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Use of Cardiac Imaging to Evaluate Cardiac Function and Pulmonary Hemodynamics in Patients with Heart Failure

Purpose of Review: Noninvasive hemodynamic assessments in patients with heart failure (HF) are essential for appropriate diagnosis and establishment of the best treatment strategies. Recently, the impact of pulmonary circulation and right ventricular function on prognosis in HF patients has drawn increasing attention. In this article, we explore the usefulness of cardiac imaging for hemodynamic assessments, mainly focusing on echocardiographic evaluation. Recent Findings: The reliability of Doppler echocardiography as a noninvasive alternative to Swan-Ganz catheterization has been well investigated with higher than 80% accuracy for estimating pulmonary artery pressure. Strain measurement and three-dimensional echocardiography are useful for evaluating right ventricular function together with pulmonary circulation. The accuracy of analyzing left and right ventricular functions by cardiac computed tomography and cardiac magnetic resonate imaging has also been established. These modalities can provide myocardial tissue information and allow calculation of the extracellular volume fraction as well. Summary: According to the rapid improvement of technologies, cardiac imaging has become an essential tool for hemodynamic evaluation in HF management.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Sex affects myocardial blood flow and fatty acid substrate metabolism in humans with nonischemic heart failure

Background: In animal models of heart failure (HF), myocardial metabolism shifts from high-energy fatty acid (FA) metabolism toward glucose. However, FA (vs glucose) metabolism generates more ATP/mole; thus, FA metabolism may be especially advantageous in HF. Sex modulates myocardial blood flow (MBF) and substrate metabolism in normal humans. Whether sex affects MBF and metabolism in patients with HF is unknown. Methods and Results: We studied 19 well-matched men and women with nonischemic HF (EF ≤ 35%). MBF and myocardial substrate metabolism were quantified using positron emission tomography. Women had higher MBF (mL/g/minute), FA uptake (mL/g/minute), and FA utilization (nmol/g/minute) (P < 0.005, P < 0.005, P < 0.05, respectively) and trended toward having higher FA oxidation than men (P = 0.09). These findings were independent of age, obesity, and insulin resistance. There were no sex-related differences in fasting myocardial glucose uptake or metabolism. Higher MBF was related to improved event-free survival (HR 0.31, P = 0.02). Conclusions: In nonischemic HF, women have higher MBF and FA uptake and metabolism than men, irrespective of age, obesity, or insulin resistance. Moreover, higher MBF portends a better prognosis. These sex-related differences should be taken into account in the development and targeting of novel agents aimed at modulating MBF and metabolism in HF.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Prediction of sudden cardiac death in patients with chronic heart failure by regional washout rate in cardiac MIBG SPECT imaging

Background: The sympathetic nervous system provides an important trigger for major arrhythmic events through regional heterogeneity of sympathetic activity, which could be evaluated by SPECT imaging as the regional MIBG washout rate (WR). There is little information available on the prognostic value of regional WR in SPECT imaging for the prediction of sudden cardiac death (SCD) in patients with chronic heart failure (CHF). Methods: We studied 73 CHF outpatients with LVEF < 40%. At study entry, the regional WR was measured in 17 segments on the polar map. We defined abnormal regional WR as both the regional WR range (maximum − minimum regional WR) and maximum regional WR > mean value + 2SD obtained in 15 normal controls. Results: During a mean follow-up of 7.5 ± 4.1 years, 15 of 73 patients had SCD. The abnormal regional WR and abnormal global WR on planar images were significantly and independently associated with SCD. Patients with both the abnormal regional WR and global WR had a significantly higher risk of SCD than those with none of these criteria. Conclusions: The analysis of regional MIBG WR on SPECT imaging provides additional prognostic value to global WR on planar images for SCD prediction in CHF patients.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Comparison of CZT SPECT and conventional SPECT for assessment of contractile function, mechanical synchrony and myocardial scar in patients with heart failure

