Pop-up screening nested within routine community activities unmasks an addressed cardiovascular risk: A pilot study (Gippsland Healthy Heart Study).

OBJECTIVE: To evaluate the benefits of a pop-up health screening for cardiovascular risk factors (CVRF) in the Gippsland region, and to assess the acceptability of the screening and to determine whether such a process results in attendance at a general practitioner (GP). PARTICIPANTS: Overall, 454 participants over the age of 18 who were residents of the Gippsland region were enrolled. METHODS: This is a community-based, observational, prospective cohort study using pop-up screening sites at six retail locations or workplaces, where participants' blood pressure, body weight and lipid profile were measured. The primary outcome was to assess the proportion of participants with at least one unaddressed CVRF (hypertension [blood pressure >140/90 mmHg], overweight and obesity [body mass index >25 kg/m2 ] or hypercholesterolaemia [low-density lipoprotein cholesterol >2.5 mmol/L]). Email surveys were performed after 4 weeks of follow-up. RESULTS: Overall, 85.8% (95% confidence interval [CI], 82.1%-88.8%) of participants had at least one unaddressed CVRF. Among the 54 participants who responded to the email survey, 50 participants (92.6% [95% CI, 81.3%-97.6%]) found the screening approach acceptable, and 31 (57.4% [95% CI, 43.3%-70.5%]) considered a discussion with the GP. CONCLUSIONS: This study supported the feasibility and effectiveness of pop-up screening to detect CVRF in rural communities.

Effect of Evolocumab on Coronary Plaque Phenotype and Burden in Statin-Treated Patients Following Myocardial Infarction.

BACKGROUND: The proprotein convertase subtilisin kexin type-9 inhibitor evolocumab produced coronary atheroma regression in statin-treated patients. OBJECTIVES: The purpose of this study was to determine the effect of evolocumab on optical coherence tomography (OCT) measures of plaque composition. METHODS: Patients with a non-ST-segment elevation myocardial infarction were treated with monthly evolocumab 420 mg (n = 80) or placebo (n = 81) for 52 weeks. Patients underwent serial OCT and intravascular ultrasound imaging within a matched arterial segment of a nonculprit vessel. The primary analysis determined the change in the minimum fibrous cap thickness and maximum lipid arc throughout the imaged arterial segment. Additional analyses determined changes in OCT features in lipid-rich plaque regions and plaque burden. Safety and tolerability were evaluated. RESULTS: Among treated patients (age 60.5 ± 9.6 years; 28.6% women; low-density lipoprotein cholesterol [LDL-C], 141.3 ± 33.1 mg/dL), 135 had evaluable imaging at follow-up. The evolocumab group achieved lower LDL-C levels (28.1 vs 87.2 mg/dL; P < 0.001). The evolocumab group demonstrated a greater increase in minimum fibrous cap thickness (+42.7 vs +21.5 µm; P = 0.015) and decrease in maximum lipid arc (-57.5o vs. -31.4o; P = 0.04) and macrophage index (-3.17 vs -1.45 mm; P = 0.04) throughout the arterial segment. Similar benefits of evolocumab were observed in lipid-rich plaque regions. Greater regression of percent atheroma volume was observed with evolocumab compared with placebo (-2.29% ± 0.47% vs -0.61% ± 0.46%; P = 0.009). The groups did not differ regarding changes in microchannels or calcium. CONCLUSIONS: The combination of statin and evolocumab after a non-ST-segment elevation myocardial infarction produces favorable changes in coronary atherosclerosis consistent with stabilization and regression. This demonstrates a potential mechanism for the improved clinical outcomes observed achieving very low LDL-C levels following an acute coronary syndrome. (Imaging of Coronary Plaques in Participants Treated With Evolocumab; NCT03570697).

Assessing the Impact of Colchicine on Coronary Plaque Phenotype After Myocardial Infarction with Optical Coherence Tomography: Rationale and Design of the COCOMO-ACS Study.

