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: Surgery is the st and ard treatment for patients with resectable esophageal carcinoma , but the long term prognosis of these patients is unsatisfactory . Some r and omized trials of preoperative chemotherapy suggest that the prognosis of patients who respond may be improved Background Multiple studies have shown that promoter methylation of tumor suppressor genes underlies esophageal carcinogenesis . Hypothetically , methylation result ing in tumor suppressor gene inactivation might result in tumors that are unresponsive to chemotherapy and radiation . Accordingly , our aim was to investigate if aberrant methylation of the apoptosis-related gene Death-Associated Protein Kinase ( DAPK ) could be used as a predictor of response to neoadjuvant therapy in locally advanced cancer of the esophagus . Methods Tumor and normal esophageal tissues were obtained from 50 patients with locally advanced cancer of the esophagus prior to neoadjuvant radiochemotherapy .  DAPK methylation analysis was performed on all sample s by methylation-specific real-time polymerase chain reaction ( PCR ) . Results Seventeen ( 34 % ) patients showed a major and 33 ( 66 % ) a minor histomorphological response to neoadjuvant therapy .  DAPK methylation was detectable in normal esophageal tissues with a frequency of 10 % and in tumor tissue with a frequency of 78 % . The median methylation level for DAPK was 2.7 × 10−3 in tumor compared with 0.1 × 10−3 in normal tissues ( p < 0.001 ) . DAPK methylation was not associated with response to neoadjuvant therapy or prognosis after esophagectomy . Conclusion Aberrant DAPK methylation in tumor tissues is significantly higher compared with matching normal esophageal tissues , suggesting a fundamental role of this epigenetic alteration in the pathogenesis of this disease . The level of DAPK methylation in pretreatment biopsies of patients with locally advanced cancer of the esophagus is no marker for the prediction of histomorphological regression or prognosis following neoadjuvant chemoradiation in this disease BACKGROUND Initial results of the ChemoRadiotherapy for Oesophageal cancer followed by Surgery Study ( CROSS ) comparing neoadjuvant chemoradiotherapy plus surgery versus surgery alone in patients with squamous cell carcinoma and adenocarcinoma of the oesophagus or oesophagogastric junction showed a significant increase in 5-year overall survival in favour of the neoadjuvant chemoradiotherapy plus surgery group after a median of 45 months ' follow-up . In this Article , we report the long-term results after a minimum follow-up of 5 years . METHODS Patients with clinical ly resectable , locally advanced cancer of the oesophagus or oesophagogastric junction ( clinical stage T1N1M0 or T2 - 3N0 - 1M0 , according to the TNM cancer staging system , sixth edition ) were r and omly assigned in a 1:1 ratio with permuted blocks of four or six to receive either weekly administration of five cycles of neoadjuvant chemoradiotherapy ( intravenous carboplatin [ AUC 2 mg/mL per min ] and intravenous paclitaxel [ 50 mg/m(2 ) of body-surface area ] for 23 days ) with concurrent radiotherapy ( 41·4 Gy , given in 23 fractions of 1·8 Gy on 5 days per week ) followed by surgery , or surgery alone . The primary endpoint was overall survival , analysed by intention-to-treat . No adverse event data were collected beyond those noted in the initial report of the trial . This trial is registered with the Netherl and s Trial Register , number NTR487 , and has been completed . FINDINGS Between March 30 , 2004 , and Dec 2 , 2008 , 368 patients from eight participating centres ( five academic centres and three large non-academic teaching hospitals ) in the Netherl and s were enrolled into this study and r and omly assigned to the two treatment groups : 180 to surgery plus neoadjuvant chemoradiotherapy and 188 to surgery alone . Two patients in the neoadjuvant chemoradiotherapy group withdrew consent , so a total of 366 patients were analysed ( 178 in the neoadjuvant chemoradiotherapy plus surgery group and 188 in the surgery alone group ) . Of 171 patients who received any neoadjuvant chemoradiotherapy  in this group , 162 ( 95 % ) were able to complete the entire neoadjuvant chemoradiotherapy regimen . After a median