M0) underwent a combined modality treatment, including induction chemotherapy, followed by extrapleural pneumonectomy (EPP) and radical radiotherapy. After pathologic examination of the surgical specimen, a complete remission (pT0N0) was observed. The complete disappearance of solid tumour tissue after induction chemotherapy is a rarely observed and documented finding in the combined modality treatment of malignant pleural mesothelioma. The real prognostic value of the pathologic complete remission of a malignant pleural mesothelioma definitely needs to be further evaluated in a larger series of patients. Key words: mesothelioma, pleura, combined modality treatment, surgery
INTRODUCTION Malignant pleural mesothelioma (MPM) is a locally invasive tumour of the pleura, strongly associated with previous exposure to asbestos. The use of asbestos has been widespread in the late twentieth century, explaining the increasing incidence of MPM, which is predicted to peak in the next 10-20 years (1). The median
Acta Clinica Belgica, 2013; 68-5
survival time of MPM amounts to 4-12 months (2). In general, the role of single modality therapy for MPM with radiotherapy or surgery remains controversial while the survival of MPM patients can only modestly be prolonged with platin-pemetrexed combination chemotherapy. Consequently, combined modality treatment regimens have been developed and increasingly investigated. Here, we report a case of pathologic complete remission of MPM after surgical combined modality treatment.
CASE REPORT A 50-year-old man consulted because of dyspnoea, left chest pain, fever and malaise. His medical history revealed a deep vein thrombosis and surgery for varicose veins one year before. In spite of a treatment with amoxicillin-clavulanate, the fever reappeared and the chest pain persisted. Further imaging with positron emission tomography-computed tomography (PET-CT) scan confirmed the radiologically documented presence of a pleural effusion with an irregular thickened pleura and pleural calcifications on the left side (Figure 1A, B). During thoracoscopy, pleural thickening was observed and biopsied. A talc poudrage was also performed. Pathologic examination confirmed the presence of a malignant pleural mesothelioma of the epithelial subtype (Figure 1C). The staging was completed with a videomediastinoscopy and a laparoscopy, which were both negative. The final staging of this malignant pleural mesothelioma was cT1bN0M0. The patient started a combined modality treatment, including induction chemotherapy, followed by extrapleural
doi: 10.2143/ACB.3362
PATHOLOGIC COMPLETE REMISSION OF MALIGNANT PLEURAL MESOTHELIOMA
A B C
D E F Figure 1: Before induction chemotherapy: A. CT-scan: thickened, contrast-captating pleura and small amount of pleural fluid on the left side. B. PET-scan: increased FDG accumulation in the left pleura, physiological FDG accumulation in the heart; C. microscopic view of malignant pleural mesothelioma, epithelial subtype (haematoxylin and eosin 100×). After induction chemotherapy: D. CT-scan: slight decrease of pleural thickening and pleural fluid on the left side. E. PET-scan: visible but decreased FDG accumulation in the left pleura; F. microscopic view of scarred pleura with presence of scarred vessel and siderosis due to previous haemorrhagic necrosis (haematoxylin and eosin 50×).
neumonectomy and radical radiotherapy. Induction chemotherp apy consisted of 3 cycles of cisplatin 75 mg/m2 and pemetrexed 500 mg/m2, administered once every 21 days. Whole body PET-CT examination performed after induction chemotherapy showed a slight decrease in pleural thickness and 16F-fluorodeoxyglucose (FDG) uptake (Figure 1B, E). A left extrapleural pneumonectomy was performed without any postoperative complications. Macroscopically, no remaining tumour tissue was seen. Extensive sampling for histologic examination revealed scar tissue, but no residual tumour cells (Figure 1C, F). The final pathologic staging was pT0N0M0. Postoperative left hemithoracic radiotherapy was given to a dose of 54 Gy in 30 fractions of 1.8 Gy. Our patient survived for 73 months post-surgery without any documented relapse of his mesothelioma (6-monthly PET-CT evaluation). In the years following combined modality treatment, his physical condition became, however, increasingly impaired by chronic cardiac failure, for which he needed medical care. He died after a cardiac arrest.
