***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
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    Input: BACKGROUND Trimodality therapy seems to be the best treatment for malignant pleural mesothelioma ( MPM ) . A large experience served to evaluate the efficacy of surgery followed by adjuvant chemo-radiotherapy . Trimodality therapy results have led us to test induction chemotherapy followed by EPP and adjuvant radiotherapy in stages I-III of MPM . The aim of our study was to evaluate the feasibility of this protocol and to estimate survival . METHODS From 2000 to 2003 , 21 patients with MPM ( 14 males and 7 females , median age 59 years ) were enrolled in the prospect i ve study .  Induction chemotherapy consisted of Carboplatin ( AUC 5mg/mL/min on Day 1 ) and Gemcitabine ( 1000mg/m(2 ) on Days 1 , 8 , 15 ) for three to four cycles . EPP was performed 3 - 5 weeks after induction therapy , while post-operative RT was given 4 - 6 weeks after operation . RESULTS Ten patients received three cycles of chemotherapy , 10 patients received four cycles and 1 patient had two cycles . Grade s 3 - 4 haematological toxicity occurred in eight ( 38.1 % ) patients . Chemotherapy response rate was : complete 0 % , partial 33.3 % and stable disease 66.7 % . Seventeen ( 80.9 % ) out of 21 patients underwent EPP with no intra or post-operative mortality with an overall major and minor morbidity rate at 52.4 % . Median survival was 25.5 months , with an overall 1 , 3 and 5-year survival rate of 71 , 33 and 19 % , respectively . CONCLUSIONS In MPM , the combined modality approach using the Carboplatin/Gemcitabine combination as induction chemotherapy is feasible , with good results in terms of survival and morbidity . Our results are similar to those of other studies using a heavier modality treatment The first report of the Mesothelioma and Radical Surgery ( MARS ) trial appeared in the Journal of Thoracic Oncology [ 1 ] . The objective of MARS was to establish the possibility of allocating patients , at r and om , to have either extrapleural pneumonectomy ( EPP ) or no surgical resection . The target — 50 r and omised patients — was reached in late 2008 . Outcomes are not yet available ; however , the trial was not powered to prove effectiveness but to address the question of feasibility . In the MARS trial protocol ( Fig. 1 ) , patients were allocated to either trimodality therapy ( chemotherapy , EPP and radical hemithoracic radiotherapy ) or identical chemotherapy followed by any non-surgical treatment thought appropriate . The trial employed a two-stage consent process . Patients consented to participate in the study for completion of staging , chemotherapy and other work-up ( N = 112 ) . The 2—3 months required for chemotherapy between the first and second consent allowed patients and teams to come to terms with r and omisation as a means of unbiased allocation . Of the 112 patients , 50 ( 45 % ) were eventually r and omised . MARS has shown that unbiased allocation to surgery versus no surgery is not impossible — but it is far from easy . The story of MARS goes back 5 years . Cl aims were being made that EPP had the potential to prolong life [ 2 ] . The data were derived from follow-up studies of multimodality therapy ; one could not discern the effect attributable to surgery . There were no data concerning the denominator from which the cases were drawn , and it is likely that the EPP series include fitter patients with slower progressing cancer . Then , if only patients completing treatment are reported , it follows that these patients must be sufficiently well to receive the second and thirdmodalities of treatment , further biasing the interpretation of outcome . These are some of the pitfalls in the reporting of follow-up studies [ 3 ] . It was against that background that the cancer epidemiologist Julian Peto urged European surgeons to put the question of radical surgery for mesothelioma to the test in the form of a r and omised trial [ 4 ] . While MARS has been recruiting , cl aims for the benefit of EPP have moderated . The Boston group have raised a caution ary note in reporting the high burden of complications occurring in over 60 % of patients [ 5 ] . This was echoed in the Mayo clinic follow-up study in which the authors report The European Organisation for Research and Treatment of Cancer ( EORTC ; protocol 08031 ) phase II trial investigated the feasibility of trimodality therapy consisting of induction chemotherapy followed by extrapleural pneumonectomy and post-operative radiotherapy in patients with malignant pleural mesothelioma ( with a severity of cT3N1M0 or less ) .  