Immunohistochemical ERG positivity is associated with decreased PSMA expression and lower visibility in corresponding [68Ga]Ga-PSMA-11 PET scans of primary prostate cancer.

PURPOSE: TMPRSS2:ERG gene fusion negatively regulates PSMA expression in prostate adenocarcinoma (PCa) cell lines. Therefore, immunohistochemical (IHC) ERG expression, a surrogate for an underlying ERG rearrangement, and PSMA expression patterns in radical prostatectomy (RPE) specimens of primary PCa, including corresponding PSMA-PET scans were investigated. METHODS: Two cohorts of RPE samples (total n=148): In cohort #1 (n=62 patients) with available RPE and preoperative [68Ga]Ga-PSMA-11 PET, WHO/ISUP grade groups, IHC-ERG (positive vs. negative) and IHC-PSMA expression (% PSMA-negative tumour area, PSMA%neg) were correlated with the corresponding SUVmax. In the second cohort #2 (n=86 patients) including RPE only, same histopathological parameters were evaluated. RESULTS: Cohort #1: PCa with IHC-ERG expression (35.5%) showed significantly lower IHC-PSMA expression and lower SUVmax values on the corresponding PET scans. Eight of 9 PCa with negative PSMA-PET scans had IHC-ERG positivity, and confirmed TMPRSS2::ERG rearrangement. In IHC-PSMA positive PCa, IHC-ERG positivity was significantly associated with lower SUVmax values. In cohort #2, findings of higher IHC-PSMA%neg and IHC-ERG expression was confirmed with only 0-10% PSMA%neg tumour areas in IHC-ERG-negative PCa. CONCLUSION: IHC-ERG expression is significantly associated with more heterogeneous and lower IHC-PSMA tissue expression in two independent RPE cohorts. There is a strong association of ERG positivity in RPE tissue with lower [68Ga]Ga-PSMA-11 uptake on corresponding PET scans. Results may serve as a base for future biomarker development to enable tumour-tailored, individualized imaging approaches.

18F-fluorodeoxyglucose uptake patterns in positron emission tomography/computed tomography caused by inflammation and/or infection after graft surgery for thoracic aortic dissection.

BACKGROUND: To identify 18F-fluorodeoxyglucose (FDG) uptake patterns in positron emission tomography/computed tomography (PET/CT) caused by infection, inflammation, surgical material, and/or graft coating. METHODS AND RESULTS: Of 610 consecutive patients with thoracic aortic graft surgery, 60 patients with 187 PET/CT were retrospectively included. We quantified FDG uptake in all grafts using maximum standardized uptake value (SUVmax) alone and in relation to liver background (SUVratio) and determined the uptake pattern. Mixed linear regression models with random slope and intercept were applied for the analysis of SUVratio over time and generalized estimating equations to analyze the associations with anastomosis uptake. FDG uptake was frequently focal (90%), higher in infected than in noninfected grafts (mean SUVratio 2.19; 95% CI 2.05-2.32 vs. 1.63; 1.46-1.79, P < 0.001), and decreasing slowly over time (SUVratio per year since surgery -0.048; 95% CI -0.15- 0.051, P = 0.34), without a difference in slope between infected and noninfected grafts (P = 0.52). There was no evidence of an interaction between SUVratio and use of BioGlue® surgical adhesive (intercept P = 0.73, slope P = 0.71), or graft coating (gelatin and collagen, all P > 0.7). FDG uptake at the anastomosis was more frequent in noninfected grafts than in infected grafts (66% vs. 21%, odds ratio (OR) 11.34; 95% CI 3.61-35.66, P < 0.001). This effect was attenuated by the use of BioGlue® (OR 5.05; 95% CI 0.45-56.9, P = 0.19). CONCLUSIONS: FDG uptake in PET/CT after thoracic aortic graft surgery is higher in infected grafts than in noninfected grafts. In noninfected grafts, focal uptake is also frequent, mostly anastomosis-associated, not associated with graft coating, and possibly affected by the use of BioGlue®.

Development and external validation of a multivariable [68Ga]Ga-PSMA-11 PET-based prediction model for lymph node involvement in men with intermediate or high-risk prostate cancer.

