***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 We evaluated the contribution of sentinel-node biopsy to outcomes in patients with newly diagnosed melanoma . METHODS Patients with a primary cutaneous melanoma were r and omly assigned to wide excision and postoperative observation of regional lymph nodes with lymphadenectomy if nodal relapse occurred , or to wide excision and sentinel-node biopsy with immediate lymphadenectomy if nodal micrometastases were detected on biopsy . RESULTS Among 1269 patients with an intermediate-thickness primary melanoma , the mean ( + /-SE ) estimated 5-year disease-free survival rate for the population was 78.3+/-1.6 % in the biopsy group and 73.1+/-2.1 % in the observation group ( hazard ratio for recurrence[corrected ] , 0.74 ; 95 % confidence interval [ CI ] , 0.59 to 0.93 ; P=0.009 ) . Five-year melanoma-specific survival rates were similar in the two groups ( 87.1+/-1.3 % and 86.6+/-1.6 % , respectively ) . In the biopsy group , the presence of metastases in the sentinel node was the most important prognostic factor ; the 5-year survival rate was 72.3+/-4.6 % among patients with tumor-positive sentinel nodes and 90.2+/-1.3 % among those with tumor-negative sentinel nodes ( hazard ratio for death , 2.48 ; 95 % CI , 1.54 to 3.98 ; P<0.001 ) . The incidence of sentinel-node micrometastases was 16.0 % ( 122 of 764 patients ) , and the rate of nodal relapse in the observation group was 15.6 % ( 78 of 500 patients ) . The corresponding mean number of tumor-involved nodes was 1.4 in the biopsy group and 3.3 in the observation group ( P<0.001 ) , indicating disease progression during observation . Among patients with nodal metastases , the 5-year survival rate was higher among those who underwent immediate lymphadenectomy than among those in whom lymphadenectomy was delayed ( 72.3+/-4.6 % vs. 52.4+/-5.9 % ; hazard ratio for death , 0.51 ; 95 % CI , 0.32 to 0.81 ; P=0.004 ) . CONCLUSIONS The staging of intermediate-thickness ( 1.2 to 3.5 mm ) primary melanomas according to the results of sentinel-node biopsy provides important prognostic information and identifies patients with nodal metastases whose survival can be prolonged by immediate lymphadenectomy . ( Clinical Trials.gov number , NCT00275496 [ Clinical Trials.gov ] . ) Analysing specific non-fatal events in isolation may lead to spurious conclusions about efficacy unless the events considered are combined with all-cause mortality . The use of combined endpoints has therefore become widespread , at least in cardiovascular disease trials . Combining all-cause mortality with selected non-fatal events is useful because event-free survival , an important criterion in therapy evaluation , is addressed in this manner . In many clinical trials , symptoms , signs or para clinical measures ( for example , blood pressure , exercise duration , quality of life scores ) are used as endpoints . If the patient died before the endpoint was measured , or it was otherwise not possible to perform follow-up assessment s as planned , the effect of treatment on these endpoints may be distorted if the patients concerned are ignored in the analysis . Examples are given of how distortion can be avoided by including all patients r and omized in an analysis that uses a ranked combined endpoint based both on clinical events and on para clinical measures . A distinction is made between a pseudo intention-to-treat analysis that disregards study medication status at the time of endpoint assessment but is confined to patients with data , and a true intention-to-treat analysis that takes into account all patients r and omized based on a ranked combined endpoint BACKGROUND This study addressed the question of whether limited surgery for primary malignant melanoma with a 2-cm margin is as good as a 5-cm margin . An up date of a 16-year follow-up is provided . METHODS Nine European Centers , over a period of 5 years , prospect ively r and omized 337 patients with melanoma measuring less than 2.1 mm in thickness to undergo a local excision  with either a 2-cm or a 5-cm margin . Three hundred twenty-six patients were eligible for statistical analysis . Excluded from the trial were patients older than 70 years ; those with melanomas from the toe , nail , or finger ; and those with acral-lentiginous melanoma . A