Higher Validity, Lower Radiation: A New Ictal Single-Photon Emission Computed Tomography Framework.

OBJECTIVE: To assess whether arterial spin labeling perfusion images of healthy controls can enhance ictal single-photon emission computed tomography analysis and whether the acquisition of the interictal image can be omitted. METHODS: We developed 2 pipelines: The first uses ictal and interictal images and compares these to single-photon emission computed tomography and arterial spin labeling of healthy controls. The second pipeline uses only the ictal image and the analogous healthy controls. Both pipelines were compared to the gold standard analysis and evaluated on data of individuals with epilepsy who underwent ictal single-photon emission computed tomography imaging during presurgical evaluation between 2010 and 2022. Fifty healthy controls prospectively underwent arterial spin labeling imaging. The correspondence between the detected hyperperfusion and the postoperative resection cavity or the presumably affected lobe was assessed using Dice score and mean Euclidean distance. Additionally, the outcomes of the pipelines were automatically assigned to 1 of 5 concordance categories. RESULTS: Inclusion criteria were met by 43 individuals who underwent epilepsy surgery and by 73 non-surgical individuals with epilepsy. Compared to the gold standard analysis, both pipelines resulted in significantly higher Dice scores and lower mean distances (p < 0.05). The combination of both provided localizing results in 85/116 cases, compared to 54/116 generated by the current gold standard analysis and the ictal image alone produced localizing results in 60/116 (52%) cases. INTERPRETATION: We propose a new ictal single-photon emission computed tomography protocol; it finds relevantly more ictal hyperperfusion, and halves the radiation dose in about half of the individuals. ANN NEUROL 2024.

Amyloid and SCD jointly predict cognitive decline across Chinese and German cohorts.

INTRODUCTION: Subjective cognitive decline (SCD) in amyloid-positive (Aß+) individuals was proposed as a clinical indicator of Stage 2 in the Alzheimer's disease (AD) continuum, but this requires further validation across cultures, measures, and recruitment strategies. METHODS: Eight hundred twenty-one participants from SILCODE and DELCODE cohorts, including normal controls (NC) and individuals with SCD recruited from the community or from memory clinics, underwent neuropsychological assessments over up to 6 years. Amyloid positivity was derived from positron emission tomography or plasma biomarkers. Global cognitive change was analyzed using linear mixed-effects models. RESULTS: In the combined and stratified cohorts, Aß+ participants with SCD showed steeper cognitive decline or diminished practice effects compared with NC or Aß- participants with SCD. These findings were confirmed using different operationalizations of SCD and amyloid positivity, and across different SCD recruitment settings. DISCUSSION: Aß+ individuals with SCD in German and Chinese populations showed greater global cognitive decline and could be targeted for interventional trials. HIGHLIGHTS: SCD in amyloid-positive (Aß+) participants predicts a steeper cognitive decline. This finding does not rely on specific SCD or amyloid operationalization. This finding is not specific to SCD patients recruited from memory clinics. This finding is valid in both German and Chinese populations. Aß+ older adults with SCD could be a target population for interventional trials.

Study Protocol of a Randomized, Two-Arm, Phase I/II Trial Investigating the Feasibility, Safety, and Efficacy of Local Treatment with US-Guided High-Intensity Focused Ultrasound in Combination with Palliative Chemotherapy in Inoperable Pancreatic Cancer.

BACKGROUND: Pancreatic adenocarcinoma (PaC) still has a dismal prognosis, and despite medical advances, a bleak 5-year survival rate of only 8%, largely due to late diagnosis and limited curative surgical options for most patients. Frontline palliative treatment shows some survival advantages. However, the high disease mortality is accompanied by high morbidity including cancer-related pain and additional symptoms, which strongly impair patients' quality of life (QOL). At present, there is no established strategy for local therapy for PaC primarily aiming to manage local tumor growth and alleviate associated symptoms, particularly pain. In recent years, non-invasive high-intensity focused ultrasound (HIFU) has shown promising results in reducing cancer pain and tumor mass, improving patients' QOL with few side effects. STUDY DESIGN: This is the first randomized controlled trial worldwide including 40 patients with inoperable pancreatic adenocarcinoma randomized into two groups: group A undergoing standard chemotherapy; and group B undergoing standard chemotherapy plus local HIFU treatment. This study aims to establish a robust evidence base by examining the feasibility, safety, and efficacy of US-guided HIFU in combination with standard palliative systemic therapy for unresectable PaC. Primary endpoint assessments will focus on parameters including safety issues (phase I), and local response rates (phase II).

