Vittoria Rufini

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.

The role of positron emission tomography using carbon-11 and fluorine-18 choline in tumors other than prostate cancer: a systematic review

To systematically review published data on the role of positron emission tomography (PET) or PET/computed tomography (PET/CT) using either Carbon-11 (11C) or Fluorine-18 (18F) choline tracer in tumors other than prostatic cancer. A comprehensive literature search of studies published in PubMed/MEDLINE and Embase databases through January 2012 and regarding 11C-choline or 18F-choline PET or PET/CT in patients with tumors other than prostatic cancer was carried out. Fifty-two studies comprising 1800 patients were included and discussed. Brain tumors were evaluated in 15 articles, head and neck tumors in 6, thoracic tumors (including lung and mediastinal neoplasms) in 14, liver tumors (including hepatocellular carcinoma) in 5, gynecologic malignancies (including breast tumors) in 5, bladder and upper urinary tract tumors in 5, and musculoskeletal tumors in 7. Radiolabeled choline PET or PET/CT is useful to differentiate high-grade from low-grade gliomas and malignant from benign brain lesions, to early detect brain tumor recurrences and to guide the stereotactic biopsy sampling. The diagnostic accuracy of radiolabeled choline PET is superior compared to Fluorine-18 fluorodeoxyglucose (18F-FDG) PET in this setting. Radiolabeled choline PET or PET/CT seems to be accurate in differential diagnosis between malignant and benign thoracic lesions and in staging lung tumors; nevertheless, a superiority of radiolabeled choline compared to 18F-FDG has not been demonstrated in this setting, except for the detection of brain metastases. Few but significant studies on radiolabeled choline PET and PET/CT in patients with hepatocellular carcinoma (HCC) and musculoskeletal tumors are reported in the literature. The combination of radiolabeled choline and 18F-FDG PET increases the detection rate of HCC. The diagnostic accuracy of radiolabeled choline PET or PET/CT seems to be superior compared to 18F-FDG PET or PET/CT and conventional imaging methods in patients with bone and soft tissue tumors. Limited experience exists about the role of radiolabeled choline PET and PET/CT in patients with head and neck tumors, bladder cancer and gynecologic malignancies including breast cancer.

Treatment of advanced neuroblastoma: feasibility and therapeutic potential of a novel approach combining 131-I-MIBG and multiple drug chemotherapy

Biological and clinical observations suggest that initial marked reduction of resistant clones may be critical in any attempt to improve long-term results in advanced neuroblastoma (NB). The aim of this pilot study is to determine short-term toxicity and efficacy of a new therapeutic model based on the simultaneous use of multiple drug chemotherapy and specific irradiation using 131-I-MIBG. The study population consisted of 21 patients, from 1 to 8 years of age with good 131-I-MIBG uptake. 16 extensively pre-treated patients with refractory or relapsed disease were divided into 2 groups. In Group 1 (9 patients) the basic chemotherapy regimen consisted in cisplatin at the dose of 20 mg/m2i.v. per day infused over 2 h, for 4 consecutive days; on day 4 Cy 2 g/m2i.v. was administered over 2 h followed by Mesna. Group 2 (7 patients) was treated with basic chemotherapeutic regimen plus VP16 and Vincristine. VP16 at the dose of 50 mg/m2i.v. per day was administered as a 24 h infusion on days 1–3; Vincristine 1.5 mg/m2i.v. was administered on days 1 and 6. On day 10 a single dose of 131-I-MIBG (200 mCi) with a high specific activity (>1.1 GBq/mg) was administered to both Groups by i.v. infusion over 4–6 hours. A further 5 patients were treated at diagnosis: 2 with the same regimen as Group 1 and 3 with the same as Group 2. The severity of toxicity was graded according to World Health Organization (WHO) criteria. Assessment of tumour response was monitored 4–6 weeks after the beginning of combined therapy (CO-TH). Response was defined according to INSS (International Neuroblastoma Staging System) criteria. No extra-medullary toxicity was observed in any patient. Haematological toxicity was the only toxicity observed and seemed mainly related to chemotherapy. Myelosuppression was mild in the 5 patients treated at diagnosis. No serious infections or significant bleeding problems were observed. In the 16 resistant patients, 12 PR, 1 mixed response and 3 SD were obtained. In the 5 patients treated at diagnosis 2 PR, 1 CR and 2 VGPR were observed. No alteration in 131-I-MIBG uptake was observed after the chemotherapy preceding radio-metabolic treatment. The therapeutic results of this pilot regimen of CO-TH resulted in a high percentage of major response after only a single course in both resistant patients and patients treated at diagnosis. Because of the minimal toxicity observed in patients studied at diagnosis so far, there is room for gradual intensification of the treatment. It is to be hoped that this suggested novel approach may represent an important route of investigation to improve final outcome in patients with advanced NB.

Clinical significance of incidental focal colorectal (18)F-fluorodeoxyglucose uptake: our experience and a review of the literature.

