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Most head and neck paragangliomas (PGLs) are biochemically silent and often present with recurrence and metastases in association with hereditary syndromes. Whole-body functional imaging is increasingly used to detect tumor extent and guide treatment planning of PGLs. [68Ga]-DOTATATE, which targets somatostatin receptor 2 (SSTR2) overexpression, has emerged as a sensitive functional imaging modality in PGLs. We present a patient with metastatic glomus caroticum PGL in whom [68Ga]-DOTATATE PET/MRI provided a more accurate characterization of metastatic extent, as compared to gadolinium-enhanced MRI of the neck and whole body [18F]-FDG PET/CT. We then review the current literature and discuss the imaging implications of [68Ga]-DOTATATE PET/MRI in PGLs.

18F-Fluorodeoxyglucose positron emission tomography (FDG-PET) underperforms in detecting prostate cancer (PCa) due to inherent characteristics of primary and metastatic tumors, including relatively low rate of glucose utilization. Consequently, alternate PCa PET imaging agents targeting other aspects of PCa cell biology have been developed for clinical practice. The most common dedicated PET imaging tracers include 68Ga/18F prostate-specific membrane antigen (PSMA), 11C-Choline, and 18F-fluciclovine (Axumin™). This review will describe how these agents target specific inherent characteristics of PCa and explore the current literature for these agents for both primary and recurrent PCa, comparing the advantages and limitations of each tracer. Both 11C-Choline and 18F-Fluciclovine PET have been shown to detect nodal and osseous disease at higher rates compared to FDG-PET but offer no additional benefit in detecting prostate disease, especially in primary staging. As a result, PSMA PET, specifically 68Ga-PSMA-11, has emerged as a key imaging option for both primary and recurrent cancer. PSMA PET may be more sensitive than MRI at the local level and more sensitive than 11C-Choline and 18F-Fluciclovine PET for distant disease. Furthermore, compared to 11C-Choline and 18F-Fluciclovine PET, 68Ga-PSMA-11 PET has higher detection rates at low PSA levels (

Peptide-based prostate-specific membrane antigen (PSMA) targeted radionuclide therapy (TRT) agent [177Lu]-PSMA-617 has emerged as leading TRT candidate for treatment of castration-resistant prostate cancer (mCRPC). [177Lu]-PSMA-617 and other small molecule–based PSMA ligands have shown efficacy in reducing the tumor burden in mCRPC patients but irradiation to the salivary gland and kidneys is a concern and dose-limiting factor. Therefore, methods to reduce non-target organ toxicity are needed to safely treat patients and preserve their quality of life. Herein, we report that addition of cold PSMA ligand PSMA-11 can aid in reducing the uptake of [177Lu]-PSMA-617 in the salivary glands and kidneys. Groups of athymic nude mice (n = 4) bearing PC3-PIP (PSMA+) tumor xenografts were administered with [177Lu]-PSMA-617 along with 0, 5, 100, 500, 1000, and 2000 pmoles of PSMA-11 and biodistribution studies were performed at 1 h. Biodistribution studies at 1 h post-administration revealed that [177Lu]-PSMA-617 uptake in PC3-PIP tumors was 21.71 ± 6.13, 18.7 ± 2.03, 26.44 ± 2.94, 16.21 ± 3.5, 13.52 ± 3.68, and 12.03 ± 1.96 %ID/g when 0, 5, 100, 500, 1000, and 2000 pmoles of PSMA-11 were added, respectively. Corresponding uptake values in kidney were 123.14 ± 52.52, 132.31 ± 47.4, 84.29 ± 78.25, 2.12 ± 1.88, 1.16 ± 0.36, and 0.64 ± 0.23 %ID/g, respectively. Corresponding salivary gland uptake values were 0.48 ± 0.11, 0.45 ± 0.15, 0.38 ± 0.3, 0.08 ± 0.03, 0.09 ± 0.07, and 0.05 ± 0.02 % ID/g, respectively. The uptake of [177Lu]-PSMA-617 in the salivary gland and kidney can be substantially reduced without significantly impacting tumor uptake by adding cold PSMA-11.

