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: BACKGROUND Results from a previous phase 3 study suggested that prophylactic cranial irradiation reduces the incidence of symptomatic brain metastases and prolongs overall survival compared with no prophylactic cranial irradiation in patients with extensive-disease small-cell lung cancer . However , because of the absence of brain imaging before enrolment and variations in chemotherapeutic regimens and irradiation doses , concerns have been raised about these findings . We did a phase 3 trial to reassess the efficacy of prophylactic cranial irradiation in the treatment of extensive-disease small-cell lung cancer . METHODS We did this r and omised , open-label , phase 3 study at 47 institutions in Japan . Patients with extensive-disease small-cell lung cancer who had any response to platinum-based doublet chemotherapy and no brain metastases on MRI were r and omly assigned ( 1:1 ) to receive prophylactic cranial irradiation ( 25 Gy in ten daily fractions of 2·5 Gy ) or observation . All patients were required to have brain MRI at 3-month intervals up to 12 months and at 18 and 24 months after enrolment . R and omisation was done by computer-generated allocation sequence , with age as a stratification factor and minimisation by institution , Eastern Cooperative Oncology Group performance status , and response to initial chemotherapy . The primary endpoint was overall survival , analysed in the intention-to-treat population . This trial is registered with the UMIN Clinical Trials Registry , number UMIN000001755 , and is closed to new participants . FINDINGS Between April 3 , 2009 , and July 17 , 2013 , 224 patients were enrolled and r and omly assigned ( 113 to prophylactic cranial irradiation and 111 to observation ) . In the planned interim analysis on June 18 , 2013 , of the first 163 enrolled patients , Bayesian predictive probability of prophylactic cranial irradiation being superior to observation was 0·011 % , result ing in early termination of the study because of futility . In the final analysis , median overall survival was 11·6 months ( 95 % CI 9·5 - 13·3 ) in the prophylactic cranial irradiation group and 13·7 months ( 10·2 - 16·4 ) in the observation group ( hazard ratio 1·27 , 95 % CI 0·96 - 1·68 ; p=0·094 ) . The most frequent grade 3 or worse adverse events at 3 months were anorexia ( six [ 6 % ] of 106 in the prophylactic cranial irradiation group vs two [ 2 % ] of 111 in the observation group ) , malaise ( three [ 3 % ] vs one [ < 1 % ] ) , and muscle weakness in a lower limb ( one [ < 1 % ] vs six [ 5 % ] ) . No treatment-related deaths occurred in either group . INTERPRETATION In this Japanese trial , prophylactic cranial irradiation did not result in longer overall survival compared with observation in patients with extensive-disease small-cell lung cancer .  Prophylactic cranial irradiation is therefore not essential for patients with extensive-disease small-cell lung cancer with any response to initial chemotherapy and a confirmed absence of brain metastases when patients receive periodic MRI examination during follow-up . FUNDING The Ministry of Health , Labour and Welfare of Japan Between 1981 and 1986 , a total of 46 patients with small cell lung cancer ( SCLC ) achieving a complete response by chemotherapy with or without chest irradiation  were r and omized either to receive prophylactic cranial irradiation ( PCI ) or not . With a median follow-up time of 8.5 years for both groups , only five of 23 patients ( 22 % ) in the PCI group developed brain relapse , while 12 out of 23 ( 52 % ) in the no PCI group did so ( P < 0.05 ) . The frequency of patients developing a sole brain relapse during their whole clinical course was 4 % for the PCI group and 17 % for the no PCI group , however , the difference was not statistically significant . Patient survival was better for the PCI group ( median survival time of 21 months , and 5-year survival rate of 22 % ) as compared with the no PCI group ( median survival time of 15 months , and 5-year survival rate of 13 % ) , showing a marginal significance ( P = 0.097 ) . Late neurologic toxicity was infrequent ; only one developed a mild deterioration among seven long-term disease-free survivors in the PCI