Search

Following on from the 2015 Lancet Oncology Commission on expanding global access to radiotherapy, Radiotherapy and theranostics: a Lancet Oncology Commission was created to assess the access and availability of radiotherapy to date and to address the important issue of access to the promising field of theranostics at a global level. A marked disparity in the availability of radiotherapy machines between high-income countries and low-income and middle-income countries (LMICs) has been identified previously and remains a major problem. The availability of a suitably trained and credentialled workforce has also been highlighted as a major limiting factor to effective implementation of radiotherapy, particularly in LMICs. We investigated initiatives that could mitigate these issues in radiotherapy, such as extended treatment hours, hypofractionation protocols, and new technologies. The broad implementation of hypofractionation techniques compared with conventional radiotherapy in prostate cancer and breast cancer was projected to provide radiotherapy for an additional 2·2 million patients (0·8 million patients with prostate cancer and 1·4 million patients with breast cancer) with existing resources, highlighting the importance of implementing new technologies in LMICs. A global survey undertaken for this Commission revealed that use of radiopharmaceutical therapy-other than 131 I-was highly variable in high-income countries and LMICs, with supply chains, workforces, and regulatory issues affecting access and availability. The capacity for radioisotope production was highlighted as a key issue, and training and credentialling of health professionals involved in theranostics is required to ensure equitable access and availability for patient treatment. New initiatives-such as the International Atomic Energy Agency's Rays of Hope programme-and interest by international development banks in investing in radiotherapy should be supported by health-care systems and governments, and extended to accelerate the momentum generated by recognising global disparities in access to radiotherapy. In this Commission, we propose actions and investments that could enhance access to radiotherapy and theranostics worldwide, particularly in LMICs, to realise health and economic benefits and reduce the burden of cancer by accessing these treatments., Competing Interests: Declaration of interests HH serves (unpaid) on an external advisory board of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, on the International Advisory Board of the University of Vienna, on the Scientific Committee of the German Cancer Research Center (DKFZ), on the Board of Trustees of the DKFZ, and on the advisory board of The Lancet Oncology; is remunerated for serving on the Board of Directors of Ion Beam Applications; receives stock options for serving on the Board of Directors of iCAD; and reports research funding to their institution (Memorial Sloan-Kettering Center Support Grant/Core Grant P30 CA008748) from the National Institutes of Health (NIH)–National Cancer Institute (NCI). AA reports funding to their institution from the National Institute for Health and Care Research (NIHR) and the NIH. GB reports research funding to their institution from the Science and Technology Facilities Council UK and reports travel support from International Council Expert Corps. MD reports research funding to their institution from Science and Technology Facilities Council UK and reports travel support from International Council Expert Corps. TE reports honoraria from the University of Washington and the Japanese Society for Radiation Oncology (JASTRO) and reports receiving travel support to attend meetings from JASTRO, the Turkish Society for Radiation Oncology, and the American Society for Radiation Oncology (ASTRO). SGr reports receiving grants from the NCI; reports consulting fees from Lumonus and the Sustainable Dialogue on Peaceful Uses; and has stock options in Harbinger Health. KH reports research funding to their institution from Novartis and Sofie Biosciences; reports consulting fees from Advanced Accelerator Applications, Amgen, AstraZeneca, Bain Capital, Bayer, Boston Scientific, Convergent, Curiun, Debiopharm, EcoR1, Fusion, GE Healthcare, Immedica, Isotopen Technologien Munchen, Janssen, Merck, Molecular Partners, Nvision, POINT Biopharma, Pfizer, Radiopharm Theranostics, Telix, Theragnostics, and Ymabs; reports honoraria for lectures from PeerVoice; serves on paid advisory boards for Fusion and GE Healthcare; reports travel support from Janssen; and has stock options from Sofie Biosciences, Pharma15, Nvision, Convergent, Aktis Oncology, and AdvanCell. MSH reports research funding to their institution from the Prostate Cancer Foundation, the US Department of Defence, Movember, and the Peter MacCallum Foundation; reports clinical trial funding to their institution from Bayer and Isotopia; reports clinical trial support to their institution from the Australian Nuclear Science and Technology Organisation; reports consulting fees from Merck Sharp & Dohme and Novartis; reports speaker fees from Janssen and AstraZeneca; reports fees to their institution for serving on the advisory board on Novartis; reports unremunerated participation in the Scientific Committee at the Australian Friends of Sheba; and is supported by a National Health and Medical Research Council (NHMRC) Investigator grant. DJ reports royalties from Elekta Oncology System, Precision X-ray System, and Modus Medical; reports license of technology to iRT; reports board membership on Break Through Cancer; reports being an advisor to ACS BrightEdge; and is a founder and stockholder in Nanovista. JK reports participation on a data safety monitoring board and advisory board from Novartis (personal fees) and reports lecture honoraria from Monrol. JSL reports research support from Clarity Pharmaceuticals and Avid Radiopharmaceuticals; has acted as an adviser of Alpha-9 Theranostics, Clarity Pharmaceuticals, Earli, Evergreen Theragnostics, Suba Therapeutics, Inhibrx, Precirix, Solve, Goldman Sachs, TPG Capital, Curie Therapeutics, NextTech Invest, and Telix Pharmaceuticals; is