Aim: The aim of this study was to compare CZT-SPECT (CZT SPECT) to conventional SPECT (C-SPECT) in the assessment of left ventricular myocardial scar, contractile function, and mechanical synchrony in patients with heart failure (HF). Methods: Fifty-nine patients with HF who were referred for myocardial perfusion/metabolism imaging were enrolled. All patients underwent resting {sup 99m}Tc-MIBI gated myocardial perfusion imaging using a CZT SPECT camera and a C-SPECT camera, respectively, and {sup 18}F-FDG PET myocardial metabolism imaging within three days. Summed rest score (SRS) and total perfusion defect (TPD) (as indices of perfusion abnormality), left ventricular (LV), end diastolic volume (EDV), end systolic volume (ESV), and ejection fraction (EF) (as indices of LV systolic function), and histogram band width (BW) and standard deviation (SD) (as indices of mechanical synchrony) were analyzed by automated software while the perfusion/metabolism patterns were analyzed visually. Results: There was a good correlation between CZT SPECT and C-SPECT for SRS and TPD. CZT SPECT tended to underestimate SRS and TPD compared to C-SPECT. CZT-SPECT and C-SPECT showed excellent agreement in assessing the perfusion/metabolism pattern though a small proportion of normal segments (6.6%) identified by CZT/PET exhibited mismatch pattern on C-SPECT/PET. CZT SPECT also showed excellent correlation with C-SPECT in measuring EDV, ESV, and EF. Finally, BW and SD measured by CZT SPECT correlated well with C-SPECT but CZT SPECT tended to overestimate BW and SD compared to C-SPECT. Conclusion: CZT SPECT provided comparable data to C-SPECT for measuring LV scar, function and synchrony at a considerable reduction in imaging time. CZT SPECT holds a promise for comprehensive evaluation of myocardial performance in patients with HF.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Effect of liraglutide on myocardial glucose uptake and blood flow in stable chronic heart failure patients: A double-blind, randomized, placebo-controlled LIVE sub-study

Background: The glucagon-like peptide-1 analog liraglutide increases heart rate and may be associated with more cardiac events in chronic heart failure (CHF) patients. We studied whether this could be ascribed to effects on myocardial glucose uptake (MGU), myocardial blood flow (MBF) and MBF reserve (MFR). Methods and Results: CHF patients with left ventricular ejection fraction ≤45% and without type 2 diabetes were randomized to liraglutide (N = 18) 1.8 mg once daily or placebo (N = 18) for 24 weeks in a double-blinded design. Changes in MGU during an oral glucose tolerance test (OGTT) and changes in MBF and MFR from baseline to follow-up were measured quantitatively by {sup 18}F-FDG and {sup 15}O-H{sub 2}O positron emission tomography. Compared with placebo, liraglutide reduced weight (P = 0.03), HbA1c (P = 0.03) and the 2-hour glucose value during the OGTT (P = 0.004). Despite this, changes in MGU (P = 0.98), MBF (P = 0.76) and MFR (P = 0.89) from baseline to follow-up did not differ between groups. Furthermore, there was no association between the level of insulin resistance at baseline and changes in MGU in patients treated with liraglutide. Conclusion: Liraglutide did not affect MGU, MBF, or MFR in non-diabetic CHF patients. Any potential increase in cardiac events in these patients seems not to involve changes in MGU, MBF, or MFR. Trial Registration: Trial registry: http://www.ClinicalTrials.org . Identifier: NCT01472640. Url: https://clinicaltrials.gov/ct2/show/NCT01472640?term=NCT01472640&rank=1.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Relationship of left ventricular global longitudinal strain with cardiac autonomic denervation as assessed by {sup 123}I-mIBG scintigraphy in patients with heart failure with reduced ejection fraction submitted to cardiac resynchronization therapy

Background: Heart failure (HF) is associated with cardiac autonomic denervation (AD), which can be non-invasively assessed by {sup 123}I-metaiodobenzylguanidine ({sup 123}I-mIBG) scintigraphy and has prognostic implications. We aimed to study the relationship between myocardial contractility assessed by global longitudinal strain (GLS) and AD assessed by {sup 123}I-mIBG scintigraphy in advanced HF. Methods/Results: BETTER-HF is a prospective randomized clinical trial including HF patients (pts) submitted to cardiac resynchronization therapy (CRT) who are submitted to a clinical, echocardiographic, and scintigraphic assessment before and 6 months after CRT. 81 pts were included. An echocardiographic response (absolute increase in left ventricular ejection fraction ≥ 10%) was observed in 73.7% of pts. A higher baseline late heart-to-mediastinum ratio (HMR) was associated with a better echocardiographic response. There was a significant association between late HMR and GLS at baseline and 6 months. At baseline, GLS had an AUC of 0.715 for discrimination for a late HMR < 1.6. A GLS cut-off of − 9% maximized the likelihood of correctly classifying a pt as having severe AD (HMR < 1.6). Conclusion: Myocardial contractility as assessed by GLS is moderately correlated with AD as assessed by {sup 123}I-mIBG scintigraphy and has a good discrimination for the identification of severe cardiac denervation. GLS may allow for a more readily accessible estimation of the degree of AD in advanced HF pts.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Role of cardiac {sup 123}I-mIBG imaging in predicting arrhythmic events in stable chronic heart failure patients with an ICD

