Longitudinal cognitive decline in mild cognitive impairment subjects with early amyloid-ß neocortical deposition.

PURPOSE: The rate of clinical progression of cognitive impairment in subjects with early amyloid deposition is unknown. The primary aim of the study was to follow the rate of cognitive decline over 1 year in patients with amnestic mild cognitive impairment (aMCI) by determining amyloid retention levels in terms of standardized uptake value ratios (SUVr) that ranged from 0.85 to 1.57. The secondary objective was to compare the rate of cognitive decline between subjects with and without early amyloid positivity. METHODS: Of 66 aMCI subjects evaluated with [18F]florbetaben PET imaging and neuropsychological tests at baseline, 41 completed the 1-year follow-up. Amyloid status was determined with SUVr cut-off values generated from baseline images by visual assessment by three independent certified readers. Repeated-measures ANOVA with amyloid load and neuropsychological scores as the main effects was use to test group, time and group-by-time interactions. The Tukey post-hoc test was used to analyse all significant interactions. RESULTS: Of the 41 aMCI subjects, 38 completed the assessment according to the study protocol. Amyloid-positive (Aß+ ) subjects (N = 18, age 75.6 ± 5.8 years, six men, 12 women) showed greater clinical deterioration according to the Mattis Dementia Rating Scale (MDRS) score (p = 0.006). Amyloid-negative (Aß-) subjects (N = 20, age 72.4 ± 5.8 years, 11 men, 6 women) showed no significant changes in MDRS score over 1 year. MDRS score significantly decreased (MDRS+) in 37% of the aMCI subjects, and remained stable (MDRS-) in the remaining 63%. Among subjects with cognitive deterioration, 86% were Aß+ and 14% were Aß-, while 25% of the MDRS- subjects were Aß+ and 75% were Aß- (χ2 = 13, P = 0.0003). SUVr above 1.21 identified individuals who would show significant progression over 1 year, with a sensitivity of 67% and a specificity of 90%, as compared to Aß- subjects. The positive predictive value, negative predictive value, and likelihood ratio were 86% (95% CI 70-94%), 75% (95% CI 58-87%), 7 (95% CI 5-10). CONCLUSION: This study demonstrated that early amyloid deposition predicts cognitive decline in subjects with aMCI, with a higher rate of decline in those with SUVr above a threshold of 1.21. Detection of early amyloid positivity may help in selecting the target population for preventive therapeutic interventions and in designing treatment trials (Trial number, EudraCT 2015-001184-39).

(11)C-Choline PET/CT as a guide to radiation treatment planning of lymph-node relapses in prostate cancer patients.

PURPOSE: To evaluate, in prostate cancer (PCa) patients the potential of (11)C-choline PET/CT as a guide to helical tomotherapy (HTT) of lymph-node (LN) relapses with simultaneous integrated boost (SIB). The efficacy and feasibility of HTT in terms of acute toxicity were assessed. METHODS: We enrolled 83 PCa patients (mean age 68 years, range 51 - 82 years) with biochemical recurrence after radical primary treatment (mean serum PSA 7.61 ng/ml, range 0.37 - 187.00 ng/ml; PSA0) who showed pathological findings on (11)C-choline PET/CT only at the LN site. (11)C-Choline PET/CT was performed for restaging and then for radiation treatment planning (PET/CT0). Of the 83 patients, 8 experienced further LN relapse, of whom 5 were retreated once and 3 were retreated twice (total 94 radiotherapy treatments). All pelvic and/or abdominal LNs positive on PET/CT0 were treated with high doses using SIB. Doses were in the range 36 - 74 Gy administered in 28 fractions. After the end of HTT (mean 83 days, range 16 - 365 days), serum PSA was measured in all patients (PSA1) and compared with PSA0 to evaluate early biochemical response. In 47 patients PET/CT was repeated (PET/CT1) to assess metabolic responses at the treated areas. Toxicity criteria of the Radiation Therapy Oncology Group (RTOG) were used to assess acute toxicity. RESULTS: PET/CT0 revealed pathological LNs in the pelvis in 49 patients, pathological LNs in the abdomen in 15 patients pathological LNs in both the pelvis and abdomen in 18 patients, and pathological LNs in the pelvis or abdomen and other sites in 12 patients. All these sites were treated with HTT. With respect to PSA0, PSA1 (mean 6.28 ng/ml, range 0.00 - 220.46 ng/ml) showed a complete biochemical response after 66 of the 94 HTT treatments, a partial response after 12 treatments, stable disease after 1 treatment and progression of disease after 15 treatments. Of the 47 patients receiving PET/CT1, 20 showed a complete metabolic response at the treated area, 22 a partial metabolic response, 3 progression of disease and 2 stable disease. HTT with SIB was well tolerated in all patients. Grade 3 acute toxicity in the genitourinary tract was observed in two patients. CONCLUSION: (11)C-Choline PET/CT is a valuable tool for planning and monitoring HTT in LN relapse after primary treatment. High-dose hypofractionated (11)C-choline PET/CT-guided HTT with SIB is well tolerated and is associated with a high early biochemical response rate.

