PET/MRI in Endometrial Cancer: Imaging Biomarkers are Associated with Disease Progression and Overall Survival.

RATIONALE AND OBJECTIVES: To evaluate the association between positron emission tomography (PET)/magnetic resonance imaging (MRI) biomarkers and survival outcomes in patients with endometrial cancer. MATERIALS AND METHODS: Between April 2014 and April 2016, 88 patients with newly diagnosed endometrial cancer participated this prospective study and underwent [18F] fluorodeoxyglucose PET/MRI. Sixty-nine patients with measurable tumors on PET/MRI were included in the image analysis. Imaging biomarkers included the minimum and mean apparent diffusion coefficients (ADCmin and ADCmean), maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of the primary tumors. The log-rank test and Cox proportional hazards model were used to assess the relationship between imaging biomarkers and survival. RESULTS: After a median follow-up of 80 months, 15 (22%) patients had tumor progression and six (9%) patients died. The results of ADCmin, ADCmean, and SUVmax did not show a significant association with progression-free survival (PFS) and overall survival (OS). Significantly shorter PFS was noted in patients with primary tumors with higher MTV (P < 0.001) and TLG (P < 0.001). Significantly shorter OS was also noted in patients with primary tumors with higher MTV (P = 0.048) and TLG (P = 0.034). In the multivariate analysis, MTV was an independent predictor of PFS (hazard ratio = 10.84, P = 0.033). CONCLUSION: PET/MRI biomarkers, particularly MTV and TLG, are associated with PFS and OS in patients with endometrial cancer. MTV was an independent predictor of PFS.

Clinical practice consensus for the diagnosis and management of melanoma in Taiwan.

Melanoma is rare in Taiwan. Asian melanoma is distinct from Western melanoma because acral and mucosal melanoma accounts for the majority of melanoma cases, leading to distinct tumor behaviors and genetic profiling. With consideration of the clinical guidelines in Western countries, Taiwanese experts developed a local clinical practice consensus guideline. This consensus includes diagnosis, staging, and surgical and systemic treatment, based only on clinical evidence, local epidemiology, and available resources evaluated by experts in Taiwan. This consensus emphasizes the importance of surgical management, particularly for sentinel lymph node biopsies. In addition, molecular testing for BRAF is mandatory for patients before systemic treatment. Furthermore, immunotherapy and targeted therapy are prioritized for systemic treatment. This consensus aimed to assist clinicians in Taiwan in diagnosing and treating patients according to available evidence.

Comparison of post-COVID-19 vaccination hypermetabolic lymphadenopathy on 18F-fluorodeoxyglucose PET/CT between virus-vector vaccine and mRNA vaccine.

PURPOSE: We compared hypermetabolic lymphadenopathy (HLN) on 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) after virus-vector and mRNA vaccines for coronavirus disease 2019 (COVID-19). METHODS: This retrospective study included 573 participants who underwent FDG PET/CT after receiving a virus-vector vaccine (ChAdOx1, AstraZeneca [AZ] group) or an mRNA vaccine (mRNA-1273, Moderna [M] group) from July 2021 to October 2021. The incidence and avidity of HLN were evaluated and correlated with clinical features and vaccine type. The final analysis was conducted with 263 participants in the AZ group and 310 participants in the M group. RESULTS: The HLN incidence was significantly lower in the AZ group than in the M group (38/263 [14%] vs. 74/310 [24%], p = 0.006). The FDG avidity of HLN was comparable between the two groups. The HLN incidence in both groups was significantly higher within 4 weeks after the vaccination compared with more than 4 weeks. The HLN incidence within 4 weeks of the vaccination was significantly higher in the M group than in the AZ group (p = 0.008), whereas a difference in HLN incidence between the two groups was not observed after the same duration (p = 0.11). CONCLUSIONS: The mRNA mRNA-1273 COVID-19 vaccine was found to be associated with higher glucose hypermetabolism in regional lymph nodes within the first 4 weeks compared with the virus-vector vaccine, as indicated by the presence of HLN on FDG PET/CT. The degree of glucose hypermetabolism was comparable between the two vaccines.

