Higher tumor mutational burden is associated with inferior outcomes among pediatric patients with neuroblastoma.

INTRODUCTION: Neuroblastoma is a pediatric malignancy with heterogeneous clinical outcomes. Our aim was to identify prognostic genetic markers for patients with neuroblastoma, who were treated with the Taiwan Pediatric Oncology Group (TPOG) neuroblastoma N2002 protocol, to improve risk stratification and inform treatment. METHODS: Our analysis was based on 53 primary neuroblastoma specimens, diagnosed pre-chemotherapy, and 11 paired tumor relapse specimens. Deep sequencing of 113 target genes was performed using a custom panel. Multiplex ligation-dependent probe amplification was performed to identify clinical outcomes related to copy-number variations. RESULTS: We identified 128 variations associated with survival, with the number of variations being higher in the relapse than that in the diagnostic specimen (p = .03). The risk of event and mortality was higher among patients with a tumor mutational burden ≥10 than that in patients with a lower burden (p < .0001). Multivariate analysis identified tumor mutational burden, MYCN amplification, and chromosome 3p deletion as significant prognostic factors, independent of age at diagnosis, sex, and tumor stage. The 5-year event-free survival and overall survival rate was lower among patients with high tumor burden than in patients with low tumor burden. Furthermore, there was no survival of patients with an ALK F1147L variation at 5 years after diagnosis. CONCLUSIONS: Genome sequencing to determine the tumor mutational burden and ALK variations can improve the risk classification of neuroblastoma and inform treatment.

Feasibility of 18F-DOPA and 18F-FDG PET/CT for guiding decision-making for localized incidental neuroblastoma in infants under 18 months of age.

BACKGROUND: Neuroblastoma varies widely in risk. Risk indicators in infants with incidental neuroblastoma refine treatment confidence for observation or intervention. The potential of functional imaging, particularly PET/CT, remains to be defined. PROCEDURE: A retrospective review of infants under 18 months diagnosed with incidental neuroblastoma from 2008 to May 2022 in our institute was conducted. Before October 2015, incidental patients were treated similarly to symptomatic cases, undergoing biopsy or surgical excision upon diagnosis (early cohort). Post October 2015 (late cohort), treatment decisions were guided by PET/CT findings, with 18F-DOPA PET/CT confirming diagnosis and staging. For tumors with low 18F-FDG uptake, an expectant observation approach was considered. Patient characteristics, diagnostic methods, image findings at diagnosis, treatment courses, and responses were compared between cohorts. RESULTS: Thirty infants less than 18 months were identified with incidental neuroblastoma and completed PET/CT at diagnosis. The early and late cohorts each comprised 15 patients. In the late cohort, nine out of 15 patients (60%) presented with localized FDG non-avid tumors were offered the option of expectant observation. Of these, seven patients opted for observation, thereby avoiding surgery. Treatment outcomes were comparable between early and late cohorts, except for one mortality of a patient who, despite showing 18F-FDG activity, declined treatment. CONCLUSIONS: This study demonstrates the potential utility of 18F-DOPA and 18F-FDG PET/CT scans in aiding clinical decision-making for infants with localized, incidental neuroblastoma. Given the concerns regarding radiation exposure, such imaging may be valuable for cases with suspected metastasis, initial large tumor size, or growth during follow-up.

Myocardial Flow Assessment After Heart Transplantation Using Dynamic Cadmium-Zinc-Telluride Single-Photon Emission Computed Tomography With 201Tl and 99mTc Tracers and Validated by 13N-NH3 Positron Emission Tomography.