PURPOSE: To develop and evaluate a lymph node invasion (LNI) prediction model for men staged with [68Ga]Ga-PSMA-11 PET. METHODS: A consecutive sample of intermediate to high-risk prostate cancer (PCa) patients undergoing [68Ga]Ga-PSMA-11 PET, extended pelvic lymph node dissection (ePLND), and radical prostatectomy (RP) at two tertiary referral centers were retrospectively identified. The training cohort comprised 173 patients (treated between 2013 and 2017), the validation cohort 90 patients (treated between 2016 and 2019). Three models for LNI prediction were developed and evaluated using cross-validation. Optimal risk-threshold was determined during model development. The best performing model was evaluated and compared to available conventional and multiparametric magnetic resonance imaging (mpMRI)-based prediction models using area under the receiver operating characteristic curves (AUC), calibration plots, and decision curve analysis (DCA). RESULTS: A combined model including prostate-specific antigen, biopsy Gleason grade group, [68Ga]Ga Ga-PSMA-11 positive volume of the primary tumor, and the assessment of the [68Ga]Ga-PSMA-11 report N-status yielded an AUC of 0.923 (95% CI 0.863-0.984) in the external validation. Using a cutoff of ≥ 17%, 44 (50%) ePLNDs would be spared and LNI missed in one patient (4.8%). Compared to conventional and MRI-based models, the proposed model showed similar calibration, higher AUC (0.923 (95% CI 0.863-0.984) vs. 0.700 (95% CI 0.548-0.852)-0.824 (95% CI 0.710-0.938)) and higher net benefit at DCA. CONCLUSIONS: Our results indicate that information from [68Ga]Ga-PSMA-11 may improve LNI prediction in intermediate to high-risk PCa patients undergoing primary staging especially when combined with clinical parameters. For better LNI prediction, future research should investigate the combination of information from both PSMA PET and mpMRI for LNI prediction in PCa patients before RP.

Atypical patterns of spinal segment degeneration in patients with abdominal aortic aneurysms.

PURPOSE: Abdominal aortic aneurysms (AAAs) affect the vascular perfusion of the lumbar spine. The treatment of AAAs with endovascular aortic aneurysm repair (EVAR) completely occludes the direct vascular supply to the lumbar spine. We hypothesized that patients with AAA who undergo EVAR show a different pattern of spinal degeneration than individuals without AAA. METHODS: In this retrospective institutional review board-approved study, 100 randomly selected patients with AAA who underwent EVAR with computed tomography (CT) scans between 2005 and 2017 were compared with age- and gender-matched controls without AAA. In addition, long-term follow-up CT images (> 6 months before EVAR, at the time of EVAR, and > 12 months after EVAR) of the patients were analysed to compare the progression of degeneration from before to after EVAR. Degeneration scores, lumbar levels with the most severe degeneration, and lumbar levels with progressive degeneration were analysed in all CT images. Fisher's exact test, Wilcoxon signed-rank test, and Mann-Whitney U test were performed for statistical analyses. RESULTS: Compared with the control group (n = 94), the most severe degeneration was more commonly detected in the mid-lumbar area in the patient group (n = 100, p = 0.016), with significantly more endplate erosions being detected in the lumbar spine (p = 0.015). However, EVAR did not result in significant additional acceleration of the degenerative process in the long-term follow-up analysis (n = 51). CONCLUSION: AAA is associated with atypical, more cranially located spinal degradation, particularly in the mid-lumbar segments; however, EVAR does not seem to additionally accelerate the degenerative process. This observation underlines the importance of disc and endplate vascularization in the pathomechanism of spinal degeneration. LEVEL OF EVIDENCE I: Diagnostic: individual cross-sectional studies with consistently applied reference standard and blinding.

[18F]FDG uptake of axillary lymph nodes after COVID-19 vaccination in oncological PET/CT: frequency, intensity, and potential clinical impact.

OBJECTIVES: To assess the frequency, intensity, and clinical impact of [18F]FDG-avidity of axillary lymph nodes after vaccination with COVID-19 vaccines BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) in patients referred for oncological FDG PET/CT. METHODS: One hundred forty patients referred for FDG PET/CT during February and March 2021 after first or second vaccination with Pfizer-BioNTech or Moderna were retrospectively included. FDG-avidity of ipsilateral axillary lymph nodes was measured and compared. Assuming no knowledge of prior vaccination, metastatic risk was analyzed by two readers and the clinical impact was evaluated. RESULTS: FDG PET/CT showed FDG-avid lymph nodes ipsilateral to the vaccine injection in 75/140 (54%) patients with a mean SUVmax of 5.1 (range 2.0 - 17.3). FDG-avid lymph nodes were more frequent in patients vaccinated with Moderna than Pfizer-BioNTech (36/50 [72%] vs. 39/90 [43%] cases, p < 0.001). Metastatic risk of unilateral FDG-avid axillary lymph nodes was rated unlikely in 52/140 (37%), potential in 15/140 (11%), and likely in 8/140 (6%) cases. Clinical management was affected in 17/140 (12%) cases. CONCLUSIONS: FDG-avid axillary lymph nodes are common after COVID-19 vaccination. The avidity of lymph nodes is more frequent in Moderna compared to that in Pfizer-BioNTech vaccines. To avoid relatively frequent clinical dilemmas, we recommend carefully taking the history for prior vaccination in patients undergoing FDG PET/CT and administering the vaccine contralateral to primary cancer. KEY POINTS: • PET/CT showed FDG-avid axillary lymph nodes ipsilateral to the vaccine injection site in 54% of 140 oncological patients after COVID-19 vaccination. • FDG-avid lymphadenopathy was observed significantly more frequently in Moderna compared to patients receiving Pfizer-BioNTech-vaccines. • Patients should be screened for prior COVID-19 vaccination before undergoing PET/CT to enable individually tailored recommendations for clinical management.

What's behind 68Ga-PSMA-11 uptake in primary prostate cancer PET? Investigation of histopathological parameters and immunohistochemical PSMA expression patterns.

