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: PURPOSE Combining cisplatin or cetuximab with radiation improves overall survival ( OS ) of patients with stage III or IV head and neck carcinoma ( HNC ) .  Cetuximab plus platinum regimens also increase OS in metastatic HNC . The Radiation Therapy Oncology Group launched a phase III trial to test the hypothesis that adding cetuximab to the radiation-cisplatin platform improves progression-free survival ( PFS ) . PATIENTS AND METHODS Eligible patients with stage III or IV HNC were r and omly assigned to receive radiation and cisplatin without ( arm A ) or with ( arm B ) cetuximab .  Acute and late reactions were scored using Common Terminology Criteria for Adverse Events ( version 3 ) . Outcomes were correlated with patient and tumor features and markers . RESULTS Of 891 analyzed patients , 630 were alive at analysis ( median follow-up , 3.8 years ) . Cetuximab plus cisplatin-radiation , versus cisplatin-radiation alone , result ed in more frequent interruptions in radiation therapy ( 26.9 % v. 15.1 % , respectively ) ; similar cisplatin delivery ( mean , 185.7 mg/m2 v. 191.1 mg/m2 , respectively ) ; and more grade 3 to 4 radiation mucositis ( 43.2 % v. 33.3 % , respectively ) , rash , fatigue , anorexia , and hypokalemia , but not more late toxicity . No differences were found between arms A and B in 30-day mortality ( 1.8 % v. 2.0 % , respectively ; P = .81 ) , 3-year PFS ( 61.2 % v. 58.9 % , respectively ; P = .76 ) , 3-year OS ( 72.9 % v. 75.8 % , respectively ; P = .32 ) , locoregional failure ( 19.9 % v. 25.9 % , respectively ; P = .97 ) , or distant metastasis ( 13.0 % v. 9.7 % , respectively ; P = .08 ) . Patients with p16-positive oropharyngeal carcinoma ( OPC ) , compared with patients with p16-negative OPC , had better 3-year probability of PFS ( 72.8 % v. 49.2 % , respectively ; P < .001 ) and OS ( 85.6 % v. 60.1 % , respectively ; P < .001 ) , but tumor epidermal growth factor receptor ( EGFR ) expression did not distinguish outcome . CONCLUSION Adding cetuximab to radiation-cisplatin did not improve outcome and hence should not be prescribed routinely . PFS and OS were higher in patients with p16-positive OPC , but outcomes did not differ by EGFR expression Aim and background Radiotherapy is the conventional treatment for locally advanced inoperable head and neck squamous cell carcinoma . However , the poor therapeutic results justify the development of radiochemotherapy combinations . In an attempt to improve local control and survival in patients with stage III and IV unresectable head and neck squamous cell carcinoma and based on the results of our previous dose escalation study , we undertook a prospect i ve multicentric r and omized trial . Material s and methods From November 1992 through December 1995 , a total of 164 patients were r and omized to receive radiotherapy alone ( arm I ) or combined ( arm II ) with daily low-dose carboplatin . Results The 3 , 5 and 10-year local-regional recurrence-free survival rates were better in arm II(21.7 % , 15.1 % and 15.1 % , respectively ) than in arm I ( 15 % , 10.7 % and 10.7 % ) , but without statistical significance ( P = 0.11 ) . The 3 , 5 and 10-year disease-free survival rates showed the same positive trend for arm II ( 16 % , 6.8 % and 6.8 % vs 9 % , 5.5 % and 5.5 % , in arm I , respectively ) , again without statistical significance ( P = 0.09 ) . Instead , a statistical advantage was found in overall survival rates at 3 , 5 and 10-years ( 28.9 % , 9 % and 5.5 % in arm II and 11.1 % , 6.9 % and 6.9 % in arm I , respectively ) ( P = 0.02 ) . The 3 , 5 and 10-year local-regional recurrence-free survival rates in stage IV disease were statistically better in arm II ( 21.5 % , 15.9 % and 15.9 % ) than in arm I ( 12.8 % , 7.7 % and 7.7 % , respectively ) ( P = 0.04 ) . Conclusions Long-term results in both treatment arms of the trial appear less positive than