Accuracy and reproducibility of a cone beam CT-based virtual parenchymal perfusion algorithm in the prediction of SPECT/CT anatomical and volumetric results during the planification of radioembolization for HCC.

OBJECTIVES: To evaluate anatomical and volumetric predictability of a cone beam computed tomography (CBCT)-based virtual parenchymal perfusion (VPP) software for the single-photon-emission computed tomography (SPECT)/CT imaging results during the work-up for transarterial radioembolization (TARE) procedure in patients with hepatocellular carcinoma (HCC). METHODS: VPP was evaluated retrospectively on CBCT data of patients treated by TARE for HCC. 99mTc macroaggregated albumin particles (99mTc-MAA) uptake territories on work-up SPECT/CT was used as ground truth for the evaluation. Semi-quantitative evaluation consisted of the ranking of visual consistency of the parenchymal enhancement and portal vein tumoral involvement on VPP and 99mTc-MAA SPECT/CT, using a three-rank scale and two-rank scale, respectively. Inter-reader agreement was evaluated using a kappa coefficient. Quantitative evaluation included absolute volume error calculation and Pearson correlation between volumes enhanced territories on VPP and 99mTc-MAA SPECT/CT. RESULTS: Fifty-two CBCTs were performed in 33 included patients. Semi-quantitative evaluation showed a good concordance between actual 99mTc-MAA uptake and the virtual enhanced territories in 73% and 75% of cases; a mild concordance in 12% and 10% and a poor concordance in 15%, for the two readers. Kappa coefficient was 0.86. Portal vein involvement evaluation showed a good concordance in 58.3% and 66.7% for the two readers, respectively, with a kappa coefficient of 0.82. Quantitative evaluation showed a volume error of 0.46 ± 0.78 mL [0.01-3.55], and Pearson R2 factor at 0.75 with a p value < 0.01. CONCLUSION: CBCT-based VPP software is accurate and reliable to predict 99mTc-MAA SPECT/CT anatomical and volumetric results in HCC patients during TARE. KEY POINTS: • Virtual parenchymal perfusion (VPP) software is accurate and reliable in the prediction of 99mTc-MAA SPECT volumetric and targeting results in HCC patients during transarterial radioembolization (TARE). • VPP software may be used per-operatively to optimize the microcatheter position for 90Y infusion allowing precise tumor targeting while preserving non-tumoral parenchyma. • Post-operatively, VPP software may allow an accurate estimation of the perfused volume by each arterial branch and, thus, a precise 90Y dosimetry for TARE procedures.

Chest PET/MRI in Solid Cancers: Comparing the Diagnostic Performance of a Free-Breathing 3D-T1-GRE Stack-of-Stars Volume Interpolated Breath-Hold Examination (StarVIBE) Acquisition With That of a 3D-T1-GRE Volume Interpolated Breath-Hold Examination (VIBE) for Chest Staging During Whole-Body PET/MRI.

BACKGROUND: Whole-body positron emission tomography/magnetic resonance imaging (WB-PET/MRI) is increasingly used in oncology. However, chest staging remains challenging. PURPOSE: To compare the diagnostic performance of a free-breathing 3D-T1-GRE stack-of-stars volume interpolated breath-hold examination (StarVIBE) with that of a 3D-T1-GRE volume interpolated breath-hold examination (VIBE) during WB-PET/MRI for chest staging. STUDY TYPE: Retrospective, cohort study. POPULATION: One hundred and twenty-three patients were referred for initial staging of solid cancer, 46 of whom had pulmonary nodules and 14 had pulmonary metastasis. FIELD STRENGTH/SEQUENCE: Free-breathing 3D-T1-GRE stack-of-stars (StarVIBE) and Cartesian 3D-T1-GRE VIBE at 3.0 T. ASSESSMENT: Image quality was assessed using a 4-point scale and using the signal-to-noise ratio (SNR) of lung parenchyma and contrast-to-noise ratio (CNR) of pulmonary nodules. Diagnostic performances of both sequences were determined by three independent radiologists for detection of pulmonary nodules, lymph node involvement, and bone metastases using chest CT, pathology, and follow-up as reference standards. STATISTICAL TESTS: Paired Student's t-test; chi-squared; Fisher's exact test. A P value <0.05 was considered statistically significant. RESULTS: StarVIBE quality was judged as better in 34% of cases and at least equivalent to VIBE in 89% of cases, with significantly higher quality scores (4 [4-4] vs. 3 [3-4], respectively). SNR and CNR values were significantly higher with StarVIBE (8 ± 1.3 and 9.7 ± 4.6, respectively) than with VIBE (1.8 ± 0.2 and 5.5 ± 3.3, respectively). Compared to VIBE, StarVIBE showed significantly higher sensitivity (73% [95% CI 62-82] vs. 44% [95% CI 33-55], respectively) and specificity (95% [95% CI 88-99] vs. 67% [95% CI 56-77]) for pulmonary nodules detection and significantly higher sensitivity (100% [95% CI 89-100] vs. 67% [95% CI 48-82], respectively) for detection of lymph node involvement. Sensitivities for bone metastases detection were not significantly different (100% [95% CI 88-100] vs. 82% [95% CI 63-94], P = 0.054). DATA CONCLUSION: Owing to improved SNR and CNR and spatial resolution, a free-breathing 3D stack-of-stars T1-GRE sequence improves chest staging in comparison with standard 3D-T1-GRE VIBE and may be integrated in WB-PET/MRI acquisitions for initial staging of solid cancer. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.