DISCUSSION Traditionally, malignant pleural mesothelioma is regarded by the medical community as a non-curable disease with a
poor median survival of less than 12 months (1). This is largely due to the aggressive nature of MPM and its resistance to any single-treatment modality (1, 2). The majority of MPM patients are offered chemotherapy only. The combination treatment of cisplatin and pemetrexed has been demonstrated to significantly increase median survival, compared to single cisplatin treatment and is the only reimbursed chemotherapy regimen for MPM (1). Even after initial successful chemotherapy results, MPM will relapse but no further chemotherapy regimens have been registered yet. No molecular targeted treatments have to date been proven to impact significantly on the course of MPM disease. Therefore, combining different treatment modalities in MPM patients has been intensively investigated to improve prognosis. The combination of neoadjuvant chemotherapy, extrapleural pneumonectomy (EPP) and adjuvant pleural intensity-modulated radiation therapy (IMRT) appears to be a promising multi- or tri-modality treatment for selected MPM patients (3). This tri-modality treatment may not only result in a prolonged survival, but also may improve quality of life, as has been assessed in several, mostly retrospective or non-randomized prospective studies (2). The lack of large randomized clinical trials (RCT) and the relatively small number of selected MPM patients make it difficult for combined modality treatment (with EPP) to become generally accepted
Acta Clinica Belgica, 2013; 68-5
387
388
PATHOLOGIC COMPLETE REMISSION OF MALIGNANT PLEURAL MESOTHELIOMA
in treatment guidelines of MPM (1, 3). In 2011, the results of the Mesothelioma and Radical Surgery randomised feasibility study (MARS trial) were published (4). After registering 122 patients, only 50 MPM patients were randomised between EPP or no EPP. No survival advantage for the EPP surgery group was noted and also no differences in quality of life between both study groups were observed. Although these data were obtained in a limited group of patients, it was nevertheless concluded that radical surgery with EPP within trimodality treatment of MPM had no benefit to offer and could even possibly harm patients. As a reaction to the MARS paper, a statement of the International Mesothelioma Interest Group was published after their Congress Meeting in Boston in 2012 (5). A multidisciplinary panel of experts stated that the treatment of all solid tumours, also including MPM, is dependent on macroscopic complete resection and treatment of micrometastatic disease. The role of surgery, either EPP or lungsparing pleurectomy/decortication (P/D), was discussed. After pointing in detail to all shortcomings of the MARS trial results, they stated that surgery, whether P/D or EPP, with the goal of obtaining a macroscopic complete resection should be performed in the multimodality approach of MPM. This statement was based on multiple large, mainly non-randomised and often retrospective institutional series of surgical combined modality treatment for MPM. The type of surgery will depend on clinical factors and on individual surgical judgement and expertise (6). EPP, as in our patient, has been performed and accepted by many as a feasible treatment option in wellselected patients (1). This procedure involves en bloc resection of the parietal and visceral pleura, lung, ipsilateral hemidiaphragm and ipsilateral pericardium. However, there remains some concern about the morbidity, mortality and the efficacy of this major surgical procedure (1, 2). Debulking of the pleura by P/D, which implies resection of the parietal and visceral pleura, pericardium and diaphragm (if needed), while leaving the lung intact, is another surgical option (3). Recently, an analysis of 667 patients (in a non-randomised, multi-institutional study) showed that patients who underwent EPP generally had a poorer survival compared to P/D (7). However, because this was a retrospective analysis, selection bias may have played a role in the observed survival differences. Another problem observed with tri-modality treatment is the high proportion of MPM patients not being able to complete all 3 treatment modalities (1, 2). This all illustrates the importance of a careful patient selection at diagnosis. First, because there are case reports describing MPM patients, as in our case, who are in complete remission after multimodality treatment and therefore may survive longer (8, 9). Second, because patients who survive at least three years postoperatively, have a fifty procent chance of surviving also beyond 5 years (10). In order to improve the results of combined modality therapy, patient selection should ideally be further refined. The currently accepted MPM staging systems have not consistently stratified the survival of patients with MPM (10). This is why Sugarbaker et al. investigated, in a retrospective study of 636 patients, several additional factors that could play a role in determining outcome (10). They found that patients who survived longer than three years after surgery for MPM
Acta Clinica Belgica, 2013; 68-5
(when compared to less than three years survivors), were relatively younger and relatively more frequent of female gender. They had also more tumours of epithelial histologic subtype (less of the sarcomatoid or mixed type) and were more likely to have normal preoperative counts for white blood cells, haemoglobin and platelets (10). The longest median survival (more than seven years) was experienced by women under the median age of 56 (10). Our MPM patient was also a younger patient (50 years at diagnosis) and his tumour was of the epithelial subtype. Because of the relative rarity of MPM, its aggressive nature and the lack of useful predictive and prognostic biomarkers there remains a multitude of challenges in the randomization process between P/D and EPP. Until now, no large RCT examining combined modality with EPP versus P/D has been performed (1, 2). In conclusion, trimodality treatment with neoadjuvant chemotherapy, surgery and adjuvant radiotherapy may be advantageous for some MPM patients by increasing the median survival and may sometimes even lead not only to a macroscopic but occasionally also to a complete pathologic remission in few patients. The real prognostic value of pathologic complete remission after combined modality treatment of MPM definitely needs to be further evaluated in a larger series of patients (9). Elaborating how exactly to preselect MPM patients for better ‘personalising’ their surgical modality will finally be the key research question in future clinical management trials of malignant pleural mesothelioma.
CONFLICT OF INTEREST: None. REFERENCES 1. Scherpereel A, Astoul P, Baas P, et al. Guidelines for the European Respiratory Society and the European Society of Thoracic Surgeons for the management of malignant pleural mesothelioma. Eur Respir J 2010; 35: 479-495. 2. Cao CQ, Yan TD, Bannon PG, McCaughan BC. A systematic review of extrapleural pneumonectomy for malignant pleural mesothelioma. J Thorac Oncol 2010; 5: 1692-1703. 3. Zauderer MG, Krug LM. The evaluation of multimodality therapy for malignant pleural mesothelioma. Curr Treat Options Oncol 2011; 12(2): 163-172. 4. 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) randomized feasibility study. Lancet Oncol 2011; 12(8): 763-772. 5. Rusch V, Baldini EH, Bueno R, 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: 909-910. 6. Baas P. Primum non nocere? Does this also apply to mesothelioma? Lung Cancer 2012; 77(1): 1. 7. 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(3): 620-626. 8. Takanen S, Resuli B, Graziano V, et al. Complete response and long-term survival in malignant pleural mesothelioma: case report. Anticancer Research 2012; 32: 1485-1488. 9. Bech C, Sörensen JB. Chemotherapy induced pathologic complete response in malignant pleural mesothelioma. A review and case report. J Thoracic Oncol 2010; 5(5): 735-740. 10. Sugarbaker DJ, Wolf SA, 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(2): 298-303.