most published series . However , our findings do not exclude that carboplatin may be beneficial , but the benefit in local control must be lower than the 15 % assumed to dimension the trial PURPOSE To determine whether , in the postoperative setting , accelerated fractionation ( AF ) radiotherapy ( RT ) yields a superior locoregional control rate compared with conventional fractionation ( CF ) RT in locally advanced squamous cell carcinomas of the oral cavity , oropharynx , larynx , or hypopharynx . METHODS AND MATERIAL S Patients from four institutions with one or more high-risk features ( pT4 , positive resection margins , pN > 1 , perineural/lymphovascular invasion , extracapsular extension , subglottic extension ) after surgery were r and omly assigned to either RT with one daily session of 2 Gy up to 60 Gy in 6 weeks or AF . Accelerated fractionation consisted of a " biphasic concomitant boost " schedule , with the boost delivered during the first and last weeks of treatment , to deliver 64 Gy in 5 weeks . Informed consent was obtained . The primary endpoint of the study was locoregional control . Analysis was on an intention-to-treat basis . RESULTS From March 1994 to August 2000 , 226 patients were r and omized . At a median follow-up of 30.6 months ( range , 0 - 110 months ) , 2-year locoregional control estimates were 80 % + /- 4 % for CF and 78 % + /- 5 % for AF ( p = 0.52 ) , and 2-year overall survival estimates were 67 % + /- 5 % for CF and 64 % + /- 5 % for AF ( p = 0.84 ) . The lack of difference in outcome between the two treatment arms was confirmed by multivariate analysis . However , interaction analysis with median values as cut-offs showed a trend for improved locoregional control for those patients who had a delay in starting RT and who were treated with AF compared with those with a similar delay but who were treated with CF ( hazard ratio = 0.5 , 95 % confidence interval 0.2 - 1.1 ) . Fifty percent of patients treated with AF developed confluent mucositis , compared with only 27 % of those treated with CF ( p = 0.006 ) . However , mucositis duration was not different between arms . Although preliminary , actuarial Grade 3 + late toxicity estimates at 2 years were 18 % + /- 4 % and 27 % + /- 6 % for CF and AF , respectively ( p = 0.10 ) . CONCLUSION Accelerated fractionation does not seem to be worthwhile for squamous cell carcinoma of the head and neck after resection ; however , AF might be an option for patients who delay starting RT BACKGROUND A r and omized phase 3 trial of the treatment of squamous-cell carcinoma of the head and neck compared induction chemotherapy with docetaxel plus cisplatin and fluorouracil ( TPF ) with cisplatin and fluorouracil ( PF ) , followed by chemoradiotherapy . METHODS We r and omly assigned 501 patients ( all of whom had stage III or IV disease with no distant metastases and tumors considered to be unresectable or were c and i date s for organ preservation ) to receive either TPF or PF induction chemotherapy  , followed  by chemoradiotherapy with weekly carboplatin therapy and radiotherapy for 5 days per week . The primary end point was overall survival . RESULTS With a minimum of 2 years of follow-up ( > or =3 years for 69 % of patients ) , significantly more patients survived in the TPF group than in the PF group ( hazard ratio for death , 0.70 ; P=0.006 ) . Estimates of overall survival at 3 years were 62 % in the TPF group and 48 % in the PF group ; the median overall survival was 71 months and 30 months , respectively ( P=0.006 ) . There was better locoregional control in the TPF group than in the PF group ( P=0.04 ) , but the incidence of distant metastases in the two groups did not differ significantly ( P=0.14 ) . Rates of neutropenia and febrile neutropenia were higher in the TPF group ; chemotherapy was more frequently delayed because of hematologic adverse events in the PF group . CONCLUSIONS Patients with squamous-cell carcinoma of the head and neck who received docetaxel plus cisplatin and fluorouracil induction chemotherapy plus chemoradiotherapy had a significantly longer survival than did patients who received cisplatin and fluorouracil induction chemotherapy plus chemoradiotherapy . ( Clinical Trials.gov number , NCT00273546 [ Clinical Trials.gov ] . ) Background Platinum-based chemoradiation ( CCRT ) is the st and ard treatment for Locally Advanced Head and Neck Squamous-Cell Carcinoma ( LAHNSCC ) .  