follow-up for surviving patients of 84·1 months ( range 61·1 - 116·8 , IQR 70·7 - 96·6 ) , median overall survival was 48·6 months ( 95 % CI 32·1 - 65·1 ) in the neoadjuvant chemoradiotherapy plus surgery group and 24·0 months ( 14·2 - 33·7 ) in the surgery alone group ( HR 0·68 [ 95 % CI 0·53 - 0·88 ] ; log-rank p=0·003 ) . Median overall survival for patients with squamous cell carcinomas was 81·6 months ( 95 % CI 47·2 - 116·0 ) in the neoadjuvant chemoradiotherapy plus surgery group and 21·1 months ( 15·4 - 26·7 ) in the surgery alone group ( HR 0·48 [ 95 % CI 0·28 - 0·83 ] ; log-rank p=0·008 ) ; for patients with adenocarcinomas , it was 43·2 months ( 24·9 - 61·4 ) in the neoadjuvant chemoradiotherapy plus surgery group and 27·1 months ( 13·0 - 41·2 ) in the surgery alone group ( HR 0·73 [ 95 % CI 0·55 - 0·98 ] ; log-rank p=0·038 ) . INTERPRETATION Long-term follow-up confirms the overall survival benefits for neoadjuvant chemoradiotherapy when added to surgery in patients with resectable oesophageal or oesophagogastric junctional cancer . This improvement is clinical ly relevant for both squamous cell carcinoma and adenocarcinoma subtypes . Therefore , neoadjuvant chemoradiotherapy according to the CROSS trial followed by surgical resection should be regarded as a st and ard of care for patients with resectable locally advanced oesophageal or oesophagogastric junctional cancer . FUNDING Dutch Cancer Foundation ( KWF Kankerbestrijding ) This paper is an overview of the new response evaluation criteria in solid tumours :  revised RECIST guideline ( version 1 . 1 ) , with a focus on up date d contents BACKGROUND Resection remains the best treatment for carcinoma of the oesophagus in terms of local control , but local recurrence and distant metastasis remain an issue after surgery . We aim ed to assess whether a short preoperative chemoradiotherapy regimen improves outcomes for patients with resectable oesophageal cancer . METHODS 128 patients were r and omly assigned to surgery alone and 128 patients to surgery  after 80 mg/m(2 ) cisplatin on day 1 , 800 mg/m(2 ) fluorouracil on days 1 - 4 , with concurrent radiotherapy of 35 Gy given in 15 fractions . The primary endpoint was progression-free survival . Secondary endpoints were overall survival , tumour response , toxic effects , patterns of failure , and quality of life . Analysis was done by intention to treat . FINDINGS Neither progression-free survival nor overall survival differed between groups ( hazard ratio [ HR ] 0.82 [ 95 % CI 0.61 - 1.10 ] and 0.89 [ 0.67 - 1.19 ] , respectively ) . The chemoradiotherapy- and -surgery group had more complete resections with clear margins than did the surgery-alone group ( 103 of 128 [ 80 % ] vs 76 of 128 [ 59 % ] , p=0.0002 ) , and had fewer positive lymph nodes ( 44 of 103 [ 43 % ] vs 69 of 103 [ 67 % ] , p=0.003 ) . Subgroup analysis showed that patients with squamous-cell tumours had better progression-free survival with chemoradiotherapy than did those with non-squamous tumours ( HR 0.47 [ 0.25 - 0.86 ] vs 1.02 [ 0.72 - 1.44 ] ) . However , the trial was underpowered to determine the real magnitude of benefit in this subgroup . INTERPRETATION Preoperative chemoradiotherapy with cisplatin and fluorouracil does not significantly improve progression-free or overall survival for patients with resectable oesophageal cancer compared with surgery alone . However , further assessment is warranted of the role of chemoradiotherapy in patients with squamous-cell tumours We assessed whether expression of excision repair cross-complementation group 1 ( ERCC1 ) and /or thymidylate synthase ( TS ) can predict clinical outcome after preoperative chemoradiotherapy ( CRT ) in patients with localised oesophageal cancer . Paraffin-embedded pretreatment tumour specimens collected by endoscopic biopsy from patients treated with preoperative CRT ( 5-fluorouracil/cisplatin or capecitabine/cisplatin plus radiation )  were analysed by immunohistochemical assay .  