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Background: No direct prospective studies comparing laser ablation (LA) and radiofrequency ablation (RFA) for debulking benign non-functioning thyroid nodules (BNTNs) exist. We aimed at comparing t...

Liver is the predominant site of metastatization for neuroendocrine tumors (NETs). Up to 75% of patients affected by intestinal NETs present liver metastases at diagnosis. For hepatic NET, surgery represents the most effective approach but is often unfeasible due to the massive involvement of multifocal disease. In such cases, chemotherapy, peptide receptor radionuclide therapy and loco-regional treatments may represent alternative therapeutic options. In particular, radioembolization with 90Y-microspheres has been introduced as a novel technique for treating hepatic malignant lesions, combining the principles of embolization and radiation therapy. In order to evaluate the response to 90Y-radioembolization, standard radiologic criteria have been demonstrated to present several limitations. 18Fluoro-deoxyglucose (FDG) Positron Emission Tomography (PET) is routinely used for monitoring the response to therapy in oncology. Nevertheless, NETs often present low glycolytic activity thus the conventional 18FDG PET may not be adequate for these tumors. For many years, somatostatin receptor scintigraphy (SRS) with 111In-pentetreotide has been used for diagnosis and staging of NETs. More recently, three 68Ga-DOTA-compounds have been developed and introduced for the imaging of NETs with PET technology. The aim of the present paper was to review the existing literature concerning the application of different metabolic and molecular probes for the imaging evaluation of hepatic NETs following 90Y-RE.

Introduction: Theranostics is an emerging field in which diagnosis and specific targeted therapy are combined to achieve a personalized treatment approach to the patient. In nuclear medicine clinical practice, theranostics is often performed utilizing the same molecule labeled with two different radionuclides, one radionuclide for imaging and another for therapy.Areas covered: The authors review the clinical applications of different radiopharmaceuticals in the field of interest, including the well-established use of radioactive iodine in differentiated thyroid cancer, radiolabeled metaiodobenzylguanidine (MIBG) in neuroblastoma and the clinical impact of peptide radionuclide receptorial therapy (PRRT) in the management of neuroendocrine tumors. Furthermore, the more cutting-edge and recently introduced theranostic approaches will be reviewed, such as the radioligand therapy with 177Lu-prostate specific membrane antigen (PSMA) and targeted alpha therapy in castration-resistant prostate cancer. Finally, the main applications of PET for the imaging of biomarkers suitable for the non-radionuclide targeted therapy will be covered.Expert opinion: Theranostics is envisaging a revolutionary clinical approach which is deeply connected with the concept of personalized medicine and ruled by a 'patient-centered' vision. In this perspective, the theranostic applications will need well-trained specialists, capable to manage not only the technological aspects of the discipline, but also to deal with the more innovative oncological therapies in a multidisciplinary setting.

The aim of this study was to investigate the prognostic value of neutrophil-to-lymphocyte ratio (NLR) and its relationship with several metabolic parameters obtained through PET in intrahepatic cholangiocarcinoma (ICC) submitted to radioembolization with Y-microspheres (Y-radioembolization).Records of 20 subjects affected by ICC and submitted to Y-radioembolization were retrospectively evaluated. In all cases, pretreatment NLR was carried out and fluorine-18-fluorodeoxyglucose (F-FDG) PET/CT was acquired with the calculation of the following metabolic parameters: maximum and mean standardized uptake value (SUVmax and SUVmean), metabolic total volume and total lesion glycolysis. After Y-radioembolization, all patients underwent regular imaging and laboratory follow-up.All patients presented F-FDG-avid hepatic tumors at pretreatment PET/CT examination. NLR significantly correlated with SUVmax (r = 0.64; P = 0.002) and SUVmean (r = 0.67; P = 0.001). After treatment with Y-microspheres, the mean OS resulted 12.5 ± 1.5 months. When the average pretreatment NLR value (i.e. 2.7) was used as a cutoff for patients' stratification, subjects with low NLR (2.7) had a significantly longer OS than those with high NLR (2.7). At Cox regression analysis including bilirubin, age, the presence of extrahepatic disease, hepatitis C virus/hepatitis B virus status and PET-derived parameters, only NLR resulted to be a significant predictor of OS (P = 0.01; hazard ratio = 13.1, 95% confidence interval = 1.6-102.7).NLR is correlated with SUVmax-mean values in ICC and resulted to be an easy available predictor of survival in patients submitted to treatment with Y-microspheres.

Background: critically ill patients with SARS-CoV-2 infection present a hypercoagulable condition. Anticoagulant therapy is currently recommended to reduce thrombotic risk, leading to potentially severe complications like spontaneous bleeding (SB). Percutaneous transcatheter arterial embolization (PTAE) can be life-saving in critical patients, in addition to medical therapy. We report a major COVID-19 Italian Research Hospital experience during the pandemic, with particular focus on indications and technique of embolization. Methods: We retrospectively included all subjects with SB and with a microbiologically confirmed SARS-CoV-2 infection, over one year of pandemic, selecting two different groups: (a) patients treated with PTAE and medical therapy, (b) patients treated only with medical therapy. Computed tomography (CT) scan findings, clinical conditions, and biological findings were collected. Results: 21/1075 patients presented soft tissue SB with an incidence of 1.95%. 10/21 patients were treated with PTAE and medical therapy with a 30-days survival of 70%. Arterial blush, contrast late enhancement, and dimensions at CT scan were found discriminating for the embolization (p &lt, 0.05). Conclusions: PTAE is an important tool in severely ill, bleeding COVID-19 patients. The decision for PTAE of COVID-19 patients must be carefully weighted with particular attention paid to the clinical and biological condition, hematoma location and volume.