BACKGROUND: Cardiac allograft vasculopathy (CAV) is an obliterative and diffuse form of vasculopathy and is the most common cause of long-term cardiovascular mortality in heart transplant patients. This study aimed to investigate the diagnostic performance of 99mTc and 201Tl tracers in the assessment of CAV using cadmium-zinc-telluride (CZT) single-photon emission computed tomography (SPECT) for myocardial blood flow (MBF) and myocardial flow reserve (MFR) quantification, which was further validated using 13 N-NH3 positron emission tomography (PET). METHODS: Thirty-eight patients with prior heart transplantation who underwent CZT SPECT and 13 N-NH3 PET dynamic scans were included in this study. CZT SPECT with 99mTc-sestamibi was used in the first 19 patients and 201Tl-chloride for the remaining patients. To determine the diagnostic accuracy of angiographically defined moderate-to-severe CAV, the analysis included patients who underwent angiographic examinations within 1 year of their second scan. RESULTS: There were no significant differences in the patient characteristics between the 201Tl and 99mTc tracer groups. Both 201Tl and 99mTc CZT SPECT-derived stress MBF and MFR values globally and in 3 coronary territories showed good correlations with 13 N-NH3 PET. The 201Tl and 99mTc cohorts did not differ significantly in the correlation coefficients of CZT SPECT versus PET for MBF and MFR, except for stress MBF (201Tl:0.95 versus 99mTc:0.80, P=0.03). 201Tl and 99mTc CZT SPECT were satisfactory for detecting PET MFR <2.0 (201Tl area under the curve, 0.92 [0.71-0.99], 99mTc area under the curve, 0.87 [0.64-0.97]) and angiographically defined moderate-to-severe CAV, and CZT SPECT results were comparable to that of 13 N-NH3 PET (CZT area under the curve, 0.90 [0.70-0.99], PET area under the curve, 0.86 [0.64-0.97]). CONCLUSIONS: This small study suggests that CZT SPECT using 201Tl and 99mTc tracers showed comparable MBF and MFR, and the results correlated well with those of 13 N-NH3 PET. Hence, CZT SPECT with 201Tl or 99mTc tracers can be used to detect moderate-to-severe CAV in patients with prior heart transplantation. However, validation using larger studies is warranted.

Reducing scan time in 177 Lu planar scintigraphy using convolutional neural network: A Monte Carlo simulation study.

PURPOSE: The aim of this study was to reduce scan time in 177 Lu planar scintigraphy through the use of convolutional neural network (CNN) to facilitate personalized dosimetry for 177 Lu-based peptide receptor radionuclide therapy. METHODS: The CNN model used in this work was based on DenseNet, and the training and testing datasets were generated from Monte Carlo simulation. The CNN input images (IMGinput ) consisted of 177 Lu planar scintigraphy that contained 10-90% of the total photon counts, while the corresponding full-count images (IMG100% ) were used as the CNN label images. Two-sample t-test was conducted to compare the difference in pixel intensities within region of interest between IMG100% and CNN output images (IMGoutput ). RESULTS: No difference was found in IMGoutput for rods with diameters ranging from 13 to 33 mm in the Derenzo phantom with a target-to-background ratio of 20:1, while statistically significant differences were found in IMGoutput for the 10-mm diameter rods when IMGinput containing 10% to 60% of the total photon counts were denoised. Statistically significant differences were found in IMGoutput for both right and left kidneys in the NCAT phantom when IMGinput containing 10% of the total photon counts were denoised. No statistically significant differences were found in IMGoutput for any other source organs in the NCAT phantom. CONCLUSION: Our results showed that the proposed method can reduce scan time by up to 70% for objects larger than 13 mm, making it a useful tool for personalized dosimetry in 177 Lu-based peptide receptor radionuclide therapy in clinical practice.

Polar map-free 3D deep learning algorithm to predict obstructive coronary artery disease with myocardial perfusion CZT-SPECT.