Cetuximab/RT ( CET/RT ) is an alternative treatment option to CCRT . The efficacy of induction chemotherapy ( IC ) followed by chemoradiation compared to chemoradiation alone has not been demonstrated in r and omized clinical trials . The goals of this phase II-III trial were to assess : ( i ) the overall survival ( OS ) of  IC  versus no-induction ( no-IC  ) and ( ii ) the Grade 3 - 4 in-field mucosal toxicity of CCRT versus CET/RT . The present paper focuses on the analysis of efficacy . Material s and methods Patients with LAHNSCC were r and omized to receive concomitant treatment alone [ CCRT ( Arm A1 ) or CET/RT ( Arm A2 ) ] , or three cycles of induction docetaxel/cisplatin/5 fluorouracil ( TPF ) followed by CCRT ( Arm B1 ) or followed by CET/RT ( Arm B2 ) . The superiority hypothesis of OS comparison of IC versus no-IC ( Arms B1 + B2 versus A1 + A2 ) required 204 deaths to detect an absolute 3-year OS difference of 12 % ( HR 0.675 , with 80 % power at two-sided 5 % significance level ) . Results 414 out of 421 patients were finally analyzed : 206 in the IC and 208 in the no-IC arm . Six patients were excluded because of major violation and one because of metastatic disease at diagnosis . With a median follow-up of 44.8 months , OS was significantly higher in the IC arm ( HR 0.74 ; 95 % CI 0.56 - 0.97 ; P = 0.031 ) . Complete Responses ( P = 0.0028 ) , Progression Free Survival ( P = 0.013 ) and the Loco-regional Control ( P = 0.036 ) were also significantly higher in the IC arm . Compliance to concomitant treatments was not affected by induction TPF . Conclusions IC followed by concomitant treatment improved the outcome of patients with LAHNSCC without compromising compliance to the concomitant treatments . The degree of the benefit of IC could be different according to the type of the subsequent concomitant strategy . Clinical Trial Number NCT01086826 , www . clinical trials.gov BACKGROUND Cetuximab combined with radiotherapy ( RT ) is a treatment option for head and neck cancer . The objectives of this r and omized , phase II trial were to evaluate the efficacy and safety of cetuximab maintenance therapy following definitive RT with concomitant cetuximab in patients with oropharyngeal cancer . PATIENTS AND METHODS Ninety-one patients with stage III-IV M0 oropharyngeal tumors were r and omly assigned to the treatment with accelerated concomitant boost RT ( 69.9 Gy ) + cetuximab or the same treatment with the addition of 12 consecutive weeks of cetuximab maintenance therapy . The primary end point was locoregional control ( LRC ) at 1 year . RESULTS LRC at 1 year was superior among patients in the experimental arm , treated with cetuximab maintenance ( 59 % versus 47 % ) . However , LRC was similar between both arms after 2 years of follow-up , as a result of increased locoregional recurrences after the first year in the maintenance group . Patients treated with adjuvant cetuximab do recover very soon from toxic effect after combined treatment . CONCLUSIONS Twelve weeks of cetuximab maintenance therapy after concomitant cetuximab + RT in locally advanced oropharyngeal carcinoma is feasible and improves clinical outcomes measured at 1 year . This improvement is not maintained after the second year suggesting that epidermal growth factor receptor blockade is not sufficient to completely eliminate the minimal residual disease In 1986 , we initiated a multic 