Background: The aim of this study was to evaluate the safety and efficacy of repeated administration of 90Y-microspheres in intrahepatic cholangiocarcinoma (ICC) relapsed after the first radioembolization (RE). Methods: Nine patients with ICC relapsed after the first 90Y-RE were enrolled. Six patients presented recurrence in the right hepatic lobe, 3 in the left lobe. All subjects underwent a second administration of 90Y-resin microspheres. Toxicity was assessed according to Common Terminology Criteria for Adverse Events (CTCAE, version 4.02). After the repeated treatment, all patients were submitted to follow-up with laboratory, imaging, and clinical examinations. Results: The mean cumulative activity administered considering both treatments was 2.7 ± 0.5 GBq. After the second treatment, 3 patients presented complete metabolic response (33.3%) and 6 had partial response (66.6%). The following adverse events were registered: transient increased levels of liver enzymes (grade 1 = 4; grade 2 = 2), hyperbilirubinemia (grade 1 = 2), ascites (grade 2 = 1), and duodenal ulcer (grade 2 = 1). Two patients developed a significant shrinking of the targeted hepatic lobe, as for radiation lobectomy. No case of RE-induced liver disease was registered. Median overall survival was 16.5 ± 1.4 months after the first RE. Conclusions: The authors' results suggest that repeated administration of 90Y-microspheres may be considered in patients affected by ICC relapsed after the first 90Y-RE.

ABSTRACT Background: Up to now, there are no direct prospective studies comparing Laser (LA) and radiofrequency ablation (RFA). We aimed to compare, in a head- to-head clinical trial, the efficacy and safety of both techniques in a population affected by solid or predominantly solid benign non-functioning thyroid nodules (BNTN). Methods. LARA is a six-month, single-use, randomized, superiority, open-label, parallel trial. We enrolled subjects with a solitary BNTN or dominant nodule characterized by pressure symptoms/cosmetic problems or patients without symptoms who experienced a volume increase >20% in one year. Nodules underwent core needle biopsy (CNB) to evaluate the histological architecture. Patients were randomly assigned (1:1) to receive treatment with either LA or RFA. The primary endpoint was to evaluate the difference in nodule volume reduction between the RF and the LA group at six months. Moreover, we aimed to assess the differences between groups in the rate of nodules with greater than 50% base volume reduction (successful rate) at six months after treatment. ClinicalTrials.gov: number NCT02714946. Findings: From January 2016 to November 2018, 60 patients were randomly assigned (30 participants per group). In the whole study population, the average volume of nodules was 25 ml. The two groups were similar in terms of basal nodule volume, thyroid function, histology, symptoms/cosmetic score and procedure time. At six months, participants in the RFA group showed a reduction volume of 64·3% (95% CI: 57·5% - 71·2%) compared to 53·2% (95% CI: 47·2% - 59·2%) in the LA group (p= 0·015) and this difference was also confirmed in a linear regression model adjusted for age, baseline volume and proportion of cellular component (Laser vs. RFA percent change Delta= -12·8, P=0·018).We have not recorded any significant difference in terms of successful rate at six months after treatment between the two groups (86·7% in the RFA vs 66·7% in the LA, p=0·127). At six months, both symptoms and cosmetic scores improved (compressive symptom score: 2·13 vs 3·9 for RFA, p < 0·001; 2·4 vs. 3·87 for LA, p < 0·001; cosmetic score: 1·65 vs 2·2 for RFA p Interpretation: Both techniques are very effective in reducing the volume of thyroid nodules. RFA appears to be more effective than LA, but both techniques showed no difference in terms of success rate six months after treatment. The safety of the two techniques is very satisfactory.

The aim of the present paper is twofold. Firstly, to assess the absorbed dose in small lesions using Monte Carlo calculations in a scenario of intratumoral injection of 90Y (e.g., percutaneous ablation). Secondly, to derive a practical analytical formula for the calculation of the absorbed dose that incorporates the absorbed fractions for 90Y. The absorbed dose per unit administered activity was assessed using Monte Carlo calculations in spheres of different size (diameter 0.5&ndash, 20 cm). The spheres are representative of tumor regions and are assumed to be uniformly filled with 90Y. Monte Carlo results were compared with the macrodosimetric approach used for dose calculation in liver radioembolization. The results of this analysis indicate that the use of the analytic model provides dose overestimates below 10% for lesions with diameter larger than approximately 2 cm. However, for lesions smaller than 2 cm the analytic model is likely to deviate significantly (&gt, 10%) from Monte Carlo results, providing dose overestimations larger than 50% for lesions of 0.5 cm diameter. In this paper an analytical formula derived from MC calculations that incorporates the absorbed fractions for 90Y is proposed. In a scenario of intratumoral injection of microspheres, the proposed equation can be usefully employed in the treatment planning of spherical lesions of small size (down to 0.5 cm diameter) providing dose estimates in close agreement with Monte Carlo calculations (maximum deviation below 0.5%).

