***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 To know the effectiveness and tolerance of weekly cisplatin added to radiotherapy ( RT ) in advanced carcinoma of oropharynx and nasopharynx . PATIENTS AND METHODS Stage II-IV cancer patients were r and omly assigned to either radical RT , 70 Gy/35 fractions over 7 weeks ( RT arm ) , or chemoradiotherapy ( CRT ) , cisplatin 40 mg/m² weekly for seven doses plus RT . Primary end points were ( i ) the responses , ( ii ) toxicity profile , and ( iii ) overall survival ( OS ) in two groups . Study period was from June 2003 to July 2005 . RESULTS One hundred and fifty-three patients were r and omly allocated to the study , 76 in RT arm and 77 in CRT arm . Seventy-one in each arm completed the planned treatment ; complete response ( CR ) : 67.1 % versus 80.5 % in RT and CRT arms ( P = 0.04 ) . Grade III and IV toxicity were 16 % and 40 % in RT and CRT arms , respectively ( P = 0.01 ) . There were frequent treatment interruptions ( 9.3 % versus 28.9 % ; P = 0.003 ) and hospitalization ( 20 % versus 40.8 % ) in the CRT group . OS was superior in the CRT arm ( P = 0.02 ) : 27 months [ 95 % confidence interval ( CI ) 15.2 - 36.8 ] for RT versus not reached for CRT . Three-year OS was 42 % for RT and 62 % for CRT group . CRT and CR were independent prognostic factors . CONCLUSION This trial on Indian head and neck squamous cell carcinoma patients confirms that the use of weekly cisplatin is safe and CRT is superior to RT alone result ing in higher OS 5555 Background : In loco-regionally advanced head and neck squamous cell cancer ( HNSCC ) , concurrent 3-weekly cisplatin improves the overall survival ( OS ) of patients compared to radiotherapy ( RT ) alone , but is often associated with renal toxicity . METHODS Retrospective analysis of treatment outcome and nephrotoxicity frequency of intensity-modulated radiotherapy ( IMRT ) associated with either 3-weekly ( 100 mg/m2 on day 1 , 22 , 43 ) or weekly cisplatin ( 40 mg/m2 on day 1 , 8 , 15 , 22 , 29 , 36 , 43 ) in 94 patients with stage III/IV HNSCC . RESULTS Patients treated with weekly cisplatin ( N=40 ) were significantly older ( median age 65 vs. 58 years , p=0.0014 ) and received a significantly lower total cisplatin dose ( median 186 mg/m2 vs. 228 mg/m2 , p=0.0002 ) and these differences have likely contributed to the clinical outcome . At a median follow up of 2.8 years , the median progression-free survival ( PFS ) was 1.5 years with weekly and 2.1 years with 3-weekly cisplatin ( p= 0.47 ) . OS was significantly longer ( 4.3 vs. 1.9 years , p= 0.041 ) in patients treated with the 3-weekly regimen ( N=54 ) ; indeed cisplatin doses > 360 mg total or > 240 mg/m2 were associated with better OS but not better PFS . At univariate analysis , a history of alcohol abuse and /or smoking was associated with worse PFS ( p=0.013 ) . Multivariate analysis confirmed the impact of alcohol and smoking habits on both PFS and OS , while the treatment schedule only affected OS . Acute renal failure rate was 35 % with the weekly and 54 % with the 3-weekly regime ( p=0.07 ) ; chronic renal failure rate was 5 % and 30 % , respectively ( p=0.04 ) . No patient required renal replacement therapy . CONCLUSIONS Both schedules can be combined to IMRT , but weekly cisplatin is less nephrotoxic . PFS was not significantly different despite patients treated with the weekly schedule being significantly older and under-treated . The study suggests that cisplatin schedule may not be relevant when combined to IMRT . Controlled prospect i ve studies are needed to compare the clinical activity of different cisplatin schedules in combination with IMRT Background The aim of this study was to compare the outcomes of postoperative adjuvant concomitant chemoradiotherapy using two different schedules of cisplatin for patients with high-risk oral squamous cell carcinoma ( OSCC ) . Methods From Feb. 2008 