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 BACKGROUND Single-modality radiotherapy is still considered st and ard treatment for patients with locally advanced unresectable cancer of the head and neck . As treatment outcome is poor , attempts to integrate chemotherapy into the overall management of these patients are ongoing . PATIENTS AND METHODS A r and omized study was undertaken to compare a sequential with a simultaneous chemoradiotherapy program . Between February 1986 and February 1991 , 93 eligible patients with locally advanced unresectable cancer of the head and neck were stratified by WHO PS , T and N class and primary site and then r and omized to receive either three courses of neoadjuvant chemotherapy with cisplatin ( 100 mg/m2 i.v . d 1 ) and 5-fluorouracil 1000 mg/m2/days 1 - 5 by continuous i.v . infusion every 3 weeks prior to definitive conventional radiotherapy of 65 - 70 Gy ( sequential treatment ) , or cisplatin 100 mg/m2 on days 1 , 22 , 43 given simultaneously for the duration of the same conventional radiotherapy ( simultaneous treatment ) . RESULTS At the end of the entire treatment 18 complete responses ( 47 % ) in the sequential-treatment arm and 18 ( 41 % ) in the simultaneous treatment arm were obtained . No statistically significant differences in the 5-yr progression-free survival , in the median time to loco-regional and distant progression and in the 5-yr overall survival were observed . Leukopenia was more frequent in the simultaneous than in the sequential arm ( p = 0.03 ) , whereas alopecia ( p = 0.008 ) and phlebitis ( p < 0.0001 ) were more frequent in the sequential-treatment arm . A better compliance was associated with the concomitant treatment , with 87 % of the patients completing the entire radiotherapy program versus 63 % of those in the sequential arm ( p = 0.01 ) . CONCLUSIONS In the present study , the two treatment arms showed similar activity ( complete response , progression-free and overall survival rates ) . Compliance to treatment was better in the concomitant arm . These data suggest that concomitant chemo-radiation therapy might be considered an option in unresectable locally advanced cancer of the head and neck . Phase III studies are needed in order to establish the superiority of this combination of cisplatin and radiotherapy versus radiotherapy alone 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 This study was design ed to ascertain whether a prior reduction of tumor size by drugs could affect the final outcome of tumors treated with radiation . 142 patients with head and neck cancer ( oropharynx , maxillary antrum and intra-oral ) were r and omized for the study . In 72 cases , irradiation was preceded by a continuous intra-arterial infusion of 3 - 5 mg/day methotrexate to a total dose of 90 - 120 mg ; the other 70 patients were treated with radiotherapy alone . Chemotherapy , given prior to radiotherapy , caused a shift in the tumor stage ( i.e. a reduction in tumor size ) in more than one third of the cases . The overall 5-year survival was 43 % in the combined treatment group and 25 % in the group treated with radiation alone ( statistical difference : p less than .05 ) . However , when analysed separately the difference was statistically significant only in oral cavity tumors ( 5-year survival of 54 % in the combined modality group vs. 27 % in the control group ) , although local control rates after both single and combined modalities were not statistically different from those of oropharynx and maxillary antrum tumors . In these last lesions , however , the dissemination of disease was more frequent ; therefore , the lack of improvement of cure rate with the combined modality in these cases seems to be related to both the higher tendency of these tumors to disseminate and the low effectiveness of intra-arterial chemotherapy in controlling distant metastases . Mild and transient local and systemic toxicities were observed during chemotherapy infusion , but no radiosensitising effect on normal skin and mucosa was seen during radiotherapy in patients who had received pre-irradiation chemotherapy In 1986 , we initiated a multicenter , r and omized trial to compare induction chemotherapy with cisplatin and 5-fluorouracil