Effect of testosterone replacement therapy on prostate tissue in men with late-onset hypogonadism: a randomized controlled trial. 12-Month Observation of Testosterone Replacement Effectiveness in a General Population of Men Testosterone replacement therapy in older male subjective memory complainers: double-blind randomized crossover placebo-controlled clinical trial of physiological assessment and safety. Testosterone deficiency is associated with increased risk of mortality and testosterone replacement improves survival in men with type 2 diabetes. Incidence of prostate cancer in hypogonadal men receiving testosterone therapy: observations from 5-year median followup of 3 registries. Dutasteride reduces prostate size and prostate specific antigen in older hypogonadal men with benign prostatic hyperplasia undergoing testosterone replacement therapy. Short term testosterone replacement therapy improves libido and body composition. Sequential vs. concurrent chemoradiation for stage III non-small cell lung cancer: randomized phase III trial RTOG 9410. Prostatic specific antigen in patients with hypogonadism: effect of testosterone replacement. Randomized phase II trial of non-platinum induction or consolidation chemotherapy plus concomitant chemoradiation in stage III NSCLC patients: mature results of the Spanish Lung Cancer Group 0008 study. Effectiveness of RF capacitive hyperthermia combined with radiotherapy for stages III and IV oro-hypopharyngeal cancers: a non-randomized comparison between thermoradiotherapy and radiotherapy. Tinnitus Retraining Therapy (TRT): outcomes after one-year treatment. The effect of resistance training set configuration on strength, power, and hormonal adaptation in female volleyball players. Identification of late-onset hypogonadism in middle-aged and elderly men. PROCLAIM: Randomized Phase III Trial of Pemetrexed-Cisplatin or Etoposide-Cisplatin Plus Thoracic Radiation Therapy Followed by Consolidation Chemotherapy in Locally Advanced Nonsquamous Non-Small-Cell Lung Cancer. Palliative Thoracic Radiotherapy in Locally Advanced Non-small Cell Lung Cancer: Can Quality-Of-Life Assessments Help in Selection of Patients for Short- or Long-Course Radiotherapy? Predictors of long-term survival in patients with lung cancer included in the randomized Spanish Lung Cancer Group 0008 phase II trial using concomitant chemoradiation with docetaxel and carboplatin plus induction or consolidation chemotherapy. Randomized phase II study of pemetrexed, carboplatin, and thoracic radiation with or without cetuximab in patients with locally advanced unresectable non-small-cell lung cancer: Cancer and Leukemia Group B trial 30407. Multimodal therapy for the management of nonpelvic, localized Ewing's sarcoma of bone: intergroup study IESS-II. Combined chemoradiotherapy regimens of paclitaxel and carboplatin for locally advanced non-small-cell lung cancer: a randomized phase II locally advanced multi-modality protocol.
CONTEXT Prostate safety is a primary concern when aging men receive testosterone replacement therapy ( TRT ) , but little information is available regarding the effects of TRT on prostate tissue in men . OBJECTIVE To determine the effects of TRT on prostate tissue of aging men with low serum testosterone levels . DESIGN , SETTING , AND PARTICIPANTS R and omized , double-blind , placebo-controlled trial of 44 men , aged 44 to 78 years , with screening serum testosterone levels lower than 300 ng/dL ( < 10.4 nmol/L ) and related symptoms , conducted at a US community-based research center between February 2003 and November 2004 . INTERVENTION Participants were r and omly assigned to receive 150 mg of testosterone enanthate or matching placebo intramuscularly every 2 weeks for 6 months . MAIN OUTCOME MEASURES The primary outcome measure was the 6-month change in prostate tissue and rogen levels ( testosterone and dihydrotestosterone ) . Secondary outcome measures included 6-month changes in prostate-related clinical features , histology , biomarkers , and epithelial cell gene expression . RESULTS Of the 44 men r and omized , 40 had prostate biopsies performed both at baseline and at 6 months and qualified for per- protocol analysis ( TRT , n = 21 ; placebo , n = 19 ) . Testosterone replacement therapy increased serum testosterone levels to the mid-normal range ( median at baseline , 282 ng/dL [ 9.8 nmol/L ] ; median at 6 months , 640 ng/dL [ 22.2 nmol/L ] ) with no significant change in serum testosterone levels in matched , placebo-treated men . However , median prostate tissue levels of testosterone ( 0.91 ng/g ) and dihydrotestosterone ( 6.79 ng/g ) did not change significantly in the TRT group . No treatment-related change was observed in prostate histology , tissue biomarkers ( and rogen receptor , Ki-67 , CD34 ) , gene expression ( including AR , PSA , PAP2A , VEGF , NXK3 , CLU [ Clusterin ] ) , or cancer incidence or severity . Treatment-related changes