***TASK*** the task is to summarize an input biomedical literature in six sentences 
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    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
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    Input: Background In a prior r and omized phase II trial comparing hyperthermic isolated limb perfusion ( HILP ) with four different doses of tumor necrosis factor alpha ( TNF-α ) , no dose effect was detected for response , but systemic toxicity was far lower with low-dose TNF-α . The objective of the present study was to confirm these data on a larger sample size of locally advanced or recurrent extremity soft tissue sarcomas with low-dose TNF-α . Methods We assessed a prospect i ve data base comprising 100 HILP ( 38–40 ° C ) with melphalan ( 10 mg/L ) and TNF-α ( 1 mg ) . The remnant tumor was resected 2 months later . Results Among 52 recurrences , 18 were in a previously irradiated field . Stages according to the American Joint Committee on Cancer classification were II ( 19 patients ) , III ( 78 patients ) , and IV ( 3 patients ) . The site/size were : 30 patients /57 mm and 70 patients /86 mm for the upper and lower limbs , respectively . Tumor grade s ( FNCLCC ) were 1 ( 23 patients ) , 2 ( 34 patients ) , and 3 ( 43 patients ) . Fifty-one patients had received systemic chemotherapy before HILP . Responses on magnetic resonance imaging were 30 % complete , 49 % partial , 9 % no change , and 12 % progression . No mortality or systemic toxicity occurred . Local toxicity ( Wieberdink ) attained grade 2 ( 16 patients ) , 3 ( 5 patients ) , and 4 ( 1 patient ) . Limbs were able to be saved in 87 % patients . Three-year overall survival and the local recurrence rate were 89 % and 18 % , respectively . Age , sex , tumor size , recurrence , uni- or multifocality , grade , preoperative chemotherapy , and a previously irradiated field were not predictive of response or local toxicity . Conclusions We confirm that 1 mg of TNF-α is as effective as the st and ard dose and results in no systemic toxicity Background Isolated limb perfusion with tumor necrosis factor alpha and melphalan ( TM-ILP ) has proven to be a successful option in treating advanced soft tissue sarcomas ( STS ) , where amputation otherwise is needed to achieve safe surgical margins . Methods From 2000 to 2009 , 54 patients with locally advanced STS , who all were c and i date s for amputation , were treated with totally 57 TM-ILP procedures and then followed prospect ively . The median follow-up time was 30 months . Median tumor size was 10 cm , and 94 % of the patients had high- grade tumors . Results The clinical overall response after TM-ILP was 71 % ( including 21 % CR ) , and 60 % of the patients underwent resection of the tumor remnant after a median of 2 months . The histopathologic response rate in the resected specimens was 76 % . Local recurrence/progress occurred in 37 % of the patients after a median of 7 months . Thirteen patients finally underwent amputation after a median of 11 months , giving a long-term limb salvage of 76 % . Conclusions TM-ILP of advanced soft tissue sarcoma of the extremities makes limb-sparing surgery possible in a high proportion of patients Isolated limb infusion ( ILI ) is a minimally invasive technique of delivering regional chemotherapy in patients with advanced melanoma or soft-tissue sarcoma of the limb . We report the final results of the first clinical trial of ILI in North America ( NCT00004250 ) . Eligible patients had recurrent melanoma or unresectable soft-tissue sarcoma of the limb . Angiographic catheters were positioned just above the knee or elbow of the extremity . General anesthesia was performed , a proximal tourniquet inflated , and a normothermic , low flow , hypoxic infusion of melphalan and dactinomycin circulated through the involved limb for 20 min . Tumor response and morbidity were assessed using st and ard criteria . Thirty-seven patients were accrued to the trial and 44  ILIs were performed ( eight patients had two ILIs ) ; one patient was not treated . Of the 32 evaluable patients , 17 ( 53 % ) had a significant response at 3 months : 25 % of patients had a complete response and 28 % of patients had a partial response . The median duration of complete response was 1 year ( 5–32 months ) . Morbidity was acceptable , with peak erythema , edema , and pain experienced at 2 weeks and considered ‘ moderate ’ in most patients . No patients developed compartment syndrome or required amputation because of ILI . ILI is well tolerated . More than half of the treated patients experienced a complete or partial response Between May 1975 and April 1981 , 43 adult patients with high- grade soft tissue sarcomas of the extremities were prospect ively r and omized to receive either amputation at or above  the  joint proximal to the tumor , including all involved muscle groups , or to receive a limb-sparing resection plus adjuvant radiation therapy . The limb-sparing resection group received wide local excision followed by 5000 rads to the entire anatomic area at risk for local spread and 6000 to 7000 rads to the tumor bed . Both r and omization groups received postoperative chemotherapy with doxorubicin ( maximum cumulative dose 550 mg/m2 ) , cyclophosphamide , and high-dose methotrexate .  Twenty-seven patients r and omized to receive limb-sparing resection and radiotherapy , and 16 received amputation ( r and omization was 2:1 ) . There were four local recurrences in the limb-sparing group and none in the amputation group ( p1 = 0.06 generalized Wilcoxon test ) . However , there were no differences in disease-free survival rates ( 71 % and 78 % at five years ; p2 = 0.75 ) or overall survival rates ( 83 % and 88 % at five years ; p2 = 0.99 ) between the limb-sparing group and the amputation treatment groups . Multivariate analysis indicated that the only correlate of local recurrence was the final margin of resection . Patients with positive margins of resection had a higher likelihood of local recurrence compared with those with negative margins ( p1 less than 0.0001 ) even when postoperative radiotherapy was used . A simultaneous prospect i ve r and omized study of postoperative chemotherapy in 65 patients with high- grade soft-tissue sarcomas of the extremities revealed a marked advantage in patients receiving chemotherapy compared with those without chemotherapy in three-year continuous disease-free ( 92 % vs. 60 % ; p1 = 0.0008 ) and overall survival ( 95 % vs. 74 % ; p1 = 0.04 ) . Thus limb-sparing surgery , radiation therapy , and adjuvant chemotherapy appear capable of successfully treating the great majority of adult patients with soft tissue sarcomas of the extremity Background Isolated limb infusion ( ILI ) is a therapeutic option for patients with recurrent , unresectable extremity malignancies . Methods A prospect ively collected single-institution data base of patients undergoing ILI  was analyzed for preoperative , intraoperative , and postoperative parameters and outcomes . Results From May 2007 to January 2012 , a total of 76 patients successfully underwent initial ILI , and 28 after either previous hyperthermic isolated limb perfusion or ILI . Seventy-nine patients ( 74 % ) had melanoma , 24 ( 22 % ) sarcoma , 3 ( 3 % ) Merkel cell , and 1 ( 1 % ) squamous cell carcinoma . There were 55 ( 72 % ) initial and 22 ( 79 % ) repeat lower extremity ( LE ) ILIs , and 21 ( 78 % ) initial and 6 ( 22 % ) repeat upper extremity ( UE ) ILIs . Serologic toxicity , measured by serum creatine kinase ( CK ) , peaked higher and later in LE ILIs , median 620 versus 124 IU/L , and postoperative day 4 versus 2 , respectively ( P < 0.05 ) . LE ILIs had a longer hospital length of stay ( LOS ) , median 6 versus 5 days ( P < 0.0001 ) . A median grade II Wieberdink regional toxicity was observed . Three-month follow-up was available in 94 ( 90 % ) . A response ( overall response rate , ORR ) was seen in 72 % of ILIs performed for melanoma and 58 % for sarcoma . No difference in response was observed between UE versus LE or between initial versus repeat ILIs . Repeat UE ILIs , however , appeared to have an improved ORR than repeat LE ILIs , 83 versus 64 % . Conclusions ILI may be successfully performed for cutaneous and soft tissue malignancies . LE ILIs have higher CK levels and slightly longer LOS . Repeat ILIs are not associated with increased toxicity and similar ORR . UE ILIs may have better ORR BACKGROUND Isolated limb