PURPOSE: Prostate-specific membrane antigen (PSMA-) PET has become a promising tool in staging and restaging of prostate carcinoma (PCa). However, specific primary tumour features might impact accuracy of PSMA-PET for PCa detection. We investigated histopathological parameters and immunohistochemical PSMA expression patterns on radical prostatectomy (RPE) specimens and correlated them to the corresponding 68Ga-PSMA-11-PET examinations. METHODS: RPE specimens of 62 patients with preoperative 68Ga-PSMA-11-PET between 2016 and 2018 were analysed. WHO/ISUP grade groups, growth pattern (expansive vs. infiltrative), tumour area and diameter as well as immunohistochemical PSMA heterogeneity, intensity and negative tumour area (PSMA%neg) were correlated with spatially corresponding SUVmax on 68Ga-PSMA-11-PET in a multidisciplinary analysis. RESULTS: All tumours showed medium to strong membranous (2-3 +) and weak to strong cytoplasmic (1-3 +) PSMA expression. Heterogeneously expressed PSMA was found in 38 cases (61%). Twenty-five cases (40%) showed at least 5% and up to 80% PSMA%neg. PSMA%neg, infiltrative growth pattern, smaller tumour area and diameter and WHO/ISUP grade group 2 significantly correlated with lower SUVmax values. A ROC curve analysis revealed 20% PSMA%neg as an optimal cutoff with the highest sensitivity and specificity (89% and 86%, AUC 0.923) for a negative PSMA-PET scan. A multiple logistic regression model revealed tumoural PSMA%neg (p < 0.01, OR = 9.629) and growth pattern (p = 0.0497, OR = 306.537) as significant predictors for a negative PSMA-PET scan. CONCLUSIONS: We describe PSMA%neg, infiltrative growth pattern, smaller tumour size and WHO/ISUP grade group 2 as parameters associated with a lower 68Ga-PSMA-11 uptake in prostate cancer. These findings can serve as fundament for future biopsy-based biomarker development to enable an individualized, tumour-adapted imaging approach.

68Ga-PSMA-11 PET has the potential to improve patient selection for extended pelvic lymph node dissection in intermediate to high-risk prostate cancer.

INTRODUCTION: Radical prostatectomy with extended pelvic lymph node dissection (ePLND) is a curative treatment option for patients with clinically significant localised prostate cancer. The decision to perform an ePLND can be challenging because the overall incidence of lymph node metastasis is relatively low and ePLND is not free of complications. Using current clinical nomograms to identify patients with nodal involvement, approximately 75-85% of ePLNDs performed are negative. The aim of this study was to assess the added value of 68Ga-PSMA-11 PET in predicting lymph node metastasis in men with intermediate- or high-risk prostate cancer. METHODS: 68Ga-PSMA-11 PET scans of 60 patients undergoing radical prostatectomy with ePLND were reviewed for qualitative (visual) assessment of suspicious nodes and assessment of quantitative parameters of the primary tumour in the prostate (SUVmax, total activity (PSMAtotal) and PSMA positive volume (PSMAvol)). Ability of quantitative PET parameters to predict nodal metastasis was assessed with receiver operating characteristics (ROC) analysis. A multivariable logistic regression model combining PSA, Gleason score, visual nodal status on PET and primary tumour PSMAtotal was built. Net benefit at each risk threshold was compared with five nomograms: MSKCC nomogram, Yale formula, Roach formula, Winter nomogram and Partin tables (2016). RESULTS: Overall, pathology of ePLND specimens revealed 31 pelvic metastatic lymph nodes in 12 patients. 68Ga-PSMA-11 PET visual analysis correctly detected suspicious nodes in 7 patients, yielding a sensitivity of 58% and a specificity of 98%. The area under the ROC curve for primary tumour SUVmax was 0.70, for PSMAtotal 0.76 and for PSMAvol 0.75. The optimal cut-off for nodal involvement was PSMAtotal > 49.1. The PET model including PSA, Gleason score and quantitative PET parameters had a persistently higher net benefit compared with all clinical nomograms. CONCLUSION: Our model combining PSA, Gleason score and visual lymph node analysis on 68Ga-PSMA-11 PET with PSMAtotal of the primary tumour showed a tendency to improve patient selection for ePLND over the currently used clinical nomograms. Although this result has to be validated, 68Ga-PSMA-11 PET showed the potential to reduce unnecessary surgical procedures in patients with intermediate- or high-risk prostate cancer.

Impact of 68Ga-PSMA-11 PET staging on clinical decision-making in patients with intermediate or high-risk prostate cancer.

