***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 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    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 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 Malignant pleural mesothelioma ( MPM ) is a rare tumour but with increasing incidence and a poor prognosis . In 2008 , the European Respiratory Society/European Society of Thoracic Surgeons Task Force brought together experts to propose practical and up-to- date d guidelines on the management of MPM . To obtain an earlier and reliable diagnosis of MPM , the experts recommend performing thoracoscopy , except in cases of pre-operative contraindication or pleural symphysis . The st and ard staining procedures are insufficient in ∼10 % of cases . Therefore , we propose using specific immunohistochemistry markers on pleural biopsies . In the absence of a uniform , robust and vali date d staging system , we advice use of the most recent TNM based classification , and propose a three step pre-treatment assessment . Patient 's performance status and histological subtype are currently the only prognostic factors of clinical importance in the management of MPM . Other potential parameters should be recorded at baseline and reported in clinical trials . MPM exhibits a high resistance to chemotherapy and only a few patients are c and i date s for radical surgery . New therapies and strategies have been review ed . Because of limited data on the best combination treatment , we emphasise that patients who are considered c and i date s for a multimodal approach should be included in a prospect i ve trial at a specialised centre 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 Purpose : MORAb-009 is a chimeric monoclonal antibody that targets mesothelin , a tumor differentiation antigen overexpressed in pancreatic cancer , ovarian cancer , mesothelioma , and other malignancies . We conducted a phase I clinical trial of MORAb-009 in patients with advanced mesothelin-expressing cancers to determine its safety , dose-limiting toxicity ( DLT ) , and maximum tolerated dose ( MTD ) . Methods : Cohorts consisting of 3 to 6 subjects each received MORAb-009 intravenously on days 1 , 8 , 15 , and 22 at progressively increasing doses ranging from 12.5 to 400 mg/m2 . Disease evaluation with computed tomography occurred on day 35 . Subjects with responding or stable disease could receive additional cycles of MORAb-009 . Results : A total of 24 subjects were treated including 13 mesothelioma , 7 pancreatic cancer , and 4 ovarian cancer patients . The median number of MORAb-009 infusions was 4 ( range 1–24 infusions ) . At the 400 mg/m2 dose level , 2 subjects experienced DLT ( grade 4 transaminitis and a grade 3 serum sickness ) . Thus , although there were other contributing causes of these adverse events , 200 mg/m2 was considered the MTD . Other adverse events at least possibly related to MORAb-009 included 7 drug hypersensitivity events ( all grade 1 or 2 ) and a thromboembolic event ( grade 4 ) . Eleven subjects had stable disease . There was a dose-dependent increase in serum MORAb-009 concentration . Conclusion : MORAb-009 is well tolerated and the MTD when administered weekly is conservatively set at 200 mg/m2 . In this group of previously treated patients , 11 subjects had stable disease . Phase II studies of MORAb-009 in different mesothelin-expressing cancers are ongoing 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 
    Output:
    
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