Background: Despite therapeutic improvement, the prognosis of chronic heart failure (CHF) remains unfavorable partly due to arrhythmia and sudden cardiac death (SCD). This prospective study evaluated myocardial {sup 123}I-meta-iodobenzylguanidine ({sup 123}I-mIBG) scintigraphy as a predictor of arrhythmic events (AE) in CHF patients. Methods: 170 CHF patients referred for implantable cardioverter-defibrillator (ICD) implantation for both primary and secondary prevention were enrolled. All patients underwent planar and SPECT imaging. Early and late heart-to-mediastinum (H/M) ratio, {sup 123}I-mIBG washout (WO), early and late summed SPECT scores were calculated The primary endpoint was an AE: sustained ventricular tachycardia, resuscitated cardiac arrest, appropriate ICD therapy or SCD. The secondary endpoint was appropriate ICD therapy. Results: During a median follow-up of 23.3 months, 69 patients experienced an AE. Early summed score (ESS) was the only independent predictor of AE [HR 1.023 (1.003-1.043)]. Focussing on only patients with an ICD for primary prevention, ESS was the only independent predictor of AE [HR 1.028 (1.007-1.050)]. {sup 123}I-mIBG-derived parameters failed to be independent predictors of appropriate ICD therapy. However there was a “bell-shaped” relation between {sup 123}I-mIBG scintigraphy-derived parameters and AE and appropriate ICD therapy, i.e., those with intermediate {sup 123}I-mIBG abnormalities tended to be at higher risk of events. Conclusion: Although SPECT {sup 123}I-mIBG scintigraphy was associated with AE in CHF patients with ICD implantation for primary and secondary prevention, no association was found between {sup 123}I-mIBG scintigraphy-derived parameters and appropriate ICD therapy.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Dynamic deformation and failure of ultrafine-grained titanium

Dynamic deformation and shear localization of ultrafine-grained (~120 nm) pure titanium are examined. The strain hardening can be considered as having two regimes: below and above a strain ~0.04; at this point there is a drastic decrease in the slope. The strain-rate sensitivity of ultrafine-grained titanium is found to be approximately the same as its coarse grained counterpart. Based on experimentally determined parameters, the Zerilli-Armstrong equation is modified to describe the mechanical response of the ultrafine-grained titanium over the strain rate range 10 -5 to 10 3 s -1 . Adiabatic shear banding is examined in a forced shear configuration where large strain is imposed in a narrow region. The microstructure inside the adiabatic shear band consists of a mixture of elongated grains and equiaxed nanograins (~40 nm) that are significantly smaller than the initial grains (~120 nm). The formation of equiaxed nanograins is modeled through a mechanism of rotational dynamic recrystallization. This further reduction in grain size from the one generated by ECAP is interpreted in terms of the Zener-Hollomon parameter for quasistatic and dynamic deformation. The adiabatic shear band eventually fractures by a combination of brittle and ductile failure.

36 MATERIALS SCIENCE↗

Farnesoid-X-receptor expression in monocrotaline-induced pulmonary arterial hypertension and right heart failure