BACKGROUND: Accurate staging is of major importance to determine the optimal treatment modality for patients with prostate cancer. Positron emission tomography (PET) with prostate-specific membrane antigen (PSMA) is a promising technique that outperformed conventional imaging in the detection of nodal and distant metastases in previous studies. However, it is still unclear whether the superior sensitivity and specificity also translate into improved patient management. The aim of this study was to assess the performance of 68Ga-PSMA-11 PET for staging of intermediate and high-risk prostate cancer and its potential impact on disease management. METHODS: In this retrospective analysis, 116 patients who underwent 68Ga-PSMA-11 PET/CT or MRI scans for staging of their intermediate or high-risk prostate cancer between April 2016 and May 2018 were included. The potential impact of 68Ga-PSMA-11 PET staging on patient management was assessed within a simulated multidisciplinary tumour board where hypothetical treatment decisions based on clinical information and conventional imaging alone was determined. This treatment decision was compared with the treatment recommendation based on clinical information and 68Ga-PSMA-11 PET imaging. RESULTS: The primary tumour was positive on 68Ga-PSMA-11 PET in 113 patients (97%). Nodal metastases were detected in 28 patients (24%) and bone metastases in 14 patients (12%). Compared with clinical staging and conventional imaging, 68Ga-PSMA-11 PET resulted in new information in 42 of 116 patients (36%). In 32 of 116 patients (27%), this information would most likely have changed the management into a different therapy modality (15 patients, 13%) or adjusted treatment details (e.g. modification of radiotherapy field or lymph node dissection template; 17 patients, 14%). CONCLUSION: Information from 68Ga-PSMA-11 PET staging has the potential to change the management in more than a fourth of the patients who underwent PET staging for their intermediate to high-risk prostate cancer. Whether these more personalized 68Ga-PSMA-11 PET-based treatment decisions will improve patient outcome needs further investigation.

Manual prostate cancer segmentation in MRI: interreader agreement and volumetric correlation with transperineal template core needle biopsy.

OBJECTIVES: To assess interreader agreement of manual prostate cancer lesion segmentation on multiparametric MR images (mpMRI). The secondary aim was to compare tumor volume estimates between MRI segmentation and transperineal template saturation core needle biopsy (TTSB). METHODS: We retrospectively reviewed patients who had undergone mpMRI of the prostate at our institution and who had received TTSB within 190 days of the examination. Seventy-eight cancer lesions with Gleason score of at least 3 + 4 = 7 were manually segmented in T2-weighted images by 3 radiologists and 1 medical student. Twenty lesions were also segmented in apparent diffusion coefficient (ADC) and dynamic contrast enhanced (DCE) series. First, 20 volumetric similarity scores were computed to quantify interreader agreement. Second, manually segmented cancer lesion volumes were compared with TTSB-derived estimates by Bland-Altman analysis and Wilcoxon testing. RESULTS: Interreader agreement across all readers was only moderate with mean T2 Dice score of 0.57 (95%CI 0.39-0.70), volumetric similarity coefficient of 0.74 (0.48-0.89), and Hausdorff distance of 5.23 mm (3.17-9.32 mm). Discrepancy of volume estimate between MRI and TTSB was increasing with tumor size. Discrepancy was significantly different between tumors with a Gleason score 3 + 4 vs. higher grade tumors (0.66 ml vs. 0.78 ml; p = 0.007). There were no significant differences between T2, ADC, and DCE segmentations. CONCLUSIONS: We found at best moderate interreader agreement of manual prostate cancer segmentation in mpMRI. Additionally, our study suggests a systematic discrepancy between the tumor volume estimate by MRI segmentation and TTSB core length, especially for large and high-grade tumors. KEY POINTS: • Manual prostate cancer segmentation in mpMRI shows moderate interreader agreement. • There are no significant differences between T2, ADC, and DCE segmentation agreements. • There is a systematic difference between volume estimates derived from biopsy and MRI.

68Ga-PSMA-11 dose reduction for dedicated pelvic imaging with simultaneous PET/MR using TOF BSREM reconstructions.

OBJECTIVES: When increasing the PET acquisition time to match the longer MRI protocol in simultaneous PET/MR, the injected PET tracer dose can possibly be lowered to reduce radiation exposure. Moreover, applying new commercially available time-of-flight (TOF) block sequential regularized expectation maximization (BSREM)-based reconstruction algorithms could allow for further dose reductions. The purpose of this study was to find the minimal dose of the tracer targeting the prostate specific membrane antigen (68Ga-PSMA-11) for a dedicated 15-min pelvic PET/MR scan that still matches the image quality of a reference 3-min scan at 100% (150 MBq) dose. METHODS: In this retrospective analysis, 25 patients were included. PET emission datasets were edited to simulate stepwise reductions of injected tracer dose. Reference TOF ordered subset expectation maximum (OSEM) and new TOF BSREM reconstructions were performed and differences in the resulting PET images were visually and quantitatively assessed. RESULTS: Visually, TOF BSREM reconstructions with relatively high regularization parameter (ß) values are preferred. Quantitatively, however, high ß-values result in lower lesion maximum standardized uptake values (SUVmax) compared to the reference. A ß-value of 550 was considered the optimal compromise for the lowest possible 10% dose reconstructions, resulting in comparable visual assessment and lesion SUVmax. CONCLUSIONS: This study indicates that the injected 68Ga-PSMA-11 tracer dose for a standard 3-min PET scan can be reduced to approximately 10% (15 MBq) when the PET acquisition time is matched to the 15-min pelvic MRI protocol, and when reconstructed with TOF BSREM using ß = 550. This decreases the effective dose from 3.54 to 0.35 mSv. KEY POINTS: • Low-dose dedicated pelvic68Ga-PSMA-11 PET/MR reduces radiation exposure for patients. • Retrospective study investigating the minimal dose needed for adequate image quality for 15-min PET frames over the pelvis showed using quantitative and qualitative analysis that a substantial dose reduction is possible without significant loss of image quality when using the TOF BSREM reconstruction algorithm. • With the introduction of low-dose pelvic68Ga-PSMA-11 PET/MR, new potential applications of68Ga-PSMA-11 PET for local staging or investigation of equivocal MRI findings could become applicable, even for patients without confirmed prostate cancer.