Meningiomas are the most common non-malignant primary intracranial tumors, accounting for nearly 40% of all primary brain tumors, usually expressing high levels of somatostatin receptors (SSTR), particularly SSTR2. Because 68Ga-DOTATATE targets SSTR2, it is increasingly used clinically for meningioma evaluation. While previous apparent lack of SSTR expression in meningiomas has been reported in isolated cases, these prior studies utilized Indium-111 (111In) Octreotide, which is of lesser diagnostic accuracy compared to 68Ga-DOTATATE, as well as Technetium-99m (99mTc)-DTPA scintigraphy, which necessitates an intact blood-tumor-permeability barrier. This paper presents a histopathologic proven atypical meningioma, WHO Grade II, with low level avidity on 68Ga-DOTATATE PET/MRI, subsequently proven to be SSTR2-negative by immunohistochemistry, with a review and discussion of the current literature and imaging implications.

PURPOSE: To evaluate dynamic gallium 68 ((68)Ga) tetraazacyclododecane tetraacetic acid octreotate (DOTATATE) brain PET/MRI as an adjunct modality in meningioma, enabling multiparametric standardized uptake value (SUV) and Patlak net binding rate constant (K(i)) imaging, and to optimize static acquisition period. MATERIALS AND METHODS: In this prospective study (ClinicalTrials.gov no. NCT04081701, DOMINO-START), (68)Ga-DOTATATE PET/MRI–derived time-activity curves (TACs) were measured in 84 volumes of interest in 19 participants (mean age, 63 years; range, 36–89 years; 13 women; 2019–2021) with meningiomas. Region- and voxel-specific K(i) were determined using Patlak analysis with a validated population-based reference tissue TAC model built from an independent data set of nine participants. Mean and maximum absolute and relative-to-superior-sagittal-sinus SUVs were extracted from the entire 50 minutes (SUV(50)) and last 10 minutes (SUV(10)) of acquisition. SUV versus K(i) Spearman correlation, SUV and K(i) meningioma versus posttreatment-change Mann-Whitney U tests, and SUV(50) versus SUV(10) Wilcoxon matched-pairs signed rank tests were performed. RESULTS: Absolute and relative maximum SUV(50) demonstrated a strong positive correlation with Patlak K(i) in meningioma (r = 0.82, P < .001 and r = 0.85, P < .001, respectively) and posttreatment-change lesions (r = 0.88, P = .007 and r = 0.83, P = .02, respectively). Patlak K(i) images yielded higher lesion contrast by mitigating nonspecific background signal. All SUV(50) and SUV(10) metrics differed between meningioma and posttreatment-change regions (P < .001). Within the meningioma group, SUV(10) attained higher mean scores than SUV(50) (P < .001). CONCLUSION: Combined SUV and Patlak K (i) (68)Ga-DOTATATE PET/MRI enabled multiparametric evaluation of meningioma, offering the potential to enhance lesion contrast with K(i) imaging and optimize the SUV measurement postinjection window. Keywords: Molecular Imaging–Clinical Translation, Neuro-Oncology, PET/MRI, Dynamic, Patlak ClinicalTrials.gov registration no. NCT04081701 © RSNA, 2022

Distinguishing frontotemporal lobar degeneration (FTLD) and Alzheimer Disease (AD) on FDG-PET based on qualitative review alone can pose a diagnostic challenge. SPM has been shown to improve diagnostic performance in research settings, but translation to clinical practice has been lacking. Our purpose was to create a heuristic scoring method based on statistical parametric mapping z-scores. We aimed to compare the performance of the scoring method to the initial qualitative read and a machine learning (ML)-based method as benchmarks. FDG-PET/CT or PET/MRI of 65 patients with suspected dementia were processed using SPM software, yielding z-scores from either whole brain (W) or cerebellar (C) normalization relative to a healthy cohort. A non-ML, heuristic scoring system was applied using region counts below a preset z-score cutoff. W z-scores, C z-scores, or WC z-scores (z-scores from both W and C normalization) served as features to build random forest models. The neurological diagnosis was used as the gold standard. The sensitivity of the non-ML scoring system and the random forest models to detect AD was higher than the initial qualitative read of the standard FDG-PET [0.89-1.00 vs. 0.22 (95% CI, 0-0.33)]. A categorical random forest model to distinguish AD, FTLD, and normal cases had similar accuracy than the non-ML scoring model (0.63 vs. 0.61). Our non-ML-based scoring system of SPM z-scores approximated the diagnostic performance of a ML-based method and demonstrated higher sensitivity in the detection of AD compared to qualitative reads. This approach may improve the diagnostic performance.