followed by locoregional treatment ( surgery and radiotherapy or radiotherapy alone ) with locoregional treatment alone in patients with head and neck squamous cell carcinoma . Here we report the long-term results of the trial . A total of 237 patients with nonmetastatic stage III or IV head and neck carcinoma were r and omly assigned to receive four cycles of neoadjuvant chemotherapy followed by locoregional treatment ( group A ) or locoregional treatment alone ( group B ) . Among all patients , overall survival at 5 and 10 years was 23 % ( 95 % confidence interval [ CI ] = 15.3 % to 30.9 % ) and 19 % ( 95 % CI = 11.6 % to 26.4 % ) , respectively , for those in group A and 16 % ( 95 % CI = 9.6 % to 23.4 % ) and 9 % ( 95 % CI = 3.5 % to 14.7 % ) , respectively , for those in group B ( P = .13 ) . Among operable patients , we observed no difference between group A and group B in overall survival at 5 and 10 years ( group A , 31 % [ 95 % CI = 14.9 % to 47.3 % ] and 22.7 % [ 95 % CI = 7.1 % to 38.3 % ] , respectively ; group B , 43.3 % [ 95 % CI = 25.6 % to 61.0 % ] and 14.2 % [ 95 % CI = 0.1 % to 28.3 % ] , respectively ; P = .73 ) . Among inoperable patients , overall survival at 5 and 10 years was 21 % ( 95 % CI = 12.3 % to 30.1 % ) and 16 % ( 95 % CI = 7.7 % to 23.9 % ) , respectively , for group A and 8 % ( 95 % CI = 1.5 % to 12.3 % ) and 6 % ( 95 % CI = 0.1 % to 9.1 % ) , respectively , for group B ( log-rank P = .04 ) . Four cycles of neoadjuvant chemotherapy is a promising approach for treating patients with inoperable advanced head and neck cancer but not for treating patients with operable disease PURPOSE We report the 5-year survival and late toxicity results of a r and omized clinical trial , which showed a 3-year improvement in overall survival and locoregional control of stage III or IV oropharynx carcinoma , using concomitant radiochemotherapy ( arm B ) , compared with st and ard radiotherapy ( arm A ) . PATIENTS AND METHODS A total of 226 patients were entered onto a phase III multicenter r and omized trial comparing radiotherapy alone ( 70 Gy in 35 fractions ; arm A ) with 
    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 BACKGROUND Single-modality radiotherapy is still considered st and ard treatment for patients with locally advanced unresectable cancer of the head and neck . As treatment outcome is poor , attempts to integrate chemotherapy into the overall management of these patients are ongoing . PATIENTS AND METHODS A r and omized study was undertaken to compare a sequential with a simultaneous chemoradiotherapy program . Between February 1986 and February 1991 , 93 eligible patients with locally advanced unresectable cancer of the head and neck were stratified by WHO PS , T and N class and primary site and then r and omized to receive either three courses of neoadjuvant chemotherapy with cisplatin ( 100 mg/m2 i.v . d 1 ) and 5-fluorouracil 1000 mg/m2/days 1 - 5 by continuous i.v . infusion every 3 weeks prior to definitive conventional radiotherapy of 65 - 70 Gy ( sequential treatment ) , or cisplatin 100 mg/m2 on days 1 , 22 , 43 given simultaneously for the duration of the same conventional radiotherapy ( simultaneous treatment ) . RESULTS At the end of the entire treatment 18 complete responses ( 47 % ) in the sequential-treatment arm and 18 ( 41 % ) in the simultaneous treatment arm were obtained . No statistically significant differences in the 5-yr progression-free survival , in the median time to loco-regional and distant progression and in the 5-yr overall survival were observed . Leukopenia was more frequent in the simultaneous than in the sequential arm ( p = 0.03 ) , whereas alopecia ( p = 0.008 ) and phlebitis ( p < 0.0001 ) were more frequent in the sequential-treatment arm . A better compliance was associated with the concomitant treatment , with 87 % of the patients completing the entire radiotherapy program versus 63 % of those in the sequential arm ( p = 0.01 ) . CONCLUSIONS In the present study , the two treatment arms showed similar activity ( complete response , progression-free and overall survival rates ) . Compliance to treatment was better in the concomitant arm . These data suggest that concomitant chemo-radiation therapy might be considered an option in unresectable locally advanced cancer of the head and neck . Phase III studies are needed in order to establish the superiority of this combination of cisplatin and radiotherapy versus radiotherapy alone 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 This study was design ed to ascertain whether a prior reduction of tumor size by drugs could affect the final outcome of tumors treated with radiation . 