BACKGROUND AND OBJECTIVES:Iatrogenic cerebral amyloid angiopathy (iCAA) is a rare form of CAA believed to result from β-amyloid (Aβ) transmission during neurosurgical procedures. We aimed to compare amyloid PET burden, CSF biomarkers, and APOE genotype between iCAA and sporadic CAA (sCAA). METHODS:In this single-center, cross-sectional study, adults fulfilling diagnostic criteria for probable sCAA or iCAA who underwent amyloid PET and CSF assessment between 2021 and 2024 were included. Amyloid burden was quantified using Centiloid scaling of 18Fflutemetamol or 18Fflorbetaben PET scans. CSF Aβ42, Aβ40, Aβ42/Aβ40 ratio, p-tau181, and total tau (t-tau) were measured with Lumipulse assays. Multivariable regression adjusted for age and sex examined associations with Centiloid values. RESULTS:Ninety-five patients were included (24 with iCAA, 71 with sCAA; median age 56.5 vs 70 years). Patients with iCAA showed significantly higher amyloid deposition (median Centiloid 57.3 vs 30.5; p = 0.0026). iCAA diagnosis was independently associated with +34.99 Centiloid units (95% CI 15.25-54.74; p = 0.001) after adjusting for age and sex. In patients with sCAA, Centiloid values correlated inversely with CSF Aβ42 and Aβ42/Aβ40 ratio, whereas no significant correlations were observed in patients with iCAA. APOE ε4 was markedly less frequent in iCAA (4.5% vs 34.2%). DISCUSSION:Patients with iCAA exhibit higher amyloid burden and a distinct biomarker profile compared with those with sCAA, supporting a divergent-possibly exogenous-mechanism of amyloid propagation. TRIAL REGISTRATION INFORMATION:SENECA, ClinicalTrials.gov Identifier: NCT04204642 (submitted on December 19, 2019).

Cerebral amyloid angiopathy (CAA)-related features on neuroimaging often coexist with signs of arteriolosclerosis-small vessel disease on neuroimaging in people with intracranial hemorrhage (ICH). This study aimed at defining the value of amyloid pathology detected by

OBJECTIVES:Cerebral amyloid angiopathy (CAA)-related features on neuroimaging often coexist with signs of arteriolosclerosis-small vessel disease on neuroimaging in people with intracranial hemorrhage (ICH). This study aimed at defining the value of amyloid pathology detected by 18Fflutemetamol PET in reclassification and stratification of risk of bleeding in people with mixed CAA-arteriolosclerosis features. METHODS:We included consecutive patients admitted to 2 institutions (2018-2023) with spontaneous symptomatic ICH, subarachnoid hemorrhage (SAH), transient focal neurologic episodes (TFNE), or cognitive impairment and MRI showing CAA hallmarks. All patients underwent brain magnetic resonance imaging (MRI) with susceptibility weighted imaging and 18Fflutemetamol PET imaging and were followed up for at least 1 year. We compared cases with CAA and arteriolosclerosis + CAA features and defined long-term outcomes (composite outcome including death, ICH, ischemic stroke, SAH, TFNE) depending on PET status (CAA/amyloid pathology vs arteriolosclerosis-predominant groups). RESULTS:Among 47 patients, according to PET and MRI imaging, 38 patients were reclassified in the CAA/amyloid pathology group and 9 in the arteriolosclerosis-predominant group, with similar cardiovascular risk factors but a significantly higher lobar microbleed burden for the former group. The CAA/amyloid pathology group had higher rates of composite outcome (43.9 vs 11.1 events per 100 patient-year; p = 0.039) and ICH (36.5 vs 5.6 events per 100 patient-years; p = 0.04) compared with the arteriolosclerosis-predominant group. DISCUSSION:18FFlutemetamol PET imaging can help in reclassification of mixed arteriolosclerosis + CAA into CAA/amyloid pathology and arteriolosclerosis-predominant, with implications on long-term risk of recurrent events. CLASSIFICATION OF EVIDENCE:This study provides Class IV evidence that 18Fflutemetamol PET can distinguish between CAA + arteriolosclerosis and arteriolosclerosis-predominant pathology.

