Radiotherapy for malignant pleural mesothelioma (Review)

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1 Chapman E, García Diéguez M This is a reprint of a Cochrane review, prepared and maintained by The Cochrane Collaboration and published in The Cochrane Library 2010, Issue 4

2 T A B L E O F C O N T E N T S HEADER ABSTRACT PLAIN LANGUAGE SUMMARY BACKGROUND OBJECTIVES METHODS RESULTS DISCUSSION AUTHORS CONCLUSIONS ACKNOWLEDGEMENTS REFERENCES CHARACTERISTICS OF STUDIES DATA AND ANALYSES WHAT S NEW HISTORY CONTRIBUTIONS OF AUTHORS DECLARATIONS OF INTEREST INDEX TERMS i

3 [Intervention Review] Radiotherapy for malignant pleural mesothelioma Evelina Chapman 1, Marcelo García Diéguez 1 1 Epidemiological Research Center, National Academy of Medicine, Buenos Aires, Argentina Contact address: Evelina Chapman, Epidemiological Research Center, National Academy of Medicine, Carlos Gardel 768, Dpto 3, Buenos Aires, 4000, Argentina. Editorial group: Cochrane Lung Cancer Group. Publication status and date: Edited (no change to conclusions), published in Issue 4, Review content assessed as up-to-date: 5 June Citation: Chapman E, García Diéguez M. Radiotherapy for malignant pleural mesothelioma. Cochrane Database of Systematic Reviews 2006, Issue 3. Art. No.: CD DOI: / CD pub4. Background A B S T R A C T Malignant pleural mesothelioma is a relatively uncommon disease, but the incidence is increasing and is expected to peak in many developed countries in the next two decades. The management of patients with malignant mesothelioma is controversial. Very few patients are suitable for any potentially curative treatment and the effectiveness of radical therapy with surgery, radiotherapy and/or chemotherapy in curing patients or prolonging survival is uncertain. The role of radiotherapy is controversial although it has been used as part of multimodal therapy. The present review will try to clarify these uncertainties. Objectives To assess the effectiveness and safety of radiotherapy on patients with malignant pleural mesothelioma in any stage of the disease. Search methods We searched the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 4, 2008), MEDLINE (1966 to January 2009) and EMBASE (1974 to January 2009). We performed handsearches aimed at the identification of evidence by reviewing journals not indexed in databases, conference proceedings and/or scientific meetings. Selection criteria We included all randomised controlled clinical trials using radiotherapy for malignant pleural mesothelioma in any stage, alone or combined with other therapies in patients of either sex and any age. We excluded studies without a control group. Data collection and analysis No studies fulfilled the inclusion criteria. Main results We found no reports of randomised comparisons of radiotherapy alone or combined for patients with malignant pleural mesothelioma. Authors conclusions As radiotherapy has never been compared to chemotherapy or surgery or to best supportive care (as part of combination therapy) in a prospective, randomised trial, there are no data to support one or the other treatment as a better option for patients with malignant pleural mesothelioma. There is a need for multicentre controlled randomised trials assessing the role of radiotherapy in the radical treatment of malignant pleural mesothelioma. The studies should be limited to patients with malignant pleural mesothelioma, classified 1

