Graft-Versus-Host-Disease and Health-Related Quality of Life in Young Long-term Survivors of Cancer and Allogeneic Hematopoietic Stem Cell Transplantation.

Purpose: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an established treatment predominantly for malignancies. Chronic graft-versus-host disease (cGVHD) is the leading long-term complication after allo-HSCT, but knowledge on cGVHD and health-related quality of life (HRQOL) in long-term survivors of allo-HSCT performed in childhood, adolescence, and young adulthood (CAYA) is scarce. Therefore, we aimed to (1) assess prevalence and risk factors of active cGVHD using the 2014 National Institutes of Health-Consensus criteria, (2) investigate associations between cGVHD severity, patient-reported symptom burden, and HRQOL, and (3) compare HRQOL of survivors to population norms. Methods: We conducted a nationwide cross-sectional study in long-term survivors of CAYA allo-HSCT combining clinical examinations and patient-reported outcome measures. Results: We included 103 survivors, 55 (53%) females, median age of 19.6 years [range 0.3-29.9] at HSCT, 16.8 years [6.0-32.0] from HSCT, and 77 (75%) with underlying malignancy. Overall, 32 (31%) survivors were diagnosed with active cGVHD. The risk of active cGVHD was increased with prior acute GVHD and reduced with in vivo T cell depletion. cGVHD severity was associated with increased symptom burden, but not with adverse HRQOL. Compared to Norwegian population norms, allo-HSCT survivors reported significantly lower HRQOL. Conclusion: These results indicate a high prevalence of cGVHD in long-term survivors of CAYA allo-HSCT. Although we did not find an association between cGVHD severity and HRQOL, survivors reported significantly poorer HRQOL compared to population norms. Knowledge on the long-term consequences of cGVHD will be important for optimizing treatment and long-term follow-up care after CAYA allo-HSCT.

Late-Onset, Noninfectious Pulmonary Complications following Allogeneic Hematopoietic Stem Cell Transplantation: A Nationwide Cohort Study of Long-Term Survivors.

BACKGROUND: Survivors of allogeneic hematopoietic stem cell transplantation (allo-HSCT) are at risk for pulmonary adverse events. Data on late-onset noninfectious pulmonary complications in long-term adult survivors of allo-HSCT are limited and incomplete. OBJECTIVES: This study aimed (1) to determine occurrence and degree of pulmonary sequelae in adult survivors of allo-HSCT and (2) to identify associations between pulmonary function, high-resolution CT (HRCT), and clinical characteristics. METHOD: In a nationwide, single-center cross-sectional study, 103 survivors (aged median [range] 35 [17-58] years, 53% females) were examined 17 (6-32) years after allo-HSCT and compared with healthy controls (n = 105). Methods included pulmonary function tests and HRCT. RESULTS: Chronic graft-versus-host disease was diagnosed in 33% of survivors, including 12% with bronchiolitis obliterans syndrome (BOS). Mean lung volumes (TLC, FVC, and FEV1) and gas diffusing capacity were >80% of predicted for the survivors as a group, but significantly lower than in healthy controls. Pathological HRCT findings were detected in 48% of the survivors (71% airways disease, 35% interstitial lung disease, and 24% apical subpleural interstitial thickening). Air trapping (%) on HRCT correlated with % predicted FEV1, p < 0.001. In a multiple logistic regression model, both BOS and pathological findings on HRCT were associated with chemotherapy prior to allo-HSCT, p < 0.05. CONCLUSIONS: Long-term allo-HSCT survivors had significantly lower pulmonary function than age- and gender-matched healthy controls and nearly half had pathological findings on HRCT. Longitudinal data will determine if pulmonary sequelae will remain stable or progress. We recommend lifelong monitoring of pulmonary function in allo-HSCT survivors. HRCT provides additional information, but is not suited for surveillance.

