Rationale
The development of consensus guidelines for interpretation of Prostate-Specific Membrane Antigen (PSMA)-Positron Emission Tomography (PET) is needed to provide more consistent reports in ...clinical practice. The standardization of PSMA-PET interpretation may also contribute to increasing the data reproducibility within clinical trials. Finally, guidelines in PSMA-PET interpretation are needed to communicate the exact location of findings to referring physicians, to support clinician therapeutic management decisions.
Methods
A panel of worldwide experts in PSMA-PET was established. Panelists were selected based on their expertise and publication record in the diagnosis or treatment of PCa, in their involvement in clinical guidelines and according to their expertise in the clinical application of radiolabeled PSMA inhibitors. Panelists were actively involved in all stages of a modified, nonanonymous, Delphi consensus process.
Results
According to the findings obtained by modified Delphi consensus process, panelist recommendations were implemented in a structured report for PSMA-PET.
Conclusions
The E-PSMA standardized reporting guidelines, a document supported by the European Association of Nuclear Medicine (EANM), provide consensus statements among a panel of experts in PSMA-PET imaging, to develop a structured report for PSMA-PET in prostate cancer and to harmonize diagnostic interpretation criteria.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, SIK, UILJ, UKNU, UL, UM, UPUK, VKSCE, VSZLJ, ZAGLJ
Information has been collected from PET/MRI operational sites to identify its present and future applications. This may help to focus discussions on common interests of the PET/MRI community.
A ...web-based survey of PET/MRI users was conducted from June to October 2015. The survey was composed of 26 questions related to the PET/MRI center, present use and imaging protocols, and perspectives on key applications.
Responses were collected from 39 international sites that operated PET/MRI for a median of 30 mo (range, 2-62 mo). Most installations were located in public institutions with an academic focus (n = 26, 67%). Systems were primarily operated by nuclear medicine departments (n = 13, 33%), jointly by nuclear medicine and radiology (n = 11, 28%), and radiology only (n = 10, 26%). PET/MRI operation was equally focused on clinic routine and research (47% vs. 45% of sites, respectively). Sites reported a strong focus on oncology (76% of research and 88% of clinical applications). Other applications included neurology (9% clinical, 12% research) and cardiology (3% clinical, 6% research). Perceived superiority over PET/CT was identified as the strongest driver for clinical adoption. Over half the operators expect PET/MRI to excel in clinical routine within 3-5 y. Emerging key applications for future PET/MRI use were cardiovascular disease and imaging of inflammation.
An international survey of early PET/MR adopters reveals a mixed use of this combined imaging modality, with a focus on oncology. The future of PET/MRI is seen in expanded application for oncology and neurology, but also cardiovascular disease and inflammation.
Background Salvage radiotherapy (SRT) for prostate cancer (PCa) recurrence after prostatectomy offers long-term biochemical control in about 50–60% of patients. SRT is commonly initiated in patients ...with serum PSA levels < 1 ng/mL, a threshold at which standard-of-care imaging is insensitive for detecting recurrence. As such, SRT target volumes are usually drawn in the absence of radiographically visible disease. 68Ga-PSMA-11 (PSMA) PET/CT molecular imaging is highly sensitive and may offer anatomic localization of PCa biochemical recurrence. However, it is unclear if incorporation of PSMA PET/CT imaging into the planning of SRT could improve its likelihood of success. The purpose of this trial is to evaluate the success rate of SRT for recurrence of PCa after prostatectomy with and without planning based on PSMA PET/CT. Methods We will randomize 193 patients to proceed with standard SRT (control arm 1, n = 90) or undergo a PSMA PET/CT scan (free of charge for patients) prior to SRT planning (investigational arm 2, n = 103). The primary endpoint is the success rate of SRT measured as biochemical progression-free survival (BPFS) after initiation of SRT. Biochemical progression is defined by PSA ≥ 0.2 ng/mL and rising. The randomization ratio of 1:1.13 is based on the assumption that approximately 13% of subjects randomized to Arm 2 will not be treated with SRT because of PSMA-positive extra-pelvic metastases. These patients will not be included in the primary endpoint analysis but will still be followed. The choice of treating the prostate bed alone vs prostate bed and pelvic lymph nodes, with or without androgen deprivation therapy (ADT), is selected by the treating radiation oncologist. The radiation oncologist may change the radiation plan depending on the findings of the PSMA PET/CT scan. Any other imaging is allowed for SRT planning in both arms if done per routine care. Patients will be followed until either one of the following conditions occur: 5 years after the date of initiation of randomization, biochemical progression, diagnosis of metastatic disease, initiation of any additional salvage therapy, death. Discussion This is the first randomized phase 3 prospective trial designed to determine whether PSMA PET/CT molecular imaging can improve outcomes in patients with PCa early BCR following radical prostatectomy. Acronym PSMA-SRT Phase 3 trial. Clinical trial registration * ■ IND#130649 * ◦ Submission: 04.26.2016 * ◦ Safe-to-proceed letter issued by FDA: 05.25.2016 * ■ UCLA IRB #18–000484, * ■ First submission: 3.27.2018 * ■ Date of approval: 5.31.2018 * ■ UCLA JCCC Short Title NUC MED 18–000484 * ■ NCI Trial Identifier NCI-2018-01518 * ■ ClinicalTrials.gov Identifier NCT03582774 * ■ First Submitted: 06.19.2018 * ■ First Submitted that Met QC Criteria: 06.27.2018 * ■ First Posted: 07.11.2018 * ■ Last Update Submitted that Met QC Criteria: 07.17.2018 * ■ Last Update Posted: 07.19.2018 Trial status Current Trial Status Active as of 08/13/2018 Trial Start Date 09/01/2018-Actual Primary Completion Date 09/01/2023-Anticipated Trial Completion Date 09/01/2024-Anticipated
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The LKB1 (also called STK11) tumor suppressor is mutationally inactivated in ∼20% of non-small cell lung cancers (NSCLC). LKB1 is the major upstream kinase activating the energy-sensing kinase AMPK, ...making LKB1-deficient cells unable to appropriately sense metabolic stress. We tested the therapeutic potential of metabolic drugs in NSCLC and identified phenformin, a mitochondrial inhibitor and analog of the diabetes therapeutic metformin, as selectively inducing apoptosis in LKB1-deficient NSCLC cells. Therapeutic trials in Kras-dependent mouse models of NSCLC revealed that tumors with Kras and Lkb1 mutations, but not those with Kras and p53 mutations, showed selective response to phenformin as a single agent, resulting in prolonged survival. This study suggests phenformin as a cancer metabolism-based therapeutic to selectively target LKB1-deficient tumors.