Induction chemotherapy consisted of three courses of cisplatin 75 mg·m−2 and pemetrexed 500 mg·m−2 . Nonprogressing patients underwent extrapleural pneumonectomy followed by post-operative radiotherapy ( 54 Gy , 30 fractions ) . Our primary end-point was “ success of treatment ” and our secondary end-points were toxicity , and overall and progression-free survival . 59 patients were registered , one of whom was ineligible . Subjects ’ median age was 57 yrs . The subjects ’ TNM scores were as follows : cT1 , T2 and T3 , 36 , 16 and six patients , respectively ; cN0 and N1 , 57 and one patient , respectively . 55 ( 93 % ) patients received three cycles of chemotherapy with only mild toxicity . 46 ( 79 % ) patients received surgery and 42 ( 74 % ) had extrapleural pneumonectomy with a 90-day mortality of 6.5 % .  Post-operative radiotherapy was completed in 37 ( 65 % ) patients . Grade 3–4 toxicity persisted after 90 days in three ( 5.3 % ) patients . Median overall survival time was 18.4 months ( 95 % CI 15.6–32.9 ) and median progression-free survival was 13.9 months ( 95 % CI 10.9–17.2 ) . Only 24 ( 42 % ) patients met the definition of success ( one-sided 90 % CI 0.36–1.00 ) . Although feasible , trimodality therapy in patients with mesothelioma was not completed within the strictly defined timelines of this protocol and adjustments are necessary BACKGROUND The aim of this multicenter trial was to prospect ively evaluate neo-adjuvant chemotherapy followed by extrapleural pneumonectomy ( EPP ) and radiotherapy , including quality of life as outcome . PATIENTS AND METHODS Eligible patients had malignant pleural mesothelioma of all histological types , World Health Organization performance status of zero to two and clinical stage T1-T3 , N0 - 2 , M0 disease considered completely resectable .  Neo-adjuvant chemotherapy consisted of three cycles of cisplatin and gemcitabine followed by EPP . Postoperative radiotherapy was considered for all patients . RESULTS In all , 58 of 61 patients completed three cycles of neo-adjuvant chemotherapy . Forty-five patients ( 74 % ) underwent EPP and in 37 patients ( 61 % ) the resection was complete . Postoperative radiotherapy was initiated in 36 patients . The median survival of all patients was 19.8 months [ 95 % confidence interval ( CI ) 14.6 - 24.5 ] . For the 45 patients undergoing EPP , the median survival was 23 months ( 95 % CI 16.6 - 32.9 ) . Psychological distress showed minor variations over time with distress above the cut-off score indicating no morbidity with 82 % ( N = 36 ) at baseline and 76 % ( N = 26 ) at 3 months after surgery ( P = 0.5 ) . CONCLUSIONS The observed rate of operability is promising . A median survival of 23 months for patients undergoing EPP  compares favourably with the survival reported from single center studies of upfront surgery . This approach was not associated with an increase in psychological distress BACKGROUND Malignant pleural mesothelioma ( MPM ) is an aggressive form of cancer arising from the pleural mesothelium . Trimodality therapy ( TMT ) involving extrapleural pneumonectomy with neoadjuvant or adjuvant chemotherapy and adjuvant radiotherapy is a recognized treatment option with a curative intent . Despite encouraging results from institutional studies , TMT in the treatment of MPM remains controversial . The present systematic review aims to assess the safety and efficacy of TMT in the current literature . METHODS A systematic review was performed using five electronic data bases from 1 January 1985 to 1 October 2012 . Studies were selected independently by two review ers according to predefined selection criteria . The primary endpoint was overall survival . Secondary endpoints included disease-free survival , disease recurrence , perioperative morbidity and length of stay . RESULTS Sixteen studies were included for quantitative assessment , including one r and omized controlled trial and five prospect i ve series . Median overall survival ranged from 12.8 - 46.9 months . Disease-free survival ranged from 10 - 16.3 months . Perioperative mortality ranged from 0 - 12.5 % . Overall perioperative morbidity ranged from 50 - 82.6 % and the average length of stay was 9 - 