4 by stage, cytology and type of radiotherapy. The type of radiotherapy should be defined in advance and variables of radiotherapy dose definition and delivery should be carefully controlled. P L A I N L A N G U A G E S U M M A R Y There is no evidence that radiotherapy could help to cure or to prolong the survival of patients with malignant pleural mesothelioma The incidence of malignant pleural mesothelioma is increasing and is expected to peak in many developed countries in the next two decades. In 80% of the patients with malignant pleural mesothelioma there is a clear history of occupational or domestic exposure to asbestos. Very few patients are suitable for any potentially curative treatment and the effectiveness of radical therapy with surgery, radiotherapy and/or chemotherapy in curing patients or prolonging survival is uncertain. The role of radiotherapy is controversial. It has been used as a component of multimodal therapy (plus chemotherapy and/or surgery). The reviewers have not found any reports of randomised controlled trials (RCTs) that show that radiotherapy is an effective option for malignant pleural mesothelioma. There is a need for multicentre experimental studies assessing the role of radiotherapy in this disease. B A C K G R O U N D Malignant mesothelioma is a tumour affecting the pleura or the peritoneum. Malignant pleural mesothelioma was described by J. Wagner (Wagner 1960). The disease mainly occurs in the fifth to seventh decade of life, and in men more often than in women (3.6:1) (Scagliotti 2005). Mesothelioma is a relatively uncommon disease, but the incidence is increasing and is expected to peak in many developed countries in the next two decades (Price 1997; Peto 1999). The main aetiological factor is exposure to asbestos, especially the form known as blue asbestos or crocidolite. In 80% of patients with mesothelioma there is a clear history of occupational or domestic exposure to asbestos, but there is usually a long latent period between the exposure and clinical presentation (Bianchi 1997; Peto 1999). Another possible aetiological factor of less certain significance is the SV-40 simian virus (Bocchetta 2000). The two most common symptoms are breathlessness due to pleural effusion or diffuse pleural thickening, and chest pain, developing insidiously over several months (Pisani 1988; Yates 1997). As the disease progresses, systemic symptoms develop with weight loss, anorexia, cough and fever, and in the terminal stages nodal and other metastases are not uncommon, although rare at presentation (Elmes 1976; Hillerdahl 1983). Survival from the onset of symptoms is approximately one year (Yates 1997; Curran 1998). Although the clinical history and radiological findings are usually typical, a diagnosis can only be confirmed by histopathology. There are three main subtypes of malignant mesothelioma: epithelial, sarcomatoid and mixed (Metintas 1995). Disease stage at diagnosis is one of the most important prognostic factors. Several staging systems for this condition have been proposed, and none has been accepted universally. The oldest staging system, introduced by Butchart et al (Butchart 1976), has already been abandoned due to a lack of prognostic value, in favour of TNM-based systems. The International Mesothelioma Interest Group (IMIG) proposed a TNM-based staging system based on an analysis of information about the impact of tumour and nodal status on survival (Rusch 1995). Computed tomography (CT) or magnetic resonance imaging (MRI) are necessary for accurate clinical staging. Using the IMIG system, surgical staging has been shown to be superior to clinical staging (Heelan 1999) and the experts recommend obtaining an earlier and reliable diagnosis by thoracoscopy except in cases of preoperative contraindication or pleural symphysis (Scherpereel 2009). A major limitation of these staging systems is the fact that only a small minority of patients are considered suitable for surgery. The management of patients with malignant mesothelioma is controversial. Very few patients are suitable for any potentially curative treatment and the effectiveness of radical therapy with surgery, radiotherapy and/or chemotherapy in curing patients or prolonging survival is uncertain. Pleurectomy and extrapleural pneumonectomy are the most widely investigated surgical procedures (Butchart 1976; Sugarbaker 1996). Other modalities such as immunological therapy are being tested at present but the results are inconclusive. In patients with advanced disease, response rates with single or multiple chemotherapy agents rarely exceed 25%. Doxorubicin is the most widely studied drug but the overall rate of therapeutic response is still poor (Ong 1996; Ryan 1998). 2