Emerging evidence indicates that the etiologic agent responsible for coronavirus disease 2019 (COVID-19), can cause neurological complications. COVID-19 may induce cognitive impairment through multiple mechanisms. The aim of the present study was to describe the possible neuropsychological and metabolic neuroimaging consequences of COVID-19 12 months after patients’ hospital discharge. We retrospectively recruited 7 patients (age [mean ± SD] = 56 years ± 12.39, 4 men) who had been hospitalized for COVID-19 with persistent neuropsychological deficits 12 months after hospital discharge. All patients underwent cognitive assessment and brain (18F-FDG) PET/CT, and one also underwent 18F-amyloid PET/CT. Of the seven patients studied, four had normal glucose metabolism in the brain. Three patients showed various brain hypometabolism patterns: (1) unilateral left temporal mesial area hypometabolism; (2) pontine involvement; and (3) bilateral prefrontal area abnormalities with asymmetric parietal impairment. The patient who showed the most widespread glucose hypometabolism in the brain underwent an 18F-amyloid PET/CT to assess the presence of Aβ plaques. This examination showed significant Aβ deposition in the superior and middle frontal cortex, and in the posterior cingulate cortex extending mildly in the rostral and caudal anterior cingulate areas. Although some other reports have already suggested that brain hypometabolism may be associated with cognitive impairment at shorter intervals from SarsCov-2 infection, our study is the first to assess cognitive functions, brain metabolic activity and in a patient also amyloid PET one year after COVID-19, demonstrating that cerebral effects of COVID-19 can largely outlast the acute phase of the disease and even be followed by amyloid deposition.

BACKGROUND AND PURPOSE:Iatrogenic cerebral amyloid angiopathy (iCAA) is a specific type of cerebral amyloid angiopathy which is becoming increasingly diagnosed. It has been hypothesized that iCAA might arise as a late consequence of past neurosurgical interventions involving dural patch grafts. Positron emission tomography (PET) scans with amyloid tracers and the assay of beta-amyloid levels in cerebrospinal fluid (CSF) are auxiliary criteria, however, definite diagnosis remains histopathologically determined.METHODS:Case report.RESULTS:We present a 48-year-old patient who suffered multiple lobar cerebral haemorrhages from the age of 47. The patient had undergone surgery for remolval of hemangioblastoma with lyophilized dural graft at the age of 11, in 1987. Brain MRI, amiloid PET and CSF analysis led to a diagnosis of probable iCAA.CONCLUSION:It is necessary to increase the awareness of iCAA, in order to avoid overlooking the potential causal involvement of surgical procedures which took place far back in time. Moreover, the diagnostic relevance of amyloid PET and beta-amyloid levels in CSF must be emphasised.

BACKGROUND AND PURPOSE:Cognitive dysfunction has been observed following recovery from COVID-19. To the best of our knowledge, however, no study has assessed the progression of cognitive impairment after 1 year. The aim was to assess cognitive functioning at 1 year from hospital discharge, and eventual associations with specific clinical variables. METHODS:Seventy-six patients (aged 22-74 years) who had been hospitalized for COVID-19 were recruited. Patients received neuropsychological assessments at 5 (n = 76) and 12 months (n = 53) from hospital discharge. RESULTS:Over half (63.2%) of the patients had deficits in at least one test at 5 months. Compared to the assessment at 5 months, verbal memory, attention and processing speed improved significantly after 1 year (all p < 0.05), whereas visuospatial memory did not (all p > 0.500). The most affected domains after 1 year were processing speed (28.3%) and long-term visuospatial (18.1%) and verbal (15.1%) memory. Lower PaO2 /FiO2 ratios in the acute phase were associated with worse verbal long-term memory (p = 0.029) and visuospatial learning (p = 0.041) at 5 months. Worse visuospatial long-term memory at 5 months was associated with hyposmia (p = 0.020) and dysgeusia (p = 0.037). CONCLUSION:Our study expands the results from previous studies showing that cognitive impairment can still be observed after 1 year. Patients with severe COVID-19 should receive periodic cognitive follow-up evaluations, as cognitive deficits in recovered patients could have social and occupational implications.

