The purpose of these guidelines is to assist physicians in recommending, performing, interpreting and reporting the results of FDG PET/CT for oncological imaging of adult patients. PET is a ...quantitative imaging technique and therefore requires a common quality control (QC)/quality assurance (QA) procedure to maintain the accuracy and precision of quantitation. Repeatability and reproducibility are two essential requirements for any quantitative measurement and/or imaging biomarker. Repeatability relates to the uncertainty in obtaining the same result in the same patient when he or she is examined more than once on the same system. However, imaging biomarkers should also have adequate reproducibility, i.e. the ability to yield the same result in the same patient when that patient is examined on different systems and at different imaging sites. Adequate repeatability and reproducibility are essential for the clinical management of patients and the use of FDG PET/CT within multicentre trials. A common standardised imaging procedure will help promote the appropriate use of FDG PET/CT imaging and increase the value of publications and, therefore, their contribution to evidence-based medicine. Moreover, consistency in numerical values between platforms and institutes that acquire the data will potentially enhance the role of semiquantitative and quantitative image interpretation. Precision and accuracy are additionally important as FDG PET/CT is used to evaluate tumour response as well as for diagnosis, prognosis and staging. Therefore both the previous and these new guidelines specifically aim to achieve standardised uptake value harmonisation in multicentre settings.
LuLu-PSMA-617 radioligand therapy (
Lu-PSMA) is a novel treatment for metastatic castration-resistant prostate cancer (mCRPC), which could also be applied to patients with metastatic ...hormone-sensitive prostate cancer (mHSPC) with PSMA expression. In this prospective study (NCT03828838), we analyzed toxicity, radiation doses, and treatment effect of
Lu-PSMA in pateints with low-volume mHSPC.
Ten progressive patients with mHSPC following local treatment, with a maximum of ten metastatic lesions on
GaGa-PSMA-11 PET/diagnostic-CT imaging (PSMA-PET) and serum PSA doubling time <6 months received two cycles of
Lu-PSMA. Whole-body single-photon emission CT/CT (SPECT/CT) and blood dosimetry was performed to calculate doses to the tumors and organs at risk (OAR). Adverse events (AE), laboratory values (monitoring response and toxicity), and quality of life were monitored until week 24 after cycle 2, the end of study (EOS). All patients underwent PSMA-PET at screening, 8 weeks after cycle 1, 12 weeks after cycle 2, and at EOS.
All patients received two cycles of
Lu-PSMA without complications. No treatment-related grade III-IV adverse events were observed. According to dosimetry, none of the OAR reached threshold doses for radiation-related toxicity. Moreover, all target lesions received a higher radiation dose than the OAR. All 10 patients showed altered PSA kinetics, postponed androgen deprivation therapy, and maintained good quality of life. Half of the patients showed a PSA response of more than 50%. One patient had a complete response on PSMA-PET imaging until EOS and two others had only minimal residual disease.
Lu-PSMA appeared to be a feasible and safe treatment modality in patients with low-volume mHSPC.
The aim of this guideline is to provide a minimum standard for the acquisition and interpretation of PET and PET/CT scans with 18F-fluorodeoxyglucose (FDG). This guideline will therefore address ...general information about 18F-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET/CT) and is provided to help the physician and physicist to assist to carrying out, interpret, and document quantitative FDG PET/CT examinations, but will concentrate on the optimisation of diagnostic quality and quantitative information.
Abstract
Background
The BULLSEYE trial is a multicenter, open-label, randomized controlled trial to test the hypothesis if
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Lu-PSMA is an effective treatment in oligometastatic hormone-sensitive ...prostate cancer (oHSPC) to prolong the progression-free survival (PFS) and postpone the need for androgen deprivation therapy (ADT). The original study protocol was published in 2020. Here, we report amendments that have been made to the study protocol since the commencement of the trial.
Changes in methods and materials
Two important changes were made to the original protocol: (1) the study will now use
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Lu-PSMA-617 instead of
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Lu-PSMA-I&T and (2) responding patients with residual disease on
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F-PSMA PET after the first two cycles are eligible to receive additional two cycles of 7.4 GBq
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Lu-PSMA in weeks 12 and 18, summing up to a maximum of 4 cycles if indicated. Therefore, patients receiving
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Lu-PSMA-617 will also receive an interim
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F-PSMA PET scan in week 4 after cycle 2. The title of this study was modified to; “Lutetium-177-PSMA in Oligo-metastatic Hormone Sensitive Prostate Cancer” and is now partly supported by Advanced Accelerator Applications, a Novartis Company.
Conclusions
We present an update of the original study protocol prior to the completion of the study. Treatment arm patients that were included and received
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Lu-PSMA-I&T under the previous protocol will be replaced.