142 patients with head and neck cancer ( oropharynx , maxillary antrum and intra-oral ) were r and omized for the study . In 72 cases , irradiation was preceded by a continuous intra-arterial infusion of 3 - 5 mg/day methotrexate to a total dose of 90 - 120 mg ; the other 70 patients were treated with radiotherapy alone . Chemotherapy , given prior to radiotherapy , caused a shift in the tumor stage ( i.e. a reduction in tumor size ) in more than one third of the cases . The overall 5-year survival was 43 % in the combined treatment group and 25 % in the group treated with radiation alone ( statistical difference : p less than .05 ) . However , when analysed separately the difference was statistically significant only in oral cavity tumors ( 5-year survival of 54 % in the combined modality group vs. 27 % in the control group ) , although local control rates after both single and combined modalities were not statistically different from those of oropharynx and maxillary antrum tumors . In these last lesions , however , the dissemination of disease was more frequent ; therefore , the lack of improvement of cure rate with the combined modality in these cases seems to be related to both the higher tendency of these tumors to disseminate and the low effectiveness of intra-arterial chemotherapy in controlling distant metastases . Mild and transient local and systemic toxicities were observed during chemotherapy infusion , but no radiosensitising effect on normal skin and mucosa was seen during radiotherapy in patients who had received pre-irradiation chemotherapy In 1986 , we initiated a multicenter , r and omized trial to compare induction chemotherapy with cisplatin and 5-fluorouracil followed by locoregional treatment ( surgery and radiotherapy or radiotherapy alone ) with locoregional treatment alone in patients with head and neck squamous cell carcinoma . Here we report the long-term results of the trial . A total of 237 patients with nonmetastatic stage III or IV head and neck carcinoma were r and omly assigned to receive four cycles of neoadjuvant chemotherapy followed by locoregional treatment ( group A ) or locoregional treatment alone ( group B ) . Among all patients , overall survival at 5 and 10 years was 23 % ( 95 % confidence interval [ CI ] = 15.3 % to 30.9 % ) and 19 % ( 95 % CI = 11.6 % to 26.4 % ) , respectively , for those in group A and 16 % ( 95 % CI = 9.6 % to 23.4 % ) and 9 % ( 95 % CI = 3.5 % to 14.7 % ) , respectively , for those in group B ( P = .13 ) . Among operable patients , we observed no difference between group A and group B in overall survival at 5 and 10 years ( group A , 31 % [ 95 % CI = 14.9 % to 47.3 % ] and 22.7 % [ 95 % CI = 7.1 % to 38.3 % ] , respectively ; group B , 43.3 % [ 95 % CI = 25.6 % to 61.0 % ] and 14.2 % [ 95 % CI = 0.1 % to 28.3 % ] , respectively ; P = .73 ) . Among inoperable patients , overall survival at 5 and 10 years was 21 % ( 95 % CI = 12.3 % to 30.1 % ) and 16 % ( 95 % CI = 7.7 % to 23.9 % ) , respectively , for group A and 8 % ( 95 % CI = 1.5 % to 12.3 % ) and 6 % ( 95 % CI = 0.1 % to 9.1 % ) , respectively , for group B ( log-rank P = .04 ) . Four cycles of neoadjuvant chemotherapy is a promising approach for treating patients with inoperable advanced head and neck cancer but not for treating patients with operable disease PURPOSE We report the 5-year survival and late toxicity results of a r and omized clinical trial , which showed a 3-year improvement in overall survival and locoregional control of stage III or IV oropharynx carcinoma , using concomitant radiochemotherapy ( arm B ) , compared with st and ard radiotherapy ( arm A ) . PATIENTS AND METHODS A total of 226 patients were entered onto a phase III multicenter r and omized trial comparing radiotherapy alone ( 70 Gy in 35 fractions ; arm A ) with 
    Output:
    