***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 
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    Input: PURPOSE Erythropoietin , an oxygen-regulated glycoprotein hormone , is a hematopoietic cytokine that stimulates erythropoiesis by binding to its cellular receptor [ erythropoietin receptor ( EPOR ) ] . The recombinant form of human erythropoietin is used to prevent or treat anemia in cancer patients . However , in a recent r and omized , placebo-controlled trial involving patients receiving curative radiotherapy for squamous cell carcinoma of the head and neck , erythropoietin treatment was associated with poorer locoregional progression-free survival . The purpose of our study was to determine whether EPOR and its lig and erythropoietin are expressed in primary head and neck cancer . We also investigated the hypothesis that erythropoietin expression in malignant cells may be associated with the presence of tumor hypoxia , an important factor involved in resistance to radiation treatment , tumor aggressiveness , and poor prognosis . EXPERIMENTAL DESIGN Twenty-one patients received an i.v . infusion of the hypoxia marker pimonidazole hydrochloride before multiple tumor biopsies . Contiguous sections from 74 biopsies were analyzed by immunohistochemistry for EPOR and erythropoietin expression and pimonidazole binding . RESULTS EPOR expression was present in tumor cells in 97 % of the biopsies . Coexpression of erythropoietin was observed in 90 % of biopsies . Erythropoietin and pimonidazole adduct staining did not always colocalize within tumors , but there was a significant positive correlation between levels of microregional erythropoietin expression and pimonidazole binding . CONCLUSIONS The coexpression of erythropoietin and EPOR in tumor cells suggests that erythropoietin may potentially function as an autocrine or paracrine factor in head and neck cancer . The expression of the hypoxia-inducible protein erythropoietin in tumor cells correlates with levels of tumor hypoxia Background In the literature we find many indices of size of treatment effect ( effect size : ES ) . The preferred index of treatment effect in evidence -based medicine is the number needed to treat ( NNT ) , while the most common one in the medical literature is Cohen 's d when the outcome is continuous . There is confusion about how to convert Cohen 's d into NNT . Methods We conducted meta-analyses of individual patient data from 10 r and omized controlled trials of second generation antipsychotics for schizophrenia ( n = 4278 ) to produce Cohen 's d and NNTs for various definitions of response , using cutoffs of 10 % through 90 % reduction on the symptom severity scale . These actual NNTs were compared with NNTs calculated from Cohen 's d according to two proposed methods in the literature ( Kraemer , et al. , Biological Psychiatry , 2006 ; Furukawa , Lancet , 1999 ) . Results NNTs from Kraemer 's method overlapped with the actual NNTs in 56 % , while those based on Furukawa 's method fell within the observed ranges of NNTs in 97 % of the examined instances . For various definitions of response corresponding with 10 % through 70 % symptom reduction where we observed a non-small number of responders , the degree of agreement for the former method was at a chance level ( ANOVA ICC of 0.12 , p = 0.22 ) but that for the latter method was ANOVA ICC of 0.86 ( 95%CI : 0.55 to 0.95 , p<0.01 ) . Conclusions Furukawa 's method allows more accurate prediction of NNTs from Cohen 's d. Kraemer 's method gives a wrong impression that NNT is constant for a given d even when the event rate differs Cancer-related anaemia is associated with a wide spectrum of symptoms that can negatively affect quality of life . Because epoetin alfa has demonstrated efficacy in correcting cancer-related anaemia , the impact of this treatment on quality of life was evaluated in a multinational , r and omised , double-blind , placebo-controlled trial in 375 anaemic cancer patients receiving non-platinum-based chemotherapy .  