PURPOSE: Deep learning (DL) models have been shown to outperform total perfusion deficit (TPD) quantification in predicting obstructive coronary artery disease (CAD) from myocardial perfusion imaging (MPI). However, previously published methods have depended on polar maps, required manual correction, and normal database. In this study, we propose a polar map-free 3D DL algorithm to predict obstructive disease. METHODS: We included 1861 subjects who underwent MPI using cadmium-zinc-telluride camera and subsequent coronary angiography. The subjects were divided into parameterization and external validation groups. We implemented a fully automatic algorithm to segment myocardium, perform registration, and apply normalization. We further flattened the image based on spherical coordinate system transformation. The proposed model consisted of a component to predict patent arteries and a component to predict disease in each vessel. The model was cross-validated in the parameterization group, and then further tested using the external validation group. The performance was assessed by area under receiver operating characteristic curves (AUCs) and compared with TPD. RESULTS: Our algorithm preprocessed all images accurately as confirmed by visual inspection. In patient-based analysis, the AUC of the proposed model was significantly higher than that for stress-TPD (0.84 vs 0.76, p < 0.01). In vessel-based analysis, the proposed model also outperformed regional stress-TPD (AUC = 0.80 vs 0.72, p < 0.01). The addition of quantitative images did not improve the performance. CONCLUSIONS: Our proposed polar map-free 3D DL algorithm to predict obstructive CAD from MPI outperformed TPD and did not require manual correction or a normal database.

Investigating the lesion detectability of Tc-99m planar scintigraphy acquired with LEHRS collimator for patients with different body sizes: A phantom study.

PURPOSE: The aim of this work was to investigate the lesion detectability of Tc-99m planar scintigraphy acquired with a low-energy high-resolution and sensitivity (LEHRS) collimator and processed by Clarity 2D for patients with different body sizes through phantom study. METHODS: A NEMA IEC body phantom set was covered by two layers of 25-mm-thick bolus to construct phantom in three different sizes. All image data were performed on a Discovery NM/CT 870 DR with an LEHRS collimator and processed by Clarity 2D with blend ratio a of 0%, 20%, 40%, 60%, 80%, and 100%. The lesion detectability in gamma scintigraphy was evaluated by calculating the contrast-to-noise ratio (CNR). Multiple linear regression methods were used to analyze the impact of body size, target size, and Clarity 2D blending weight on the lesion detectability of Tc-99m planar scintigraphy. RESULTS: It was found that changing the blend ratio could improve CNR, and this phenomenon was more significant in anterior view than in posterior view. Our results also suggested that the blend ratio should be selected according to patient body size in order to maintain consistent CNR. Hence, when a blend ratio of 60% was used for a patient before cancer treatment, a lower blend ratio should be used for the same patient experiencing treatment-related weight loss to achieve consistent lesion detectability in Tc-99m planar scintigraphy acquired with LEHRS and processed by Clarity 2D. CONCLUSION: The magnitude of photon attenuation and scattering is higher in patients with larger body size, so Tc-99m planar scintigraphy usually has lower lesion detectability in obese patients. Although photon attenuation and scattering are inevitable during image formation, their impacts on image quality can be eased by employing appropriate image protocol parameters.

Prognostic Value of Interim 18F-DOPA and 18F-FDG PET/CT Findings in Stage 3-4 Pediatric Neuroblastoma.

PURPOSE: This retrospective study aimed to determine the prognostic value of imaging parameters derived from midtherapy 18F-fluorodihydroxyphenylalanine (18F-DOPA) and 18F-FDG PET in pediatric patients with stage 3-4 neuroblastoma. METHODS: We enrolled 32 stage 3-4 pediatric neuroblastoma patients who underwent 18F-DOPA and 18F-FDG PET/CT scans before and after 3 chemotherapy cycles. We measured metabolic and volumetric parameters and applied a metabolic burden scoring system to evaluate the primary tumor extent and soft tissue metastases and that of bone/bone marrow involvement. The associations between these parameters and clinical outcomes were investigated. RESULTS: Over a median follow-up period of 47 months (range, 3-137 months), 16 patients experienced disease progression, and 13 died. After adjustment for clinical factors, multivariate Cox proportional hazard models showed that interim tumor FDG/FDOPA SUVmax (hazard ratio [HR], 5.94; 95% confidence interval [CI], 1.10-34.98) and interim FDOPA whole-body metabolic burden scores (WBMB) (HR, 7.30; 95% CI, 1.50-35.50) were significant prognostic factors for overall survival (OS). Only interim FDOPA WBMB scores (HR, 7.05; 95% CI, 1.02-48.7) were predictive of progression-free survival. Based on median cutoff values, prognosis (OS and progression-free survival) was significantly associated with an interim FDOPA WBMB score ≥21.92 (all P < 0.05) and interim tumor FDG/FDOPA (SUVmax) score ≥0.57 with poor OS (P < 0.05). CONCLUSIONS: Our results indicate that midtreatment FDG and FDOPA PET/CT could serve as prognostic markers in stage 3-4 neuroblastoma patients.