Utility of Early Posttreatment PET/CT Evaluation Using FDG or 18F-FCH to Predict Response to 90Y Radioembolization in Patients With Hepatocellular Carcinoma.

BACKGROUND. Assessment of hepatocellular carcinoma (HCC) treatment response after transarterial radioembolization (TARE) is challenging, because response by conventional imaging criteria may not become apparent until 6 months after treatment. Though HCC exhibits variable avidity for FDG, some cases of HCC without avidity for FDG show avidity for 18F-fluorocholine (18F-FCH). OBJECTIVE. The purpose of this study was to evaluate the utility of early posttreatment evaluation by PET/CT using FDG or 18F-FCH to predict 6-month treatment response and survival after TARE in patients with HCC. METHODS. This retrospective study included 37 patients (mean age, 67 years; 34 men, three women) with documented HCC treated by TARE who underwent both pre-treatment FDG PET/CT and 18F-FCH PET/CT and early FDG PET/CT and/or 18F-FCH PET/CT 4-8 weeks after treatment; FDG PET/CT and 18F-FCH PET/CT examinations were performed on separate dates. Only one of 73 initially identified potentially eligible patients was excluded because of lack of HCC avidity for both FDG and 18F-FCH. Response assessment by modified RECIST (mRECIST) on multiphase CT or MRI was performed at 1 month and 6 months in 23 patients. Early responses seen on PET/CT and 1-month mRECIST response were assessed as predictors of 6-month mRECIST response. Univariable and multivariable predictors of overall survival (OS) were identified. RESULTS. On pretreatment PET/CT, 28 (76%) patients were FDG-positive (showed visual uptake on FDG PET/CT and tumor-to-normal liver ratio > 1.15), 15 (41%) were FCH-positive (showed visual uptake on 18F-FCH PET/CT), and six (16%) were both FDG-positive and FCH-positive. Twelve of 28 FDG-positive HCCs exhibited early response by FDG PET/CT; seven of 15 FCH-positive HCCs exhibited early response by 18F-FCH PET/CT. Twelve (52%) patients exhibited 6-month mRECIST response. Response seen on early posttreatment PET/CT exhibited 100% (12/12) sensitivity and 100% (11/11) specificity for 6-month mRECIST response, whereas 1-month mRECIST response exhibited 67% (8/12) sensitivity and 100% (11/11) specificity for 6-month mRECIST response. Response seen on early posttreatment PET/CT was a significant independent predictor of OS on univariable (hazard ratio [HR], 0.4; 95% CI, 0.2-0.9; p = .03) and multivariable (HR, 0.2; 95% CI, 0.1-0.8; p = .01) analyses. CONCLUSION. Early evaluation after TARE by PET/CT using FDG or 18F-FCH may pre dict 6-month response and OS in patients with HCC. CLINICAL IMPACT. Early posttreatment evaluation with PET/CT could help more reliably identify true nonresponders after TARE, which in turn could prompt early response-adapted therapeutic management.

Hepatocellular Carcinomas With Mutational Activation of Beta-Catenin Require Choline and Can Be Detected by Positron Emission Tomography.

