Laura Evangelista

Choline PET or PET/CT and biochemical relapse of prostate cancer: a systematic review and meta-analysis.

Aim The increase of prostate-specific antigen (PSA) after radical retropubic prostatectomy (RP) or external beam radiotherapy (EBRT) is the most sensitive tool for detecting prostate cancer (PCa) recurrence, although this measure cannot distinguish between local, regional, or distant recurrence. The aim of this meta-analysis was to evaluate the diagnostic performance of 18F-choline and 11C-choline PET or PET/CT in detection of locoregional or distant metastases in PCa. Materials and Methods Medline, Web of Knowledge, and Google Scholar search was carried out in order to select English-language articles dealing with diagnostic performance of both 18F-choline and 11C-choline PET for the detection of PCa recurrence after RP or EBRT. Articles were included only if absolute numbers of true-positive, true-negative, false-positive, and false-negative test results were available or derivable from the text and regarded local, lymph node, and distant metastases. Reviews, clinical reports, and editorial articles were excluded. All complete studies were re-analyzed thus performing a quantitative analysis. Results From the years 2000 to 2012, we found 53 complete articles that critically evaluated the role of choline PET in restaging patients with PCa recurrence. The meta-analysis was carried out and dealt with 19 selected studies (12 studies for all sites of disease, 3 for lymph node metastases, and 4 for local recurrence), with a total of 1555 patients. The meta-analysis provided a pooled sensitivity of 85.6% (95% CI: 82.9%–88.1%) and pooled specificity of 92.6% (95% CI: 90.1%–94.6%) for all sites of disease (prostatic fossa, lymph nodes, and bone), a pooled sensitivity of 75.4% (95% CI: 66.9%–82.6%) and pooled specificity of 82% (95% CI: 68.6%–91.4%) for prostatic fossa recurrence, and a pooled sensitivity of 100% (95% CI: 90.5%–100%) and pooled specificity of 81.8% (95% CI: 48.2%–97.7%) for lymph node metastases. The heterogeneity ranged between 0.00% and 88.6%. The diagnostic odds ratios were 62.123 (95% CI: 24.783–155.72), 5.869 (95% CI: 1.818–18.946), and 138.57 (95% CI: 11.27–1703.8), respectively, for all sites of disease, local recurrence, and lymph node disease. Conclusions Choline PET and PET/CT represent high sensitivity and specificity techniques for the detection of locoregional and distant metastases in PCa patients with recurrence of disease. Moreover, a high diagnostic odds ratio was found for the identification of lymph node disease in patients with biochemical recurrence of PCa.

Utility of choline positron emission tomography/computed tomography for lymph node involvement identification in intermediate- to high-risk prostate cancer: a systematic literature review and meta-analysis.

CONTEXT Determination of tumour involvement of regional lymph nodes in patients with prostate cancer (PCa) is of key importance for the proper planning of treatment. OBJECTIVES To provide a critical overview of published reports and to perform a meta-analysis about the diagnostic performance of 18F-choline and 11C-choline positron emission tomography (PET) or PET/computed tomography (CT) in the lymph node staging of PCa. EVIDENCE ACQUISITION A Medline, Web of Knowledge, and Google Scholar search was carried out to select English-language articles published before January 2012 that discussed the diagnostic performance of choline PET to individualise lymph node disease at initial staging in PCa patients. Articles were included only if absolute numbers of true-positive, true-negative, false-positive, and false-negative test results were available or derivable from the text and focused on lymph node metastases. Reviews, clinical reports, and editorial articles were excluded. All complete studies were reviewed; thus qualitative and quantitative analyses were performed. EVIDENCE SYNTHESIS From the year 2000 to January 2012, we found 18 complete articles that critically evaluated the role of choline PET and PCa at initial staging. The meta-analysis was carried out and consisted of 10 selected studies with a total of 441 patients. The meta-analysis provided the following results: pooled sensitivity 49.2% (95% confidence interval [CI], 39.9-58.4) and pooled specificity 95% (95% CI, 92-97.1). The area under the curve was 0.9446 (p<0.05). The heterogeneity ranged between 22.7% and 78.4%. The diagnostic odds ratio was 18.999 (95% CI, 7.109-50.773). CONCLUSIONS Choline PET and PET/CT provide low sensitivity in the detection of lymph node metastases prior to surgery in PCa patients. A high specificity has been reported from the overall studies. Studies carried out on a larger scale with a homogeneous patient population together with the evaluation of cost effectiveness are warranted.

