***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 Malignant pleural mesothelioma is an aggressive tumor that has a poor prognosis and is resistant to unimodal approaches . Multimodal treatment has provided encouraging results . Methods Phase II , open-label study of the combination of chemotherapy ( pemetrexed 500 mg/m2+cisplatin 75 mg/m2 IV every 21 days × 3 cycles ) , followed by surgery ( en-bloc extrapleural pneumonectomy , 3–8 weeks after chemotherapy ) and hemithoracic radiation ( total radiation beam 54 Gy , received 4–8 weeks post-surgery ) . The primary endpoint was event-free survival , defined as the time from enrollment to time of first observation of disease progression , death due to any cause , or early treatment discontinuation . Results Fifty-four treatment-naïve patients with T1 - 3 N0 - 2 malignant pleural mesothelioma were enrolled , 52 ( 96.3 % ) completed chemotherapy , 45 ( 83.3 % ) underwent surgery , 22 ( 40.7 % ) completed the whole treatment including 90-day post-radiation follow-up . The median event-free survival was 6.9 months ( 95%CI : 5.0 - 10.5 ) , median overall survival was 15.5 months ( 95%CI 11.0-NA ) while median time-to-tumor response was 4.8 months ( 95%CI : 2.5 - 8.0 ) . Eighteen ( 33.3 % ) and 13 ( 24.1 % ) patients were still event-free after 1 and 2 years , respectively . The most common treatment-emergent adverse events were nausea ( 63.0 % ) , anemia ( 51.9 % ) and hypertension (42.6%).Following two cardiopulmonary radiation-related deaths the protocol was amended ( 21 [ 38.9 % ] patients were already enrolled in the study ): the total radiation beam was reduced from 54 Gy to 50.4 Gy and a more accurate selection of patients was recommended . Conclusions The combination of pemetrexed plus cisplatin followed by surgery and hemithoracic radiation is feasible and has a manageable toxicity profile in carefully selected patients . It may be worthy of further investigation . Trial registration Clinical trial.com registration ID # NCT00087698 Summary Background The effects of extra-pleural pneumonectomy ( EPP ) on survival and quality of life in patients with malignant pleural mesothelioma have , to our knowledge , not been assessed in a r and omised trial . We aim ed to assess the clinical outcomes of patients who were r and omly assigned to EPP or no EPP  in the context of trimodal therapy in the Mesothelioma and Radical Surgery ( MARS ) feasibility study . Methods MARS was a multicentre r and omised controlled trial in 12 UK hospitals . Patients aged 18 years or older who had pathologically confirmed mesothelioma and were deemed fit enough to undergo trimodal therapy were included . In a prer and omisation registration phase , all patients underwent induction platinum-based chemotherapy followed by clinical review . After further consent , patients were r and omly assigned ( 1:1 ) to EPP followed by postoperative hemithorax irradiation or to no EPP . R and omisation was done central ly with computer-generated permuted blocks stratified by surgical centre . The main endpoints were feasibility of r and omly assigning 50 patients in 1 year ( results detailed in another report ) , proportion r and omised who received treatment , proportion eligible ( registered ) who proceeded to r and omisation , perioperative mortality , and quality of life . Patients and investigators were not masked to treatment allocation . This is the principal report of the MARS study ; all patients have been recruited . Analyses were by intention to treat . This trial is registered , number IS RCT N95583524 . Findings Between Oct 1 , 2005 , and Nov 3 , 2008 , 112 patients were registered and 50 were subsequently r and omly assigned : 24 to EPP and 26 to no EPP . The main reasons for not proceeding to r and omisation were disease progression ( 33 patients ) , inoperability ( five patients ) , and patient choice ( 19 patients ) . EPP was completed satisfactorily in 16 of 24 patients assigned to EPP ; in five patients EPP was not started and in three patients it was ab and oned . Two patients in the EPP group died within 30 days and a further patient died without leaving hospital . One patient in the no EPP group died perioperatively after receiving EPP off trial in a non-MARS centre . The hazard ratio [ HR ] for overall survival between the EPP and no EPP groups was 1·90 ( 95 % CI 0·92–3·93 ; exact p=0·082 ) , and after adjustment for sex , histological subtype , stage , and age at r and omisation the HR was 2·75 ( 1·21–6·26 ; p=0·016 ) . Median survival was 14·4 months ( 5·3–18·7 ) for the EPP group and 19·5 months ( 13·4 to time not yet reached ) for the no EPP group . Of the 49 r and omly assigned patients who consented to quality of life assessment ( EPP n=23 ; no EPP n=26 ) , 12 patients in the EPP group and 19 in the no EPP group completed the quality of life question naires . Although median quality of life scores were lower in the EPP group than the no EPP group , no significant