Background Meningiomas express high levels of somatostatin receptor 2 (SSTR2). SSTR2-targeted PET imaging with [68Ga]-DOTATATE can aid with distinguishing residual meningioma from reactive changes in the postoperative setting. We present initial dosimetric analyses, acute events, and local control data utilizing [68Ga]-DOTATATE PET/MRI-assisted target delineation for prospectively-treated intermediate-risk meningiomas. Methods Twenty-nine patients underwent DOTATATE PET/MRI meningioma evaluation in 2019. Eight patients with 9 postoperative meningiomas met RTOG 0539 intermediate-risk criteria (recurrent WHO grade I, 1/9; WHO grade II, 8/9). Target volumes were created using DOTATATE PET/MRI to determine residual disease and received a nominal dose of 35.0 Gy over 5 fractions. For comparison, cases were recontoured and planned with MRI alone per RTOG 0539 guidelines. Mean and maximum equivalent 2 Gy doses were generated for target volumes and organs at risk (OAR) within 1 cm of the PTV and compared using Wilcoxon matched pairs signed rank test. Results DOTATATE PET/MRI-guided planning significantly reduced mean PTV (11.12 cm3 compared to 71.39 cm3 based on MRI alone, P < .05) and mean and max dose to the whole brain, optic nerves, and scalp. PET/MRI plans resulted in at least 50% reduction of mean and max doses to the lens, eyes, chiasm, cochlea, brainstem, and hippocampi. One patient experienced focal alopecia. There were no local recurrences at 6 months. Conclusion Incorporating DOTATATE-PET/MRI for postoperative target delineation in patients with intermediate-risk intracranial meningiomas results in PTV reduction and decreased OAR dose. Our findings warrant larger studies evaluating DOTATATE-PET/MRI in the radiotherapeutic planning of postoperative meningiomas.

Background and aim: Dysregulation of glucose metabolism is a common complication of transfusions in Transfusion Dependent Thalassemia (TDT) patients. For early diagnosis of glucose disturbances, screening is recommended. The age of starting and the type of screening vary; the more common methods are assessment of RPG, FPG, 2h PG and 2 hours OGTT. The combined assessment of glucose tolerance and insulin response during OGTT is rarely recommended. The main objective of the study is the evaluation of simultaneous assessment of Glucose Tolerance (GT) and Insulin Response (IR) during OGTT in patients with TDT. Methods: 43 TDT patients aged 12-28years, without clinical evidence of glucose disturbances, were randomly selected for the study. The 2-hour OGTT in 30 minutes intervals was applied. Plasma glucose and insulin were assessed in all samples using routine laboratory methods. Results: Of 43 patients 31(72%) had Normal GT; of them 9 (29%) had normal insulin response (NIR), 14 (45%) high IR and 8(26%) delayed peak IR. Delayed peak IR was found in 8 of the 9 patients with Impaired GT and in 2 of the 3 with diabetic GT. Deficient IR (hypoinsulinemia) was found in two patients. Conclusions: Simultaneous assessment of GT and IR during OGTT in TDT patients, seems to be a most sensitive and creditable screening test for early diagnosis of glucose disturbances. High IR and delayed peak IR in normoglycemic patients are valuable indices for diagnosis of the pre-diabetic state that precede the development of glucose disturbances in TDT patients and start proper follow and management. (www.actabiomedica.it).

Background: While MRI is the gold standard for meningioma diagnosis and treatment planning, it poses limitations in differentiating residual/recurrent disease from post-treatment-change. 68Ga-DOTATATE PET/MR of 50 min with standardized uptake value (SUV) analysis has demonstrated clinical utility in patients with meningioma. However, SUV is considered semi-quantitative with limited reproducibility depending on several variable parameters not accounted for in its definition. Dynamic PET acquisitions enable parametric imaging accounting for post-injection time to improve quantification. Our purpose was to assess feasibility and clinical utility of dynamic 68Ga-DOTATATE PET/MR with multi-parametric SUV and Patlak analysis in the diagnosis and management of intracranial meningioma. Results: 19 subjects with meningioma underwent dynamic 68Ga-DOTATATE PET/MR. Time-activity curves were generated in 84 volumes of interest (53 meningioma, 9 post-treatment-change, 22 cranial blood pool reference in superior sagittal sinus, SSS). Region-specific net binding rate constant Ki was determined using the standard and generalized Patlak (sPatlak and gPatlak) methods with a population-based reference input function. Absolute and relative mean and maximum SUVs were extracted from the 50 minutes (SUV50) and the last 10 minutes (SUV10) of acquisition. Spearman correlation, Mann-Whitney, and Wilcoxon tests were performed. In meningioma, absolute and relative maximum SUV50 demonstrated a strong, significant, positive correlation with sPatlak Ki (r = 0.82, p < 0.0001 and r = 0.85, p < 0.0001, respectively). Similar results were found in post-treatment-change regions (r = 0.88, p = 0.007 and r = 0.83, p = 0.015, respectively). Mean SUV50 demonstrated similar correlations with sPatlak Ki in both subgroups. No significant differences were observed between sPatlak and gPatlak Ki correlations with SUV. All SUV and Ki metrics were significantly higher in meningioma versus post-treatment-change regions. SUV50 and SUV10 metrics for each sub-cohort were not significantly different. No lesions were reclassified based on SUV10 or Ki compared to SUV50. Conclusions: Multi-parametric SUV and Patlak Ki analysis with 68Ga-DOTATATE PET/MR is feasible and can differentiate meningioma from post-treatment-change. Ki may improve quantification of postoperative residual/ recurrent meningioma. SUV10 and SUV50 yielded comparable quantification suggesting feasibility for shorter PET scans.Trial Registration Number (ClinicalTrials.gov ID): NCT04081701, Registration Date: September 9, 2019