separate r and omization was performed to independently test an adjuvant treatment with a nonspecific immunostimulant , isoprinosine , compared with observation . The median follow-up time was 192 months ( 16 years ) for the estimation of survival and disease recurrences . RESULTS There were 22 tumor recurrences in the 2-cm arm and 33 in the 5-cm arm . The median time to disease recurrence was 43 months and 37.6 months , respectively . The 10-year disease-free survival rates were 85 % for the group with a 2-cm margin and 83 % for the group with a 5-cm margin . There was no difference in the 10-year overall survival rates ( 87 % vs. 86 % ) . Isoprinosine did not demonstrate any activity in this setting . CONCLUSIONS The authors concluded that for melanoma less than 2.1-mm thick , a margin of excision of 2 cm is sufficient . A larger margin of 5 cm does not appear to have any impact on either the rate or the time to disease recurrence or on survival Abstract Background : In the past , radical margins of excision were prescribed for cutaneous melanoma based on preconceived notions rather than on hard clinical evidence . Methods : In a prospect i ve study of 742 patients with intermediate-thickness melanoma ( 1–4 mm ) , 470 patients with trunk or proximal extremity lesions were r and omized into a 2-or 4-cm margin . Patients with distal extremity or head and neck lesions ( n=272 ) received uniformly a 2-cm margin . Results : The overall rate of local recurrence was 3.8 % . This rate in the r and omized portion ( n=470 ) was 2.1 % for the 2-cm margin and 2.6 % for the 4-cm margin ( p=0.72 ) . A progressive increase in local recurrence rates was observed with thickness : 2.3 % for lesions 1.0–2.0 mm , 4.2 % for those 2.01–3.0 mm , and 11.7 % for those 3.01–4.0 mm thick ( p=0.001 ) . Local recurrence occurred in 1.5 % of those without ulceration and in 10.6 % of those with ulceration of the primary lesion ( p=0.001 ) . The local recurrence rate was not significantly affected by the margin of resection even among the thicker or ulcerated lesions . It also was not affected significantly by the method of closure of the primary site or management of the regional nodes , or the age or gender of the patients . Conclusions : A 2-cm margin is as effective as a 4-cm margin in local control and survival of intermediate-thickness melanomas . The local recurrence rate is significantly affected by the thickness of the primary lesion and the presence or not of ulceration BACKGROUND Controversy exists concerning the necessary margin of excision for cutaneous melanoma 2 mm or greater in thickness . METHODS We conducted a r and omized clinical trial comparing 1-cm and 3-cm margins . RESULTS Of the 900 patients who were enrolled , 453 were r and omly assigned to undergo surgery with a 1-cm margin of excision and 447 with a 3-cm margin of excision ; the median follow-up was 60 months . A 1-cm margin of excision was associated with a significantly increased risk of locoregional recurrence . There were 168 locoregional recurrences ( as first events ) in the group with 1-cm margins of excision , as compared with 142 in the group with 3-cm margins ( hazard ratio , 1.26 ; 95 percent confidence interval , 1.00 to 1.59 ; P=0.05 ) . There were 128 deaths attributable to melanoma in the group with 1-cm margins , as compared with 105 in the group with 3-cm margins ( hazard ratio , 1.24 ; 95 percent confidence interval , 0.96 to 1.61 ; P=0.1 ) ; overall survival was similar in the two groups ( hazard ratio for death , 1.07 ; 95 percent confidence interval , 0.85 to 1.36 ; P=0.6 ) . CONCLUSIONS A 1-cm margin of excision for melanoma with a poor prognosis ( as defined by a tumor thickness of at least 2 mm ) is associated with a significantly greater risk of regional recurrence than is a 3-cm margin , but with a similar overall survival rate BACKGROUND A prospect i ve , multi-institutional , r and omized surgical trial involving 486 localized melanoma patients was conducted to determine whether excision margins for intermediate-thickness melanomas ( 1.0 to 4.0 mm ) could be safely reduced from the st and ard 4-cm radius . METHODS Patients with 1- to 4-mm-thick melanomas on the trunk or proximal extremities were r and omly assigned to receive either a 2- or 4-cm surgical margin . RESULTS The median follow-up time