Role of 18FDG-PET/CT in detecting relapse during follow-up of patients with Hodgkin's lymphoma.

The role of 18FDG-PET/CT during follow-up of patients affected by Hodgkin's lymphoma (HL) in complete remission after treatment is not fully elucidated, since a wide use of 18F fluorodeoxyglucose positron emission tomography/computed tomography (18FDG-PET/CT) in this setting could be limited by a relative high rate of false-positive results. Herein, we summarize a retrospective analysis of 27 patients with Hodgkin's lymphoma in complete remission after the first-line (n = 20) or salvage (n = 7) therapy receiving serial 18FDG-PET/CT scans during follow-up. Out of 165 scans, 13 were suspected for relapse, which was confirmed in seven patients. All relapses were correctly identified by 18FDG-PET/CT positivity, with a 100% sensitivity; false-positive rate was 46% and negative predictive value was 100%. True-positive findings were mostly associated with multiple sites, subdiaphragmatic involvement, and/or previous sites of disease. According to our results, we conclude that performing routine PET/CT scan during follow-up of those patients who are at high risk of relapse would be advisable, although caution must be adopted when interpreting PET/CT results due to the relatively high rate of false-positive findings. If FDG abnormal uptake is present at multiple nodal sites, subdiaphragmatic lymph nodes, or previous sites of disease, histological verification of PET abnormal findings is warranted.

Positron emission tomography/computed tomography introduction in the clinical management of patients with suspected recurrence of ovarian cancer: a cost-effectiveness analysis.

Aim of this study was to evaluate the economic impact of the introduction of positron emission tomography/computed tomography (PET/CT) in the early detection of recurrent ovarian cancer through a cost-effectiveness analysis of different diagnostic strategies. Thirty-two consecutive patients with suspected ovarian cancer recurrence, studied by both contrast enhanced abdominal CT and PET/CT, were retrospectively included in the study. Three different diagnostic strategies were evaluated and compared: (1) CT only or baseline strategy; (2) PET/CT for negative CT or strategy A; (3) PET/CT for All or strategy B. For each one, expected costs, avoided surgery and incremental cost-effectiveness ratio (ICER) were calculated to identify the most cost-effective strategy. The number of positive patients increased from baseline strategy (20/32) to strategy A and B (30/32 and 29/32 respectively). Positron emission tomography/computed tomography reoriented physician choice in 31% and 62% of patients (strategies A and B respectively). Strategy A is dominated by strategy B, which is more expensive (2909 euro vs. 2958 euro), but also more effective (3 cases of surgery avoided) and presents an ICER of 226.77 euro per surgery avoided (range: 49.50-433.00 euro). Positron emission tomography/computed tomography introduction in this population is cost-effective and allowed to redirect the clinical management of patients towards more appropriate therapeutic choices.

Restaging prostate cancer patients with biochemical failure with PET/CT and radiolabeled choline.