    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: PURPOSE Combining cisplatin or cetuximab with radiation improves overall survival ( OS ) of patients with stage III or IV head and neck carcinoma ( HNC ) .  Cetuximab plus platinum regimens also increase OS in metastatic HNC . The Radiation Therapy Oncology Group launched a phase III trial to test the hypothesis that adding cetuximab to the radiation-cisplatin platform improves progression-free survival ( PFS ) . PATIENTS AND METHODS Eligible patients with stage III or IV HNC were r and omly assigned to receive radiation and cisplatin without ( arm A ) or with ( arm B ) cetuximab .  Acute and late reactions were scored using Common Terminology Criteria for Adverse Events ( version 3 ) . Outcomes were correlated with patient and tumor features and markers . RESULTS Of 891 analyzed patients , 630 were alive at analysis ( median follow-up , 3.8 years ) . Cetuximab plus cisplatin-radiation , versus cisplatin-radiation alone , result ed in more frequent interruptions in radiation therapy ( 26.9 % v. 15.1 % , respectively ) ; similar cisplatin delivery ( mean , 185.7 mg/m2 v. 191.1 mg/m2 , respectively ) ; and more grade 3 to 4 radiation mucositis ( 43.2 % v. 33.3 % , respectively ) , rash , fatigue , anorexia , and hypokalemia , but not more late toxicity . No differences were found between arms A and B in 30-day mortality ( 1.8 % v. 2.0 % , respectively ; P = .81 ) , 3-year PFS ( 61.2 % v. 58.9 % , respectively ; P = .76 ) , 3-year OS ( 72.9 % v. 75.8 % , respectively ; P = .32 ) , locoregional failure ( 19.9 % v. 25.9 % , respectively ; P = .97 ) , or distant metastasis ( 13.0 % v. 9.7 % , respectively ; P = .08 ) . Patients with p16-positive oropharyngeal carcinoma ( OPC ) , compared with patients with p16-negative OPC , had better 3-year probability of PFS ( 72.8 % v. 49.2 % , respectively ; P < .001 ) and OS ( 85.6 % v. 60.1 % , respectively ; P < .001 ) , but tumor epidermal growth factor receptor ( EGFR ) expression did not distinguish outcome . CONCLUSION Adding cetuximab to radiation-cisplatin did not improve outcome and hence should not be prescribed routinely . PFS and OS were higher in patients with p16-positive OPC , but outcomes did not differ by EGFR expression Aim and background Radiotherapy is the conventional treatment for locally advanced inoperable head and neck squamous cell carcinoma . However , the poor therapeutic results justify the development of radiochemotherapy combinations . In an attempt to improve local control and survival in patients with stage III and IV unresectable head and neck squamous cell carcinoma and based on the results of our previous dose escalation study , we undertook a prospect i ve multicentric r and omized trial . Material s and methods From November 1992 through December 1995 , a total of 164 patients were r and omized to receive radiotherapy alone ( arm I ) or combined ( arm II ) with daily low-dose carboplatin . Results The 3 , 5 and 10-year local-regional recurrence-free survival rates were better in arm II(21.7 % , 15.1 % and 15.1 % , respectively ) than in arm I ( 15 % , 10.7 % and 10.7 % ) , but without statistical significance ( P = 0.11 ) . The 3 , 5 and 10-year disease-free survival rates showed the same positive trend for arm II ( 16 % , 6.8 % and 6.8 % vs 9 % , 5.5 % and 5.5 % , in arm I , respectively ) , again without statistical significance ( P = 0.09 ) . Instead , a statistical advantage was found in overall survival rates at 3 , 5 and 10-years ( 28.9 % , 9 % and 5.5 % in arm II and 11.1 % , 6.9 % and 6.9 % in arm I , respectively ) ( P = 0.02 ) . The 3 , 5 and 10-year local-regional recurrence-free survival rates in stage IV disease were statistically better in arm II ( 21.5 % , 15.9 % and 15.9 % ) than in arm I ( 12.8 % , 7.7 % and 7.7 % , respectively ) ( P = 0.04 ) . Conclusions Long-term results in both treatment arms of the trial appear less positive than most