5 New approaches are being developed for treating pleural malignant mesothelioma, such as combined pemetrexed/cisplatin chemotherapy (Vogelzang 2003), biological agents and targeted therapies (Pistolesi 2004). The role of radiotherapy in the management is controversial. There is no evidence to suggest that radiotherapy alone affects survival although it may have a role in the palliation of pain (Munter 2003; Davis 1994). Because mesothelioma typically involves large areas of the pleura at diagnosis, radical, potentially curative radiotherapy is difficult to deliver to patients because of the large volumes of lung, liver, heart and spinal cord that would receive potentially toxic doses (Brady 1981; Gordon 1982; Bissett 1991; Hakkinen 1996). Also, there have been described cases of fatal pneumonitis in some patients undergoing radiotherapy (Allen 2006). Radiotherapy has been used as a component of multimodal therapy. Following radical surgery, radiotherapy may be effective in reducing local recurrence of the tumour and improving overall survival (Rusch 2001). Some authors have suggested that radiotherapy plus chemotherapy as an adjuvant to surgery results in a 22% survival at five years (Sugarbaker 1996; Maggi 2001). The effectiveness of radiotherapy alone or in combination for curative or palliative purposes remains uncertain and the most appropriate and effective dose and techniques are unclear (Law 1984; Alberts 1988; Baldini 2004). The present review will try to clarify these uncertainties. O B J E C T I V E S To assess the effectiveness and safety of radiotherapy on patients with malignant pleural mesothelioma in any stage of the disease. M E T H O D S Criteria for considering studies for this review Types of studies All randomised controlled clinical trials using radiotherapy for malignant pleural mesothelioma in any stage, alone or combined with other therapies. We excluded studies without a control group and studies on prophylactic treatment to incision sites. Types of participants Patients of either sex and any age with a diagnosis of malignant pleural mesothelioma, confirmed by histopathology, of any stage at presentation. Types of interventions a) Megavoltage external beam radiotherapy, either conventional, conformal or intensity modulated. b) Kilovoltage radiotherapy c) Brachytherapy with interstitial implants or non-sealed sources. Both curative and palliative radiotherapy were considered. Types of outcome measures The primary outcome was overall survival (defined from the time of randomisation to the time of death due to any cause). We also considered the following additional outcomes for inclusion: 1) Studies with curative intent: a. Progression-free survival b. Symptom relief, particularly of breathlessness and pain. c. Objective tumour response d. Radiation adverse events 2) Studies with palliative intent: a. Symptom relief, particularly of breathlessness and pain. b. Radiation adverse events Search methods for identification of studies We conducted electronic and handsearches. 1. Electronic search: we searched all randomised controlled clinical trials in electronic databases such as the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library Issue 4, 2008), MEDLINE (1966 to January 2009) and EMBASE (1974 to January 2009). Searches were designed according to the recommendations by the Cochrane Collaboration (Higgins 2008) and run by the Trials Search Co-ordinator. 2. Handsearching was aimed at the identification of evidence by reviewing journals not indexed in databases, proceedings of conferences and/or scientific meetings. We located other studies by searching in the literature references identified by the first search of the review. 3. We contacted other researchers, scientific societies and experts. SEARCH STRATEGY #1 (((tumour* AND pleura) OR (tumour* AND peritoneum) OR (tumour* AND pericardium)) AND mesothelioma[tw]) OR ((pleura* AND neoplasm*) AND mesothelioma[tw]) OR (pleural neoplasm[mh] AND mesothelioma[tw]) OR (mesothelioma[mh] OR mesothelioma*[tw]) #2 (radiotherapy[mh] OR radiation oncology[mh] OR (thoracic* AND radiotherap*) OR (thoracic* AND radiation*) OR (radiation[tw] AND therap*[tw])) #3 1 AND 2 Data collection and analysis 3