INTRODUCTION: Recurrent event rates after myocardial infarction (MI) remain unacceptably high, in part because of the continued growth and destabilization of residual coronary atherosclerotic plaques, which may occur despite lipid-lowering therapy. Inflammation is an important contributor to this ongoing risk. Recent studies have shown that the broad-acting anti-inflammatory agent, colchicine, may reduce adverse cardiovascular events in patients post-MI, although the mechanistic basis for this remains unclear. Advances in endovascular arterial wall imaging have allowed detailed characterization of the burden and compositional phenotype of coronary plaque, along with its natural history and responsiveness to treatment. One such example has been the use of optical coherence tomography (OCT) to demonstrate the plaque-stabilizing effects of statins on both fibrous cap thickness and the size of lipid pools within plaque. METHODS: The Phase 2, multi-centre, double-blind colchicine for coronary plaque modification in acute coronary syndrome (COCOMO-ACS) study will evaluate the effect of colchicine 0.5 mg daily on coronary plaque features using serial OCT imaging in patients following MI. Recruitment for the trial has been completed with 64 participants with non-ST elevation MI randomized 1:1 to colchicine or placebo in addition to guideline recommended therapies, including high-intensity statins. The primary endpoint is the effect of colchicine on the minimal fibrous cap thickness of non-culprit plaque over an 18-month period. The COCOMO-ACS study will determine whether addition of colchicine 0.5 mg daily to standard post-MI treatment has incremental benefits on high-risk features of coronary artery plaques. If confirmed, this will provide new mechanistic insights into how colchicine may confer clinical benefits in patients with atherosclerotic cardiovascular disease. TRIAL REGISTRATION: ANZCTR trial registration number: ACTRN12618000809235. Date of trial registration: 11th of May 2018.

Assessing the impact of PCSK9 inhibition on coronary plaque phenotype with optical coherence tomography: rationale and design of the randomized, placebo-controlled HUYGENS study.

BACKGROUND: Technological advances in arterial wall imaging permit the opportunity to visualize coronary atherosclerotic plaque with sufficient resolution to characterize both its burden and compositional phenotype. These modalities have been used extensively in clinical trials to evaluate the impact of lipid lowering therapies on serial changes in disease burden. While the findings have unequivocally established that these interventions have the capacity to either slow disease progression or promote plaque regression, depending on the degree of lipid lowering achieved, their impact on plaque phenotype is less certain. More recently optical coherence tomography (OCT) has been employed with a number of studies demonstrating favorable effects on both fibrous cap thickness (FCT) and the size of lipid pools within plaque in response to statin treatment. METHODS: The phase 3, multi-center, double-blind HUYGENS study will assess the impact of incremental lipid lowering with the proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitor, evolocumab, on plaque features using serial OCT imaging, in statin-treated patients following an acute coronary syndrome (ACS). Subjects with non-ST-elevation ACS (n=150) will be randomized 1:1 into two groups to receive monthly injections of evolocumab 420 mg or placebo. RESULTS: The primary endpoint is the effect of evolocumab on coronary atherosclerotic plaques will be assessed by OCT at baseline and at week 50. CONCLUSIONS: The HUYGENS study will determine whether intensified lipid lowering therapy with evolocumab in addition to maximally tolerated statin therapy will have incremental benefits on high-risk features of coronary artery plaques. TRIAL REGISTRATION: This study was registered on Clinicaltrials.gov (NCT03570697).

Polygenic Risk Scores for Atherosclerotic Cardiovascular Disease in the Asia-Pacific Region.

Approximately one-half of the phenotypic susceptibility to atherosclerotic cardiovascular disease (ASCVD) has a genetic basis. Although individual allelic variants generally impart a small effect on risk for ASCVD, an emerging body of data has shown that the aggregation and weighting of many of these genetic variations into "scores" can further discriminate an individual's risk beyond traditional risk factors alone. Consistent with the theory of population genetics, such polygenic risk scores (PRS) appear to be ethnicity specific because their elements comprise single-nucleotide variants that are always ethnicity specific. The currently available PRS are derived predominantly from European ancestry and thus predictably perform less well among non-European participants, a fact that has implications for their use in the Asia-Pacific region. This paper describes the current state of knowledge of PRS, the available data that support their use in this region, and highlights the needs moving forward to safely and effectively implement them in clinical care in the Asia-Pacific region.

Statin intolerance: an updated, narrative review mainly focusing on muscle adverse effects.

INTRODUCTION: Statins have been established as the standard of care for dyslipidemia and preventing cardiovascular diseases while posing few safety concerns. However, misconceptions about statin intolerance lead to their underuse, indicating a need to improve the understanding of the safety of this treatment. AREAS COVERED: We searched PubMed and reviewed literatures related to statin intolerance published between February 2015 and February 2020. Important large-scale or landmark studies published before 2015 were also cited as key evidence. EXPERT OPINION: Optimal lowering of low-density lipoprotein cholesterol with statins substantially reduces the risk of cardiovascular events. Muscle adverse events (AEs) were the most frequently reported AEs by statin users in clinical practice, but they usually occurred at a similar rate with statins and placebo in randomized controlled trials and had a spurious causal relationship with statin treatment. We proposed a rigorous definition for identifying true statin intolerance and present the criteria for defining different forms of muscle AEs and an algorithm for their management. True statin intolerance is uncommon, and every effort should be made to exclude false statin intolerance and ensure optimal use of statins. For the management of statin intolerance, statin-based approaches should be prioritized over non-statin approaches.