Objective: The farnesoid-X-receptor (FXR) is a metabolic nuclear receptor superfamily member that is highly expressed in enterohepatic tissue and is also expressed in the cardiovascular system. Multiple nuclear receptors, including FXR, play a pivotal role in cardiovascular disease (CVD). Pulmonary arterial hypertension (PAH) is an untreatable cardiovascular system disease that leads to right heart failure (RHF). However, the potential physiological/pathological roles of FXR in PAH and RHF are unknown. We therefore compared FXR expression in the cardiovascular system in PAH, RHF and a control. Methods and results: Hemodynamic parameters and morphology were assessed in blank solution-exposed control, monocrotaline (MCT)-exposed PAH (4 weeks) and RHF (7 weeks) Sprague–Dawley rats. Real-time reverse transcription polymerase chain reaction (real-time RT-PCR), Western blot (WB), immunohistochemistry (IHC) analysis and immunofluorescence (IF) analysis were performed to assess FXR levels in the lung and heart tissues of MCT-induced PAH and RHF rats. In normal rats, low FXR levels were detected in the heart, and nearly no FXR was expressed in rat lungs. However, FXR expression was significantly elevated in PAH and RHF rat lungs but reduced in PAH and RHF rat right ventricular (RV) tissues. FXR expression was reduced only in RHF rat left ventricular (LV) tissues. Conclusions: The differential expression of FXR in MCT-induced PAH lungs and heart tissues in parallel with PAH pathophysiological processes suggests that FXR contributes to PAH. - Highlights: • FXR was expressed in rat lung and heart tissues. • FXR expression increased sharply in the lung tissues of PAH and RHF rats. • FXR expression was reduced in PAH and RHF rat RV tissue. • FXR expression was unaltered in PAH LV but reduced in RHF rat LV tissue. • FXR expression was prominent in the neovascularization region.

60 APPLIED LIFE SCIENCES↗

Effect of electrical field on TSA failure of cement-based materials

The impact of electrical field on the sulfate attack of cement-based materials at low temperatures was studied to rapidly detect Thaumasite Sulfate Attack (TSA) in the laboratory and in future engineering. Sulfate attack of cement paste with 30 wt% replacement of CaCO{sub 3} powder soaked in Na{sub 2}SO{sub 4} solution, MgSO{sub 4} solution, or CaSO{sub 4} solution was measured under the condition of 5 ± 2 °C when an electrical field was applied. Appearance changes and compressive strength of the samples were tested to evaluate the corrosion degree. Scanning Electron Microscopy (SEM), X-ray Diffraction (XRD), Fourier Transform Infrared Spectroscopy (FTIR) and Raman Spectroscopic measurements were applied to study the microstructure of the corrosion product. The test results indicate that sample damage was obvious, compression strength declined rapidly, and ettringite and/or thaumasite were found in the corrosion product after applying the electrical field for 90 days. A muddy product with TSA characteristics was formed, and thaumasite composition was found in the corrosion product after applying the electrical field for 120 days when MgSO{sub 4} solution was used as the corrosion medium. It is confirmed that an electrical field can accelerate TSA failure in cement-based materials.

36 MATERIALS SCIENCE↗

Hydrate failure in ITZ governs concrete strength: A micro-to-macro validated engineering mechanics model

Ever since the early days of Féret (1892) and Abrams (1919), concrete research has targeted at relating concrete composition to uniaxial compressive strength. While these activities were mainly characterized by empirical fitting functions, we here take a more fundamental approach based on continuum micromechanics. The loading applied at the concrete level, is first concentrated (''downscaled'') to maximum stresses related to cement paste volumes which are directly adjacent to the aggregates, i.e. to the interfacial transition zones (ITZ). These maximum stresses are further ''downscaled'' to the micron-sized hydrates, in terms of higher-order stress averages. The latter enter a Drucker-Prager failure criterion with material constants derived from nanoindentation tests. The model is successfully validated across the hydrate-to-concrete scales. Strength magnitude is governed by ITZ stress concentrations, and the water-to-cement ratio is its dominant mixture design parameter.

36 MATERIALS SCIENCE↗

Critical review of the Mogi failure criterion based on true-triaxial laboratory data analysis and theoretical considerations

The influence of the intermediate principal stress, σ 2 , is disregarded when rock strength is analyzed using the Mohr-Coulomb or Hoek-Brown criteria. Several polyaxial strength criteria have been proposed to account for the influence of σ 2 . One of the methods that received considerable attention is the Mogi criterion. The criterion modifies the Nadai or Drucker-Prager approaches by exchanging the normal octahedral stress with what is introduced as the mean effective stress, σ m,2 . This change is based on experimental evidence that the influence of the intermediate principal stress on strength is less pronounced than the influence of the minimum principal stress. However, the Mogi criterion was derived somewhat empirically and consequently it is essential to analyze its potential theoretical deficiencies. In the current note, we analyzed the Mogi failure criterion, describing its characteristics in both τ oct –σ m,2 and σ 1 -σ 2 spaces. We investigated the relation between Mohr-Coulomb and Mogi criteria, which marks the basis for the commonly used Mogi-Coulomb approach. Here, we compared the performance of the Mogi criterion against available polyaxial strength data using three fitting approaches: Mogi-Coulomb based on triaxial compression results only, linear Mogi based on all polyaxial strength results, and power law Mogi also based on all data. The analysis reveals several serious deficiencies of the Mogi approach which all suggest that the Mogi criterion cannot properly represent the σ 2 dependence of rock strength in many cases.

