***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 Isolated limb infusion ( ILI ) is a minimally invasive technique for delivering regional chemotherapy in patients with advanced and metastatic melanoma confined to a limb . It is essentially a low-flow isolated limb perfusion ( ILP ) performed via percutaneous catheters without oxygenation . Methods From our prospect i ve data base 185 patients with advanced metastatic melanoma of the limb treated with a single ILI between 1993 and 2007 were identified . In all patients a cytotoxic drug combination of melphalan and actinomycin-D was used . Drug circulation time was 20–30 min under mild hyperthermic conditions ( 38–39 ° C ) . Results The majority of patients ( 62 % ) were female . Their average age was 74 years ( range 29–93 years ) . Most patients had MD And erson stage III disease ( 134/185 ) .  The overall response rate was 84 % [ complete response ( CR ) rate 38 % , partial response rate 46 % ] . Median response duration was 13 months ( 22 months for patients with CR ; P = 0.01 ) . Median follow-up was 20 months and median survival was 38 months . In those patients with a CR , the median survival was 53 months ( P = 0.005 ) . CR rate and survival time decreased with increasing stage of disease . On multivariate analysis significant factors for a favorable outcome were achievement of CR , stage of disease , thickness of primary melanoma , the CO2 level in the isolated circuit , and a Wieberdink limb toxicity score of III ( considerable erythema and edema ) . Conclusion The response rates and duration of response after ILI are comparable to those achieved by conventional ILP . ILI is a minimally invasive alternative to the much more complex and morbid conventional ILP technique for patients with advanced metastatic melanoma confined to a limb OBJECTIVE To describe initial experience with the new technique of isolated limb infusion ( ILI ) for in-transit melanoma . DESIGN A prospect i ve case series . SETTING The major tertiary care oncology centre for the state of Victoria , Australia . PATIENTS Nine patients having for extensive in-transit limb melanoma INTERVENTIONS All patients received ILI ( 13 treatments ) . OUTCOME MEASURES Patient survival , response to treatment and complications of treatment . RESULTS There were no perioperative deaths and morbidity was limited to deep venous thrombosis and pulmonary embolism in 1 patient . Control of the in-transit metastases was achieved to some degree in all patients and was complete in 4 . CONCLUSIONS ILI is an alternative treatment modality for patients suffering from multiple , advanced in-transit melanoma metastases . It provides effective palliation with limited morbidity and offers a safe , quick , inexpensive alternative to isolated limb perfusion with comparable results Introduction : The treatment of elderly patients with advanced metastatic melanoma confined to a limb remains controversial . Isolated limb infusion ( ILI ) is an effective minimally invasive alternative to isolated limb perfusion ( ILP ) and is therefore a potentially valuable therapeutic option for this group . Methods : From our prospect i ve data base 185 patients with advanced metastatic melanoma of the limb treated with a single ILI between 1992 and 2007 were identified . In all patients a cytotoxic combination of melphalan and actinomycin-D was used . Results : Eighty-six patients ( 46 % ) were ≥75 years of age ( range : 75–93 ) . The patient characteristics in both groups were comparable except that the older group comprised more women ( 71 % vs. 54 % ; P = 0.02 ) and had a lower body mass index ( median : 24.4 vs. 26.4 ; P = 0.008 ) . Complete response rates were 34 % for those ≥75 years and 41 % in the younger group ( P = 0.28 ) . There was no difference in limb recurrence free interval after a complete response ( median : 24 months for both groups ; P = 0.51 ) or in survival ( median : 36 months for < 75 , 39 months for ≥75 ; P = 0.36 ) between both groups . Older patients experienced less limb toxicity after the procedure ( Wieberdink grade III/IV toxicity in 36 % ) compared with younger patients ( 51 % ; P = 0.009 ) while systemic toxicity , complications , and long-term morbidity were similar . Conclusions : Elderly patients with advanced metastatic melanoma of the limb experience the same or lower toxicity after ILI compared with younger patients while response rates , limb recurrence free interval , survival , and morbidity are similar . ILI is an attractive alternative to the more laborious ILP , especially for older patients Background Isolated limb infusion ( ILI ) with cytotoxic drugs has been used since 1992 to treat advanced melanoma confined to a limb . Over this time the technique has undergone progressive modification . In this study we evaluated our experience with ILI by analyzing outcome and toxicity from an “ early ” and a “ late ” treatment period . Methods We compared the results from our institution for 94 patients treated by ILI in the early period ( 1992–1999 ) with the results for 91 patients treated in the late period ( 2000–2007 ) . All patients had advanced limb melanoma and received a combination of melphalan and actinomycin D.  