Selective internal radiotherapy (SIRT) with yttrium-90 (Y-90)-labeled resin microspheres may have a role in consolidating the response to chemotherapy in patients with metastatic colorectal cancer unamenable to resection after assessment of the best response to first-line chemotherapy.This was a retrospective analysis of outcomes in patients who had received SIRT as consolidation therapy after one or more lines of chemotherapy. Eligible patients were 18 years or older, had confirmed colorectal liver metastases, and had disease unsuitable for surgical resection or local ablation with curative intent. The primary endpoint was progression-free survival.Sixty-eight patients with colorectal liver metastases were treated with at least one SIRT procedure after receiving one or more lines of chemotherapy. Median progression-free survival was significantly longer in patients who received SIRT after prior first-line chemotherapy compared to those who received SIRT after two or more lines of chemotherapy (9 vs. 3 months, respectively; hazard ratio = 0.07; 95% confidence interval, 0.02854‒0.2039; P .001), and in patients with liver-only disease compared to those who had extrahepatic metastases (6.4 vs. 4.1 months, respectively; hazard ratio = 0.57; 95% confidence interval, 0.34-0.95; P = .0318). There were no grade 3 or higher adverse events.SIRT represents a valid option for the treatment of colorectal liver metastases. Earlier use of SIRT may provide a greater survival benefit compared to that afforded by the procedure when used in salvage settings.

PURPOSE This study aims to evaluate the prognostic role of the decrease in total lesion glycolysis (TLG) assessed by fluorine-18-fluorodeoxyglucose (F-FDG) PET-computed tomography (CT) 1 month after yttrium-90-radioembolization (Y-RE) in patients affected by hepatocellular carcinoma (HCC) with portal vein tumour thrombosis (PVTT). PATIENTS AND METHODS Twenty-one patients with histologically proven poorly differentiated HCC and evidence of PVTT at the enhanced multislice CT underwent Y-RE. All patients underwent an F-FDG PET-CT scan at baseline and 1 month after the loco-regional therapy. The variation in TLG (ΔTLG) between the two studies was calculated. Patients were divided in two groups (group 1: 1 month ΔTLG >50%, group 2: ΔTLG

Intrahepatic cholangiocarcinoma (ICC) is a severe and rapidly progressive hepatic tumor. Surgery is often impracticable due to locally advanced presentation. On the other hand, chemotherapy has demonstrated only limited effectiveness. For these reasons, liver-directed therapies have been successfully applied for treating ICC. In particular, radioembolization with Yttrium-90 (90Y)-labeled spheres has been reported to be a promising therapeutic approach for this neoplasia. Two commercial forms of 90Y-labeled spheres are available: glass (TheraSphere®) and resin (SIR-Spheres®) microspheres. The aim of the present paper is to review the existing literature on the use of the resin microspheres for the treatment of unresectable and chemorefractory ICC, focusing on the methodology, clinical applications and side effects.

The majority of benign thyroid nodules are asymptomatic, remain stable in size and do not require treatment. However, a minority of patients with growing nodules may have local symptoms or cosmetic concerns, and thus demand surgical therapy. The timely use of ultrasound-guided, minimally invasive thermal therapies has changed the natural history of benign, enlarging thyroid nodules (TNs). These procedures produce persistent shrinkage of TNs and an improvement of local symptoms. Among the various procedures, percutaneous ethanol injection represents the first-line treatment for thyroid cysts, while in solid cold nodules, laser and radiofrequency ablation (RFA) have proven to be very effective and safe techniques in producing significant volume reduction that remains stable over several years. In particular, RFA seems to be suited for the management of small and medium nodules, while larger nodules may require repeated RFA treatments, and could be difficult to treat if they extend into the chest. RFA is performed in outpatient clinics and has a lower risk of complications compared to surgery. However, to date, there is still no unanimous consensus on the percutaneous treatment of benign nodules using such minimally invasive thermal techniques. In this review, we critically revise the literature to identify patients who are more likely to benefit from RFA treatment as an alternative to surgery.

To compare technique efficacy and safety of laser ablation (LA) and radiofrequency ablation (RFA) in treatment of benign thyroid nodules.Institutional review board approval was obtained, and patients' consent was waived. 601 nodules were treated from May 2009 to December 2014 at eight centres, 449 (309 females, age 57 ± 14 years) with LA and 152 (107 females, age 57 ± 14 years) with RFA. A matched cohort composed of 138 patients from each group was selected after adjustment with propensity score matching. Factors influencing volume reduction at 6 and 12 months and complications were evaluated.No significant differences were observed in the baseline characteristics between groups after propensity score matching adjustment. Mean nodule reduction at 6 and 12 months was -67 ± 19% vs. -57 ± 21% (p 0.001) - 70 ± 19% vs. -62 ± 22% (p = 0.001) in LA group and in RFA group, respectively. Nodules with volume 30 mL had significantly higher percentage volume reduction at 6 and 12 months (-69 ± 19 vs. -50 ± 21, p = 0.001) and (-73 ± 18 vs. -54 ± 23 8, p = 0.001) in the LA group than in the RFA group, respectively. In both groups, operator's skills affected the results. Major complications occurred in 4 cases in each group (p = 0.116) Conclusions: LA and RFA showed nearly similar outcome but LA was slightly more effective than RFA in large nodules. Operator's skills could be crucial in determining the extent of nodule volume reduction regardless of the used technique.