in prostate volume , serum prostate-specific antigen , voiding symptoms , and urinary flow were minor . CONCLUSIONS These preliminary data suggest that in aging men with late-onset hypogonadism , 6 months of TRT normalizes serum and rogen levels but appears to have little effect on prostate tissue and rogen levels and cellular functions . Establishment of prostate safety for large population s of older men undergoing longer duration of TRT requires further study . Trial Registration clinical trials.gov Identifier : NCT00161304 Abstract Background : Testosterone decline becomes more prevalent as men age and symptomatic testosterone deficiency is associated with potentially serious comorbidities . Despite limitations , registries can provide an opportunity to accumulate data regarding disease management in a typical patient population , including diagnosis , treatment , and outcomes . Material s and Methods : The Testim Registry in the United States ( TRiUS ) was a prospect i ve , 12-month , observational cohort registry of men prescribed Testim ® ( 1 % testosterone gel ; Auxilium Pharmaceuticals , Inc. ) for the first time ; patients previously on other forms of testosterone replacement therapy ( TRT )  were eligible to participate in the study as well . The registry recorded total testosterone ( TT ) and free testosterone ( FT ) levels , prostate-specific antigen ( PSA ) , sexual function , mood/depression , and cardiometabolic and anthropometric criteria before and after TRT . Changes over time were analyzed by analysis of variance , and linear regression and Pearson product-moment correlation coefficients were used to examine relationships between variables . Results : At baseline , 849 patients from 72 sites were enrolled , with 743 of 849 started on 5 g gel/day ( 50 mg testosterone/day ) and 106 of 849 started on 10 g gel/day ( 100 mg testosterone/day ) . Mean TT and FT levels increased significantly after 3 months of TRT ( TT level , 16.8 ± 9.87 nmol/L [ 485 ± 284 ng/dL ] , P < 0.001 ; FT level , 286.3 ± 224.9 pmol/L [ 82.5 ± 64.8 pg/mL ] , P < 0.001 ) and were maintained at eugonadal levels . Mean PSA levels increased significantly ( P = 0.004 ) from 1.12 ± 1.11 μg/L ( 1.12 + 1.11 ng/mL ) at baseline to 1.26 ± 1.22 μg/L ( 1.26 ± 1.22 ng/mL ) after 12 months of TRT , although changes were well within guidelines ( < 1.4 μg/L/year increase ) . Significant improvements were seen in sexual function and mood/depression at 3 months and in metabolic parameters at 12 months . Conclusion : Testosterone deficiency symptoms improved with TRT use in men ; sexual function and mood/depression improvements were seen before metabolic improvements . Prostate-specific antigen levels increased , although increases were within guideline -determined safety limits Testosterone replacement therapy ( TRT ) has been investigated in older men as a preventative treatment against Alzheimer 's disease and dementia . However , previous studies have been contradictory . We assessed TRT physiological effects in 44 older men ( aged 61 ± 7.7 years ) with subjective memory complaints using a double blind , r and omized , crossover , placebo-controlled study . Participants were r and omized into 2 groups , one group received transdermal testosterone ( 50 mg ) daily for 24 weeks , followed by a 4 week wash-out period , then 24 weeks of placebo ; the other group received the reverse treatment . Blood evaluation revealed significant increases in total testosterone , free ( calculated ) testosterone , dihydrotestosterone , and a decrease in luteinizing hormone levels ( p<0.001 ) following TRT . Although there were significant increases in red blood cell counts , hemoglobin and prostate specific antigen levels  following TRT , they remained within normal ranges . No significant differences in plasma amyloid beta , estradiol , sex hormone binding globulin , insulin levels , body fat percentage , or body mass index were detected . This is the first carefully controlled study that has investigated the influence of TRT in Indonesian men  on blood biomarkers linked to dementia risk . Our study suggests TRT is safe and well-tolerated in this Indonesian cohort , yet longitudinal studies with larger cohorts are needed to assess TRT further , and to establish whether TRT  reduces dementia risk OBJECTIVE Men with type 2 diabetes are known to have a high prevalence of testosterone deficiency . No long-term data are available regarding testosterone and mortality in men with type 2 diabetes or any effect of testosterone replacement therapy ( TRT ) . We report a 6-year follow-up study to examine the effect of baseline testosterone and TRT on all-cause mortality in men with type 2 diabetes and low testosterone . RESEARCH DESIGN AND METHODS A total of 581 men with type 2 diabetes who had testosterone levels performed between 2002 and 2005 were followed up for a mean period of 5.81.3 S.D. years . mortality rates were compared