Aim  The aims of the present study were: (i) to evaluate the focal incidental colorectal uptake of 18F‐fluorodeoxyglucose ([18F]FDG) and to correlate it with colonoscopy and histological findings; (ii) to evaluate the relationship between the presence/absence of neoplastic disease and clinical data and the anatomical site of [18F]FDG uptake; and (iii) to compare our results with those reported for incidental colorectal uptake of [18F]FDG in the literature and those obtained from various screening programmes for colorectal cancer.

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.

Diagnostic accuracy of [18F]DOPA PET and PET/CT in patients with neuroendocrine tumors: a meta-analysis

The aim of this study was to systematically review and meta-analyze published data on the diagnostic accuracy of positron emission tomography (PET) using fluorine-18-dihydroxyphenylalanine ([18F]DOPA) in patients with neuroendocrine tumors (NETs). A comprehensive computer literature search of the PubMed/MEDLINE, Embase and Scopus databases was conducted to identify studies on the use of [18F]DOPA PET or PET/computed tomography (PET/CT) in patients with proven or suspected NETs. Pooled sensitivity and specificity of [18F]DOPA PET and PET/CT on a per patient-based analysis were calculated. The area under the ROC curve was calculated to measure the accuracy of [18F]DOPA PET or PET/CT. Eight articles on gastroenteropancreatic and thoracic NETs, 13 on pheochromocytoma/paraganglioma (Pheo/PGL) and eight on recurrent medullary thyroid carcinoma (MTC) were included in our meta-analysis. The pooled sensitivity and specificity of [18F]DOPA PET or PET/CT in patients with thoracic and gastroenteropancreatic NETs were 77% (95% CI 71–82) and 95% (95% CI 87–98), respectively. The area under the ROC curve was 0.94. The pooled sensitivity and specificity of [18F]DOPA PET or PET/CT in patients with Pheo/PGL were 92% (95% CI 88–95) and 92% (95% CI 85–97), respectively. The area under the ROC curve was 0.95. The pooled sensitivity of [18F]DOPA PET or PET/CT in patients with recurrent MTC was 62% (95% CI 54–69). Heterogeneity was found between the studies with regard to the sensitivity of [18F]DOPA PET or PET/CT. Evidence-based data show that [18F]DOPA PET and PET/CT are accurate methods in patients with proven or suspected NETs. Large multicenter studies are necessary to substantiate the diagnostic accuracy of [18F]DOPA PET and PET/CT in this setting.

18F-Fluorodeoxyglucose positron emission tomography in evaluating treatment response to imatinib or other drugs in gastrointestinal stromal tumors: a systematic review☆

OBJECTIVE To systematically review the role of (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET) in evaluating treatment response to imatinib or other drugs in gastrointestinal stromal tumors (GIST). METHODS A comprehensive literature search of published studies through February 2011 in PubMed/MEDLINE and EMBASE databases was performed. RESULTS We identified 19 studies including 628 patients with GIST. Main findings of included studies are presented. CONCLUSIONS (18)F-FDG PET has a significant value in assessing treatment response to imatinib or other drugs in GIST patients. (18)F-FDG PET allows an early assessment of treatment response and is a strong predictor of clinical outcome.

Radio-guided surgery for lymph node recurrences of differentiated thyroid cancer

The objectives of this study were to assess the reliability of radioiodine (131I) and a gamma probe for radio-guided surgery (RGS) to detect and then radically dissect lymph node recurrences (LNRs) in 10 patients with differentiated thyroid cancer (DTC). The major inclusion criterion was the presence of an iodine-positive LNR after previous total thyroidectomy and at least two ineffective 131I treatments. The protocol was designed as follows. Day 0: all patients were hospitalized and received 3.7 GBq of 131I in the hypothyroid condition. Day 3: presurgery whole-body scan with a therapeutic dose (TxWBS). Day 5: neck surgery using a gamma probe (Navigator GPS, AutoSuture, Italy), recording the absolute counts and the lesion/background (L/B) counts ratio. Day 7: post-surgery TxWBS performed using the remaining radioactivity. The presurgery TxWBS was positive in all patients, and the post-surgery TxWBS showed a negative pattern in 7 of 10 patients, suggesting the efficacy of the surgical procedure in most of the patients. After RGS the mean decrease in the absolute counts and the L/B counts ratio were 77.6% (52.7% minimum, 94.6% maximum) and 77.4% (52.3% minimum, 94.8% maximum), respectively. After operation the surgeon judged the procedure to be decisive in two patients, favorable in six, and irrelevant in two. The final histologic examination showed the presence of 78 lymph node metastases (mean of 8 per patient). There were 33 neoplastic lesions found by both TxWBS and gamma probe evaluations; 41 were shown only by gamma probe, and 4 were negative by both TxWBS and gamma probe evaluations. This protocol permitted us to look for neoplastic foci with high sensitivity and specificity, and we were able to remove lymph node metastases resistant to radioiodine therapy at a single session. The protocol also allowed detection of some additional tumoral foci in sclerotic areas or behind vascular structures that are difficult to identify and were not seen at the presurgery TxWBS evaluation. However, because of the possible false-negative results, complete excision must be undertaken in high risk patients with a local recurrence to eradicate the largest number of lymph nodes, independent of the counts measured by the gamma probe.

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.