Background: Data regarding the role of positron emission tomography/computed tomography (PET/CT) to stage lymph nodes in patients receiving neoadjuvant immunotherapy before radical cystectomy are lacking. The aim of this study is to evaluate the role of PET/ CT to predict the pathologic lymph node involvement (LNI) in patients with MIBC receiving neoadjuvant pembrolizumab within the PURE-01 trial (NCT02736266). Material and methods: Three courses of pembrolizumab were administered before radical cystectomy and extended pelvic lymph node dissection in clinical T2-4aN0M0 MIBC based on contrast-enhanced CT scan. LNI was also assessed with PET/CT before and after treatment. PET/CT results were compared with histopathological findings. The ability of baseline and post-therapy PET/CT to evaluate LNI was assessed, and univariate logistic regression analyses were performed. Results: From February 2017 to August 2019, a total of 108 patients and 105 patients had evaluable baseline and post-pembrolizumab scans, respectively. The sensitivity to detect LNI was 27% and 37.5% for pre- and post-pembrolizumab PET/CT, and specificity was 97% and 98%, respectively. In total, 4 of 7 patients (57%) showing baseline FDG-uptake had LNI vs. 11 of 101 (11%) with no baseline uptake. All but 1 of the 7 patients did not respond to pembrolizumab. Both pre- and post-pembrolizumab PET/CT significantly predicted LNI (P = 0.004 and P < 0.001) at univariate analyses. Our results warrant further validation in larger datasets. Conclusions: PET/CT performance does not justify its use in routine practice for cN0 MIBC. However, our preliminary data revealed opportunities for the use of baseline PET/CT, within clinical trials, to optimally select patients with MIBC who are best suited for neoadjuvant immunotherapy strategies. Validation in larger datasets, as well as a cost analysis, are needed. (C) 2020 Elsevier Inc. All rights reserved.

Background: Data regarding the incidence and prognostic impact of immune-related imaging changes, assessed by (18)[F] fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) scan, in patients receiving immune-checkpoint inhibitors (ICIs) are lacking. We relied on the population of patients enrolled in the PURE-01 study to evaluate such changes. Objective: To evaluate the role of PET/CT to visualize the immune-related adverse events (irAEs) following pembrolizumab. Design, setting, and participants: From February 2017 to August 2019, in 103 patients with nonmetastatic, clinical T2-4aN0M0 bladder cancer, PET/CT scan was performed before and after neoadjuvant pembrolizumab (N = 206 scans), before radical cystectomy. Intervention: PET/CT before and after neoadjuvant pembrolizumab, before radical cystectomy. Outcome measurements and statistical analysis: We analyzed the occurrence of irAEs, evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, against the development of inflammatory FDG uptake described at PET/CT (irAEs + PET/CT). Logistic regression analyses evaluated the association between irAEs + PET/CT and the pathological response to pembrolizumab. Kaplan-Meier curves tested their association with progression-free survival (PFS) after pembrolizumab and radical cystectomy. Results and limitations: Forty patients (39%) developed irAEs + PET/CT in several target organs. The most frequent target organs were the thyroid (N = 18), stomach (N = 14), mediastinal lymph nodes (N = 9), and lung (N = 5). These changes were clinically evident in 18 (45%) and were not associated with the pathological response, neither in terms of complete response (ypT0N0, p = 0.07) nor as downstaging to ypT <= 1N0 disease (p = 0.1), although ypT0N0 responses were numerically more frequent in patients with irAEs(+) PET/CT (47.5% vs 32%). Furthermore, irAE(+) PET/CT events were associated with longer, not statistically significant, 24-mo PFS: 88.3% versus 76.5% (p = 0.5). Our results warrant further validation in larger datasets. Conclusions: We presented unique surrogate data of PET/CT that could help improve our understanding of nonclinically evident effects of ICI administration, especially in patients at the early disease stage. Patient summary: We evaluated the utility of PET/CT to visualize the occurrence of inflammatory changes after pembrolizumab in patients with localized bladder cancer without metastases. After immunotherapy, 39% of the patients developed (18)[F] fluorodeoxyglucose uptake consistent of inflammatory changes. Overall, our data improve our knowledge on the effects induced by immunotherapy, which may have a clinical impact at longer follow-up. (C) 2020 European Association of Urology. Published by Elsevier B.V. All rights reserved.