A Clinicopathological Study of Cytomegalovirus Lymphadenitis and Tonsillitis and Their Association with Epstein-Barr Virus.

INTRODUCTION: Histopathological characteristics of cytomegalovirus (CMV) lymphadenitis have been well described. Rare studies have reported the immune status and clinical features. Clinically, experts believed that CMV lymphadenitis develops in immunocompromised and immunocompetent patients. Infectious mononucleosis (IM)-like syndrome is the most well-known clinical presentation. METHODS: We reviewed archived CMV immunohistochemical stains on lymphoid tissues. The clinicopathological features of CMV-positive cases were studied. RESULTS: For lymph nodes, we detected CMV in 29% (5/17) allogeneic peripheral blood hematopoietic stem cell transplantation (PBSCT) recipients, 29% (4/14) post-autologous PBSCT patients, 13% (6/47) patients treated with intravenous chemotherapy, and 9% (9/96) immunocompetent patients. We detected CMV in 7% (2/24) of tonsils but not in the nasopharynx, tongue base, or spleen specimens. The patients with iatrogenic immunodeficiency ranged from 37 to 76 years old. CMV infections developed a few years after lymphoma treatment (median duration after allogeneic PBSCT, 932 days; after autologous PBSCT, 370 days; and after chemotherapy, 626 days). The most common clinical presentation was neck mass (13/25, 42%), followed by asymptomatic image finding (10/25, 40%). Positron emission tomography/computed tomography (PET/CT) scan showed increased uptake compared to the liver in all patients (11/11, 100%). Of 10 lymphoma patients, 8 (80%) had a Deauville score of 4-5; they accounted for 30% (8/27) of lymphoma patients with false-positive PET/CT scan results. All cases were self-limiting. 96% (23/25) cases had Epstein-Barr virus coinfection, and EBER-positive cells were predominantly in a few germinal centers. CONCLUSIONS: Cytomegalovirus (CMV) lymphadenitis and tonsillitis were subclinical infections, not primary CMV infection with IM-like syndrome. The lymphadenopathy typically developed a few years after lymphoma treatments in the middle-aged and the elderly. The lesions mimicked lymphoma relapse in PET scans. Therefore, recognizing CMV infection in lymphoid tissues is of clinical importance.

Clinical significance of quantitative assessment of glucose utilization in patients with ischemic cardiomyopathy.

BACKGROUND: The aim of this study was to prospectively quantify the rate of myocardial glucose uptake (MRGlu) in myocardium with different perfusion-metabolism patterns and determine its prognostic value in patients with ischemic cardiomyopathy. METHODS AND RESULTS: 79 patients with ischemic cardiomyopathy were prospectively enrolled for dynamic cardiac FDG PET, and then followed for at least 6 months. Perfusion-metabolism patterns were determined based on visual score analysis of 201Tl SPECT and FDG PET. MRGlu was analyzed using the Patlak kinetic model. The primary end-point was cardiovascular mortality. Significantly higher MRGlu was observed in viable compared with non-viable areas. Negative correlations were found between MRGlu in transmural match and a history of hyperlipidemia, statin usage, and triglyceride levels. Diabetic patients receiving dipeptidyl peptidase-4 inhibitors (DPP4i) had a significantly lower MRGlu in transmural match, mismatch, and reverse mismatch. Patients with MRGlu in transmural match ≥ 23.40 or reverse mismatch ≥ 36.90 had a worse outcome. CONCLUSIONS: Myocardial glucose utilization was influenced by substrates and medications, including statins and DPP4i. MRGlu could discriminate between viable and non-viable myocardium, and MRGlu in transmural match and reverse mismatch may be prognostic predictors of cardiovascular death in patients with ischemic cardiomyopathy.