Objective The objective of our study is to evaluate the clinical outcomes and safety of radiofrequency thermal ablation (RFA) for benign thyroid nodules (BTNs) over a 1-year follow-up. Subjects and methods This is a monocentric retrospective study. Forty-eight patients with solid, non-functioning BTNs were treated by RFA using a 17G internally cooled electrode. We categorized thyroid nodules as small (≤ 12 mL), medium (12 to 30 mL), or large (over 30 mL). BTNs volume reduction, thyroid function, cosmetic and compressive score changes and side effect evaluation at 6 and 12 months were evaluated. Results BTN volume decreased significantly from baseline to 6 (mean percentage decrease of BTN volume was 66.8 ± 13.6%, p < 0.001). At 12 months, the mean percentage reduction of BTN volume compared to six months was 13.7 ± 17.1% (p < 0.001). At 6-month, symptom score had improved significantly (p < 0.001) while it does not change significantly between 6 and 12 months. In particular, symptom score improved significantly in the medium (p < 0.001) and large (p < 0.01) subgroups. Cosmetic score improved significantly between baseline and 6 months (p < 0.001) and between 6 and 12 months (p < 0.01). In all the subgroups, cosmetic score improved significantly between baseline and 6 months, while between 6 and 12 months it improved significantly only in the large group (p < 0.05). RFA was well tolerated. Only one patient experienced permanent right paramedian vocal cord palsy. Conclusions A single RFA treatment was effective in reducing BTNs volume, in particular small and medium nodules. Cosmetic score improved in all treated BTNs while symptom score only got better in the medium and large BTNs.

Purpose: Radioembolisation is part of the multimodal treatment of hepatocellular carcinoma (HCC) at specialist liver centres. This study analysed the impact of prior treatment on tolerability and survival following radioembolisation. Methods: This was a retrospective analysis of 325 consecutive patients with a confirmed diagnosis of HCC, who received radioembolisation with yttrium-90 resin microspheres at eight European centres between September 2003 and December 2009. The decision to treat was based on the clinical judgement of multidisciplinary teams. Patients were followed from the date of radioembolisation to last contact or death and the nature and severity of all adverse events (AEs) recorded from medical records. Results: Most radioembolisation candidates were Child-Pugh class A (82.5%) with multinodular HCC (75.9%) invading both lobes (53.1%); 56.3% were advanced stage. Radioembolisation was used first-line in 57.5% of patients and second-line in 34.2%. Common prior procedures were transarterial (chemo)embolisation therapies (27.1%), surgical resection/transplantation (17.2%) and ablation (8.6%). There was no difference in AE incidence and severity between prior treatment subgroups. Median (95% confidence interval [CI]) survival following radioembolisation was similar between procedure-naive and prior treatment groups for Barcelona Clinic Liver Cancer (BCLC) stage A: 22.1 months (15.1–45.9) versus 30.9 months (19.6–46.8); p = 0.243); stage B: 18.4 months (11.2–19.4) versus 22.8 months (10.9–34.2); p = 0.815; and stage C: 8.8 months (7.1–10.8) versus 10.8 months (7.7–12.6); p = 0.976. Conclusions: Radioembolisation is a valuable treatment option for patients who relapse following surgical, ablative or vascular procedures and remain suitable candidates for this treatment.

To assess the prognostic role of total lesion glycolysis (TLG) in patients with breast cancer liver metastases (BCLM) after sequential lobar (90)Y-radioembolization ((90)Y-RE). Seventeen patients with bilobar BCLM underwent FDG PET/CT and TLG calculation before (90)Y-RE. The hepatic lobe with the highest TLG was treated in the first session. PET was performed 6 weeks postprocedure and decrease in TLG (ΔTLG) in the treated lobe was calculated before the second (90)Y administration. Subjects were divided in two groups (group 1: ΔTLG50%, group 2: ΔTLG50%). After the two consecutive (90)Y-therapies, patients underwent follow-up until death. Statistical analysis was performed to identify prognostic factors on overall survival (OS). After the first (90)Y administration, 10 cases showed a ΔTLG50% and seven had a ΔTLG value50%. After the two consecutive procedures, the mean OS for all patients was 13.5 ± 0.8 months. Subjects with a ΔTLG50% and ΔTLG50% had a mean OS of 16.4 ± 0.6 and 10.3 ± 0.4 months, respectively (p 0.001). Cox regression analysis demonstrated hepatic tumor load (p = 0.048) and ΔTLG as the only significant (p = 0.005) predictors of survival. ΔTLG after the first (90)Y administration agrees with final outcome in BCLM patients after separate sequential lobar (90)Y-RE.

We investigated the prognostic role of (68)Ga-DOTANOC in patients affected by hepatic metastases from neuroendocrine tumours (NET) undergoing (90)Y radioembolization ((90)Y-RE).A group of 15 consecutive patients with unresectable NET liver metastases underwent (68)Ga-DOTANOC PET at baseline and 6 weeks after (90)Y-RE. Molecular response was defined as a reduction of50% in the tumour-to-spleen ratio (ΔT/S). The patients were divided into two groups (responders with ΔT/S50% and nonresponders with ΔT/S50%) Patients were followed up by imaging and laboratory tests every 3 months until death or for at least 36 months following (90)Y-RE. Statistical analysis was performed to identify factors predicting overall survival (OS) and progression-free survival (PFS).A decrease in T/S ratio was seen in all patients on (68)Ga-DOTANOC PET scans performed after (90)Y-RE. Nine patients were classified as responders and six as nonresponders. The mean OS in all patients was 31.0 months. Responders had a significantly (p 0.001) longer OS (mean 36.0 ± 2.5 months) and PFS (mean 29.7 ± 3.4 months) than nonresponders. In a multivariate analysis, none of the other examined variables including age, unilobar vs. bilobar locations, bilirubin levels, radiological response or the presence of extrahepatic disease significantly predicted patient outcome.Molecular response assessed with (68)Ga-DOTANOC PET might be a useful predictor of survival in patients affected by NET liver metastases treated with (90)Y-RE.