Tackling cardiometabolic risk in the Asia Pacific region.

With the global spread of abdominal obesity, cardiovascular disease continues to spread to all countries of the world. Given the large population, the challenges presented by cardiometabolic risk in the Asia Pacific region are considerable. In addition to the clinical consequences of cardiovascular disease, in terms of its morbidity and mortality, the diversity of the Asia Pacific region brings heterogeneity in approaches to prevention, diagnosis and treatment of cardiometabolic risk. In this manuscript, we will review the current state of knowledge of cardiometabolic risk in Asia Pacific and highlight the needs moving forward to tackle this public health challenge.

Cytokinesis Block Micronucleus Cytome (CBMN Cyt) Assay Biomarkers and Their Association With Radiation Sensitivity Phenotype in Prostate Cancer Cases and DNA Repair Gene hOGG1 (C1245G) Polymorphism.

Prostate cancer (PC) is commonly diagnosed cancer in men but only a few risk factors, such as family history, ethnicity, and age have been established. Chromosomal instability is another possible risk factor but this has not been adequately explained previously. In this study, we tested the hypotheses that peripheral blood lymphocytes (PBL) of PC patients have (1) an abnormally high level of chromosomal instability; (2) that they are hypersensitive to ionizing radiation-induced DNA damage; and (3) that these phenotypes are affected by hOGG1 (C1245G) polymorphism. These experiments were performed using the cytokinesis-block micronucleus Cytome (CBMN cyt) assay in PC cases and controls. We found that spontaneous or radiation-induced (3G) micronucleus (MN) frequency is not significantly different between both groups. However, spontaneous frequency of nucleoplasmic bridges (NPBs) and radiation-induced nuclear buds (NBuds) were significantly higher in patients vs. controls (P < 0.0001; P = 0.0005, respectively). In addition, apoptosis and nuclear division index (NDI) was significantly higher in patients compared to controls after radiation treatment (P = 0.006; P = 0.0002, respectively). Furthermore carriage of at least one G allele of hOGG1 (C1245G) polymorphism was associated with a significantly increased odds ratio (OR) to have a base-line MN, NPB, or NBud frequency greater than medium level compared to homozygotes for C allele (OR:1.94, 1.77, 2.36, respectively, P = 0.02; 0.04, and 0.004, respectively). Our results support the hypotheses that those who develop PC have significantly higher level of genomic instability which is further increased in those who carry G allele of the hOGG1 (C1245G) polymorphism. Environ. Mol. Mutagen. 59:813-821, 2018. © 2018 Wiley Periodicals, Inc.

Effect of Serial Infusions of CER-001, a Pre-ß High-Density Lipoprotein Mimetic, on Coronary Atherosclerosis in Patients Following Acute Coronary Syndromes in the CER-001 Atherosclerosis Regression Acute Coronary Syndrome Trial: A Randomized Clinical Trial.

