human
***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 Surgical resection with curative intent for giant cell tumor of bone ( GCTB ) may be associated with severe morbidity . This interim analysis evaluated reduction in surgical invasiveness after denosumab treatment in patients with resectable GCTB . Methods Patients with primary or recurrent GCTB , for whom the initially planned surgery was associated with functional compromise or morbidity , received denosumab 120 mg subcutaneously every 4 weeks ( additional doses on days 8 and 15 of the first cycle ) . Planned and actual GCTB-related surgical procedures before and after denosumab treatment were reported . Patients were followed for surgical outcome , adverse events , and recurrence following resection . Results Overall , 222 patients were evaluable for surgical downstaging ( 54 % were women ; median age 34 years ) . Lesions ( 67 % primary and 33 % recurrent ) were located in the axial ( 15 % ) and appendicular skeleton ( 85 % ) . At the data cutoff date , most patients had not yet undergone surgery ( n = 106 ; 48 % ) or had a less morbid procedure ( n = 84 ; 38 % ) than originally planned . Median ( interquartile range ) time on denosumab was 19.5 ( 12.4–28.6 ) months for the 106 patients who had not undergone surgery and were continuing on monthly denosumab . Native joint preservation was 96 % ( n = 24/25 ) for patients with planned joint/prosthesis replacement and 86 % ( n = 30/35 ) for patients with planned joint resection/fusion . Of the 116 patients who had surgery ( median postsurgical follow-up 13.0 [ 8.5–17.9 ] months ) , local recurrence occurred in 17 ( 15 % ) patients . Conclusion For patients with resectable GCTB , neoadjuvant denosumab therapy result ed in beneficial surgical downstaging , including either no surgery or a less morbid surgical procedure Background : Recent clinical studies have suggested that denosumab is associated with tumor response and reduced surgical morbidity in patients with giant-cell tumor of bone ( GCTB ) . We therefore evaluated the recurrence-free survival rate of patients who had GCTB in an extremity and were treated with surgery and denosumab  , to determine the influence of denosumab and clinical factors on the risk of local recurrence . Methods : We retrospectively review ed the medical records of 408 patients treated for GCTB in an extremity in a single institution from 1990 through 2013 . Two hundred and forty-seven patients underwent curettage ( intralesional surgery ) with a high-speed burr , and 161 underwent resection . Phenol adjuvant was used in 221 of the 247 patients who had  curettage . We also review ed the medical records of 30 patients treated surgically ( 25 with curettage and 5 with resection ) and with denosumab from 2010 through 2013 and compared their clinical results with 378 historical control subjects . The overall minimum duration of follow-up was 24 months . Results : The local recurrence rates were 60 % ( 15 ) of 25 patients treated with curettage and denosumab and 16 % ( 36 ) of 222 patients treated with curettage alone . The joint preservation rates were 80 % ( 20 ) of 25 patients treated with curettage and denosumab and 94 % ( 209 ) of 222 patients treated with curettage alone . Univariate and multivariable analyses showed that denosumab was the only independent factor associated with a poor prognosis when recurrence-free survival and joint preservation were considered . The overall median duration of follow-up was 85.6 months ( interquartile range , 54.3 to 125.1 months ) . Viable tumor was present in all 30 specimens from patients treated with denosumab . Conclusions : There was a higher rate of recurrence in the cohort exposed to denosumab . Because there were substantial differences in the cohorts and r and omization was not applied , however , causation could not be evaluated . Level of Evidence : Therapeutic Level III . See Instructions for Authors for a complete description of levels of evidence Study Design . A prospect i ve cohort study . Objective . The aim of this study was to evaluate the interest of denosumab in the treatment of spinal giant-cells tumors ( GCTs ) and aneurysmal bone cysts ( ABCs ) . Summary of Background Data . To treat GCTs and ABCs , surgical resection remains the best treatment to limit local recurrence ( LR ) but constitutes an aggressive treatment with potential morbidity . Denosumab , a human antibody anti-RankL , inhibiting the differentiation of osteoclasts , could be an alternative treatment to avoid aggressive surgery . Methods . Patients suffering from GCTs and ABCs of the spine were included . Patients received a monthly subcutaneous injection of denosumab ( 120 mg ) during a minimum of 6 months either as a neoadjuvant or as an adjuvant therapy . In association with denosumab , an osteo synthesis was added in case of vertebral fracture and a laminectomy in case of spinal cord compression . Clinical and computed tomography (CT)-scan outcomes were analyzed . Results . Eight GCTs and one ABC were included . The mean age was 35 years ( range : 22–55 yr ) . Five patients had