Paola Castaldi

Diagnostic performance of Gallium-68 somatostatin receptor PET and PET/CT in patients with thoracic and gastroenteropancreatic neuroendocrine tumours: a meta-analysis

Gallium-68 somatostatin receptor (SMSR) positron emission tomography (PET) and positron emission tomography/computed tomography (PET/CT) are valuable diagnostic tools for patients with neuroendocrine tumours (NETs). To date, a meta-analysis about the diagnostic accuracy of these imaging methods is lacking. Aim of our study is to meta-analyse published data about the diagnostic performance of SMSR PET or PET/CT in patients with thoracic and/or gastroenteropancreatic (GEP) NETs. A comprehensive computer literature search of studies published in PubMed/MEDLINE, Scopus and Embase databases through October 2011 and regarding SMSR PET or PET/CT in patients with NETs was carried out. Only studies in which SMSR PET or PET/CT were performed in patients with thoracic and/or GEP NETs were selected (medullary thyroid tumours and neural crest derived tumours were excluded from the analysis). Pooled sensitivity, pooled specificity and area under the ROC curve were calculated to measure the diagnostic accuracy of SMSR PET and PET/CT in NETs. Results: Sixteen studies comprising 567 patients were included in this meta-analysis. The pooled sensitivity and specificity of SMSR PET or PET/CT in detecting NETs were 93% (95% confidence interval [95% CI]: 91–95%) and 91% (95% CI: 82–97%), respectively, on a per patient-based analysis. The area under the ROC curve was 0.96. In patients with suspicious thoracic and/or GEP NETs, SMSR PET and PET/CT demonstrated high sensitivity and specificity. These accurate techniques should be considered as first-line diagnostic imaging methods in patients with suspicious thoracic and/or GEP NETs.

Comparison of 18F-DOPA, 18F-FDG and 68Ga-somatostatin analogue PET/CT in patients with recurrent medullary thyroid carcinoma

PurposeTo retrospectively evaluate and compare 18F-FDG, 18F-DOPA and 68Ga-somatostatin analogues for PET/CT in patients with residual/recurrent medullary thyroid carcinoma (MTC) suspected on the basis of elevated serum calcitonin levels.MethodsIncluded in the study were 18 patients with recurrent MTC in whom functional imaging with the three tracers was performed. The PET/CT results were compared on a per-patient basis and on a per-lesion-basis.ResultsAt least one focus of abnormal uptake was observed on PET/CT in 13 patients with 18F-DOPA (72.2% sensitivity), in 6 patients with 68Ga-somatostatin analogues (33.3%) and in 3 patients with 18F-FDG (16.7%) (p < 0.01). There was a statistically significant difference in sensitivity between 18F-DOPA and 18F-FDG PET/CT (p < 0.01) and between 18F-DOPA and 68Ga-somatostatin analogue PET/CT (p = 0.04). Overall, 72 lesions were identified on PET/CT with the three tracers. 18F-DOPA PET/CT detected 85% of lesions (61 of 72), 68Ga-somatostatin analogue PET/CT 20% (14 of 72) and 18F-FDG PET/CT 28% (20 of 72). There was a statistically significant difference in the number of lymph node, liver and bone lesions detected with the three tracers (p < 0.01). In particular, post-hoc tests showed a significant difference in the number of lymph node, liver and bone lesions detected by 18F-DOPA PET/CT and 18F-FDG PET/CT (p < 0.01 for all the analyses) and by 18F-DOPA PET/CT and 68Ga-somatostatin analogue PET/CT (p < 0.01 for all the analyses). The PET/CT results led to a change in management of eight patients (44%).Conclusion18F-DOPA PET/CT seems to be the most useful imaging method for detecting recurrent MTC lesions in patients with elevated serum calcitonin levels, performing better than 18F-FDG and 68Ga-somatostatin analogue PET/CT. 18F-FDG may complement 18F-DOPA in patients with an aggressive tumour.