Clinical experience with shear wave elastography (SWE) for assessing healthy uterus in a transabdominal approach.

Aim of the study was to evaluate the diagnostic performance and feasibility of transabdominal ultrasound shear wave elastography (SWE) in assessing sonoelastographic features of the uterus. Twenty-seven premenopausal women were enrolled between 2021 and 2022. Transabdominal SWE measured myometrial stiffness in various uterine segments. Additionally, tissue stiffness of the quadriceps femoris muscle and autochthonous back muscle was measured. Statistical analysis employed non-parametric tests, t test, and a robust mixed linear model. Stiffness values of the uterus and the two investigated muscle types exhibited a similar spectrum: 6.38 ± 2.59 kPa (median 5.61 kPa; range 2.76-11.31 kPa) for the uterine myometrium, 7.22 ± 1.24 kPa (6.82 kPa; 5.11-9.39 kPa) for the quadriceps femoris musle, and 7.43 ± 2.73 kPa (7.41 kPa; 3.10-13.73 kPa) for the autochthonous back muscle. A tendency for significant differences in myometrial stiffness was observed concerning the type of labor mode (mean stiffness of 9.17 ± 1.35 kPa after vaginal birth vs. 3.83 ± 1.35 kPa after Caesarian section, p = 0.01). No significant differences in myometrial stiffness were observed concerning age, BMI, previous pregnancies, uterine flexion and menstrual cycle phase. Transabdominal SWE of uterine stiffness seems to be a fast and practicable method in a clinical setting. Uterine stiffness appears to be largely independent of various factors, except for the mode of delivery. However, further studies are needed to validate these results.

Discovering single cannabidiol or synergistic antitumor effects of cannabidiol and cytokine-induced killer cells on non-small cell lung cancer cells.

Introduction: A multitude of findings from cell cultures and animal studies are available to support the anti-cancer properties of cannabidiol (CBD). Since CBD acts on multiple molecular targets, its clinical adaptation, especially in combination with cancer immunotherapy regimen remains a serious concern. Methods: Considering this, we extensively studied the effect of CBD on the cytokine-induced killer (CIK) cell immunotherapy approach using multiple non-small cell lung cancer (NSCLC) cells harboring diverse genotypes. Results: Our analysis showed that, a) The Transient Receptor Potential Cation Channel Subfamily V Member 2 (TRPV2) channel was intracellularly expressed both in NSCLC cells and CIK cells. b) A synergistic effect of CIK combined with CBD, resulted in a significant increase in tumor lysis and Interferon gamma (IFN-g) production. c) CBD had a preference to elevate the CD25+CD69+ population and the CD62L_CD45RA+terminal effector memory (EMRA) population in NKT-CIK cells, suggesting early-stage activation and effector memory differentiation in CD3+CD56+ CIK cells. Of interest, we observed that CBD enhanced the calcium influx, which was mediated by the TRPV2 channel and elevated phosphor-Extracellular signal-Regulated Kinase (p-ERK) expression directly in CIK cells, whereas ERK selective inhibitor FR180204 inhibited the increasing cytotoxic CIK ability induced by CBD. Further examinations revealed that CBD induced DNA double-strand breaks via upregulation of histone H2AX phosphorylation in NSCLC cells and the migration and invasion ability of NSCLC cells suppressed by CBD were rescued using the TRPV2 antagonist (Tranilast) in the absence of CIK cells. We further investigated the epigenetic effects of this synergy and found that adding CBD to CIK cells decreased the Long Interspersed Nuclear Element-1 (LINE-1) mRNA expression and the global DNA methylation level in NSCLC cells carrying KRAS mutation. We further investigated the epigenetic effects of this synergy and found that adding CBD to CIK cells decreased the Long Interspersed Nuclear Element-1 (LINE-1) mRNA expression and the global DNA methylation level in NSCLC cells carrying KRAS mutation. Conclusions: Taken together, CBD holds a great potential for treating NSCLC with CIK cell immunotherapy. In addition, we utilized NSCLC with different driver mutations to investigate the efficacy of CBD. Our findings might provide evidence for CBD-personized treatment with NSCLC patients.

