***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: Several experimental studies have shown that melatonin has an oncostatic action , either by stimulating host antitumor immune defenses or by directly inhibiting the growth of some cancer histotypes , including melanoma . Our previous clinical studies demonstrated that melatonin may induce stabilization of the disease in untreatable metastatic solid tumor patients , and these results have been confirmed by others , at least in patients with metastatic melanoma . On the contrary , at present there are no data related to the possible efficacy of melatonin as an adjuvant endocrine therapy . This study was performed to investigate the impact of melatonin therapy on the disease-free survival ( DFS ) in melanoma patients surgically treated for regional node recurrence . The study included 30 node-relapsed melanoma patients , who were r and omized to receive no treatment or adjuvant therapy of melatonin  ( 20 mg/day orally in the evening ) every day until disease progression . After a median follow up of 31 months , the percent of DFS was significantly higher in melatonin-treated individuals than in controls . The DFS curve was also significantly longer in melatonin group than in controls . No melatonin-related toxicity was observed . This preliminary study suggests that an adjuvant endocrine therapy with melatonin may be effective in preventing disease progression in node-relapsed melanoma patients Aims and Background The theraputic role of chemotherapy in advanced non-small cell lung cancer ( NSCLC ) is controversial because of its potentially detrimental action on host anticancer defenses . On the contrary , IL-2 would seem to prolong survival time by improving the immune status , even though it is generally less effective in determining tumor regression in NSCLC . Our previous studies have suggested the possibility of increasing tumor sensitivity to IL-2 by concomitant administration of immunomodulating neurohormones , such as the pineal hormone melatonin ( MLT ) . On this basis , a study was carried out to evaluate the efficacy of immunotherapy with low-dose IL-2 plus MLT versus chemotherapy in advanced NSCLC . Methods The study included 60 patients with locally advanced or metastatic NSCLC , who were r and omized to receive immunotherapy or chemotherapy .  The immunotherapy consisted of IL-2 ( 3 million IU/day subcutaneously for 6 days/week for 4 weeks ) and MLT ( 40 mg/day orally every day , starting 7 days before IL-2 ) ; in nonprogressing patients , a second cycle was repeated after a 21-day rest period , then they underwent a maintenance period consisting of one week of therapy every month until progression . Chemotherapy consisted of cisplatin ( 20 mg/m2 ) and etoposide ( 100 mg/m2)/day intravenously for 3 days ; cycles of chemotherapy were repeated every 21 days until progression . Results No complete response was obtained . A partial response was achieved in 7/29 patients treated with chemotherapy and in 6/31 patients receiving chemotherapy . The difference was not significant . In contrast , the mean progression-free period and the percentage survival at 1 year was significantly higher in patients treated with immunotherapy than in those treated with chemotherapy .  Toxicity was substantially lower in patients receiving immunotherapy than in those given chemotherapy . Conclusions This r and omized study showed that immunotherapy with low-dose IL-2 plus MLT is a better tolerated and more effective therapy in terms of survival time than chemotherapy containing cisplatin in patients affected by advanced NSCLC Our previous experimental studies have shown that the best approach to increase the biological anti-tumour activity of interleukin 2 ( IL-2 ) is not co-administration of another cytokine , but the association with immunomodulating neurohormones , in an attempt to reproduce the physiological links between psychoendocrine and immune systems , which play a fundamental role in the regulation of the immune responses . In particular , the association with the pineal neurohormone melatonin ( MLT ) has been shown to cause tumour regressions in neoplasms that are generally non-responsive to IL-2 alone . To confirm these preliminary results , a clinical trial was performed in locally advanced or metastatic patients with solid tumours other than renal cell cancer and melanoma . The study included 80 consecutive patients , who were r and omised to be treated with IL-2 alone subcutaneously  ( 3 million IU day-1 at 8.00 p.m. 6 days a week for 4 weeks ) or IL-2 plus MLT  ( 40 mg day-1 orally at 8.00 p.m. every day starting 7 days before IL-2 ) . A complete response was obtained in 3/41 patients treated with IL-2 plus MLT and in none of the patients receiving IL-2 alone . A partial response was achieved in 8/41 patients treated with IL-2 plus MLT and in only 1/39 patients treated with IL-2 alone . Tumour objective regression rate was significantly higher in patients treated with IL-2 and MLT than in those receiving IL-2 alone ( 11/41 vs 1/39 , P < 0.001 ) . The survival at 1 year was significantly higher in patients treated with IL-2 and MLT than in the IL-2 group ( 19/41 vs 6/39 , P < 0.05 ) . Finally , the mean increase in lymphocyte and eosinophil number was significantly higher in the IL-2 plus MLT