between total testosterone 10.4nmol/l ( 300ng/dl ; n=343 ) and testosterone 10.4nmol/l ( n=238 ) . the effect of TRT ( as per normal clinical practise : 85.9 % testosterone gel and 14.1 % intramuscular testosterone undecanoate ) was assessed retrospectively within the low testosterone group . RESULTS Mortality was increased in the low testosterone group ( 17.2 % ) compared with the normal testosterone group ( 9 % ; P=0.003 ) when controlled for covariates . In the Cox regression model , multivariate-adjusted hazard ratio ( HR ) for decreased survival was 2.02 ( P=0.009 , 95 % CI 1.2 - 3.4 ) . TRT ( mean duration 41.6±20.7 months ; n=64 ) was associated with a reduced mortality of 8.4 % compared with 19.2 % ( P=0.002 ) in the untreated group ( n=174 ) . The multivariate-adjusted HR for decreased survival in the untreated group was 2.3 ( 95 % CI 1.3 - 3.9 , P=0.004 ) . CONCLUSIONS Low testosterone levels predict an increase in all-cause mortality during long-term follow-up . Testosterone replacement may improve survival in hypogonadal men with type 2 diabetes PURPOSE Although there is no evidence that testosterone therapy increases the risk of prostate cancer , there is a paucity of long-term data . We determined whether the incidence of prostate cancer is increased in hypogonadal men receiving long-term testosterone therapy .  MATERIAL S AND METHODS In 3 parallel , prospect i ve , ongoing , cumulative registry studies 1,023 hypogonadal men received testosterone therapy .  Two study cohorts were treated by urologists ( since 2004 ) and 1 was treated at an academic and rology center ( since 1996 ) . Patients were treated when  total testosterone was 12.1 nmol/l or less ( 350 ng/dl ) and symptoms of hypogonadism were present . Maximum followup was 17 years ( 1996 to 2013 ) and median followup was 5 years . Mean baseline patient age in the urological setting s was 58 years and in the and rology setting it was 41 years . Patients received testosterone undecanoate injections in 12-week intervals . Pretreatment examination of the prostate and monitoring during treatment were performed . Prostate biopsies were performed according to EAU guidelines . RESULTS Numbers of positive and negative biopsies were assessed . The incidence of prostate cancer and post-prostatectomy outcomes was studied . A total of 11 patients were diagnosed with prostate cancer in the 2 urology setting s at proportions of 2.3 % and 1.5 % , respectively . The incidence per 10,000 patient-years was 54.4 and 30.7 , respectively . No prostate cancer was reported by the and rology center . Limitations are inherent in the registry design without a control group . CONCLUSIONS Testosterone therapy in hypogonadal men does not increase the risk of prostate cancer . If guidelines for testosterone therapy are properly applied , testosterone treatment is safe in hypogonadal men PURPOSE Benign prostatic hyperplasia and hypogonadism are common disorders in aging men . There is concern that and rogen replacement in older men may increase prostate size and symptoms of benign prostatic hyperplasia . We examined whether combining dutasteride , which inhibits testosterone to dihydrotestosterone conversion , with testosterone treatment in older hypogonadal men with benign prostatic hyperplasia reduces and rogenic stimulation of the prostate compared to testosterone alone . MATERIAL S AND METHODS We conducted a double-blind , placebo controlled trial of 53 men 51 to 82 years old with symptomatic benign prostatic hyperplasia , prostate volume 30 cc or greater and serum total testosterone less than 280 ng/dl ( less than 9.7 nmol/l ) . Subjects were r and omized to daily transdermal 1 % T gel plus oral placebo or dutasteride for 6 months . Testosterone dosing was adjusted to a serum testosterone of 500 to 1,000 ng/dl . The primary outcomes were prostate volume measured by magnetic resonance imaging , serum prostate specific antigen and and rogen levels . RESULTS A total of 46 subjects completed all procedures . Serum testosterone increased similarly into the mid-normal range in both groups . Serum dihydrotestosterone increased in the testosterone only but decreased in the testosterone plus dutasteride group . In the testosterone plus dutasteride  group prostate volume and prostate specific antigen ( mean ± SEM ) decreased 12 % ± 2.5 % and 35 % ± 5 % , respectively , compared to the testosterone only group in which prostate volume and prostate specific antigen increased 7.5 % ± 3.3 % and 19 % ± 7 % ( p = 0.03 and p = 0.008 ) , respectively , after 6 months of treatment . Prostate symptom scores improved in both groups . CONCLUSIONS Combined treatment with testosterone plus dutasteride reduces prostate volume and prostate specific antigen compared to testosterone only . Coadministration of a 5α-reductase inhibitor with testosterone appears to spare the prostate from and rogenic stimulation during testosterone replacement in older , hypogonadal