► Phenformin is a mitochondrial inhibitor that selectively kills LKB1−/− NSCLC cells ► LKB1−/− NSCLC cells exhibit defective mitochondria and ROS following phenformin ► Phenformin improves tumors and survival in KrasG12DLkb1−/−, not KrasG12Dp53−/− mice ► eIF2α signaling markers are AMPK-independent biomarkers of biguanide treatment
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
We aimed to systematically determine the impact of tumor burden on 68Ga-prostate-specific membrane antigen-11 (68Ga-PSMA) PET biodistribution by the use of quantitative measurements. Methods: This ...international multicenter, retrospective analysis included 406 men with prostate cancer who underwent 68Ga-PSMA PET/CT. Of these, 356 had positive findings and were stratified by quintiles into a very low (quintile 1, ≤25 cm3), low (quintile 2, 25–189 cm3), moderate (quintile 3, 189–532 cm3), high (quintile 4, 532–1,355 cm3), or very high (quintile 5, ≥1,355 cm3) total PSMA-positive tumor volume (PSMA-VOL). PSMA-VOL was obtained by semiautomatic segmentation of total tumor lesions using qPSMA software. Fifty prostate cancer patients with no PSMA-positive lesions (negative scan) served as a control group. Normal organs, which included salivary glands, liver, spleen, and kidneys, were semiautomatically segmented using 68Ga-PSMA PET images, and SUVmean was obtained. Correlations between the SUVmean of normal organs and PSMA-VOL as continuous and categoric variables by quintiles were evaluated. Results: The median PSMA-VOL was 302 cm3 (interquartile range IQR, 47–1,076 cm3). The median SUVmean of salivary glands, kidneys, liver, and spleen was 10.0 (IQR, 7.7–11.8), 26.0 (IQR, 20.0–33.4), 3.7 (IQR, 3.0–4.7), and 5.3 (IQR, 4.0–7.2), respectively. PSMA-VOL showed a moderate negative correlation with the SUVmean of the salivary glands (r = −0.44, P < 0.001), kidneys (r = −0.34, P < 0.001), and liver (r = −0.30, P < 0.001) and a weak negative correlation with the spleen SUVmean (r = −0.16, P = 0.002). Patients with a very high PSMA-VOL (quintile 5, ≥1,355 cm3) had a significantly lower PSMA uptake in the salivary glands, kidneys, liver, and spleen than did the control group, with an average difference of −38.1%, −40.0%, −43.2%, and −34.9%, respectively (P < 0.001). Conclusion: Tumor sequestration affects 68Ga-PSMA biodistribution in normal organs. Patients with a very high tumor load showed a significantly lower uptake of 68Ga-PSMA in normal organs, confirming a tumor sink effect. As similar effects might occur with PSMA-targeted radioligand therapy, these patients might benefit from increased therapeutic activity without exceeding the radiation dose limit for organs at risk.
This study gathered information about clinical PET/CT operations worldwide to help guide discussions on the use and standardization of clinical PET/CT.
A Web-based survey of PET/CT users was ...initiated in November 2009 through e-mail advertising using Academy of Molecular Imaging databases. Recipients were asked 58 questions related to demographics (e.g., location, number of PET/CT systems, and staffing), PET/CT operations and use, and variations in (18)F-FDG oncology imaging protocols.
The responders were from centers in the Americas (71%), Europe (22%), Asia-Pacific (6%), and Middle East (1%), with most responding sites representing public health care institutions (60%). PET/CT systems were most frequently installed in nuclear medicine departments (59%). Of the sites operating a PET/CT system, 16% had 10 y or more of stand-alone PET experience. About 40% of all sites operated at least 2 PET/CT systems. PET/CT was most frequently used for applications in torso or whole-body oncology (87%), radiation therapy planning (4%), cardiology (4%), and neurology (5%). The average interval of fasting before an (18)F-FDG PET/CT examination was 7 ± 3 h (range, 4-12 h). Blood glucose levels were measured at 99% of sites, but acceptable maximal glucose levels varied substantially (an upper limit of 200 mg/dL was applied at >50% of the institutions). A weight-based radioactivity dose injection was performed at 44% of sites. The mean (18)F-FDG activity injected was 390 MBq (range, 110-585 MBq) for 3-dimensional PET of a 75-kg patient. The mean uptake time was 64 ± 14 min (range, 20-90 min). Split protocols involving patient repositioning and adapted imaging parameters were used at 51% of sites. Only 41% used patient positioning aids. Intravenous or oral CT contrast material was used at 52% of sites in up to 25% of patients. Most sites (90%) measured maximum standardized uptake value as an index of tissue glucose use. Only 62% of sites provided a fully integrated PET/CT report.
An international survey among clinical PET/CT users revealed significant variations in standard (18)F-FDG PET/CT protocols. This finding illustrates the need for continuous training and ongoing standardization in an effort to optimize PET/CT in oncology.
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