published series . However , our findings do not exclude that carboplatin may be beneficial , but the benefit in local control must be lower than the 15 % assumed to dimension the trial PURPOSE To determine whether , in the postoperative setting , accelerated fractionation ( AF ) radiotherapy ( RT ) yields a superior locoregional control rate compared with conventional fractionation ( CF ) RT in locally advanced squamous cell carcinomas of the oral cavity , oropharynx , larynx , or hypopharynx . METHODS AND MATERIAL S Patients from four institutions with one or more high-risk features ( pT4 , positive resection margins , pN > 1 , perineural/lymphovascular invasion , extracapsular extension , subglottic extension ) after surgery were r and omly assigned to either RT with one daily session of 2 Gy up to 60 Gy in 6 weeks or AF . Accelerated fractionation consisted of a " biphasic concomitant boost " schedule , with the boost delivered during the first and last weeks of treatment , to deliver 64 Gy in 5 weeks . Informed consent was obtained . The primary endpoint of the study was locoregional control . Analysis was on an intention-to-treat basis . RESULTS From March 1994 to August 2000 , 226 patients were r and omized . At a median follow-up of 30.6 months ( range , 0 - 110 months ) , 2-year locoregional control estimates were 80 % + /- 4 % for CF and 78 % + /- 5 % for AF ( p = 0.52 ) , and 2-year overall survival estimates were 67 % + /- 5 % for CF and 64 % + /- 5 % for AF ( p = 0.84 ) . The lack of difference in outcome between the two treatment arms was confirmed by multivariate analysis . However , interaction analysis with median values as cut-offs showed a trend for improved locoregional control for those patients who had a delay in starting RT and who were treated with AF compared with those with a similar delay but who were treated with CF ( hazard ratio = 0.5 , 95 % confidence interval 0.2 - 1.1 ) . Fifty percent of patients treated with AF developed confluent mucositis , compared with only 27 % of those treated with CF ( p = 0.006 ) . However , mucositis duration was not different between arms . Although preliminary , actuarial Grade 3 + late toxicity estimates at 2 years were 18 % + /- 4 % and 27 % + /- 6 % for CF and AF , respectively ( p = 0.10 ) . CONCLUSION Accelerated fractionation does not seem to be worthwhile for squamous cell carcinoma of the head and neck after resection ; however , AF might be an option for patients who delay starting RT BACKGROUND A r and omized phase 3 trial of the treatment of squamous-cell carcinoma of the head and neck compared induction chemotherapy with docetaxel plus cisplatin and fluorouracil ( TPF ) with cisplatin and fluorouracil ( PF ) , followed by chemoradiotherapy . METHODS We r and omly assigned 501 patients ( all of whom had stage III or IV disease with no distant metastases and tumors considered to be unresectable or were c and i date s for organ preservation ) to receive either TPF or PF induction chemotherapy  , followed  by chemoradiotherapy with weekly carboplatin therapy and radiotherapy for 5 days per week . The primary end point was overall survival . RESULTS With a minimum of 2 years of follow-up ( > or =3 years for 69 % of patients ) , significantly more patients survived in the TPF group than in the PF group ( hazard ratio for death , 0.70 ; P=0.006 ) . Estimates of overall survival at 3 years were 62 % in the TPF group and 48 % in the PF group ; the median overall survival was 71 months and 30 months , respectively ( P=0.006 ) . There was better locoregional control in the TPF group than in the PF group ( P=0.04 ) , but the incidence of distant metastases in the two groups did not differ significantly ( P=0.14 ) . Rates of neutropenia and febrile neutropenia were higher in the TPF group ; chemotherapy was more frequently delayed because of hematologic adverse events in the PF group . CONCLUSIONS Patients with squamous-cell carcinoma of the head and neck who received docetaxel plus cisplatin and fluorouracil induction chemotherapy plus chemoradiotherapy had a significantly longer survival than did patients who received cisplatin and fluorouracil induction chemotherapy plus chemoradiotherapy . ( Clinical Trials.gov number , NCT00273546 [ Clinical Trials.gov ] . ) Background Platinum-based chemoradiation ( CCRT ) is the st and ard treatment for Locally Advanced Head and Neck Squamous-Cell Carcinoma ( LAHNSCC ) .  