Diagnostic Accuracy of Multiparametric MRI versus 68Ga-PSMA-11 PET/MRI for Extracapsular Extension and Seminal Vesicle Invasion in Patients with Prostate Cancer.

Background Recent studies have reported the additive value of combined gallium 68 (68Ga)-labeled Glu-urea-Lys (Ahx)-HBED-CC ligand targeting the prostate-specific membrane antigen (PSMA) (hereafter called 68Ga-PSMA-11) PET/MRI for the detection and localization of primary prostate cancer compared with multiparametric MRI. Purpose To compare the diagnostic accuracy and interrater agreement of multiparametric MRI and 68Ga-PSMA-11 PET/MRI for the detection of extracapsular extension (ECE) and seminal vesicle infiltration (SVI) in patients with prostate cancer. Materials and Methods Retrospective analysis of 40 consecutive men who underwent multiparametric MRI and 68Ga-PSMA-11 PET/MRI within 6 months for suspected prostate cancer followed by radical prostatectomy between April 2016 and July 2018. Four readers blinded to clinical and histopathologic findings rated the probability of ECE and SVI at multiparametric MRI and PET/MRI by using a five-point Likert-type scale. The prostatectomy specimen served as the reference standard. Accuracy was assessed with a multireader multicase analysis and by calculating reader-average areas under the receiver operating characteristics curve (AUCs), sensitivity, and specificity for ordinal and dichotomized data in a region-specific and patient-specific approach. Interrater agreement was assessed with the Fleiss multirater κ. Results For multiparametric MRI versus PET/MRI in ECE detection, respectively, AUC, sensitivity, and specificity in the region-specific analysis were 0.67 and 0.75 (P = .07), 28% (21 of 76) and 47% (36 of 76) (P = .09), and 94% (529 of 564) and 90% (509 of 564) (P = .007). For the patient-specific analysis, AUC, sensitivity, and specificity were 0.66 and 0.73 (P = .19), 46% (22 of 48) and 69% (33 of 48) (P = .04), and 75% (84 of 112) and 67% (75 of 112) (P = .19), respectively. For multiparametric MRI versus PET/MRI in SVI detection, respectively, AUC, sensitivity, and specificity of the region-specific analysis were 0.66 and 0.74 (P = .21), 35% (seven of 20) and 50% (10 of 20) (P = .25), and 98% (295 of 300) and 94% (282 of 300) (P < .001). For the patient-specific analysis, AUC, sensitivity, and specificity were 0.65 and 0.79 (P = .25), 35% (seven of 20) and 55% (11 of 20) (P = .20), and 98% (137 of 140) and 94% (131 of 140) (P = .07), respectively. Interrater reliability for multiparametric MRI versus PET/MRI did not differ for ECE (κ, 0.46 vs 0.40; P = .24) and SVI (κ, 0.23 vs 0.33; P = .39). Conclusion Our results suggest that gallium 68 (68Ga)-labeled Glu-urea-Lys (Ahx)-HBED-CC ligand targeting the prostate-specific membrane antigen (PSMA) (68Ga-PSMA-11) PET/MRI and multiparametric MRI perform similarly for local staging of prostate cancer in patients with intermediate-to-high-risk prostate cancer. The increased sensitivity of 68Ga-PSMA-11 PET/MRI for the detection of extracapsular disease comes at the cost of a slightly reduced specificity. © RSNA, 2019.

Clinical impact of 68Ga-PSMA-11 PET on patient management and outcome, including all patients referred for an increase in PSA level during the first year after its clinical introduction.