group than in patients treated with IL-2 alone ; on the contrary , the mean increase in the specific marker of macrophage activation neopterin was significantly higher in patients treated with IL-2 alone . The treatment was well tolerated in both groups of patients . This study shows that the concomitant administration of the pineal hormone MLT may increase the efficacy of low-dose IL-2 subcutaneous therapy Systematic Review Series Series Editors : Cynthia Mulrow , MD , MSc Deborah Cook , MD , MSc The last article in this series outlined methods with which to search the literature for studies on the clinical question that generates a systematic review [ 1 ] . Herein , we discuss the subsequent steps of selecting and appraising  studies  for a review . Both of these steps involve important judgments that can influence the results of a review . In selecting studies , review ers judge the relevance of the studies to the review question . In appraising studies , review ers judge numerous features of design and analysis . Some of these judgments are easy to make ; others are more difficult and prone to error . To be confident in their decisions , review ers should use methods that are reliable ( the results do not change if the procedure is repeated ) , impartial ( not influenced by the study results ) , and explicit ( unambiguous ) [ 2 ] . These strategies for selection and appraisal are sensible , and they distinguish most systematic review s from most narrative review s. However , evidence to support the importance of some of the methods we suggest is either scant or conflicting ; readers are referred to the original research on these approaches for more details . Selecting Studies for Systematic Review s If review ers perform a comprehensive search of the literature using the methods described previously in this series [ 1 ] , they will probably have assembled a large sample of articles . This sample will include most ( ideally , all ) studies that are relevant to the review question ( that is , the sensitivity of the search will be high ) . Inevitably , because such a wide net is cast , articles not pertinent to the clinical question will be retrieved ( that is , the specificity of the search will be modest ) . Thus , the review ers ' next task is to sort through all of the potentially relevant articles and select those that will be included in the review . To do so , review ers adopt several of the tactics listed in Table 1 and Table 2 for planning and executing the selection process ( in effect , improving the specificity of the search ) ; these tactics are described below . Table 1 . Planning Study Selection Table 2 . Strategies for Selecting and Appraising Studies Begin with a Well-Built Clinical Question Review ers should ensure that the question for review includes the four elements of a well-built clinical question [ 3 , 4 ] : the patients of interest , the main interventions under investigation , the comparison interventions , and the clinical outcomes of interest . By including these four elements , review ers can better focus the selection process . Choose Selection Criteria That Fit the Clinical Question Consider a systematic review of the effectiveness of a drug treatment ( for example , a proton-pump inhibitor ) for patients with a particular disorder ( such as esophageal reflux ) . Review ers need to decide whether to include studies of patients with any symptoms of reflux , only those with classic symptoms , or only those in whom definitive diagnostic tests have confirmed the presence of reflux . In addition , review ers might choose to include studies of patients with different comorbid conditions ; patients from different demographic or geographic or cultural background s ; or patients from different health systems , such as inpatient or community population s. Similarly , review ers should use selection criteria that reflect the main and comparison interventions of interest . In our esophageal reflux example , review ers would need to decide whether to include studies of a particular drug or studies of all agents in that drug 's class and whether to include studies of any dose and regimen or only studies with a specific regimen . For the comparison interventions , the review ers would decide whether to include studies that compare the experimental drug with alternate treatments ( such as antacids or histamine-2-receptor antagonists ) , with placebo , or with both . For the clinical outcomes , review ers have analogous tasks of defining the outcomes and translating them into criteria . In our example , the review ers would start by listing each clinical outcome ( for example , whether the outcome was endoscopic or clinical and whether it focused on cure or persistence ) and then decide whether to include studies that reported any outcome or only those with certain clinical ly important outcomes ( such as improvement in symptoms at 1 year ) . After thoroughly considering each element of the review question , review ers compile a set of explicit selection criteria . When these criteria are not explicit , the results of the review are more prone to error [ 5 , 6 ] . Reporting the selection criteria used in a review is extremely important to readers because the criteria indicate the relevance of the review to the readers ' clinical practice . Specify the Types of Study Design To Be Included After creating selection criteria that appropriately reflect the review question , review ers should consider which study design s to include . Ideally , review ers choose study design s that are most likely to produce valid results . For example , to answer questions about therapy or harm , review ers may want to include r and omized trials [ 7 ] because they provide more accurate estimates of benefit or harm than do cohort studies , casecontrol studies , and case series [ 8 ] . In reality , however , r and omized trials may not be conducted to address questions of harm [ 9 ] . Therefore , review ers need to consider which study design s are likely to be available to answer their question ; this information may necessitate modification of originally conceptualized selection criteria to incorporate observational ( nonexperimental ) studies . Specify Criteria Related to Type and Form of Publication Review ers also need to consider issues related to type and form of publication . Ideally , all of the relevant studies would be published as peer- review ed journal articles . However , some completed studies may be published only as abstract s , in non-peer- review ed form , or not at all . Review ers decide whether to include these incompletely reported studies when planning their literature search . By including all articles in various stages of publication and subjecting them to rigorous critical appraisal , review ers minimize the threat of publication bias ( the preferential reporting of studies with positive results ) [ 10 - 12 ] , which could generate misleading review s. Other studies may be reported more than once . To avoid over-representing duplicate studies in the review , investigators should plan to look for and exclude duplicate publications [ 13 ] . Finally , because studies may be published in different language s and because excluding studies published in different language s may bias the results of review s [ 14 , 15 ] , articles should be included , as appropriate , regardless of the language of publication ( translating as necessary ) . Limited time and re sources , however , may preclude such an approach . Construct and Pretest Selection Forms After deciding on selection criteria , review ers can prepare customized forms that contain checklists of the selection criteria ( Figure 1 ) . Using these forms can simplify the selection process , increase reliability , and provide a record of the judgments made about each study . After drafting form prototypes , review ers pretest these forms for clarity , ease of application , and reliability . To pretest the forms , two or more independent review ers typically apply them to a r and om sample of studies identified by the literature search . Review ers compare their results to identify sources of ambiguity and then revise the forms accordingly . If the revisions are substantial , this process may need to be repeated before the forms can be used . Figure 1 . Example of a form that might be developed for the selection of studies for a systematic review evaluating the efficacy of -blockers for secondary prevention of variceal bleeding .  Write a Detailed Protocol Having a selection protocol as part of a larger protocol for the entire review helps review ers in two ways . First , it provides a document that explicitly states the review question and the selection criteria , making the process accountable . Review ers can later return to the protocol for guidance in resolving disagreements about article selection . Second , the selection protocol identifies what work will be done , by whom , in what manner , when , and for what reason ; thus , it provides a mode of communication within the review team . When review ers have a very large sample of studies from which to select , they can simplify this task by review ing all of the titles , then the abstract s , and then the full articles , excluding studies that do not meet one or more selection criteria at each step . In doing so , review ers should record ( on the selection forms ) the reasons for exclusion . After review ers have selected studies for the systematic review , they will move to the next task of critical appraisal . This procedure also requires careful planning . Appraising Studies for Systematic Review s Review ers appraise the studies selected for review with three objectives in mind : 1 ) to underst and the validity of the studies , 2 ) to uncover reasons for differences among study results other than chance , and 3 ) to provide readers with sufficient information with which to judge for themselves the applicability of the systematic review to their clinical practice . To achieve these goals , review ers use the strategies outlined in Table 2 and Table 3 to carefully reexamine many important features of the primary studies . Table 3 . Planning Study Appraisal Examine Important Clinical Features Although the selection criteria for a systematic review define the population , interventions , and outcomes of interest , the apprais 
    Output:
    
Effects were consistent across melatonin dose , and type of cancer .
The substantial reduction in risk of death , low adverse events reported and low costs related to this intervention suggest great potential for melatonin in treating cancer .