secretary/treasurer of the Society of Nuclear Medicine and Molecular Imaging (SNMMI); holds equity in Curie Therapeutics, Summit Biomedical Imaging, Telix Pharmaceuticals, and Evergreen Theragnostics; and is supported by NIH R35 CA232130. YL reports funding to their institution for the European Society for Radiotherapy and Oncology (ESTRO) Chair on Health Economics in Radiation Oncology (HERO)–Value-Based Radiation Oncology, for a proton beam project from the Research Foundation Flanders (FWO)–Applied Biomedical Research with a Primary Finality, and for the ARCHERY trial; reports unpaid positions on advisory boards for the HALT trial and PROSECCA trial; is a member of the ESTRO Scientific Council and the Belgian Board of Oncology; is co-chair of the ESTRO-HERO project; and is principal investigator of the E2-Radiate trial, a joint project of ESTRO, and the European Organisation for Research and Treatment of Cancer (EORTC). JRP reports being an unpaid chair of the American Association of Physicists in Medicine (AAPM) International Council. AAR received consulting fees from Novartis; received honoraria for lectures from the European Society for Medical Oncology, Sociedade Brasileira de Mastologia, and Instituto Oncoclinicas; received financial support for attending meetings from ASTRO, Congresso Gramado, and Congresso Oncolinicas; reports an unpaid leadership position at the Sociedade Brasileira de Radioterapia; and has stock and stock options in Grupo Oncoclinicas. MMS reports research funding to their institution from Aktis, Point Biopharma, and Telix Pharmaceuticals; reports speaker honoraria from Novartis, Ion Beam Applications, and Johnson and Johnson; and holds positions in the Africa Health Research Institute and Adcock. VV holds positions as editor of the Journal of Clinical Oncology/Global Oncology and Translational Oncology and is a member of the board for City Cancer Challenge. RLW reports research funding to their institution from Siemens Healthineers, White Rabbit AI, Fusion, Perspective Therapeutics, Rayze, and Bayer; provides consulting services to Voximetry, Molecular Targeting Technologies (MTT), Perspective, Siemens, Abdera, and Seno; reports speaker payment from Hamad Health Qatar; reports travel support from Rayze and Hamad Health Qatar; has stock options in Voximetry and MTT; is a stockholder in Clarity Pharmaceuticals; participates on advisory boards for Perspective and Fusion; is a member of the SNMMI Mars Shot Board; and was a past president of SNMMI. JSY reports funding to their institution from the NIH, the IVY Foundation, and the Falk Research Medical Trust; reports honoraria from the University of Maryland and the Dana Farber/Harvard Cancer Center; and holds an unpaid position in the Clinical Advisory Council at the American Brain Tumor Association. AMS reports trial funding to their institution from EMD Serono, ITM, Telix Pharmaceuticals, AVID Radiopharmaceuticals, Fusion Pharmaceuticals, and Cyclotek; reports research funding to their institution from Medimmune, Antengene, Humanigen, and Telix Pharmaceuticals; is on advisory boards of Imagion and ImmunOs; reports unpaid board membership of the Australian and New Zealand Society of Nuclear Medicine and the World Federation of Nuclear Medicine and Biology; and is supported by a NHMRC Investigator grant (number 1177837). All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Background: FHIR (Fast Healthcare Interoperability Resources) has been proposed to enable health data interoperability. So far, its applicability has been demonstrated for selected research projects with limited data., Objective: This study aimed to design and implement a conceptual medical intelligence framework to leverage real-world care data for clinical decision-making., Methods: A Python package for the use of multimodal FHIR data (FHIRPACK [FHIR Python Analysis Conversion Kit]) was developed and pioneered in 5 real-world clinical use cases, that is, myocardial infarction, stroke, diabetes, sepsis, and prostate cancer. Patients were identified based on the ICD-10 (International Classification of Diseases, Tenth Revision) codes, and outcomes were derived from laboratory tests, prescriptions, procedures, and diagnostic reports. Results were provided as browser-based dashboards., Results: For 2022, a total of 1,302,988 patient encounters were analyzed. (1) Myocardial infarction: in 72.7% (261/359) of cases, medication regimens fulfilled guideline recommendations. (2) Stroke: out of 1277 patients, 165 received thrombolysis and 108 thrombectomy. (3) Diabetes: in 443,866 serum glucose and 16,180 glycated hemoglobin A 1c measurements from 35,494 unique patients, the prevalence of dysglycemic findings was 39% (13,887/35,494). Among those with dysglycemia, diagnosis was coded in 44.2% (6138/13,887) of the patients. (4) Sepsis: In 1803 patients, Staphylococcus epidermidis was the primarily isolated pathogen (773/2672, 28.9%) and piperacillin and tazobactam was the primarily prescribed antibiotic (593/1593, 37.2%). (5) PC: out of 54, three patients who received radical prostatectomy were identified as cases with prostate-specific antigen persistence or biochemical recurrence., Conclusions: Leveraging FHIR data through large-scale analytics can enhance health care quality and improve patient outcomes across 5 clinical specialties. We identified (1) patients with sepsis requiring less broad antibiotic therapy, (2) patients with myocardial infarction who could benefit from statin and antiplatelet therapy, (3) patients who had a stroke with longer than recommended times to intervention, (4) patients with hyperglycemia who could benefit from specialist referral, and (5) patients with PC with early increases in cancer markers., (©Alexander Brehmer, Christopher Martin Sauer, Jayson Salazar Rodríguez, Kelsey Herrmann, Moon Kim, Julius Keyl, Fin Hendrik Bahnsen, Benedikt Frank, Martin Köhrmann, Tienush Rassaf, Amir-Abbas Mahabadi, Boris Hadaschik, Christopher Darr, Ken Herrmann, Susanne Tan, Jan Buer, Thorsten Brenner, Hans Christian Reinhardt, Felix Nensa, Michael Gertz, Jan Egger, Jens Kleesiek. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 31.10.2024.)

