***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
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    Input: BACKGROUND Oropharyngeal squamous-cell carcinomas caused by human papillomavirus ( HPV ) are associated with favorable survival , but the independent prognostic significance of tumor HPV status remains unknown . METHODS We performed a retrospective analysis of the association between tumor HPV status and survival among patients with stage III or IV oropharyngeal squamous-cell carcinoma who were enrolled in a r and omized trial comparing accelerated-fractionation radiotherapy ( with acceleration by means of concomitant boost radiotherapy ) with st and ard-fractionation radiotherapy , each combined with cisplatin therapy  , in patients with squamous-cell carcinoma of the head and neck . Proportional-hazards models were used to compare the risk of death among patients with HPV-positive cancer and those with HPV-negative cancer . RESULTS The median follow-up period was 4.8 years . The 3-year rate of overall survival was similar in the group receiving accelerated-fractionation radiotherapy and the group receiving st and ard-fractionation radiotherapy ( 70.3 % vs. 64.3 % ; P=0.18 ; hazard ratio for death with accelerated-fractionation radiotherapy , 0.90 ; 95 % confidence interval [ CI ] , 0.72 to 1.13 ) , as were the rates of high- grade acute and late toxic events . A total of 63.8 % of patients with oropharyngeal cancer ( 206 of 323 ) had HPV-positive tumors ; these patients had better 3-year rates of overall survival ( 82.4 % , vs. 57.1 % among patients with HPV-negative tumors ; P<0.001 by the log-rank test ) and , after adjustment for age , race , tumor and nodal stage , tobacco exposure , and treatment assignment , had a 58 % reduction in the risk of death ( hazard ratio , 0.42 ; 95 % CI , 0.27 to 0.66 ) . The risk of death significantly increased with each additional pack-year of tobacco smoking . Using recursive-partitioning analysis , we classified our patients as having a low , intermediate , or high risk of death on the basis of four factors : HPV status , pack-years of tobacco smoking , tumor stage , and nodal stage . CONCLUSIONS Tumor HPV status is a strong and independent prognostic factor for survival among patients with oropharyngeal cancer . ( Clinical Trials.gov number , NCT00047008 . The purpose of the current study was to determine quality of life and tumor control from a prospect i ve phase 2 clinical trial evaluating deintensified chemoradiotherapy for favorable risk , human papillomavirus (HPV)‐associated oropharyngeal squamous cell carcinoma Purpose Chemoradiation with cisplatin 100 mg/m2 given once every 3 weeks is the st and ard of care in locally advanced head and neck squamous cell cancer ( LAHNSCC ) . Increasingly , low-dose once-a-week cisplatin is substituted because of perceived lower toxicity and convenience . However , there is no level 1 evidence of comparable efficacy to cisplatin once every 3 weeks . Patients and Methods In this phase III r and omized trial , we assessed the noninferiority of cisplatin 30 mg/m2 given once a week compared with cisplatin 100 mg/m2 given once every 3 weeks , both administered concurrently with curative intent radiotherapy in patients with LAHNSCC . The primary end point was locoregional control ( LRC ) ; secondary end points included toxicity , compliance , response , progression-free survival , and overall survival . Results Between 2013 and 2017 , we r and omly assigned 300 patients , 150 to each arm . Two hundred seventy-nine patients ( 93 % ) received chemoradiotherapy in the adjuvant setting . At a median follow-up of 22 months , the estimated cumulative 2-year LRC rate was 58.5 % in the once-a-week arm and 73.1 % in the once-every-3-weeks arm , leading to an absolute difference of 14.6 % ( 95 % CI , 5.7 % to 23.5 % ) ; P = .014 ; hazard ratio ( HR ) , 1.76 ( 95 % CI , 1.11 to 2.79 ) . Acute toxicities of grade 3 or higher occurred in 71.6 % of patients in the once-a-week arm and in 84.6 % of patients in the once-every-3-weeks arm ( P = .006 ) . Estimated median progression-free survival in the once-a-week arm was 17.7 months ( 95 % CI , 0.42 to 35.05 months ) and in the once-every-3-weeks arm , 28.6 months ( 95 % CI , 15.90 to 41.30 months ) ; HR , 1.24 ( 95 % CI , 0.89 to 1.73 ) ; P = .21 . Estimated median overall survival in the once-a-week arm was 39.5 months and was not reached in the once-every-3-weeks arm ( HR , 1.14 [ 95 % CI , 0.79 to 1.65 ] ; P = .48 ) . Conclusion Once-every-3-weeks cisplatin at 100 mg/m2 result ed in superior LRC , albeit with more toxicity , than did once-a-week cisplatin at 30 mg/m2 , and should remain the preferred chemoradiotherapy regimen for LAHNSCC in the adjuvant setting BACKGROUND The relative efficacy of the addition of induction chemotherapy to chemoradiotherapy compared with chemoradiotherapy alone for patients with head and neck cancer is unclear . The PARADIGM study is a multicentre open-label phase 3 study comparing the use of docetaxel , cisplatin , and fluorouracil ( TPF ) induction chemotherapy followed by concurrent chemoradiotherapy with cisplatin-based concurrent chemoradiotherapy alone in patients with locally advanced head and neck cancer . METHODS Adult patients with previously untreated , non-metastatic , newly diagnosed head and neck cancer were eligible . Patients were eligible if their tumour was either unresectable or of low surgical curability on the basis of advanced tumour stage ( 3 or 4 ) or regional-node stage ( 2 or 3 , except T1N2 ) , or if they were a c and i date for organ preservation . Patients were r and omly assigned ( in a 1:1 ratio ) to receive either induction chemotherapy with three cycles of TPF followed by concurrent chemoradiotherapy with either docetaxel or carboplatin or concurrent chemoradiotherapy alone with two cycles of bolus cisplatin . A computer-generated r and omisation schedule using minimisation was prepared and the treatment assignment was done central ly at one of the study sites . Patients , study staff , and investigators were not masked to group assignment . Stratification factors were WHO performance status , primary disease site , and stage . The primary endpoint was overall survival . Analysis was by intention to treat . Patient accrual was terminated in December , 2008 , because of slow enrolment . The trial is registered with Clinical Trials.gov , number NCT00095875 . FINDINGS Between Aug 24 , 2004 , and Dec 29 , 2008 , we enrolled 145 patients across 16 sites . After a median follow-up of 49 months ( IQR 39 - 63 ) , 41 patients had died-20 in the induction chemotherapy followed by chemoradiotherapy group and 21 in the chemoradiotherapy  alone group . 3-year overall survival was 73 % ( 95 % CI 60 - 82 ) in the induction therapy followed by chemoradiotherapy group and 78 % ( 66 - 86 ) in the chemoradiotherapy alone group ( hazard ratio 1·09 , 95 % CI 0·59 - 2·03 ; p=0·77 ) . More patients had febrile neutropenia in the induction chemotherapy followed by chemoradiotherapy group ( 16 patients ) than in the chemoradiotherapy alone group ( one patient ) . INTERPRETATION Although survival results were good in both groups there was no difference noted between those patients treated with induction chemotherapy followed by chemoradiotherapy and those who received chemoradiotherapy alone . We can not rule out the possibility of a difference in survival going undetected due to early termination of the trial . Clinicians should still use their best judgment , based on the available data , in the decision of how to best treat patients . The addition of induction chemotherapy remains an appropriate approach for advanced disease with high risk for local or distant failure . FUNDING Sanofi-Aventis PURPOSE Induction chemotherapy ( IC ) before radiotherapy lowers distant failure ( DF ) rates in locally advanced squamous cell carcinoma of the head and neck ( SCCHN ) . The goal of this phase III trial was to determine whether IC before chemoradiotherapy ( CRT ) further improves survival compared with CRT alone in patients with N2 or N3 disease . PATIENTS AND METHODS Treatment-naive patients with nonmetastatic N2 or N3 SCCHN were r and omly assigned to CRT alone ( CRT arm ; docetaxel , fluorouracil , and hydroxyurea plus radiotherapy 0.15 Gy twice per day every other week ) versus two 21-day cycles of IC ( docetaxel 75 mg/m(2 ) on day 1 , cisplatin 75 mg/m(2 ) on day 1 , and fluorouracil 750 mg/m(2 ) on days 1 to 5 ) followed by the same CRT regimen ( IC + CRT arm ) . The primary end point was overall survival ( OS ) . Secondary end points included DF-free survival , failure pattern , and recurrence-free survival ( RFS ) . RESULTS A total of 285 patients were r and omly assigned . The most common grade 3 to 4 toxicities during IC were febrile neutropenia ( 11 % ) and mucositis ( 9 % ) ; during CRT ( both arms combined ) , they were mucositis ( 49 % ) , dermatitis ( 21 % ) , and leukopenia ( 18 % ) . Serious adverse events were more common in the IC arm ( 47 % v 28 % ; P = .002 ) . With a minimum follow-up of 30 months , there were no statistically significant differences in OS ( hazard ratio , 0.91 ; 95 % CI , 0.59 to 1.41 ) , RFS , or DF-free survival . CONCLUSION IC did not translate into improved OS compared with CRT alone . However , the study was underpowered because it did not meet the planned accrual target , and OS was higher than predicted in both arms . IC can not be recommended routinely in patients with N2 or N3 locally advanced SCCHN BACKGROUND Concurrent chemoradiotherapy ( CCRT ) is the st and ard treatment for patients with unresectable , nonmetastatic locoregionally advanced squamous-cell carcinoma of the head and neck ( LASCCHN ) . This r and omized , open-label , phase III clinical trial compared the efficacy between st and ard CCRT and two different induction chemotherapy ( ICT ) regimens followed by CCRT . PATIENTS AND METHODS Patients with untreated LASCCHN were r and omly assigned to ICT ( three cycles ) , with either docetaxel ( Taxotere ) , cisplatin and 5-fluorouracil ( TPF arm ) or cisplatin and 5-fluorouracil ( PF arm ) , followed by CCRT [ 7 weeks of radiotherapy ( RT ) with cisplatin 100 mg/m(2 ) on days 1 , 22 and 43 ] ; or 7 weeks of CCRT alone . The primary end points were progression-free survival ( PFS ) and time-to-treatment failure ( TTF ) . RESULTS In the intention-to-treat ( ITT ) population ( n = 439 ) , the median PFS times were 14.6 ( 95 % CI , 11.6 - 20.4 ) , 14.3 ( 95 % CI , 11.8 - 19.3 ) and 13.8 months ( 95 % CI , 11.0 - 17.5 ) at TPF-CCRT , PF-CCRT and CCRT arms , respectively ( log-rank P = 0.56 ) . The median TTF were 7.9 ( 95 % CI , 5.9 - 11.8 ) , 7.9 ( 95 % CI , 6.5 - 11.8 ) and 8.2 months ( 95 % CI , 6.7 - 12.6 ) for TPF-CCRT , PF-CCRT and CCRT alone , respectively ( log-rank P = 0.90 ) . There were no statistically significant differences for overall survival ( OS ) . Toxic effects from ICT-CCRT were manageable . CONCLUSION Overall , this trial failed to show any advantage of ICT-CCRT over CCRT alone in patients with unresectable LASCCHN Purpose Human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma ( OPSCC ) is treatment-responsive . Definitive chemoradiation results in high cure rates but causes long-term toxicity and may represent overtreatment of some patients . This phase II trial evaluated 
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Taken together , dose-reduced chemoradiotherapy ( with or without induction chemotherapy for patient/biology selection purpose s ) seems to be a promising de-escalation strategy for HPV-associated OPC , although replacement of concurrent cisplatin by cetuximab is not recommended .