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.

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.

Factors predicting one or two sentinel lymph nodes to be accepted for sentinel lymph node biopsy alone after neoadjuvant therapy in initially node-positive breast cancer patients.

BACKGROUND: Current guidelines recommend harvesting ≥3 sentinel nodes if sentinel lymph node biopsy (SLNB) alone is considered after neoadjuvant therapy (NAT) for initially node-positive (cN+) breast cancer. We attempted to investigate factors predicting one or two sentinel lymph nodes harvested to be accepted for SLNB alone after NAT in initially cN + patients. METHODS: Overall, 157 patients who received NAT (clinically T1-3/N1-2/M0) and underwent SLNB were identified from a prospectively maintained database. Significant factors were identified using a multiple logistic regression model. RESULTS: The overall SLN identification rate was 83.4%. Failed SLN identification was associated with a 2-day protocol using a single tracer (odds ratio: 0.331 [95% confidence interval {CI}: 0.132-0.830], p = 0.018), age >52 years (0.345 [0.131-0.913], p = 0.032), and lobular histology (0.156 [0.026-0.944], p = 0.043). The overall false-negative SLNB rate was 14.7%. Its increased risk was associated with radioactivity count >530 for any SLN during SLNB (96.4 [4.00-2320], p = 0.005), age ≥57 years (34.2 [1.92-610], p = 0.016), and taxane use (105 [1.02-10700], p = 0.049); its decreased risk was associated with more harvested SLNs (0.191 [0.054-0.669], p = 0.01) and dual tracers (0.101 [0.012-0.843], p = 0.034). A predictive model using these factors achieved an area under the curve of 0.935 (95% CI: 0.878-0.991). CONCLUSION: When taxane was administered during NAT, the false-negative rate was predicted at <5% for patients aged <57 years, if 1-2 SLNs were harvested using dual tracers, and when the count of every SLN was lower than 530 after NAT in cN + breast cancer.

Diagnostic Performance of Proton Magnetic Resonance Spectroscopy and 18F-Fluorocholine PET to Differentiate Benign From Malignant Breast Lesions.

PURPOSE: The aim of this study was to evaluate the diagnostic performance of the proton magnetic resonance spectroscopy (MRS) and 18F-fluorocholine (FCH) PET for suspicious breast findings on conventional imaging (mammography and breast ultrasound). METHODS: From September 2012 to December 2015, 37 women with 39 breast lesions on conventional imaging were enrolled and underwent proton MRS and FCH PET. The MRS parameters of choline signal-to-noise ratio (SNR), choline integral (I(cho)), and the PET parameters including SUVmax in the prone (SUV1) and supine (SUV2) positions were analyzed. Receiver operating characteristic curves with the area under the curve, sensitivity, and specificity under the optimal cutoff points for the different parameters were determined. RESULTS: Twenty-three lesions (59%) were malignant, and 16 (41.0%) were benign. The malignant lesions tended to show significantly higher MRS and PET parameters than benign lesions (choline SNR, P = 0.007; I(cho), P = 0.003; SUV1 and SUV2, P < 0.0001). Fair to moderate correlations were noted between the choline SNR and PET parameters (SUV1, Spearman rank correlation coefficient, ρ = 0.477; SUV2, ρ = 0.483), as well as I(cho) and PET parameters (SUV1, ρ = 0.493; SUV2, ρ = 0.549). The SUV2 showed the highest diagnostic performance (area under the curve, 0.918). Using 2.5 as the optimal cutoff point, the SUV2 yields 89.5% sensitivity and 87.5% specificity for differentiating malignant from benign lesions. CONCLUSION: The MRS parameters were fairly to moderately correlated with FCH PET parameters, and both could differentiate malignant from benign breast lesions with SUV2 showing best diagnostic performance.