Introduction and Aim: Radioligand therapy (RLT) with 177 Lu-labelled prostate specific membrane antigen ([ 177 Lu]Lu-PSMA-X, referring with "PSMA-X" to a generic PSMA chemical compound) inhibitors has emerged as a viable treatment option in metastatic castration resistant prostate cancer patients having previously progressed on taxane and androgen receptor inhibitors. The aim of this study was to perform a systematic review and meta-analysis to assess the therapeutic efficacy of [ 177 Lu]Lu-PSMA-X compared to taxane chemotherapy in taxane-chemo-naïve patients with metastatic castration-resistant prostate cancer., Materials and Methods: Searches in several bibliographic databases were made using relevant key words, and articles published up to March 2024 were included. The endpoints included prostate specific antigen (PSA) response rate (RR), progression-free survival, and overall survival. Individual patient data were pooled when feasible. PSA50 was defined as the median proportion of patients achieving at least a 50% decline in serum PSA from baseline. A meta-analysis of the PSA50 response rate (proportion meta-analysis) was performed, generating pooled estimates and 95% confidence intervals (95% CI)., Results: From the initially selected 8,414 studies published between 2019 and 2023, 24 were included in the [ 177 Lu]Lu-PSMA-X treated group and 17 in the taxane treated group. Our findings show that [ 177 Lu]Lu-PSMA-X RLT yielded comparable PSA50 responses in taxane-naïve patients versus those receiving taxane chemotherapy, despite considerable study heterogeneity. Notably, the taxane-naïve group had more extensive pretreatment., Conclusions: This meta-analysis combines the largest cohorts of taxane-naïve mCRPC patients treated with [ 177 Lu]Lu-PSMA-X RLT and taxane-treated mCRPC. It underscores similar PSA50 response rates in both groups, suggesting a potential role for [ 177 Lu]Lu-PSMA-X RLT in taxane-naïve patients who cannot or choose not to undergo chemotherapy., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: FAPI-PET/CT exhibits high tumor uptake and low background accumulation, enabling high-sensitivity tumor detection. We compared the diagnostic performance of 68  Ga-FAPI-46 PET/CT plus contrast-enhanced CT (CE-CT), 18 F-FDG PET/CT plus CE-CT, and standalone CE-CT in patients with various malignancies., Methods: 232 patients underwent 68  Ga-FAPI-46 PET/CT, 18 F-FDG PET/CT, and CE-CT each within 4 weeks. Detection rates were assessed by a blinded reader, with ≥ 2 weeks between scans of the same patient to avoid recall bias. A sub-analysis of diagnostic performance was performed for 490 histopathologically validated lesions. Detection rates were compared using McNemar's test., Results: Lesion-based detection rates in 68  Ga-FAPI-46 PET/CT plus CE-CT, 18 F-FDG PET/CT plus CE-CT, and CE-CT alone were 91.2% (1540/1688), 82.5% (1393/1688) and 60.2% (1016/1688). The detection rates were significantly higher for 68  Ga-FAPI-46 PET/CT plus CE-CT than for 18 F-FDG PET/CT plus CE-CT (p < 0.02 for primary lesions and p < 0.001 for total, abdominopelvic nodal, liver and other visceral lesions) and CE-CT (p < 0.0001 for total, primary, cervicothoracic nodal, abdominopelvic nodal, liver, other visceral, and bone lesions). In the sub-analysis, sensitivity, specificity, positive and negative predictive value, and accuracy were 61.3%, 96.7%, 81.4%, 91.4% and 90.0% for 68  Ga-FAPI-46 PET/CT plus CE-CT, 57.0%, 95.7%, 75.7%, 90.5% and 88.4% for 18 F-FDG PET/CT plus CE-CT, and 51.6%, 97.2%, 81.4%, 89.6% and 88.6% for CECT, respectively., Conclusions: 68  Ga-FAPI-46 PET/CT plus CE-CT demonstrates a higher tumor detection rate than 18 F-FDG PET/CT plus CE-CT and CE-CT in a diverse spectrum of malignancies, especially for primary, abdominopelvic nodal, liver, and other visceral lesions. Further studies on which entities draw particular benefit from 68  Ga-FAPI-46 PET/CT are warranted to aid appropriate diagnostic workup., Trial Registration: A total of N = 232 patients were analyzed. Of these, N = 50 patients were included in a prospective interventional trial (NCT05160051), and N = 175 in a prospective observational trial (NCT04571086) for correlation and clinical follow-up of PET findings; N = 7 patients were analyzed retrospectively., (© 2024. The Author(s) under exclusive licence to The Japanese Society of Nuclear Medicine.)