Diagnostic performance of 18 F-dihydroxyphenylalanine positron emission tomography in patients with paraganglioma: a meta-analysis

PurposeThe aim of this study was to systematically review and conduct a meta-analysis of published data about the diagnostic performance of 18F-dihydroxyphenylalanine (DOPA) positron emission tomography (PET) in patients with paraganglioma (PG).MethodsA comprehensive computer literature search of studies published through 30 June 2011 regarding 18F-DOPA PET or PET/computed tomography (PET/CT) in patients with PG was performed in PubMed/MEDLINE, Embase and Scopus databases. Pooled sensitivity and specificity of 18F-DOPA PET or PET/CT in patients with PG on a per patient- and on a per lesion-based analysis were calculated. The area under the receiver-operating characteristic (ROC) curve was calculated to measure the accuracy of 18F-DOPA PET or PET/CT in patients with PG. Furthermore, a sub-analysis taking into account the different genetic mutations in PG patients was also performed.ResultsEleven studies comprising 275 patients with suspected PG were included in this meta-analysis. The pooled sensitivity of 18F-DOPA PET and PET/CT in detecting PG was 91% [95% confidence interval (CI) 87–94%] on a per patient-based analysis and 79% (95% CI 76–81%) on a per lesion-based analysis. The pooled specificity of 18F-DOPA PET and PET/CT in detecting PG was 95% (95% CI 86–99%) on a per patient-based analysis and 95% (95% CI 84–99%) on a per lesion-based analysis. The area under the ROC curve was 0.95 on a per patient- and 0.94 on a per lesion-based analysis. Heterogeneity between the studies about sensitivity of 18F-DOPA PET or PET/CT was found. A significant increase in sensitivity of 18F-DOPA PET or PET/CT was observed when a sub-analysis excluding patients with succinate dehydrogenase subunit B (SDHB) gene mutations was performed.ConclusionIn patients with suspected PG 18F-DOPA PET or PET/CT demonstrated high sensitivity and specificity. 18F-DOPA PET or PET/CT are accurate methods in this setting. Nevertheless, possible sources of false-negative results should be kept in mind. Furthermore, SDHB gene mutations could influence 18F-DOPA PET or PET/CT diagnostic performance.

Role of PET/CT in the functional imaging of endocrine pancreatic tumors

Endocrine pancreatic tumors (EPTs) are a heterogeneous group of neoplasms with variable clinical and biological features and prognosis, ranging from very slow-growing tumors to highly aggressive and very malignant ones. As other neuroendocrine tumors, EPTs are characterized by the presence of neuroamine uptake mechanisms and/or peptide receptors at the cell membrane and these features constitute the basis of the clinical use of specific radiolabeled ligands, both for imaging and therapy. The more widespread use of hybrid machines, i.e., positron emission tomography/computed tomography (PET/CT), allows to perform imaging with high resolution and high diagnostic accuracy especially for small lesions, and to correlate anatomic location with function. The recent WHO recommendations for classification and prognostic factors help the selection of tracers likely to show a positive image on PET; therefore, tracers exploiting specific metabolic patterns (18F-DOPA and 11C-5-HTP) or specific receptor expression (68Ga-DOTA-peptides) are suited to well-differentiated tumors, while the use of 18F-FDG is preferred for poorly-differentiated neoplasms with high proliferative activity and loss of neuroendocrine features. In differentiated EPTs, 11C-5-HTP performs better than 18F-DOPA even though its use is hampered by its complex production and limited availability and experience; 68Ga-peptides are indicated for all type of gastroenteropancreatic (GEP) neuroendocrine tumors, regardless of their functional activity. In addition, 68Ga-DOTA-peptides play a distinctive role in planning peptide receptor radionuclide therapy.

Comparison of 123I-MIBG SPECT-CT and 18F-DOPA PET-CT in the evaluation of patients with known or suspected recurrent paraganglioma.

