You will be presented with a collection of medical randomized controlled trial (RCT) reports addressing a shared clinical question -- for instance, the efficacy of a medical intervention on a disease or condition. Given the titles and abstracts of these reports, your task is to generate the conclusion of the systematic review article synthesizing the key findings. Your conclusion should be a few sentences long. In your response, include only the conclusion and no other text. The RCT reports are below.



Title 1:
Memantine for the prevention of cognitive dysfunction in patients receiving whole-brain radiotherapy: a randomized, double-blind, placebo-controlled trial.
Abstract 1:
BACKGROUND To determine the protective effects of memantine on cognitive function in patients receiving whole-brain radiotherapy ( WBRT ) . METHODS Adult patients with brain metastases received WBRT  and were r and omized to receive placebo or memantine ( 20 mg/d ) , within 3 days of initiating radiotherapy for 24 weeks . Serial st and ardized tests of cognitive function were performed . RESULTS Of 554 patients who were accrued , 508 were eligible . Grade 3 or 4 toxicities and study compliance were similar in the 2 arms . There was less decline in delayed recall in the memantine arm at 24 weeks ( P = .059 ) , but the difference was not statistically significant , possibly because there were only 149 analyzable patients at 24 weeks , result ing in only 35 % statistical power . The memantine arm had significantly longer time to cognitive decline ( hazard ratio 0.78 , 95 % confidence interval 0.62 - 0.99 , P = .01 ) ; the probability of cognitive function failure at 24 weeks was 53.8 % in the memantine arm and 64.9 % in the placebo arm . Superior results were seen in the memantine arm for executive function at 8 ( P = .008 ) and 16 weeks ( P = .0041 ) and for processing speed ( P = .0137 ) and delayed recognition ( P = .0149 ) at 24 weeks . CONCLUSIONS Memantine was well tolerated and had a toxicity profile very similar to placebo . Although there was less decline in the primary endpoint of delayed recall at 24 weeks , this lacked statistical significance possibly due to significant patient loss . Overall , patients treated with memantine had better cognitive function over time ; specifically , memantine delayed time to cognitive decline and reduced the rate of decline in memory , executive function , and processing speed in patients receiving WBRT . RTOG 0614 , Clinical Trials.gov number CT00566852


Title 2:
Prophylactic cranial irradiation in extensive disease small-cell lung cancer: short-term health-related quality of life and patient reported symptoms: results of an international Phase III randomized controlled trial by the EORTC Radiation Oncology and Lung Cancer Groups.
Abstract 2:
PURPOSE Prophylactic cranial irradiation ( PCI ) in patients with extensive-disease small-cell lung cancer ( ED-SCLC ) leads to significantly fewer symptomatic brain metastases and improved survival . Detailed effects of PCI on health-related quality of life ( HRQOL ) are reported here . PATIENTS AND METHODS Patients ( age , 18 to 75 years ; WHO < or = 2 ) with ED-SCLC , and any response to chemotherapy  , were r and omly assigned to either observation or PCI .  Health-related quality of life ( HRQOL ) and patient-reported symptoms were secondary end points . The European Organisation for the Research and Treatment of Cancer core HRQOL tool ( Quality of Life Question naire C30 ) and brain module ( Quality of Life Question naire Brain Cancer Module ) were used to collect self-reported patient data . Six HRQOL scales were selected as primary HRQOL end points : global health status ; hair loss ; fatigue ; and role , cognitive and emotional functioning . Assessment s were performed at r and om assignment , 6 weeks , 3 months , and then 3-monthly up to 1 year and 6-monthly thereafter . RESULTS Compliance with the HRQOL assessment was 93.7 % at baseline and dropped to 60 % at 6 weeks . Short-term results up to 3 months showed that there was a negative impact of PCI on selected HRQOL scales . The largest mean difference between the two arms was observed for fatigue and hair loss . The impact of PCI on global health status as well as on functioning scores was more limited . For global health status , the observed mean difference was eight points on a scale 0 to 100 at 6 weeks ( P = .018 ) and 3 months ( P = .055 ) . CONCLUSION PCI should be offered to all responding ED SCLC patients . Patients should be informed of the potential adverse effects from PCI . Clinicians should be alert to these ; monitor their patients ; and offer appropriate support , clinical , and psychosocial care