neurologic deficit . All patients were operated : six osteo synthesis , one “ en bloc ” resection , four curettages , and two of them associated with an osteo synthesis . Average duration of denosumab therapy was 12.9 months ( range : 3.2–24 months ) . Among them , four patients began denosumab 6 months at least before the surgery . With a mean follow-up of 19.3 months ( range : 3.2–52.4 months ) , back pain and neurologic deficit improved for all patients . Systematic CT-scan at 6 months showed decrease of tumor size and bone consolidation . Regarding patients treated by neoadjuvant denosumab treatment , intraoperative histologic analysis showed an absence of giant cells and a maximum of 10 % of alive tumor cells . Conclusion . Denosumab allows bone formation and tumor regression with a maximum efficacy after 6 months of treatment without widely substituting surgery . Long-term results are m and atory to confirm the interest of denosumab and to evaluate LR when stopping denosumab . Level of Evidence : OBJECT Giant cell tumors ( GCTs ) of the spine are rare and complex to treat . They have a propensity for local recurrence and the potential to metastasize . Treatment is currently surgical and presents unique challenges due to the proximity of neural structures and the need for reconstruction . Denosumab has been shown in clinical trials to be an effective treatment for GCT , but has not yet been studied specifically in GCT of the spine or as a surgical adjunct . To the authors ' knowledge this is the first such reported series . METHODS A multicenter , prospect i ve series of 5 patients with GCT of the spine treated with denosumab were included . Patient demographic data , oncological history , neurological status , tumor staging , treatment details and adverse events , surgical procedure , complications , radiological and histological responses , and patient outcome were analyzed . RESULTS All patients were women , with a mean age of 38 years , and presented with pain ; 2 patients had additional neurological signs and symptoms .  The mean  duration of symptoms was 62 weeks . No patient had a prior tumor or metastatic disease at presentation . All patients had Enneking Stage III tumors and were treated with monthly cycles of 120 mg of denosumab , with initial additional loading doses on Days 8 and 15 . Patients were given daily supplements of calcium ( 500 mg ) and vitamin D ( 400 IU ) . There were no  denosumab-related adverse events . All patients had a radiological response to denosumab . One patient failed to have a histological response to denosumab , with > 90 % of tumor cells found to be viable on histological investigation . CONCLUSIONS This study reports the early experience of using denosumab in the treatment of spinal GCT . The results demonstrate a clinical ly beneficial radiological response and an impressive histological response in most but not all patients . Further experience with denosumab and longer patient follow-up is required . Denosumab has the potential to change the treatment paradigm for spinal GCT BACKGROUND Giant cell tumour of bone ( GCTB ) is a very rare , aggressive , and progressive osteolytic tumour for which no st and ard medicinal treatment or chemotherapy exists . We report interim safety and efficacy results from a phase 2 study of denosumab in patients with GCTB . METHODS We did an international , open-label , parallel-group , phase 2 trial of patients with histologically confirmed GCTB and radiographically measurable active disease . Eligible patients were adults or skeletally mature adolescents with radiographic evidence of at least one mature long bone who were at least 12 years old and weighed at least 45 kg . We divided patients into three cohorts -- those with surgically unsalvageable GCTB ( cohort 1 ) , those with salvageable GCTB whose surgery was associated with severe morbidity ( cohort 2 ) , and those who transferred from a previous study of denosumab for GCTB ( cohort 3 ) . Patients in cohorts 1 and 2 received 120 mg of subcutaneous denosumab every 4 weeks with loading doses on days 8 and 15 of the first cycle ; those in cohort 3 continued the regimen from the previous study . Investigator-determined disease status and clinical benefit were assessed every 4 weeks . Our primary endpoint was the safety profile of denosumab in terms of adverse events and laboratory abnormalities . Prespecified secondary endpoints were time to disease progression in cohort 1 and the proportion of patients without any surgery at 6 months in cohort 2 . Safety analyses included all patients who received at least one dose of denosumab . Efficacy analyses included all eligible patients who received at least one dose of denosumab . This study is registered with Clinical Trials.gov , identifier NCT00680992 . FINDINGS 282 patients , including ten adolescents , were included between Sept 9 , 2008 , and March 25 , 2011 . Of the 281 patients analysable for safety , three ( 1 % ) had osteonecrosis of the jaw and 15 ( 5 % ) hypocalcaemia . The most common grade 3 - 4 adverse events were hypophosphataemia , which occurred in nine ( 