ObjectivesDetection of recurrent disease is essential for treatment planning in patients with paraganglioma. The aim of this study was to compare 123I-metaiodobenzylguanidine (123I-MIBG) scintigraphy [whole-body and single-photon emission computed tomography (SPECT) computed tomography (CT) scanning] and fluorine-18-L-dihydroxyphenylalanine positron emission tomography CT (18F-DOPA PET-CT) in the re-staging of patients with known or suspected recurrent paraganglioma. MethodsTwelve patients with known or suspected recurrent paraganglioma after initial surgery were included in the study. 18F-DOPA PET-CT and 123I-MIBG scintigraphy (whole-body and SPECT-CT scanning) were performed in all patients; the results were compared on a per patient and a per lesion basis. Cytohistology (when available) and a combination of laboratory and imaging studies and follow-up were used as reference standard; any modification in treatment planning was recorded. In all cases recurrent disease (local or distant) was confirmed by cytohistology (four cases) or at subsequent follow-up (eight cases). ResultsAll patients had positive 18F-DOPA studies (100% sensitivity) whereas nine had positive 123I-MIBG studies (75% sensitivity; P=not significant). 18F-DOPA detected 98% of lesions, whereas 38% were detected with 123I-MIBG (P=0.04). 18F-DOPA showed more lesions than 123I-MIBG in eight patients; both techniques showed the same number of lesions in two cases whereas in two patients 123I-MIBG showed a greater number of lesions. A change in treatment planning was suggested by 18F-DOPA in one patient. ConclusionThese data support the superiority of 18F-DOPA PET-CT over 123I-MIBG scintigraphy to assess disease extension in patients with recurrent paraganglioma; however, in cases with inoperable disease, 123I-MIBG maintains a unique role in allowing the selection of patients suitable for 131I-MIBG therapy.

Impact of 111In-DTPA-octreotide SPECT/CT fusion images in the management of neuroendocrine tumours

PurposeSomatostatin receptor scintigraphy with [111In]-diethylene triamine pentaacetate acid (DTPA)-octreotide is an accurate method for detecting neuroendocrine tumours (NETs) but often does not provide clear anatomical localisation of lesions. The aim of this study was to assess the clinical usefulness of anatomical-functional image fusion.Materials and methodsFifty-four patients with known or suspected NET were included in the study. Planar and single-photon-emission computed tomography (SPECT) imaging was performed using a dual-head gamma camera equipped with an integrated X-ray transmission system, and the images were first interpreted alone by two nuclear medicine physicians and then compared with SPECT/CT fusion images together with a radiologist. The improvement provided by SPECT/CT in the interpretation of SPECT data alone and any modification in patientmanagement were recorded.ResultsFusion images improved SPECT interpretation in 23 cases, providing precise anatomical localisation of increased tracer uptake in 20 cases and disease exclusion in sites of physiological uptake in 5. In 10 patients, SPECT/CT allowed definition of the functional significance of lesions detected by diagnostic CT. SPECT/CT data modified clinical management in 14 cases by changing the diagnostic approach in 8 and the therapeutic modality in 6.ConclusionsOur study demonstrates that image fusion is clearly superior to SPECT alone, allowing precise localisation of lesions and reducing false-positive results.RiassuntoObiettivoLa scintigrafia con 111In-DTPA-octreotide rappresenta un metodo accurato per la diagnosi dei tumori neuroendocrini, ma spesso non fornisce una corretta localizzazione anatomica delle lesioni. Scopo di questo studio è valutare l’utilità clinica della fusione di immagini SPECT-TC.Materiali e metodiSono stati inclusi 54 pazienti con tumore neuroendocrino sospetto o noto. Le immagini planari e SPECT, ottenute utilizzando una gamma-camera a doppia testata con integrato sistema trasmissivo TC, sono state interpretate prima separatamente da due medici nucleari e poi confrontate con immagini di fusione insieme ad un radiologo, per valutare i miglioramenti apportati dalla fusione nell’interpretazione delle immagini SPECT e nella gestione del paziente.RisultatiLe immagini di fusione hanno migliorato l’interpretazione SPECT in 23 casi, permettendo una precisa localizzazione anatomica dei siti patologici in 20 casi e l’esclusione di malattia in siti di accumulo fisiologico in 5. In 10 pazienti SPECT/TC ha permesso la definizione funzionale di lesioni evidenziate alla TC diagnostica. SPECT/TC ha modificato il management clinico in 14 pazienti, modificando l’approccio diagnostico in 8 e quello terapeutico in 6.ConclusioniIl nostro studio dimostra che la fusione di immagini è chiaramente superiore alla sola SPECT, permettendo una precisa localizzazione delle lesioni individuate e riducendo i risultati falsi positivi.

Thyroid carcinomas with a variable insular component : Prognostic significance of histopathologic patterns

An insular growth pattern may be observed focally both in papillary and follicular thyroid carcinoma. The aim of the current study was to determine whether a greater extension of the insular component (IC) influences different clinical and histologic features at diagnosis, and a different tumor aggressiveness in terms of frequency in the occurrence of metastases as well as survival.