Background and Objective: This review aims to provide an overview of novel diagnostic and therapeutic radiopharmaceuticals tested recently or used currently in genitourinary cancers within prospective phase 1-2 clinical trials, summarizing progresses and future directions., Methods: A systematic search was conducted using the PubMed/MEDLINE and ClinicalTrials.gov databases for original prospective research studies following the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines., Key Findings and Limitations: Forty-six papers were systematically reviewed; 74 ongoing clinical trials were identified. The results of 27 novel radiopharmaceuticals (ie, not approved by the Food and Drug Administration/European Medicines Agency and not listed in the Pharmacopeia) prospectively investigated in genitourinary cancers, mostly prostate, for diagnostic, theranostic, or therapeutic purposes (21, one, and five of the 27 radiopharmaceuticals, respectively) over the past 5 yr were presented. Most were prostate-specific membrane antigen-targeting agents (17/27); other targets included gastrin-releasing peptide receptor, carbonic anhydrase IX, Cu, six transmembrane epithelial antigen of the prostate 1, tumor-associated glycoprotein 42, and urokinase-type plasminogen activator receptor. Ongoing research confirms the same trend. Fibroblast activation protein inhibitor, PD-L1, CD8, nectin-4, and HER2 are other targets under investigation. Among the 22 ongoing therapeutic trials (out of the 74 ongoing clinical trials), targeted alpha therapy is being explored in 12, and five are evaluating combinations of radioligand therapy with other treatments. We confirmed the safety of radiopharmaceuticals (regardless of the diagnostic/therapeutic purpose) and showed promising results in terms of diagnostic accuracy and therapeutic efficacy in genitourinary cancers., Conclusions and Clinical Implications: There continues to be expansion in radiopharmaceutical approaches to genitourinary cancers, reflecting a strong emphasis on improving tumor detection and treatment, which will likely impact future management across the disease spectrum, with the potential for improved patient care and outcomes., (Copyright © 2024 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: [ 177 Lu]Lu-PSMA-617 ( 177 Lu-PSMA-617) plus protocol-permitted standard of care (SOC) prolonged overall survival (OS) and radiographic progression-free survival (rPFS) versus SOC in patients with prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer (mCRPC) in the phase 3 VISION study, in addition to beneficial effects on symptomatic skeletal events (SSEs) and health-related quality of life (HRQOL)., Methods: Post hoc analyses used the full analysis set from the VISION study (N = 831) overall and by randomized treatment arm ( 177 Lu-PSMA-617 plus SOC, n = 551; SOC, n = 280). Correlations were determined between OS and rPFS and between rPFS or OS and time to SSE or to worsening HRQOL (Functional Assessment of Cancer Therapy-Prostate [FACT-P] and 5-level EQ-5D [EQ-5D-5L]). Correlation analyses used an iterative multiple imputation copula-based approach (correlation coefficients [rho] of <0.3 were defined as weak, ≥0.3 and <0.5 as mild, ≥0.5 and <0.7 as moderate, and ≥0.7 as strong)., Results: In the overall population, rPFS correlated strongly with OS (rho, ≥0.7). Correlations between rPFS or OS and time to SSE without death were weak or mild. Time to worsening in the FACT-P total score and emotional and physical well-being domains correlated mildly or moderately with rPFS and moderately with OS. Correlation coefficients for time-to-worsening EQ-5D-5L scores were mild to moderate for both rPFS and OS. Correlation coefficients were similar between treatment arms., Conclusions: In this analysis of the VISION study, rPFS correlated strongly with OS but not with time to SSE or worsening HRQOL. These findings require further investigation., (© 2024 The Author(s). Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Background and Objective: Innovations have improved outcomes in advanced prostate cancer (PC). Nonetheless, we continue to lack high-level evidence on a variety of topics that greatly impact daily practice. The 2024 Advanced Prostate Cancer Consensus Conference (APCCC) surveyed experts on key questions in clinical management in order to supplement evidence-based guidelines. Here we present voting results for questions from APCCC 2024., Methods: Before the conference, a panel of 120 international PC experts used a modified Delphi process to develop 183 multiple-choice consensus questions on eight different topics. Before the conference, these questions were administered via a web-based survey to the voting panel members ("panellists")., Key Findings and Limitations: Consensus was a priori defined as ≥75% agreement, with strong consensus defined as ≥90% agreement. The voting results show varying degrees of consensus, as discussed in this article and detailed in the Supplementary material. These findings do not include a formal literature review or meta-analysis., Conclusions and Clinical Implications: The voting results can help physicians and patients navigate controversial areas of clinical management for which high-level evidence is scant or conflicting. The findings can also help funders and policymakers in prioritising