Title 3:
Decline in tested and self-reported cognitive functioning after prophylactic cranial irradiation for lung cancer: pooled secondary analysis of Radiation Therapy Oncology Group randomized trials 0212 and 0214.
Abstract 3:
PURPOSE To assess the impact of prophylactic cranial irradiation ( PCI ) on self-reported cognitive functioning ( SRCF ) , a functional scale on the European Organization for Research and Treatment of Cancer Core Quality of Life Question naire ( EORTC QLQ-C30 ) . METHODS AND MATERIAL S Radiation Therapy Oncology Group ( RTOG ) protocol 0214 r and omized patients with locally advanced non-small cell lung cancer to PCI or observation ; RTOG 0212 r and omized patients with limited-disease small cell lung cancer to high- or st and ard-dose PCI .  In both trials ,  Hopkins Verbal Learning Test (HVLT)-Recall and -Delayed Recall and SRCF were assessed at baseline ( after locoregional therapy but before PCI or observation ) and at 6 and 12 months . Patients developing brain relapse before follow-up evaluation were excluded . Decline was defined using the reliable change index method and correlated with receipt of PCI versus observation using logistic regression modeling . Fisher 's exact test correlated decline in SRCF with HVLT decline . RESULTS Of the eligible patients pooled from RTOG 0212 and RTOG 0214 , 410 ( 93 % ) receiving PCI and 173 ( 96 % ) undergoing observation completed baseline HVLT or EORTC QLQ-C30 testing and were included in this analysis . Prophylactic cranial irradiation was associated with a higher risk of decline in SRCF at 6 months ( odds ratio 3.60 , 95 % confidence interval 2.34 - 6.37 , P<.0001 ) and 12 months ( odds ratio 3.44 , 95 % confidence interval 1.84 - 6.44 , P<.0001 ) . Decline on HVLT-Recall at 6 and 12 months was also associated with PCI ( P=.002 and P=.002 , respectively ) but was not closely correlated with decline in SRCF at the same time points ( P=.05 and P=.86 , respectively ) . CONCLUSIONS In lung cancer patients who do not develop brain relapse , PCI is associated with decline in HVLT-tested and self-reported cognitive functioning . Decline in HVLT and decline in SRCF are not closely correlated , suggesting that they may represent distinct elements of the cognitive spectrum


Title 4:
Donepezil for Irradiated Brain Tumor Survivors: A Phase III Randomized Placebo-Controlled Clinical Trial.
Abstract 4:
PURPOSE Neurotoxic effects of brain irradiation include cognitive impairment in 50 % to 90 % of patients . Prior studies have suggested that donepezil , a neurotransmitter modulator , may improve cognitive function . PATIENTS AND METHODS A total of 198 adult brain tumor survivors ≥ 6 months after partial- or whole-brain irradiation were r and omly assigned to receive a single daily dose ( 5 mg for 6 weeks , 10 mg for 18 weeks ) of donepezil or placebo . A cognitive test battery assessing memory , attention , language , visuomotor , verbal fluency , and executive functions was administered before r and om assignment and at 12 and 24 weeks . A cognitive composite score ( primary outcome ) and individual cognitive domains were evaluated . RESULTS Of this mostly middle-age , married , non-Hispanic white sample , 66 % had primary brain tumors , 27 % had brain metastases , and 8 % underwent prophylactic cranial irradiation . After 24 weeks of treatment , the composite scores did not differ significantly between groups ( P = .48 ) ; however , significant differences favoring donepezil were observed for memory ( recognition , P = .027 ; discrimination , P = .007 ) and motor speed and dexterity ( P = .016 ) . Significant interactions between pretreatment cognitive function and treatment were found for cognitive composite ( P = .01 ) , immediate recall ( P = .05 ) , delayed recall ( P = .004 ) , attention ( P = .01 ) , visuomotor skills ( P = .02 ) , and motor speed and dexterity ( P < .001 ) , with the benefits of donepezil greater for those who were more cognitively impaired before study treatment . CONCLUSION Treatment with donepezil did not significantly improve the overall composite score , but it did result in modest improvements in several cognitive functions , especially among patients with greater pretreatment impairments
RESULTS Steroids provide relief of symptoms due to intra-cerebral edema .
The steroid of choice is dexamethasone .
Surgery or radiosurgery improves survival for selected patients with single brain metastasis as compared to WBRT alone .