BACKGROUND & AIMS: In one-third of hepatocellular carcinomas (HCCs), cancer cells have mutations that activate ß-catenin pathway. These cells have alterations in glutamine, bile, and lipid metabolism. We investigated whether positron emission tomography (PET) imaging allows identification of altered metabolic pathways that might be targeted therapeutically. METHODS: We studied mice with activation of ß-catenin in liver (Apcko-liv mice) and male C57Bl/6 mice given injections of diethylnitrosamine, which each develop HCCs. Mice were fed a conventional or a methionine- and choline-deficient diet or a choline-deficient (CD) diet. Choline uptake and metabolism in HCCs were analyzed by micro-PET imaging of mice; livers were collected and analyzed by histologic, metabolomic, messenger RNA quantification, and RNA-sequencing analyses. Fifty-two patients with HCC underwent PET imaging with 18F-fluorodeoxyglucose, followed by 18F-fluorocholine tracer metabolites. Human HCC specimens were analyzed by immunohistochemistry, quantitative polymerase chain reaction, and DNA sequencing. We used hepatocytes and mouse tumor explants for studies of incorporation of radiolabeled choline into phospholipids and its contribution to DNA methylation. We analyzed HCC progression in mice fed a CD diet. RESULTS: Livers and tumors from Apcko-liv mice had increased uptake of dietary choline, which contributes to phospholipid formation and DNA methylation in hepatocytes. In patients and in mice, HCCs with activated ß-catenin were positive in 18F-fluorocholine PET, but not 18F-fluorodeoxyglucose PET, and they overexpressed the choline transporter organic cation transporter 3. The HCC cells from Apcko-liv mice incorporated radiolabeled methyl groups of choline into phospholipids and DNA. In Apcko-liv mice, the methionine- and choline-deficient diet reduced proliferation and DNA hypermethylation of hepatocytes and HCC cells, and the CD diet reduced long-term progression of tumors. CONCLUSIONS: In mice and humans, HCCs with mutations that activate ß-catenin are characterized by increased uptake of a fluorocholine tracer, but not 18F-fluorodeoxyglucose, revealed by PET. The increased uptake of choline by HCCs promotes phospholipid formation, DNA hypermethylation, and hepatocyte proliferation. In mice, the CD diet reverses these effects and promotes regression of HCCs that overexpress ß-catenin.

Hepatobiliary MR contrast agent uptake as a predictive biomarker of aggressive features on pathology and reduced recurrence-free survival in resectable hepatocellular carcinoma: comparison with dual-tracer 18F-FDG and 18F-FCH PET/CT.

OBJECTIVES: To compare the performance of the quantitative analysis of the hepatobiliary phase (HBP) tumor enhancement in gadobenate dimeglumine (Gd-BOPTA)-enhanced MRI and of dual-tracer 18F-FDG and 18F-fluorocholine (FCH) PET/CT for the prediction of tumor aggressiveness and recurrence-free survival (RFS) in resectable hepatocellular carcinoma (HCC). METHODS: This retrospective, IRB approved study included 32 patients with 35 surgically proven HCCs. All patients underwent Gd-BOPTA-enhanced MRI including delayed HBP images, 18F-FDG PET/CT, and (for 29/32 patients) 18F-FCH PET/CT during the 2 months prior to surgery. For each lesion, the lesion-to-liver contrast enhancement ratio (LLCER) on MRI HBP images and the SUVmax tumor-to-liver ratio (SUVT/L) for both tracers were calculated. Their predictive value for aggressive pathological features-including the histological grade and microvascular invasion (MVI)-and RFS were analyzed and compared using area under receiver operating characteristic (AUROC) curves and Cox regression models, respectively. RESULTS: The AUROCs for the identification of aggressive HCCs on pathology with LLCER, 18F-FDG SUVT/L, and 18F-FCH SUVT/L were 0.92 (95% CI 0.78, 0.98), 0.89 (95% CI 0.74, 0.97; p = 0.70), and 0.64 (95% CI 0.45, 0.80; p = 0.035). At multivariate Cox regression analysis, LLCER was identified as an independent predictor of RFS (HR (95% CI) = 0.91 (0.84, 0.99), p = 0.022). LLCER - 4.72% or less also accurately predicted moderate-poor differentiation grade (Se = 100%, Sp = 92.9%) and MVI (Se = 93.3%, Sp = 60%) and identified patients with poor RFS after surgical resection (p = 0.030). CONCLUSIONS: HBP tumor enhancement after Gd-BOPTA injection may help identify aggressive HCC pathological features, and patients with reduced recurrence-free survival after surgical resection. KEY POINTS: • In patients with resectable HCC, the quantitative analysis of the HBP tumor enhancement in Gd-BOPTA-enhanced MRI (LLCER) accurately identifies moderately-poorly differentiated and/or MVI-positive HCCs. • After surgical resection for HCC, patients with LLCER - 4.72% or less had significantly poorer recurrence-free survival than patients with LLCER superior to - 4.72%. • Gd-BOPTA-enhanced MRI with delayed HBP images may be suggested as part of pre-surgery workup in patients with resectable HCC.