PURPOSE: The fast-increasing use of positron emission tomography (PET) with prostate-specific membrane antigen (PSMA) ligand for the imaging of prostate cancer (PCA) biochemical recurrence has led to a rapid change in treatment concepts. Since the superiority of 68Ga-PSMA-11 PET in detecting recurrent PCA is well established, the aim of our study was to assess its effect on management and outcome in all patients imaged during the first year after its introduction into clinical routine. METHODS: Of 327 patients imaged, 223 were referred for recurrent PCA and gave written informed consent for further analysis of their data for this retrospective consecutive cohort analysis. Twenty patients were lost to further follow-up. The rate of detection of recurrence by 68Ga-PSMA-11 PET was based on the clinical reports. Management before the availability of PET diagnostic information was assessed according to guidelines (therapy option without 68Ga-PSMA-11 PET). In the 203 patients with follow-up 6 months after 68Ga-PSMA-11 PET, the therapies effectively implemented as well as follow-up PSA levels were evaluated, with a PSA value of <0.2 ng/ml representing a complete response and a decrease in PSA value of at least 50% from baseline representing a partial response. RESULTS: 68Ga-PSMA-11 PET was positive and identified recurrence in 166 of the 223 patients (74%), with a detection rate of 50% for recurrent disease at low PSA values of <0.5 ng/ml. 68Ga-PSMA-11 PET led to a change in management in 122 of the 203 patients (60%). A substantial increase in the use of metastasis-targeted treatment and a reduction in the use of systemic treatment were observed, with 59 of the 203 patients (29%) undergoing targeted radiotherapy (RTXa) only, and 20 patients (10%) undergoing RTXa with hormonal therapy as the two most frequently selected therapy options. The proportion of patients in whom systemic therapy was selected decreased from 60% (133 of 223 patients) to 34% (70 of 203 patients) on the basis of the information provided by the 68Ga-PSMA-11 PET scan. PSMA PET-directed metastasis-targeted treatment led to a complete response after 6 months in 45% of patients. CONCLUSION: The high rate of recurrence detection by PSMA PET was confirmed and PSMA PET led to a change in management in 60% of patients. Focal therapy for PSMA-positive lesions is a promising approach with complete responses in 45% of patients.

Vertebral body insufficiency fractures: detection of vertebrae at risk on standard CT images using texture analysis and machine learning.

PURPOSE: To evaluate the diagnostic performance of bone texture analysis (TA) combined with machine learning (ML) algorithms in standard CT scans to identify patients with vertebrae at risk for insufficiency fractures. MATERIALS AND METHODS: Standard CT scans of 58 patients with insufficiency fractures of the spine, performed between 2006 and 2013, were analyzed retrospectively. Every included patient had at least two CT scans. Intact vertebrae in a first scan that either fractured ("unstable") or remained intact ("stable") in the consecutive scan were manually segmented on mid-sagittal reformations. TA features for all vertebrae were extracted using open-source software (MaZda). In a paired control study, all vertebrae of the study cohort "cases" and matched controls were classified using ROC analysis of Hounsfield unit (HU) measurements and supervised ML techniques. In a within-subject vertebra comparison, vertebrae of the cases were classified into "unstable" and "stable" using identical techniques. RESULTS: One hundred twenty vertebrae were included. Classification of cases/controls using ROC analysis of HU measurements showed an AUC of 0.83 (95% confidence interval [CI], 0.77-0.88), and ML-based classification showed an AUC of 0.97 (CI, 0.97-0.98). Classification of unstable/stable vertebrae using ROC analysis showed an AUC of 0.52 (CI, 0.42-0.63), and ML-based classification showed an AUC of 0.64 (CI, 0.61-0.67). CONCLUSION: TA combined with ML allows to identifying patients who will suffer from vertebral insufficiency fractures in standard CT scans with high accuracy. However, identification of single vertebra at risk remains challenging. KEY POINTS: • Bone texture analysis combined with machine learning allows to identify patients at risk for vertebral body insufficiency fractures on standard CT scans with high accuracy. • Compared to mere Hounsfield unit measurements on CT scans, application of bone texture analysis combined with machine learning improve fracture risk prediction. • This analysis has the potential to identify vertebrae at risk for insufficiency fracture and may thus increase diagnostic value of standard CT scans.

Patterns of metastatic spread and tumor burden in unselected cancer patients using PET imaging: Implications for the oligometastatic spectrum theory.

Introduction and background: Metastatic disease has been proposed as a continuum, with no clear cut-off between oligometastatic and polymetastatic disease. This study aims to quantify tumor burden and patterns of spread in unselected metastatic cancer patients referred for PET-based staging, response assessment of restaging. Materials and methods: All oncological fluorodeoxyglucose (FDG-) and prostate-specific membrane antigen (PSMA-) positron emission tomography (PET) scans conducted at a single academic center in 2020 were analyzed. Imaging reports of all patients with metastatic disease were reviewed and assessed. Results: For this study, 7,000 PET scans were screened. One third of PET scans (n = 1,754; 33 %) from 1,155 unique patients showed presence of metastatic disease from solid malignancies, of which 601 (52 %) and 554 (48 %) were classified as oligometastatic (maximum 5 metastases) and polymetastatic (>5 metastases), respectively. Lung and pleural cancer, skin cancer, and breast cancer were the most common primary tumor histologies with 132 (23.8 %), 88 (15.9 %), and 72 (13.0 %) cases, respectively. Analysis of the number of distant metastases showed a strong bimodal distribution of the metastatic burden with 26 % of patients having one solitary metastasis and 43 % of patients harboring >10 metastases. Yet, despite 43 % of polymetastatic patients having >10 distant metastases, their pattern of distribution was restricted to one or two organs in about two thirds of patients, and there was no association between the number of distant metastases and the number of involved organs. Conclusion: The majority of metastatic cancer patients are characterized by either a solitary metastasis or a high tumor burden with >10 metastases, the latter was often associated with affecting a limited number of organs. These findings support both the spectrum theory of metastasis and the seed and soil hypothesis and can support in designing the next generation of clinical trials in the field of oligometastatic disease.