to Aug. 2010 , 55 patients with high-risk OSCC were included in this study . Patients were r and omized into treatment groups that either received 100 mg/m2 cisplatin once every 3 weeks ( arm A ) or 40 mg/m2 cisplatin once per week ( arm B ) . All patients were irradiated with 66 Gy in 33 fractions . Results Of the 50 eligible patients , 26 were assigned to arm A , and 24 were assigned to arm B. Both groups of patients received the same mean doses of radiotherapy and cisplatin . However , 88.5 % of patients in arm A and 62.5 % of those in arm B ( p = 0.047 ) received ≥ 200 mg/m2 of cisplatin in total . The overall toxicity was significantly greater in arm B ( p = 0.020 ) , and all of the grade 4 toxicities occurred in patients in arm B. Conclusions Three-weekly high-dose cisplatin treatment showed higher compliance , and lower acute toxicity compared to weekly low-dose cisplatin treatment PURPOSE Although p16 protein expression , a surrogate marker of oncogenic human papillomavirus ( HPV ) infection , is recognized as a prognostic marker in oropharyngeal squamous cell carcinoma ( OPSCC ) , its prevalence and significance have not been well established in cancer of the oral cavity , hypopharynx , or larynx , collectively referred as non-OPSCC , where HPV infection is less common than in the oropharynx . PATIENTS AND METHODS p16 expression and high-risk HPV status in non-OPSCCs from RTOG 0129 , 0234 , and 0522 studies were determined by immunohistochemistry ( IHC ) and in situ hybridization ( ISH ) . Hazard ratios from Cox models were expressed as positive or negative , stratified by trial , and adjusted for clinical characteristics . RESULTS p16 expression was positive in 14.1 % ( 12 of 85 ) , 24.2 % ( 23 of 95 ) , and 19.0 % ( 27 of 142 ) and HPV ISH was positive in 6.5 % ( six of 93 ) , 14.6 % ( 15 of 103 ) , and 6.9 % ( seven of 101 ) of non-OPSCCs from RTOG 0129 , 0234 , and 0522 studies , respectively . Hazard ratios for p16 expression were 0.63 ( 95 % CI , 0.42 to 0.95 ; P = .03 ) and 0.56 ( 95 % CI , 0.35 to 0.89 ; P = .01 ) for progression-free ( PFS ) and overall survival ( OS ) , respectively . Comparing OPSCC and non-OPSCC , patients with p16-positive OPSCC have better PFS and OS than patients with p16-positive non-OPSCC , but patients with p16-negative OPSCC and non-OPSCC have similar outcomes . CONCLUSION Similar to results in patients with OPSCC , patients with p16-negative non-OPSCC have worse outcomes than patients with p16-positive non-OPSCC , and HPV may also have a role in outcome in a subset of non-OPSCC . However , further development of a  p16 IHC scoring system in non-OPSCC and improvement of HPV detection methods are warranted before broad application in the clinical setting PURPOSE Previous analysis of this Intergroup trial demonstrated that with a median follow-up among surviving patients of 45.9 months , the concurrent postoperative administration of cisplatin and radiation therapy improved local-regional control and disease-free survival of patients who had high-risk resectable head- and -neck carcinomas . With a minimum of 10 years of follow-up potentially now available for all patients , these results are up date d here to examine long-term outcomes . METHODS AND MATERIAL S A total of 410 analyzable patients who had high-risk resected head- and -neck cancers were prospect ively r and omized to receive either radiation therapy ( RT : 60 Gy in 6 weeks ) or identical RT plus cisplatin , 100 mg/m(2)i.v . on days 1 , 22 , and 43 ( RT + CT ) . RESULTS At 10 years , the local-regional failure rates were 28.8 % vs 22.3 % ( P=.10 ) , disease-free survival was 19.1 % vs 20.1 % ( P=.25 ) , and overall survival was 27.0 % vs 29.1 % ( P=.31 ) for patients treated by RT vs RT + CT , respectively . In the unplanned subset analysis limited to patients who had microscopically involved resection margins and /or extracapsular spread of disease , local-regional failure occurred in 33.1 % vs 21.0 % ( P=.02 ) , disease-free survival was 12.3 % vs 18.4 % ( P=.05 ) , and overall survival was 19.6 % vs 27.1 % ( P=.07 ) , respectively . CONCLUSION At a median follow-up of 9.4 years for surviving patients , no significant differences in outcome were observed in the analysis of all r and omized eligible patients . However , analysis of the subgroup of patients who had either microscopically involved resection margins and /or extracapsular spread of disease showed improved local-regional control and disease-free survival with concurrent administration of chemotherapy . The remaining subgroup of patients who were enrolled only because they had tumor in 2 or more lymph nodes did not benefit from the addition of CT to RT Background The dominant pattern of failure for squamous cell carcinoma of head and neck remains loco-regional , although distant metastases are now being increasingly documented . Radical radiotherapy with concurrent chemotherapy is contemporary st and ard of care in the non-surgical management of these loco-regionally advanced cancers , based on large r and omized controlled trials utilizing high-dose cisplatin ( 80–100 mg/m2 ) cycled every three-weekly during definitive radiotherapy . Although efficacious , this is associated with high acute morbidity necessitating intensive supportive care with attendant re source implication s. The aim of this retrospective study was to assess the efficacy and acute toxicity of an alternative schedule i.e. concurrent weekly cisplatin-based radical radiotherapy and it 's potential to be an optimal regimen in advanced head and neck cancers . Methods Outcome data of patients with Stage III & IV head and neck squamous cell carcinoma , excluding nasopharynx , planned for radical radiotherapy ( 66–70 Gy ) with concurrent weekly cisplatin ( 30 mg/m2 ) treated in a single unit between 1996–2004 was extracted . Results The data set consisted of 264 patients with a median age of 54 years . The median radiotherapy dose was 70 Gy ( range 7.2–72 Gy ) and median number of chemotherapy cycles was 6 ( range 1–7 ) . Two-thirds ( 65 % ) of patients received ≥85 % of planned cisplatin dose . With a mean follow-up of 19 months , the 5-year local control ; loco-regional control ; and disease free survival was 57 % ; 46 % ; and 43 % respectively . Acute grade 3 or worse mucositis and dermatitis was seen in 77 ( 29 % ) and 92 ( 35 % ) patients respectively , essentially in patients receiving doses ≥66 Gy and 6 or more cycles of chemotherapy . Other toxicities ( hematologic , nausea and vomiting ) were mild and self-limiting . Overall , the acute toxicity of this concurrent weekly chemo-radiation regimen though mildly increased did not m and ate intensive supportive care . Stage grouping , primary site , and intensity of treatment were significant predictors of loco-regional control and disease free survival . Conclusion Radical radiotherapy with concurrent weekly cisplatin has moderate efficacy and acceptable acute toxicity with potential to be an optimal regimen in loco-regionally advanced squamous cell carcinoma of the head and neck , particularly in limited-re source setting s. Stage grouping , primary site , and treatment intensity are important determinants of outcome BACKGROUND We compared concomitant cisplatin and irradiation with radiotherapy alone as adjuvant treatment for stage III or IV head and neck cancer . METHODS After undergoing surgery with curative intent , 167 patients were r and omly assigned to receive radiotherapy alone ( 66 Gy over a period of 6 1/2 weeks ) and 167 to receive the same radiotherapy regimen combined with 100 mg of cisplatin per square meter of body-surface area 
    Output:
    
Results support the conclusion that the cumulative dose of cisplatin in concurrent chemoradiation protocol s for HNSCC has a significant positive correlation with survival .