NP-59 Adrenal Scintigraphy as an Imaging Biomarker to Predict KCNJ5 Mutation in Primary Aldosteronism Patients.

Purpose: Somatic KCNJ5 mutation occurs in half of unilateral primary aldosteronism (PA) and is associated with more severe phenotype. Mutation status can only be identified by tissue sample from adrenalectomy. NP-59 adrenal scintigraphy is a noninvasive functional study for disease activity assessment. This study aimed to evaluate the predictive value of NP-59 adrenal scintigraphy in somatic KCNJ5 mutation among PA patients who received adrenalectomy. Methods: Sixty-two PA patients who had NP-59 adrenal scintigraphy before adrenalectomy with available KCNJ5 mutation status were included. Two semiquantitative parameters, adrenal to liver ratio (ALR) and lesion to contralateral ratio of bilateral adrenal glands (CON) derived from NP-59 adrenal scintigraphy, of mutated and wild-type patients were compared. Cutoff values calculated by receiver-operating characteristic (ROC) analysis were used as a predictor of KCNJ5 mutation. Results: Twenty patients had KCNJ5 mutation and 42 patients were wild type. Patients harboring KCNJ5 mutation had both higher ALR and CON (p = 0.0031 and 0.0833, respectively) than wild-type patients. With ALR and CON cutoff of 2.10 and 1.95, the sensitivity and specificity to predict KCNJ5 mutation were 85%, 57% and 45%, 93%, respectively. Among 20 patients with KCNJ5 mutation, 16 showed G151R point mutation (KCNJ5- G151R) and 4 showed L168R point mutation (KCNJ5-L168R), which former one had significantly lower ALR (p=0.0471). Conclusion: PA patients harboring somatic KCNJ5 mutation had significantly higher NP-59 uptake regarding to ALR and CON than those without mutation. APAs with KCNJ5-L168R point mutation showed significantly higher ALR than those with KCNJ5-G151R point mutation.

2021 Advocacy Statements for the Role of 99mTc-Pyrophosphate Scintigraphy in the Diagnosis of Transthyretin Cardiac Amyloidosis: A Report of the Taiwan Society of Cardiology and the Society of Nuclear Medicine of the Republic of China.

Transthyretin cardiac amyloidosis (ATTR-CM) is an increasingly recognized cause of heart failure with preserved ejection fraction. Favorable prognosis depends on early diagnosis and correct treatment strategy. Among patients for whom there is a high clinical suspicion of cardiac amyloidosis, 99mTc-labeled bone avid scintigraphy including 99mTc-pyrophosphate (PYP) scintigraphy may be of diagnostic and prognostic importance. Various international guidelines support the non-biopsy diagnosis of ATTR-CM using 99mTc-PYP scintigraphy, yet emphasize the gap in standardization of acquisition and imaging analysis protocols, as well as the appropriateness of its clinical use. Therefore, a joint expert consensus has been reached by the Taiwan Society of Cardiology and the Society of Nuclear Medicine of the Republic of China, to advocate for the application of 99mTc-PYP scintigraphy in the diagnosis of ATTR-CM. This article aims to highlight the recommendations on image acquisition, qualitative and quantitative assessments of cardiac 99mTc-PYP uptake, and diagnostic algorithms. We hope the implementation of these recommendations in Taiwan will facilitate the process and enhance the diagnostic rate of ATTR-CM.

Assessing tumor angiogenesis using dynamic contrast-enhanced integrated magnetic resonance-positron emission tomography in patients with non-small-cell lung cancer.