areas for future research. Diagnostic and treatment decisions should always be individualised on the basis of patient and cancer characteristics, and should incorporate current and emerging clinical evidence, guidelines, and logistic and economic factors. Enrolment in clinical trials is always strongly encouraged. Importantly, APCCC 2024 once again identified important gaps (areas of nonconsensus) that merit evaluation in specifically designed trials., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Our rationale was to investigate whether 18 F-FDG PET/MRI in addition to (guideline-recommended) conventional staging leads to changes in therapeutic management in patients with newly diagnosed breast cancer and compare the diagnostic accuracy of 18 F-FDG PET/MRI with that of conventional staging for determining the Union for International Cancer Control (UICC) stage. Methods: In this prospective, double-center study, 208 women with newly diagnosed, therapy-naïve invasive breast cancer were enrolled in accordance with the inclusion criteria. All patients underwent guideline-recommended conventional staging and whole-body 18 F-FDG PET/MRI with a dedicated breast examination. A multidisciplinary tumor board served to determine 2 different therapy recommendations for each patient, one based on conventional staging alone and another based on combined assessment of conventional staging and 18 F-FDG PET/MRI examinations. Major changes in therapy recommendations and differences between the conventional staging algorithm and 18 F-FDG PET/MRI for determining the correct UICC stage were reported and evaluated. Results: Major changes in therapeutic management based on combined assessment of conventional staging and 18 F-FDG PET/MRI were detected in 5 of 208 patients, amounting to changes in therapeutic management in 2.4% (95% CI, 0.78%-5.2%) of the study population. In determining the UICC stage, the guideline-based staging algorithm and 18 F-FDG PET/MRI were concordant in 135 of 208 (64.9%; 95% CI, 58%-71.4%) patients. The conventional guideline algorithm correctly determined the UICC stage in 130 of 208 (62.5%; 95% CI, 55.5%-69.1%) patients, and 18 F-FDG PET/MRI correctly determined the UICC stage in 170 of 208 (81.9%; 95% CI, 75.8%-86.7%) patients. Conclusion: Despite the diagnostic superiority of 18 F-FDG PET/MRI over conventional staging in determining the correct UICC stage, the current (guideline-recommended) conventional staging algorithm is sufficient for adequate therapeutic management of patients with newly diagnosed breast cancer, and 18 F-FDG PET/MRI does not have an impact on patient management., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

Background: [ 177 Lu]Lu-PSMA-617 ( 177 Lu-PSMA-617) prolonged life in patients with metastatic castration-resistant prostate cancer (mCRPC) in VISION (NCT03511664). However, distinguishing between patients likely and unlikely to respond remains a clinical challenge. We present the first multivariable models of outcomes with 177 Lu-PSMA-617 built using data from VISION, a large prospective phase 3 clinical trial powered for overall survival., Methods: Adults with progressive post androgen receptor pathway inhibitor and taxane prostate-specific membrane antigen (PSMA)-positive mCRPC received 177 Lu-PSMA-617 plus protocol-permitted standard of care (SoC) or SoC alone. In this post hoc analysis, multivariable Cox proportional hazards models of overall survival (OS) and radiographic progression-free survival (rPFS), and a logistic regression model of prostate-specific antigen response (≥50% decline; PSA50) were constructed and evaluated using C-index or receiver operating characteristic (ROC) analyses with bootstrapping validation. Nomograms were constructed for visualisation., Findings: Patients were randomised between June 2018 and October 2019. Data from all 551 patients in the 177 Lu-PSMA-617 arm were analysed in multivariable modelling. The OS nomogram (C-index, 0.73; 95% confidence interval [CI], 0.70-0.76) included whole-body maximum standardised uptake value (SUV max ), time since diagnosis, opioid analgesic use, aspartate aminotransferase, haemoglobin, lymphocyte count, presence of PSMA-positive lesions in lymph nodes, lactate dehydrogenase (LDH), alkaline phosphatase (ALP), and neutrophil count. The rPFS nomogram (C-index, 0.68; 0.65-0.72) included SUV max , time since diagnosis, opioid analgesic use, lymphocyte count, presence of liver metastases by computed tomography, LDH, and ALP. The PSA50 nomogram (area under ROC curve, 0.72; 95% CI, 0.68-0.77) included SUV max , lymphocyte count and ALP. Performances of the OS and rPFS models were maintained when they were reconstructed excluding SUV max ., Interpretation: These models of outcomes with 177 Lu-PSMA-617 are the first built using prospective phase 3 data. They show that a combination of pretreatment laboratory, clinical, and imaging parameters, reflecting both patient and tumour status, influences outcomes. These models are important for aiding treatment selection, patient management, and clinical trial design., Funding: Novartis., Competing Interests: KH reports receiving grants or contracts from Boston Scientific, Janssen, and Novartis; consulting fees from Amgen, AstraZeneca, Bain Capital, Bayer, Boston Scientific, Convergent, Curium, Debiopharm, EcoR1, Fusion, GE