Ilaria Rambaldi

18F-FDG PET/CT focal, but not osteolytic, lesions predict the progression of smoldering myeloma to active disease

Identification of patient sub-groups with smoldering multiple myeloma (SMM) at high risk of progression to active disease (MM) is an important goal. 18F-FDG PET/CT (positron emission tomography (PET) integrated with computed tomography (PET/CT) using glucose labelled with the positron-emitting radionuclide 18F) allows for assessing early skeletal involvement. Identification of osteolytic lesions by this technique has recently been incorporated into the updated International Myeloma Working Group criteria for MM diagnosis. However, no data are available regarding the impact of focal lesions (FLs) without underlying osteolysis on time to progression (TTP) to MM. We hence prospectively studied a cohort of 120 SMM patients with PET/CT. PET/CT was positive in 16% of patients (1 FL: 8, 2 FLs: 3, >3 FLs: 6, diffuse bone marrow involvement: 2). With a median follow-up of 2.2 years, 38% of patients progressed to MM, in a median time of 4 years, including 21% with skeletal involvement. The risk of progression of those with positive PET/CT was 3.00 (95% confidence interval 1.58–5.69, P=0.001), with a median TTP of 1.1 versus 4.5 years for PET/CT-negative patients. The probability of progression within 2 years was 58% for positive versus 33% for negative patients. In conclusion, PET/CT positivity significantly increased the risk of progression of SMM to MM. PET/CT could become a new tool to define high-risk SMM.

Image interpretation criteria for FDG PET/CT in multiple myeloma: a new proposal from an Italian expert panel. IMPeTUs (Italian Myeloma criteria for PET USe)

PurposeFDG PET/CT is able to detect active disease in patients with multiple myeloma (MM) and can be helpful for staging and assessing therapy response, but no standard interpretation criteria have been proposed for the evaluation of FDG PET/CT in MM.MethodsA group of Italian nuclear medicine physicians and haematologists met to propose new visual interpretation criteria to standardize FDG PET/CT evaluation in MM patients (Italian Myeloma criteria for PET USe; IMPeTUs) and the reproducibility of these criteria was tested. This Italian multicentre protocol was set up as a subprotocol of EMN02, an international prospective multicentre trial of the European Myeloma Network. The criteria were agreed at multidisciplinary consensus meetings. They include a description of the metabolic state of the bone marrow (BM), number and site of focal PET-positive lesions, the number of osteolytic lesions, and the presence and site of extramedullary disease, paramedullary disease and fractures. A visual degree of uptake was defined for the target lesion and extramedullary lesions according to modified Deauville criteria. MM patients who had undergone FDG PET/CT at baseline (PET-0), after induction (PET-AI) and at the end of treatment (PET-EoT) were enrolled. The patients had been prospectively enrolled in EMN02 and their PET scans were a posteriori reinterpreted in a blinded independent central review process managed by WIDEN®. Five expert nuclear medicine physicians scored the scans according to the new criteria. A case was considered read when four out of the five reviewers completed the report. Concordance among reviewers on different metrics was calculated using Krippendorff’s alpha coefficient.ResultsA total of 17 consecutive patients were enrolled. On PET-0, the alpha coefficients for the BM score, the score for the hottest focal lesion, the number of focal lesions and the number of lytic lesions were 0.33 and 0.47, 0.40 and 0.32, respectively. On PET-AI, the alpha coefficients were 0.09 and 0.43, 0.22 and 0.21, respectively, and on PET-EoT, the alpha coefficients were 0.07, 0.28, 0.25 and 0.21, respectively. BM was generally difficult to score since grades 2 and 3 are difficult to discriminate. However, since neither of the two grades is related to BM myelomatous involvement, the difference was not clinically relevant. Agreement on focal lesion scores and on the number of focal lesions was good.ConclusionThe new visual criteria for interpreting FDG PET/CT imaging in MM patients, IMPeTUs, were found to be feasible in clinical practice.

PET/CT Improves the Definition of Complete Response and Allows to Detect Otherwise Unidentifiable Skeletal Progression in Multiple Myeloma