6 The search did not identify any studies that fulfilled the inclusion criteria. Methods that would be applied if trials were included in a future update of the review: All studies would be selected and assessed independently by two qualified reviewers. Included studies would be assessed in accordance with The Cochrane Collaboration s tool for assessing risk of bias (Higgins 2008). For each study, the following should be considered: Selection bias: systematic differences between baseline characteristics of the comparison groups. - Sequence generation: a description for allocating interventions to participants based on a random process. - Allocation concealment: a description of any method to secure implementation of the random assignments to prevent that those allocations could have been foreseen. Performance bias: systematic differences between groups in the care provided or in other factors different from the intervention. - Blinding of participants, personnel and outcome assessors: a description of measures used to blind study participants and personnel for knowledge of which intervention a participant received. Description of any evaluation of effective blinding should be considered. Blinding should be considered important for the outcomes of symptom relief, particularly of breathlessness and pain, tumour response and adverse events. Attrition bias: systematic differences between groups in withdrawals from the study. - Incomplete outcome data: a description of the level of completeness of each outcome, including attrition and exclusions. Number of randomised patients in each group and number of evaluated patients with reasons for attrition or exclusion reported. For each domain, two authors independently should judge the of risk of bias in accordance with the following classification: Yes, for low risk of bias; No, for high risk of bias; Unclear, for insufficient information reported. Data extraction To ensure validity, two qualified team members would extract all data independently, any difference would be resolved by a third team member. We would contact authors of the studies for further information. We would enter details of studies meeting the selection criteria using ProCite. We would analyse heterogeneity among studies using the Chi 2 test, and P < 0.01 would indicate heterogeneity. If we identified heterogeneity, we would conduct a further analysis to identify possible causes. Statistical analysis For normally distributed continuous outcomes, we would calculate mean differences. For binary outcomes, where sufficient data were available, we would present relative treatment effects in the form of odds ratios (OR) and 95% confidence intervals. We would perform the analysis using RevMan 5.0. We would perform a sensitivity analysis and we would measure publication bias depending on how much information was available. For time to event outcomes we would present log hazard ratios (log HR). We would pool data only if this made sense clinically. If estimates of log HR and its variance were not quoted directly in trial reports, we would extract alternative aggregate data (e.g., log rank test P value) in order to calculate pooled HR estimates. Another alternative would be the analysis for different follow-up periods using different time points as part of the outcome, which may approximate a survival analysis (survival). We would analyse adverse events as the number of patients experiencing each of the adverse events described in the studies. We would also perform intention-to-treat analysis. R E S U L T S Description of studies See: Characteristics of excluded studies. Excluded studies The initial electronic search found 263 references (123 in MED- LINE, 22 in CENTRAL and 118 in EMBASE), 225 studies were selected for further evaluation (123 in MEDLINE, 18 in CEN- TRAL and 84 in EMBASE). A second review cut down to 22 the number of studies finally evaluated. The new electronic search up to January 2009, found 171 references (37 in MEDLINE and 134 in EMBASE). Seven studies were finally evaluated for possible inclusion but did not fulfill the criteria. Prophylactic treatment of incision sites studies Four studies (Boutin 1995; Ratto 1999; Bydder 2004; Cellerin 2004) were excluded because they used radiotherapy (RT) for the prophylactic treatment of incision sites after invasive diagnostic or therapeutic procedures to prevent chest wall implantation. Bimodal therapy studies Eleven studies on bimodal therapy were evaluated (Law 1984; Sauter 1995; Linden 1996; Herscher 1998; Rusch 2001; Ahamad 2003; Munter 2003; Yajnik 2003; Halstead 2004; Rosenzweig 2005; Allen 2007). All were case series without control group 4

7 treated with different modalities of radiotherapy, usually after surgery. Multimodal therapy studies Thirteen studies on multimodal therapy were evaluated ( Calavrezos 1988; Maasilta 1991; Mattson 1992; Sugarbaker 1996; Holsti 1997; Sugarbaker 1999; Maggi 2001; Lee 2002; Weder 2004; Flores 2006; Pagan 2006; Lucchi 2007; Rea 2007). All were case series without control group treated with surgery, radiotherapy and chemotherapy, all with different modalities. Risk of bias in included studies No studies fulfilled the inclusion criteria. No studies were excluded because of poor methodology. Effects of interventions To date we have not found any reports of randomised comparisons of radiotherapy alone or combined for patients with malignant pleural mesothelioma. D I S C U S S I O N The rapidly increasing incidence of malignant pleural mesothelioma underlines the urgent need to achieve a consensus about the management of this tumour. Despite malignant pleural mesothelioma being a relatively rare disease, the incidence is increasing, and in the identified studies, the rates of median survival varied between about six months and two years but these results came from studies of low methodological quality. We have found no clinical trials involving radiotherapy as a treatment for malignant pleural mesothelioma. Nevertheless, survival of malignant pleural mesothelioma has improved with the treatment with pemetrexed in addition to cisplatin (Vogelzang 2003). There has been no consensus in the literature to guide the most appropriate management of patients with malignant pleural mesothelioma. This has been primarily due to a lack of convincing data identifying any single radiotherapy treatment modality or combination that might offer a clinically meaningful and significant improvement in survival or quality of life over best supportive care. Adverse effects and serious complications (sometimes fatal) should also be evaluated properly in randomised studies. We obtained some evidence from the literature for using radiotherapy to treat incision sites after invasive diagnostic or therapeutic studies to prevent chest wall implantation, but this issue is outside the scope of this review. Finally, as we had previously agreed not to accept non-randomised studies, all the identified papers had to be excluded because all were retrospective or prospective series of cases. All provided nonrandomised comparisons that were considered unacceptable for supporting an evidence-based recommendation. In the absence of direct evidence on the effectiveness and safety of radiotherapy compared to other therapies for malignant pleural mesothelioma, we can only conclude that further specific research by prospective randomised trials is needed. A U T H O R S C O N C L U S I O N S Implications for practice As radiotherapy has never been compared to chemotherapy or surgery or to best supportive care (as part of combined therapy) in a prospective, randomised trial, there are no data to support one or other treatment as a better option for patients with malignant pleural mesothelioma, and there is insufficient information about its safety. Implications for research There is a need for multicentre randomised controlled trials assessing the role of radiotherapy in the treatment of malignant pleural mesothelioma as well as adverse effects. The studies should be limited to patients with malignant pleural mesothelioma, classified by stages, cytology and type of radiotherapy. The type of radiotherapy should be defined in advance and variables of radiotherapy dose definition and delivery should be carefully controlled. A C K N O W L E D G E M E N T S Authors would like to thank Graciela Berenstein and Zulma Ortiz, co-authors of the previous version of the review. Thanks to Sera Tort and José Expósito for their methodological support and to Ivan Solà for the search strategy. 5