Trial registration
ClinicalTrials.gov
NCT04443062
. First posted: June 23, 2020.
In recent years, there is increasing evidence showing a beneficial outcome (e.g. progression free survival; PFS) after metastases-directed therapy (MDT) with external beam radiotherapy (EBRT) or ...targeted surgery for oligometastatic hormone sensitive prostate cancer (oHSPC). However, many patients do not qualify for these treatments due to prior interventions or tumor location. Such oligometastatic patients could benefit from radioligand therapy (RLT) with
Lu-PSMA; a novel tumor targeting therapy for end-stage metastatic castration-resistant prostate cancer (mCRPC). Especially because RLT could be more effective in low volume disease, such as the oligometastatic status, due to high uptake of radioligands in smaller lesions. To test the hypothesis that
Lu-PSMA is an effective treatment in oHSPC to prolong PFS and postpone the need for androgen deprivation therapy (ADT), we initiated a multicenter randomized clinical trial. This is globally, the first prospective study using
Lu-PSMA-I&T in a randomized multicenter setting.
This study compares
Lu-PSMA-I&T MDT to the current standard of care (SOC); deferred ADT. Fifty-eight patients with oHSPC (≤5 metastases on PSMA PET) and high PSMA uptake (SUVmax > 15, partial volume corrected) on
F-PSMA PET after prior surgery and/or EBRT and a PSA doubling time of < 6 months, will be randomized in a 1:1 ratio. The patients randomized to the interventional arm will be eligible for two cycles of 7.4GBq
Lu-PSMA-I&T at a 6-week interval. After both cycles, patients are monitored every 3 weeks (including adverse events, QoL- and xerostomia questionnaires and laboratory testing) at the outpatient clinic. Twenty-four weeks after cycle two an end of study evaluation is planned together with another
F-PSMA PET and (whole body) MRI. Patients in the SOC arm are eligible to receive
Lu-PSMA-I&T after meeting the primary study objective, which is the fraction of patients who show disease progression during the study follow up. A second primary objective is the time to disease progression. Disease progression is defined as a 100% increase in PSA from baseline or clinical progression.
This is the first prospective randomized clinical study assessing the therapeutic efficacy and toxicity of
Lu-PSMA-I&T for patients with oHSPC.
Clinicaltrials.gov identifier: NCT04443062 .
Prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) scan is the standard imaging procedure for biochemical recurrent prostate cancer postprostatectomy ...because of its high detection rate at low serum prostate-specific antigen levels. However, existing guidelines for clinical target volume (CTV) in prostate bed salvage external beam radiation therapy (sEBRT) are primarily based on experience-based clinical consensus and have been validated using conventional imaging modalities. Therefore, this study aimed to optimize CTV definition in sEBRT by using PSMA PET/CT-detected local recurrences (LRs).
Patients with suspected LR on PSMA PET/CT postprostatectomy were retrospectively enrolled in 9 Dutch centers. Anonymized scans were centrally reviewed by an expert nuclear medicine physician. Each boundary of the CTV guideline from the Groupe Francophone de Radiothérapie en Urologie (GFRU) was evaluated and adapted to improve the accuracy and coverage of the area at risk of LR (CTV) on PSMA PET/CT. The proposed CTV adaptation was discussed with the radiation oncologists of the participating centers, and final consensus was reached. To assess reproducibility, the participating centers were asked to delineate 3 new cases according to the new PERYTON-CTV, and the submitted contours were evaluated using the Dice similarity coefficient (DSC).
After central review, 93 LRs were identified on 83 PSMA PET/CTs. The proposed CTV definition improved the coverage of PSMA PET/CT-detected LRs from 67% to 96% compared with the GFRU-CTV, while reducing the GFRU-CTV by 25%. The new CTV was highly reproducible, with a mean DSC of 0.82 (range, 0.81-0.83).
This study contributes to the optimization of CTV definition in postprostatectomy sEBRT by using the pattern of LR detected on PSMA PET/CT. The PERYTON-CTV is highly reproducible across the participating centers and ensures coverage of 96% LRs while reducing the GFRU-CTV by 25%.
Introduction
Several studies have shown the usefulness of positron emission tomography (PET) quantification using standardised uptake values (SUV) for diagnosis and staging, prognosis and response ...monitoring. Many factors affect SUV, such as patient preparation procedures, scan acquisition, image reconstruction and data analysis settings, and the variability in methodology across centres prohibits exchange of SUV data. Therefore, standardisation of 2-
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F fluoro-2-deoxy-D-glucose (FDG) PET whole body procedures is required in multi-centre trials.