18F-FDG PET/CT predicts microvascular invasion and early recurrence after liver resection for hepatocellular carcinoma: A prospective observational study.

BACKGROUND: This study assessed the prognostic value of 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) in the prediction of MVI and early recurrence following resection. METHOD: This prospective study (ClinicalTrials.gov ID: NCT02145013) included 78 consecutive HCC patients who underwent 18F-FDG PET/CT before curative-intent resection from 2014 to 2017. Prognostic factors available before surgery for predicting MVI and early recurrence (≤2 years) were identified by univariate and multivariate analyses. RESULTS: The 18F-FDG PET/CT result was positive in 30 (38%) patients. MVI was present in 33% (26/78) of specimens. Early recurrence occurred in 19% (14/74) of surviving patients. PET/CT positivity was the sole independent predictor of MVI (odds ratio [OR] = 3.6, 95% confidence interval [CI] = 1.1-11.2; p = 0.03), with a specificity and sensitivity for predicting MVI of 73% and 62%, respectively. Analysis of variables available before surgery showed that PET/CT positivity (hazard ratio [HR] = 5.8, 95% CI = 1.6-20.4; p = 0.006) and the male sex (HR = 6.6; 95% CI = 1.8-24.2; p = 0.005) were independent predictors of early recurrence. CONCLUSION: 18F-FDG PET/CT predicts MVI and early recurrence after surgery for HCC and could be used to select patients for neoadjuvant treatment.

Positron emission tomography/computed tomography with 18F-fluorocholine improve tumor staging and treatment allocation in patients with hepatocellular carcinoma.

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) staging according to the Barcelona Clinical Liver Cancer (BCLC) classification is based on conventional imaging. The aim of our study was to assess the impact of dual-tracer 18F-fluorocholine and 18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) on tumor staging and treatment allocation. METHODS: A total of 192 dual-tracer PET/CT scans (18F-fluorocholine and 18F-fluorodeoxyglucose PET/CT) were performed in 177 patients with HCC. BCLC staging and treatment proposal were retrospectively collected based on conventional imaging, along with any new lesions detected, and changes in BCLC classification or treatment allocation based on dual-tracer PET/CT. RESULTS: Patients were primarily men (87.5%) with cirrhosis (71%) due to alcohol ±â€¯non-alcoholic steatohepatitis (26%), viral infection (62%) or unknown causes (12%). Among 122 patients with PET/CT performed for staging, BCLC stage based on conventional imaging was 0/A in 61 patients (50%), B in 32 patients (26%) and C in 29 patients (24%). Dual-tracer PET/CT detected new lesions in 26 patients (21%), upgraded BCLC staging in 14 (11%) and modified treatment strategy in 17 (14%). In addition, dual-tracer PET/CT modified the final treatment in 4/9 (44%) patients with unexplained elevation of alpha-fetoprotein (AFP), 10/25 patients (40%) with doubtful lesions on conventional imaging and 3/36 patients (8%) waiting for liver transplantation without active HCC after tumor response following bridging therapy. CONCLUSION: When used for HCC staging, dual-tracer PET/CT enabled BCLC upgrading and treatment modification in 11% and 14% of patients, respectively. Dual-tracer PET/CT might also be useful in specific situations (an unexplained rise in AFP, doubtful lesions or pre-transplant evaluation of patients without active HCC). LAY SUMMARY: Using a combination of tracers 18F-fluorocholine and 18F-fluorodeoxyglucose when performing positron emission tomography/computed tomography (PET/CT), often called a PET scan, helps to identify new tumor lesions in patients with hepatocellular carcinoma. This technique enabled staging modification of patients' tumors and led to changes in treatment allocation in certain patients.

[18F]-NaF PET/CT imaging in cardiac amyloidosis.

Cardiac amyloidosis (CA) is recognized as a common cause of restrictive cardiomyopathy and heart failure due to the deposition of insoluble proteins in the myocardial interstitium. We emphasize the role of [18F]-sodium fluoride (NaF) PET/CT as a potential noninvasive tool to identify and differentiate the transthyretin-related cardiac amyloidosis from the light-chain cardiac amyloidosis. We report cases of a 73-year-old man and a 75-year-old woman followed in our center for congestive heart failure with marked alteration of the left ventricular ejection fraction due to familial transthyretin Val122Ile cardiac amyloidosis and light-chain cardiac amyloidosis, respectively, confirmed on endomyocardial biopsy.