group . These results appear to warrant further clinical trials to clarify the utility of  PCI  in patients with SCLC achieving a complete response Background In 2007 , the European Organization for Research and Treatment of Cancer ( EORTC ) study ( Clinical Trials.gov identifier , NCT00016211 ) demonstrated a beneficial effect on overall survival ( OS ) with the use of prophylactic cranial irradiation ( PCI ) for extensive disease ( ED ) small‐cell lung cancer ( SCLC ) . Nevertheless , debate is ongoing regarding the role of PCI , because the patients in that trial did not undergo magnetic resonance imaging ( MRI ) of the brain before treatment . Also , a recent Japanese r and omized trial showed a detrimental effect of PCI on OS in patients with negative pretreatment brain MRI findings . Material s and Methods We examined the medical records of 136 patients with ED SCLC who had initially responded to chemotherapy and undergone PCI from 2007 to 2015 . The outcomes , radiation toxicity , neurologic progression‐free survival , and OS after PCI were analyzed . Survival and correlations were calculated using log‐rank and univariate Cox proportional hazard ratio analyses . Results The median OS and the median neurologic progression‐free survival  after PCI was 12 and 19 months , respectively . No significant survival difference was seen for patients who had undergone MRI before PCI compared with patients who had undergone contrast‐enhanced computed tomography ( P = .20 ) . Univariate analysis for OS did not show a statistically significant effect for known cofactors . Conclusion In the present cohort , PCI was associated with improved survival compared with the PCI arm of the EORTC trial , with a nearly doubled median OS period . Also , the median OS was prolonged by 2 months compared with the irradiation arm of the Japanese trial . Micro‐ Abstract In 2007 , a European Organization for Research and Treatment of Cancer ( EORTC ) study demonstrated a beneficial effect on overall survival ( OS ) with the use of prophylactic cranial irradiation ( PCI ) in extensive disease small‐cell lung cancer . Nevertheless , debate is ongoing regarding the role of PCI , because the patients in that trial did not undergo imaging of the brain before treatment . Also , a recent Japanese r and omized trial showed a detrimental effect of PCI on OS in patients with negative pretreatment brain magnetic resonance imaging findings . Of our patients , 87 % underwent brain imaging before PCI . In the present retrospective analysis , we found that PCI leads to a nearly doubled median OS compared with the irradiation arm of the EORTC trial , with a 2‐month prolonged median OS compared with the irradiation arm of the Japanese trial BACKGROUND We conducted a r and omized trial of prophylactic cranial irradiation in patients with extensive small-cell lung cancer who had had a response to chemotherapy . METHODS Patients between the ages of 18 and 75 years with extensive small-cell lung cancer were r and omly assigned to undergo prophylactic cranial irradiation ( irradiation group ) or receive no further therapy ( control group ) . The primary end point was the time to symptomatic brain metastases . Computed tomography or magnetic resonance imaging of the brain was performed when any predefined key symptom suggestive of brain metastases was present . RESULTS The two groups ( each with 143 patients ) were well balanced regarding baseline characteristics . Patients in the irradiation group had a lower risk of symptomatic brain metastases ( hazard ratio , 0.27 ; 95 % confidence interval [ CI ] , 0.16 to 0.44 ; P<0.001 ) . The cumulative risk of brain metastases within 1 year was 14.6 % in the irradiation group ( 95 % CI , 8.3 to 20.9 ) and 40.4 % in the control group ( 95 % CI , 32.1 to 48.6 ) . Irradiation was associated with an increase in median disease-free survival from 12.0 weeks to 14.7 weeks and in median overall survival from 5.4 months to 6.7 months after r and omization . The 1-year survival rate was 27.1 % ( 95 % CI , 19.4 to 35.5 ) in the irradiation group and 13.3 % ( 95 % CI , 8.1 to 19.9 ) in the control group . Irradiation had side effects but did not have a clinical ly significant effect on global health status . CONCLUSIONS Prophylactic cranial