BACKGROUND: Angiogenesis assessment is important for personalized therapeutic intervention in patients with non-small-cell lung cancer (NSCLC). This study investigated whether radiologic parameters obtained by dynamic contrast-enhanced (DCE)-integrated magnetic resonance-positron emission tomography (MR-PET) could be used to quantitatively assess tumor angiogenesis in NSCLC. METHODS: This prospective cohort study included 75 patients with NSCLC who underwent DCE-integrated MR-PET at diagnosis. The following parameters were analyzed: metabolic tumor volume (MTV), maximum standardized uptake value (SUVmax), reverse reflux rate constant (kep), volume transfer constant (Ktrans), blood plasma volume fraction (vp), extracellular extravascular volume fraction (ve), apparent diffusion coefficient (ADC), and initial area under the time-to-signal intensity curve at 60 s post enhancement (iAUC60). Serum biomarkers of tumor angiogenesis, including vascular endothelial growth factor-A (VEGF-A), angiogenin, and angiopoietin-1, were measured by enzyme-linked immunosorbent assays simultaneously. RESULTS: Serum VEGF-A (p = 0.002), angiogenin (p = 0.023), and Ang-1 (p <  0.001) concentrations were significantly elevated in NSCLC patients compared with healthy individuals. MR-PET parameters, including MTV, Ktrans, and kep, showed strong linear correlations (p <  0.001) with serum angiogenesis-related biomarkers. Serum VEGF-A concentrations (p = 0.004), MTV values (p <  0.001), and kep values (p = 0.029) were significantly higher in patients with advanced-stage disease (stage III or IV) than in those with early-stage disease (stage I or II). Patients with initial higher values of angiogenesis-related MR-PET parameters, including MTV > 30 cm3 (p = 0.046), Ktrans > 200 10- 3/min (p = 0.069), and kep > 900 10- 3/min (p = 0.048), may have benefited from angiogenesis inhibitor therapy, which thus led to significantly longer overall survival. CONCLUSIONS: The present findings suggest that DCE-integrated MR-PET provides a reliable, non-invasive, quantitative assessment of tumor angiogenesis; can guide the use of angiogenesis inhibitors toward longer survival; and will play an important role in the personalized treatment of NSCLC.

Preoperative 2-[18F]FDG PET-CT aids in the prognostic stratification for patients with primary ampullary carcinoma.

OBJECTIVES: We sought to investigate whether preoperative dual-phase 2-[18F]FDG PET-CT identify predictors for poor survival in patients with ampullary carcinoma receiving pancreaticoduodenectomy. METHODS: The preoperative PET-CT images of patients with resected ampullary carcinoma from June 2007 to July 2017 were analyzed. Survival curves were analyzed using the Kaplan-Meier method and compared with the log-rank test. Cox proportional hazard model was used to identify potential prognostic factors associated with disease-free survival (DFS) and overall survival (OS). RESULTS: Fifty-four subjects (26 men, 28 women) were enrolled with a median tumor size of 20 mm. All patients were followed for a median period of 36.9 months with 3- and 5-year DFS of 50.3% and 44.2%, and OS of 77.0% and 68.2%, respectively. Parameters associated with DFS in multivariate analysis were lymphovascular invasion (hazard ratio [HR]: 9.45, p < 0.001), involved margin in pathology (HR: 7.67, p < 0.001), and tumor retention index (RI) from the dual-phase PET (HR: 2.41, p = 0.03), whereas involved margin (HR: 13.14, p < 0.001), post-recurrence chemotherapy (HR: 0.10, p < 0.001), and metabolic tumor volume (MTV) (HR: 4.62, p = 0.009) emerged as independent prognostic factors for OS. CONCLUSIONS: Preoperative 2-[18F]FDG PET-CT offered independent prognostic biomarkers in patients with ampullary carcinoma receiving standard surgical resection. KEY POINTS: • 2-[18F]FDG PET-CT offers good survival prediction before operation in primary malignant neoplasms at ampulla of Vater. • Dual-phase PET scan with bowel distention can better delineate Ampulla of Vater and characterize tumor physiology. • Preoperative risk stratification might aid in better treatment planning.

Effects of Focal Radiation on [18 F]-Fluoro-D-Glucose Positron Emission Tomography in the Brains of Miniature Pigs: Preliminary Findings on Local Metabolism.