Selective internal radiation therapy for unresectable HCC: The SIRT downstaging study.

BACKGROUND: Selective internal radiation therapy (SIRT) is recommended as a downstaging (DS) strategy for solitary unresectable HCC <8 cm. The aim of this study was to report the results of acquired experience in a tertiary center for all unresectable HCCs. METHODS: We conducted a retrospective, observational study using data collected from consecutive patients undergoing SIRT between October 2013 and June 2020. DS was considered achieved when a curative treatment could be proposed 6 months after SIRT. RESULTS: One hundred twenty-seven patients were included (male = 90%, 64 ± 11 y), of whom 112 (n = 88%) had cirrhosis. HCC was classified as BCLC stage C in 64 patients (50%), with a median diameter of 61 mm, an infiltrative pattern in 51 patients (40%), and portal vein invasion in 62 (49%) patients. Fifty patients (39%) achieved DS 6 months following SIRT, with 29 of them (23%) undergoing curative treatment in a median time of 4.3 months: 17 (13%) were transplanted, 11 (85%) had liver resection, and 1 patient had a radiofrequency ablation. The median overall survival of patients with or without DS was 51 versus 10 months, respectively (p < 0.001). In patients who achieved DS, progression-free survival was higher in patients who underwent surgery: 47 versus 11 months (p < 0.001). Four variables were independently associated with DS: age (OR: 0.96, 95% CI: [0.92, 0.99]; p = 0.032), baseline α-fetoprotein (OR: 1.00, 95% CI: [1.00, 1.00]; p = 0.034), HCC distribution (OR: 0.3, 95% CI: [0.11, 0.75]; p = 0.012), and ALBI grade (OR: 0.34. 95% CI: [0.14, 0.80]; p = 0.014). CONCLUSIONS: These results suggest that SIRT in patients with unresectable HCC could be an effective treatment: DS was achieved for around 39% of the patients and more than half of these then underwent curative treatment.

Long-Term Overall Survival After Selective Internal Radiation Therapy for Locally Advanced Hepatocellular Carcinomas: Updated Analysis of DOSISPHERE-01 Trial.

Interim analysis of the DOSISPHERE-01 study demonstrated a strong improvement in response and overall survival (OS) on using 90Y-loaded glass microspheres with personalized dosimetry compared with standard dosimetry in patients with nonoperable locally advanced hepatocellular carcinoma. This report sought to provide a long-term analysis of OS. Methods: In this phase II study (ClinicalTrials.gov identifier NCT02582034), treatment was randomly assigned (1:1) with the goal to deliver either at least 205 Gy (if possible >250-300 Gy) to the index lesion in the personalized dosimetry approach (PDA) or 120 ± 20 Gy to the treated volume in the standard dosimetry approach (SDA). The 3-mo response of the index lesion was the primary endpoint, with OS being one of the secondary endpoints. This report is a post hoc long-term analysis of OS. Results: Overall, 60 hepatocellular carcinoma patients with at least 1 lesion larger than 7 cm and more than 30% of hepatic reserve were randomized (intent-to-treat population: PDA, n = 31; SDA, n = 29), with 56 actually treated (modified intent-to-treat population: n = 28 in each arm). The median follow-up for long-term analysis was 65.8 mo (range, 2.1-73.1 mo). Median OS was 24.8 mo and 10.7 mo (hazard ratio [HR], 0.51; 95% CI, 0.29-0.9; P = 0.02) for PDA and SDA, respectively, in the modified intent-to-treat population. Median OS was 22.9 mo for patients with a tumor dose of at least 205 Gy, versus 10.3 mo for those with a tumor dose of less than 205 Gy (HR, 0.42; 95% CI, 0.22-0.81; P = 0.0095), and was 22.9 mo for patients with a perfused liver dose of 150 Gy or higher, versus 10.3 mo for those with a perfused liver dose of less than 150 Gy (HR, 0.42; 95% CI, 0.23-0.75; P = 0.0033). Lastly, median OS was not reached in patients who were secondarily resected (n = 11, 10 in the PDA group and 1 in the SDA group), versus 10.8 mo in those without secondary resection (n = 45) (HR, 0.17; 95% CI, 0.065-0.43; P = 0.0002). Only resected patients displayed favorable long-term OS rates, meaning an OS of more than 50% at 5 y. Conclusion: After longer follow-up, personalized dosimetry sustained a meaningful improvement in OS, which was dramatically improved for patients who were accurately downstaged toward resection, including most portal vein thrombosis patients.