Key learnings from concordant systematic biopsies in prostate-specific membrane antigen positron emission tomography/computed tomography-guided prostate biopsies: Enhancing targeting accuracy.

BACKGROUND: Prostate cancer (PCa) diagnosis and staging have evolved with the advent of 68Ga-Prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA-PET/CT). This study investigates the role of complementary systematic biopsies (SB) during PSMA-PET/CT-guided targeted prostate biopsies (PET-TB) for PCa detection, grading, and distribution. We address the uncertainty surrounding the necessity of SB in conjunction with PET-TB. METHODS: We analyzed PCa grading and distribution in 30 men who underwent PET-TB and SB because of contraindication to magnetic resonance imaging or high clinical suspicion of PCa. Tumor distribution was assessed in relation to the PET-highlighted lesions. Standardized reporting schemes, encompassing SUVmax, PRIMARY score, and miTNM classification, were evaluated. RESULTS: 80% of patients were diagnosed with PCa, with 70% classified as clinically significant (csPCa). SB detected more csPCa cases than PET-TB, but the differences were not statistically significant. Discordant results were observed in 25% of cases, where SB outperformed PET-TB. Spatial analysis revealed that tumor-bearing cores from SB were often located in close proximity to the PET-highlighted region. Reporting schemes showed potential for csPCa detection with significantly increased SUVmax in csPCA patients. Subsequent follow-up data underscored the importance of SB in precise PCa grading and staging. CONCLUSIONS: While PET-TB can simplify prostate biopsy and reduce invasiveness by core number, SB cannot be omitted yet due to potential PET-TB targeting errors. Factors such as limited spatial resolution and fusion inaccuracies contribute to the need for SB. Standardization in reporting schemes currently cannot compensate for targeting errors highlighting the need for refinement.

Expression of the microtubule-associated protein 2 (MAP2) as a potential independent prognostic marker in prostate cancer.

PURPOSE: Investigation of Microtubuli-associated Protein 2 (MAP2) expression and its clinical relevance in prostate cancer. MATERIAL AND METHODS: MAP2 expression was immunohistochemically analysed on radical prostatectomy specimens using whole block sections (n = 107) and tissue microarrays (TMA; n = 310). The staining intensity was evaluated for carcinoma, benign tissue and prostatic intraepithelial neoplasia. Expression data were correlated with clinicopathological parameters and biochemical recurrence-free survival. Additionally, MAP2 protein expression was quantitatively analysed in the serum of histologically confirmed prostate carcinoma patients and the control group using a commercial enzyme-linked immunosorbent assay. RESULTS: MAP2 staining was significantly stronger in neoplastic tissue than in non-neoplastic prostatic glands, both in whole block sections (p < 0.01) and in TMA sections (p < 0.05). TMA data revealed significantly stronger MAP2 staining in high-grade tumors. Survival analysis showed a significant correlation between strong MAP2 staining in carcinoma and shortened biochemical recurrence-free survival after prostatectomy (p < 0.001). Multivariate Cox regression analysis confirmed MAP2 as an independent predictor for an unfavourable course. Mean MAP2 serum levels for non-PCA vs. PCA patients differed significantly (non-PCA = 164.7 pg/ml vs. PCA = 242.5 pg/ml, p < 0.001). CONCLUSION: The present data support MAP2 as a novel biomarker in PCA specimens. MAP2 is correlated with tumor grade and MAP2 high-expressing PCA is associated with an increased risk of biochemical recurrence after radical prostatectomy. Future studies are necessary to evaluate MAP2 as a valuable immunohistochemical biomarker in preoperative PCA diagnostic procedures, in particular with regard to treatment modalities.

US-guided high-intensity focused ultrasound in pancreatic cancer treatment: a consensus initiative between Chinese and European HIFU centers.