Results The patient characteristics of the early and late groups were similar , but there was greater tumor load in the late group , who had a significantly greater number of lesions ( median 4 vs. 5 ; p = 0.02 ) and deeper tumor infiltration ( p = 0.03 ) . Drug circulation times were longer in the late group : 22 vs. 31 min ( p < 0.0001 ) . In the late group , higher initial and final limb temperatures were achieved . Overall response rates were 85 % in both groups . The late treatment group showed a trend towards less toxicity ( p = 0.06 ) . Conclusions Response rates and survival following ILI for advanced melanoma in our late treatment period were similar to those of our early treatment period , despite the significantly greater tumor load of the patients treated in the late period . This could be attributed to increased experience and protocol modifications , which allowed longer drug exposure times and higher limb temperatures to be achieved without increased toxicity Introduction Isolated limb infusion ( ILI ) with cytotoxic drugs is a low-flow isolated limb perfusion ( ILP ) performed via percutaneous catheters without oxygenation to treat metastatic melanoma confined to a limb .  Response rates and duration of response following ILI are similar to those after ILP . Previously we have shown that more significant limb toxicity is not associated with a higher response rate or improved patient outcome . In this study we sought to determine factors predicting toxicity following ILI . Methods From our prospect i ve data base 185 patients with advanced metastatic melanoma of the limb treated with a single ILI between 1992 and 2007 were identified . In all patients a cytotoxic combination of melphalan and actinomycin D was used . Drug circulation time was 20–30 min under mild hyperthermic conditions ( 38–39 ° C ) . Limb toxicity was assessed using the Wieberdink scale . Results The average patient age was 74 years ( range 29–93 years ) and 62 % were female . Most patients ( 134/185 ) had MD And erson stage III disease ( satellites and in-transit metastases ) . Toxicity grade I ( no reaction ) occurred in 3 patients , grade II ( slight erythema and edema ) in 105 patients , grade III ( considerable erythema and edema ± blistering ) in 72 patients , and grade IV ( threatened or actual compartment syndrome ) in 5 patients . No patient developed grade V toxicity ( requiring amputation ) . On univariate analysis high peak and high final melphalan concentrations were found to be predictive factors for grade III/IV limb toxicity as well as the area under the curve of the melphalan concentration . Surprisingly , a greater rise in the CO2 level during the procedure was associated with lower toxicity in the univariate analysis . Increased serum creatine phosphokinase ( CK ) postoperatively was related to higher toxicity score . In the multivariate analysis high final melphalan concentration and shorter tourniquet time were independent predictive risk factors for developing grade III/IV limb toxicity . Conclusions ILI is a safe alternative to the more invasive and laborious ILP technique to treat melanoma confined to a limb . Regional acute toxicity following ILI is mild to moderate in most patients . Based on the predictive factors found in this series , altering melphalan dose and tourniquet time may allow further reductions in post-ILI toxicity without compromising effectiveness Background Isolated limb infusion with melphalan ( ILI-M ) corrected for ideal body weight ( IBW ) is a well-tolerated treatment for patients with in-transit extremity melanoma with an approximate 29 % complete response ( CR ) rate .  Sorafenib , a multi-kinase inhibitor , has been shown to augment tumor response to chemotherapy in pre clinical studies . Methods A multi-institutional , dose-escalation , phase I study was performed to evaluate the safety and antitumor activity of sorafenib in combination with ILI-M.  Patients with AJCC stage IIIB/IIIC/IV melanoma were treated with sorafenib starting at 400 mg daily for 7 days before and 7 days after ILI-M corrected for IBW .  