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: The results of 44 patients with early operable non-small cell lung cancer treated from January 1975 through 1981 are retrospectively analysed . All were proven by pathology and /or cytology and denied surgery in our joint Chest Clinic for various reasons . 55 - 70 Gy/6 - 7 weeks was delivered by conventional fractionation through A-P portals by telecobalt and /or 25 - 35 MeV high energy electron beam or 8 MV X-ray . 40 Gy/4 weeks was given prophylactically to the mediastinum . The 1- , 3- , and 5-year survival rates , 93 , 55 , and 32 % , are superior to what is reported in the literature . In the present series , the favorable factors are : ( 1 ) patients without any intercurrent disease but refused operation ; ( 2 ) T1 lesions ; ( 3 ) complete regression of the lesion at the conclusion of radiotherapy ; ( 4 ) doses ranging from 69 to 70 Gy . It is shown that early non-small cell lung cancer can be cured by radiotherapy alone giving survival rates comparable to surgery . Prospect i ve r and omized clinical trials are warranted To compare the use of  r and omized controls ( RCTs ) and historical controls ( HCTs )  for clinical trials , we search ed the literature for therapies studied by both methods . We found six therapies for which 50 RCTs and 56 HCTs were reported . Forty-four of 56 HCTs  ( 79 percent ) found the therapy better than the control regimen , but only 10 of 50 RCTs ( 20 percent ) agreed . For each therapy , the treated patients in RCTs and HCTs of the same therapy was largely due to differences in outcome for the control groups , with HCT control patients generally doing worse than the RCT control groups . Adjustment of the outcomes of the HCTs for prognostic factors , when possible , did not appreciably change the results . The data suggest that biases in patient selection may irretrievably weight the outcome of HCts in favor of new therapies . RCTs may miss clinical ly important benefits because of inadequate attention to sample size . The predictive value of each might be improved by reconsidering the use of p less than 0.05 as the significance level for all types of clinical trials , and by the use of confidence intervals around estimates of treatment effects The relation between tumor characteristics , irradiation technique , local tumor control and survival was retrospectively studied in 323 patients with non-small cell lung cancer who started radical radiotherapy in 1974 - 1981 . At that time three non-r and omized different fractionation schedules were used : 16 x 3.25 Gy , total dose 52 Gy , 3 fractions/week ( schedule 1 ) , 11 x 4 Gy , total dose 44 Gy , 2 fractions/week ( schedule 2 ) and 25 x 2 Gy , total dose 50 Gy , 5 fractions/week ( schedule 3 ) . The highest survival rates were observed in the patient group treated according to schedule 2 . The 2-year survival rate was 30 % compared with 18 % and 6 % in the patients treated according to schedule 1 and 3 respectively . However , this can at least partly be explained by patient selection . A correlation between size of the tumor , target volume and survival was observed : the larger the tumor , the poorer the survival . Pleural effusion showed to be an unfavorable prognostic factor . The prognosis of inoperable lung cancer on the whole remained poor : the 1-year survival rate was 43 % and 2-year survival rate 16 % . Only 3 % of the patients lived at least five years PURPOSE To determine if thoracic radiotherapy improves the survival of non-small cell lung cancer ( NSCLC ) patients . METHODS AND MATERIAL S A Cox proportional hazards model with prognostic and treatment covariates was estimated using prospect i ve data for 129 NSCLC patients presenting at the Victoria Clinic ( ViCC ) of the British Columbia Cancer Agency ( BCCA ) 1990 - 1991 . The estimated model was simulated to predict survival curves for groups of patients with and without treatment . The difference between the predicted median survival with treatment and without treatment is the gain in survival attributable to treatment . RESULTS After adjusting for the effect of TNM staging , Karnofsky performance status , weight loss , tumor size , and tumor histology on survival , high-dose palliative radiotherapy ( RT ) ( 30 - 50 Gy in 10 - 20 fractions ) increased median survival by 79 days ( 95 % confidence interval : 31 - 106 days ) , and lowered the relative risk of death rate to 0.53 ( 95 % confidence interval : 0.35 - 0.85 ) . Radical RT ( 50 or more Gy , in 20 or more fractions ) increased median survival by 424 days ( 95 % confidence interval : 302 - 488 days ) , and lowered the relative risk of death to 0.24 ( 95 % confidence interval : 0.14 - 0.43 ) . CONCLUSION Our results support the hypothesis that the increased survival of patients receiving aggressive palliative , or radical , RT  is due not solely to patient selection , but also partly to a response to treatment PURPOSE The treatment of nonsmall cell lung