Between March 1993 and June 2005 , 129 patients were treated with preoperative CRT followed by surgery ;  of these , 108 biopsy specimens were available for analysis , and 40 % and 35 % were positive for ERCC1 and TS , respectively . Patients with ERCC1-negative ( p<0.001 ) or TS-negative ( p=0.04 ) tumours were significantly more likely to achieve pathologic major response . In multivariate analysis , ERCC1 was the only independent variable predicting pathologic response ( p<0.001 ) . Patients with ERCC1-negative tumours showed tendencies toward prolonged overall survival ( p=0.10 ) and event free survival ( p=0.08 ) . Prospect i ve studies are required to determine the benefit of preoperative CRT in ERCC1-negative tumours Introduction The esophageal squamous cell carcinoma ( ESCC ) is the predominant pathological type and accounts for more than 80 % of esophageal cancer in China . The successful use of anti-epidermal growth factor receptor ( EGFR ) treatment in head and neck squamous cell carcinoma provides the rationale for introducing anti-EGFR targeting treatment in ESCC . One of our prospect i ve phase II clinical trials analyzed the efficacy of nimotuzumab , an anti-EGFR agent , combined with chemotherapy ( paclitaxel and cisplatin ) to treat unresectable ESCC . Material s and methods We analyzed the correlation of the clinical response with EGFR expression by immunohistochemical staining ( IHC ) . Results Totally 55 tumor sample s were analyzed . 18/55 ( 32.7 % ) cases were with high EGFR expression while the other 37/55 ( 67.3 % ) cases were with low to moderate EGFR expression . The expression of EGFR was not related to gender , age , tumor location , tumor differentiation and clinical stage of disease . The objective response rate ( ORR ) in high EGFR expression group was 55.6 % ( 10/18 ) while that in low to moderate EGFR expression group was 54.1 % ( 20/37 ) ( P = 0.57 ) . Both the progression-free survival ( PFS ) and overall survival ( OS ) in high EGFR expression group were much shorter than those in low to moderate EGFR expression group ( PFS : 5.8 ± 0.5 vs. 11.0 ± 2.8 months , P = 0.007 ; OS : 9.7 ± 0.5 vs. 21.5 ± 1.5 months , P = 0.03 ) . Conclusions The results showed that over-expression of EGFR was related to poor survival of ESCC . The over-expression of EGFR by IHC might not be an ideal predictive biomarker of nimotuzumab treatment . Other EGFR pathway-associated molecules should be analyzed in further studies 
    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: Surgery is the st and ard treatment for patients with resectable esophageal carcinoma , but the long term prognosis of these patients is unsatisfactory . Some r and omized trials of preoperative chemotherapy suggest that the prognosis of patients who respond may be improved Background Multiple studies have shown that promoter methylation of tumor suppressor genes underlies esophageal carcinogenesis . Hypothetically , methylation result ing in tumor suppressor gene inactivation might result in tumors that are unresponsive to chemotherapy and radiation . Accordingly , our aim was to investigate if aberrant methylation of the apoptosis-related gene Death-Associated Protein Kinase ( DAPK ) could be used as a predictor of response to neoadjuvant therapy in locally advanced cancer of the esophagus . Methods Tumor and normal esophageal tissues were obtained from 50 patients with locally advanced cancer of the esophagus prior to neoadjuvant radiochemotherapy .  DAPK methylation analysis was performed on all sample s by methylation-specific real-time polymerase chain reaction ( PCR ) . Results Seventeen ( 34 % ) patients showed a major and 33 ( 66 % ) a minor histomorphological response to neoadjuvant therapy .  DAPK methylation was detectable in normal esophageal tissues with a frequency of 10 % and in tumor tissue with a frequency of 78 % . The median methylation level for DAPK was 2.7 × 10−3 in tumor compared with 0.1 × 10−3 in normal tissues ( p < 0.001 ) . DAPK methylation was not associated with response to neoadjuvant therapy or prognosis after esophagectomy . Conclusion Aberrant DAPK methylation in tumor tissues is significantly higher compared with matching normal esophageal tissues , suggesting a fundamental role of this epigenetic alteration in the pathogenesis of this disease . The level of DAPK methylation in pretreatment biopsies of patients with locally advanced cancer of the esophagus is no marker for the prediction of histomorphological regression or prognosis following neoadjuvant chemoradiation in this disease BACKGROUND Initial results of the ChemoRadiotherapy for Oesophageal