Non-invasive diagnosis and follow-up of primary malignant liver tumours.

Among a wide range of malignant liver tumours, hepatocellular carcinoma (HCC) developed on a background of cirrhosis represents the most frequent clinical situation. In this setting, HCC is one of the rare solid tumours for which histological confirmation is not mandatory. The convergence of multiple arguments obtained by non-invasive parameters using radiological findings allows to avoid liver biopsy in a large proportion of patients when a diagnosis of underlying cirrhosis is ascertained. Conversely, in case of atypical presentation or in order to exclude other rare malignant tumours mostly developed in the absence of cirrhosis, liver biopsy will then be essential. Based on typical radiological patterns described by contrast-enhanced imaging, numerous clinical guidelines have endorsed non-invasive diagnosis, staging and monitoring of HCC patients under treatment since 20 years. These algorithms have evolved over the years, taking into account progress in radiological technology and advances in curative or palliative procedures. Large cohort studies have also helped to refine diagnostic criteria and prognostication in the setting of complex therapeutic strategy. Unsupervised multi-analysis approaches both at the biological and radiological levels will in the future enrich the panel of non-invasive markers useful in clinical practice to manage HCC and other malignant tumours.

Impact of the 18F-FDG-PET/MRI on Metastatic Staging in Patients with Hepatocellular Carcinoma: Initial Results from 104 Patients.

Optimal HCC therapeutic management relies on accurate tumor staging. Our aim was to assess the impact of 18F-FDG-WB-PET/MRI on HCC metastatic staging, compared with the standard of care CT-CAP/liver MRI combination, in patients with HCC referred on a curative intent or before transarterial radioembolization. One hundred and four consecutive patients followed for HCC were retrospectively included. The WB-PET/MRI was compared with the standard of care CT-CAP/liver MRI combination for HCC metastatic staging, with pathology, followup, and multidisciplinary board assessment as a reference standard. Thirty metastases were identified within 14 metastatic sites in 11 patients. The sensitivity of WB-PET/MRI for metastatic sites and metastatic patients was significantly higher than that of the CT-CAP/liver MRI combination (respectively 100% vs. 43%, p = 0.002; and 100% vs. 45%, p = 0.01). Metastatic sites missed by CT-CAP were bone (n = 5) and distant lymph node (n = 3) in BCLC C patients. For the remaining 93 nonmetastatic patients, three BCLC A patients identified as potentially metastatic on the CT-CAP/liver MRI combination were correctly ruled out with the WB-PET/MRI without significant increase in specificity (100% vs. 97%; p = 0.25). The WB-PET/MRI may improve HCC metastatic staging and could be performed as a "one-stop-shop" examination for HCC staging with a significant impact on therapeutic management in about 10% of patients especially in locally advanced HCC.

Personalised versus standard dosimetry approach of selective internal radiation therapy in patients with locally advanced hepatocellular carcinoma (DOSISPHERE-01): a randomised, multicentre, open-label phase 2 trial.