Liver transplantation (LT) for hepatocellular carcinoma (HCC) within the Milan criteria (MC) is nowadays a curative procedure. Yttrium-90 microspheres radioembolization (Y90-RE) has shown to be an effective and safe treatment of primary liver tumors. The aim of this work is to offer a view on the publications which report on the use of Y90-RE as bridge or downstaging prior to LT. Twenty articles have been considered for this world review. About 178 LT in patients were treated with Y90-RE prior to LT. Most of patients had a downstaging strategy. In all series alpha-fetoproteins decreased between Y90-RE and LT. Therefore, Y90-RE may have an important role in the bridge and downstaging treatments.

BACKGROUND: Liver transplantation (LT) is a well-established procedure for hepatocellular carcinoma (HCC) within the Milan criteria. Yttrium-90 microspheres radioembolization (Y90-RE) has shown to be an effective and safe treatment of primary liver tumors. We retrospectively evaluate the efficacy of the Y90-RE in patients with HCC prior to LT. METHODS: From January 2002 to December 2015, 365 patients were transplanted at the San Camillo Hospital Center. One hundred forty-three patients were transplanted for HCC, and in 22 cases the patients were treated with Y90-RE before LT. RESULTS: Three patients were treated with Y90-RE within the Milan criteria, and 19 patients were out of criteria before Y90-RE. Four patients had an increasing MELD score between Y90-RE and LT. On the other hand, alpha-fetoprotein decreases after Y90-RE treatment in all cases. No patient death was observed in Y90-RE procedure or at LT. In 78.9 % of cases, a successful downstaging was observed, and in 100 % of cases bridging was achieved. From Y90-RE treatment overall survival was 43.9 months. From LT, overall mean survival was 30.2 months with a free survival of 29.6 months. The overall survival after LT analysis between the patients treated with Y90-RE and patients without was not significant (p = 0.113). Free survival analysis was not significant (p = 0.897) between the two populations. CONCLUSIONS: We successfully performed LT in patients after Y90-RE treatment both as bridging and downstaging for HCC and obtained a similar overall and free survival of LT for HCC within Milan criteria. Y90-RE becomes a real option to provide curative therapy for patients who traditionally are not considered eligible for surgery.

Introduction Fine needle aspiration (FNA) is the most accurate and cost-effective method for evaluating thyroid nodules. We have reported a rare complication related to the procedure: severe retropharyngeal cellulitis. Case presentation A thirty-five-year-old female was admitted to hospital with hoarseness, laryngeal stridor and dyspnea without fever that emerged about 3 days after a first diagnostic FNA. After the procedure, the patient felt her voice became hoarse and 1 day before presentation began to have dyspnea, without fever. It had become difficult for her to swallow solids, and she felt as if food was sticking in her throat. In the emergency room, hematochemical tests and CT scan of the neck/mediastinum had been performed. This showed leukocytosis with neutrophilia and a severe cellulitis framework with involvement of the laterocervical neck area and in particular, the invasion of the retropharynx and the upper part of the mediastinum. The patient was admitted in hospital for an anti-inflammatory therapy with cortisone and antibiotic therapy. Conclusions For the first time to our knowledge, we have reported a severe retropharyngeal and upper mediastinum cellulitis, probably due to the FNA procedure in an immunocompetent young woman.

OBJECTIVES The decay of 90Y has a minor branch to the O+ first excited state of 89Zr, the de-excitation of which to the fundamental state is followed by a β+–β- emission that has been used recently for biodistribution assessment after selective internal radiotherapy (SIRT) treatments. The purpose of the present study is to demonstrate the feasibility of 90Y PET imaging for dose assessment after radioembolization with 90Y microspheres. METHODS Activity quantification was validated through preliminary phantom studies using a cylindrical body phantom composed of six inserts of different volumes filled with a calibrated amount of 90Y microspheres. A GE Discovery ST PET/CT scanner provided with bismuth germinate (BGO) crystals was used for image acquisition. Images were reconstructed with an ordered subset expectation–maximization method. The effect of object size and the effect of the number of iterations on dose evaluation and volume recovery were investigated. Microsphere dose distribution was then evaluated on one patient (one lesion) who underwent liver SIRT treatment. Dose calculations were made with a MATLAB-based code developed in our department. Dedicated Monte Carlo calculations were executed to evaluate dose S-values for the 90Y source. The activity distribution derived from 90Y PET acquisitions was convolved with the voxel S-values to obtain a three-dimensional absorbed dose distribution and dose–volume histograms. RESULTS Dosimetry studies carried out on the body phantom with ordered subset expectation–maximization algorithm, three iterations, provided an accuracy of 7.62% in determining the absorbed dose in the largest insert. The dose difference increases as the insert size reduces. Preliminary results on a patient provided a high-resolution absorbed dose distribution map. An average dose of 139.3 Gy was evaluated for the tumor area, with a maximum dose as high as 237.9 Gy. The absorbed dose to the healthy liver was below the tolerance dose of 35 Gy (33.8 Gy). A clear correlation between absorbed dose and tumor response was observed at 18F-fluorodeoxyglucose PET acquired 6 months after treatment. CONCLUSION According to our experience, 90Y PET is a promising and reliable technique for microsphere dose assessment and might pave the way for a patient-specific PET-based dosimetry after liver SIRT treatments.

