Fabrizio Bergesio

Development of standardized image interpretation for 68Ga-PSMA PET/CT to detect prostate cancer recurrent lesions

MethodsAfter primary treatment, biochemical relapse (BCR) occurs in a substantial number of patients with prostate cancer (PCa). PET/CT imaging with prostate-specific membrane antigen based tracers (68Ga-PSMA) has shown promising results for BCR patients. However, a standardized image interpretation methodology has yet to be properly agreed. The aim of this study, which was promoted and funded by European Association of Nuclear Medicine (EANM), is to define standardized image interpretation criteria for 68Ga-PSMA PET/CT to detect recurrent PCa lesions in patients treated with primary curative intent therapy (radical prostatectomy or radiotherapy) who presented a biochemical recurrence. In the first phase inter-rater agreement between seven readers from seven international centers was calculated on the reading of 68Ga-PSMA PET/CT images of 49 patients with BCR. Each reader evaluated findings in five different sites of recurrence (local, loco-regional lymph nodes, distant lymph nodes, bone, and other). In the second phase the re-analysis was limited to cases with poor, slight, fair, or moderate agreement [Krippendorff’s (K) alpha<0.61]. Finally, on the basis of the consensus readings, we sought to define a list of revised consensus criteria for 68Ga-PSMA PET/CT interpretation.ResultsBetween-reader agreement for the presence of anomalous findings in any of the five sites was only moderate (K’s alpha: 0.47). The agreement improved and became substantial when readers had to judge whether the anomalous findings were suggestive for a pathologic, uncertain, or non-pathologic image (K’s alpha: 0.64). K’s alpha calculations for each of the five sites of recurrence were also performed and evaluated. First Delphi round was thus conducted. A more detailed definition of the criteria was proposed by the project coordinator, which was then discussed and finally agreed by the seven readers. After the second Delphi round only four cases of disagreement still remained. These were evaluated for a final round, allowing a final agreement table to be written.ConclusionWe hope that by developing these consensus guidelines on the interpretation of 68Ga-PSMA PET/CT, clinicians reporting these studies will be able to provide more consistent clinical reports and that within clinical trials, abnormality classifications will be harmonized, allowing more robust assessment of its diagnostic performance.

Early Chemotherapy Intensification With Escalated BEACOPP in Patients With Advanced-Stage Hodgkin Lymphoma With a Positive Interim Positron Emission Tomography/Computed Tomography Scan After Two ABVD Cycles: Long-Term Results of the GITIL/FIL HD 0607 Trial

Purpose To investigate the progression-free survival (PFS) of patients with advanced Hodgkin lymphoma (HL) after a risk-adapted treatment strategy that was based on a positive positron emission tomography scan performed after two doxorubicin, vinblastine, vincristine, and dacarbazine (ABVD) cycles (PET2). Patients and Methods Patients with advanced-stage (IIB to IVB) HL were consecutively enrolled. After two ABVD cycles, PET2 was performed and centrally reviewed according to the Deauville five-point scale. Patients with a positive PET2 were randomly assigned to four cycles of escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) followed by four cycles of standard BEACOPP with or without rituximab. Patients with a negative PET2 continued ABVD, and those with a large nodal mass at diagnosis (≥ 5 cm) in complete remission with a negative PET at the end of chemotherapy were randomly assigned to radiotherapy or no further treatment. The primary end point was 3-year PFS. Results Of 782 enrolled patients, 150 (19%) had a positive and 630 (81%) a negative PET2. The 3-year PFS of all patients was 82%. The 3-year PFS of those with a positive and negative PET2 was 60% and 87%, respectively ( P < .001). The 3-year PFS of patients with a positive PET2 assigned to BEACOPP with or without rituximab was 63% versus 57% ( P = .53). In 296 patients with both interim and post-ABVD-negative PET who had a large nodal mass at diagnosis, radiotherapy was randomly added after chemotherapy without a significant PFS improvement (97% v 93%, respectively; P = .29). The 3-year overall survival of all 782 patients was 97% (99% and 89% for PET2 negative and positive, respectively). Conclusion The PET-driven switch from ABVD to escalated BEACOPP is feasible and effective in high-risk patients with advanced-stage HL.