Impact of initial myocardial perfusion imaging versus invasive coronary angiography on outcomes in coronary artery disease: a nationwide cohort study.

PURPOSE: In patients with stable coronary artery disease (CAD), two main options exist to guide management: initial invasive coronary angiography (CAG), or selective CAG after risk stratification using myocardial perfusion imaging (MPI). This study compared clinical outcomes between these two strategies in a large, real-world population. METHODS: The initial cohort comprised 1,000,000 randomly selected patients who had been entered in the National Health Insurance Research Database of Taiwan between 2000 and 2011. Patients with acute coronary syndromes, prior myocardial infarction (MI) or coronary revascularization, and prior treadmill testing or stress echocardiography were excluded. The remaining patients with suspected or known CAD were divided into those in whom initial CAG had been performed and those in whom initial MPI had been performed, and were followed until the end of 2011 for all-cause mortality, MI, and revascularization. A Cox proportional hazards model was used to estimate the risk of events after adjusting for covariates. RESULTS: The MPI and CAG groups each comprised 4,495 patients after frequency matching, with a similar Charlson comorbidity index (CCI). The MPI group had a significantly and dramatically lower incidence of revascularization (729 vs. 2,380, p < 0.001), MI (268 vs. 1,044, p < 0.001), and all-cause mortality (522 vs. 784, p < 0.001) than the CAG group. Multivariable analysis adjusting for age, gender, CCI, and comorbidities showed that in the MPI group fewer patients had revascularization (HR 0.24, 95% CI 0.22-0.26) and MI (HR 0.23, 95% CI 0.20-0.26), and the rate of all-cause mortality was lower (HR 0.58, 95% CI 0.52-0.64). CONCLUSIONS: In patients with suspected stable CAD, compared with initial invasive CAG, a selective strategy guided by MPI was associated with lower rates of revascularization and MI and improved survival.

Longitudinal evaluation of myocardial glucose metabolism and contractile function in obese type 2 diabetic db/db mice using small-animal dynamic 18F-FDG PET and echocardiography.

The aim was to evaluate sequential changes of myocardial glucose utilization and LV systolic function in db/db mice. Eight db/db and eight wild-type mice underwent plasma substrate analysis and dynamic 18F-FDG PET at week 8 (W8), W10, W12, W14, and W16. 18F-FDG uptake constant Ki and the rate of myocardial glucose uptake (MRGlu) were derived via Patlak graphic analysis. Another 8 db/db and 8 wild-type mice received echocardiography at W8, W12, and W16 and LV structure and function were measured. The db/db mice showed increased weights and glucose levels as they aged. The index of homeostasis model assessment-estimated insulin resistance, insulin, and free fatty acid concentrations were higher in db/db mice compared with wild-type. MRGlu of db/db mice across all time points was markedly higher than that of wild-type. An age-dependent elevation of MRGlu was observed in db/db mice. Ki and MRGlu of db/db mice showed negative correlation with triglyceride levels. When two groups were pooled together, Ki and MRGlu were significantly proportional to glucose levels. No significant difference in LV structure and function was noted between db/db and control mice. In conclusion, we demonstrated altered myocardial glucose utilization preceding the onset of LV systolic dysfunction in db/db mice.

Risk Stratification of Pediatric Patients With Neuroblastoma Using Volumetric Parameters of 18F-FDG and 18F-DOPA PET/CT.