Purpose: Ultrasound-guided high-intensity focused ultrasound (USgHIFU) represents a safe and effective non-invasive thermoablative technique for managing inoperable pancreatic cancer. This treatment method significantly alleviates disease-related symptoms and reduces pancreatic tumor volume. However, the current body of evidence is constrained by a lack of randomized controlled trials. The utilization of USgHIFU is primarily indicated for patients with unresectable, locally advanced, or metastatic pancreatic cancer, particularly those experiencing symptoms due to a locally advanced primary tumor.Methods: This collaborative consensus paper, involving European and Chinese HIFU centers treating pancreatic cancer, delineates criteria for patient selection, focusing on those most likely to benefit from USgHIFU treatment. Consideration is given to endpoints encompassing symptom alleviation, local response rates, other oncological outcomes, as well as overall and progression-free survival. Additionally, this paper defines relevant contraindications, side effects, and complications associated with USgHIFU. The publication also explores the feasibility and role of USgHIFU within the context of palliative care, including standard systemic chemotherapy.Results: The non-invasive local treatment of advanced pancreatic cancer using HIFU should be regarded as an adjunctive option alongside systemic chemotherapy or best supportive care for managing this aggressive disease. Based on the ability of USgHIFU therapy to mitigate pain and reduce primary tumor volume, it should be considered as a complementary therapy for symptomatic patients with inoperable pancreatic cancer and as a potential means of tumor debulking. The underutilized yet promising USgHIFU exhibits the potential to enhance patients' quality of life by alleviating cancer-related pain. Experts in the field should evaluate this treatment option be evaluated by experts in this field, with this consensus paper potentially serving as a guiding resource for the medical community.Conclusions: US-guided HIFU for advanced pancreatic cancer addresses treatment goals, available options, success rates, and limitations. As a non-invasive, effective local therapy, complementary to chemotherapy and best supportive care, it plays a pivotal role in pain relief, reducing of tumor volume, and potentially improving survival rates.

177Lu-Prostate-Specific Membrane Antigen Therapy in Patients with Metastatic Castration-Resistant Prostate Cancer and Prior 223Ra (RALU Study).

223Ra-dichloride (223Ra) and 177Lu-prostate-specific membrane antigen (PSMA) are approved treatments for metastatic castration-resistant prostate cancer (mCRPC). The safety and effectiveness of sequential use of 223Ra and 177Lu-PSMA in patients with mCRPC are not well described. This study aimed to evaluate 177Lu-PSMA safety and efficacy in patients with mCRPC previously treated with 223Ra. Methods: The radium→lutetium (RALU) study was a multicenter, retrospective, medical chart review. Participants had received at least 1 223Ra dose and, in any subsequent therapy line, at least 1 177Lu-PSMA dose. Primary endpoints included the incidence of adverse events (AEs), serious AEs, grade 3-4 hematologic AEs, and abnormal laboratory values. Secondary endpoints included overall survival, time to next treatment/death, and change from baseline in serum prostate-specific antigen and alkaline phosphatase levels. Results: Data were from 133 patients. Before 177Lu-PSMA therapy, 56% (75/133) of patients received at least 4 life-prolonging therapies; all patients received 223Ra (73% received 5-6 injections). Overall, 27% (36/133) of patients received at least 5 177Lu-PSMA infusions. Any-grade treatment-emergent AEs were reported in 79% (105/133) of patients and serious AEs in 30% (40/133). The most frequent grade 3-4 laboratory abnormalities were anemia (30%, 40/133) and thrombocytopenia (13%, 17/133). Median overall survival was 13.2 mo (95% CI, 10.5-15.6 mo) from the start of 177Lu-PSMA. Conclusion: In this real-world setting, 223Ra followed by 177Lu-PSMA therapy in heavily pretreated patients with mCRPC was clinically feasible, with no indication of impairment of 177Lu-PSMA safety or effectiveness.

Study Protocol of a Prospective, Monocentric, Single-Arm Study Investigating the Safety and Efficacy of Local Ablation of Symptomatic Uterine Fibroids with US-Guided High-Intensity Focused Ultrasound (HIFU).

Uterine fibroids are the most common benign tumors of the uterus. Approximately 20-50% of women with myomas experience a variety of symptoms such as vaginal bleeding, abdominal pain, pelvic pain and pressure, and urological problems, possibly interfering with fertility and pregnancy. Although surgery remains the standard treatment option for fibroids, non-invasive therapeutic options, such as high-intensity focused ultrasound (HIFU), have emerged over the last dec ade. During HIFU, ultrasound is focused on the target tissue causing coagulation necrosis. HIFU has, meanwhile, become an established method for treating uterine fibroids in many countries. Clinical data have shown that it effectively alleviates fibroid-related symptoms and reduces fibroid size with a very low rate of side effects. However, there is a lack of data on how this treatment affects laboratory parameters and structural features of uterine tissue. As our center is the only one in German-speaking countries where ultrasound-guided HIFU technology is currently established, the aim of this prospective, monocentric, single-arm trial is not only to evaluate the safety and efficacy of local US-guided HIFU in symptomatic uterine fibroid patients according to GCP standards but also to explore its effects on blood parameters and the structural integrity of uterine tissue using elastographic methods.