Healthcare, Immedica, Isotopen Technologien München, Janssen, Merck, Molecular Partners, Novartis, NVision, POINT Biopharma, Pfizer, Radiopharm Theranostics, Rhine Pharma, Siemens Healthineers, Sofie Biosciences, Telix, Theragnostics, and ymabs; and stock or other ownership in AdvanCell, Aktis Oncology, Convergent, NVision, Pharma 15, and Sofie Biosciences. JSdB reports receiving grants or contracts from Amgen, Astellas, AstraZeneca, Bayer, Bioxcel Therapeutics, Crescendo, Daiichi-Sankyo, Endocyte, Genentech/Roche, GlaxoSmithKline, ImCheck Therapeutics, Janssen, Merck Serono, Merck Sharp & Dohme, Novartis, Pfizer, and Sanofi Aventis; consulting or advisory fees from Astellas, AstraZeneca, Bayer, Daiichi-Sankyo, Genentech/Roche, GlaxoSmithKline, Janssen, Merck Serono, Merck Sharp & Dohme, Orion, Pfizer, Sanofi Aventis, and Taiho; payment or honorarium from Astellas, AstraZeneca, Bayer, Cellcentric, Crecendo, Daiichi, Genentech, Genmab, GlaxoSmithKline, Janssen, Merck Serono, Mycrix, MSD, Orion, Pfizer, Sanofi Aventis, and Taiho; being an inventor on patent 8,822,438; participating on a data safety monitoring or advisory board for Amgen, AstraZeneca, Bayer, Bioxcel Therapeutics, Crescendo, Daiichi-Sankyo, Endocyte, Genentech/Roche, GlaxoSmithKline, ImCheck Therapeutics, Janssen, Merck Serono, Merck Sharp & Dohme, Novartis, Oncternal, Pfizer, and Sanofi Aventis; and receiving institutional royalties or licenses related to abiraterone, PARP inhibitor, and PI3K/AKT. OS reports receiving support for the present manuscript from Novartis; institutional grants or contracts from Amgen, AstraZeneca, Bayer, Endocyte, Invitae, Janssen, Lantheus, Merck, Novartis, Progenics, and Tenebio; consulting fees from ARTBIO, AstraZeneca, Bayer, Blue Earth Diagnostics, Clarity Pharmaceuticals, Fusion, Isotopen Technologien Muenchen, Janssen, Merck, Myovant, Myriad, Noria Therapeutics, NorthStar, Novartis, Pfizer, POINT Biopharma, Sanofi, Telix, and Tenebio; travel and accommodation expenses from Lantheus, NorthStar, and Novartis; participation on a data safety monitoring or advisory board for AstraZeneca, Merck, and Pfizer; and stock or stock options in ARTBIO, Clarity Pharmaceuticals, Convergent, Fusion, Lilly, Pfizer, Ratio, and Telix. KNC reports receiving grants or contracts from AstraZeneca, Bayer, Janssen, Merck, Novartis, Pfizer, POINT Biopharma, and Roche; and consulting fees from Astellas, AstraZeneca, Bayer, Janssen, Merck, Novartis, Pfizer, POINT Biopharma, and Roche. BJK reports receiving consultant or advisory fees from Bayer, Isotope Technologies Munich, and Novartis; and research funding from Novartis. KR reports receiving consultant fees from ABX, ABX-CRO, Amgen, Bayer Healthcare, Janssen Cilag, Novartis, and Sirtex; and lecture payments from AstraZeneca, Bayer Healthcare, Novartis, and Siemens Healthcare. STT reports receiving institutional fees from AbbVie, Ambrx, Amgen, Astellas, AstraZeneca, Aveo, Bayer, Bristol Myers Squibb, Clarity, Clovis, Endocyte, Genentech, Gilead, Inovio, Janssen, Karyopharm, Medivation, Merck, Newlink, Novartis, POINT Biopharma, Rexahn, Sanofi, and Seattle Genetics; and consultant fees from AbbVie, Aikido Pharma, Ambrx, Amgen, Astellas, Bayer, Blue Earth, Clarity Pharma, Clovis, Convergent Therapeutics, Daiichi Sankyo, Eisai, EMD Serono, Genentech, Genomic Health, Janssen, Medivation, Merck, Myovant, Novartis, Pfizer, POINT Biopharma, Regeneron, Sanofi, Seattle Genetics, Telix, Tolmar, and TransThera. JC reports stock or other ownership interest in Sofie Biosciences, Inc., and Trethera; acting as an uncompensated founder for Trethera; and an uncompensated adviser for Amgen, Atkis Oncology, Jubilant Radiopharma, Novartis, POINT Biopharma, and RayzeBio. GEH reports receiving consultant fees from Bayer HealthCare, Boston Scientific Corporation, NorthStar Medical Radioisotopes, Novartis, and Terumo; and stock ownership in Johnson and Johnson. CCW reports employment and stock ownership with Novartis. ZZ reports previous employment and current stock ownership with Novartis. CW reports employment and stock ownership with Novartis. OM reports employment and stock ownership with Novartis. MJM reports receiving consulting or advisory fees from Amgen, AstraZeneca, Blue Earth Diagnostics, Clarity Pharmaceuticals, Convergent Therapeutics, Daiichi, ITM Isotope Technologies Munich, Lantheus Medical Imaging, Pfizer, POINT Biopharma, Progenics, Telix Pharmaceuticals, and Z-Alpha; stock and other ownership in Doximity; travel, accommodations, and expenses from APCCC, AstraZeneca, and Memorial Sloan-Kettering Cancer Center; institutional research funding from Astellas Pharma, Bayer, Celgene, Corcept Therapeutics, Janssen, Novartis, Progenics, and Roche/Genentech; patents pending with Novartis; and royalties from Telix. KF reports receiving institutional honorarium or payments to Gustave Roussy Institute from Astellas, AstraZeneca, Bayer, Janssen, MSD, Novartis, and Sanofi; institutional participation on data safety monitoring or advisory boards for Amgen, Astellas, AstraZeneca, Bayer, Clovis, Daiichi Sankyo, Janssen, MSD, Novartis, Pfizer, and Sanofi; and personal participation on a data safety monitoring or advisory board for Arvinas, CureVac, Macrogenics, Orion. No other potential conflict of interest relevant to this article was reported., (© 2024 The Authors.)