445 Background: FDG-PET/CT has limited utility in clinical N0 (cN0) patients (pts) with MIBC who receive neoadjuvant chemotherapy and RC or RC alone (Dason, AUA19). Methods: In PURE-01 (NCT02736266), 3 courses of 200 mg pembrolizumab, q3 weeks, were administered prior to RC. Pts were assessed with thorax-abdomen CT scan and with PET/CT scan during screening and before RC. Imaging review and analysis was internally performed. For each pt with lymph node (LN) increased uptake in abdomino-pelvic area, the SUVmax and the short-axis size of the most intense LN were recorded. All pts underwent extended pelvic LN dissection (LND) with packeted node submission. Results: From 02/17 to 06/2019, 103 total evaluable pts (206 PET/TC scans) were enrolled ad treated. Six pts (5.8%) had LN uptake at baseline PET/CT: mean SUVmax=2.75; mean short axis: 6.2 mm. Eight pts (7.8%) had LN uptake at PET/CT post-pembrolizumab: mean SUVmax=4.21; mean short axis: 7.2mm. The rate of pathologic LN positive (pN+) disease was 15.5% (16 pts). The performance of post-pembrolizumab PET/CT in predicting pN+ disease is indicated in the Table. In total, 4/6 pts (66.7%) with baseline FDG uptake revealed as pN+ vs 12/97 (12.4%) with no baseline FDG uptakes (p=0.005). A total of 39 pts (37.9%) developed inflammatory FDG-uptakes post-pembrolizumab in several target organs/regions: top 5 sites were thyroid (N=21, 61.8%), stomach and mediastinum (13 pts each, 12.6%), lung (N=10, 9.7%), other lymph nodes (N=4, 3.9%). These changes were clinically evident (signs/symptoms or laboratory changes) in 15 pts (38.5%). Conclusions: Criteria for eligibility of cN0 pts to single-agent neoadjuvant pembrolizumab trials may be enhanced with PET/CT use. Three cycles of pembrolizumab determined profound inflammatory changes, whose long-term impact on safety is still to be determined. Clinical trial information: NCT02736266 . [Table: see text]

INTRODUCTION AND OBJECTIVE: FDG-PET/CT has limited utility in clinical N0 (cN0) patients (pts) with MIBC who receive neoadjuvant chemotherapy and RC or RC alone (Dason, AUA19). We present a secondary analysis aimed at evaluating the role of PET/CT in lymph node (LN) involvement assessment. METHODS: In PURE-01 (NCT02736266), 3 courses of 200 mg pembrolizumab, every 3 weeks, were administered prior to RC. Pts were assessed with thorax-abdomen CT scan and with PET/CT scan during screening and after treatment, before RC. Imaging review and analysis was performed by two experienced nuclear medicine physicians blinded to clinical information. Semiquantitative and volumetric analysis was performed. For each patient with LN increased uptake in abdomino-pelvic area, the SUVmax and the short-axis size of the most intense LN were recorded. All pts underwent templated pelvic LN dissection (LND) with packeted node submission. PET/TC diagnostic ability was assessed using sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV), and accuracy. RESULTS: From 02/17 to 06/2019, 114 pts were enrolled ad treated. 11 pts received additional chemotherapy post-pembrolizumab and were excluded from the analyses, resulting in 103 total evaluable pts (and 206 PET/TC scans). Six pts (5.8%) had positive nodes at baseline PET/CT: mean SUVmax=2.75; mean short axis: 6.2 mm. Eight pts (7.8%) had positive LN at PET/CT post-pembrolizumab: mean SUVmax=4.21; mean short axis: 7.2mm. The rate of pathologic LN positive (pN+) disease was 15.5% (16 pts). The performance of post-pembrolizumab PET/CT in predicting pN+ disease is indicated in the Table. 4/6 pts (66.7%) with baseline FDG uptake revealed as pN+ vs 12/97 (12.4%) with no baseline FDG uptakes (p=0.005). A total of 39 pts (37.9%) developed inflammatory FDG-uptakes post-pembrolizumab in several target organs/regions: top 5 sites were thyroid (N=21, 61.8%), stomach and mediastinum (13 pts each, 12.6%), lung (N=10, 9.7%), other lymph nodes (N=4, 3.9%). These changes were clinically evident (signs/symptoms or laboratory changes) in 15 pts (38.5%). CONCLUSIONS: Criteria for eligibility of cN0 pts to single-agent neoadjuvant pembrolizumab trials may be enhanced with PET/CT use. Three cycles of pembrolizumab determined profound inflammatory changes, whose long-term impact on safety is still to be determined.Source of Funding: None