cancer followed by Surgery Study ( CROSS ) comparing neoadjuvant chemoradiotherapy plus surgery versus surgery alone in patients with squamous cell carcinoma and adenocarcinoma of the oesophagus or oesophagogastric junction showed a significant increase in 5-year overall survival in favour of the neoadjuvant chemoradiotherapy plus surgery group after a median of 45 months ' follow-up . In this Article , we report the long-term results after a minimum follow-up of 5 years . METHODS Patients with clinical ly resectable , locally advanced cancer of the oesophagus or oesophagogastric junction ( clinical stage T1N1M0 or T2 - 3N0 - 1M0 , according to the TNM cancer staging system , sixth edition ) were r and omly assigned in a 1:1 ratio with permuted blocks of four or six to receive either weekly administration of five cycles of neoadjuvant chemoradiotherapy ( intravenous carboplatin [ AUC 2 mg/mL per min ] and intravenous paclitaxel [ 50 mg/m(2 ) of body-surface area ] for 23 days ) with concurrent radiotherapy ( 41·4 Gy , given in 23 fractions of 1·8 Gy on 5 days per week ) followed by surgery , or surgery alone . The primary endpoint was overall survival , analysed by intention-to-treat . No adverse event data were collected beyond those noted in the initial report of the trial . This trial is registered with the Netherl and s Trial Register , number NTR487 , and has been completed . FINDINGS Between March 30 , 2004 , and Dec 2 , 2008 , 368 patients from eight participating centres ( five academic centres and three large non-academic teaching hospitals ) in the Netherl and s were enrolled into this study and r and omly assigned to the two treatment groups : 180 to surgery plus neoadjuvant chemoradiotherapy and 188 to surgery alone . Two patients in the neoadjuvant chemoradiotherapy group withdrew consent , so a total of 366 patients were analysed ( 178 in the neoadjuvant chemoradiotherapy plus surgery group and 188 in the surgery alone group ) . Of 171 patients who received any neoadjuvant chemoradiotherapy  in this group , 162 ( 95 % ) were able to complete the entire neoadjuvant chemoradiotherapy regimen . After a median follow-up for surviving patients of 84·1 months ( range 61·1 - 116·8 , IQR 70·7 - 96·6 ) , median overall survival was 48·6 months ( 95 % CI 32·1 - 65·1 ) in the neoadjuvant chemoradiotherapy plus surgery group and 24·0 months ( 14·2 - 33·7 ) in the surgery alone group ( HR 0·68 [ 95 % CI 0·53 - 0·88 ] ; log-rank p=0·003 ) . Median overall survival for patients with squamous cell carcinomas was 81·6 months ( 95 % CI 47·2 - 116·0 ) in the neoadjuvant chemoradiotherapy plus surgery group and 21·1 months ( 15·4 - 26·7 ) in the surgery alone group ( HR 0·48 [ 95 % CI 0·28 - 0·83 ] ; log-rank p=0·008 ) ; for patients with adenocarcinomas , it was 43·2 months ( 24·9 - 61·4 ) in the neoadjuvant chemoradiotherapy plus surgery group and 27·1 months ( 13·0 - 41·2 ) in the surgery alone group ( HR 0·73 [ 95 % CI 0·55 - 0·98 ] ; log-rank p=0·038 ) . INTERPRETATION Long-term follow-up confirms the overall survival benefits for neoadjuvant chemoradiotherapy when added to surgery in patients with resectable oesophageal or oesophagogastric junctional cancer . This improvement is clinical ly relevant for both squamous cell carcinoma and adenocarcinoma subtypes . Therefore , neoadjuvant chemoradiotherapy according to the CROSS trial followed by surgical resection should be regarded as a st and ard of care for patients with resectable locally advanced oesophageal or oesophagogastric junctional cancer . FUNDING Dutch Cancer Foundation ( KWF Kankerbestrijding ) This paper is an overview of the new response evaluation criteria in solid tumours :  revised RECIST guideline ( version 1 . 