BACKGROUND: All randomised phase 3 studies of selective internal radiation therapy for advanced hepatocellular carcinoma published to date have reported negative results. However, these studies did not use personalised dosimetry. We aimed to compare the efficacy of a personalised versus standard dosimetry approach of selective internal radiation therapy with yttrium-90-loaded glass microspheres in patients with hepatocellular carcinoma. METHODS: DOSISPHERE-01 was a randomised, multicentre, open-label phase 2 trial done at four health-care centres in France. Patients were eligible if they were aged 18 years or older and had unresectable locally advanced hepatocellular carcinoma, at least one measurable lesion 7 cm or more in size, a hepatic reserve of at least 30% after selective internal radiation therapy, no extrahepatic spread (other than to the lymph nodes of the hilum, with a lesion <2 cm in size), and no contraindications to selective internal radiation therapy, as assessed by use of a technetium-99m macro-aggregated albumin scan. Patients were randomly assigned (1:1) by use of a permutated block method, with block sizes of four and without stratification, to receive either standard dosimetry (120 ±â€ˆ20 Gy) targeted to the perfused lobe; standard dosimetry group) or personalised dosimetry (≥205 Gy targeted to the index lesion; personalised dosimetry group). Investigators, patients, and study staff were not masked to treatment. The primary endpoint was the investigator-assessed objective response rate in the index lesion, according to European Association for the Study of the Liver criteria, at 3 months after selective internal radiation therapy in the modified intention-to-treat population. Safety was assessed in all patients who received at least one selective internal radiation therapy injection, and analysed on the basis of the treatment actually received (defined by central dosimetry assessment). The trial is registered with ClinicalTrials.gov, NCT02582034, and has been completed. FINDINGS: Between Dec 5, 2015, and Jan 4, 2018, 93 patients were assessed for eligibility. Of these patients, 60 were randomly assigned: 31 to the personalised dosimetry group and 29 to the standard dosimetry group (intention-to-treat population). 56 (93%) patients (28 in each group) were treated (modified intention-to-treat population). In the modified intention-to-treat population, 20 (71% [95% CI 51-87]) of 28 patients in the personalised dosimetry group and ten (36% [19-56]) of 28 patients in the standard dosimetry group had an objective response (p=0·0074). In the safety analysis population, a least one serious adverse event was reported in seven (20%) of the 35 patients who received personalised dosimetry, and in seven (33%) of the 21 patients who received standard dosimetry. The most frequent (ie, occurring in >5% of patients) grade 3 or higher adverse events were ascites (one [3%] patient who received personalised dosimetry vs two [10%] patients who received standard dosimetry), hepatic failure (two [6%] vs none), lymphopenia (12 [34%] vs nine [43%]), increased aspartate aminotransferase concentrations (three [9%] vs two [10%]), increased alanine aminotransferase concentrations (three [9%] vs none), anaemia (two [6%] vs one [5%]), gastrointestinal haemorrhage (none vs two [10%]), and icterus (none vs two [10%]). One treatment-related death occurred in each group. INTERPRETATION: Compared with standard dosimetry, personalised dosimetry significantly improved the objective response rate in patients with locally advanced hepatocellular carcinoma. The results of this study suggest that personalised dosimetry is likely to improve outcomes in clinical practice and should be used in future trials of selective internal radiation therapy. FUNDING: Biocompatibles UK, a Boston Scientific Group company.

FDG PET/CT of Cervical Gout With Spinal Cord Compression.

We report FDG PET/CT images of a 63-year-old woman referred for characterization of osteolytic lesions of the cervical spine. This patient with chronic renal failure had a history of follicular thyroid carcinoma with undifferentiated cells, treated by a total thyroidectomy, completed by radioactive iodine in 2017. Because of cancer history, a FDG PET/CT was performed and showed multiple moderately hypermetabolic osteolytic lesions of the spine from C3 to T1, with joint erosion on CT. A laminectomy was performed for cervical spinal cord decompression and revealed a gouty tophus.

Clinical impact of dual-tracer FDOPA and FDG PET/CT for the evaluation of patients with parkinsonian syndromes.

Parkinsonian syndromes include typical cases of idiopathic Parkinson's disease (PD) and atypical parkinsonian syndromes (APS) associated with cognitive and vegetative disorders, which are more challenging to diagnose. The aim of this study was to assess -the value of dual-tracer imaging 6-fluoro-(18F)-L-DOPA (FDOPA) and fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT), performed in routine patients demonstrating extrapyramidal signs and cognitive complains, for the diagnosis and management of parkinsonian syndromes.We retrospectively included 143 consecutive patients who underwent both FDOPA PET/CT (for the evaluation of parkinsonism) and FDG PET/CT (for the evaluation of cognitive complaints) in the same institution. The suspected clinical diagnosis before imaging and the final post-imaging diagnosis were collected by a dedicated questionnaire.FDOPA was pathological in 90.2% of cases, including 74.1% of PD, 3.5% of parkinsonian dementia and 7% of APS. FDG was normal or near normal in 58.7% of patients. A pattern of diffuse cortical hypometabolism was observed in the remaining patients, more frequently in APS than in PD patients (P = .001). Importantly, in 7.7% of cases dual-tracer PET/CT allowed to decide between several diagnostic hypotheses and led to a new diagnosis in 14.0%. Therefore, the management of these patients was modified, with clinical re-evaluation in a specialized unit and a control of neuropsychological tests and imaging.Dual-tracer PET/CT imaging may be a precious help in the diagnosis and management of parkinsonian syndromes.

Brain 18F-FDG PET Metabolic Abnormalities in Patients with Long-Lasting Macrophagic Myofascitis.