Cetuximab/RT ( CET/RT ) is an alternative treatment option to CCRT . The efficacy of induction chemotherapy ( IC ) followed by chemoradiation compared to chemoradiation alone has not been demonstrated in r and omized clinical trials . The goals of this phase II-III trial were to assess : ( i ) the overall survival ( OS ) of  IC  versus no-induction ( no-IC  ) and ( ii ) the Grade 3 - 4 in-field mucosal toxicity of CCRT versus CET/RT . The present paper focuses on the analysis of efficacy . Material s and methods Patients with LAHNSCC were r and omized to receive concomitant treatment alone [ CCRT ( Arm A1 ) or CET/RT ( Arm A2 ) ] , or three cycles of induction docetaxel/cisplatin/5 fluorouracil ( TPF ) followed by CCRT ( Arm B1 ) or followed by CET/RT ( Arm B2 ) . The superiority hypothesis of OS comparison of IC versus no-IC ( Arms B1 + B2 versus A1 + A2 ) required 204 deaths to detect an absolute 3-year OS difference of 12 % ( HR 0.675 , with 80 % power at two-sided 5 % significance level ) . Results 414 out of 421 patients were finally analyzed : 206 in the IC and 208 in the no-IC arm . Six patients were excluded because of major violation and one because of metastatic disease at diagnosis . With a median follow-up of 44.8 months , OS was significantly higher in the IC arm ( HR 0.74 ; 95 % CI 0.56 - 0.97 ; P = 0.031 ) . Complete Responses ( P = 0.0028 ) , Progression Free Survival ( P = 0.013 ) and the Loco-regional Control ( P = 0.036 ) were also significantly higher in the IC arm . Compliance to concomitant treatments was not affected by induction TPF . Conclusions IC followed by concomitant treatment improved the outcome of patients with LAHNSCC without compromising compliance to the concomitant treatments . The degree of the benefit of IC could be different according to the type of the subsequent concomitant strategy . Clinical Trial Number NCT01086826 , www . clinical trials.gov BACKGROUND Cetuximab combined with radiotherapy ( RT ) is a treatment option for head and neck cancer . The objectives of this r and omized , phase II trial were to evaluate the efficacy and safety of cetuximab maintenance therapy following definitive RT with concomitant cetuximab in patients with oropharyngeal cancer . PATIENTS AND METHODS Ninety-one patients with stage III-IV M0 oropharyngeal tumors were r and omly assigned to the treatment with accelerated concomitant boost RT ( 69.9 Gy ) + cetuximab or the same treatment with the addition of 12 consecutive weeks of cetuximab maintenance therapy . The primary end point was locoregional control ( LRC ) at 1 year . RESULTS LRC at 1 year was superior among patients in the experimental arm , treated with cetuximab maintenance ( 59 % versus 47 % ) . However , LRC was similar between both arms after 2 years of follow-up , as a result of increased locoregional recurrences after the first year in the maintenance group . Patients treated with adjuvant cetuximab do recover very soon from toxic effect after combined treatment . CONCLUSIONS Twelve weeks of cetuximab maintenance therapy after concomitant cetuximab + RT in locally advanced oropharyngeal carcinoma is feasible and improves clinical outcomes measured at 1 year . This improvement is not maintained after the second year suggesting that epidermal growth factor receptor blockade is not sufficient to completely eliminate the minimal residual disease In 1986 , we initiated a multic 
    Output:
    