To demonstrate the feasibility of 90Y-PET imaging for biodistribution assessment after selective internal radiotherapy treatments with 90Y-microspheres, comparing the results with 99mTc-macroaggregated albumin (MAA) images obtained with single-photon emission computed tomography.Preliminary studies were performed with the aim of evaluating the imaging system spatial resolution and scanner sensitivity for detecting annihilation photons. Subsequently, microsphere distribution was evaluated in 10 patients who underwent liver selective internal radiotherapy treatment. 99mTc-MAA and 90Y-microsphere were simultaneously injected for immediate monitoring after treatment. For each patient, the metastases detected with 90Y-PET and 99mTc-MAA were assessed and compared with 18F-fluorodeoxyglucose-PET (18F-FDG-PET) obtained before treatment and used as an imaging benchmark procedure. The correlation between these techniques was thus investigated in terms of matching lesions. Lesions were considered true positive in the case of matching with 18F-FDG-PET. The sensitivity of both techniques was evaluated as the true-positive fraction of detected spots in the treated liver sectors.With our experimental setup, a maximum scanner sensitivity of 0.577 and 0.077 cps/MBq was obtained for three-dimensional and two-dimensional acquisitions, respectively. A good correlation was obtained between images obtained before and after treatment, with 90Y-PET being by far the most accurate technique in detecting microsphere distribution and tumor nonhomogeneity areas. A sensitivity as high as 0.91 was obtained with 90Y-PET, whereas 99mTc-MAA imaging showed a SE of 0.75.90Y-PET is a promising and reliable technique for microsphere biodistribution evaluation after liver selective internal radiotherapy treatment. Because of the better resolution and the possibility to perform computed tomography fusion, 90Y-PET images are more accurate than 99mTc-MAA single-photon emission computed tomography, which is now considered the gold standard for biodistribution assessment.

A multicenter analysis was conducted to evaluate the main prognostic factors driving survival after radioembolization using yttrium-90-labeled resin microspheres in patients with hepatocellular carcinoma at eight European centers. In total, 325 patients received a median activity of 1.6 GBq between September 2003 and December 2009, predominantly as whole-liver (45.2%) or right-lobe (38.5%) infusions. Typically, patients were Child-Pugh class A (82.5%), had underlying cirrhosis (78.5%), and had good Eastern Cooperative Oncology Group (ECOG) performance status (ECOG 0-1; 87.7%), but many had multinodular disease (75.9%) invading both lobes (53.1%) and/or portal vein occlusion (13.5% branch; 9.8% main). Over half had advanced Barcelona Clinic Liver Cancer (BCLC) staging (BCLC C, 56.3%) and one-quarter had intermediate staging (BCLC B, 26.8%). The median overall survival was 12.8 months (95% confidence interval, 10.9-15.7), which varied significantly by disease stage (BCLC A, 24.4 months [95% CI, 18.6-38.1 months]; BCLC B, 16.9 months [95% CI, 12.8-22.8 months]; BCLC C, 10.0 months [95% CI, 7.7-10.9 months]). Consistent with this finding, survival varied significantly by ECOG status, hepatic function (Child-Pugh class, ascites, and baseline total bilirubin), tumor burden (number of nodules, alpha-fetoprotein), and presence of extrahepatic disease. When considered within the framework of BCLC staging, variables reflecting tumor burden and liver function provided additional prognostic information. The most significant independent prognostic factors for survival upon multivariate analysis were ECOG status, tumor burden (nodules >5), international normalized ratio >1.2, and extrahepatic disease. Common adverse events were: fatigue, nausea/vomiting, and abdominal pain. Grade 3 or higher increases in bilirubin were reported in 5.8% of patients. All-cause mortality was 0.6% and 6.8% at 30 and 90 days, respectively. Conclusion: This analysis provides robust evidence of the survival achieved with radioembolization, including those with advanced disease and few treatment options. © 2011 American Association for the Study of Liver Diseases.

Background: Ocular melanoma (OM) metastasizes to the liver and is rapidly fatal despite aggressive therapy. Yttrium-90 microspheres (radioembolization) delivered via the hepatic artery is an established and effective approach for primary and metastatic hepatic tumors, although 90Y use in OM has not been reported previously. Methods: A retrospective review was performed for all patients with OM who received radioembolization at 5 centers. Results: 11 patients received 12 treatments with a median activity of 1.55 GBq delivered per treatment. Toxicity was minimal, with PET/CT at 3 months posttreatment showing a response in all patients; 1 patient had a complete response. Conclusions: Radioembolization can control hepatic metastases of OM with very few side effects.