men with symptomatic benign prostatic hyperplasia OBJECTIVE To assess the efficacy and safety of testosterone replacement in males with late-onset hypogonadism compared to hypogonadal men without replacement , and controls , during six months . METHODS We assessed , through ADAM , AMS , IIEF-5 and SF-36 question naires , and through clinical and laboratory examinations , 62 patients divided into three groups : 17 hypogonadal males ( HR ) used intramuscular testosterone every three weeks ; 14 hypogonadal males ( HV ) and 31 non-hypogonadal males ( CV ) used  oral vitamins daily . RESULTS When compared to others , HR group obtained libido improvement assessed by ADAM 1 ( p = 0.004 ) , and borderline sexual potency improvement assessed by IIEF-5 ( p = 0.053 ) , besides a decrease in waist circumference after eight weeks ( p = 0.018 ) . The remaining parameters did not differ between the groups . PSA and hematocrit remained stable in those using testosterone . CONCLUSION Six months of testosterone replacement improved sexuality and body composition , with prostatic and hematological safety BACKGROUND The combination of chemotherapy with thoracic radiotherapy ( TRT ) compared with TRT alone has been shown to confer a survival advantage for good performance status patients with stage III non-small cell lung cancer . However , it is not known whether sequential or concurrent delivery of these therapies is the optimal combination strategy . METHODS A total of 610 patients were r and omly assigned to two concurrent regimens and one sequential chemotherapy and TRT regimen in a three-arm phase III trial . The sequential arm included cisplatin at 100 mg/m2 on days 1 and 29 and vinblastine at 5 mg/m2 per week for 5 weeks with 63 Gy TRT delivered as once-daily fractions beginning on day 50 . Arm 2 used the same chemotherapy regimen as arm 1 with 63 Gy TRT delivered as once-daily fractions beginning on day 1 [ corrected ] . Arm 3 used cisplatin at 50 mg/m2 on days 1 , 8 , 29 , and 36 with oral etoposide at 50 mg twice daily for 10 weeks on days 1 , 2 , 5 , and 6 with 69.6 Gy delivered as 1.2 Gy twice-daily fractions beginning on day 1 . The primary endpoint was overall survival , and secondary endpoints included tumor response and time to tumor progression . Kaplan-Meier analyses were used to assess survival , and toxic effects were examined using the Wilcoxon rank sum test . All statistical tests were two-sided . RESULTS Median survival times were 14.6 , 17.0 , and 15.6 months for arms 1 - 3 , respectively . Five-year survival was statistically significantly higher for patients treated with the concurrent regimen with once-daily TRT compared with the sequential treatment ( 5-year survival : sequential , arm 1 , 10 % [ 20 patients ] , 95 % confidence interval [ CI ] = 7 % to 15 % ; concurrent , arm 2 , 16 % [ 31 patients ] , 95 % CI = 11 % to 22 % , P = .046 ; concurrent , arm 3 , 13 % [ 22 patients ] , 95 % CI = 9 % to 18 % ) . With a median follow-up time of 11 years , the rates of acute grade 3 - 5 nonhematologic toxic effects were higher with concurrent than sequential therapy , but late toxic effects were similar . CONCLUSION Concurrent delivery of cisplatin-based chemotherapy with TRT confers a long-term survival benefit compared with the sequential delivery of these therapies INTRODUCTION The effect of parenteral testosterone replacement therapy on prostatic specific antigen ( PSA ) level or the development or growth of prostate cancer is unclear . AIM To assess the effect of testosterone replacement on PSA level in patients with hypogonadism associated with erectile dysfunction ( ED ) . METHODS A total of 187 male patients above the age of 45 with hypogonadism associated with ED were enrolled in this study . Patients were screened for ED by the erectile function domain of the International Index of Erectile Function ( IIEF ) . Patients underwent routine laboratory investigations , plus total testosterone , and PSA assessment . Replacement treatment with parenteral testosterone every 2 - 4 weeks for 1 year was instituted .  Total testosterone and PSA serum levels were assessed every 3 months during the treatment course . RESULTS Mean age + /- SD was 62.8 + /- 11.4 . Of the patients 87.7 % were sexually active . Of the patients 10.2 % had mild , 40.6 % had moderate and 49.2 % had severe ED . Of the study population , 62.5 % had ED complaints for less than 5 years and 84.5 % had gradual onset of their complaint . The majority of the patients ( 91.4 % ) had either progressive or stationary course while the minority reported regressive course and improvement of the condition . There was a significant increase of the post-treatment testosterone level in comparison to pretreatment level ( P < 0.05 ) . No significant increase in the post-treatment PSA level in comparison to pretreatment ( P > 0.05 ) . No significant difference between pre- and post-treatment categories of PSA level ( normal , borderline , high ) in relation to the severity of ED ( P > 0.05 ) . There was no significant association between PSA level and the duration of  testosterone replacement therapy in the study population ( P > 0.05 ) . CONCLUSION The current study demonstrated that the level of PSA was not significantly changed after 1 year of testosterone replacement therapy in patients with hypogonadism associated with ED The optimal schedule and regimen of chemotherapy ( CT ) in association with chemoradiation has not been established in stage III non-small-cell lung cancer ( NSCLC ) . We have compared three schedules of non-platinum-based CT plus either radiotherapy or chemoradiation . From May 2001 to June 2006 , 158 patients with unresectable stage III NSCLC were enrolled in a r and omized phase II trial with overall response rate ( ORR ) as the primary endpoint . The initial design included three arms : sequential CT followed by thoracic radiation ( TRT ) ; concurrent CT/TRT followed by consolidation CT ; and induction CT followed by concurrent CT/TRT . However , based on the preliminary results of the RTOG 9410 trial , the sequential arm was closed when 19 patients had been enrolled . All patients received two cycles of docetaxel 40 mg/m(2 ) days 1 and 8 plus gemcitabine 1200 mg/m(2 ) days 1 and 8 , as either induction or consolidation therapy . Concurrent CT/TRT consisted of docetaxel 20 mg/m(2 ) and carboplatin AUC 2 weekly plus 60 Gy TRT . No differences were found in ORR between the two arms ( 56 % and 57 % ) . Hematological toxicity was mild but significantly superior with consolidation CT ; the esophagitis rate was similar in both arms ( 16 % and 15 % ) . With a median follow-up of 57 months , no differences were found in median survival ( 13.07 and 13.8 months ) or 5-year survival ( 16.4 % and 22 % ) . This regimen can not be recommended as an alternative to platinum-based CT/TRT although it has an acceptable toxicity profile and encouraging long-term survival data ( Clinical Trials.gov NCT01652820 ) Seventy-two patients with Stages III and IV ( TNM , UICC , 1987 ) squamous-cell carcinoma of the oropharynx and hypopharynx ( oro-hypopharyngeal cancer ) were treated with external irradiation , or irradiation plus 13.56 MHz radiofrequency ( RF ) capacitive hyperthermia from 1989 to 1995 . This study compared initial response , histological effect and 5-year survival rate of  thermoradiotherapy ( TRT ) group with those of radiotherapy alone ( RT ) group . In the TRT group , 15 patients were treated definitively , and 18 patients preoperatively . In the RT group , 15 patients were treated definitively , and 24 patients preoperatively . With definitive irradiation , the complete response rate of the primary lesions was 73 % in the TRT group and 27 % in the RT group ( p = 0.009 ) and the complete response rate of the metastatic lymph nodes was 80 % in the TRT group and 27 % in the RT group ( p = 0.005 ) . With preoperative irradiation , the pathological CR ( No residual cancerous cells ) rate of the primary lesions was 56 % in the TRT group and 8 % in the RT group ( p = 0.01 ) , and the pathological CR rate of the lymph nodes was 72 % in the TRT group and 21 % in the RT group ( p = 0.001 ) . The 5-year survival rates with definitive irradiation were 47.6 % in the TRT group and 18.7 % in the RT group ( p = 0.025 ) . Thus TRT was more effective than RT for advanced oro-hypopharyngeal cancer The aim of the study is to present our results regarding the efficacy of TRT for  tinnitus relief in patients with clinical ly significant tinnitus compared to a group treated with vasoactive agents . In a nonr and omized prospect i ve study , 63 patients with disabling tinnitus were recruited . Greek translation of the Tinnitus H and icap Inventory ( THI ) and visual analogue scale ( VAS ) for annoyance caused by tinnitus when conducting four major activities of everyday life ( work , sleep , relaxation and concentration ) were examined in a 12-month period . The THI score was significantly improved in the TRT group , as well as mean VAS scores , in all measures . Comparison of the mean improvement of THI and VAS scores after treatment showed significant differences between the two groups , favoring TRT treatment . Our data suggest that TRT is an effective treatment . It reduces the level of annoyance induced by tinnitus and improves the ability of patients to work , sleep , relax or be concentrated The primary purpose of this investigation was to determine the impact of altering the set structure during an 8-week resistance training program on anthropometric , hormonal , and strength power characteristics . Thirty female volleyball players were recruited for participation and then r and omly assigned to 1 of 3 resistance training groups : ( i ) cluster sets ( CRT ; n = 10 ) , ( ii ) traditional sets ( TRT ; n = 10 ) , or ( iii ) control ( CON ; n = 10 ) . All athletes were evaluated for thigh and