Cortical Amyloid Burden Relates to Basal Forebrain Volume in Subjective Cognitive Decline.

BACKGROUND: Atrophy of cholinergic basal forebrain (BF) nuclei is a frequent finding in magnetic resonance imaging (MRI) volumetry studies that examined patients with prodromal or clinical Alzheimer's disease (AD), but less clear for individuals in earlier stages of the clinical AD continuum. OBJECTIVE: To examine BF volume reductions in subjective cognitive decline (SCD) participants with AD pathologic changes. METHODS: The present study compared MRI-based BF volume measurements in age- and sex-matched samples of N = 24 amyloid-positive and N = 24 amyloid-negative SCD individuals, based on binary visual ratings of Florbetaben positron emission tomography (PET) measurements. Additionally, we assessed associations of BF volume with cortical amyloid burden, based on semiquantitative Centiloid (CL) analyses. RESULTS: Group differences approached significance for BF total volume (p = 0.061) and the Ch4 subregion (p = 0.059) only, showing the expected relative volume reductions for the amyloid-positive subgroup. There were also significant inverse correlations between BF volumes and CL values, which again were most robust for BF total volume and the Ch4 subregion. CONCLUSIONS: The results are consistent with the hypothesis that amyloid-positive SCD individuals, which are considered to represent a transitional stage on the clinical AD continuum, already show incipient alterations of BF integrity. The negative association with a continuous measure of cortical amyloid burden also suggests that this may reflect an incremental process. Yet, further research is needed to evaluate whether BF changes already emerge at "grey zone" levels of amyloid accumulation, before amyloidosis is reliably detected by PET visual readings.

Cytokine-Induced Killer Cells in Combination with Heat Shock Protein 90 Inhibitors Functioning via the Fas/FasL Axis Provides Rationale for a Potential Clinical Benefit in Burkitt's lymphoma.

Constant efforts are being made to develop methods for improving cancer immunotherapy, including cytokine-induced killer (CIK) cell therapy. Numerous heat shock protein (HSP) 90 inhibitors have been assessed for antitumor efficacy in preclinical and clinical trials, highlighting their individual prospects for targeted cancer therapy. Therefore, we tested the compatibility of CIK cells with HSP90 inhibitors using Burkitt's lymphoma (BL) cells. Our analysis revealed that CIK cytotoxicity in BL cells was augmented in combination with independent HSP90 inhibitors 17-DMAG (17-dimethylaminoethylamino-17-demethoxygeldanamycin) and ganetespib. Interestingly, CIK cell cytotoxicity did not diminish after blocking with NKG2D (natural killer group 2, member D), which is a prerequisite for their activation. Subsequent analyses revealed that the increased expression of Fas on the surface of BL cells, which induces caspase 3/7-dependent apoptosis, may account for this effect. Thus, we provide evidence that CIK cells, either alone or in combination with HSP90 inhibitors, target BL cells via the Fas-FasL axis rather than the NKG2D pathway. In the context of clinical relevance, we also found that high expression of HSP90 family genes (HSP90AA1, HSP90AB1, and HSP90B1) was significantly associated with the reduced overall survival of BL patients. In addition to HSP90, genes belonging to the Hsp40, Hsp70, and Hsp110 families have also been found to be clinically significant for BL survival. Taken together, the combinatorial therapy of CIK cells with HSP90 inhibitors has the potential to provide clinical benefits to patients with BL.

Computational analysis of heat shock proteins and ferroptosis-associated lncRNAs to predict prognosis in acute myeloid leukemia patients.

Owing to their functional diversity in many cancers, long noncoding RNAs (lncRNAs) are receiving special attention. LncRNAs not only function as oncogenes or tumor suppressors by participating in various signaling pathways but also serve as predictive markers for various types of cancer, including acute myeloid leukemia (AML). Considering this, we investigated lncRNAs that may act as a mediator between two processes, i.e., heat shock proteins and ferroptosis, which appear to be closely related in tumorigenesis. Using a comprehensive bioinformatics approach, we identified four lncRNAs (AL138716.1, AC000120.1, AC004947.1, and LINC01547) with prognostic value in AML patients. Of interest, two of them (AC000120.1 and LINC01547) have already been reported to be AML-related, and AC004947.1 is considered to have oncogenic potential. In particular, the signature obtained showed a lower survival probability with high-risk patients, and vice versa. To our knowledge, this is the first predictive model of lncRNA that may correlate with the processes of heat shock proteins and ferroptosis in AML. Nevertheless, validation using patient samples is warranted.