Transarterial radioembolization (TARE) is, by all standards, a radiation therapy. As such, according to Euratom Directive 2013/59, it should be optimized by a thorough treatment plan based on the distinct evaluation of absorbed dose to the lesions and to the non-tumoural liver (two-compartment dosimetry). Since the dosimetric prediction with 99mTc albumin macro-aggregates (MAA) of non-tumoural liver is much more accurate than the same prediction on lesions, treatment planning should focus on non-tumoural liver rather than on lesion dosimetry. The aim of this study was to determine a safety limit through the analysis of pre-treatment dosimetry with 99mTc-MAA single photon emission computed tomography (SPECT/CT), in order to deliver the maximum tolerable absorbed dose to non-tumoural liver. Data from intermediate/advanced hepato-cellular carcinoma (HCC) patients treated with 90Y glass microspheres were collected in this single-arm retrospective study. Injection was always lobar, even in case of bilobar disease, to avoid treating the whole liver in a single session. A three-level definition of liver decompensation (LD) was introduced, considering toxicity only in cases of liver decompensation requiring medical action (LD type C, LDC). We report LDC rates, receiver operating characteristic (ROC) analysis between LDC and NO LDC absorbed dose distributions, normal tissue complication probability (NTCP) curves and uni- and multivariate analysis of risk factors associated with toxicity. A 6-month timeline was defined as necessary to capture all treatment-related toxicity events. Previous transarterial chemoembolization (TACE), presence or extension of portal vein tumoural thrombosis (PVTT) and tumour pattern (nodular versus infiltrative) were not associated with tolerance to TARE. On the contrary, at the multivariate analysis, the absorbed dose averaged over the whole non-tumoural liver (including the non-injected lobe) was a prognostic indicator correlated with liver decompensation (odds ratio = 4.24). Basal bilirubin > 1.1 mg/dL was a second even more significant risk factor (odds ratio = 6.35). NTCP analysis stratified with this bilirubin cut-off determined a 15% liver decompensation risk at 50 Gy/90 Gy for bilirubin >/< 1.1 mg/dL. These results are valid for a 90Y glass microsphere administration 4 days after the reference time. Given the low predictive accuracy of 99mTc-MAA on lesion absorbed dose reported by several authors, an optimized TARE with 90Y glass microspheres with lobar injection 4 days after reference time should aim at an absorbed dose averaged over the whole non-tumoural liver of 50 Gy/90 Gy for basal bilirubin higher/lower than 1.1 mg/dL, respectively.

Differentiated thyroid cancer (DTC) accounts for 95% of all thyroid cancers and is generally an indolent tumor, tending to present with limited loco-regional disease with an excellent long-term survival after treatment. However, 5–10% present with locally advanced disease and aero-digestive tract invasion or distant metastases that are the main cause of thyroid cancer-related deaths. The present review aims to underline the complex management of advanced DTC including treatment of gross extra-thyroidal extension, recurrent loco-regional, or distant metastatic disease. Radioiodine therapy is an effective treatment of advanced and/or metastatic DTC which contributes significantly to patients’ life expectancy. Multimodal approach based on surgical resection in combination with radioiodine therapy, interventional imaging treatment, and TSH suppression can significantly improve outcomes for this patients’ population.