Image Quality Measured From Ultra-Low Dose Chest Computed Tomography Examination Protocols Using 6 Different Iterative Reconstructions From 4 Vendors, a Phantom Study.

PURPOSE: This study aimed to evaluate image quality of ultra-low dose chest computed tomography using 6 iterative reconstruction (IR) algorithms. METHOD: A lung phantom was scanned on 4 computed tomography scanners using fixed tube voltages and the lowest mAs available on each scanner, resulting in dose levels of 0.1 to 0.2 mGy (80 kVp) and 0.3 to 1 mGy (140 kVp) volume CT dose index (CTDIvol). Images were reconstructed with IR available on the scanners. Image noise, signal-to-noise ratios, contrast-to-noise ratios, uniformity, and noise power spectrum (NPS) were assessed for evaluation of image quality. RESULTS: Image quality parameters increased with increasing dose for all algorithms. At constant dose levels, model-based techniques improved the contrast-to-noise ratio of lesions more than the statistical algorithms. All algorithms tested at 0.1 mGy showed lower NPS peak frequencies compared with 0.39 mGy. In contrast to the statistical techniques, model-based algorithms showed lower NPS peak frequencies at the lowest doses, indicating a coarser and blotchier noise texture. CONCLUSION: This study shows the importance of evaluating IR when introduced clinically.

Semiautomated biventricular segmentation in three-dimensional echocardiography by coupled deformable surfaces.

With the advancement of three-dimensional (3-D) real-time echocardiography in recent years, automatic creation of patient specific geometric models is becoming feasible and important in clinical decision making. However, the vast majority of echocardiographic segmentation methods presented in the literature focus on the left ventricle (LV) endocardial border, leaving segmentation of the right ventricle (RV) a largely unexplored problem, despite the increasing recognition of the RV's role in cardiovascular disease. We present a method for coupled segmentation of the endo- and epicardial borders of both the LV and RV in 3-D ultrasound images. To solve the segmentation problem, we propose an extension of a successful state-estimation segmentation framework with a geometrical representation of coupled surfaces, as well as the introduction of myocardial incompressibility to regularize the segmentation. The method was validated against manual measurements and segmentations in images of 16 patients. Mean absolute distances of [Formula: see text], [Formula: see text], and [Formula: see text] between the proposed and reference segmentations were observed for the LV endocardium, RV endocardium, and LV epicardium surfaces, respectively. The method was computationally efficient, with a computation time of [Formula: see text].

Exercise capacity and peak oxygen consumption in asymptomatic patients with chronic aortic regurgitation.

BACKGROUND: In patients with chronic, hemodynamically significant aortic regurgitation (AR), a long period of left ventricular remodeling usually occurs prior to the development of symptoms or left ventricular dysfunction. The value of cardiopulmonary exercise testing in patients with asymptomatic AR is not established. MATERIAL AND METHODS: Sixty-six asymptomatic patients aged 44±14 years with hemodynamically significant, chronic AR and no indication for aortic valve replacement were evaluated by echocardiography, cardiac magnetic resonance imaging and exercise testing with measurement of peak oxygen consumption. RESULTS: The average left ventricular end diastolic volume was 244±62ml and the aortic regurgitant fraction 34±13%. At an average of 35.8±8.9ml/kg/min, peak oxygen consumption was well preserved. As in healthy individuals, a high peak oxygen consumption was associated with a relatively large LV end diastolic volume (r=0.51; p<0.001) and a low resting heart rate (r=-0.37; p=0.002). The aortic regurgitant fraction was not predictive of maximum oxygen consumption. Higher levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP) were independently associated with poorer exercise capacity and oxygen uptake (adjusted ß -0.35; p=0.003). CONCLUSION: Our results suggest that in asymptomatic patients with moderate to severe AR and moderately dilated left ventricles, remodeling is primarily adaptive. An increased level of NT-proBNP is associated with a reduced capacity for work and reduced oxygen consumption, possibly heralding the onset of adverse remodeling.