OBJECTIVES: It would be a medically important advance if durable and focal neuromodulation of the brain could be delivered noninvasively and without ablation. This ongoing study seeks to elucidate the effects of precisely delivered ionizing radiation upon focal brain metabolism and the corresponding cellular integrity at that target. We hypothesize that focally delivered ionizing radiation to the brain can yield focal metabolic changes without lesioning the brain in the process. MATERIALS AND METHODS: We used stereotactic radiosurgery to deliver doses from 10 Gy to 120 Gy to the left primary motor cortex (M1) of Lee Sung miniature pigs (n = 8). One additional animal served as a nonirradiated control. We used positron emission tomography-computed tomography (PET-CT) to quantify radiation dose-dependent effects by calculating the ratio of standard uptake values (SUV) of 2-deoxy-2-[18 F]-fluoro-D-glucose (18 F-FDG) between the radiated (left) and irradiated (right) hemispheres across nine months. RESULTS: We found that the FDG-PET SUV ratio at the targeted M1 was significantly lowered from the pre-radiation baseline measurements for animals receiving 60 Gy or higher, with the effect persisting at nine months after radiosurgery. Only at 120 Gy was a lesion suggesting ablation visible at the M1 target. Animals treated at 60-100 Gy showed a reduced signal in the absence of an identifiable lesion, a result consistent with the occurrence of neuromodulation. CONCLUSION: Focal, noninvasive, and durable changes in brain activity can be induced without a magnetic resonance imaging (MRI)-visible lesion, a result that may be consistent with the occurrence of neuromodulation. This approach may provide new venues for the investigation of neuromodulatory treatments for disorders involving dysfunctional brain circuits. Postmortem pathological analysis is needed to elucidate whether there have been morphological changes not detected by MRI.

Endoscopic ultrasound ablation in a patient with multiple metastatic pancreatic tumors from adrenocorticotropic hormone-producing thymic neuroendocrine neoplasm.

Adrenocorticotropic hormone (ACTH)-producing neuroendocrine neoplasm (NEN) of the thymus is rare. Lymph nodes and bones are the most common metastatic sites. Most cases present with florid Cushing's syndrome (CS). Here, we reported a 58-year-old woman, who presented with intermittent flush and weight loss. Imaging studies revealed tumors in the mediastinum, pancreas, and bones. Contrast-enhanced harmonic endoscopic ultrasound (EUS) of the pancreatic tumors showed heterogeneous and hyperenhancing characteristics. EUS elastography revealed a heterogeneous stiff pattern. EUS-fine needle biopsy to the pancreatic lesion confirmed the NEN nature. Serum ACTH and cortisol levels were abnormally high. Immunohistochemical staining of the thymic and pancreatic specimens was positive for ACTH. However, the patient did not have obvious CS appearance. The patient underwent surgery, radiation, EUS-guided ethanol injection, and anti-cancer medications, but the disease still progressed. The patient died from infection 16 months after NEN was diagnosed. In conclusion, the pancreas can be a metastatic site for ACTH-producing thymic NEN. EUS-associated procedures can help in the diagnosis and treatment of pancreatic metastatic NEN.

Dermoid cyst with secretion of CA 19-9 detected by 18F-FDG PET/CT: A case report.

INTRODUCTION: Carbohydrate antigen 19-9 (CA 19-9) is a tumor glycolipid, frequently elevated in the serum of patients due to malignancies from gastrointestinal organs; in particular, the pancreas. This carbohydrate antigen is also expressed in benign diseases. PATIENT CONCERNS: A case of a 27-year-old female who has an unknown origin CA 19-9 elevation for 2 years. DIAGNOSIS: After the left ovarian cystectomy and microscopic examination, the final diagnosis is a dermoid cyst. The dermoid cyst shows increased F-fluorodeoxyglucose (F-FDG) uptake in the F-FDG positron emission tomography (PET)/computed tomography (CT) study. INTERVENTION AND OUTCOMES: The laparoscopic oophorocystectomy was performed. It was observed that the patient's CA 19-9 level returned to normal after the surgery 6 months later. This showed that the dermoid cyst was responsible for the abnormal CA 19-9 level. CONCLUSION: In this case, we can learn that the F-FDG PET/CT scan has potential use in patients with unknown origin of elevation CA 19-9.