Background Prostate-specific membrane antigen (PSMA)-targeted radionuclide therapy (TRT) has demonstrated efficacy and tolerability with a dose-response effect in phase I/II trials in men with metastatic castration-resistant prostate cancer (mCRPC). The need for positive PSMA imaging before PSMA-TRT to select patients is largely practiced, but its utility is not proven. Given target heterogeneity, developing a biomarker to identify the optimal patient population remains an unmet need. The aim of this study was to assess PSMA uptake by imaging and response to PSMA-TRT. Methods We performed an analysis of men with mCRPC enrolled in sequential prospective phase I/II trials of PSMA-TRT. Each patient had baseline PSMA imaging by planar 111 In and/or 177 Lu SPECT (N = 171) or 68 Ga-PSMA-11 PET/CT (N = 44), but the results were not used to include/exclude treatment. Semiquantitative imaging scores (IS) on a 0-4 scale were assigned based on PSMA uptake in tumors compared to liver uptake. We compared the ≥50% PSA decline response proportions between low (0-1) and high (2-4) PSMA IS using the χ2 -test. We used multivariable logistic regression analysis to understand the relationship between independent and dependent variables, including IS, radionuclide activity (dose) administered, CALGB (Halabi) prognostic risk score, prior taxane use. Results 215 men with progressive mCRPC received PSMA-TRT as follows: 177 Lu-J591 (n = 137), 177 Lu-PSMA-617 (n = 44), 90 Y-J591 (n = 28), 177 Lu-J591 + 177 Lu-PSMA-617 (n = 6). High PSMA expression (IS 2-4) was found in 160 (74.4%) patients and was significantly associated with more frequent ≥ 50% PSA reduction (26.2 vs. 7.3%, p = .006). On multivariate logistic regression analysis, higher IS was associated with a ≥50% decrease in PSA, even after accounting for CALGB (Halabi) prognostic score, the dose administered, and previous taxane use (OR, 4.72; 95% CI, 1.71-16.85; p = .006). Patients with low PSMA expression (N = 55, 24.7%) were less likely to respond. Thirteen of 26 (50%) with no PSMA uptake (IS = 0) had post-PSMA-TRT PSA decline with 2 (7.7%) having ≥ 50% PSA declines. Conclusion Collectively, the data provide evidence in favor of the hypothesis that patients with high PSMA uptake and high administered radionuclide dose correlate with a higher chance of response.

Prostate-specific membrane antigen (PSMA) is a cell membrane glycoprotein that is selectively expressed in prostate cells, with expression levels increasing dramatically in prostatic adenocarcinoma. PSMA-based radioligand therapy (RLT) has emerged as a viable therapeutic modality for the treatment of progressive metastatic prostate cancer. One commonly employed combination involves lutetium-177 conjugated to the ligand PSMA-617 (177Lu-PSMA-617). In this meta-analysis, we examine therapeutic responses in patients with metastatic disease who have received 177Lu-PSMA-617 therapy. We conducted a literature search with the following inclusion criteria: clinical trials involving more than 10 patients and solely utilizing 177Lu-PSMA-617. Seventeen studies were included in the final analysis. Variables documented included the number of patients, the total therapeutic dose administered, the percentage of any prostate-specific antigen (PSA) decline, the percentage with PSA decline exceeding 50% baseline, and toxicities. Overall, a majority of patients responded to therapy, and in the prospective studies, survival was found to be upwards of one year. Significant toxicities included cytopenias, which were infrequent. Patients who had PSA declines in response to therapy had longer survival. Performance status and tumor grade were also key predictors of outcome.