Automated Segmentation of the Right Ventricle in 3D Echocardiography: A Kalman Filter State Estimation Approach.

As the right ventricle's (RV) role in cardiovascular diseases is being more widely recognized, interest in RV imaging, function and quantification is growing. However, there are currently few RV quantification methods for 3D echocardiography presented in the literature or commercially available. In this paper we propose an automated RV segmentation method for 3D echocardiographic images. We represent the RV geometry by a Doo-Sabin subdivision surface with deformation modes derived from a training set of manual segmentations. The segmentation is then represented as a state estimation problem and solved with an extended Kalman filter by combining the RV geometry with a motion model and edge detection. Validation was performed by comparing surface-surface distances, volumes and ejection fractions in 17 patients with aortic insufficiency between the proposed method, magnetic resonance imaging (MRI), and a manual echocardiographic reference. The algorithm was efficient with a mean computation time of 2.0 s. The mean absolute distances between the proposed and manual segmentations were 3.6 ± 0.7 mm. Good agreements of end diastolic volume, end systolic volume and ejection fraction with respect to MRI ( -26±24 mL , -16±26 mL and 0 ± 10%, respectively) and a manual echocardiographic reference (7 ± 30 mL, 13 ± 17 mL and -5±7% , respectively) were observed.

Controlled release metoprolol for aortic regurgitation: a randomised clinical trial.

OBJECTIVE: Chronic aortic regurgitation (AR) creates a volume load on the left ventricle, which induces adaptive responses. With time, excessive left ventricular (LV) dilatation may precipitate heart failure. ß-adrenergic receptor antagonists (ß-blockers) are beneficial in patients with heart failure, but their effect in AR is unclear. This trial was designed to evaluate the effect of controlled release metoprolol on LV remodelling in patients with AR. METHODS: In this double blind trial, 75 asymptomatic patients aged 44±14 years, 89% males, fulfilling at least two echocardiographic criteria for moderate or severe chronic AR, were randomised to receive metoprolol CR/XL up-titrated to 200 mg/day, or matching placebo. The primary endpoint was LV end diastolic volume, measured by MRI after 6 months of treatment. RESULTS: After 6 months, the difference in the baseline-adjusted LV end diastolic volume between patients allocated to metoprolol and those allocated to placebo was 8 (95% CI -8 to 25) mL (p=0.32). The adjusted LV ejection fraction was 2.7 (95% CI 0.1 to 5.3) percentage points higher in the metoprolol group than in the placebo group (p=0.04). The exercise capacity and peak oxygen consumption did not differ between treatment arms. Serum concentrations of N-terminal pro-B-type natriuretic peptide were 138 (95% CI 71 to 205) pg/mL higher in the metoprolol group (p<0.001). There were no serious adverse events in either treatment arm. CONCLUSIONS: Treatment with metoprolol of adults with chronic, moderate to severe AR had no effect on LV volumes. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Identifier: NCT01157572-results.

Coronary calcium score in 12-year breast cancer survivors after adjuvant radiotherapy with low to moderate heart exposure - Relationship to cardiac radiation dose and cardiovascular risk factors.

BACKGROUND/PURPOSE: We explored the relation between coronary artery calcium (CAC) and cardiac radiation doses in breast cancer survivors (BCS) treated with radiotherapy (RT). Additionally, we examined the impact of other risk factors and biomarkers of coronary artery disease (CAD). MATERIALS AND METHODS: 236 BCS (median age 51years [range 30-70], median observation time 12years [9.2-15.7]), treated with 4-field RT of 50GY, were included and examined in 2004 (T1), 2007 (T2) and 2011 (T3) with clinical examination, blood tests and questionnaires. At T3, cardiac computed tomography was performed with quantification of CAC using Agatston score (AS). For 106 patients cardiac dose volume histograms were available. RESULTS: The cohort-based median of the mean cardiac dose was 2.5 (range 0.5-7.0) Gy. There was no correlation between measures of cardiac dose and AS. AS was correlated with high cholesterol at T1/T2 (p=0.022), high proBNP at T1/T2 (p<0.022) and T3 (p<0.022) and high HbA1c at T3 (p=0.022). In addition, a high AS was significantly associated with hypertension (p=0.022). Age (p<0.001) and cholesterol at T1/T2 (p=0.001) retained significant associations in multivariate analysis. CONCLUSIONS: Traditional, modifiable risk factors of CAD correlate with CAC and may be important for the long term risk of CAD after RT. With low to moderate cardiac radiation exposure, a contribution of radiation dose to CAC could not be demonstrated.