New Clinical Indications for (18)F/(11)C-choline, New Tracers for Positron Emission Tomography and a Promising Hybrid Device for Prostate Cancer Staging: A Systematic Review of the Literature

CONTEXT Radiolabelled choline positron emission tomography has changed the management of prostate cancer patients. However, new emerging radiopharmaceutical agents, like radiolabelled prostate specific membrane antigen, and new promising hybrid imaging will begin new challenges in the diagnostic field. OBJECTIVE The continuous evolution in nuclear medicine has led to the improvement in the detection of recurrent prostate cancer (PCa), particularly distant metastases. New horizons have been opened for radiolabelled choline positron emission tomography (PET)/computed tomography (CT) as a guide for salvage therapy or for the assessment of systemic therapies. In addition, new tracers and imaging tools have been recently tested, providing important information for the management of PCa patients. Herein we discuss: (1) the available evidence in literature on radiolabelled choline PET and their recent indications, (2) the role of alternative radiopharmaceutical agents, and (3) the advantages of a recent hybrid imaging device (PET/magnetic resonance imaging) in PCa. EVIDENCE ACQUISITION Data from recently published (2010-2015), original articles concerning the role of choline PET/CT, new emerging radiotracers, and a new imaging device are analysed. This review is reported according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. EVIDENCE SYNTHESIS In the restaging phase, the detection rate of choline PET varies between 4% and 97%, mainly depending on the site of recurrence and prostate-specific antigen levels. Both 68gallium (68Ga)-prostate specific membrane antigen and 18F-fluciclovine are shown to be more accurate in the detection of recurrent disease as compared with radiolabelled choline PET/CT. Particularly, Ga68-PSMA has a detection rate of 50% and 68%, respectively for prostate-specific antigen levels < 0.5ng/ml and 0.5-2ng/ml. Moreover, 68Ga- PSMA PET/magnetic resonance imaging demonstrated a particularly higher accuracy in detecting PCa than PET/CT. New tracers, such as radiolabelled bombesin or urokinase-type plasminogen activator receptor, are promising, but few data in clinical practice are available today. CONCLUSIONS Some limitations emerge from the published papers, both for radiolabelled choline PET/CT and also for new radiopharmaceutical agents. Efforts are still needed to enhance the impact of published data in the world of oncology, in particular when new radiopharmaceuticals are introduced into the clinical arena. PATIENT SUMMARY In the present review, the authors summarise the last evidences in clinical practice for the assessment of prostate cancer, by using nuclear medicine modalities, like positron emission tomography/computed tomography and positron emission tomography/magnetic resonance imaging.

Gleason Score at Diagnosis Predicts the Rate of Detection of 18F-Choline PET/CT Performed When Biochemical Evidence Indicates Recurrence of Prostate Cancer: Experience with 1,000 Patients

The objective of this study was to explore the ability of the initial Gleason score (GS) to predict the rate of detection of recurrent prostate cancer (PCa) with 18F-choline PET/CT in a large cohort of patients. Methods: Data from 1,000 patients who had undergone 18F-choline PET/CT because of biochemical evidence of relapse of PCa between 2004 and 2013 were retrieved from databases at 4 centers. Continuous data were compared by the Student t test or ANOVA, and categoric variables were compared by the χ2 test. Univariable and multivariable analyses were performed by logistic regression. Results: The GS at diagnosis was less than or equal to 6 in 257 patients, 7 in 347 patients, and greater than 7 in 396 patients. The results of 645 PET/CT scans were positive for PCa recurrence. Eighty-one percent of the positive PET/CT results were found in patients with a PSA level of greater than or equal to 2 ng/mL, 43% were found in patients with a PSA level of 1–2 ng/mL, and 31% were found in patients with a PSA level of less than or equal to 1 ng/mL; 78.8% of patients with positive PET/CT results had a GS of greater than 7. The results of 18F-choline PET/CT scans were negative in 300 patients; 44% had a GS of less than or equal to 6, 35% had a GS of 7, and 17% had a GS of greater than 7. PET/CT results were rated as doubtful in only 5.5% of patients (median PSA, 1.8 ng/mL). When the GS was greater than 7, the rates of detection of 18F-choline PET/CT were 51%, 65%, and 91% for a PSA level of less than 1 ng/mL, 1–2 ng/mL, and greater than 2 ng/mL, respectively. In univariable and multivariable analyses, both a GS of 7 and a GS of greater than 7 were independent predictors for positive 18F-choline PET/CT results (odds ratios, 0.226 and 0.330, respectively; P values for both, <0.001). Conclusion: A high GS at diagnosis is a strong predictive factor for positive 18F-choline PET/CT scan results for recurrent PCa, even when the PSA level is low (i.e., ≤1 ng/mL).