Predicting tumor responses and patient survival in chemoradiotherapy-treated patients with non-small-cell lung cancer using dynamic contrast-enhanced integrated magnetic resonance-positron-emission tomography.

PURPOSE: We investigated whether radiologic parameters by dynamic contrast-enhanced (DCE) integrated magnetic resonance-positron-emission tomography (MR-PET) predicts tumor response to treatment and survival in non-metastatic non-small-cell lung cancer (NSCLC) patients receiving chemoradiotherapy (CRT). METHODS: Patients underwent DCE integrated MR-PET imaging 1 week before CRT. The following parameters were analyzed: primary tumor size, gross tumor volume, maximal standardized uptake value (SUVmax), total lesion glycolysis (TLG), apparent diffusion coefficient (ADC), volume transfer constant (Ktrans), reverse reflux rate constant (kep), extracellular extravascular volume fraction (ve), blood plasma volume fraction (vp), and initial area under the time-concentration curve defined over the first 60 s post-enhancement (iAUC60). CRT responses were defined using the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1). RESULTS: Thirty patients were included. Non-responders demonstrated higher baseline TLG (p = 0.012), and lower baseline Ktrans (p = 0.020) and iAUC60 (p = 0.016) compared to responders, indicating the usefulness of DCE integrated MR-PET to predict treatment responses. Receiver operating characteristic curve indicated that TLG has the best differentiation capability to predict responders. By setting the threshold of TLG to 277, the sensitivity, specificity, and accuracy were 66.7%, 83.3%, and 75.0%, respectively, with an area under the curve of 0.776. The median follow-up time was 19.6 (range 7.8-32.0) months. In univariate analyses, baseline TLG >277 (p = 0.005) and baseline Ktrans <254 (10-3 min-1; p = 0.015) correlated with poor survival after CRT. In multivariate analysis, baseline TLG >277 remained the significant factor in predicting progression (p = 0.012) and death (p = 0.031). CONCLUSIONS: The radiologic parameters derived from DCE integrated MR-PET scans are useful for predicting treatment response in NSCLC patients treated with CRT; furthermore, these parameters are correlated with clinical and survival outcomes including tumor progression and death.

Surgical outcomes of patients with primary aldosteronism lateralized with I-131-6 ß-iodomethyl-norcholesterol single photon emission/computed tomography without discontinuation or modification of antihypertensive medications.

OBJECTIVES: Adrenocortical scintigraphy for patients with primary aldosteronism (PA) without discontinuation or modification of antihypertensive medications is of concern because of drug interference with the renin-angiotensin-aldosterone system. We report the surgical outcomes of patients with PA lateralized with adrenocortical scintigraphy without drug discontinuation or modification. MATERIALS AND METHODS: We retrospectively reviewed 34 patients with PA with computed tomography (CT)-documented adrenal tumors who had undergoing subsequent I-131-6 ß-iodomethyl-norcholesterol (NP-59) single photon emission CT (SPECT)/CT followed by unilateral adrenalectomy according to the results of NP-59 uptake between May 2005 and December 2014. All enrolled patients underwent standard confirmatory tests and lateralization with NP-59 SPECT/CT without discontinuation of existing antihypertensive medications, including spironolactone. The pathological findings, hypertension outcomes, and biochemical changes were reported. The accuracy of NP-59 SPECT/CT without drug discontinuation or modification was also evaluated. RESULTS: None of the 34 enrolled patients (M:F = 16:18) had complications such as a hypertensive crisis, life-threatening hypokalemic event, or cardiac arrhythmia. Pathology disclosed 31 (91%) adenomas and three cases of hyperplasia. Hypertension cure and improvement were observed in 12 (35%) and 18 (53%) patients, respectively. All of the 30 patients (100%) without postoperative use of beta-blockers and with an available postoperative aldosterone/renin ratio achieved a biochemical cure. The positive predictive values of NP-59 SPECT/CT were 91%, 88%, and 100% for the pathological findings, hypertension outcomes, and biochemical changes, respectively. CONCLUSION: Noninvasive NP-59 SPECT/CT without discontinuation or modification of antihypertensive medications not only provided accurate lateralization and safety but also resulted in a high improvement rate for PA-associated hypertension.