arm circumference , vertical jump , 20-m sprint , 4 × 9-m shuttle-run , 1-repetition maximum ( 1RM ) back squat , bench press , military press , and deadlift prior to and after an 8-week periodized training intervention . Blood sample s were taken before and after the 8-week training period to evaluate resting testosterone , cortisol , and insulin-like growth factor 1 responses to the training period . After 8 weeks of training the CRT group displayed a small but significant improvement in vertical jump ( CRT : effect size ( ES ) = 038 , 7.1 % ) performance when compared with the TRT group ( ES = 0.34 , 5.6 % ) . Both the CRT and TRT training interventions result ed in very large increases in the 1RM squat ( CRT : 8.4 % ± 1.2 % ; TRT : 7.3 % ± 0.6 % ) , bench press ( CRT : 8.3 % ± 2.0 % ; TRT : 8.7 % ± 1.9 % ) , military press ( CRT : 5.7 % ± 1.2 % ; TRT : 5.5 % ± 1.6 % ) , and deadlift ( CRT : 8.2 % ± 1.6 % ; TRT : 8.3 % ± 2.2 % ) . There were no significant differences in 20-m sprint or 4 × 9-m shuttle run times between the CRT , TRT , and CON groups . These results suggest that cluster sets allow for greater improvements in vertical jump performance and equal improvements in strength gains to those seen with traditional sets BACKGROUND The association between aging-related testosterone deficiency and late-onset hypogonadism in men remains a controversial concept . We sought evidence -based criteria for identifying late-onset hypogonadism in the general population on the basis of an association between symptoms and a low testosterone level . METHODS We surveyed a r and om population sample of 3369 men between the ages of 40 and 79 years at eight European centers . Using question naires , we collected data with regard to the subjects ' general , sexual , physical , and psychological health . Levels of total testosterone  were measured in morning blood sample s by mass spectrometry , and  free testosterone levels  were calculated with the use of Vermeulen 's formula . Data were r and omly split into separate training and validation sets for confirmatory analyses . RESULTS In the training set , symptoms of poor morning erection , low sexual desire , erectile dysfunction , inability to perform vigorous activity , depression , and fatigue were significantly related to the testosterone level . Increased probabilities of the three sexual symptoms and limited physical vigor were discernible with decreased testosterone levels ( ranges , 8.0 to 13.0 nmol per liter [ 2.3 to 3.7 ng per milliliter ] for total testosterone and 160 to 280 pmol per liter [ 46 to 81 pg per milliliter ] for free testosterone ) . However , only the three sexual symptoms had a syndromic association with decreased testosterone levels . An inverse relationship between an increasing number of sexual symptoms and a decreasing testosterone level was observed . These relationships were independently confirmed in the validation set , in which the strengths of the association between symptoms and low testosterone levels determined the minimum criteria necessary to identify late-onset hypogonadism . CONCLUSIONS Late-onset hypogonadism can be defined by the presence of at least three sexual symptoms associated with a total testosterone level of less than 11 nmol per liter ( 3.2 ng per milliliter ) and a free testosterone level of less than 220 pmol per liter ( 64 pg per milliliter ) PURPOSE The phase III PROCL AIM study evaluated overall survival ( OS ) of concurrent pemetrexed-cisplatin and thoracic radiation therapy ( TRT ) followed by consolidation pemetrexed , versus etoposide-cisplatin and TRT followed by nonpemetrexed doublet consolidation therapy . PATIENTS AND METHODS Patients with stage IIIA/B unresectable nonsquamous non-small-cell lung cancer r and omly received ( 1:1 ) pemetrexed 500 mg/m(2 ) and cisplatin 75 mg/m(2 ) intravenously every 3 weeks for three cycles plus concurrent TRT ( 60 to 66 Gy ) followed by pemetrexed consolidation every 3 weeks for four cycles ( arm A ) , or st and ard therapy with etoposide 50 mg/m(2 ) and cisplatin 50 mg/m(2 ) intravenously , every 4 weeks for two cycles plus concurrent TRT ( 60 to 66 Gy ) followed by two cycles of consolidation platinum-based doublet chemotherapy ( arm B ) . The primary objective was OS . The study was design ed as a superiority trial with 80 % power to detect an OS hazard ratio of 0.74 with a type 1 error of .05 . RESULTS Enrollment was stopped early because of futility . Five hundred ninety-eight patients were r and omly assigned ( 301 to arm A , 297 to arm B ) and 555 patients ( 283 in arm A , 272 in arm B ) were treated . Arm A was not superior to arm B in terms of OS ( hazard ratio , 0.98 ; 95 % CI , 0.79 to 1.20 ; median , 26.8 v 25.0 months ; P = .831 ) . Arm A had a significantly lower incidence of any drug-related grade 3 to 4 adverse events ( 64.0 % v 76.8 % ; P = .001 ) , including neutropenia ( 24.4 % v 44.5 % ; P < .001 ) , during the overall