FDG-PET/CT and parathyroid carcinoma: Review of literature and illustrative case series

Parathyroid cancer is an uncommon malignant cancer and is associated with a poor prognosis. The staging of parathyroid cancer represents an important issue both at initial diagnosis and after surgery and medical treatment. The role of positron emission tomography/computed tomography (PET/CT) with 18F-Fluorodeoxyglucose (18F-FDG) as an imaging tool in parathyroid cancer is not clearly reported in the literature, although its impact in other cancers is well-defined. The aim of the following illustrative clinical cases is to highlight the impact of PET/CT in the management of different phases of parathyroid cancer. We describe five patients with parathyroid malignant lesions, who underwent FDG PET/CT at initial staging, restaging and post-surgery evaluation. In each patient we report the value of PET/CT comparing its findings with other common imaging modalities (e.g., CT, planar scintigraphy with 99mTc-sestamibi, magnetic resonance imaging) thus determining the complementary benefit of FDG PET/CT in parathyroid carcinoma. We hope to provide an insight into the potential role of PET/CT in assessing the extent of disease and response to treatment which are the general principles used to correctly evaluate disease status.

Early bone marrow metastasis detection: the additional value of FDG-PET/CT vs. CT imaging.

OBJECTIVE To assess the addition value of ¹⁸F-Fluorodeoxyglucose (FDG) PET/computed tomography (FDG-PET/CT) vs. CT in detecting early metastatic deposits in bone marrow (BM). METHODS From January 2009 to December 2010, 198 consecutive patients (88 male, 110 female; median age: 64 years) were retrospectively examined. All patients underwent ¹⁸F-FDG-PET/CT for disease evaluation: 65 for lung cancer, 66 for breast cancer, 57 for lymphoma and 10 for multiple myeloma. All scans were reviewed by a radiologist and a specialist in nuclear medicine for the identification of bone lesions. The presence of BM metastases was confirmed by biopsy, sequential PET/CT scan or magnetic resonance imaging when available. A patient-based analysis was performed. RESULTS Investigating the presence of skeletal metastasis, 94 (48%) patients had positive and 104 (52%) negative CT scan whereas 110 (56%) had positive and 88 (44%) negative FDG-PET/CT scan (P<0.001). The two imaging modalities were concordant in 178 (90%) patients for bone lesions; on the contrary 20 (10%) patients had discordant results (P<0.001). In 21 out of 178 concordant patients BM lesions were identified both in CT and FDG-PET, whereas nine out of the 20 discordant patients showed BM involvement at PET/CT only. Overall, PET/CT was able to identify 30 (15%) patients with BM lesions. In these latter patients, the maximum standardized uptake value (SUVmax) for BM metastases was 7.9±4.5 (range: 3.1-19.0), resulting slightly higher in patients with negative than positive CT scan (8.3±5.1 vs. 7.8±4.3, respectively; P=0.79). CONCLUSIONS FDG-PET/CT resulted more accurate than CT in early detection of BM metastases. The FDG-PET/CT images improve the staging of about 15% of our study population. PET/CT detected BM lesions mainly on the basis of their increased metabolic activity rather than on anatomical alterations. Moreover, it provided an accurate identification of tumour viability that was useful for treatment planning and follow-up.

Comparison between conventional imaging (abdominal–pelvic computed tomography and bone scan) and [18F]choline positron emission tomography/computed tomography imaging for the initial staging of patients with intermediate- tohigh-risk prostate cancer: A retrospective analysis

Abstract Objective. The aim of this study was to evaluate the efficiency of [18F]fluorocholine positron emission tomography/computed tomography (FCH PET/CT) in detecting lymph-node and bone involvement in comparison with conventional imaging, such as abdominal–pelvic CT and bone scan, in the initial staging of prostate cancer (PCa). Materials and methods. The study retrospectively evaluated 48 patients who had FCH PET/CT for the initial staging of PCa. At the same time, 32 of the 48 patients had a bone scan and 26 of the 48 patients had abdominal–pelvic diagnostic CT. Diagnostic performance of FCH PET/CT, i.e. sensitivity, specificity and accuracy, was evaluated on a per-patient basis for the whole population and then separately on a per-risk classification, and later in comparison with conventional imaging. Histological specimens or follow-up data were used as the standard of reference. Results. The overall accuracy of FCH PET/CT for lymph-node involvement was 83.3%. The sensitivity of FCH was higher in the high-risk subset (83.3%) than in the intermediate-risk group (33.3%), whereas FCH specificity was similar. In comparison with dedicated CT scan, FCH PET/CT showed a higher sensitivity and a similar specificity (46.2% vs 69.2% and 92.3% vs 92.3%, respectively). Moreover, the sensitivity and specificity of PET/CT were higher than those of bone scan (100% vs 90% and 86.4% vs 77.2%, respectively). In contrast with conventional imaging, PET/CT changed the staging of the PCa in 33.3% patients. Conclusions. The efficiency of FCH PET/CT in detecting both bone and lymph-node involvement of PCa at initial staging was found to be higher than that of conventional imaging. Prospective clinical trials are needed to confirm these findings.