was 6 years . The local recurrence rate was 0.8 % for 2-cm margins and 1.7 % for 4-cm margins ( p value not significant [ NS ] ) . The rates of in-transit metastases were 2.1 % and 2.5 % , respectively ( p = NS ) . Of the six patients with local recurrences , five have died . Recurrence rates did not correlate with surgical margins , even among stratified thickness groups . The overall 5-year survival rate was 79.5 % for the 2-cm margin patients and 83.7 % for the 4-cm margin patients ( p = NS ) . The need for skin grafting was reduced from 46 % with 4-cm surgical margins to 11 % with 2-cm surgical margins ( p < 0.001 ) . The hospital stay was shortened from 7.0 days for patients receiving 4-cm surgical margins to 5.2 days for those receiving 2-cm margins ( p = 0.0001 ) . This reduction was largely due to reduced need for skin grafting , since the hospital stay for those who had a skin graft was 2.5 days longer than that for those who had a primary wound closure ( p < 0.01 ) . CONCLUSION Margins of excision can be safely reduced to 2 cm for patients with intermediate-thickness melanomas . The narrower margins significantly reduced the need for skin grafting and shortened the hospital stay The traditional surgical treatment for primary malignant melanoma has often been a wide excision with a margin of about 5 cm . Since the risk of local recurrences is dependent on tumor thickness , thin tumors ( < 1 mm ) have routinely been excised with a narrow margin . For thick tumors , the optimal resection margin is controversial , and can be determined only by prospect i ve , r and omized trials A quality -of-life study was carried out to test the hypothesis that melanoma patients treated with a 3-cm margin of excision  suffer greater impairment of their quality of life than those treated with a 1-cm margin . The secondary aim was to determine the predictors of a poor patient perception of their excision scar . A postal question naire study was carried out using Hospital Anxiety and Depression ( HAD ) , Psychosocial Adjustment of Illness Scale-Self-Report ( PAIS-SR ) , Medical Outcomes Survey-Short Form 36 ( MOS-SF36 ) , and the Cassileth Scar question naires .  Data were collected from 426 of the 537 patients who were mailed the question naires ( response rate 79 % ) . Fourteen percent had clinical ly significant anxiety and 5 % had significant depression . A poor attitude toward quality of health care was associated with youth . Patients treated with a 3-cm margin excision had significantly poorer mental and physical function 1 mo after surgery , which disappeared within 6 mo . The greater difficulties experienced by the 3-cm margin group were particularly in their domestic , sexual , and social roles . Women , younger patients , those with poor physical and mental function after surgery , and those treated by a 3-cm margin were more likely to report a poorer perception of their scar . The poorer scar perception of patients in the 3-cm group persisted throughout the study period . Use of a 3-cm margin of excision for melanoma is associated with significantly more morbidity than use of a 1-cm margin , but this effect disappears in 6 mo . Patients treated by 3-cm excision were more likely , however , to have a persistent poor view of their scar . Youth and being female were also predictors of poor perception of the scar INTRODUCTION The incidence of melanoma has increased fivefold during the past three decades . Melanoma can no longer be classified as rare ; rather , it is now one of the more frequent tumors . METHODS Recommendations for the diagnosis and treatment of melanoma are laid out in the interdisciplinary S2 guidelines of the German Cancer Society , upon which the present review is based . The goal of this article is to present the clinical core recommendations for treatment in all disease stages . RESULT 
    Output:
    
This systematic review summarises the evidence regarding width of excision margins for primary cutaneous melanoma .
The summary estimate for recurrence free survival favoured wide excision [ Hazard Ratio 1.13 ; P = 0.06 ; 95 % confidence interval 0.99 to 1.28 ] but again the result did not reach statistical significance ( P < 0.05 level).Current r and omised trial evidence is insufficient to address optimal excision margins for primary cutaneous melanoma