Test-retest repeatability of organ uptake on PSMA-targeted 18 F-DCFPyL PET/CT in patients with prostate cancer.

OBJECTIVES: We evaluated 18 F-DCFPyL test-retest repeatability of uptake in normal organs. METHODS: Twenty-two prostate cancer (PC) patients underwent two 18 F-DCFPyL PET scans within 7 days within a prospective clinical trial (NCT03793543). In both PET scans, uptake in normal organs (kidneys, spleen, liver, and salivary and lacrimal glands) was quantified. Repeatability was determined by using within-subject coefficient of variation (wCOV), with lower values indicating improved repeatability. RESULTS: For SUVmean , repeatability was high for kidneys, spleen, liver, and parotid glands (wCOV, range: 9.0%-14.3%) and lower for lacrimal (23.9%) and submandibular glands (12.4%). For SUVmax , however, the lacrimal (14.4%) and submandibular glands (6.9%) achieved higher repeatability, while for large organs (kidneys, liver, spleen, and parotid glands), repeatability was low (range: 14.1%-45.2%). CONCLUSION: We found acceptable repeatability of uptake on 18 F-DCFPyL PET for normal organs, in particular for SUVmean in the liver or parotid glands. This may have implications for both PSMA-targeted imaging and treatment, as patient selection for radioligand therapy and standardized frameworks for scan interpretation (PROMISE, E-PSMA) rely on uptake in those reference organs.

Altered limbic functional connectivity in individuals with subjective cognitive decline: Converging and diverging findings across Chinese and German cohorts.

INTRODUCTION: It remains unclear whether functional brain networks are consistently altered in individuals with subjective cognitive decline (SCD) of diverse ethnic and cultural backgrounds and whether the network alterations are associated with an amyloid burden. METHODS: Cross-sectional resting-state functional magnetic resonance imaging connectivity (FC) and amyloid-positron emission tomography (PET) data from the Chinese Sino Longitudinal Study on Cognitive Decline and German DZNE Longitudinal Cognitive Impairment and Dementia cohorts were analyzed. RESULTS: Limbic FC, particularly hippocampal connectivity with right insula, was consistently higher in SCD than in controls, and correlated with SCD-plus features. Smaller SCD subcohorts with PET showed inconsistent amyloid positivity rates and FC-amyloid associations across cohorts. DISCUSSION: Our results suggest an early adaptation of the limbic network in SCD, which may reflect increased awareness of cognitive decline, irrespective of amyloid pathology. Different amyloid positivity rates may indicate a heterogeneous underlying etiology in Eastern and Western SCD cohorts when applying current research criteria. Future studies should identify culture-specific features to enrich preclinical Alzheimer's disease in non-Western populations. HIGHLIGHTS: Common limbic hyperconnectivity across Chinese and German subjective cognitive decline (SCD) cohorts was observed. Limbic hyperconnectivity may reflect awareness of cognition, irrespective of amyloid load. Further cross-cultural harmonization of SCD regarding Alzheimer's disease pathology is required.

[Diagnosis and staging of metastatic hormone-sensitive prostate cancer]. / Diagnostik und Stadieneinteilung beim metastasierten hormonsensitiven Prostatakarzinom.

BACKGROUND: Risk stratification of patients with metastatic hormone-sensitive prostate cancer (mHSPC) has undergone significant changes in recent years in light of new therapies and innovative imaging. OBJECTIVES: Established and innovative methods for detection of metastasis, risk group stratification, and treatment of mHSPC are outlined and compared. MATERIALS AND METHODS: Background knowledge and treatment-relevant guideline recommendations on mHSPC are presented and complemented by recent study results. RESULTS: Integration of modern imaging techniques, especially prostate-specific membrane antigen (PSMA) PET/CT, into the diagnostic algorithm has the potential to significantly improve risk stratification and treatment of mHSPC. By using PSMA PET/CT, metastases are detected early and sensitively. This leads to the definition of new subgroups amenable to modern therapeutic strategies. The prognostic value of using PSMA PET/CT with regard to established risk categories in mHSPC is currently being evaluated. CONCLUSIONS: Modern imaging, especially PSMA PET/CT, has significant added value for the diagnosis and treatment of mHSPC in almost all subgroups. In particular, it helps to select patients who will benefit from intensification or de-escalation of systemic therapy.