Comparison between anatomical cross-sectional imaging and 18F-FDG PET/CT in the staging, restaging, treatment response, and long-term surveillance of squamous cell head and neck cancer: A systematic literature overview

The outcome of head and neck squamous cell cancer depends primarily on its prompt diagnosis and treatment. Unfortunately, in many cases ominous prognostic factors such as lymph node metastases or osteomandibular extension are present at the time of diagnosis. We review the relative efficacy of contrast-enhanced computed tomography (ceCT), MRI, and 18F-fluorodeoxyglucose (18F-FDG) PET/computed tomography (CT) in the early detection of head and neck squamous cell cancer, as well as its impact on treatment management and outcomes. Medline and Web of Knowledge databases, from 2000 to January 2013, were evaluated. Ninety-seven reports were selected, but only 11 studies comparing PET or PET/CT with CT and 11 comparing PET or PET/CT with MRI were found appropriate for analysis. ceCT and MRI continue to be the reference imaging modalities for the study of primary tumors, especially in the evaluation of the extension of disease and its relationship with nearby anatomical structures. There is increasing evidence that 18F-FDG PET/ceCT can provide accurate anatomical details similar to ceCT alone, as well as accurate information on osteomandibular tumor invasion similar to MRI. The major advantage of PET/CT over other imaging methods is its ability to detect relatively small lymph node metastases located in difficult-to-interpret positions. PET/CT is also highly sensitive for the detection of distant metastases and in assessing the response to chemotherapy or chemoradiation treatment and in predicting outcome. ceCT and MRI are the gold standards for evaluating primary and osteomandibular tumoral infiltration. 18F-FDG PET/CT plays a major role in the detection of lymph node and distant metastases, in assessing the response to neoadjuvant/adjuvant chemotherapy or chemoradiation therapy, and in predicting outcome.

Follow-up of patients with early breast cancer: Is it time to rewrite the story?

The guidelines for follow-up in breast cancer survivors support only performance of periodic physical examination and annual mammography. However, medical oncologists and primary care physicians routinely recommend both blood tests and non-mammographic imaging tests in asymptomatic patients, leading to an increased anxiety related to false-positive results and higher medical expenses. Recently, advanced imaging technologies have improved sensitivity/specificity to detect metastatic lesions before symptoms arise. Considering the progress made in the treatment of metastatic disease and the rapid evolution of targeted therapy, that requires customization of the strategy according to molecular characteristics of the disease, patients could derive real benefit to early detection of disease recurrence. This hypothesis must be tested in a prospective clinical trial.

Impact of inducible ischemia by stress SPECT in cardiac risk assessment in diabetic patients: Rationale and design of a prospective, multicenter trial

BackgroundA prospective, multiconter trial has been designed to evaluate the impact of inducible ischemia by stress single photon emission computed tomography (SPECT) in diabetic patients and to define the role of SPECT in assessing the cardiac risk in such patients. This report presents the details and implications of the Impact of Inducible Ischemia by Stress SPECT (IDIS) trial design.Methods and ResultsBetween January 2002 and September 2005, 1006 consecutive patients (649 men and 357 women; mean age, 63±9 years) with at least a 5-year history of type 2 diabetes mellitus were enrolled. All patients underwent stress-rest sestamibi SPECT imaging with physical exercise (n=573) or dipyridamole (n=433). SPECT studies will be analyzed by use of a 17-segment scoring system to calculate left ventricular ejection fraction, summed stress score, summed rest score, and summed difference score. The SPECT study will be considered abnormal if the summed stress score is 3 or greater. Patients with abnormal studies will be considered to have ischemia if the summed difference score is 2 or greater.ConclusionThe results of this trial should help to define the role of SPECT in assesing cardiac risk in diabetic patients. Furthermore, this trial will prospectively evaluate subsequent patient outcome during long-term follow-up.