Importance: CER-001 is a negatively charged, engineered pre-ß high-density lipoprotein (HDL) mimetic containing apolipoprotein A-I and sphingomyelin. Preliminary studies demonstrated favorable effects of CER-001 on cholesterol efflux and vascular inflammation. A post hoc reanalysis of a previously completed study of intravenous infusion of CER-001, 3 mg/k, showed that the intravenous infusion in patients with a high coronary plaque burden promoted regression as assessed by intravascular ultrasonography. Objective: To determine the effect of infusing CER-001 on coronary atherosclerosis progression in statin-treated patients. Design, Setting, and Participants: A double-blind, randomized, multicenter trial evaluating the effect of 10 weekly intravenous infusions of CER-001, 3 mg/kg, (n = 135) or placebo (n = 137) in patients with an acute coronary syndrome (ACS) and baseline percent atheroma volume (PAV) greater than 30% in the proximal segment of an epicardial artery by intravascular ultrasonography. The study included 34 academic and community hospitals in Australia, Hungary, the Netherlands, and the United States in patients with ACS presenting for coronary angiography. Patients were enrolled from August 15, 2015, to November 19, 2016. Interventions: Participants were randomized to receive weekly CER-001, 3 mg/kg, or placebo for 10 weeks in addition to statins. Main Outcomes and Measures: The primary efficacy measure was the nominal change in PAV from baseline to day 78 measured by serial intravascular ultrasonography imaging. The secondary efficacy measures were nominal change in normalized total atheroma volume and percentage of patients demonstrating plaque regression. Safety and tolerability were also evaluated. Results: Among 293 patients (mean [SD] age, 59.8 [9.4] years; 217 men [79.8%] and 261 white race/ethnicity [96.0%]), 86 (29%) had statin prior use prior to the index ACS and 272 (92.8%) had evaluable imaging at follow-up. The placebo and CER-001 groups had similar posttreatment median levels of low-density lipoprotein cholesterol (74 mg/dL vs 79 mg/dL; P = .15) and high-density lipoprotein cholesterol (43 mg/dL vs 44 mg/dL; P = .66). The primary efficacy measure, PAV, decreased 0.41% with placebo (P = .005 compared with baseline), but not with CER-001 (-0.09%; P = .67 compared with baseline; between group differences, 0.32%; P = .15). Similar percentages of patients in the placebo and CER-001 groups demonstrated regression of PAV (57.7% vs 53.3%; P = .49). Infusions were well tolerated, with no differences in clinical and laboratory adverse events observed between treatment groups. Conclusions and Relevance: Infusion of CER-001 did not promote regression of coronary atherosclerosis in statin-treated patients with ACS and high plaque burden. Trial Registration: ClinicalTrials.gov Identifier: NCT2484378.

Regression of coronary atherosclerosis with infusions of the high-density lipoprotein mimetic CER-001 in patients with more extensive plaque burden.

BACKGROUND: CER-001 is an engineered pre-beta high-density lipoprotein (HDL) mimetic, which rapidly mobilizes cholesterol. Infusion of CER-001 3 mg/kg exhibited a potentially favorable effect on plaque burden in the CHI-SQUARE (Can HDL Infusions Significantly Quicken Atherosclerosis Regression) study. Since baseline atheroma burden has been shown as a determinant for the efficacy of HDL infusions, the degree of baseline atheroma burden might influence the effect of CER-001. METHODS: CHI-SQUARE compared the effect of 6 weekly infusions of CER-001 (3, 6 and 12 mg/kg) vs. placebo on coronary atherosclerosis in 369 patients with acute coronary syndrome (ACS) using serial intravascular ultrasound (IVUS). Baseline percent atheroma volume (B-PAV) cutoff associated with atheroma regression following CER-001 infusions was determined by receiver-operating characteristics curve analysis. 369 subjects were stratified according to the cutoff. The effect of CER-001 at different doses was compared to placebo in each group. RESULTS: A B-PAV ≥30% was the optimal cutoff associated with PAV regression following CER-001 infusions. CER-001 induced PAV regression in patients with B-PAV ≥30% but not in those with B-PAV <30% (-0.45%±2.65% vs. +0.34%±1.69%, P=0.01). Compared to placebo, the greatest PAV regression was observed with CER-001 3mg/kg in patients with B-PAV ≥30% (-0.96%±0.34% vs. -0.25%±0.31%, P=0.01), whereas there were no differences between placebo (+0.09%±0.36%) versus CER-001 in patients with B-PAV <30% (3 mg/kg; +0.41%±0.32%, P=0.39; 6 mg/kg; +0.27%±0.36%, P=0.76; 12 mg/kg; +0.32%±0.37%, P=0.97). CONCLUSIONS: Infusions of CER-001 3 mg/kg induced the greatest atheroma regression in ACS patients with higher B-PAV. These findings identify ACS patients with more extensive disease as most likely to benefit from HDL mimetic therapy.

Clinical Outcomes in Trials Evaluating Lipid-Lowering Drugs.

While statins have formed the cornerstone of strategies for cardiovascular prevention, the residual risk related to low-density lipoprotein cholesterol (LDL-C) and other lipoprotein factors provides a landscape for development of new therapies. However, a number of lipid-modifying therapies have failed to reduce cardiovascular event rates in contemporary clinical trials of statin-treated patients. The factors considered in outcome measure selection for clinical trials of novel lipid-lowering therapies are reviewed. Evaluation of lipid-modifying drugs in clinical trials spans a spectrum from their effects on conventional circulating lipid parameters through to their impact on atherosclerotic plaque and ultimately clinical outcomes. The design of these trials has an important impact on the result and ultimate interpretation of these studies.