The aim of this study was to characterize brain metabolic abnormalities in patients with macrophagic myofascitis (MMF) and the relationship with cognitive dysfunction through the use of PET with 18F-FDG. Methods:18F-FDG PET brain imaging and a comprehensive battery of neuropsychological tests were performed in 100 consecutive MMF patients (age [mean ± SD], 45.9 ± 12 y; 74% women). Images were analyzed with statistical parametric mapping (SPM12). Through the use of analysis of covariance, all 18F-FDG PET brain images of MMF patients were compared with those of a reference population of 44 healthy subjects similar in age (45.4 ± 16 y; P = 0.87) and sex (73% women; P = 0.88). The neuropsychological assessment identified 4 categories of patients: those with no significant cognitive impairment (n = 42), those with frontal subcortical (FSC) dysfunction (n = 29), those with Papez circuit dysfunction (n = 22), and those with callosal disconnection (n = 7). Results: In comparison with healthy subjects, the whole population of patients with MMF exhibited a spatial pattern of cerebral glucose hypometabolism (P < 0.001) involving the occipital lobes, temporal lobes, limbic system, cerebellum, and frontoparietal cortices, as shown by analysis of covariance. The subgroup of patients with FSC dysfunction exhibited a larger extent of involved areas (35,223 voxels vs. 13,680 voxels in the subgroup with Papez circuit dysfunction and 5,453 voxels in patients without cognitive impairment). Nonsignificant results were obtained for the last subgroup because of its small population size. Conclusion: Our study identified a peculiar spatial pattern of cerebral glucose hypometabolism that was most marked in MMF patients with FSC dysfunction. Further studies are needed to determine whether this pattern could represent a diagnostic biomarker of MMF in patients with chronic fatigue syndrome and cognitive dysfunction.

Brain (18)F-FDG, (18)F-Florbetaben PET/CT, (123)I-FP-CIT SPECT and Cardiac (123)I-MIBG Imaging for Diagnosis of a "Cerebral Type" of Lewy Body Disease.

A 67-year-old man was referred for fluctuating neuropsychiatric symptoms, featuring depression, delirious episodes, recurrent visual hallucinations and catatonic syndrome associated with cognitive decline. No parkinsonism was found clinically even under neuroleptic treatment. (18)F-FDG PET/CT showed hypometabolism in the posterior associative cortex including the occipital cortex, suggesting Lewy body dementia, but (123)I-FP-CIT SPECT was normal and cardiac (123)I-MIBG imaging showed no signs of sympathetic denervation. Alzheimer's disease was excluded by a normal (18)F-florbetaben PET/CT. This report suggests a rare case of α-synucleinopathy without brainstem involvement, referred to as "cerebral type" of Lewy body disease.

Functional imaging of hepatocellular carcinoma using diffusion-weighted MRI and (18)F-FDG PET/CT in patients on waiting-list for liver transplantation.

BACKGROUND: To compare the apparent diffusion coefficient (ADC) on diffusion-weighted imaging (DWI) with the standardized uptake values (SUV) measured by(18)F-FDG-PET/CT in naïve hepatocellular carcinoma (HCC) nodules, and to determine whether these markers are associated with tumours at high-risk of aggressiveness. METHODS: From 2007 to 2010, all patients with HCC on the waiting list for liver transplantation and who underwent both FDG-PET/CT and 1.5-T DWI-MRI (b values: 0, 200, 400, and 800 s/mm(2)) were included in this institutional review board-approved retrospective study. Tumour size, tumour ADC, tumour-to-liver ADC ratio (ADCT/L), maximal tumour SUV and tumour-to-liver SUV ratio (SUVT/L) were measured and compared to serum alpha-fetoprotein (AFP) levels, tumour size and differentiation grade on explanted specimens. RESULTS: A total of 37 HCC nodules in 28 patients were available for correlation between MRI and PET/CT, 7 of which (in 7 patients) showed a SUVT/L > 1.15. We did not find any correlation between tumour ADC or ADCT/L and tumour SUV or SUVT/L. To note, SUVT/L was positively correlated with AFP levels (R = 0.95, P ≤ 0.0001), while ADCT/L was not (P = 0.73). Twenty-four patients (with 32 nodules) underwent liver transplantation. In this subgroup, an increased SUVT/L ratio was associated with larger tumours (average size, 32 ± 14 mm; range, 18-60 mm; P < 0.0001) and with poor differentiation on pathology (grades 3 and 4; P = 0.04), while ADCT/L was neither associated with tumour size or differentiation grade. CONCLUSIONS: ADC and SUV measures in HCC nodules are not correlated. SUVT/L ratio correlates with AFP levels, tumour size and poor differentiation, and should probably be integrated as a co-variable in a predictive outcome model of patients on the waiting-list for liver transplantation.