Clinical management of oligometastatic cancer: Applying multidisciplinary tumor board recommendations in practice.

Aims: Multidisciplinary tumor boards (MDTs) are an integral part of ensuring high-quality, evidence-based and personalized cancer care. In this study, we aimed to evaluate the adherence to and implementation of MDT recommendations in patients with oligometastatic disease (OMD). Methods: We screened all oncologic positron emission tomography (PET) scans conducted at a single comprehensive cancer center in 2020. Patients were included if they had evidence of imaging-based OMD from a solid organ malignancy on the index scans, had their OMD case discussed at an MDT, and were treated and followed up at the same center. A switch away from the MDT-recommended treatment modalities was classified as a major deviation; non-MDT-mandated adjustments to a recommended treatment modality were coded as minor deviation. Clinical data was obtained via chart review; statistical calculations were computed using the R software. Results: After review of PET and/or concurrent brain scans, 787 cases of OMD were identified. Thereof, 347 (44.1 %) cases were discussed at MDT, of which 331 (42.1 %) were therapeutically managed and subsequently followed. The three most commonly recommended therapies were systemic therapy (35.6 %), multimodality treatment including definitive local therapy (17.8 %), and radiotherapy (13.9 %). A major deviation was recorded in 16.3 % of cases (most commonly: none of the MDT-recommended treatment modalities were performed: 19 (35.2 %); not all MDT-planned treatment modalities were performed: 12 (22.2 %); and additional treatment modality was performed: 11 (20.3 %). A minor deviation was found in 1.5 % of cases. On multivariable regression, number of distant metastases (n > 1) was associated with a major deviation (OR: 1.85; 95 % CI, 1.0-3.52). Major deviations were associated with a significantly worse OS (p = 0.0034). Conclusions: Adherence to and implementation of MDT recommendations in OMD patients was generally high (83.7%). Major deviations might be further reduced by more careful and elaborate discussions of OMD patient characteristics s and patient preferences.

Influence of brain metastases on the classification, treatment, and outcome of patients with extracranial oligometastasis: a single-center cross-sectional analysis.

BACKGROUND AND INTRODUCTION: Increasing evidence suggests that a subgroup of patients with oligometastatic cancer might achieve a prolonged disease-free survival through local therapy for all active cancer lesions. Our aims are to investigate the impact of brain metastases on the classification, treatment, and outcome in these patients. MATERIALS AND METHODS: We analyzed a total of 7,000 oncological positron emission tomography scans to identify patients with extracranial oligometastatic disease (defined as ≤ 5 intra- or extra-cranial metastases). Concurrent magnetic resonance imaging brain was assessed to quantify intracranial tumor burden. We investigated the impact of brain metastases on oligometastatic disease state, therapeutic approaches, and outcome. Predictors for transitioning from oligo- to polymetastatic states were evaluated using regression analysis. RESULTS: A total of 106 patients with extracranial oligometastases and simultaneous brain metastases were identified, primarily originating from skin or lung/pleura cancers (90%, n = 96). Brain metastases caused a transition from an extracranial oligometastatic to a whole-body polymetastatic state in 45% (n = 48) of patients. While oligometastatic patients received systemic therapy (55% vs. 35%) more frequently and radiotherapy for brain metastases was more often prescribed to polymetastatic patients (44% vs. 26%), the therapeutic approach did not differ systematically between both sub-groups. The oligometastatic sub-group had a median overall survival of 28 months compared to 10 months in the polymetastatic sub-group (p < 0.01). CONCLUSION: In patients with brain metastases, a low total tumor burden with an oligometastatic disease state remained a significant prognostic factor for overall survival. Presence of brain metastases should therefore not serve as exclusion criterion for clinical trials in the field of oligometastatic disease. Moreover, it underscores the importance of considering a multimodality treatment strategy in oligometastatic cancer patients.

The Monocle Sign on 18 F-FDG PET Indicates Contralateral Peripheral Facial Nerve Palsy.

BACKGROUND: The aim of our study was to retrospectively analyze FDG PET/CT data in patients with facial nerve palsy (FNP) for the presence of the monocle sign. PATIENTS AND METHODS: A total of 85 patients with unilateral FNP were included into our study, thereof 73 with peripheral FNP and 12 with central FNP. FDG uptake (SUV max , SUV mean , total lesion glycolysis) was measured in both orbicularis oculi muscles (OOMs). FDG uptake of paretic and nonparetic muscles was compared in patients with FNP (Wilcoxon test and Mann-Whitney U test) and was also compared with FDG uptake in 33 patients without FNP (Mann-Whitney U test). SUV max ratios of OOM were compared. A receiver operating characteristic curve and Youden Index were used to determine the optimal cutoff SUV max ratio for the prevalence of contralateral peripheral FNP. RESULTS: The SUV max ratio of OOM was significantly higher in patients with peripheral FNP compared with patients with central FNP and those without FNP (1.70 ± 0.94 vs 1.16 ± 0.09 vs 1.18 ± 0.21, respectively; P < 0.001). The SUV max ratio of OOM yielded an area under the curve (AUC) of 0.719 (95% confidence interval, 0.630-0.809), with an optimal cutoff of 1.41, yielding a specificity of 94.4% and a sensitivity of 44.1% for identifying contralateral peripheral FNP. One hundred percent specificity is achieved using a cutoff of 1.91 (sensitivity, 29.4%). CONCLUSIONS: Asymmetrically increased FDG uptake of the OOM (the "monocle sign") indicates contralateral peripheral FNP. A nearly 2-fold higher SUV max represents a practically useful cutoff.