Effect of serial infusions of reconstituted high-density lipoprotein (CER-001) on coronary atherosclerosis: rationale and design of the CARAT study.

BACKGROUND: High-density lipoprotein (HDL) is believed to have atheroprotective properties, but an effective HDL-based therapy remains elusive. Early studies have suggested that infusion of reconstituted HDL promotes reverse cholesterol transport and vascular reactivity. The CER-001 Atherosclerosis Regression Acute Coronary Syndrome Trial (CARAT) is investigating the impact of infusing an engineered pre-beta HDL mimetic containing sphingomyelin (SM) and dipalmitoyl phosphatidlyglycerol (CER-001) on coronary atheroma volume in patients with a recent acute coronary syndrome (ACS). METHODS: The CARAT is a phase 2, multicenter trial in which 292 patients with an ACS undergoing intracoronary ultrasonography and showing percent atheroma volume (PAV) greater than 30% are randomly assigned to treatment with ten infusions of CER-001 3 mg/kg or matching placebo, administered at weekly intervals. Intracoronary ultrasonography is repeated at the end of the treatment period. RESULTS: The primary endpoint is the nominal change in PAV. Safety and tolerability will also be evaluated. CONCLUSIONS: CARAT will establish whether serial 3 mg/kg infusions of an engineered pre-beta HDL mimetic containing SM and dipalmitoyl phosphatidlyglycerol (CER-001) will regress atherosclerotic plaque in patients with a recent ACS.

Predictors of radiation-induced gastrointestinal morbidity: A prospective, longitudinal study following radiotherapy for carcinoma of the prostate.

Background Chronic gastrointestinal (GI) morbidity occurs in ≥50% of patients after external beam radiotherapy (EBRT) for carcinoma of prostate (CaP). This prospective, longitudinal study examines which baseline measurements of: 1) homocysteine and micronutrients in plasma; 2) chromosome damage/misrepair biomarkers; and 3) anal and rectal dose volume metrics predict GI morbidity after EBRT. Patients and methods In total, 106 patients with CaP had evaluations of GI symptoms (modified LENT-SOMA questionnaires) before EBRT and at one month, one, two and three years after its completion. Other variables measured before EBRT were: 1) plasma concentrations of homocysteine and micronutrients including caroteinoids and selenium; 2) chromosome damage/DNA misrepair (micronuclei/nucleoplasmic bridge) indices; and 3) mean anal and rectal wall doses and volumes of anal and rectal walls receiving ≥40 Gy and ≥60 Gy. Univariate and multivariate analyzes examined the relationships among: 1) plasma levels of homocysteine and micronutrients; 2) indices of chromosome damage/DNA misrepair; and 3) mean anal and rectal wall doses and volumes of anal and rectal walls receiving ≥40 Gy and ≥60 Gy and total GI symptom scores from one month to three years after EBRT. Results Increased frequency and urgency of defecation, rectal mucous discharge and bleeding after EBRT resulted in sustained rises in total GI symptom scores above baseline at three years. On univariate analysis, total GI symptom scores were significantly associated with: 1) plasma selenium and α tocopherol; 2) micronuclei indices of DNA damage; 3) mean anal and rectal wall doses; and 4) volumes of anal and rectal wall receiving ≥40 Gy and ≥60 Gy (p = 0.08-<0.001). On multivariate analysis, only volume of anal wall receiving ≥40 Gy was significant for increased GI symptoms after EBRT (p < 0.001). Conclusion The volume of anal wall receiving ≥40 Gy predicts chronic GI morbidity after EBRT for CaP.

Pathophysiology and natural history of anorectal sequelae following radiation therapy for carcinoma of the prostate.

PURPOSE: To characterize the prevalence, pathophysiology, and natural history of chronic radiation proctitis 5 years following radiation therapy (RT) for localized carcinoma of the prostate. METHODS AND MATERIALS: Studies were performed in 34 patients (median age 68 years; range 54-79) previously randomly assigned to either 64 Gy in 32 fractions over 6.4 weeks or 55 Gy in 20 fractions over 4 weeks RT schedule using 2- and later 3-dimensional treatment technique for localized prostate carcinoma. Each patient underwent evaluations of (1) gastrointestinal (GI) symptoms (Modified Late Effects in Normal Tissues Subjective, Objective, Management and Analytic scales including effect on activities of daily living [ADLs]); (2) anorectal motor and sensory function (manometry and graded balloon distension); and (3) anal sphincteric morphology (endoanal ultrasound) before RT, at 1 month, and annually for 5 years after its completion. RESULTS: Total GI symptom scores increased after RT and remained above baseline levels at 5 years and were associated with reductions in (1) basal anal pressures, (2) responses to squeeze and increased intra-abdominal pressure, (3) rectal compliance and (4) rectal volumes of sensory perception. Anal sphincter morphology was unchanged. At 5 years, 44% and 21% of patients reported urgency of defecation and rectal bleeding, respectively, and 48% impairment of ADLs. GI symptom scores and parameters of anorectal function and anal sphincter morphology did not differ between the 2 RT schedules or treatment techniques. CONCLUSIONS: Five years after RT for prostate carcinoma, anorectal symptoms continue to have a significant impact on ADLs of almost 50% of patients. These symptoms are associated with anorectal dysfunction independent of the RT schedules or treatment techniques reported here.