58 GEOSCIENCES↗

Influence of Androgen Deprivation Therapy on All-Cause Mortality in Men With High-Risk Prostate Cancer and a History of Congestive Heart Failure or Myocardial Infarction

Purpose: It is unknown whether the excess risk of all-cause mortality (ACM) observed when androgen deprivation therapy (ADT) is added to radiation for men with prostate cancer and a history of congestive heart failure (CHF) or myocardial infarction (MI) also applies to those with high-risk disease. Methods and Materials: Of 14,594 men with cT1c-T3aN0M0 prostate cancer treated with brachytherapy-based radiation from 1991 through 2006, 1,378 (9.4%) with a history of CHF or MI comprised the study cohort. Of these, 22.6% received supplemental external beam radiation, and 42.9% received a median of 4 months of neoadjuvant ADT. Median age was 71.8 years. Median follow-up was 4.3 years. Cox multivariable analysis tested for an association between ADT use and ACM within risk groups, after adjusting for treatment factors, prognostic factors, and propensity score for ADT. Results: ADT was associated with significantly increased ACM (adjusted hazard ratio [AHR] = 1.76; 95% confidence interval [CI], 1.32-2.34; p = 0.0001), with 5-year estimates of 22.71% with ADT and 11.62% without ADT. The impact of ADT on ACM by risk group was as follows: high-risk AHR = 2.57; 95% CI, 1.17-5.67; p = 0.019; intermediate-risk AHR = 1.75; 95% CI, 1.13-2.73; p = 0.012; low-risk AHR = 1.52; 95% CI, 0.96-2.43; p = 0.075). Conclusions: Among patients with a history of CHF or MI treated with brachytherapy-based radiation, ADT was associated with increased all-cause mortality, even for patients with high-risk disease. Although ADT has been shown in Phase III studies to improve overall survival in high-risk disease, the small subgroup of high-risk patients with a history of CHF or MI, who represented about 9% of the patients, may be harmed by ADT.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Adaptive Image-Guided Radiotherapy (IGRT) Eliminates the Risk of Biochemical Failure Caused by the Bias of Rectal Distension in Prostate Cancer Treatment Planning: Clinical Evidence

Purpose: Rectal distension has been shown to decrease the probability of biochemical control. Adaptive image-guided radiotherapy (IGRT) corrects for target position and volume variations, reducing the risk of biochemical failure while yielding acceptable rates of gastrointestinal (GI)/genitourinary (GU) toxicities. Methods and Materials: Between 1998 and 2006, 962 patients were treated with computed tomography (CT)-based offline adaptive IGRT. Patients were stratified into low (n = 400) vs. intermediate/high (n = 562) National Comprehensive Cancer Network (NCCN) risk groups. Target motion was assessed with daily CT during the first week. Electronic portal imaging device (EPID) was used to measure daily setup error. Patient-specific confidence-limited planning target volumes (cl-PTV) were then constructed, reducing the standard PTV and compensating for geometric variation of the target and setup errors. Rectal volume (RV), cross-sectional area (CSA), and rectal volume from the seminal vesicles to the inferior prostate (SVP) were assessed on the planning CT. The impact of these volumetric parameters on 5-year biochemical control (BC) and chronic Grades {>=}2 and 3 GU and GI toxicity were examined. Results: Median follow-up was 5.5 years. Median minimum dose covering cl-PTV was 75.6 Gy. Median values for RV, CSA, and SVP were 82.8 cm{sup 3}, 5.6 cm{sup 2}, and 53.3 cm{sup 3}, respectively. The 5-year BC was 89% for the entire group: 96% for low risk and 83% for intermediate/high risk (p < 0.001). No statistically significant differences in BC were seen with stratification by RV, CSA, and SVP in quartiles. Maximum chronic Grades {>=}2 and 3 GI toxicities were 21.2% and 2.9%, respectively. Respective values for GU toxicities were 15.5% and 4.3%. No differences in GI or GU toxicities were noted when patients were stratified by RV. Conclusions: Incorporation of adaptive IGRT reduces the risk of geometric miss and results in excellent biochemical control that is independent of rectal volume/distension while maintaining very low rates of chronic GI toxicity.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Locoregional Failure in Early-Stage Breast Cancer Patients Treated With Radical Mastectomy and Adjuvant Systemic Therapy: Which Patients Benefit From Postmastectomy Irradiation?