14 days . CONCLUSIONS Outcomes of patients who underwent TMT  in the current literature appeared to be inconsistent . Four prospect i ve series involving a st and ardised treatment regimen with neoadjuvant chemotherapy indicated encouraging results based on intention-to-treat analysis . However , a small study assessing the feasibility of conducting a r and omized controlled trial for TMT versus conservative treatment reported poor short- and long-term outcomes for patients who underwent pneumonectomy . Overall , results of the present systematic review suggest TMT may offer acceptable perioperative outcomes and long-term survival in selected patients treated in specialized centers Hypothesis : The effectiveness of extrapleural pneumonectomy ( EPP ) to extend quality -adjusted survival in malignant pleural mesothelioma within multimodality treatment should be proven in a r and omized controlled trial if this radical surgery is to be regarded as the st and ard of care . The question was whether r and omization to surgery versus no surgery would be possible . Methods : The Mesothelioma and Radical Surgery trial was planned to r and omize 50 patients to test feasibility . There was a two-stage consent process . At first consent , the patients who were possible c and i date s for radical surgery  were registered into the trial for completion of assessment and staging . All received platinum-based chemotherapy . If still eligible , they completed a second consent to be r and omized to have either EPP followed by radical hemithorax radiotherapy or to have continued best care . Results : Patients were recruited through 11 collaborating centers in the United Kingdom . One hundred twelve potentially eligible patients gave informed consent to enter the registration phase and undergo chemotherapy . One died , 27 progressed , five were inoperable , four were treated off trial , and 18 withdrew either during or after chemotherapy but before final review . Additionally six were deemed inoperable at review after completing chemotherapy and one more patient withdrew . The remaining 50 were r and omized ; 24 to EPP and 26 to continued best care . Conclusions : In this study , 50/112 ( 45 % ) of patients entering the evaluation and induction phase of the trial went on to be r and omized . We have shown that this r and omization between surgery and no surgery is feasible . This was the primary aim of the Mesothelioma and Radical Surgery trial Introduction : To compare the outcomes of two different multimodality regimens involving neoadjuvant chemotherapy , extrapleural pneumonectomy ( EPP ) and adjuvant radiotherapy versus pleurectomy/decortication ( P/D ) , hyperthermic pleural lavage with povidone-iodine , and adjuvant chemotherapy in patients with malignant pleural mesothelioma . Methods : Nonr and omized prospect i ve study of patients treated by multimodality therapy and operated on between January 2004 and June 2011 . Second-line treatments were administered when appropriate . Survival and prognostic factors were analyzed by the Kaplan Meier method , log rank test , and Cox regression analysis . Results : Twenty-five consecutive patients received neoadjuvant chemotherapy , 22 underwent EPP , and 17 received adjuvant radiotherapy .  Over the same period , 54 consecutive patients underwent P/D and hyperthermic pleural lavage and received prophylactic radiotherapy and adjuvant chemotherapy . The 30-day mortality rate was 4.5%in the EPP group and nil in the P/D group . Fifteen patients ( 68 % ) in the EPP group and 15 ( 27.7 % ) in the P/D group experienced complications . There were no differences between the EPP and P/D groups for age , sex , histology , pathologic stage , and nodal status . Trimodality therapy was completed by 68%of the patients in the EPP group and 100%in the P/D group . Survival was significantly better in the P/D group : median survival was 23 months versus 12.8 months , 2-year survival was 49%versus 18.2 % , and 5-year survival was 30.1%versus 9 % , respectively ( p = 0.004 ) . At multivariate analysis , epithelioid histology , P/D , 
    Output:
    
The present study indicated that selected patients who underwent extended P/D  had lower perioperative morbidity and mortality with similar , if not superior , long-term survival compared to EPP , in the context of multi-modality therapy .
This may represent an important paradigm shift in the surgical management of MPM