Hypofractionated versus conventionally fractionated radiotherapy for prostate carcinoma: final results of phase III randomized trial.

PURPOSE: To evaluate the long-term efficacy and toxicity of a hypofractionated (55 Gy in 20 fractions within 4 weeks) vs. a conventionally fractionated (64 Gy in 32 fractions within 6.5 weeks) dose schedule for radiotherapy (RT) for localized carcinoma of the prostate. METHODS AND MATERIALS: A total of 217 patients were randomized to either the hypofractionated (n=108) or the conventional (n=109) dose schedule. Most patients (n=156) underwent RT planning and RT using a two-dimensional computed tomography method. Efficacy using the clinical, radiologic, and prostate-specific antigen data in each patient was evaluated before RT and at predetermined intervals after RT until death. Gastrointestinal and genitourinary toxicity using the modified Late Effect in Normal Tissue-Subjective Objective Management Analytic (LENT-SOMA) scales was also evaluated before and at intervals after RT to 60 months. RESULTS: The whole group has now been followed for a median of 90 months (range, 3-138). Of the 217 patients, 85 developed biochemical relapse (nadir prostate-specific antigen level+2 µg/L), 36 in the hypofractionated and 49 in the conventional group. The biochemical relapse-free, but not overall, survival at 90 months was significantly better with the hypofractionated (53%) than with the conventional (34%) schedule. Gastrointestinal and genitourinary toxicity persisted 60 months after RT and did not differ between the two dose schedules. Multivariate analyses revealed that the conventional schedule was of independent prognostic significance, not only for biochemical failure, but also for an increased risk of worse genitourinary symptoms at 4 years. CONCLUSIONS: A therapeutic advantage of the hypofractionated compared with the conventional dose schedule for RT of prostate cancer was evident at 90 months in the present study.

Hypofractionated versus conventionally fractionated radiation therapy for prostate carcinoma: updated results of a phase III randomized trial.

PURPOSE: The aim of this study was to compare the toxicity and efficacy of radiation therapy (RT) for localized carcinoma of the prostate, using a hypofractionated (55 Gy/20 fractions/4 weeks) vs. a conventionally fractionated (64 Gy/32 fractions/6.5 weeks) dose schedule. METHODS AND MATERIALS: A total of 217 patients were randomized to either the hypofractionated (108 patients) or the conventional (109 patients) dose schedule, with planning with two-dimensional (2D) CT scan planning methodology in the majority of cases. All patients were followed for a median of 48 (6-108) months. Gastrointestinal (GI) and genitourinary (GU) toxicity was evaluated before RT and after its completion using modified late effects of normal tissue-subjective, objective, management, analytic (LENT-SOMA) scales and the European Organization for Research and Treatment of Cancer sexual function questionnaire. Efficacy of RT based on clinical, radiologic, and prostate-specific antigen data were also evaluated at baseline and after RT. RESULTS: Gastrointestinal and GU toxicity persisted 5 years after RT and did not differ between the two dose schedules other than in regard to urgency of defecation. However, 1-month GI toxicity was not only worse in patients with the hypofractionated RT schedule but also adversely affected daily activities. Nadir prostate-specific antigen values occurred at a median of 18.0 (3.0-54.0) months after RT. A total of 76 biochemical relapses, with or without clinical relapses, have occurred since; of these, 37 were in the hypofractionated and 39 in the conventional schedule. The 5-year biochemical +/- clinical relapse-free and overall survival was 55.9% and 85.3% respectively for all patients, and did not differ between the two schedules. CONCLUSIONS: Radiation therapy for prostate carcinoma causes persistent GI toxicity that is largely independent of the two dose schedules. The hypofractionated schedule is equivalent in efficacy to the conventional schedule.