High Interobserver Agreement on PSMA PET/CT Even in the Absence of Clinical Data.

BACKGROUND: Recommended by current guidelines, prostate-specific membrane antigen (PSMA)-directed PET/CT is increasingly used in men with prostate cancer (PC). We aimed to provide concordance rates using the PSMA reporting and data system (RADS) for scan interpretation and also determine whether such agreement rates are affected by available patient characteristics at time of scan. PATIENTS AND METHODS: Sixty men with PC, who all underwent 68Ga-PSMA-11 PET/CT, were included. Three independent, experienced readers indicated general scan parameters (including overall scan result, organ or lymph node [LN] involvement, and appropriateness of radioligand therapy). Applying PSMA-RADS 1.0, observers also had to conduct RADS scoring on a target lesion (TL) and overall scan level. During the first read, observers were masked to all relevant clinical information, whereas on a second read, relevant patient characteristics were displayed, thereby allowing for determination of impact of available clinical information for scan interpretation. We used intraclass correlation coefficients (ICCs; with 95% confidence intervals [CIs]), which were then rated according to Cicchetti (0.4-0.59 fair, 0.6-0.74 good, and 0.75-1 excellent agreement). RESULTS: For general parameters, agreement rates were excellent, including an overall scan result (ICC, 0.85; 95% CI, 0.76-0.90), LN metastases (ICC, 0.89; 95% CI, 0.83-0.93), organ involvement (ICC, 0.82; 95% CI, 0.72-0.89), and indication for radioligand therapy (ICC, 0.94; 95% CI, 0.90-0.96). Overall RADS scoring was also excellent with an ICC of 0.91 (95% CI, 0.96-09.4). On a TL-based level, 251 different lesions were selected by the 3 observers (with 73 chosen by all 3 readers). RADS-based concordance rates were fair to excellent: all lesions, ICC of 0.78 (95% CI, 0.67-0.85); LN, ICC of 0.81 (95% CI, 0.63-0.92); skeleton, ICC of 0.55 (95% CI, 0-0.84); and prostate, ICC of 0.48 (95% CI, 0.17-0.78). When performing a second read displaying patient's characteristics, there were only minor modifications to the previously applied RADS scoring on a TL-based level (overall, n = 8): each reader 1 and 2 in 3/60 (5%) instances, and reader 3 in 2/60 (3.3%) instances. The main reason for recategorization (mainly upstaging) was provided information on PSA levels (4/8, 50%). CONCLUSIONS: Applying PSMA-RADS, concordance rates were fair to excellent, whereas relevant modifications were rarely observed after providing clinical data. As such, even in the absence of patient information, standardized frameworks still provide guidance for reading PSMA PETs. Those findings may have implications for a high throughput in a busy PET practice, where patient details cannot always be retrieved at time of scan interpretation or in the context of clinical trials or central reviews in which readers may be blinded to clinical data.

Deep learning enables automated MRI-based estimation of uterine volume also in patients with uterine fibroids undergoing high-intensity focused ultrasound therapy.

BACKGROUND: High-intensity focused ultrasound (HIFU) is used for the treatment of symptomatic leiomyomas. We aim to automate uterine volumetry for tracking changes after therapy with a 3D deep learning approach. METHODS: A 3D nnU-Net model in the default setting and in a modified version including convolutional block attention modules (CBAMs) was developed on 3D T2-weighted MRI scans. Uterine segmentation was performed in 44 patients with routine pelvic MRI (standard group) and 56 patients with uterine fibroids undergoing ultrasound-guided HIFU therapy (HIFU group). Here, preHIFU scans (n = 56), postHIFU imaging maximum one day after HIFU (n = 54), and the last available follow-up examination (n = 53, days after HIFU: 420 ± 377) were included. The training was performed on 80% of the data with fivefold cross-validation. The remaining data were used as a hold-out test set. Ground truth was generated by a board-certified radiologist and a radiology resident. For the assessment of inter-reader agreement, all preHIFU examinations were segmented independently by both. RESULTS: High segmentation performance was already observed for the default 3D nnU-Net (mean Dice score = 0.95 ± 0.05) on the validation sets. Since the CBAM nnU-Net showed no significant benefit, the less complex default model was applied to the hold-out test set, which resulted in accurate uterus segmentation (Dice scores: standard group 0.92 ± 0.07; HIFU group 0.96 ± 0.02), which was comparable to the agreement between the two readers. CONCLUSIONS: This study presents a method for automatic uterus segmentation which allows a fast and consistent assessment of uterine volume. Therefore, this method could be used in the clinical setting for objective assessment of therapeutic response to HIFU therapy.