Purpose: To assess the locoregional failure in patients with Stage I-II breast cancer treated with radical mastectomy and to evaluate whether a subset of these patients might be at sufficiently high risk of locoregional recurrence (LRR) to benefit from postmastectomy irradiation (PMRT). Methods and Materials: Stage I-II breast cancer patients (n = 150) treated with radical mastectomy without adjuvant irradiation between 1999 and 2005 were analyzed. The pattern of LRR was reported. Kaplan-Meier analysis was used to calculate rates of LRR, and Cox proportional hazards methods were used to evaluate potential risk factors. Results: Median follow-up was 75 months. Mean patient age was 56 years. One-hundred forty-three (95%) patients received adjuvant systemic therapy: 85 (57%) hormonal therapy alone, 14 (9%) chemotherapy alone, and 44 (29%) both chemotherapy and hormonal therapy. Statistically significant factors associated with increased risk of LRR were premenopausal status (p = 0.004), estrogen receptor negative cancer (p = 0.02), pathologic grade 3 (p = 0.02), and lymphovascular invasion (p = 0.001). T and N stage were not associated with increased risk of regional recurrence. The 5-year LRR rate for patients with zero or one, two, three, and four risk factors was 1%, 10.3%, 24.2%, and 75%, respectively. Conclusions: A subset of patients with early-stage breast cancer is at high risk of LRR, and therefore PMRT might be beneficial.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Impact of Neoadjuvant Prostate-Specific Antigen Kinetics on Biochemical Failure and Prostate Cancer Mortality: Results From a Prospective Patient Database

Purpose: To confirm findings from an earlier report showing that neoadjuvant (NA) prostate-specific antigen (PSA) halving time (PSAHT) impacts biochemical failure (BF) rates, and to examine its association with prostate cancer-specific survival (PCSS), in a large prospective cohort of patients. Methods and Materials: A total of 502 patients were selected from a prospective database, who had localized prostate adenocarcinoma treated with 2-12 months of neoadjuvant androgen deprivation therapy (N-ADT) followed by external beam radiation therapy (EBRT) between 1994 and 2000, and had at least 2 NA PSA values. Seventy-four percent of patients had high-risk prostate cancer. Median initial PSA value, N-ADT duration, total ADT duration, and radiation therapy dose were 14 ng/mL, 6.9 months, 10.8 months, and 68 Gy, respectively. Results: At a median follow-up of 9.9 years, 210 patients have had a BF. Median PSAHT was 18 days. On univariate analysis, PSAHT was not shown to predict for BF (P=.69) or PCSS (P=.28). However, NA nadir PSA (nanPSA) and post-therapy nadir PSA (ptnPSA), when analyzed as continuous or categoric variables, predicted for BF (P<.001) and PCSS (P<.001). On multivariate analysis, nanPSA (P=.037) and ptnPSA (P<.001) continued to be significantly associated with BF. However, N-ADT duration lost significance (P=.67), and PSAHT remained a nonsignificant predictor (P=.97). For PCSS, multivariate analysis showed nanPSA (P=.049) and ptnPSA (P<.001) to be significant. Again PSAHT (P=.49) remained nonsignificant. Conclusions: In this large, prospective cohort of patients, NA PSA kinetics, expressed as PSAHT, did not predict BF or PCSS. However, nadir PSAs, in both the NA and post-therapy settings, were significant predictors of BF and PCSS. Optimization of therapy could potentially be based on early PSA response, with shorter durations of ADT for those predicted to do favorably, and intensification of therapy for those likely to have poorer outcomes.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Patterns of Failure in Advanced Stage Diffuse Large B-Cell Lymphoma Patients After Complete Response to R-CHOP Immunochemotherapy and the Emerging Role of Consolidative Radiation Therapy