3 % ) patients , and anaemia , back pain , and pain in extremities , each of which occurred in three patients ( 1 % ) . Serious adverse events were reported in 25 ( 9 % ) patients . No treatment-related deaths were reported . On the basis of investigators ' assessment of disease status , 163 of 169 ( 96 % ) analysable patients in cohort 1 had no disease progression after median follow-up of 13 months ( IQR 5·8 - 21·0 ) . In cohort 2 , 74 of 100 ( 74 % ) analysable patients had no surgery and 16 of 26 ( 62 % ) patients who had surgery underwent a less morbid procedure than planned . Median follow-up in cohort 2 was 9·2 months ( IQR 4·2 - 12·9 ) . INTERPRETATION Adverse events were consistent with the known safety profile of denosumab . Denosumab was associated with tumour responses and reduced the need for morbid surgery in patients with GCTB . Denosumab represents a new treatment option for patients with GCTB . FUNDING Amgen A RANK lig and -specific inhibitor , denosumab , was predicted to reduce osteolysis and control disease progression in patients with giant cell tumor of bone ( GCTB ) . We report , for the first time , the results of the response of GCTB to denosumab obtained from a prospect i ve independent imaging assessment . The findings demonstrate that denosumab has robust clinical efficacy in the treatment of GCTB BACKGROUND Giant-cell tumour ( GCT ) of bone is a primary osteolytic bone tumour with low metastatic potential and is associated with substantial skeletal morbidity . GCT is rich in osteoclast-like giant cells and contains mononuclear ( stromal ) cells that express RANK lig and ( RANKL ) , a key mediator of osteoclast activation . We investigated the potential therapeutic effect of denosumab , a fully human monoclonal antibody against RANKL , on tumour-cell survival and growth in patients with GCT . METHODS In this open-label , single-group study , 37 patients with recurrent or unresectable GCT were enrolled and received subcutaneous denosumab 120 mg monthly ( every 28 days ) , with loading doses on days 8 and 15 of month 1 . The primary endpoint was tumour response , defined as elimination of at least 90 % of giant cells or no radiological progression of the target lesion up to week 25 . Study recruitment is closed ; patient treatment and follow-up are ongoing . The study is registered with Clinical Trials.gov , NCT00396279 . FINDINGS Two patients had insufficient histology or radiology data for efficacy assessment . 30 of 35 ( 86 % ; 95 % CI 70 - 95 ) of evaluable patients had a tumour 
    Output:
    
agent
***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 Surgical resection with curative intent for giant cell tumor of bone ( GCTB ) may be associated with severe morbidity . This interim analysis evaluated reduction in surgical invasiveness after denosumab treatment in patients with resectable GCTB . Methods Patients with primary or recurrent GCTB , for whom the initially planned surgery was associated with functional compromise or morbidity , received denosumab 120 mg subcutaneously every 4 weeks ( additional doses on days 8 and 15 of the first cycle ) . Planned and actual GCTB-related surgical procedures before and after denosumab treatment were reported . Patients were followed for surgical outcome , adverse events , and recurrence following resection . Results Overall , 222 patients were evaluable for surgical downstaging ( 54 % were women ; median age 34 years ) . Lesions ( 67 % primary and 33 % recurrent ) were located in the axial ( 15 % ) and appendicular skeleton ( 85 % ) . At the data cutoff date , most patients had not yet undergone surgery ( n = 106 ; 48 % ) or had a less morbid procedure ( n = 84 ; 38 % ) than originally planned . Median ( interquartile range ) time on denosumab was 19.5 ( 12.4–28.6 ) months for the 106 patients who had not undergone surgery and were continuing on monthly denosumab . Native joint preservation was 96 % ( n = 24/25 ) for patients with planned joint/prosthesis replacement and 86 % ( n = 30/35 ) for patients with planned joint resection/fusion . Of the 116 patients who had surgery ( median postsurgical follow-up 13.0 [ 8.5–17.9 ] months ) , local recurrence occurred in 17 ( 15 % ) patients . Conclusion For patients with resectable GCTB , neoadjuvant denosumab therapy result ed in beneficial surgical downstaging , including either no surgery or a less morbid surgical procedure Background : Recent clinical studies have suggested that denosumab is associated with tumor response and reduced surgical morbidity in patients with giant-cell tumor of bone ( GCTB ) . We therefore evaluated the recurrence-free survival rate of patients who had GCTB in an extremity and were treated with surgery and denosumab  , to determine the influence of denosumab and clinical factors on the risk of local recurrence . Methods : We retrospectively review ed the medical records of 408 patients treated for GCTB in an extremity in a single institution from 1990 through 2013 . Two hundred and forty-seven patients underwent curettage ( intralesional surgery ) with a high-speed burr , and 161 underwent