PET/CT with either [11C]choline or [18F]fluorocholine represents a powerful technique for restaging prostate cancer (PCa) patients with biochemical failure. The availability of dedicated PET/CT scanners allows fusioning of morphological and functional images, which enables accurate localization of sites of pathological tracer uptake and ease the differentiation between malignant and benign findings. A noteworthy advantage of this whole-body technique is that it provides information on multiple anatomic sites at a single time. As such, the technique has the capability of distinguishing between local relapse and distant metastases, and therefore has the potential to guide the medical treatment. The positive detection rate of [11C]choline PET/CT varies substantially in relation to the inclusion criteria. Studies which included unselected consecutive patients reported a positive detection rate ranging between 40% and 70%. Serum PSA level represents the single, most important factor affecting the rate of positive scans. Other positive predicitive factors include fast PSA kinetics (PSA velocity, PSA doubling time), advanced pathological state at initial staging, previous biochemical failure, hormone resistance and older age. Recent studies indicate that [11C]choline PET/CT has the potential to early restaging PCa patients for PSA levels lower than 1-1.5 ng/mL. However, more studies are necessary to better define the potential of this technique for low PSA levels. The previously cited risk factors can be used to identify patients that are at greater risk and that might best benefit from PET/CT scans. Patients that develop biochemical failure during androgen deprivation therapy (hormone resistance) have a higher likelihood for a positive [11C]choline PET/CT scan in comparison to patients that are drug naïve (hormone sensitive) and are not required to withdraw the anti-androgenic treatment before PET/CT.

Clinical and diagnostic assessment for therapeutic decisions in prostate cancer.

Due to the heterogeneity of prostate cancer (PCa) outcomes, there is a need for individualized treatment plans based on clinical and cancer characteristics. Recent advances in sophisticated imaging modalities have improved the ability to stratify patients according to their risk of PCa diagnosis and progression. This, in turn, has positively influenced the clinical decision making process. However, there is also an overuse of diagnostic imaging in the evaluation of PCa patients. Baseline diagnostic and re-staging evaluations need to be indeed personalized, in order to maximize the results and reduce unnecessary, lengthy and costly procedures. The aim of this review was to critically evaluate current international guidelines in order to identify clinical and diagnostic markers that might help clinicians in the selection of the most appropriate imaging approach. For this aim, different imaging modalities were analyzed in patients with newly diagnosed PCa, focusing on local, nodal and distant staging. Every step of staging was taken into consideration based on patient individualized risk, as defined by routinely available clinical variables. Second, different imaging techniques were also reviewed in the context of relapse after primary treatment, highlighting their utility and impact in the clinical decision making process. This review focuses mainly on conventional established imaging techniques, with an eye also to novel approaches that still need to be validated on large patient series.

PET-CT for treatment planning in prostate cancer.

UNLABELLED: Molecular imaging techniques, such as positron emission tomography (PET), may be of help in management treatment planning. In particular, in prostate cancer patients, PET and PET-computed tomography (PET-CT) can be successfully used in treatment planning at different steps, including: 1) tumor characterization and staging, to define the most appropriate primary treatment; 2) re-staging, to define a second line therapy on the site of possible recurrences; and 3) monitoring the disease and the efficacy of treatment. Although the most commonly used PET tracer, [(18)F]Fluorodeoxyglucose ([(18)F]FDG), presents limitations in imaging prostate cancer patients, several alternative PET tracers have been proposed to evaluate by PET these patients, with promising RESULTS: Optimal treatment for prostate cancer depends on the accuracy in tumor characterization and staging. In fact, localized primary tumor can be treated with radical prostatectomy, while metastatic tumor is usually treated with systemic therapeutic regimen. Different PET tracers, including [(11)C]Choline, [(18)F]Choline and [(11)C]Acetate, have been successfully reported. Howe-ver, further studies in large population of patients are still necessary to establish their final clinical role in the primary detection and staging of prostate cancer. The information on the site of possible recurrences is also important for therapeutic strategies. Several PET tracers have been proposed to re-stage prostate cancer patients. In particular, [11C]Choline PET has now been established as a clinical procedure to non-invasively re-stage, in a single session, prostate cancer patients presenting an increase of prostate specific antigen (PSA) after radical treatment. The role of PET and PET-CT in monitoring the disease and the effects of treatment are under investigation and still to be defined. In the present review, we focused on the use of several PET tracers in different clinical indications aimed at the treatment planning of prostate cancer patients.

Incidental detection by [11C]choline PET/CT of meningiomas in prostate cancer patients.