Ultrasound-guided radiofrequency ablation (RFA) of solid thyroid nodules (TNs) is a minimally invasive procedure that may induce a volume reduction of symptomatic solid benign TNs.The aim of the study was to evaluate the effectiveness and safety of RFA in debulking benign TNs.Eighty-four consecutive patients with symptomatic and cytologically benign solid nodules were randomly assigned to either a single RFA session (group A; n = 42) or follow-up (group B; n = 42) at our center. Entry criteria were a solid thyroid nodule or predominantly solid (with a fluid component ≤ 30% of the volume), normal thyroid function, no autoimmunity, and no previous thyroid gland treatment. Three subgroups were formed according to the baseline volume of nodules: small (≤ 12 mL), medium (from 12 to 30 mL), or large (30 mL).In group A RFA was performed in a single session with the moving-shot technique. Volume and local symptom changes were evaluated 1 and 6 months after RFA.In group A, the volume decreased from 24.5.5 ± 19.6 to 8.6 ± 9.5 6 months after RFA (P = .001). The greatest volume reduction was in small nodules. The pressure symptom score improved only in medium and large nodules (P.001), whereas the cosmetic score improved in all treated patients (P.001). The rate of thyroid volumetric reduction was not statistically different between solid and predominantly solid nodules. Only one patient experienced permanent right paramedian vocal cord palsy with inspiratory stridor without dysphonia. In group B, nodule volume remained unchanged, whereas the symptom score was worse at the 6-month evaluation (P = .01).RFA is effective in reducing thyroid nodule volume. The best reduction rate was observed in small TNs. The thyroid volumetric reduction does not change according to the sonographic features. The mean treatment duration was longer in larger TNs.

No data on the pharmacological treatment of normocalcemic hyperparathyroidism (NPHPT) are available. We treated 30 NPHPT postmenopausal women with alendronate/cholecalciferol (treated group) or vitamin D alone (control group). Over 1 year, bone mineral density (BMD) increased significantly in treated group, but not in control group. Both treatments did not affect serum or urinary calcium. Normocalcemic primary hyperparathyroidism (NPHPT) is defined by normal serum calcium and consistently elevated PTH levels after ruling out the causes of secondary hyperparathyroidism. It is likely that subjects with NPHPT may develop kidney and bone disease. As no data on the pharmacological treatment of NPHPT are available, we aimed to investigate the effects of alendronate and cholecalciferol on both BMD and bone biochemical markers in postmenopausal women with NPHPT. Safety of vitamin D was evaluated as secondary endpoint. The study was a prospective open label randomized trial comparing 15 postmenopausal women with NPHPT (PMW-NPHPT), treated with oral alendronate plus cholecalciferol (treated group) and 15 PMW-NPHPT treated only with cholecalciferol (control group). Blood samples were obtained at baseline and after 3, 6, and 12 months. Bone turnover markers (BTM) were measured at baseline, 3, and 6 months, respectively. BMD was assessed at baseline and after 12 months. After 1 year of treatment, BMD increased significantly at the lumbar, femoral neck, and hip level in the treated group, but not in the control group (p = 0.001). No differences were found between or within groups in serum calcium, PTH, and urinary calcium levels. BTM significantly decreased in the treated group but not in the control group, at 3 and 6 months (p

Our aim was to assess the prognostic value of post-treatment decrease in total lesion glycolysis (ΔTLG) assessed by 2-[(18)F]-fluorodeoxyglucose ([(18)F] FDG) PET-CT performed 6weeks after (90)Y radioembolization ((90)Y RE) in patients affected by intrahepatic cholangiocarcinoma (ICC).A total of 18 patients were accepted into our department for (90)Y RE. Before the procedure, all patients underwent [(18)F] FDG PET-CT, and total lesion glycolysis was calculated. Six weeks after (90)Y administration, PET scan was performed, and ΔTLG was determined. Patients underwent follow up by imaging and laboratory at quarterly intervals until death or for at least 24 months from (90)Y RE. Furthermore, subjects were divided in 2 groups (group 1: 6 weeks ΔTLG50%, group 2: ΔTLG50%). Kaplan-Meier method was used to achieve time to progression (TTP) and overall survival (OS) curves for each group. TTP and OS curves were compared to demonstrate eventual relevant differences between the 2 groups.Seventeen patients underwent (90)Y RE, and one subject was considered ineligible. According to PET Response Criteria in Solid Tumors, partial response was found in 14 patients (82.4%), stable disease in 3 (17.6%). No patient showed complete metabolic response. The mean OS for all patients was 64.5±5.0 weeks. Subjects with a ΔTLG50% and ΔTLG50% had a mean OS of 79.6±3.6 and 43.1±2.0 weeks, respectively (p0.001). TTP resulted of 28.9±3.8 weeks for the whole cohort. Patients with ΔTLG50% had a significantly longer TTP (mean 36.9±3.6 weeks) than those with ΔTLG50% (mean 13.7±1.7 weeks, p=0.001).Our results indicate that (90)Y RE can be an effective and safe therapy for ICC. ΔTLG calculated on post-treatment [(18)F] FDG PET-CT agrees with patients' final outcome.

Background & Aims The European Network on Radioembolization with Yttrium-90 resin microspheres study group (ENRY) conducted a retrospective study to evaluate the outcomes among elderly (≥70 years) and younger patients (

A 54-year-old woman with metastatic colorectal carcinoma underwent liver radioembolization with 90Y resin microspheres. Microsphere biodistribution was assessed 2 h after the treatment through a 20-min long 90Y PET scan. Isodose map and lesion dose-volume histogram (DVH) were then evaluated using a MATLAB-based code. Response to therapy was assessed performing a 18F-FDG PET 6 months after the treatment. At 90Y PET the patient showed a well-defined horseshoe-shaped hepatic lesion with hot margins and a cold core. The lesion presented a heterogeneous DVH with a hot margin receiving an average radiation dose as high as 287 Gy and a cold area receiving an average radiation dose of 70 Gy approximately. Six months after the treatment the patient reported a complete remission of tumour areas which received a high radiation dose, while progression of metastases was observed in the area that presented scarce microsphere localization at 90Y PET. According to our experience, the use of 90Y PET voxel dosimetry may provide a useful tool to assess possible correlations between microsphere biodistribution and clinical outcome of the treatment. In agreement with current literature findings, an average radiation dose greater than approximately 100 Gy may be required to sterilize liver metastases. © 2013 The Japanese Society of Nuclear Medicine.