Arm and shoulder morbidity following surgery and radiotherapy for breast cancer.

PURPOSE: To explore the relationship between radiotherapy (RT) dose levels in the arm/shoulder region and arm/shoulder morbidity in breast cancer patients. MATERIAL AND METHODS: This study included 183 breast cancer patients who had received locoregional RT with or without chemotherapy and/or hormone treatment during the period 1998-2002. Individual RT dose level, reflected by dose-volume histograms (DVHs), for the shoulder joint and joining structures were obtained from archived CT-based RT plans. Individual median, mean and maximum arm/shoulder RT dose levels were extracted. Arm/shoulder morbidity was assessed 29-58 months after breast cancer treatment using the following clinical endpoints: arm pain, arm stiffness, swollen arm, use of arm, numbness, shoulder flexion and shoulder abduction difference, fibrosis and breast cancer-related lymphedema. The relationship between arm/shoulder RT dose level and these clinical endpoints was assessed by Spearman's correlation and multivariate logistic regression. RESULTS: Ninety-one percent of the included patients had some degree of arm/shoulder morbidity. Neither mean nor maximum RT dose level was associated with clinical endpoints. However, significant correlations (p < 0.05) were found between DVHs and arm stiffness, arm pain, use of arm and shoulder abduction difference, when arm/shoulder RT dose levels were approximately 15 Gy. CONCLUSIONS: Three-dimensional conformal locoregional RT for breast cancer results in long-term arm/shoulder morbidity. To minimize this risk, large shoulder volumes receiving RT doses of approximately 15 Gy should be reduced.

Dose Distribution in the Heart and Cardiac Chambers Following 4-field Radiation Therapy of Breast Cancer: a Retrospective Study.

PURPOSE: To evaluate cardiac doses in breast cancer patients with stage II/III treated with 4-field radiotherapy based on computed tomography (CT) dose planning. METHODS AND MATERIALS: Based on archived CT images, whole heart and cardiac chamber radiation doses were analyzed in 216 (111 left-sided and 105 right-sided) mastectomized or lumpectomized breast cancer patients treated at a single institution, the Norwegian Radium Hospital, between 2000-2002. Individual dose volume histograms for the whole heart and for the four cardiac chambers were obtained, and mean, median and maximum doses to these structures were calculated. The dose (Gy) delivered to the 5% of the volume of each cardiac structure (D5%), and the volume percentage of each structure receiving ≥ 25 Gy (V25Gy) were reported. Normal tissue complication probability (NTCP) calculations were used to estimate the risk for ischemic heart disease (IHD). RESULTS: Cohort-based medians of the whole heart mean dose (Dmean) for left- and right-sided tumors were 3.2 Gy and 1.3 Gy, respectively, with similar ventricular but lower atrial values. The atrial doses did not differ according to laterality of the breast tumor. In 13 patients with left-sided cancer, 5% of the heart volume was exposed to >25 Gy. The NTCP estimates were generelly low, with a maximum of 2.8%. CONCLUSIONS: During adjuvant CT-based locoregional radiotherapy of women with breast cancer, the cardiac radiation doses are, at the group level, below recommended threshold values (D5% < 25 Gy), though individual patients with left-sided disease may exceed these limits.