This study evaluates the diagnostic utility of PET/MRI for primary, locoregional, and nodal head and neck squamous cell carcinoma (HNSCC) through systematic review and metaanalysis. Methods: A systematic search was conducted using PubMed and Scopus to identify studies on the diagnostic accuracy of PET/MRI for HNSCC. The search included specific terms and excluded nonhybrid PET/MRI studies, and those with a sample size of fewer than 10 patients were excluded. Results: In total, 15 studies encompassing 638 patients were found addressing the diagnostic test accuracy for PET/MRI within the chosen subject domain. Squamous cell carcinoma of the nasopharynx was the most observed HNSCC subtype ( n = 198). The metaanalysis included 12 studies, with pooled sensitivity and specificity values of 93% and 95% per patient for primary disease evaluation, 93% and 96% for locoregional evaluation, and 89% and 98% per lesion for nodal disease detection, respectively. An examination of a subset of studies comparing PET/MRI against PET/CT or MRI alone for evaluating nodal and locoregional HNSCC found that PET/MRI may offer slightly higher accuracy than other modalities. However, this difference was not statistically significant. Conclusion: PET/MRI has excellent potential for identifying primary, locoregional, and nodal HNSCC., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

Purpose: To provide practice guideline/procedure standards for diagnostics and therapy (theranostics) of meningiomas using radiolabeled somatostatin receptor (SSTR) ligands., Methods: This joint practice guideline/procedure standard was collaboratively developed by the European Association of Nuclear Medicine (EANM), the Society of Nuclear Medicine and Molecular Imaging (SNMMI), the European Association of Neurooncology (EANO), and the PET task force of the Response Assessment in Neurooncology Working Group (PET/RANO)., Results: Positron emission tomography (PET) using somatostatin receptor (SSTR) ligands can detect meningioma tissue with high sensitivity and specificity and may provide clinically relevant information beyond that obtained from structural magnetic resonance imaging (MRI) or computed tomography (CT) imaging alone. SSTR-directed PET imaging can be particularly useful for differential diagnosis, delineation of meningioma extent, detection of osseous involvement, and the differentiation between posttherapeutic scar tissue and tumour recurrence. Moreover, SSTR-peptide receptor radionuclide therapy (PRRT) is an emerging investigational treatment approach for meningioma., Conclusion: These practice guidelines will define procedure standards for the application of PET imaging in patients with meningiomas and related SSTR-targeted PRRTs in routine practice and clinical trials and will help to harmonize data acquisition and interpretation across centers, facilitate comparability of studies, and to collect larger databases. The current document provides additional information to the evidence-based recommendations from the PET/RANO Working Group regarding the utilization of PET imaging in meningiomas Galldiks (Neuro Oncol. 2017;19(12):1576-87). The information provided should be considered in the context of local conditions and regulations., (© 2024. The Author(s).)

The ecosystem of brain tumors is considered immunosuppressed, but our current knowledge may be incomplete. Here we analyzed clinical cell and tissue specimens derived from patients presenting with glioblastoma or nonmalignant intracranial disease to report that the cranial bone (CB) marrow, in juxtaposition to treatment-naive glioblastoma tumors, harbors active lymphoid populations at the time of initial diagnosis. Clinical and anatomical imaging, single-cell molecular and immune cell profiling and quantification of tumor reactivity identified CD8 + T cell clonotypes in the CB that were also found in the tumor. These were characterized by acute and durable antitumor response rooted in the entire T cell developmental spectrum. In contrast to distal bone marrow, the CB niche proximal to the tumor showed increased frequencies of tumor-reactive CD8 + effector types expressing the lymphoid egress marker S1PR1. In line with this, cranial enhancement of CXCR4 radiolabel may serve as a surrogate marker indicating focal association with improved progression-free survival. The data of this study advocate preservation and further exploitation of these cranioencephalic units for the clinical care of glioblastoma., (© 2024. The Author(s).)