AIM: Anti-androgenic hormonal therapy in prostate cancer patients with concomitant meningioma may result in tumor growth and development of neurological symptoms. Positron emission tomography/computed tomography (PET/CT) with [11C]choline is used for restaging prostate cancer patients with biochemical failure. In vitro and in vivo data support altered choline metabolism in meningiomas. METHODS: During a retrospective study in prostate cancer patients with biochemical failure referred to our institution between November 2004 and January 2007, encephalic focal uptake of [11C]choline was incidentally noted in 4 patients, 2 of which had been taking luteinizing hormone-releasing hormone analogs. RESULTS: Subsequent to the incidental finding, one patient underwent surgical removal of the meningioma; strict neuroradiological follow-up was planned for the 3 other patients. CONCLUSION: We suggest that in prostate cancer patients candidate for anti-androgenic therapy the whole body [11C]choline PET/CT scan should include the whole skull to check for the possible presence of meningiomas. This could help to identify patients at risk for the development of neurological symptoms during anti-androgenic therapy and help the referring urologist in the clinical management of these patients.

Cost-effectiveness analysis in the clinical management of patients with known or suspected lung cancer: [18F]fluorodeoxyglucose PET and CT comparison.

AIM: The aim of this study was to evaluate the economic impact of the introduction of positron emission tomography (PET) in the clinical management of patients with known or suspected lung cancer through a cost-effectiveness analysis of different diagnostic strategies. METHODS: In Italy, 75 patients with known or suspected lung cancer were included in the study. Three different diagnostic strategies were compared: 1) baseline or traditional strategy, i.e. computed tomography (CT) alone; 2) strategy A, i.e. PET for indefinite CT; 3) strategy B, i.e. PET for all. For each strategy expected costs and life expectancy, as measured by life year saved (LYS), were evaluated. Incremental cost-effectiveness ratio (ICER) was calculated to identify the most effective strategy. RESULTS: Compared to the baseline strategy, the introduction of PET changed the clinical management in 40% of cases in strategy A and in 51% of cases in strategy B, with an optimization of the clinical management. Costs of strategy A (2735.42 Euro) and strategy B (2984.52 Euro) were, respectively, 8% and 18% higher than the baseline strategy (2534.81 Euro). LYS was 2.04 and 2.64 for strategy A and B, which were, respectively, 4% and 35% higher than the baseline strategy (1.96 LYS). The ICERs were 2507.63 Euro/LYS and 415.17 Euro/LYS for strategy A and B, respectively. Strategy A is dominated by strategy B, which is more expensive, but also more effective. CONCLUSION: In Italy, the introduction of PET in the clinical management of all patients with known or suspected lung cancer previously evaluated with CT is cost-effective and allows to gain 2.64 life years at an annual cost of about 415 Euro.

Two-dimensional vs three-dimensional imaging in whole body oncologic PET/CT: a Discovery-STE phantom and patient study.

AIM: To evaluate the performance of the positron emission tomography (PET)/computed tomography (CT) Discovery-STE (D-STE) scanner for lesion detectability in two-dimensional (2D) and three-dimensional (3D) acquisition. METHODS: A NEMA 2001 Image-Quality phantom with 11 lesions (7-37 mm in diameter) filled with a solution of 18F (lesion/background concentration ratio: 4.4) was studied. 2D and 3D PET scans were sequentially acquired (10 min each) in list mode (LM). Each scan was unlisted into 4, 3 and 2-min scans. Ten [18F]FDG PET oncological patient studies were also evaluated. Each patient underwent a 3D PET/CT whole body scan, followed by a 2D PET scan (4 min LM) and a 3D PET scan (4 min LM) over a single field of view. Both 2D and 3D scans were unlisted in 3 and 2-min scans. Data were evaluated quantitatively by calculating quality measurements and qualitatively by two physicians who judged lesion detectability compared to statistical variations in background activity. RESULTS: Quantitative and qualitative evaluations showed the superiority of 3D over 2D across all measures of quality. In particular, lesion detectability was better in 3D than in 2D at equal scan times and 3D acquisition provided images comparable in quality to 2D in approximately half the time. Interobserver variability was lower in evaluation of 3D scans and lesion shape and volume were better depicted. CONCLUSION: In oncological applications, the D-STE system demonstrated good performance in 2D and 3D acquisition, while 3D exhibited better image quality, data accuracy and consistency of lesion detectability, resulting in shorter scan times and higher patient throughput.