irradiation reduces the incidence of symptomatic brain metastases and prolongs disease-free and overall survival . ( Clinical Trials.gov number , NCT00016211 [ Clinical Trials.gov ] . ) OBJECTIVE To evaluate the effect of prophylactic cranial irradiation ( PCI ) on overall survival ( OS ) in patients with extensive small cell lung cancer ( ESCLC ) . METHODS Between April 2005 and May 2014 , 204 patients with ESCLC who had any response ( according to RECIST 1.1 ) to initial chemotherapy were review ed . All patients had undergone appropriate imaging tests to exclude brain metastases before initial chemotherapy . PCI was performed on 45 patients ( 22.1 % ) and the remaining patients ( 77.9 % ) received no such treatment ( control group ) . Primary endpoint was OS . The incidence of brain metastases , brain metastases-free survival ( BMFS ) , and adverse effects were also evaluated . RESULTS Survival data of the 204 patients were analyzed statistically . PCI significantly prolonged median OS from 12.6 to 16.5 months as compared to the control group ( hazard ratio , HR , 0.63 ; 95 % confidence interval , CI , 0.41 to 0.96 ; p = 0.033 ) . PCI significantly lowered the risk of brain metastases ( HR 0.48 ; 95 % CI 0.30 to 0.76 ; p = 0.001 ) . The 1‑year incidence of brain metastases was 17.1 and 55.9 % in the PCI and control group , respectively . PCI significantly correlated with the increased median BMFS ( p = 0.002 ) . Additionally , multivariate analyses demonstrated that PCI was a favorable independent predictor of OS , BMFS , and the incidence of brain metastases . Acute and chronic adverse effects were generally low grade and well tolerated in patients receiving PCI . CONCLUSION PCI after any response to initial chemotherapy significantly improved OS of ESCLC patients analyzed in this study BACKGROUND We recently published the results of the PCI99 r and omised trial comparing the effect of a prophylactic cranial irradiation ( PCI ) at 25 or 36 Gy on the incidence of brain metastases ( BM ) in 720 patients with limited small-cell lung cancer ( SCLC ) . As concerns about neurotoxicity were a major issue surrounding PCI , we report here midterm and long-term repeated evaluation of neurocognitive functions and quality of life ( QoL ) . PATIENTS AND METHODS At predetermined intervals , the European Organisation for Research and Treatment of Cancer ( EORTC ) QLQ-C30 and brain module were used for self-reported patient data , whereas the EORTC-Radiation Therapy Oncology Group Late Effects Normal Tissue-Subjective , Objective , Management , Analytic scale was used for clinicians ' assessment . For each scale , the unfavourable status was analysed with a logistic model including age , grade at baseline , time and PCI dose . RESULTS Over the 3 years studied , there was no significant difference between the two groups in any of the 17 selected items assessing QoL and neurological and cognitive functions . We observed in both groups a mild deterioration across time of communication deficit , weakness of legs , intellectual deficit and memory ( all P < 0.005 ) . CONCLUSION Patients should be informed of these potential adverse effects , as well as the benefit of PCI on survival and BM .  PCI with a total dose of 25 Gy remains the st and ard of care in limited-stage SCLC Introduction : Conflicting data from r and omized clinical trials incite the debate over the appropriate use of prophylactic cranial irradiation ( PCI ) for patients with extensive‐stage SCLC ( ES‐SCLC ) who achieve clinical response to systemic chemotherapy . The current pattern of practice among U.S. radiation oncologists is unknown . Methods : We surveyed practicing U.S. radiation oncologists through a short online question naire . Respondents ' characteristics and their self‐rated knowledge base were analyzed for association with their treatment recommendations . Results : We received 473 responses from practicing U.S. radiation oncologists . More than half of the respondents had been practicing for more than 10 years after completing residency training , and 70 % had treated more than 10 patients with lung cancer per year . Of the respondents , 90 % recommended  brain magnetic resonance imaging ( MRI )  before initiation of PCI and 98 % recommended PCI 