The cancer-specific measures of quality of life included the general scale ( FACT-G Total ) and fatigue subscale ( FACT-An Fatigue subscale ) of the Functional Assessment of Cancer Therapy-Anaemia and the Cancer Linear Analogue Scales measuring energy , ability to do daily activities , and overall quality of life . These measures were also used to examine the relationship between haemoglobin levels and quality of life . Both univariate and multiple linear regression analyses of quality of life data were performed . Results of the univariate analysis have been reported previously . The a priori-planned multiple linear regression analysis , which accounted for the effects of disease progression and several other possibly confounding variables on quality of life , showed a significant advantage for epoetin alfa over placebo for the five scales ( all , P<0.05 ) , and confirmed the results of the univariate analysis . For cancer-specific measures , significant correlations were demonstrated between baseline haemoglobin and quality of life ( r , range : 0.14–0.26 , all P<0.05 ) and between change in haemoglobin and change in quality of life ( r , range : 0.26–0.34 , all P<0.01 ) . These findings provide evidence that increasing haemoglobin levels by epoetin alfa administration can significantly improve cancer patients ' quality of life Summary Anaemia commonly occurs in cancer patients receiving chemotherapy , often necessitating blood transfusion . This multicentre study was design ed to evaluate the efficacy and safety of epoetin α in preventing the decline in haemoglobin ( Hb ) level , and to determine whether the transfusion requirement could be reduced , in patients receiving 4–6 cycles of primarily platinum-based combination cyclic chemotherapy for small cell lung cancer ( SCLC ) . A total of 130 non-anaemic SCLC patients were r and omized to receive no additional treatment ( n = 44 ) , epoetin α 150 IU kg–1 subcutaneously ( s.c . ) three times a week ( n = 42 ) or 300 IU kg–1 s.c . three times a week ( n = 44 ) . Reductions in epoetin α dosage were made during the study if Hb level increased to > 15 g dl–1 . The mean weekly dosage was 335 and 612 IU kg–1 , respectively , in the two active treatment groups . Significantly fewer ( P < 0.05 ) epoetin α-treated patients experienced anaemia ( Hb < 10 g dl–1 ) during the course of chemotherapy ( 300 IU kg–1 , 39 % ; 150 IU kg–1 , 48 % ; untreated , 66 % ) . This was reflected in the significantly lower number of treated patients transfused [ 300 IU kg–1 , 20 % ( P < 0.001 ) ; 150 IU kg–1 , 45 % ( P < 0.05 ) ; untreated , 59 % ] . Epoetin α was well-tolerated , and there was no evidence of sustained , clinical ly significant , hypertension . In summary , epoetin α is effective and well-tolerated in maintaining Hb level and reducing transfusion requirement in patients undergoing cyclic chemotherapy for SCLC PURPOSE To investigate the effect of recombinant human erythropoietin ( epoetin beta ) on anemia , transfusion need , and quality of life ( QOL ) in severely anemic patients with low- grade non-Hodgkin 's lymphoma ( NHL ) , chronic lymphocytic leukemia ( CLL ) , or multiple myeloma ( MM ) . PATIENTS AND METHODS Transfusion-dependent patients with NHL ( n = 106 ) , CLL ( n = 126 ) , or MM ( n = 117 ) and a low serum erythropoietin concentration were r and omized to receive epoetin beta 150 IU/kg or placebo subcutaneously three times a week for 16 weeks . Primary efficacy criteria were transfusion-free and transfusion- and severe anemia-free survival ( hemoglobin [ Hb ] > 8.5 g/dL ) between weeks 5 to 16 . Response was defined as an increase in Hb > or = 2 g/dL with elimination of transfusion need . QOL was assessed by the Functional Assessment of Cancer Therapy scale . RESULTS Transfusion-free ( P = .0012 ) survival and transfusion- and severe anemia-free survival ( P = .0001 ) were significantly greater in the epoetin beta group versus placebo ( Wald chi(2 ) test ) , giving a relative risk reduction of 43 % and 51 % , respectively . The response rate was 67 % and 27 % in the epoetin beta versus the placebo group , respectively ( P < .0001 ) . After 12 and 16 weeks of treatment , QOL significantly improved in the epoetin beta group compared with placebo ( P < .05 ) ; this improvement correlated with an increase in Hb concentration ( > or = 2 g/dL ) . A target Hb that could be generally recommended could not be identified . CONCLUSION Many severely anemic and transfusion-dependent patients with advanced MM , NHL , and CLL and a low performance status benefited from epoetin therapy , with elimination of severe anemia and transfusion need , and improvement in QOL This multicentre , open-label , controlled