The past five years have seen an increasing acceptance of peptide-based prostate-specific membrane antigen (PSMA)-targeted radionuclide therapy (TRT) agents for treatment of metastatic castration-resistant prostate cancer (mCRPC), with [177Lu]-DKFZ-PSMA-617 ([177Lu]-PSMA-617) emerging as the leading candidate. [177Lu]-PSMA-617 and other PSMA ligands have shown efficacy in reducing the tumor burden in mCRPC patients but irradiation to salivary gland and kidneys is a concern and dose limiting factor. Therefore, methods to reduce non-target organ toxicity are needed to safely treat patients and preserve their quality of life. Here, we report the effects of the addition of the cold PSMA ligand DKFZ-PSMA-11 (PSMA-11) on the uptake of [177Lu]-PSMA-617 in tumor, salivary glands and kidneys. Groups of athymic nude mice (n = 4) bearing PC3-PIP (PSMA+) tumor xenografts were administered with [177Lu]-PSMA-617 along with 0, 5, 100, 500, 1000 and 2000 pmoles of PSMA-11. Biodistribution studies 1 h post-administration revealed that [177Lu]-PSMA-617 uptake in PSMA-expressing PC3-PIP tumors was 21.71±6.13, 18.7±2.03, 26.44±2.94, 16.21±3.5, 13.52±3.68, and 12.03±1.96 %ID/g when 0, 5, 100, 500, 1000 and 2000 pmoles of PSMA-11 were added, respectively. Corresponding kidney uptake values were 123.14±52.52, 132.31±47.4, 84.29±78.25, 2.12±1.88, 1.16±0.36, 0.64±0.23 %ID/g, respectively. Corresponding salivary gland uptake values were 0.48±0.11, 0.45±0.15, 0.38±0.3, 0.08±0.03, 0.09±0.07, 0.05±0.02 % ID/g, respectively. Thus, uptake of PSMA TRT agents in salivary gland and kidney can be substantially reduced without impact on tumor uptake by adding cold PSMA-11. Our data provides proof-of-concept and we propose that similar strategy be pursued in future clinical trials to prevent xerostomia and renal toxicity arising from [177Lu]-PSMA-617.

A review of the literature on COVID-19 pandemic in patients with thalassemias is presented. Globally, the prevalence of COVID-19 among β-thalassemia patients seems to be lower than in general population; associated co-morbidities aggravated the severity of COVID- 19, leading to a poorer prognosis, irrespective of age. A multicenter registry will enhance the understanding of COVID-19 in these patients and will lead to more evidence-based management recommendations. (www.actabiomedica.it)

Objectives: This study aims to investigate, retrospectively, the epidemiological and clinical characteristics, laboratory results, radiologic findings and outcomes of novel coronavirus disease-19 (COVID-19) in patients with transfusion dependent β thalassemia (β-thalassemia major-TM), non-transfusion dependent β thalassemia (β-thalassemia intermedia -TI) and sickle cell disease (SCD). Design, setting: A total of 17 Centers, from 10 countries, following 9,499 patients with hemoglobinopathies participated in the survey. Main outcome measures: Clinical, laboratory and radiologic findings and outcomes of patients with COVID-19 were collected from medical records and summarized. Results: A total of 13 patients, 7 with TM, 3 with TI and 3 with SCD, with confirmed COVID-19, were identified from 6 Centers from different countries. The overall mean age of patients was 33.7±12.3 years (range:13-66); 9/13 (69.2%) patients were females. The commonest symptoms in the 10 symptomatic patients were: fever (80%), cough (70%), headache (60%), fatigue (60%), gastrointestinal symptoms (diarrhea /vomiting/abdominal pain; 50%), tachypnea/dyspnea (40%), and sore throat (40%). Six patients had pneumonia (unilateral, bilateral or multiple opacity) and 4 needed oxygen therapy. An oxygen saturation ≤ 93% was documented in 3 patients at diagnosis. 6/10 patients had an exacerbation of anemia (2 with SCD, associated with back and chest pain in 1 patient), and 3 (

INTRODUCTION AND OBJECTIVE:PSMA is established for TRT with either monoclonal antibodies (mAb) or small molecule ligands. The molecular weight, pharmacokinetics, and biodistribution of mAb vs ligan...