Clinical applications of 18 F-FDG PET in the management of hepatobiliary and pancreatic tumors

The assessment of hepatobiliary and pancreatic tumors is commonly achieved by ultrasound, computed tomography (CT), and magnetic resonance. The 2-[fluorine-18]fluoro-2-deoxy-d-glucose (FDG) positron emission tomography (PET) detects increased glucose metabolism associated with neoplastic lesions, provides high accuracy in most cancer imaging applications and is now widely used in clinical practice. However, PET is not always useful and accurate knowledge of appropriate indications is essential for a proper clinical management. 18F-FDG is transported into cells and phosphorylated by the enzyme hexokinase to 18F-FDG-6-phosphate, which cannot proceed down the glycolytic pathway and therefore is accumulated in the malignant tissue. PET allows accurate quantification of FDG uptake in tissue, and previous studies have demonstrated that standardized uptake values provide highly reproducible parameters of tumor glucose use (Weber et al., J Nucl Med 40:1771–1777, 1999). The recent development and diffusion of hybrid PET–CT scanners allows functional and anatomic data to be obtained in a single examination, improving lesion localization and resulting in significant diagnostic improvement (Wahl, J Nucl Med 45:82S–95S, 2004). Moreover, CT can be performed diagnostically with the use of intravenous and oral contrast and simultaneous PET–contrast-enhanced CT scanning appears to be an efficient method in cancer evaluation. However, in most centers, a low-dose CT is routinely performed without contrast media infusion.Proper patient preparation, scanning protocol, combined assessment of PET and CT data, and the evaluation of conventional imaging findings are essential to define disease and to avoid diagnostic pitfalls. The role of PET and PET–CT in malignancies of the liver, biliary tract, and pancreas is here reviewed; normal patterns, representative cases, and common pitfalls are also presented.

A phase II study of sunitinib in advanced hepatocellular carcinoma

BACKGROUND In 2007, sorafenib was the first drug able to improve overall survival in patients with advanced hepatocellular carcinoma. AIM In 2005 we designed a phase II study to assess safety and efficacy of sunitinib. METHODS This is a single arm, open-label, single-centre phase II trial. Eligibility criteria were advanced hepatocellular carcinoma; no prior chemotherapy, performance status 0-1; and Child≤B8. The treatment schedule was 50mg each day orally, 4 weeks on, 2 weeks off. RESULTS Between 10/2007 and 10/2010, 34 patients were enrolled. A significant worsening of liver functional reserve after sunitinib was observed. Grade 3/4 adverse effects occurred in 80% of patients and included fatigue (47%), nausea (15%), liver failure (15%), encephalopathy (12%) and upper gastrointestinal bleeding (12%). Six patients (18%) died within 60 days of enrolment. A partial response was observed in 4 patients (12%). Median time to tumour progression was 2.8 months and median overall survival was 5.8 months. CONCLUSION A dose of 50mg/d induces a high rate of severe adverse events. Toxicity remains a key concern also at the dose of 37.5mg/d. However, sunitinib is able to induce a prolonged response in some patients. Positron Emission Tomography/Computed Tomography scans may select good responders.

Comparison of Different Positron Emission Tomography Tracers in Patients with Recurrent Medullary Thyroid Carcinoma: Our Experience and a Review of the Literature

Several morphological and functional imaging techniques are usually used to detect residual/recurrent medullary thyroid carcinoma (MTC) with variable results; currently, there is growing interest in positron emission tomography (PET) methodology. Herein, we report our experience of and a literature review about the comparison of different positron emission tomography (PET) tracers in patients with residual/recurrent MTC. (18)F-DOPA PET/CT seems to be the most useful imaging method to detect recurrent MTC lesions, performing better than (18)F-FDG and (68)Ga-somatostatin analogs PET/CT. (18)F-FDG may complement (18)F-DOPA in patients with aggressive tumors. (68)Ga-somatostatin analogs PET/CT may be useful to select patients who could benefit from radioreceptor therapy. The information provided by the various PET tracers reflects different metabolic pathways, and may help to select the most appropriate treatment.