differences between groups were reported in the quality of life analyses . There were ten serious adverse events reported in the EPP group and two in the no EPP group . Interpretation In view of the high morbidity associated with EPP in this trial and in other non-r and omised studies a larger study is not feasible . These data , although limited , suggest that radical surgery in the form of EPP within trimodal therapy offers no benefit and possibly harms patients . Funding Cancer Research UK ( CRUK/04/003 ) , the June Hancock Mesothelioma Research Fund , and Guy 's and St Thomas ' NHS Foundation Trust 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 OBJECTIVE Malignant mesothelioma ( MM ) typically presents at an advanced stage . In the UK surgical intervention has been mostly reserved for tissue diagnosis or chemical pleurodesis . However , the role of debulking surgery in symptom control has not been fully explored . METHODS In a prospect i ve cohort study , 51 consecutive patients presenting with MM underwent palliative surgical debulking for symptomatic relief ( all patients presented with dyspnoea , 39 also had pain and two had a co-existing pleural empyema ) . Patients with early disease who underwent extrapleural pneumonectomy were excluded . The treatment aims were pleural drainage , lung re-expansion , pleurodesis and pleural debulking for symptom control . If the lung re-exp and ed after drainage of the effusion a subtotal parietal pleurectomy was performed via Video Assisted Thoracic Surgery ( VATS ) . If the lung remained entrapped , a parietal and visceral decortication using VATS or thoracotomy was performed . The changes in subjective dyspnoea and pain scores were recorded at 6 weeks and 3 , 6 and 12 months after surgery . Prognostic factors were analyzed to determine their influence on survival and symptom control . RESULTS  VATS pleurectomy  was possible in 17 patients ( 34 % ) , whilst decortication was required in the remainder ( three by VATS and 31 by thoracotomy ) . Median postoperative stay was 7 days ( range 2 - 17 ) with 30-day mortality of 7.8 % ( four of 51 patients ) . Morbidity included postoperative empyema in two patients ( 4 % ) and prolonged air-leak in five ( 9.8 % ) . Overall significant symptomatic benefit was obtained up to 3 months after surgery but subsequently increasing mortality offset these benefits . Epithelial cell type and absence of weight loss prior to surgery were found to predict longer survival and successful symptom control . CONCLUSIONS Debulking surgery has a beneficial role in symptom control for unresectable MM . However , this surgery should be reserved for those patients who present with epithelial cell type and before significant loss of weight PURPOSE Patients with malignant pleural mesothelioma , a rapidly progressing malignancy with a median survival time of 6 to 9 months , have previously responded poorly to chemotherapy . We conducted a phase III trial to determine whether treatment with pemetrexed and cisplatin results in survival time superior to that achieved with cisplatin alone . PATIENTS AND METHODS Chemotherapy-naive patients who were not eligible for curative surgery were r and omly assigned to receive pemetrexed 500 mg/m2 and cisplatin 75 mg/m2 on day 1 , or cisplatin 75 mg/m2 on day 1 . Both regimens were given intravenously every 21 days . RESULTS A total of 456 patients were assigned : 226 received pemetrexed and cisplatin , 222 received cisplatin alone , and eight never received therapy .  Median survival time in the pemetrexed/cisplatin arm was 12.1 months versus 9.3 months in the control arm ( P = .020 , two-sided log-rank test ) . The hazard ratio for death of patients in the pemetrexed/cisplatin arm versus those in the control arm was 0.77 . Median time to progression was significantly longer in the pemetrexed/cisplatin arm : 5.7 months versus 3.9 months ( P = .001 ) . Response rates were 41.3 % in the pemetrexed/cisplatin arm versus 16.7 % in the control arm ( P < .0001 ) . After 117 patients had enrolled , folic acid and vitamin B12 were added to reduce toxicity , result ing in a significant reduction in toxicities in the pemetrexed/cisplatin arm . CONCLUSION Treatment with pemetrexed plus cisplatin and vitamin supplementation result ed in superior survival time , time to progression , and response rates compared with treatment with cisplatin alone in patients with malignant pleural mesothelioma . Addition of folic acid and vitamin B12 significantly reduced toxicity without adversely affecting survival time 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 , 
    Output:
    
Current evidence can not definitively answer which procedure ( EPP or P/D ) is more beneficial in terms of survival and operative risks .
This systematic review suggests that surgery in the context of trimodality therapy offers acceptable perioperative outcomes and long-term survival .
Centres specialising in MPM management have better results