resection . Phenol adjuvant was used in 221 of the 247 patients who had  curettage . We also review ed the medical records of 30 patients treated surgically ( 25 with curettage and 5 with resection ) and with denosumab from 2010 through 2013 and compared their clinical results with 378 historical control subjects . The overall minimum duration of follow-up was 24 months . Results : The local recurrence rates were 60 % ( 15 ) of 25 patients treated with curettage and denosumab and 16 % ( 36 ) of 222 patients treated with curettage alone . The joint preservation rates were 80 % ( 20 ) of 25 patients treated with curettage and denosumab and 94 % ( 209 ) of 222 patients treated with curettage alone . Univariate and multivariable analyses showed that denosumab was the only independent factor associated with a poor prognosis when recurrence-free survival and joint preservation were considered . The overall median duration of follow-up was 85.6 months ( interquartile range , 54.3 to 125.1 months ) . Viable tumor was present in all 30 specimens from patients treated with denosumab . Conclusions : There was a higher rate of recurrence in the cohort exposed to denosumab . Because there were substantial differences in the cohorts and r and omization was not applied , however , causation could not be evaluated . Level of Evidence : Therapeutic Level III . See Instructions for Authors for a complete description of levels of evidence Study Design . A prospect i ve cohort study . Objective . The aim of this study was to evaluate the interest of denosumab in the treatment of spinal giant-cells tumors ( GCTs ) and aneurysmal bone cysts ( ABCs ) . Summary of Background Data . To treat GCTs and ABCs , surgical resection remains the best treatment to limit local recurrence ( LR ) but constitutes an aggressive treatment with potential morbidity . Denosumab , a human antibody anti-RankL , inhibiting the differentiation of osteoclasts , could be an alternative treatment to avoid aggressive surgery . Methods . Patients suffering from GCTs and ABCs of the spine were included . Patients received a monthly subcutaneous injection of denosumab ( 120 mg ) during a minimum of 6 months either as a neoadjuvant or as an adjuvant therapy . In association with denosumab , an osteo synthesis was added in case of vertebral fracture and a laminectomy in case of spinal cord compression . Clinical and computed tomography (CT)-scan outcomes were analyzed . Results . Eight GCTs and one ABC were included . The mean age was 35 years ( range : 22–55 yr ) . Five patients had neurologic deficit . All patients were operated : six osteo synthesis , one “ en bloc ” resection , four curettages , and two of them associated with an osteo synthesis . Average duration of denosumab therapy was 12.9 months ( range : 3.2–24 months ) . Among them , four patients began denosumab 6 months at least before the surgery . With a mean follow-up of 19.3 months ( range : 3.2–52.4 months ) , back pain and neurologic deficit improved for all patients . Systematic CT-scan at 6 months showed decrease of tumor size and bone consolidation . Regarding patients treated by neoadjuvant denosumab treatment , intraoperative histologic analysis showed an absence of giant cells and a maximum of 10 % of alive tumor cells . Conclusion . Denosumab allows bone formation and tumor regression with a maximum efficacy after 6 months of treatment without widely substituting surgery . Long-term results are m and atory to confirm the interest of denosumab and to evaluate LR when stopping denosumab . Level of Evidence : OBJECT Giant cell tumors ( GCTs ) of the spine are rare and complex to treat . They have a propensity for local recurrence and the potential to metastasize . Treatment is currently surgical and presents unique challenges due to the proximity of neural structures and the need for reconstruction . Denosumab has been shown in clinical trials to be an effective treatment for GCT , but has not yet been studied specifically in GCT of the spine or as a surgical adjunct . To the authors ' knowledge this is the first such reported series . METHODS A multicenter , prospect i ve series of 5 patients with GCT of the spine treated with denosumab were included . Patient demographic data , oncological history , neurological status , tumor staging , treatment details and adverse events , surgical procedure , complications , radiological and histological responses , and patient outcome were analyzed . RESULTS All patients were women , with a mean age of 38 years , and presented with pain ; 2 patients had additional neurological signs and symptoms .  