Parkinson disease (PD) is the second most common neurodegenerative disorder, characterized by loss of nigrostriatal dopaminergic neurons. Impairment of the neurovascular unit (NVU) has been hypothesized to play a critical role in early PD pathophysiology, and to precede neurodegenerative mechanisms. [C-11]-PE2I (N-(3-iodoprop-2E-enyl)-2b-carbomethoxy-3b-(4-methyl-phenyl)nortropane) (PE2I) is a PET radiotracer targeting neuronal dopamine transporters (DaT) with high specificity, allowing for highly accurate and specific DaT quantification. We investigated NVU integrity using arterial spin labeling (ASL) MRI in a prospective cohort of 26 patients with PD, and correlated our findings with analysis of striatal DaT density using PE2I PET in a subcohort of 17 patients. Analysis was performed in FreeSurfer to obtain rCBF and mean standardized regional PET avidity. Pearson correlations and Mann-Whitney tests were performed. Significantly lower mean normalized striatal PE2I SUV values were seen in multiple regions in patients with greater disease duration (p < 0.05). PET uptake in the putamen correlated with disease duration independent of patient age. Stratifying patients based on Montreal Cognitive Assessment (MoCA) scores (stratified into ≥ 27 vs. < 27), there was statistically significantly lower PE2I PET avidity in the higher MoCA score group in both more and less affected sides of the caudate, putamen and pallidum (p < 0.05). A moderate negative correlation between MDS-UPDRS part 3 (motor) "off" and rCBF values was also seen in the L and R cerebellum WM (r = -0.43 and -0.47, p < 0.05). A statistically significant negative correlation was found between dominant hand pegboard test results and rCBF in the less affected pallidum (r = -0.41; p = 0.046). A statistically significant negative correlation of ASL MRI with [11C]-PE2I PET was also found (r = -0.53 to -0.58; p-value 0.017-0.033) between left cerebral WM rCBF and more and less affected striatal PET regions. Our ROI-based analyses suggest that longer disease duration is associated with lower rCBF and lower PE2I mean SUV, implying greater NVU dysfunction and dopaminergic neuronal loss, respectively. Combined ASL MRI and PE2I PET imaging could inform future prospective clinical trials providing an improved mechanistic understanding of the disease, laying the foundation for the development of early disease biomarkers and potential therapeutic targets.

Somatostatin receptors (SSTR) are upregulated in the cells of origin that define numerous neuroendocrine neoplasms. PET imaging with 68Ga-DOTATATE allows specific targeting of SSTR2A, a single species of SSTR receptor, which is commonly overexpressed in a variety of gastroenteropancreatic neuroendocrine tumors, as well as pulmonary carcinoid and head and neck tumors. Due to more specific targeting of SSTR2 as well as lower radiation dose, shorter study length, ability to quantify uptake, and lower cost, 68Ga-DOTATATE has demonstrated superior imaging attributes when compared to 111In-pentetreotide. As with any novel imaging modality, dedicated training, increasing experience and staying up-to-date with scientific publications are required to provide optimal patient care. The purpose of this review is to summarize the current state of the art in SSTR-targeted molecular imaging and discuss ongoing and future potential diagnostic and therapeutic applications.

Due to the recent alarming increase in the incidence of hepatocellular carcinoma (HCC) in thalassemias, the aim of the present report is to review briefly the frequency, the major risk factors and the surveillance of HCC in β-thalassemias. Over the past 33 years, 153 cases of HCC were reported in patients with thalassemia, mainly in Italy, and Greece. Among HCV-infected patients additional factors promoting development of HCC, included: advanced age, male sex, chronic hepatitis B (CHB) coinfection, and iron overload. For early diagnosis of HCC sequential ultrasound screening is recommended especially for thalassemia patients with chronic hepatitis C (CHC), that coincide with (one or more) additional risk factors for HCC. Here we report also the preliminary data of thalassemic patients, above the age of 30 years, followed in 13 different centers. The total number of enrolled patients was 1,313 (males: 612 and 701 females). The prevalence of HCC in thalassemia major patients [characterized by transfusion-dependency (TDT)] and thalassemia intermedia [characterized by nontransfusion dependency (NTDT)] was 1.68 % and 1.98 % ,respectively The lowest age at diagnosis was 36 years in TDT and 47 years in NTDT patients.We hope that our review can be used to develop more refined and prospective analyses of HCC magnitude and risk in patients with thalassemia, and to define specific international guidelines to support clinicians for an early diagnosis and treatment of HCC in thalassemic patients.