    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: BACKGROUND Results from a previous phase 3 study suggested that prophylactic cranial irradiation reduces the incidence of symptomatic brain metastases and prolongs overall survival compared with no prophylactic cranial irradiation in patients with extensive-disease small-cell lung cancer . However , because of the absence of brain imaging before enrolment and variations in chemotherapeutic regimens and irradiation doses , concerns have been raised about these findings . We did a phase 3 trial to reassess the efficacy of prophylactic cranial irradiation in the treatment of extensive-disease small-cell lung cancer . METHODS We did this r and omised , open-label , phase 3 study at 47 institutions in Japan . Patients with extensive-disease small-cell lung cancer who had any response to platinum-based doublet chemotherapy and no brain metastases on MRI were r and omly assigned ( 1:1 ) to receive prophylactic cranial irradiation ( 25 Gy in ten daily fractions of 2·5 Gy ) or observation . All patients were required to have brain MRI at 3-month intervals up to 12 months and at 18 and 24 months after enrolment . R and omisation was done by computer-generated allocation sequence , with age as a stratification factor and minimisation by institution , Eastern Cooperative Oncology Group performance status , and response to initial chemotherapy . The primary endpoint was overall survival , analysed in the intention-to-treat population . This trial is registered with the UMIN Clinical Trials Registry , number UMIN000001755 , and is closed to new participants . FINDINGS Between April 3 , 2009 , and July 17 , 2013 , 224 patients were enrolled and r and omly assigned ( 113 to prophylactic cranial irradiation and 111 to observation ) . In the planned interim analysis on June 18 , 2013 , of the first 163 enrolled patients , Bayesian predictive probability of prophylactic cranial irradiation being superior to observation was 0·011 % , result ing in early termination of the study because of futility . In the final analysis , median overall survival was 11·6 months ( 95 % CI 9·5 - 13·3 ) in the prophylactic cranial irradiation group and 13·7 months ( 10·2 - 16·4 ) in the observation group ( hazard ratio 1·27 , 95 % CI 0·96 - 1·68 ; p=0·094 ) . The most frequent grade 3 or worse adverse events at 3 months were anorexia ( six [ 6 % ] of 106 in the prophylactic cranial irradiation group vs two [ 2 % ] of 111 in the observation group ) , malaise ( three [ 3 % ] vs one [ < 1 % ] ) , and muscle weakness in a lower limb ( one [ < 1 % ] vs six [ 5 % ] ) . No treatment-related deaths occurred in either group . INTERPRETATION In this Japanese trial , prophylactic cranial irradiation did not result in longer overall survival compared with observation in patients with extensive-disease small-cell lung cancer .  Prophylactic cranial irradiation is therefore not essential for patients with extensive-disease small-cell lung cancer with any response to initial chemotherapy and a confirmed absence of brain metastases when patients receive periodic MRI examination during follow-up . FUNDING The Ministry of Health , Labour and Welfare of Japan Between 1981 and 1986 , a total of 46 patients with small cell lung cancer ( SCLC ) achieving a complete response by chemotherapy with or without chest irradiation  were r and omized either to receive prophylactic cranial irradiation ( PCI ) or not . With a median follow-up time of 8.5 years for both groups , only five of 23 patients ( 22 % ) in the PCI group developed brain relapse , while 12 out of 23 ( 52 % ) in the no PCI group did so ( P < 0.05 ) . The frequency of patients developing a sole brain relapse during their whole clinical course was 4 % for the PCI group and 17 % for the no PCI group , however , the difference was not statistically significant . Patient survival was better for the PCI group ( median survival time of 21 months , and 5-year survival rate of 22 % ) as compared with the no PCI group ( median survival time of 15 months , and 5-year survival rate of 13 % ) , showing a marginal significance ( P = 0.097 ) . Late neurologic toxicity was infrequent ; only one developed a mild deterioration among seven long-term disease-free survivors in the PCI group . These results appear to warrant further clinical trials to clarify the utility of  PCI  in patients with SCLC achieving a complete response Background In 2007 , the European Organization for Research and Treatment of Cancer ( EORTC ) study ( Clinical Trials.gov identifier , NCT00016211 ) demonstrated a beneficial effect on overall survival ( OS ) with the use of prophylactic cranial irradiation ( PCI ) for extensive disease ( ED ) small‐cell lung cancer ( SCLC ) . Nevertheless , debate is ongoing regarding the role of PCI , because the patients in that trial did not undergo magnetic resonance imaging ( MRI ) of the brain before treatment . Also , a recent Japanese r and omized trial showed a detrimental effect of PCI on OS in patients with negative pretreatment brain MRI findings . Material s and Methods We examined the medical records of 136 patients with ED SCLC who had initially responded to chemotherapy and undergone PCI from 2007 to 2015 . The outcomes , radiation toxicity , neurologic progression‐free survival , and OS after PCI were analyzed . Survival and correlations were calculated using log‐rank and univariate Cox proportional hazard ratio analyses . Results The median OS and the median neurologic progression‐free survival  after PCI was 12 and 19 months , respectively . No significant survival difference was seen for patients who had undergone MRI before PCI compared with patients who had undergone contrast‐enhanced computed tomography ( P = .20 ) . Univariate analysis for OS did not show a statistically significant effect for known cofactors . Conclusion In the present cohort , PCI was associated with improved survival compared with the PCI arm of the EORTC trial , with a nearly doubled median OS period . Also , the median OS was prolonged by 2 months compared with the irradiation arm of the Japanese trial . Micro‐ Abstract In 2007 , a European Organization for Research and Treatment of Cancer ( EORTC ) study demonstrated a beneficial effect on overall survival ( OS ) with the use of prophylactic cranial irradiation ( PCI ) in extensive disease small‐cell lung cancer . Nevertheless , debate is ongoing regarding the role of PCI , because the patients in that trial did not undergo imaging of the brain before treatment . Also , a recent Japanese r and omized trial showed a detrimental effect of PCI on OS in patients with negative pretreatment brain magnetic resonance imaging findings . Of our patients , 87 % underwent brain imaging before PCI . In the present retrospective analysis , we found that PCI leads to a nearly doubled median OS compared with the irradiation arm of the EORTC trial , with a 2‐month prolonged median OS compared with the irradiation arm of the Japanese trial BACKGROUND We conducted a r and omized trial of prophylactic cranial irradiation in patients with extensive small-cell lung cancer who had had a response to chemotherapy . METHODS Patients between the ages of 18 and 75 years with extensive small-cell lung cancer were r and omly assigned to undergo prophylactic cranial irradiation ( irradiation group ) or receive no further therapy ( control group ) . The primary end point was the time to symptomatic brain metastases . Computed tomography or magnetic resonance imaging of the brain was performed when any predefined key symptom suggestive of brain metastases was present . RESULTS The two groups ( each with 143 patients ) were well balanced regarding baseline characteristics . Patients in the irradiation group had a lower risk of symptomatic brain metastases ( hazard ratio , 0.27 ; 95 % confidence interval [ CI ] , 0.16 to 0.44 ; P<0.001 ) . The cumulative risk of brain metastases within 1 year was 14.6 % in the irradiation group ( 95 % CI , 8.3 to 20.9 ) and 40.4 % in the control group ( 95 % CI , 32.1 to 48.6 ) . Irradiation was associated with an increase in median disease-free survival from 12.0 weeks to 14.7 weeks and in median overall survival from 5.4 months to 6.7 months after r and omization . The 1-year survival rate was 27.1 % ( 95 % CI , 19.4 to 35.5 ) in the irradiation group and 13.3 % ( 95 % CI , 8.1 to 19.9 ) in the control group . Irradiation had side effects but did not have a clinical ly significant effect on global health status . CONCLUSIONS Prophylactic cranial irradiation