clinical trial assessed the effects of epoetin alfa treatment on haematologic and quality of life ( QOL ) parameters in 182 anaemic ( Hb⩽12 g dl−1 ) ovarian cancer patients receiving platinum chemotherapy . Patients were r and omised 2 : 1 to receive epoetin alfa 10 000–20 000 IU three times weekly plus best st and ard treatment ( BST ) or BST only . Main study end points were changes from baseline in haemoglobin ( Hb ) level , transfusion requirements , and QOL . For the epoetin alfa group , mean Hb increased by 1.8 g dl−1 by weeks 4–6 and was significantly increased from baseline through study end ( P<0.001 ) . The mean change in Hb from baseline was significantly ( P<0.001 ) greater for epoetin alfa than BST patients at all postbaseline evaluations . Significantly fewer epoetin alfa than BST patients required transfusion(s ) after the first 4 weeks of treatment ( 7.9 vs 30.5 % ; P<0.001 ) . Also , significant ( P⩽0.04 ) differences favouring the epoetin alfa group over the BST group were found for all three median CLAS scores ( Energy Level , Ability to Do Daily Activities , Overall QOL ) and the median average CLAS score during chemotherapy . These findings support use of epoetin alfa to increase Hb levels , reduce transfusion use , and improve QOL in anaemic ovarian cancer patients receiving platinum chemotherapy PURPOSE To prospect ively evaluate the effectiveness , safety , and clinical benefits of once-weekly epoetin alfa therapy as an adjunct to chemotherapy in anemic cancer patients . PATIENTS AND METHODS A total of 3,012 patients with nonmyeloid malignancies who received chemotherapy were enrolled onto this multicenter , open-label , nonr and omized study conducted in 600 United States community-based practice s. Patients received epoetin alfa 40,000 U once weekly , which could be increased to 60,000 U once weekly after 4 weeks dependent on hemoglobin response . Treatment was continued for a maximum of 16 weeks . RESULTS Among the 2,964 patients assessable for efficacy  , epoetin alfa therapy result ed in significant increases in hemoglobin levels , decreases in transfusion requirements , and improvements in functional status and fatigue as assessed by the linear analog scale assessment ( energy level , ability to perform daily activities , and overall quality of life ) and the anemia subscale of the Functional Assessment of Cancer Therapy-Anemia question naire . Improvements in quality -of-life parameters correlated significantly ( P < .001 ) with increased hemoglobin levels . The direct relationship between hemoglobin and quality -of-life improvement was sustained during the 16-week study period , which is similar to findings of large community-based trials of three-times-weekly dosing . Once-weekly epoetin alfa was well tolerated , with most adverse events attributed to the underlying disease or concomitant chemotherapy . CONCLUSION The results from this large , prospect i ve , community-based trial suggest that once-weekly epoetin alfa therapy increases hemoglobin levels , decreases transfusion requirements , and improves quality of life in patients with cancer and anemia who undergo concomitant chemotherapy . Based on the results of this study , the clinical benefits and the adverse event profile of once-weekly epoetin alfa therapy in community-based practice are similar to those observed in the historical experience with the three-times-weekly dosage schedule PURPOSE To determine whether weekly epoetin alfa could improve hemoglobin ( HgB ) levels , reduce RBC transfusions , and improve quality of life ( QOL ) in patients with advanced cancer and with anemia after receiving myelosuppressive chemotherapy . PATIENTS AND METHODS This double-blind , placebo-controlled study r and omly assigned patients to placebo or epoetin alfa ( Ortho Biotech , Bridgewater , NJ ) 40,000 U subcutaneous weekly for 16 weeks . QOL , HgB , and RBC transfusions were measured pretreatment and monthly . RESULTS The study accrued 344 patients ; 330 were assessable for efficacy and 3 
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Conclusions : In cancer patients , particularly those receiving chemotherapy , we found that ESAs provide a small but clinical ly important improvement in anaemia-related symptoms ( FACT-An ) .
For fatigue-related symptoms ( FACT-F ) , the overall effect did not reach the threshold for a CID