PURPOSE: This study determined the prognostic value of volumetric parameters derived from pretreatment F-FDG and F-DOPA PET/CT of neuroblastoma and their correlation with clinical and histopathologic features. PATIENTS AND METHODS: A total of 25 children with neuroblastoma underwent pretreatment F-FDG and F-DOPA PET/CT within 4 weeks. The SUVmax of primary tumors on F-FDG and F-DOPA PET were recorded as SUVFDG and SUVDOPA, respectively. For volumetric parameters of primary tumors, 40% of SUVmax was used to generate volume of interest. If the 40% of SUVmax was below 2.5, an SUV threshold of 2.5 was used instead. Metabolic tumor volume (MTV), total lesion glycolysis (TLG), dopaminergic tumor volume (DTV), and total lesion F-DOPA activity (TLDA) were recorded as F-FDG and F-DOPA volumetric parameters. All indices were compared between groups distinguished by survival status and clinical features, including bone marrow involvement, lymph node metastasis, amplification of the MYCN oncogene, invasive features on anatomic images, and risk categories. The Kaplan-Meier method and log-rank test were used to compare the survival curves between groups. RESULTS: The median follow-up period was 28.2 months. Nonsurvivors (20%) tended to have lower SUVDOPA, DTV, and TLDA (P ≤ 0.05), and higher SUVFDG, MTV, and TLG (all P < 0.05). Lower F-DOPA uptake is associated with bone marrow and lymph node metastases (all P < 0.05). Higher F-FDG uptake is associated with MYCN amplification (all P < 0.05) and anatomic invasive features of tumors such as vascular encasement or adjacent organ invasion (TLG, P = 0.05). Only volumetric indices (DTV, TLDA, MTV, and TLG) significantly differed among risk groups (all P < 0.05). CONCLUSIONS: Pretherapeutic F-DOPA and F-FDG PET provided complementary information, and both can be served for risk stratification. Volumetric indices of F-DOPA and F-FDG PET correlate more highly with risk grouping.

Ictal Phase Perfusion SPECT of Nonketotic Hyperglycemia-Induced Parieto-occipital Seizure.

A 68-year-old man with diabetes mellitus type 2 presented himself with visual distortion and apraxia. Nonketotic hyperglycemic seizure with both motor and sensory components was suspected. Tc-ECD perfusion SPECT demonstrated hyperperfusion at right parieto-occipital lobe during ictal phase. Normalization of hyperperfused area was noted on follow-up perfusion SPECT after intense glucose control. In nonketotic hyperglycemic state, the depletion of GABA in cerebral neurons lowers the seizure threshold. We demonstrated that ictal phase perfusion SPECT contributed to not only diagnosis but also served as a follow-up tool.

Intratumoral Heterogeneity of Pretreatment 18F-FDG PET Images Predict Disease Progression in Patients With Nasal Type Extranodal Natural Killer/T-cell Lymphoma.

PURPOSE: The aim of this study was to investigate whether the textural features of pretreatment F-FDG PET images can predict prognosis for nasal type extranodal natural killer/T-cell lymphoma (ENKTL). MATERIALS AND METHODS: A retrospective analysis of the pretreatment F-FDG PET images of the patients with newly diagnosed nasal type ENKTL from 2008 to 2013 was conducted. Progression-free survival (PFS) was the main outcome measure. The primary tumor was identified and then delineated using the 40% maximum standardized uptake value (SUVmax) thresholding method. The textural features of the pretreatment F-FDG PET images were extracted. The prognostic significance of the textural features of the PET images were examined using the receiver operating characteristic (ROC) curves and Cox regression analysis. P values <0.05 were considered statistically significant. RESULTS: In total, 17 patients were enrolled, among whom 11 showed disease progression and 6 died from the disease during the median follow-up period of 27.2 months. Dissimilarity and low-intensity short-zone emphasis (LISZE) were identified as independent predictors of PFS by using the ROC curves and multivariate Cox analysis after adjusting for the clinical variables. CONCLUSIONS: Dissimilarity and LISZE were the significant predictors of disease progression in patients with nasal type ENKTL and can improve their prognostic stratification.

18F-NaF PET/CT Images of Cardiac Metastasis From Osteosarcoma.