8 R E F E R E N C E S References to studies excluded from this review Ahamad 2003 {published data only} Ahamad A, Stevens CW, Smythe WR, Vaporciyan AA, Komaki R, Kelly JF, et al.intensity-modulated radiation therapy: a novel approach to the management of malignant pleural mesothelioma. International Journal of Radiation Oncology Biology Physics 2003;55(3): Allen 2007 {published data only} Allen AM, Schofield D, Hacker F, Court LE, Czerminska M. Restricted field IMRT dramatically enhances IMRT planning for mesothelioma. International Journal of Radiation Oncology 2007;69(5): Boutin 1995 {published data only} 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(3): Bydder 2004 {published data only} Bydder S, Phillips M, Joseph DJ, Cameron F, Spry NA, DeMelker Y, et al.a randomised trial of single-dose radiotherapy to prevent procedure tract metastasis by malignant mesothelioma. British Journal of Cancer 2004;91 (1):9 10. Calavrezos 1988 {published data only} Calavrezos A, Koschel G, Husselmann H, Taylessani A, Heilmann HP, Fabel H, et al.malignant mesothelioma of the pleura. A prospective therapeutic study of 132 patients from Wien Klin Wochenschr 1988;66(14): Cellerin 2004 {published data only} Cellerin L, Garry P, Mahe MA, Chailleux E. Malignant pleural mesothelioma: radiotherapy for the prevention of seeding Nodules. Revue des maladies respiratoires 2004;21 (1):53 8. Flores 2006 {published data only} Flores RM, Krug LM, Rosenzweig KE, Venkatraman E, Vincent A, Heelan R, et al.induction chemotherapy, extrapleural pneumonectomy, and postoperative highdose radiotherapy for locally advanced malignant pleural mesothelioma: a phase II trial. Journal of Thoracic Oncology 2006;1(4): Halstead 2004 {published data only} Halstead JC, Lim E, Venkateswaran RM, Charman SC, Goddard M, Ritchie AJ. Improved survival with VATS pleurectomy-decortication in advanced malignant mesothelioma. European Journal of Surgical Oncology 2005; 31(3): Herscher 1998 {published data only} Herscher LL, Hahn SM, Kroog G, Pass H, Temeck B, Goldspiel B, et al.phase I study of paclitaxel as a radiation sensitizer in the treatment of mesothelioma and non-smallcell lung cancer. Journal of Clinical Oncology 1998;16(2): Holsti 1997 {published data only} Holsti LR. Altered fractionation of hemithorax irradiation for pleural mesothelioma and failure patterns after treatment. Acta Oncologica 1997;36(4): Kaukel 1992 {published data only} Kaukel E, Koschel G, Schulz P. Conservative, palliative therapy of malignant pleural mesothelioma [Konservative, palliative Therapie des malignen Pleuramesothelioms]. Langenbecks Archiv fur Chirurgie Supplement Kongressband Deutsche Gesellschaft fur Chirurgie Kongress 1992: Law 1984 {published data only} Law MR, Gregor A, Hodson ME, Bloom HJ, Turner- Warwick M. Malignant mesothelioma of the pleura: a study of 52 treated and 64 untreated patients. Thorax 1984;39 (4): Lee 2002 {published data only} Lee, TT. Radical pleurectomy/decortication and intraoperative radiotherapy followed by conformal radiation with or without chemotherapy for malignant pleural mesothelioma. Journal of Thoracic and Cardiovascular Surgery 2002;124(6): Linden 1996 {published data only} Linden CJ, Mercke C, Albrechtsson U, Johansson L, Ewers SB. Effect of hemithorax irradiation alone or combined with doxorubicin and cyclophosphamide in 47 pleural mesotheliomas: a non randomized phase II study. European Respiratory Journal 1996;9(12): Lucchi 2007 {published data only} Lucchi M, Chella A, Melfi F, et al.four-modality therapy in malignant pleural mesothelioma: A phase II study. Journal of Thoracic Oncology 2007;2(3): Maasilta 1991 {published data only} Maasilta P. Deterioration in lung function following hemithorax irradiation for pleural mesothelioma. International Journal of Radiation Oncology Biology Physics 1991;20(3): Maggi 2001 {published data only} Maggi G. Trimodality management of malignant pleural mesothelioma. European Journal of Cardio-thoracic Surgery 2001;19(3): Mattson 1992 {published data only} Mattson K, Holsti LR, Tammilehto L, Maasilta P, Pyrhönen S, Mäntylä M, et al.multimodality treatment programs for malignant pleural mesothelioma using high-dose hemithorax irradiation. International Journal of Radiation Oncology Biology Physics 1992;24(4): Munter 2003 {published data only} Munter MW. Stereotactic intensity-modulated radiation therapy (IMRT) and inverse treatment planning for advanced pleural mesothelioma. Feasibility and initial results. Strahlentherapie und Onkologie 2003;179(8):