treatment period . CONCLUSION Pemetrexed-cisplatin combined with TRT followed by consolidation pemetrexed was not superior to st and ard chemoradiotherapy for stage III unresectable nonsquamous non-small-cell lung cancer Purpose : Patient-assessed health-related quality -of-life ( HRQOL ) scores , together with demographic and clinical factors in stage III non-small cell lung cancer ( NSCLC ) patients , are important prognostic factors for survival and may be helpful in determining thoracic radiotherapy ( TRT ) strategy . Methods : In a previously published r and omized trial , 301 patients were treated with different palliative radiotherapy schedules  , comparing short-term hypofractionated TRT ( arm A : 17 Gy/2 fractions [ n = 105 ] ) with more protracted TRT ( arm B : 42 Gy/15 fractions [ n = 104 ] ) ; arm C : 50 Gy/25 fractions [ n = 92 ] ) . Baseline HRQOL , demographic , and clinical data were available for all patients . All possible prognostic factors from univariate analysis were entered into the Cox multivariate regression model to identify variables of independent prognostic relevance . Results : Overall survival was similar , whereas long-term survival was restricted to higher-dose radiotherapy with 3-year survival rates of 1 , 8 , and 6 % ( p = 0.40 ) and 5-year survival rates of 0 , 4 , and 3 % ( p = 0.12 ) in arms A , B , and C , respectively . In univariate analysis , Karnofsky performance status , use of analgesics , and weight loss were highly significant non-HRQOL factors ( p < 0.001 ) , and physical function , appetite loss , cough , and pain were the most powerful HRQOL factors ( p < 0.001 ) . In multivariate analysis , appetite loss appeared as the most powerful independent prognostic indicator . In the group of patients treated with protracted fractionation ( n = 196 ) , the 2- , 3- , and 5-year survival rates in patients with no appetite loss ( n = 95 ) were 22 % ( 21/95 ) , 12 % ( 11/95 ) , and 8 % ( 8/95 ) compared with 3 % ( 3/101 ) , 1 % ( 1/101 ) , and 1 % ( 1/101 ) in patients with appetite loss present at baseline ( n = 101 ) . Conclusion : In addition to performance status and weight loss , patient-reported appetite loss should be assessed in stage III NSCLC patients before administrating TRT ; such assessment is a valuable tool for selecting patients to normofractionated or lower-dose hypofractionated palliative TRT PURPOSE The aim of this study was to analyze prognostic variables associated with long-term survival in patients with stage III non-small-cell lung cancer enrolled in a Spanish Lung Cancer Group ( SLCG ) phase II trial . PATIENTS AND METHODS Between May 2001 and June 2006 , 139 patients were enrolled . The initial design included 3 arms : sequential chemotherapy ( CT ) followed by st and ard thoracic radiation therapy ( TRT ; RT ) , concomitant CT/TRT followed by consolidation CT , or induction CT followed by CT/TRT . Based on the results of the Radiation Therapy Oncology Group 9410 trial , the sequential arm was closed . Induction or consolidation therapy comprised docetaxel plus gemcitabine . Concomitant treatment comprised docetaxel plus carboplatin plus 60 Gy TRT . A univariate and a Cox proportional hazard regression analysis of the following 11 variables were performed : age , sex , Eastern Cooperative Oncology Group performance status ( PS ) , histology , forced expiratory volume in 1 second , disease stage , nodal status , hemoglobin level , completion of RT treatment , completion of induction or consolidation plus concomitant treatment  , and RT delay . RESULTS With a median follow-up of 23 months for living patients , median survival was 13.07 months for the consolidation arm and 14.65 months for the induction arm . The 4-year survival rates were 25.37 % and 32.35 % , respectively . Only RT treatment completion ( P < .0001 ) and induction or consolidation plus concomitant treatment completion ( P < .0001 ) were associated with longer survival . CONCLUSION Based on this retrospective analysis of patients enrolled in the SLCG 0008 r and omized phase II study , age , sex , PS , and clinical parameters are not good predictors of overall survival ; however , completion of treatment is needed to achieve long-term results PURPOSE Cancer and Leukemia Group B conducted a r and omized phase II trial to investigate two novel chemotherapy regimens in combination with concurrent thoracic radiation therapy ( TRT ) . PATIENTS AND METHODS Patients with unresectable stage III non-small-cell lung cancer ( NSCLC ) were r and omly assigned to carboplatin ( area under the curve , 5 ) and pemetrexed ( 500 mg/m(2 ) ) every 21 days for four cycles and TRT ( 70 Gy ; arm A ) or the same treatment with cetuximab administered concurrent only with TRT ( arm B ) . Patients in both arms received up to four cycles of pemetrexed as consolidation therapy . The primary end point was the 18-month overall survival ( OS ) rate ; if the 18-month OS rate was ≥ 