Methods
A protocol for standardisation of quantitative FDG whole body PET studies in the Netherlands (NL) was defined. This protocol is based on standardisation of: (1) patient preparation; (2) matching of scan statistics by prescribing dosage as function of patient weight, scan time per bed position, percentage of bed overlap and image acquisition mode (2D or 3D); (3) matching of image resolution by prescribing reconstruction settings for each type of scanner; (4) matching of data analysis procedure by defining volume of interest methods and SUV calculations and; (5) finally, a multi-centre QC procedure is defined using a 20-cm diameter phantom for verification of scanner calibration and the NEMA NU 2 2001 Image Quality phantom for verification of activity concentration recoveries (i.e., verification of image resolution and reconstruction convergence).
Discussion
This paper describes a protocol for standardization of quantitative FDG whole body multi-centre PET studies.
Conclusion
The protocol was successfully implemented in the Netherlands and has been approved by the Netherlands Society of Nuclear Medicine.
Background/objectives:
Accurate and uniform interpretation and reporting of metastatic prostate cancer (PCa) lesions on prostate-specific membrane antigen (PSMA) positron emission tomography/computed ...tomography (PET/CT) are indispensable. 18F-PSMA-1007 is increasingly used because of its favorable imaging characteristics. However, increased non-specific skeletal uptake may be an important pitfall of this radioligand. Therefore, we aimed to assess the interobserver variation in reporting skeletal 18F-PSMA-1007 uptake on PET/CT.
Design/methods:
In total, 33 18F-PSMA-1007 PET/CT scans of 21 patients with primary PCa and 12 patients with biochemical recurrence were included, and a total of 85 skeletal lesions were evaluated by three independent observers. The primary endpoint was the interobserver variability of the likelihood of malignancy of the skeletal lesions on both patient and lesion level (kappa analysis).
Results:
Observers qualified most lesions as not malignant (81–91%) and the overall mean interobserver agreement was moderate on both patient (κ: 0.54) and lesion level (κ: 0.55). In 52 lesions without corresponding CT substrate, the rating resulted in not malignant in 95–100%. Availability of additional imaging (60% of lesions) did not improve interobserver agreement (κ: 0.39 on lesion level) and resulted in unchanged rating for all observers in 78%.
Conclusion:
This interobserver analysis of skeletal 18F-PSMA-1007 uptake resulted in moderate agreement, in line with rates reported in literature. Importantly, the presence of non-specific skeletal uptake without CT substrate, as a potential shortcoming of 18F-PSMA-1007, did not impair interobserver agreement.
The gastrin-releasing peptide receptor (GRPr) is overexpressed in prostate cancer (PCa) cells, making it an excellent tool for targeted imaging. The
Ga-labeled GRPr antagonist SB3 has shown excellent ...results in preclinical and clinical studies and was selected for further clinical investigation. The aims of this phase I study were to investigate
Ga-SB3 PET/CT imaging of primary PCa tumors and assess safety. More aims included an investigation of biodistribution and dosimetry and a comparison with pathology and GRPr expression.
Ten therapy-naïve, biopsy-confirmed PCa patients planned for prostatectomy were included. A 3-h extensive PET/CT imaging protocol was performed within 2 wk before prostatectomy. Prostate tissue was evaluated for tumor localization and Gleason score, and in vitro autoradiography was performed to determine GRPr expression. Available MRI scans performed within 3 mo before the study were matched. For dosimetry, residence times were estimated and effective dose to the body as well as absorbed doses to organs were calculated using the IDAC dose model, version 2.1.
Administration of
Ga-SB3 (187.4 ± 40.0 MBq, 40 ± 5 μg) was well tolerated; no significant changes in vital signs or laboratory results were observed.
Ga-SB3 PET/CT showed lesions in 8 of 10 patients. Pathologic analysis revealed a total of 16 tumor lesions, of which PET/CT showed 14, resulting in a sensitivity of 88%.
Ga-SB3 PET/CT imaging showed uptake in 2 large prostatic intraepithelial neoplasia foci, considered a precursor to PCa, resulting in an 88% specificity. Autoradiography of tumor lesions revealed heterogeneous GRPr expression and was negative in 4 patients. Both PET/CT-negative patients had a GRPr-negative tumor. In autoradiography-positive tumors, the level of GRPr expression showed a significant correlation to tracer uptake on PET/CT. Dosimetry calculations estimated the effective dose to be 0.0144 mSv/MBq, similar to other
Ga-labeled radiopeptides. The highest absorbed dose was detected in the physiologic GRPr-expressing pancreas (0.198 mGy/MBq), followed by the bladder wall and kidneys.
Ga-SB3 PET/CT is a safe imaging method and a promising tool for early PCa imaging.
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