9 Pagan 2006 {published data only} Pagan V, Ceron L, Paccagnella A, Pizzi G. 5-year prospective results of trimodality treatment for malignant pleural mesothelioma. Journal of Cardiovascular Surgery (Torino) 2006;47(5): Ratto 1999 {published data only} Ratto GB, Civalleri D, Esposito M, Spessa E, Alloisio A, De Cian F, Vannozzi MO. Pleural space perfusion with cisplatin in the multimodality treatment of malignant mesothelioma: A feasibility and pharmacokinetic study. Journal of Thoracic and Cardiovascular Surgery 1999;117(4): Rea 2007 {published data only} 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): Rosenzweig 2005 {published data only} Rosenzweig KE, Fox JL, Zelefsky MJ, Raben A, Harrison LB, Rusch VW. A pilot trial of high-dose-rate intraoperative radiation therapy for malignant pleural mesothelioma. Brachytherapy 2005;4(1):30 3. Rusch 2001 {published data only} Rusch VW, Rosenzweig K, Venkatraman E, Leon L, Raben A, Harrison L, et al.a phase II trial of surgical resection and adjuvant high-dose hemithoracic radiation for malignant pleural mesothelioma. Journal of Thoracic and Cardiovascular Surgery 2001;122(4): Sauter 1995 {published data only} Sauter ER, Langer C, Coia LR, Goldberg M, Keller SM. Optimal management of malignant mesothelioma after subtotal pleurectomy: revisiting the role of intrapleural chemotherapy and postoperative radiation. Journal of Surgical Oncology 1995;60(2): Sugarbaker 1996 {published data only} Sugarbaker DJ. Extrapleural pneumonectomy in the multimodality therapy of malignant pleural mesothelioma. Results in 120 consecutive patients. Annals of Surgery 1996; 224(3): Sugarbaker 1999 {published data only} Sugarbaker DJ. Resection margins, extrapleural nodal status, and cell type determine postoperative long-term survival in trimodality therapy of malignant pleural mesothelioma: results in 183 patients. The Journal of Thoracic and Cardiovascular Surgery 1999;117(1): Weder 2004 {published data only} Weder W. Neoadjuvant chemotherapy followed by extrapleural neumonectomy in malignant pleural mesothelioma. Journal of Clinical Oncology 2004;22(17): Yajnik 2003 {published data only} Yajnik, S. Hemithoracic radiation after extrapleural pneumonectomy for malignant pleural mesothelioma. International Journal of Radiation Oncology Biology Physics 2003;56(5): Additional references Alberts 1988 Alberts AS, Falkson G, Goedhals L, Vorobiof DA, Van der Merwe CA. Malignant pleural mesothelioma: a disease unaffected by current therapeutic maneuvers. Journal of Clinical Oncology 1988;6: Allen 2006 Allen AM, Czerminska M, Janne PA, et al.fatal pneumonitis associated with intensity modulated radiation therapy for mesothelioma. International Journal of Radiation Oncology Biology Physics 2006;65: Baldini 2004 Baldini EH. External beam radiation therapy for the treatment of pleural mesothelioma. Thoracic Surgery Clinics 2004;14(4): Bianchi 1997 Bianchi C, Giarelli L, Grandi G, Brollo A, Ramani L, Zuch C. Latency periods in asbestos-related mesothelioma of the pleura. European journal of cancer prevention 1997;6: Bissett 1991 Bissett D, Macbeth FR, Cram I. The Role of Palliative Radiotherapy in Malignant Mesothelioma. Clinical Oncology 1991;3: Bocchetta 2000 Bocchetta M, Di Resta I, Powers A, Fresno R, Tosolini A, Testa JR, et al.human mesothelioma cells are unusually susceptible to simian virus 40-mediated transformation and asbestos carcinogenity. Proceedings of the National Academy of Sciences of the United States of America 2000;97: Brady 1981 Brady LW. Mesothelioma, the role for radiation therapy. Seminars in Oncology 1981;8: Butchart 1976 Butchart EG, Ashcroft T, Barnsley WC, Holden MP. Pleuropneumonectomy in the management of diffuse malignant mesothelioma of the pleura: experience with 29 patients. Thorax 1976;31: Curran 1998 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. Journal of Clinical Oncology 1998;16: Davis 1994 Davis SR, Tan L, Ball DL. Radiotherapy in the treatment of malignant mesothelioma of the pleura, with special reference to its use in palliation. Australasian radiology 1994; 38: Elmes 1976 Elmes PC, Simpson MJC. The clinical aspects of mesothelioma. The Quarterly Journal of Medicine 1976;45: Gordon 1982 Gordon W Jr, Antman KH, Greenberger JS, Weichselbaum RR, Chaffey JT. Radiation therapy in the management 7