1 ) , with a focus on up date d contents BACKGROUND Resection remains the best treatment for carcinoma of the oesophagus in terms of local control , but local recurrence and distant metastasis remain an issue after surgery . We aim ed to assess whether a short preoperative chemoradiotherapy regimen improves outcomes for patients with resectable oesophageal cancer . METHODS 128 patients were r and omly assigned to surgery alone and 128 patients to surgery  after 80 mg/m(2 ) cisplatin on day 1 , 800 mg/m(2 ) fluorouracil on days 1 - 4 , with concurrent radiotherapy of 35 Gy given in 15 fractions . The primary endpoint was progression-free survival . Secondary endpoints were overall survival , tumour response , toxic effects , patterns of failure , and quality of life . Analysis was done by intention to treat . FINDINGS Neither progression-free survival nor overall survival differed between groups ( hazard ratio [ HR ] 0.82 [ 95 % CI 0.61 - 1.10 ] and 0.89 [ 0.67 - 1.19 ] , respectively ) . The chemoradiotherapy- and -surgery group had more complete resections with clear margins than did the surgery-alone group ( 103 of 128 [ 80 % ] vs 76 of 128 [ 59 % ] , p=0.0002 ) , and had fewer positive lymph nodes ( 44 of 103 [ 43 % ] vs 69 of 103 [ 67 % ] , p=0.003 ) . Subgroup analysis showed that patients with squamous-cell tumours had better progression-free survival with chemoradiotherapy than did those with non-squamous tumours ( HR 0.47 [ 0.25 - 0.86 ] vs 1.02 [ 0.72 - 1.44 ] ) . However , the trial was underpowered to determine the real magnitude of benefit in this subgroup . INTERPRETATION Preoperative chemoradiotherapy with cisplatin and fluorouracil does not significantly improve progression-free or overall survival for patients with resectable oesophageal cancer compared with surgery alone . However , further assessment is warranted of the role of chemoradiotherapy in patients with squamous-cell tumours We assessed whether expression of excision repair cross-complementation group 1 ( ERCC1 ) and /or thymidylate synthase ( TS ) can predict clinical outcome after preoperative chemoradiotherapy ( CRT ) in patients with localised oesophageal cancer . Paraffin-embedded pretreatment tumour specimens collected by endoscopic biopsy from patients treated with preoperative CRT ( 5-fluorouracil/cisplatin or capecitabine/cisplatin plus radiation )  were analysed by immunohistochemical assay .  Between March 1993 and June 2005 , 129 patients were treated with preoperative CRT followed by surgery ;  of these , 108 biopsy specimens were available for analysis , and 40 % and 35 % were positive for ERCC1 and TS , respectively . Patients with ERCC1-negative ( p<0.001 ) or TS-negative ( p=0.04 ) tumours were significantly more likely to achieve pathologic major response . In multivariate analysis , ERCC1 was the only independent variable predicting pathologic response ( p<0.001 ) . Patients with ERCC1-negative tumours showed tendencies toward prolonged overall survival ( p=0.10 ) and event free survival ( p=0.08 ) . Prospect i ve studies are required to determine the benefit of preoperative CRT in ERCC1-negative tumours Introduction The esophageal squamous cell carcinoma ( ESCC ) is the predominant pathological type and accounts for more than 80 % of esophageal cancer in China . The successful use of anti-epidermal growth factor receptor ( EGFR ) treatment in head and neck squamous cell carcinoma provides the rationale for introducing anti-EGFR targeting treatment in ESCC . One of our prospect i ve phase II clinical trials analyzed the efficacy of nimotuzumab , an anti-EGFR agent , combined with chemotherapy ( paclitaxel and cisplatin ) to treat unresectable ESCC . Material s and methods We analyzed the correlation of the clinical response with EGFR expression by immunohistochemical staining ( IHC ) . Results Totally 55 tumor sample s were analyzed . 18/55 ( 32.7 % ) cases were with high EGFR expression while the other 37/55 ( 67.3 % ) cases were with low to moderate EGFR expression . The expression of EGFR was not related to gender , age , tumor location , tumor differentiation and clinical stage of disease . The objective response rate ( ORR ) in high EGFR expression group was 55.6 % ( 10/18 ) while that in low to moderate EGFR expression group was 54.1 % ( 20/37 ) ( P = 0.57 ) . Both the progression-free survival ( PFS ) and overall survival ( OS ) in high EGFR expression group were much shorter than those in low to moderate EGFR expression group ( PFS : 5.8 ± 0.5 vs. 11.0 ± 2.8 months , P = 0.007 ; OS : 9.7 ± 0.5 vs. 21.5 ± 1.5 months , P = 0.03 ) . Conclusions The results showed that over-expression of EGFR was related to poor survival of ESCC . The over-expression of EGFR by IHC might not be an ideal predictive biomarker of nimotuzumab treatment . Other EGFR pathway-associated molecules should be analyzed in further studies 
    Output:
    