FDA-cleared artificial intelligence and machine learning-based medical devices and their 510(k) predicate networks.

The US Food and Drug Administration is clearing an increasing number of artificial intelligence and machine learning (AI/ML)-based medical devices through the 510(k) pathway. This pathway allows clearance if the device is substantially equivalent to a former cleared device (ie, predicate). We analysed the predicate networks of cleared AI/ML-based medical devices (cleared between 2019 and 2021), their underlying tasks, and recalls. More than a third of cleared AI/ML-based medical devices originated from non-AI/ML-based medical devices in the first generation. Devices with the longest time since the last predicate device with an AI/ML component were haematology (2001), radiology (2001), and cardiovascular devices (2008). Especially for devices in radiology, the AI/ML tasks changed frequently along the device's predicate network, raising safety concerns. To date, only a few recalls might have affected the AI/ML components. To improve patient care, a stronger focus should be placed on the distinctive characteristics of AI/ML when defining substantial equivalence between a new AI/ML-based medical device and predicate devices.

Recognition of and treatment recommendations for oligometastatic disease in multidisciplinary tumor boards.

Background and introduction: Growing evidence supports a combined modality treatment strategy for patients with oligometastatic disease. However, lack of phase III trial data and uncertainties around patient selection highlight the importance of multidisciplinary tumor boards (MDT) in therapeutic decision-making. This study aimed to analyze the recognition of and treatment recommendations for oligometastatic patients by MDTs at a large comprehensive cancer center in order to better understand current treatment patterns of oligometastasis. Materials and methods: For this retrospective single-center cross-sectional study, oligometastatic patients were identified by screening oncological PET and concurrent brain MRI scans conducted at our center in 2020. MDT discussions and recommendations within four weeks of the imaging diagnosis of oligometastasis were analyzed. Logistic regression analysis was used to identify predictors for the addition of local therapy to standard-of-care. Results: A total of 787 oligometastatic cases were identified. Lung cancer and mesothelioma, skin cancer, and prostate cancer were the most common histologies with 231 (29 %), 160 (20 %), and 84 (11 %) cases, respectively. Almost half of the cases (46 %) had one distant metastasis on imaging only. More than half (56 %) of all oligometastatic cases were discussed at an MDT. In 47 % of cases, for which a therapeutic recommendation was reached in an MDT, local therapy was part of the therapeutic strategy. On logistic regression analysis, oligometastatic skin cancer was significantly associated with a recommendation for local therapy (p < 0.05), whereas the number of oligometastases was not (p = 0.202). Conclusion: More than half of oligometastatic cases were discussed in MDTs, of which more than every second received a recommendation including the addition of local therapy. This frequency of MDT use underscores the importance of multidisciplinary decision-making, yet efforts should be increased to standardize reporting and use standard nomenclature on oligometastasis in MDTs to better frame multidisciplinary discussion.

Follow-up PET/CT of alveolar echinococcosis: Comparison of metabolic activity and immunodiagnostic testing.

PURPOSE: To investigate the potential role of follow-up 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in therapy control of inoperable patients with alveolar echinococcosis. MATERIALS AND METHODS: In this single-center retrospective cohort study, 48 PET/CT of 16 patients with confirmed alveolar echinococcosis were analysed. FDG-uptake of the most active echinococcosis manifestation was measured (i.e., maximum standardized uptake value (SUVmax) and in relation to background activity in normal liver tissue (SUVratio)) and compared to immunodiagnostic testing. For clinical patient follow-up, patient demographics, laboratory data, including E. granulosus hydatid fluid (EgHF) antibody units (AU) as well as clinical and treatment information were assessed for all patients at the time of PET/CT, and at the last recorded clinical visit. RESULTS: Metabolic activity of PET/CT measured in the echinococcosis manifestation was significantly correlated with EgHF AU (p < 0.001). The differences in metabolic activity of echinococcosis manifestations between two consecutive PET/CT examinations of the same patient and differences in EgHF AU in the respective time intervals displayed a significant positive correlation (p = 0.01). A trend for a more rapid decline in SUVratio liver over time was found in patients who stopped benzimidazole therapy versus patients who did not stop therapy (p = 0.059). CONCLUSION: In inoperable patients with alveolar echinococcosis, the course of metabolic activity in follow-up PET/CT is associated to the course EgHF antibody levels. Both parameters may potentially be used to evaluate the course of the disease and potentially predict the duration of benzimidazole therapy.