The 68Ge phantom-based FDG-PET site qualification program for clinical trials adopted by FIL (Italian Foundation on Lymphoma)

PURPOSE The quantitative assessment of Positron Emission Tomography (PET) scans using standardized uptake value and derived parameters proved to be superior to traditional qualitative assessment in several retrospective or mono-centric prospective reports. Since different scanners give different quantitative readings, a program for clinical trial qualification (CTQ) is mandatory to guarantee a reliable and reproducible use of quantitative PET in prospective multi-centre clinical trials and in every-day clinical life. METHODS We set up, under the auspices of Italian Foundation on Lymphoma (FIL), a CTQ program consisting of the PET/CT scan acquisition and analysis of (18)F and (68)Ge NEMA/IEC image quality phantoms for the reduction of inter-scanner variability. Variability was estimated on background activity concentration (BAC) and sphere to background ratio (SBR). RESULTS The use of a (68)Ge phantom allowed reducing the inter-scanner variability among different scanners from 74.0% to 20.5% in BAC and from 63.3% to 17.4% in SBR compared to using the (18)F phantom. The CTQ criteria were fulfilled at first round in 100% and 28% of PET scanners with (68)Ge and (18)F respectively. CONCLUSIONS The (68)Ge phantom proved a reliable tool for PET scanner qualification, able to significantly reduce the potential sources of error while increasing the reproducibility of PET derived quantitative parameter measurement.

The Strategies to Homogenize PET/CT Metrics: The Case of Onco-Haematological Clinical Trials

Positron emission tomography (PET) has been a widely used tool in oncology for staging lymphomas for a long time. Recently, several large clinical trials demonstrated its utility in therapy management during treatment, paving the way to personalized medicine. In doing so, the traditional way of reporting PET based on the extent of disease has been complemented by a discrete scale that takes in account tumour metabolism. However, due to several technical, physical and biological limitations in the use of PET uptake as a biomarker, stringent rules have been used in clinical trials to reduce the errors in its evaluation. Within this manuscript we will describe shortly the evolution in PET reporting, examine the main errors in uptake measurement, and analyse which strategy the clinical trials applied to reduce them.

Automatic liver detection and standardised uptake value evaluation in whole-body Positron Emission Tomography/Computed Tomography scans

BACKGROUND AND OBJECTIVE Standardised Uptake Value (SUV), in clinical research and practice, is a marker of tumour avidity in Positron Emission Tomography/Computed Tomography (PET/CT). Since many technical, physical and physiological factors affect the SUV absolute measurement, the liver uptake is often used as reference value both in quantitative and semi-quantitative evaluation. The purpose of this investigation was to automatically detect the liver position in whole-body PET/CT scans and extract its average SUV value. METHODS We developed an algorithm, called LIver DEtection Algorithm (LIDEA), that analyses PET/CT scans, and under the assumption that the liver is a large homogeneous volume near the centre of mass of the patient, finds its position and automatically places a region of interest (ROI) in the liver, which is used to calculate the average SUV. The algorithm was validated on a population of 630 PET/CT scans coming from more than 60 different scanners. The SUV was also calculated by manually placing a large ROI in the liver. RESULTS LIDEA identified the liver with a 97.3% sensitivity with PET/CT images only and reached a 98.9% correct detection rate when using the co-registered CT scan to avoid liver misidentification in the right lung. The average liver SUV obtained with LIDEA was successfully validated against its manual assessment, with no systematic difference (0.11 ± 0.36 SUV units) and a R2=0.89 correlation coefficient. CONCLUSIONS LIDEA proved to be a reliable tool to automatically identify and extract the average SUV of the liver in oncological whole-body PET/CT scans.