cancer ( NSCLC ) with conventional radiotherapy ( RT ) results in inadequate local tumor control and survival . We report results of a Phase II trial design ed to treat patients with a significantly increased total dose administered in a reduced overall treatment time using a hyperfractionated , accelerated treatment schedule with a concurrent boost technique . METHODS AND MATERIAL S A total of 49 patients with unresectable Stage IIIA/IIIB ( 38 patients ) or medically inoperable Stage I/II ( 11 patients ) NSCLC were prospect ively enrolled in this protocol . Radiation therapy was administered twice daily , 5 days/week with > 6 h between each treatment . The primary tumor and adjacent enlarged lymph nodes were treated to a total dose of 73.6 Gy in 46 fractions of 1.6 Gy each . Using a concurrent boost technique , electively irradiated nodal regions were simultaneously treated with a dose of 1.25 Gy/fraction for the first 36 fractions to a total dose of 45 Gy . RESULTS Median survival for the entire group of 49 patients is 15.3 months . Actuarial survival at 2 years is 46 % : 60 % for 11 Stage I/II patients , 55 % for 21 Stage IIIA patients , and 26 % for 17 Stage IIIB patients . The actuarial rate of freedom from local progression at 2 years is 64 % for the entire group of 49 patients : 62 % for Stage I/II patients , 70 % for Stage IIIA patients , and 55 % for Stage IIIB patients . Patients who underwent serial bronchoscopic reevaluation ( 4 Stage I/II , 8 Stage IIIA , and 6 Stage IIIB ) have an actuarial rate of local control of 71 % at 2 years . The median total treatment time was 32 days . Nine of 49 patients ( 18 % ) experienced Grade III acute esophageal toxicity . The 2-year actuarial risk of Grade III or greater late toxicity is 30 % . The 2-year actuarial rate of severe-late pulmonary and skin-subcutaneous toxicity is 20 % and 15 % , respectively . CONCLUSION This treatment regimen administers a substantially higher biologically effective dose compared with conventional and pure hyperfractionation treatment schedules . The overall rate of acute and late toxicity was acceptable . Preliminary rates of overall survival and local control and freedom from local progression compare favorably to results reported with pure hyperfractionated radiotherapy and chemoradiotherapy BACKGROUND AND METHOD A r and omised controlled trial in locally advanced non-small cell lung cancer ( NSCLC ) , compared CHART which employs 36 fractions of 1.5 Gy 3 times per day to give 54 Gy in 12 consecutive days with conventional radiotherapy-30 fractions of 2 Gy to a total dose of 60 Gy in 6 weeks . A total of 563 patients were entered between April 1990 and April 1995 . This report is based upon the data up date d to 1 April 1998 . RESULTS The analysis of the mature data shows that the benefits previously reported have been maintained . Overall there was a 22 % reduction in the relative risk of death , which is equivalent to an absolute improvement in 2 year survival of 9 % from 20 to 29 % ( P = 0.008 ) and a 21 % reduction in the relative risk of local progression ( P = 0.033 ) . In the large subgroup of patients with squamous cell cancer which accounted for 81 % of the cases , there was a 30 % reduction in the relative risk of death , which is equivalent to an absolute improvement in 2 year survival of 13 % from 20 to 33 % ( P = 0.0007 ) and a 27 % reduction in the relative risk of local progression ( P = 0.012 ) . Furthermore , in squamous carcinoma there was a 25 % reduction in the relative risk of local and /or distant progression ( P = 0.025 ) and 24 % reduction in the relative risk of metastasis ( P = 0.043 ) . There was no evidence that CHART gave more or less benefit in any other subgroup . CONCLUSION This analysis of mature data confirms that CHART is superior to conventional radiotherapy in achieving local tumour control and survival in locally advanced NSCLC . This demonstrates the importance of cellular re population as a cause of failure in the radiotherapy of NSCLC . The reduction in the risk of metastasis confirms that improved local tumour control , even in lung cancer , can reduce the incidence of metastasis . This trial shows that control of local tumour can lead to an improvement in long term survival ! [ ] [ 1 ] Rating : R and omised controlled trials are often held up as the “ gold st and ard ” of medical research , and it is commonly believed that the size of a treatment effect is exaggerated in non-r and omised studies . In these days of evidence based medicine , however , where is the empirical evidence that this is so ? A widespread criticism of r and omised controlled trials is that they are based on highly selected individuals . Are there systematic differences between patients included and excluded in such trials , and do these influence the measured treatment effect ? These are just a few … [ 1 ] : This report details the patterns of tumor recurrence in two prospect i ve r and omized studies involving 551 patients with histologically proven unresectable or medically inoperable non‐oat cell carcinoma of the lung treated with definitive radiotherapy .  