55 % , the regimen(s ) would be considered for further study . RESULTS Of the 101 eligible patients enrolled ( 48 in arm A and 53 in arm B ) , 60 % were male ; the median age was 66 years ( range , 32 to 81 years ) ; 44 % and 35 % had adenocarcinoma and squamous carcinoma , respectively ; and more patients enrolled onto arm A compared with arm B had a performance status of 0 ( 58 % v 34 % , respectively ; P = .04 ) . The 18-month OS rate was 58 % ( 95 % CI , 46 % to 74 % ) in arm A and 54 % ( 95 % CI , 42 % to 70 % ) in arm B. No significant difference in OS between patients with squamous and nonsquamous NSCLC was observed ( P = .667 ) . The toxicities observed were consistent with toxicities associated with concurrent chemoradiotherapy . CONCLUSION The combination of pemetrexed , carboplatin , and TRT met the prespecified criteria for further evaluation . This regimen should be studied further in patients with locally advanced unresectable nonsquamous NSCLC Two hundred fourteen eligible patients with previously untreated , localized Ewing 's sarcoma of bone were r and omized on IESS-II to receive Adriamycin ( ADR ; doxorubicin ; Adria Laboratories , Columbus , OH ) , cyclophosphamide , vincristine , and dactinomycin by either a high-dose intermittent method ( treatment [ trt ] 1 ) or a moderate-dose continuous method ( trt 2 ) similar to the four-drug arm of IESS-I. Patient characteristics ( sex , primary site , type of surgery ) were stratified at the time of registration ; these and other patient characteristics ( age , time from symptoms to diagnosis , race ) were distributed similarly between treatments . Surgical resection was encouraged , but not m and atory . Local radiation therapy was the same as for IESS-I. The median follow-up time is 5.6 years . The overall outcome was significantly better on trt 1 than on trt 2 . At 5 years , the estimated percentages of patients who were disease-free , relapse-free , and surviving were 68 % , 73 % , and 77 % for trt 1 and 48 % , 56 % , and 63 % for trt 2 ( P = .02 , .03 , and .05 , respectively ) . The major reason for treatment failure for both treatment groups was the development of metastatic disease . The lung was the most common site of metastases followed by bone sites . The combined incidence of severe or worse toxicity ( 67 % ) was comparable between the treatments ; however , severe or worse cardiovascular toxicity was significantly greater on trt 1 . Tne only treatment-associated deaths ( N = 3 ) were on trt 1 and were cardiac-related PURPOSE This phase II noncomparative r and omized trial was conducted to determine the optimal sequencing and integration of paclitaxel/carboplatin with st and ard daily thoracic radiation therapy ( TRT ) , in patients with locally advanced unresected stage III non-small-cell lung cancer ( NSCLC ) . Survival data were compared with historical st and ard sequential chemoradiotherapy data from the Radiation Therapy Oncology Group . PATIENTS AND METHODS Patients with unresected stages IIIA and IIIB NSCLC , with Karnofsky performance status > or = 70 % and weight loss < or = 10 % , received two cycles of induction paclitaxel ( 200 mg/m2)/carboplatin ( area under the plasma concentration time curve [ AUC ] = 6 ) followed by TRT 63.0 Gy ( arm 1 , sequential ) or two cycles of induction paclitaxel ( 200 mg/m2)/carboplatin ( AUC = 6 ) followed by weekly paclitaxel ( 45 mg/m2)/carboplatin ( AUC = 2 ) with concurrent TRT 63.0 Gy ( arm 2 , induction/concurrent ) , or weekly paclitaxel ( 45 mg/m2)/carboplatin ( AUC = 2)/TRT ( 63.0 Gy ) followed by two cycles of paclitaxel ( 200 mg/m2)/carboplatin ( AUC = 6 ; arm 3 , concurrent/consolidation ) . RESULTS With a median follow-up time of 39.6 months , median overall survival was 13.0 , 12.7 , and 16.3 months for arms 1 , 2 , and 3 , respectively . During induction chemotherapy , grade 3/4 granulocytopenia occurred in 32 % and 38 % of patients on study arms 1 and 2 , respectively . The most common locoregional grade 3/4 toxicity during and after TRT was esophagitis , which was more pronounced with the administration of concurrent chemoradiotherapy on study arms 2 and 3 ( 19 % and 28 % , respectively ) . CONCLUSION Concurrent weekly paclitaxel , carboplatin , and TRT followed by consolidation seems to be associated with the best outcome , although this schedule was associated with greater toxicity
Conclusions : This meta- analysis shows that regardless of the administration method , TRT is the short-term safety and does not promote prostate cancer development or progression but long-term data are warranted with justifiable end points
Background : Testosterone replacement therapy ( TRT ) is a widely accepted form of treatment worldwide for aging men with late-onset hypogonadism syndrome .
Urologists have been concerned about the possibility of TRT causing prostate cancer .
The aim of this study was to assess the relationship between TRT and prostate cancer .