Purpose: To evaluate the role of 18F-FDG PET/CT in 282 symptomatic multiple myeloma patients treated up-front between 2002 and 2012. Experimental Design: All patients were studied by PET/CT at baseline, during posttreatment follow-up, and at the time of relapse. Their median duration of follow-up was 67 months. Results: Forty-two percent of the patients at diagnosis had >3 focal lesions, and in 50% SUVmax was >4.2; extramedullary disease was present in 5%. On multivariate analysis, ISS stage 3, SUVmax >4.2, and failure to achieve best complete response (CR) were the leading factors independently associated with shorter progression-free survival (PFS) and overall survival (OS). These 3 variables were used to construct a prognostic scoring system based on the number of risk factors. After treatment, PET/CT negativity (PET-neg) was observed in 70% of patients, whereas conventionally defined CR was achieved in 53%. Attainment of PET-neg favorably influenced PFS and OS. PET-neg was an independent predictor of prolonged PFS and OS for patients with conventionally defined CR. Sixty-three percent of patients experienced relapse or progression; in 12%, skeletal progression was exclusively detected by systematic PET/CT performed during follow-up. A multivariate analysis revealed that persistence of SUVmax >4.2 following first-line treatment was independently associated with exclusive PET/CT progression. Conclusions: PET/CT combined with ISS stage and achievement or not of CR on first-line therapy sorted patients into different prognostic groups. PET/CT led to a more careful evaluation of CR. Finally, in patients with persistent high glucose metabolism after first-line treatment, PET/CT can be recommended during follow-up, to screen for otherwise unidentifiable progression. Clin Cancer Res; 21(19); 4384–90. ©2015 AACR.

FDG PET/CT in autoimmune pancreatitis.

A 72-year-old male patient was admitted to the Emergency Room with acute jaundice in the absence of other clinical symptoms. Laboratory data demonstrated direct hyperbilirubinaemia related to an obstruction in the biliary tree. Endoscopic retrograde cholangiopancreatography was planned and a stent was placed in the common bile duct (e, yellow arrow) with progressive resolution of the jaundice. A biopsy of the ampulla of Vater was performed and was nega-

Automated Synthesis of 68Ga-DOTA-TOC with a Cationic Purification System: Evaluation of Methodological and Technical Aspects in Routine Preparations

BACKGROUND AND OBJECTIVE Gallium-68 is a PET isotope available in each nuclear medicine departments, even those not equipped with a cyclotron, since it is easily obtained by eluting compact and transportable generator system. The preparation of Ga-68 DOTA-labeled compounds is performed by remotely controlled automated systems developed in order to ensure production efficiency, reproducibility of the results, fast reaction time, to facilitate the synthesis and minimize the radiation exposure. Many automatic synthesis systems are available on the radiopharmaceutical market, however, they requires some technical adaptations for routine use. We reported the [68Ga]Ga-DOTA-TOC production by automated cassette-based theranostic synthesizer system used in combination with a disposable GMP grade cassette system for cationic purification. METHODS The synthesizer is integrated with the 68Ge/68Ga generator systems and it allows to perform elution, eluate purification and radiolabeling in about 38 minutes. We have performed in 2 year (January 2016 - January 2018) over 100 [68Ga]Ga-DOTA-TOC preparations. RESULTS The average synthesis yield of radiopharmaceutical production was 54.4 ± 2.3 % and the radiochemical purity average was found 96.94 ± 0.74 %. Only three [68Ga]Ga-DOTA-TOC preparations have failed. CONCLUSION The methodology and the adopted technical solutions allowed to obtain a high quality radiopharmaceutical product as required by the European Pharmacopoeia.

PD11-01 COMPARISON BETWEEN THE DIAGNOSTIC ACCURACIES OF 18F-FLUORODEOXYGLUCOSE (FDG) POSITRON EMISSION TOMOGRAPHY (PET)/COMPUTED TOMOGRAPHY (CT) AND MORPHOLOGICAL IMAGING IN RECURRENT UROTHELIAL CARCINOMAS: A RETROSPECTIVE, MULTI-CENTER STUDY

outcomes is currently unknown. Here, we investigated whether the proportion of the ductal component predicts oncologic outcomes in ductal adenocarcinoma. METHODS: We retrospectively reviewed clinical data from 3,038 patients with prostate cancer who underwent radical prostatectomy at our institution between 2005 and 2014. We excluded patients who received neoadjuvant or adjuvant treatment. Patients were stratified based on the proportion of the ductal component. We compared the probability of biochemical recurrence between groups and investigated how the proportion of the ductal component influences biochemical recurrence using Kaplan-Meier estimates and Cox regression models, respectively. RESULTS: Of 2,648 patients, 101 (3.8%) had ductal adenocarcinoma and 2,547 (96.2%) had acinar adenocarcinoma. Biochemical recurrence-free survival for patients with ductal adenocarcinoma was significantly lower compared with those with acinar adenocarcinoma (p<0.001). When ductal cases were stratified by the proportion of the ductal component, biochemical recurrence-free survival for the high ductal component ( 30%) group was significantly lower compared that of the low ductal component (< 30%) group (p 1⁄4 0.023). In univariate and multivariate Cox regression analyses, a high ductal component was a significant predictor of biochemical recurrence (hazard ratio 2.508, 95% confidence interval 1.133-5.552, p 1⁄4 0.023). CONCLUSIONS: The prognosis for ductal adenocarcinoma can be stratified by the proportion of the ductal component. This marker could potentially be used as a surrogate for poor prognosis or as a determinant for adjuvant therapy.