perfusion ( TM-ILP ) achieves high response rates in soft tissue sarcomas ( STS ) . Some tumors show an insufficient association between radiological and pathological response . We investigated STS after TM-ILP with a primary emphasis on histologic regression patterns . METHODS In 53 patients with STS , TM-ILP with subsequent tumor resection was performed . Regression was assessed by the Salzer-Kuntschik regression scale . Microvessel density ( MVD ) of primary biopsies of 37 patients was determined by immunohistochemistry . Tumor regression was correlated with MVD of primary biopsies and other clinico-pathological parameters . RESULTS Regression presented mainly as necrosis or fibrosis/sclerosis upon histopathology . MFH , leiomyosarcoma , or clear cell sarcoma ( CCS ) responded well ; whereas liposarcomas , synovial sarcomas , or MPNST were poor responders . MFH often had abundant necrosis ; while other STS mainly presented with fibrosis/sclerosis . MVD had no influence on regression grade but modulated histologic regression patterns . Excellent regression demonstrated a trend toward an association with improved survival and local control . CONCLUSION TM-ILP yielded high response rates in STS . Regression after TM-ILP exhibits MVD-dependent histopathologic patterns and variable efficacy in different sarcoma types . Complete regression seems to be a favorable prognostic factor . A concerted consideration of histopathology and clinical findings may contribute to a better clinical assessment of regression after TM-ILP PURPOSE To determine in a r and omized prospect i ve multi-institutional trial whether the addition of tumor necrosis factor alpha ( TNF-alpha ) to a melphalan-based hyperthermic isolated limb perfusion ( HILP ) treatment would improve the complete response rate for locally advanced extremity melanoma . PATIENTS AND METHODS Patients with locally advanced extremity melanoma were r and omly assigned to receive melphalan or melphalan plus TNF-alpha during st and ard HILP . Patient r and omization was stratified according to disease/treatment status and regional nodal disease status . RESULTS The intervention was completed in 124 patients of the 133 enrolled .  Grade 4 adverse events were observed in 14 ( 12 % ) of 129 patients , with three ( 4 % ) of 64 in the melphalan-alone arm and 11 ( 16 % ) of 65 in the melphalan-plus-TNF-alpha arm ( P = .0436 ) . There were two toxicity-related lower extremity amputations in the melphalan-plus-TNF-alpha arm , and one disease progression-related upper extremity amputation in the melphalan-alone arm . There was no treatment-related mortality in either arm of the study . One hundred sixteen patients were assessable at 3 months postoperatively . Sixty-four percent of patients ( 36 of 58 ) in the melphalan-alone arm and 69 % of patients ( 40 of 58 ) in the melphalan-plus-TNF-alpha arm showed a response to treatment at 3 months , with a complete response rate of 25 % ( 14 of 58 patients ) in the melphalan-alone arm and 26 % ( 15 of 58 patients ) in the melphalan-plus-TNF-alpha arm ( P = .435 and P = .890 , respectively ) . CONCLUSION In locally advanced extremity melanoma treated with HILP , the addition of TNF-alpha to melphalan did not demonstrate a significant enhancement of short-term response rates over melphalan alone by the 3-month follow-up , and TNF-alpha plus melphalan was associated with a higher complication rate Background Isolated limb infusion ( ILI ) is a minimally invasive technique for delivering high-dose regional chemotherapy . We report our experience with ILI for the treatment of soft tissue sarcoma ( STS ) . Methods From our prospect i ve data base , 21 patients with STS of the limb treated with ILI between 1994 and 2007 were identified . In all patients , a high-dose cytotoxic drug combination was used . Results There were 14 men , and the median age was 60 years ( range , 18–85 years ) . Eighteen patients ( 86 % ) had lower limb tumors . All patients had advanced local disease . The procedure was well tolerated . Fourteen patients ( 67 % ) received ILI before definitive surgery . 
    Output:
    
Conclusion ILP and ILI for extremity STS can be safely performed with appreciable response rates and significant limb salvage rates .