Toxicity , drug pharmacokinetics , and tumor protein expression changes were measured and correlated with clinical response at 3 months . Results A total of 20 patients were enrolled at two institutions . The maximum tolerated dose ( MTD ) of sorafenib in combination with ILI-M was 400 mg . Four dose-limiting toxicities occurred , including soft tissue ulcerations and compartment syndrome . There were three CRs ( 15 % ) and four partial responses ( 20 % ) . Of patients with the Braf mutation , 83 % ( n = 6 ) progressed compared with only 33 % without ( n = 12 ) . Short-term sorafenib treatment did alter protein expression as measured with reverse phase protein array ( RPPA ) analysis , but did not inhibit protein expression in the MAP kinase pathway . Sorafenib did not alter melphalan pharmacokinetics . Conclusion This trial defined the MTD of systemically administered sorafenib in combination with ILI-M. Although some responses were seen , the addition of sorafenib to ILI-M did not appear to augment the effects of melphalan but did increase regional toxicity BACKGROUND Hyperthermic isolated limb perfusion ( HILP ) and isolated limb infusion ( ILI ) are used to manage advanced extremity melanoma , but no consensus exists as to which treatment is preferable and how to monitor patients post-treatment . STUDY DESIGN Using a prospect ively maintained data base , we review ed our experience with  melphalan-based HILP ( which included 62 first-time and 10 second-time ) and ILI ( which included 126 first-time and 18 second-time ) procedures performed in 188 patients .  PET/CT was obtained 3 months postregional treatment for 1 year and then every 6 months thereafter . RESULTS Overall response rate ( complete response [ CR ] + partial response ) of HILP was 81 % ( 80 % CI , 73 - 87 % ) , and overall response rate from ILI was 43 % ( 80 % CI , 37 - 49 % ) for first-time procedures only . HILP had a CR rate of 55 % with a median duration of 32 months , and ILI had a CR rate of 30 % with median duration of 24 months . Patients who experienced a regional recurrence after initial regional treatment were more likely to achieve a CR after repeat HILP ( 50 % , n = 10 ) compared with repeat ILI ( 28 % , n = 18 ) . Although the spectrum of toxicity was similar for ILI and HILP , the likelihood of rare catastrophic complication of limb loss was greater with HILP ( 2 of 62 ) than ILI ( 0 of 122 ) . PET/CT was effective for surveillance after regional therapy to identify regional nodal and pulmonary disease that was not clinical ly evident , but often amenable to surgical resection ( 25 of 49 ; 51 % of cases ) . In contrast , PET/CT was not effective at predicting complete response to treatment with an accuracy of only 50 % . CONCLUSIONS In the largest single-institution regional therapy series reported to date , we found that although ILI is effective and well-tolerated , HILP is a more definitive way to control advanced disease Diagnosis is a critical component of health care , and clinicians , policymakers , and patients routinely face a range of questions regarding diagnostic tests . They want to know whether testing improves outcome ; what test to use , purchase , or recommend in practice guidelines ; and how to interpret test results . Well- design ed  diagnostic test accuracy studies can help in making these decisions , provided that they transparently and fully report their participants , tests , methods , and results as facilitated , for example , by the STARD ( St and ards for Reporting of Diagnostic Accuracy ) statement ( 1 ) . That 25-item checklist was published in many journals and is now adopted by more than 200 scientific journals worldwide . As in other areas of science , systematic review s and meta- analysis of accuracy studies can be used to obtain more precise estimates when small studies addressing the same test and patients in the same setting are available . Review s can also be useful to establish whether and how scientific findings vary by particular subgroups , and may provide summary estimates with a stronger generalizability than estimates from a single study . Systematic review s may help identify the 
    Output:
    
This first systematic review of ILI procedures using melphalan and actinomycin D indicates that regional toxicity was generally low , with satisfactory response rates .
When comparing ILI and ILP , it must be borne in mind that ILI is often performed in significantly older patients and in patients with higher stages of disease , which decreases the likelihood of a favorable response