Patients were treated according to two protocol s , depending on the stage of the tumor : ( 1 ) Patients with T1 , 2 , 3‐NO , 1 , 2 tumors were r and omized to four different regimens : 4000 cGy split course ( 2000 cGy in five fractions , per 1 week , 2 weeks rest and additional 2000 cGy in five fractions , per 1 week ) or 4000 , 5000 , or 6000 cGy continuous courses , five fractions per week . ( 2 ) Patients with T4 , any N or N3 , any T stage tumors were r and omized to be treated with 3000 cGy tumor dose ( TD ) , ten fractions in 2 weeks , 4000 cGy split course ( described above ) , or 4000 cGy continuous course . In the patients with less advanced tumors ( Study 1 ) the intrathoracic failure rate within the irradiated volume was 48 % with 4000 cGy continuous , 38 % with 4000 cGy split course or 5000 cGy continuous , and 27 % for patients receiving 6000 cGy continuous course . The failure rate in the nonirradiated lung ranged from 25 % to 30 % in the various groups . Patients with adenocarcinoma or large cell undifferentiated carcinoma had better intrathoracic tumor control ( 35 % ) than those with squamous cell carcinoma ( 20 % ) . The incidence of distant metastases was 75 % to 80 % in all histologic groups . Distant metastases appeared sooner after therapy in the patients with adenocarcinoma or large cell undifferentiated carcinoma . The initial failure rate in the brain was 7 % in patients with squamous cell carcinoma , 19 % with adenocarcinoma , and 13 % in patients with large cell carcinoma .  The ultimate incidence of brain metastases was 16 % in squamous cell carcinoma , and 30 % for adenocarcinoma or large cell undifferentiated carcinoma . Higher doses of irradiation will be necessary in order to improve the intrathoracic tumor control . Clinical trials by the Radiation Therapy Oncology Group , some of them involving multiple daily fractionation , are in progress . Furthermore , because of the high incidence of distant metastases , effective systemic cytotoxic agents are critically needed to improve survival of lung cancer patients . The high frequency of brain metastases suggests that , as in small cell carcinoma of the lung , elective irradiation of the brain may be necessary , if not to improve survival to enhance the quality of life of patients with adenocarcinoma and large cell carcinoma 
    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: The results of 44 patients with early operable non-small cell lung cancer treated from January 1975 through 1981 are retrospectively analysed . All were proven by pathology and /or cytology and denied surgery in our joint Chest Clinic for various reasons . 55 - 70 Gy/6 - 7 weeks was delivered by conventional fractionation through A-P portals by telecobalt and /or 25 - 35 MeV high energy electron beam or 8 MV X-ray . 40 Gy/4 weeks was given prophylactically to the mediastinum . The 1- , 3- , and 5-year survival rates , 93 , 55 , and 32 % , are superior to what is reported in the literature . In the present series , the favorable factors are : ( 1 ) patients without any intercurrent disease but refused operation ; ( 2 ) T1 lesions ; ( 3 ) complete regression of the lesion at the conclusion of radiotherapy ; ( 4 ) doses ranging from 69 to 70 Gy . It is shown that early non-small cell lung cancer can be cured by radiotherapy alone giving survival rates comparable to surgery . Prospect i ve r and omized clinical trials are warranted To compare the use of  r and omized controls ( RCTs ) and historical controls ( HCTs )  for clinical trials , we search ed the literature for therapies studied by both methods . We found six therapies for which 50 RCTs and 56 HCTs were reported . Forty-four of 56 HCTs  ( 79 percent ) found the therapy better than the control regimen , but only 10 of 50 RCTs ( 20 percent ) agreed . For each therapy , the treated patients in RCTs and HCTs of the same therapy was largely due to differences in outcome for the control groups , with HCT control patients generally doing worse than the RCT control groups . Adjustment of the outcomes of the HCTs for prognostic factors , when possible , did not appreciably change the results . The data suggest that biases in patient selection may irretrievably weight the outcome of HCts in favor of new therapies . RCTs may miss clinical ly important benefits because of inadequate attention to sample size . The predictive value of each might be improved by reconsidering the use of p less than 0.05 as the significance level for all types of clinical trials , and by the use of confidence intervals around estimates of treatment effects The relation between tumor characteristics , irradiation technique , local tumor control and survival was retrospectively studied in 323 patients with non-small cell lung cancer who started radical radiotherapy in 1974 - 1981 . At that