Multiparametric PET/MR imaging biomarkers are associated with overall survival in patients with pancreatic cancer.

PURPOSE: To correlate the overall survival (OS) with the imaging biomarkers of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), diffusion-weighted imaging (DWI), magnetic resonance spectroscopy, and glucose metabolic activity derived from integrated fluorine 18 fluorodeoxyglucose positron emission tomography (18F-FDG PET)/MRI in patients with pancreatic cancer. METHODS: This prospective study was approved by the institutional review board and informed consent was obtained from all participants. Sixty-three consecutive patients (mean age, 62.7 ± 12 y; men/women, 40/23) with pancreatic cancer underwent PET/MRI before treatment. The imaging biomarkers were comprised of DCE-MRI parameters (peak, IAUC 60 , K trans , k ep , v e ), the minimum apparent diffusion coefficient (ADCmin), choline level, standardized uptake values, metabolic tumor volume, and total lesion glycolysis (TLG) of the tumors. The relationships between these imaging biomarkers with OS were evaluated with the Kaplan-Meier and Cox proportional hazard models. RESULTS: Seventeen (27%) patients received curative surgery, with the median follow-up duration being 638 days. Univariate analysis showed that patients at a low TNM stage (≦3, P = 0.041), high peak (P = 0.006), high ADCmin (P = 0.002) and low TLG (P = 0.01) had better OS. Moreover, high TLG/peak ratio was associated with poor OS (P = 0.016). Multivariate analysis indicated that ADCmin (P = 0.011) and TLG/peak ratio (P = 0.006) were independent predictors of OS after adjustment for age, gender, tumor size, and TNM stage. The TLG/peak ratio was an independent predictor of OS in a subgroup of patients who did not receive curative surgery (P = 0.013). CONCLUSION: The flow-metabolism mismatch reflected by the TLG/peak ratio may better predict OS than other imaging biomarkers from PET/MRI in pancreatic cancer patients.

Clinical Utility of FDG PET/CT in Patients with Autoimmune Pancreatitis: a Case-Control Study.

Autoimmune pancreatitis (AIP) shares overlapping clinical features with pancreatic cancer (PC). Importantly, treatment of the two conditions is different. We investigated the clinical usefulness of 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in patients with suspected AIP before treatment. From September 2008 to July 2016, 53 patients with suspected AIP at National Taiwan University Hospital had PET/CT prior to therapy to exclude malignancy and evaluate the extent of inflammation. Their scans were compared with those from 61 PC patients. PET imaging features were analyzed using logistic regression. Significant differences in pancreatic tumor uptake morphology, maximum standardized uptake value, high-order primary tumor texture feature (i.e. high-gray level zone emphasis value), and numbers and location of extrapancreatic foci were found between AIP and PC. Using the prediction model, the area under curve of receiver-operator curve was 0.95 (P < 0.0001) with sensitivity, specificity, positive predictive, and negative predictive values of 90.6%, 84.0%, 87.9%, and 87.5% respectively, in differentiating AIP from PC. FDG PET/CT offers high sensitivity, albeit slightly lower specificity in differentiating AIP from PC. Nonetheless, additional systemic inflammatory foci detected by the whole body PET/CT help confirm diagnosis of AIP in these patients before initiating steroid therapy, especially when biopsy is inconclusive.