Metastatic breast cancer is a heterogeneous disease, commonly affecting the liver. We report our experience with 90Y radioembolisation (RE) and its effects on the survival of patients with treatment-refractory breast cancer liver metastases. A total of 77 female patients affected by breast cancer were accepted into our department for RE. Inclusion criteria were inoperable and chemotherapy-refractory hepatic metastases, acceptable performance status, sufficient residual liver, no significant hepato-pulmonary shunts. Patients were divided in two groups: group 1 (29 patients) included those with Eastern Cooperative Oncology Group (ECOG) score 0, liver involvement (0–25 %) and no extrahepatic disease (EHD); group 2 (23 patient) included patients with ECOG score 1–2, liver involvement (26–50 %) and evidence of EHD. A total of 25 patients were considered ineligible. The median age of the remaining 52 patients was 57.5 years. The median overall survival was 11.5 months and better in those whose performance status and liver function were preserved (14.3 versus 8.2 months). According to Response Evaluation Criteria in Solid Tumor (RECIST), partial response (PR) was achieved in 29 patients (56 %), stable disease (SD) was achieved in a further 18 patients (35 %) and 5 patients showed progressive disease (PD) (10 %). 90Y RE is effective in the treatment of liver metastases from breast cancer. We demonstrated a relevant survival and encouragingly high response rate in patients with treatment-refractory disease. • Interventional radiological techniques are increasingly used for metastatic disease in the liver. • 90 Y radioembolisation (RE) seems effective for treating hepatic metastases from breast cancer. • RE is safe and well tolerated when performance status and liver function are preserved.

e15007Background: For patients with unresectable colorectal liver metastases, there are several locoregional liver-directed treatment options available. One such liver-directed treatment is radioem...

Here, we report a case of a febrile patient with primary bilateral adrenalitis who was successfully treated with an antituberculous regimen. Primary isolated tubercular adrenalitis is a very rare clinical entity but it should be considered in cases of fever and enlargement of the adrenal glands. Integration of radiological pattern data with epidemiological, clinical and immunological data has high accuracy and specificity, even without histological examination.

The purpose of this study was to evaluate the effectiveness of colorectal cancer (CRC) liver metastasis radioembolization with yttrium-90 (Y90), assessing toxicity and survival rates in patients with no response to chemotherapy through our 3-year experience. From February 2005 to January 2008, we treated 41 patients affected by CRC from a cohort of selective internal radiation therapy patients treated at our institution. All patients examined showed disease progression and arrived for our observation with an abdominal CT, a body PET, and a hepatic angiography followed by gastroduodenal artery coiling previously performed by us. We excluded patients with a bilirubin level >1.8 mg/dl and pulmonary shunt >20% but not patients with minor extrahepatic metastases. On treatment day, under fluoroscopic guidance, we implanted a dose of Y90 microspheres calculated on the basis of liver tumoral involvement and the body surface area formula. All patients were discharged the day after treatment. We obtained, according to Response Evaluation Criteria on Solid Tumors, a complete response in 2 patients, a partial response in 17 patients, stable disease in 14 patients, and progressive disease in 8 patients. In all cases, we obtained a carcinoembryonic antigen level decrease, especially in the week 8 evaluation. Technical success rate was 98% and technical effectiveness estimated at 3 months after treatment was 80.5%. Side effects graded by Common Terminology Criteria on Adverse Events were represented by one grade 4 hepatic failure, two grade 2 gastritis, and one grade 2 cholecystitis. The median survival and the progression-free survival calculated by Kaplan–Meier analysis were 354 and 279 days, respectively. In conclusion, according to our 3-year experience, Y90 SIR-Spheres radioembolization is a feasible and safe method to treat CRC liver metastases, with an acceptable level of complications and a good response rate.

This study was done to evaluate the effectiveness of radioembolisation of liver metastases with yttrium 90 (Y-90) in patients with no response to chemotherapy.From February 2005 to January 2008, we treated 110 patients affected by liver metastatic disease from colorectal, breast, gastric, pancreatic, pulmonary, oesophageal and pharyngeal cancers and from cholangiocarcinoma and melanoma. We excluded patients with bilirubin level1.8 mg/dl and pulmonary shunt20% but not patients with minor extrahepatic metastases.We obtained a complete /partial response in 45 patients, stable disease in 42 patients and progressive disease in 23 patients. In 90 cases, we obtained a decrease in specific tumour marker level. The technical success rate was 96%, and technical effectiveness estimated at 3 months after treatment was 83.6%. Side effects were grade 4 hepatic failure in one case, grade 2 gastritis in six cases and grade 2 cholecystitis in two cases. The median survival and progression-free survival calculated by Kaplan-Meier analysis were 323 days and 245 days, respectively.According to our 3-year experience, Y-90 radioembolisation (SIR-spheres) is a feasible and safe method to treat liver metastases with an acceptable level of complications and a good response rate.