time three non-r and omized different fractionation schedules were used : 16 x 3.25 Gy , total dose 52 Gy , 3 fractions/week ( schedule 1 ) , 11 x 4 Gy , total dose 44 Gy , 2 fractions/week ( schedule 2 ) and 25 x 2 Gy , total dose 50 Gy , 5 fractions/week ( schedule 3 ) . The highest survival rates were observed in the patient group treated according to schedule 2 . The 2-year survival rate was 30 % compared with 18 % and 6 % in the patients treated according to schedule 1 and 3 respectively . However , this can at least partly be explained by patient selection . A correlation between size of the tumor , target volume and survival was observed : the larger the tumor , the poorer the survival . Pleural effusion showed to be an unfavorable prognostic factor . The prognosis of inoperable lung cancer on the whole remained poor : the 1-year survival rate was 43 % and 2-year survival rate 16 % . Only 3 % of the patients lived at least five years PURPOSE To determine if thoracic radiotherapy improves the survival of non-small cell lung cancer ( NSCLC ) patients . METHODS AND MATERIAL S A Cox proportional hazards model with prognostic and treatment covariates was estimated using prospect i ve data for 129 NSCLC patients presenting at the Victoria Clinic ( ViCC ) of the British Columbia Cancer Agency ( BCCA ) 1990 - 1991 . The estimated model was simulated to predict survival curves for groups of patients with and without treatment . The difference between the predicted median survival with treatment and without treatment is the gain in survival attributable to treatment . RESULTS After adjusting for the effect of TNM staging , Karnofsky performance status , weight loss , tumor size , and tumor histology on survival , high-dose palliative radiotherapy ( RT ) ( 30 - 50 Gy in 10 - 20 fractions ) increased median survival by 79 days ( 95 % confidence interval : 31 - 106 days ) , and lowered the relative risk of death rate to 0.53 ( 95 % confidence interval : 0.35 - 0.85 ) . Radical RT ( 50 or more Gy , in 20 or more fractions ) increased median survival by 424 days ( 95 % confidence interval : 302 - 488 days ) , and lowered the relative risk of death to 0.24 ( 95 % confidence interval : 0.14 - 0.43 ) . CONCLUSION Our results support the hypothesis that the increased survival of patients receiving aggressive palliative , or radical , RT  is due not solely to patient selection , but also partly to a response to treatment PURPOSE The treatment of nonsmall cell lung cancer ( NSCLC ) with conventional radiotherapy ( RT ) results in inadequate local tumor control and survival . We report results of a Phase II trial design ed to treat patients with a significantly increased total dose administered in a reduced overall treatment time using a hyperfractionated , accelerated treatment schedule with a concurrent boost technique . METHODS AND MATERIAL S A total of 49 patients with unresectable Stage IIIA/IIIB ( 38 patients ) or medically inoperable Stage I/II ( 11 patients ) NSCLC were prospect ively enrolled in this protocol . Radiation therapy was administered twice daily , 5 days/week with > 6 h between each treatment . The primary tumor and adjacent enlarged lymph nodes were treated to a total dose of 73.6 Gy in 46 fractions of 1.6 Gy each . Using a concurrent boost technique , electively irradiated nodal regions were simultaneously treated with a dose of 1.25 Gy/fraction for the first 36 fractions to a total dose of 45 Gy . RESULTS Median survival for the entire group of 49 patients is 15.3 months . Actuarial survival at 2 years is 46 % : 60 % for 11 Stage I/II patients , 55 % for 21 Stage IIIA patients , and 26 % for 17 Stage IIIB patients . The actuarial rate of freedom from local progression at 2 years is 64 % for the entire group of 49 patients : 62 % for Stage I/II patients , 70 % for Stage IIIA patients , and 55 % for Stage IIIB patients . Patients who underwent serial bronchoscopic reevaluation ( 4 Stage I/II , 8 Stage IIIA , and 6 Stage IIIB ) have an actuarial rate of local control of 71 % at 2 years . The median total treatment time was 32 days . Nine of 49 patients ( 18 % ) experienced Grade III acute esophageal toxicity . The 2-year actuarial risk of Grade III or greater late toxicity is 30 % . The 2-year actuarial rate of severe-late pulmonary and skin-subcutaneous toxicity is 20 % and 15 % , respectively . CONCLUSION This treatment regimen administers a substantially higher biologically effective dose compared with conventional and pure hyperfractionation treatment schedules . The overall rate of acute and late toxicity was acceptable . Preliminary rates of overall survival and local control and freedom from local progression compare favorably to results reported with pure hyperfractionated radiotherapy and chemoradiotherapy BACKGROUND AND METHOD A r and omised controlled trial in locally advanced non-small cell lung cancer ( NSCLC ) , compared CHART which employs 36 fractions of 1.5 Gy 3 times per day to give 54 Gy