[OA143] Application of new algorithms in PET image reconstruction: Preliminary results

Purpose Important advancements have been made in PET image reconstruction algorithms, among the newest modelling of the point spread function (PSF) and noise statistics modelling (NSM) can be accounted for. Quantitative results of the application of these reconstruction techniques on 3 state-of-the-art PET/CT scanners with and without time-of-flight (TOF) technique are presented. Methods and materials A 68Ge-NEMA phantom based on a standard IQ body phantom (Data Spectrum, Durham, NC) filled with 68Ge in an epoxy resin was used. The activity concentrations in the spheres (internal diameter-ID = 6, 10, 13, 17, 22, 28, 37 mm) and in the background were measured with a radionuclide calibrator tested against a NIST traceable source and were respectively 40.67kBq/ml and 10.58 kBq/ml at reference time (uncertainty ± 3%). Nominal sphere-to-background ratio was 3.84. Total activity in the phantom was 108.4 MBq at calibration. Acquisition time was adjusted according to the age of the phantom to meet 1.5 min per frame at the reference date on each PET scanner and reconstructed with variable reconstruction parameters (iterations: 48, 72; amplitude of Gaussian filter: 5, 6.4, 8 mm) with traditional (OSEM) and by combining advanced modalities, when present: PSF, TOF, TOF+PSF, NSM. For each PET scanner and each reconstruction modality maximum Recovery Coefficient (RCmax) values were evaluated for each visible sphere. RCmax were normalised to 37 mm ID sphere result. Results For each reconstructed modality, RCmax (mean ± sd) were averaged on different reconstruction parameters and PET scanners and for increasing sphere ID respectively 6, 10, 13, 17, 22, 28, 37 mm resulted: - OSEM: (0.31  ±  0.03), (0.51  ±  0.05), (0.63  ±  0.03), (0.82  ±  0.03), (0.89  ±  0.03), (0.95  ±  0.04), (1  ±  0) - OSEM+TOF: (0.32  ±  0.01), (0.56  ±  0.08), (0.64  ±  0.07), (0.84  ±  0.03), (0.91  ±  0.00), (0.97  ±  0.04), (1  ±  0) - OSEM+PSF: (0.30  ±  0.01), (0.50  ±  0.04), (0.65  ±  0.05), (0.88  ±  0.04),(0.93  ±  0.02), (0.95  ±  0.04), (1  ±  0) - OSEM+PSF+TOF: (0.30  ±  0.01), (0.56  ±  0.08), (0.70  ±  0.11), (0.91  ±  0.03), (0.94  ±  0.00), (0.97  ±  0.04), (1  ±  0) - NSM: (0.30  ±  0.02), (0.67  ±  0.19), (0.84  ±  0.14), (0.94  ±  0.05), (0.98  ±  0.03), (0.98  ±  0.06), (1  ±  0) Conclusion The RC obtained with the 3 state-of-the-art non digital PET/CT scanners demonstrate clearly that, independently of the reconstruction method used, modern PET/CT scanner outperforms respect to older one described by EARL curve. Higher differences are recorded for smaller spheres. Moreover, applying more advanced reconstruction techniques progressively enhances RC, NSM reconstruction being the most promising algorithm. Even if RCmax of different scanners converge at larger ( > 22 mm) and smaller (10 mm) spheres, the overestimations observed in the size between 1 and 2 cm are currently under investigation.

Monitoring response in lymphomas: qualitative, quantitative, or what else?

Abstract The Deauville criteria (DC) shall always be used to report interim and final PET and to assign metabolic response categories in FDG-avid lymphoma. A recent review article supports the role of quantitative extension of the DC to improve response assessment in lymphoma. We analyze different quantitative approach, to help physician to better distinguish what has to be done in every day clinical practice respect to what represent interesting insights and ongoing research. Respect to DC, all the proposed quantitative approaches obtained in retrospective studies, requires mature follow-up and a validation in independent cohorts of lymphoma patients. Moreover, the sensitivity of the system, not the adequate specificity of the tracer and the biology of the disease together with the DC, influence the accuracy of PET/CT. In conclusions, in current clinical practice, the DC, validated in a large cohort of lymphoma patients, represent the standard criteria for PET interpretation.