Purpose: The role of consolidative radiation therapy (RT) after complete response (CR) to rituximab combined with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) for stage III-IV diffuse large B-cell lymphoma (DLBCL) patients is unclear. We aimed to evaluate our institutional experience when consolidative RT is delivered to initial presenting sites or bulky sites in these patients. Methods and Materials: We identified 211 histologically confirmed stage III-IV DLBCL patients who received R-CHOP from January 2000 to May 2012 at our institution. Patterns of failure for patients who achieved CR to R-CHOP were analyzed. Local control (LC), distant control (DC), progression-free survival (PFS), and overall survival (OS) were estimated using Kaplan-Meier method and compared between patients who received R-CHOP alone versus R-CHOP plus consolidative RT using the log–rank test. Multivariate analyses were also performed using Cox proportional hazards model. Results: Detailed treatment records were available for 163 patients. After a median 6 cycles of R-CHOP, 110 patients (67.5%) achieved CR and were entered for analysis. Fourteen patients (12.7%) received consolidative RT. After median follow-up of 32.9 months, 43.8% of patients who received R-CHOP alone failed at the initial sites with or without distant recurrence (DR), whereas isolated DR only occurred in 3.7% of these patients. Consolidative RT was associated with significantly improved LC (91.7% vs 48.8%), DC (92.9% vs 71.9%), PFS (85.1% vs 44.2%), and OS (92.3% vs 68.5%; all Ps<.0001) at 5 years compared with patients with R-CHOP alone. On multivariate analysis, consolidative RT and nonbulky disease were predictive of increased LC and PFS, whereas bone marrow involvement was associated with increased risk of DR and worse OS. Consolidative RT was also associated with marginal improved OS. Conclusions: Forty-four percent of patients with advanced stage DLBCL failed at initial presenting sites after achieving CR to R-CHOP. Incorporation of consolidative RT as part of upfront treatment in these patients was associated with improved LC, PFS, and a trend towards improved OS.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Brachytherapy Improves Biochemical Failure–Free Survival in Low- and Intermediate-Risk Prostate Cancer Compared With Conventionally Fractionated External Beam Radiation Therapy: A Propensity Score Matched Analysis

Purpose: To compare, in a retrospective study, biochemical failure-free survival (bFFS) and overall survival (OS) in low-risk and intermediate-risk prostate cancer patients who received brachytherapy (BT) (either low-dose-rate brachytherapy [LDR-BT] or high-dose-rate brachytherapy with external beam radiation therapy [HDR-BT+EBRT]) versus external beam radiation therapy (EBRT) alone. Methods and Materials: Patient data were obtained from the ProCaRS database, which contains 7974 prostate cancer patients treated with primary radiation therapy at four Canadian cancer institutions from 1994 to 2010. Propensity score matching was used to obtain the following 3 matched cohorts with balanced baseline prognostic factors: (1) low-risk LDR-BT versus EBRT; (2) intermediate-risk LDR-BT versus EBRT; and (3) intermediate-risk HDR-BT+EBRT versus EBRT. Kaplan-Meier survival analysis was performed to compare differences in bFFS (primary endpoint) and OS in the 3 matched groups. Results: Propensity score matching created acceptable balance in the baseline prognostic factors in all matches. Final matches included 2 1:1 matches in the intermediate-risk cohorts, LDR-BT versus EBRT (total n=254) and HDR-BT+EBRT versus EBRT (total n=388), and one 4:1 match in the low-risk cohort (LDR-BT:EBRT, total n=400). Median follow-up ranged from 2.7 to 7.3 years for the 3 matched cohorts. Kaplan-Meier survival analysis showed that all BT treatment options were associated with statistically significant improvements in bFFS when compared with EBRT in all cohorts (intermediate-risk EBRT vs LDR-BT hazard ratio [HR] 4.58, P=.001; intermediate-risk EBRT vs HDR-BT+EBRT HR 2.08, P=.007; low-risk EBRT vs LDR-BT HR 2.90, P=.004). No significant difference in OS was found in all comparisons (intermediate-risk EBRT vs LDR-BT HR 1.27, P=.687; intermediate-risk EBRT vs HDR-BT+EBRT HR 1.55, P=.470; low-risk LDR-BT vs EBRT HR 1.41, P=.500). Conclusions: Propensity score matched analysis showed that BT options led to statistically significant improvements in bFFS in low- and intermediate-risk prostate cancer patient populations.

62 RADIOLOGY AND NUCLEAR MEDICINE↗