in 12 consecutive days with conventional radiotherapy-30 fractions of 2 Gy to a total dose of 60 Gy in 6 weeks . A total of 563 patients were entered between April 1990 and April 1995 . This report is based upon the data up date d to 1 April 1998 . RESULTS The analysis of the mature data shows that the benefits previously reported have been maintained . Overall there was a 22 % reduction in the relative risk of death , which is equivalent to an absolute improvement in 2 year survival of 9 % from 20 to 29 % ( P = 0.008 ) and a 21 % reduction in the relative risk of local progression ( P = 0.033 ) . In the large subgroup of patients with squamous cell cancer which accounted for 81 % of the cases , there was a 30 % reduction in the relative risk of death , which is equivalent to an absolute improvement in 2 year survival of 13 % from 20 to 33 % ( P = 0.0007 ) and a 27 % reduction in the relative risk of local progression ( P = 0.012 ) . Furthermore , in squamous carcinoma there was a 25 % reduction in the relative risk of local and /or distant progression ( P = 0.025 ) and 24 % reduction in the relative risk of metastasis ( P = 0.043 ) . There was no evidence that CHART gave more or less benefit in any other subgroup . CONCLUSION This analysis of mature data confirms that CHART is superior to conventional radiotherapy in achieving local tumour control and survival in locally advanced NSCLC . This demonstrates the importance of cellular re population as a cause of failure in the radiotherapy of NSCLC . The reduction in the risk of metastasis confirms that improved local tumour control , even in lung cancer , can reduce the incidence of metastasis . This trial shows that control of local tumour can lead to an improvement in long term survival ! [ ] [ 1 ] Rating : R and omised controlled trials are often held up as the “ gold st and ard ” of medical research , and it is commonly believed that the size of a treatment effect is exaggerated in non-r and omised studies . In these days of evidence based medicine , however , where is the empirical evidence that this is so ? A widespread criticism of r and omised controlled trials is that they are based on highly selected individuals . Are there systematic differences between patients included and excluded in such trials , and do these influence the measured treatment effect ? These are just a few … [ 1 ] : This report details the patterns of tumor recurrence in two prospect i ve r and omized studies involving 551 patients with histologically proven unresectable or medically inoperable non‐oat cell carcinoma of the lung treated with definitive radiotherapy .  Patients were treated according to two protocol s , depending on the stage of the tumor : ( 1 ) Patients with T1 , 2 , 3‐NO , 1 , 2 tumors were r and omized to four different regimens : 4000 cGy split course ( 2000 cGy in five fractions , per 1 week , 2 weeks rest and additional 2000 cGy in five fractions , per 1 week ) or 4000 , 5000 , or 6000 cGy continuous courses , five fractions per week . ( 2 ) Patients with T4 , any N or N3 , any T stage tumors were r and omized to be treated with 3000 cGy tumor dose ( TD ) , ten fractions in 2 weeks , 4000 cGy split course ( described above ) , or 4000 cGy continuous course . In the patients with less advanced tumors ( Study 1 ) the intrathoracic failure rate within the irradiated volume was 48 % with 4000 cGy continuous , 38 % with 4000 cGy split course or 5000 cGy continuous , and 27 % for patients receiving 6000 cGy continuous course . The failure rate in the nonirradiated lung ranged from 25 % to 30 % in the various groups . Patients with adenocarcinoma or large cell undifferentiated carcinoma had better intrathoracic tumor control ( 35 % ) than those with squamous cell carcinoma ( 20 % ) . The incidence of distant metastases was 75 % to 80 % in all histologic groups . Distant metastases appeared sooner after therapy in the patients with adenocarcinoma or large cell undifferentiated carcinoma . The initial failure rate in the brain was 7 % in patients with squamous cell carcinoma , 19 % with adenocarcinoma , and 13 % in patients with large cell carcinoma .  The ultimate incidence of brain metastases was 16 % in squamous cell carcinoma , and 30 % for adenocarcinoma or large cell undifferentiated carcinoma . Higher doses of irradiation will be necessary in order to improve the intrathoracic tumor control . Clinical trials by the Radiation Therapy Oncology Group , some of them involving multiple daily fractionation , are in progress . Furthermore , because of the high incidence of distant metastases , effective systemic cytotoxic agents are critically needed to improve survival of lung cancer patients . The high frequency of brain metastases suggests that , as in small cell carcinoma of the lung , elective irradiation of the brain may be necessary , if not to improve survival to enhance the quality of life of patients with adenocarcinoma and large cell carcinoma 
    Output:
    