10 of patients with mesothelioma. International Journal of Radiation Oncology Biology Physics 1982;8: Hakkinen 1996 Hakkinen AM, Laasonen A, Linnainmaa K, Mattson K, Pyrhonen S. Radiosensitivity of mesothelioma cell lines. Acta Oncologica 1996;35: Heelan 1999 Heelan RT, Rusch VW, Begg CB, Panicek DM, Caravelli JF, Eisen C. Staging of malignant pleural mesothelioma: comparison of CT and MR imaging. American Journal of Roentgenology 1999;172: Higgins 2008 Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version [updated September 2008]. Cochrane Handbook for Systematic Reviews of Interventions Version [updated September 2009]. The Cochrane Collaboration, Available from handbook.org. Hillerdahl 1983 Hillerdahl G. Malignant mesothelioma: review of 4710 published cases. British Journal of Diseases of the Chest 1983; 77: Metintas 1995 Metintas M, Özdemir N, Isikoy S, Kaya T, Ekici M, Erginel S, et al.ct-guided pleural needle biopsy in the diagnosis of malignant mesothelioma. Journal of Computer Assisted Tomography 1995;19: Ong 1996 Ong ST, Vogelzang NG. Chemotherapy in malignant pleural mesothelioma. A review. Journal of Clinical Oncology 1996;14: Peto 1999 Peto J, Decarli A, La Vecchia C, Levi F, Negri E. The European mesothelioma epidemic. British Journal of Cancer 1999;79: Pisani 1988 Pisani RJ, Colby TV, Williams DE. Malignant mesothelioma of the pleura. Mayo Clinic Proceedings. 1988;63: Pistolesi 2004 Pistolesi M, Rusthoven J. Malignant pleural mesothelioma: update, current management, and newer therapeutic strategies. Chest 2004;126(4): Price 1997 Price B. Analysis of current trends in United States mesothelioma incidence. American Journal of Epidemiology 1997;145: Rusch 1995 Rusch VW. A proposed new international TNM staging system for malignant pleural mesothelioma. From the International Mesothelioma Interest Group. Chest 1995; 108(4): Ryan 1998 Ryan CW, Herndon J, Vogelzang NG. A review of chemotherapy trials for malignant mesothelioma. Chest 1998;113(Suppl 1):66S 73S. Scagliotti 2005 Scagliotti GV, Novello S. State of the art in mesothelioma. Annals of Oncology 2005;16(Supplement 2):ii Scherpereel 2009 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 management of Malignant Pleural Mesothelioma. European Respiratory Journal 2009, Aug 28. [MEDLINE: PMID ] Sugarbaker 1996 Sugarbaker DJ, Garcia JP, Richards WG, Harpole DH Jr, Healy-Baldini E, DeCamp MM Jr, et al.extrapleural pneumonectomy in the multimodality therapy of malignant pleural mesothelioma. Results in 120 consecutive patients. Annals of Surgery 1996;224: Vogelzang 2003 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. Journal of Clinical Oncology 2003;21(14): Wagner 1960 Wagner JC, Sleggs EA, Marchand P. Diffuse pleural mesothelioma and asbestos in the North Western Cape Province. British Journal of Industrial Medicine 1960;17: Yates 1997 Yates DH, Corrin B, Stidolph PN, Browne K. Malignant mesothelioma in south east England: clinicopathological experience of 272 cases. Thorax 1997;52: References to other published versions of this review Chapman 2006 Chapman E, García Diéguez M, Berenstein G, Ortiz Z. Radiotherapy for malignant pleural mesothelioma. Cochrane Database of Systematic Reviews 2006, Issue 3. [Art. No.: CD DOI: / CD pub4] Indicates the major publication for the study 8