reduces the incidence of symptomatic brain metastases and prolongs disease-free and overall survival . ( Clinical Trials.gov number , NCT00016211 [ Clinical Trials.gov ] . ) OBJECTIVE To evaluate the effect of prophylactic cranial irradiation ( PCI ) on overall survival ( OS ) in patients with extensive small cell lung cancer ( ESCLC ) . METHODS Between April 2005 and May 2014 , 204 patients with ESCLC who had any response ( according to RECIST 1.1 ) to initial chemotherapy were review ed . All patients had undergone appropriate imaging tests to exclude brain metastases before initial chemotherapy . PCI was performed on 45 patients ( 22.1 % ) and the remaining patients ( 77.9 % ) received no such treatment ( control group ) . Primary endpoint was OS . The incidence of brain metastases , brain metastases-free survival ( BMFS ) , and adverse effects were also evaluated . RESULTS Survival data of the 204 patients were analyzed statistically . PCI significantly prolonged median OS from 12.6 to 16.5 months as compared to the control group ( hazard ratio , HR , 0.63 ; 95 % confidence interval , CI , 0.41 to 0.96 ; p = 0.033 ) . PCI significantly lowered the risk of brain metastases ( HR 0.48 ; 95 % CI 0.30 to 0.76 ; p = 0.001 ) . The 1‑year incidence of brain metastases was 17.1 and 55.9 % in the PCI and control group , respectively . PCI significantly correlated with the increased median BMFS ( p = 0.002 ) . Additionally , multivariate analyses demonstrated that PCI was a favorable independent predictor of OS , BMFS , and the incidence of brain metastases . Acute and chronic adverse effects were generally low grade and well tolerated in patients receiving PCI . CONCLUSION PCI after any response to initial chemotherapy significantly improved OS of ESCLC patients analyzed in this study BACKGROUND We recently published the results of the PCI99 r and omised trial comparing the effect of a prophylactic cranial irradiation ( PCI ) at 25 or 36 Gy on the incidence of brain metastases ( BM ) in 720 patients with limited small-cell lung cancer ( SCLC ) . As concerns about neurotoxicity were a major issue surrounding PCI , we report here midterm and long-term repeated evaluation of neurocognitive functions and quality of life ( QoL ) . PATIENTS AND METHODS At predetermined intervals , the European Organisation for Research and Treatment of Cancer ( EORTC ) QLQ-C30 and brain module were used for self-reported patient data , whereas the EORTC-Radiation Therapy Oncology Group Late Effects Normal Tissue-Subjective , Objective , Management , Analytic scale was used for clinicians ' assessment . For each scale , the unfavourable status was analysed with a logistic model including age , grade at baseline , time and PCI dose . RESULTS Over the 3 years studied , there was no significant difference between the two groups in any of the 17 selected items assessing QoL and neurological and cognitive functions . We observed in both groups a mild deterioration across time of communication deficit , weakness of legs , intellectual deficit and memory ( all P < 0.005 ) . CONCLUSION Patients should be informed of these potential adverse effects , as well as the benefit of PCI on survival and BM .  PCI with a total dose of 25 Gy remains the st and ard of care in limited-stage SCLC Introduction : Conflicting data from r and omized clinical trials incite the debate over the appropriate use of prophylactic cranial irradiation ( PCI ) for patients with extensive‐stage SCLC ( ES‐SCLC ) who achieve clinical response to systemic chemotherapy . The current pattern of practice among U.S. radiation oncologists is unknown . Methods : We surveyed practicing U.S. radiation oncologists through a short online question naire . Respondents ' characteristics and their self‐rated knowledge base were analyzed for association with their treatment recommendations . Results : We received 473 responses from practicing U.S. radiation oncologists . More than half of the respondents had been practicing for more than 10 years after completing residency training , and 70 % had treated more than 10 patients with lung cancer per year . Of the respondents , 90 % recommended  brain magnetic resonance imaging ( MRI )  before initiation of PCI and 98 % recommended PCI 
    Output:
    