Osteosarcomas are aggressive with a high incidence of recurrence and metastasis. Cardiac osteosarcoma metastasis is rare. We described a 17-year-old boy who had right distal femoral osteosarcoma with lung metastases. During follow-up, right ventricular (RV) metastasis was noted and confirmed by histopathological examination of the surgical specimen. F-NaF PET/CT was then arranged 1 month after debulking surgery for residual tumor survey. The images showed intense F-NaF uptake at RV region, suggestive of residual cardiac metastases.

Clinical significance of right ventricular activity on treadmill thallium-201 myocardial single-photon emission computerized tomography using cadmium-zinc-telluride cameras.

OBJECTIVE: Identification of right ventricular (RV) abnormalities is important in patients with suspected coronary artery disease (CAD). RV activity can be better visualized on myocardial single-photon emission computerized tomography (SPECT) using a higher sensitivity cadmium-zinc-telluride (CZT) detector. The aim of this study was to investigate the clinical significance of RV/left ventricular (LV) uptake ratios during exercise thallium-201 SPECT using CZT detectors. PATIENTS AND METHODS: A total of 102 patients underwent treadmill ECG-gated SPECT, coronary angiography, and echocardiography. SPECT myocardial perfusion was interpreted using a 17-segment model and a 0-4-point scale. RV/LV uptake ratios were calculated on the basis of maximum counts per pixel within the entire RV and LV walls. The relationships between RV/LV uptake ratio and gated SPECT, presence of CAD (≥50% stenosis in the left main or ≥70% in the main branches), demographics, and echocardiographic parameters were analyzed. RESULTS: Stress RV/LV ratios correlated positively with the presence of left main or multivessel disease, and tricuspid regurgitation maximum pressure gradient. After multivariate regression, stress/rest RV/LV ratios correlated positively with mitral flow deceleration time, age, female sex, and use of ß-blockers. CONCLUSION: RV/LV uptake ratios on the basis of exercise myocardial perfusion SPECT imaging using CZT cameras are useful for the detection of severe CAD and could serve as an indicator of pulmonary hypertension and LV diastolic dysfunction.

Pregnancy Outcome After I-131 Therapy for Patients With Thyroid Cancer: A Nationwide Population-Based Cohort Study.

The aim of this study was to evaluate the influence of I-131 therapy on pregnancy outcome in patients that received therapeutic I-131 doses for thyroid cancer in Taiwan.This nationwide population-based cohort study was based on data from 1998 to 2010 obtained from the Taiwanese National Health Insurance Research Database. We identified 11,708 women with thyroid cancer (≥ 15 and ≤ 50 years of age) by International Classification of Diseases, Ninth Revision, Clinical Modification codes. Patients were divided into 2 cohorts: I-131 therapy cohort and non-I-131 therapy cohort. The mean follow-up period was 6.08 years for the I-131 cohort and 6.87 years for the non-I-131 cohort. The case cohort and the control cohort comprised 775 and 716 pregnant patients, respectively.The overall incidence of pregnancy was significantly lower in the I-131 cohort (adjusted HR = 0.77, 95% CI = 0.70-0.86) and it was also observed when the patients were stratified according to age (HR = 0.73, 95% CI = 0.64-0.83 in 25-34 years; HR = 0.63, 95% CI = 0.49-0.82 in 35-44 years). Patients in the I-131 cohort had a lower successful delivery rate, particularly among patients in 25 to 34 years (OR = 0.60, 95% CI = 0.45-0.80). No significant difference was observed for adverse pregnancy conditions between 2 cohorts.I-131 therapy is associated with decreased pregnancy and successful delivery rates. The underlying mechanism likely involves physician recommendation, patient's psychological issue, and potential impact of I-131 treatment on reproductive health. Further investigation is needed.

Incremental Diagnostic Performance of Combined Parameters in the Detection of Severe Coronary Artery Disease Using Exercise Gated Myocardial Perfusion Imaging.