11 C H A R A C T E R I S T I C S O F S T U D I E S Characteristics of excluded studies [ordered by study ID] Study Ahamad 2003 Allen 2007 Boutin 1995 Bydder 2004 Calavrezos 1988 Cellerin 2004 Flores 2006 Halstead 2004 Herscher 1998 Holsti 1997 Kaukel 1992 Law 1984 Lee 2002 Linden 1996 Lucchi 2007 Maasilta 1991 Maggi 2001 Mattson 1992 Munter 2003 Pagan 2006 Ratto 1999 Rea 2007 Reason for exclusion Preventive radiotherapy Preventive radiotherapy Preventive radiotherapy Non-controlled phase II trial of chemotherapy and radiotherapy Non-controlled case series Non-controlled phase II trial of chemotherapy and radiotherapy Preventive radiotherapy 9

12 (Continued) Rosenzweig 2005 Rusch 2001 Sauter 1995 Sugarbaker 1996 Sugarbaker 1999 Weder 2004 Yajnik

13 D A T A A N D A N A L Y S E S This review has no analyses. W H A T S N E W Last assessed as up-to-date: 5 June Date Event Description 9 March 2010 Amended Two of the previous authors were withdrawn from authors by-line and mentioned in Acknowledgements H I S T O R Y Protocol first published: Issue 2, 2006 Review first published: Issue 3, 2006 Date Event Description 30 September 2009 New search has been performed This is an update of the 2006 review. Searches were run but no new studies were identified 9 March 2006 New citation required and conclusions have changed Substantive amendment C O N T R I B U T I O N S O F A U T H O R S GB and ZO contributed to the protocol development and provided methodological support. MGD contributed to review and selection of studies. D E C L A R A T I O N S O F None known. I N T E R E S T 11

14 I N D E X T E R M S Medical Subject Headings (MeSH) Mesothelioma [ radiotherapy]; Pleural Neoplasms [ radiotherapy] MeSH check words Humans 12

Mesothelioma. Malignant Pleural Mesothelioma

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