The mean  duration of symptoms was 62 weeks . No patient had a prior tumor or metastatic disease at presentation . All patients had Enneking Stage III tumors and were treated with monthly cycles of 120 mg of denosumab , with initial additional loading doses on Days 8 and 15 . Patients were given daily supplements of calcium ( 500 mg ) and vitamin D ( 400 IU ) . There were no  denosumab-related adverse events . All patients had a radiological response to denosumab . One patient failed to have a histological response to denosumab , with > 90 % of tumor cells found to be viable on histological investigation . CONCLUSIONS This study reports the early experience of using denosumab in the treatment of spinal GCT . The results demonstrate a clinical ly beneficial radiological response and an impressive histological response in most but not all patients . Further experience with denosumab and longer patient follow-up is required . Denosumab has the potential to change the treatment paradigm for spinal GCT BACKGROUND Giant cell tumour of bone ( GCTB ) is a very rare , aggressive , and progressive osteolytic tumour for which no st and ard medicinal treatment or chemotherapy exists . We report interim safety and efficacy results from a phase 2 study of denosumab in patients with GCTB . METHODS We did an international , open-label , parallel-group , phase 2 trial of patients with histologically confirmed GCTB and radiographically measurable active disease . Eligible patients were adults or skeletally mature adolescents with radiographic evidence of at least one mature long bone who were at least 12 years old and weighed at least 45 kg . We divided patients into three cohorts -- those with surgically unsalvageable GCTB ( cohort 1 ) , those with salvageable GCTB whose surgery was associated with severe morbidity ( cohort 2 ) , and those who transferred from a previous study of denosumab for GCTB ( cohort 3 ) . Patients in cohorts 1 and 2 received 120 mg of subcutaneous denosumab every 4 weeks with loading doses on days 8 and 15 of the first cycle ; those in cohort 3 continued the regimen from the previous study . Investigator-determined disease status and clinical benefit were assessed every 4 weeks . Our primary endpoint was the safety profile of denosumab in terms of adverse events and laboratory abnormalities . Prespecified secondary endpoints were time to disease progression in cohort 1 and the proportion of patients without any surgery at 6 months in cohort 2 . Safety analyses included all patients who received at least one dose of denosumab . Efficacy analyses included all eligible patients who received at least one dose of denosumab . This study is registered with Clinical Trials.gov , identifier NCT00680992 . FINDINGS 282 patients , including ten adolescents , were included between Sept 9 , 2008 , and March 25 , 2011 . Of the 281 patients analysable for safety , three ( 1 % ) had osteonecrosis of the jaw and 15 ( 5 % ) hypocalcaemia . The most common grade 3 - 4 adverse events were hypophosphataemia , which occurred in nine ( 3 % ) patients , and anaemia , back pain , and pain in extremities , each of which occurred in three patients ( 1 % ) . Serious adverse events were reported in 25 ( 9 % ) patients . No treatment-related deaths were reported . On the basis of investigators ' assessment of disease status , 163 of 169 ( 96 % ) analysable patients in cohort 1 had no disease progression after median follow-up of 13 months ( IQR 5·8 - 21·0 ) . In cohort 2 , 74 of 100 ( 74 % ) analysable patients had no surgery and 16 of 26 ( 62 % ) patients who had surgery underwent a less morbid procedure than planned . Median follow-up in cohort 2 was 9·2 months ( IQR 4·2 - 12·9 ) . INTERPRETATION Adverse events were consistent with the known safety profile of denosumab . Denosumab was associated with tumour responses and reduced the need for morbid surgery in patients with GCTB . Denosumab represents a new treatment option for patients with GCTB . FUNDING Amgen A RANK lig and -specific inhibitor , denosumab , was predicted to reduce osteolysis and control disease progression in patients with giant cell tumor of bone ( GCTB ) . We report , for the first time , the results of the response of GCTB to denosumab obtained from a prospect i ve independent imaging assessment . The findings demonstrate that denosumab has robust clinical efficacy in the treatment of GCTB BACKGROUND Giant-cell tumour ( GCT ) of bone is a primary osteolytic bone tumour with low metastatic potential and is associated with substantial skeletal morbidity . GCT is rich in osteoclast-like giant cells and contains mononuclear ( stromal ) cells that express RANK lig and ( RANKL ) , a key mediator of osteoclast activation . We investigated the potential therapeutic effect of denosumab , a fully human monoclonal antibody against RANKL , on tumour-cell survival and growth in patients with GCT . METHODS In this open-label , single-group study , 37 patients with recurrent or unresectable GCT were enrolled and received subcutaneous denosumab 120 mg monthly ( every 28 days ) , with loading doses on days 8 and 15 of month 1 . The primary endpoint was tumour response , defined as elimination of at least 90 % of giant cells or no radiological progression of the target lesion up to week 25 . Study recruitment is closed ; patient treatment and follow-up are ongoing . The study is registered with Clinical Trials.gov , NCT00396279 . FINDINGS Two patients had insufficient histology or radiology data for efficacy assessment . 30 of 35 ( 86 % ; 95 % CI 70 - 95 ) of evaluable patients had a tumour 
    Output:
    