PURPOSE: Myocardial perfusion imaging (MPI) using gated single-photon emission tomography (gSPECT) may underestimate the severity of coronary artery disease (CAD). This study aimed to evaluate the significance of combined parameters derived from gSPECT, as well as treadmill stress test parameters, in the detection of severe CAD. METHODS: A total of 211 consecutive patients referred for exercise MPI between June 2011 and June 2013 (who received invasive coronary angiography within six months after MPI) were retrospectively reviewed. Exercise MPI was performed with Bruce protocol and 201Tl injected at peak exercise. Gated SPECT was performed using a cadmium-zinc-telluride camera and processed by QPS/QGS software. Perfusion defect abnormalities such as sum stress score (SSS); sum difference score, algorithm-derived total perfusion deficits, transient ischemic dilatation ratios of end-diastolic volumes and end-systolic volumes, post-stress changes in ejection fraction, and lung/heart ratio (LHR) were calculated. Treadmill parameters, including ST depression (STD) at the 1st and 3rd minutes of recovery stage (1'STD and 3'STD), maximal STD corrected by heart rate increment (ST/HR), heart rate decline in 1st and 3rd minutes of recovery stage, recovery heart rate ratio (HR ratio), systolic and mean blood pressure ratios (SBP ratio and MAP ratio) during recovery phase were recorded. Diagnostic performances of these parameters were analyzed with receiver operating characteristic (ROC) analysis and logistic regression for detection of left main (≥ 50%) or 3-vessel disease (all ≥ 70% luminal stenosis) on invasive angiography. RESULTS: Among various MPI and treadmill parameters used for detection of severe CAD, SSS and ST/HR had the highest AUC (0.78, 0.73, p = NS) and best cut-off values (SSS > 6, ST/HR > 17.39 10-2mV/bpm), respectively. By univariate logistic regression, all parameters except 1'HRR, 3'HRR, SBP and MAP ratios increased the odds ratio of severe CAD. Only increased L/H ratio, 3'STD, and HR ratio remained significant after multivariate regression. The predicted values of combined MPI and treadmill parameters (LHR, 3'STD, and HR ratio) gave the best ROC (AUC: 0.91) than any individual parameter or parameter combination. CONCLUSIONS: Of all treadmill and gSPECT parameters, the combination of MPI and treadmill parameters can offer better diagnostic performance for severe CAD.

(131)I treatment for thyroid cancer and the risk of developing salivary and lacrimal gland dysfunction and a second primary malignancy: a nationwide population-based cohort study.

OBJECTIVE: The aim of this study was to determine the prevalence of salivary and lacrimal gland dysfunction and a second primary malignancy in patients from Taiwan with thyroid cancer after radioiodine therapy. METHODS: This nationwide population-based cohort study was based on data obtained from the Taiwan National Health Insurance Database from 2000 to 2011. A total of 1,834 thyroid cancer patients treated with (131)I therapy and 1,834 controls (thyroid cancer without (131)I therapy) selected by 1:1 matching on a propensity score were enrolled. The cumulative (131)I dose in each patient was calculated. A Cox proportional hazards model was applied to estimate the effect of radiation from the (131)I therapy on the risk of salivary and lacrimal gland impairment as well as second primary malignancies in terms of hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: In patients treated with (131)I therapy and in controls, the incidence rates of salivary gland dysfunction were 6.76 and 1.01 per 10,000 person-years, respectively (HR 6.81, 95% CI 0.74 - 55.3), the incidence rates of keratoconjunctivitis sicca (KCS) were 13.6 and 16.3 per 10,000 person-years, respectively (HR 0.84, 95% CI 0.41 - 1.73), and the incidence rates of second primary malignancy were 76.7 and 62.4 per 10,000 person-years, respectively (HR 1.23, 95% CI 0.88 - 1.72). The risk of salivary secretion impairment significantly increased with increasing administered doses (HR 14.3, 95% CI 1.73 - 119.0). However, there was no increase in the incidence of KCS or secondary cancer in patients treated with higher doses. CONCLUSION: (131)I therapy insignificantly increased the risk of salivary gland dysfunction and second primary malignancy. In patients with higher cumulative doses, an increase in the incidence of salivary gland dysfunction was observed. By contrast, we did not find an association between (131)I treatment and KCS development.