Lack of repeatability of radiomic features derived from PET scans: Results from a 18 F-DCFPyL test-retest cohort.

OBJECTIVES: PET-based radiomic metrics are increasingly utilized as predictive image biomarkers. However, the repeatability of radiomic features on PET has not been assessed in a test-retest setting. The prostate-specific membrane antigen-targeted compound 18 F-DCFPyL is a high-affinity, high-contrast PET agent that we utilized in a test-retest cohort of men with metastatic prostate cancer (PC). METHODS: Data of 21 patients enrolled in a prospective clinical trial with histologically proven PC underwent two 18 F-DCFPyL PET scans within 7 days, using identical acquisition and reconstruction parameters. Sites of disease were segmented and a set of 29 different radiomic parameters were assessed on both scans. We determined repeatability of quantification by using Pearson's correlations, within-subject coefficient of variation (wCOV), and Bland-Altman analysis. RESULTS: In total, 230 lesions (177 bone, 38 lymph nodes, 15 others) were assessed on both scans. For all investigated radiomic features, a broad range of inter-scan correlation was found (r, 0.07-0.95), with acceptable reproducibility for entropy and homogeneity (wCOV, 16.0% and 12.7%, respectively). On Bland-Altman analysis, no systematic increase or decrease between the scans was observed for either parameter (±1.96 SD: 1.07/-1.30, 0.23/-0.18, respectively). The remaining 27 tested radiomic metrics, however, achieved unacceptable high wCOV (≥21.7%). CONCLUSION: Many common radiomic features derived from a test-retest PET study had poor repeatability. Only Entropy and homogeneity achieved good repeatability, supporting the notion that those image biomarkers may be incorporated in future clinical trials. Those radiomic features based on high frequency aspects of images appear to lack the repeatability on PET to justify further study.

The diagnostic value of ictal SPECT-A retrospective, semiquantitative monocenter study.

OBJECTIVE: Ictal single photon emission computed tomography (SPECT) can be used as an advanced diagnostic modality to detect the seizure onset zone in the presurgical evaluation of people with epilepsy. In addition to visual assessment (VSA) of ictal and interictal SPECT images, postprocessing methods such as ictal-interictal SPECT analysis using SPM (ISAS) can visualize regional ictal blood flow differences. We aimed to evaluate and differentiate the diagnostic value of VSA and ISAS in the Bonn cohort. METHODS: We included 161 people with epilepsy who underwent presurgical evaluation at the University Hospital Bonn between 2008 and 2020 and received ictal and interictal SPECT and ISAS. We retrospectively assigned SPECT findings to one of five categories according to their degree of concordance with the clinical focus hypothesis. RESULTS: Seizure onset zones could be identified more likely on a sublobar concordance level by ISAS than by VSA (31% vs. 19% of cases; OR = 1.88; 95% Cl [1.04, 3.42]; P = 0.03). Both VSA and ISAS more often localized a temporal seizure onset zone than an extratemporal one. Neither VSA nor ISAS findings were predicted by the latency between seizure onset and tracer injection (P = 0.75). In people who underwent successful epilepsy surgery, VSA and ISAS indicated the correct resection site in 54% of individuals, while MRI and EEG showed the correct resection localization in 96% and 33% of individuals, respectively. It was more likely to become seizure-free after epilepsy surgery if ISAS or VSA had been successful. There was no MR-negative case with successful surgery, indicating that ictal SPECT is more useful for confirmation than for localization. SIGNIFICANCE: The results of the most extensive clinical study of ictal SPECT to date allow an assessment of the diagnostic value of this elaborate examination and emphasize the importance of postprocessing routines.