Targeting histone deacetylase 4/ubiquitin-conjugating enzyme 9 impairs DNA repair for radiosensitization of hepatocellular carcinoma cells in mice.

Several strategies to improve the efficacy of radiation therapy against hepatocellular carcinoma (HCC) have been investigated. One approach is to develop radiosensitizing compounds. Because histone deacetylase 4 (HDAC4) is highly expressed in liver cancer and known to regulate oncogenesis through chromatin structure remodeling and controlling protein access to DNA, we postulated that HDAC4 inhibition might enhance radiation's effect on HCC cells. HCC cell lines (Huh7 and PLC5) and an ectopic xenograft were pretreated with HDAC inhibitor or short hairpin RNA to knock down expression of HDAC4 and then irradiated (2.5-10.0 Gy). We evaluated cell survival by a clonogenic assay; apoptosis by Annexin V immunofluorescence; γH2AX, Rad51, and HDAC4 by immunofluorescence staining; HDAC4, Rad51, and ubiquitin-conjugating enzyme 9 (Ubc9) in HCC cell nuclei by cell fractionation and confocal microscopy; physical interaction between HDAC4/Rad51/Ubc9 by immunoprecipitation; and the downstream targets of HDAC4 knockdown by immunoblotting. Both HDAC4 knockdown and HDAC inhibitor enhanced radiation-induced cell death and reduced homologous recombination repair of DNA double-strand breaks and protein kinase B activation, leading to increased apoptosis. HDAC4 knockdown with or without an HDAC inhibitor significantly delayed tumor growth in a radiation-treated xenograft model. Radiation stimulated nuclear translocation of Rad51 in an HDAC4-dependent manner and the binding of Ubc9 directly to HDAC4, which led to Ubc9 acetylation. Moreover, these effects were accompanied by HDAC4/Ubc9/Rad51 complex dissociation through inhibiting nuclear translocation. Conclusion: HDAC4 signaling blockade enhances radiation-induced lethality in HCC cells and xenografts. These findings raise the possibility that HDAC4/Ubc9/Rad51 complex in DNA repair may be a target for radiosensitization of HCC. (Hepatology 2018;67:586-599).

Response assessment of stereotactic body radiation therapy using dynamic contrast-enhanced integrated MR-PET in non-small cell lung cancer patients.

PURPOSE: To evaluate the response in patients undergoing SBRT using dynamic contrast-enhanced (DCE) integrated magnetic resonance positron emission tomography (MR-PET). Stereotactic body radiation therapy (SBRT) is efficacious as a front-line local treatment for non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: We prospectively enrolled 19 lung tumors in 17 nonmetastatic NSCLC patients who were receiving SBRT as a primary treatment. They underwent DCE-integrated 3T MR-PET before and 6 weeks after SBRT. The following image parameters were analyzed: tumor size, standardized uptake value (SUV), apparent diffusion coefficient, Ktrans , kep , ve , vp , and iAUC60 . Chest computed tomography (CT) was performed at 3 months after SBRT. RESULTS: SBRT treatment led to tumor changes including significant decreases in the SUVmax (-61%, P < 0.001), Ktrans mean (-72%, P = 0.005), Ktrans standard deviation (SD; -85%, P = 0.046), kep mean (-53%, P = 0.014), kep SD (-63%, P = 0.001), and vp SD (-58%, P = 0.002). The PET SUVmax was correlated with the MR kep mean (P = 0.002) and kep SD (P < 0.001). The percentage reduction in Ktrans mean (P < 0.001) and kep mean (P = 0.034) at 6 weeks post-SBRT were significantly correlated with the percentage reduction in tumor size, as measured using CT at 3 months after SBRT. Univariate analyses revealed a trend toward disease progression when the initial SUVmax > 10 (P = 0.083). CONCLUSION: In patients with NSCLC who are receiving SBRT, DCE-integrated MR-PET can be used to evaluate the response after SBRT and to predict the local treatment outcome. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2018;47:191-199.