Background: Both cabazitaxel and lutetium-177 prostate-specific membrane antigen (Lu-PSMA) improve survival in metastatic castration-resistant prostate cancer (mCRPC) after an androgen receptor pathway inhibitor and docetaxel, but there are limited data regarding Lu-PSMA activity after cabazitaxel., Objective: To assess the activity of Lu-PSMA and determinants of outcomes after cabazitaxel in mCRPC., Design, Setting, and Participants: A retrospective analysis was conducted of consecutive mCRPC patients from eight European centers treated with Lu-PSMA after cabazitaxel., Intervention: Lu-PSMA every 6-8 wk at a dose of 6-7.6 GBq., Outcome Measurements and Statistical Analysis: The primary endpoint was radiographic progression-free survival (rPFS). The secondary endpoints included time to prostate-specific antigen (PSA) progression (TTPSA), overall survival (OS), PSA decline, objective response rate (ORR), clinical benefit, and safety., Results and Limitations: Of 126 patients, 68% had International Society of Urological Pathology (ISUP) grade 4-5 disease, 21% had visceral metastases, and 7% had lymph node disease only. DNA damage repair (DDR) alterations were detected in 11/50 (22%) patients with available testing. Patients received a median number of 3 Lu-PSMA cycles (interquartile range 2-4). With a median follow-up of 12.0 mo, the median rPFS was 4.4 mo (95% confidence interval [CI] 3.2-5.4), TTPSA 3.5 mo (95% CI 3.0-4.6), and OS 8.9 mo (95% CI 6.5-12.7). The ORR was 35%, and 55 patients (44%) experienced a PSA decline of ≥50%. The time to castration resistance of <12 mo was associated with shorter rPFS (p = 0.01). A similar trend was observed for ISUP grade 4-5 (p = 0.08), and baseline positron-emission tomography parameters including PSMA mean standardized uptake value (SUV) and maximum SUV (respectively, p = 0.06 and 0.05). The duration of previous cabazitaxel or DDR status did not impact outcomes. Patients experiencing a PSA decline of ≥ 50% on therapy demonstrated longer rPFS, TTPSA, and OS (all p < 0.0001). Limitations include retrospective data collection and investigator-based rPFS assessment., Conclusions: Lu-PSMA demonstrated a substantial PSA decline but limited rPFS after cabazitaxel in a real-life setting. Adverse baseline characteristics, baseline positron-emission tomography parameters, and quality of PSA response may help identify patients less likely to benefit from Lu-PSMA., Patient Summary: Lutetium-177 prostate-specific membrane antigen (Lu-PSMA) improved outcomes in patients with castration-resistant prostate cancer, but there are limited data about its activity after cabazitaxel, a chemotherapy that is also the standard of care in this setting. We conducted a study across eight European centers and showed substantial responses on Lu-PSMA after cabazitaxel, although activity was short lived in a heavily pretreated population. Our findings prompt for real-life evaluation of Lu-PSMA in earlier settings to define the best therapeutic sequence., (Copyright © 2024 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: [ 177 Lu]Lu-PSMA-617 ( 177 Lu-PSMA-617) prolongs radiographic progression-free survival and overall survival in patients with metastatic castration-resistant prostate cancer previously treated with androgen receptor pathway inhibitor (ARPI) and taxane therapy. We aimed to investigate the efficacy of 177 Lu-PSMA-617 in patients with taxane-naive metastatic castration-resistant prostate cancer., Methods: In this phase 3, randomised, controlled trial conducted at 74 sites across Europe and North America, taxane-naive patients with prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer who had progressed once on a previous ARPI were randomly allocated (1:1) to open-label, intravenous 177 Lu-PSMA-617 at a dosage of 7·4 GBq (200 mCi) ± 10% once every 6 weeks for six cycles, or a change of ARPI (to abiraterone or enzalutamide, administered orally on a continuous basis per product labelling). Crossover from ARPI change to 177 Lu-PSMA-617 was allowed after centrally confirmed radiographic progression. The primary endpoint was radiographic progression-free survival, defined as the time from randomisation until radiographic progression or death, assessed in the intention-to-treat population. Safety was a secondary endpoint. This study is registered with ClinicalTrials.gov (NCT04689828) and is ongoing. In this primary report of the study, we present primary (first data cutoff) and updated (third data cutoff) analyses of radiographic progression-free survival; all other data are based on the third data cutoff., Findings: Overall, of the 585 patients screened, 468 met all eligibility criteria and were randomly allocated between June 15, 2021 and Oct 7, 2022 to receive 177 Lu-PSMA-617 (234 [50%] patients) or ARPI change (234 [50%]). Baseline characteristics were mostly similar between groups; median number of 177 Lu-PSMA-617 cycles was 6·0 (IQR 4·0-6·0). Of patients assigned to ARPI change, 134 (57%) crossed over to receive 177 Lu-PSMA-617. In the primary analysis (median time from randomisation to first data cutoff 7·26 months [IQR 3·38-10·55]), the median radiographic progression-free survival was 9·30 months (95% CI 6·77-not estimable) in the 177 Lu-PSMA-617 group versus 5·55 months (4·04-5·95) in the ARPI change group (hazard ratio [HR] 0·41 [95% CI 0·29-0·56]; p<0·0001). In the updated analysis at time of the third data cutoff (median time from randomisation to third data cutoff 24·11 months [IQR 20·24-27·40]), median radiographic progression-free survival was 11·60 months (95% CI 9·30-14·19) in the 177 Lu-PSMA-617 group versus 5·59 months (4·21-5·95) in the ARPI change group (HR 0·49 [95% CI 0·39-0·61]). The incidence of grade 3-5 adverse events was lower in the 177 Lu-PSMA-617 group (at least one event in 81 [36%] of 227 patients; four [2%] grade 5 [none treatment related]) than the ARPI change group (112 [48%] of 232; five [2%] grade 5 [one treatment related])., Interpretation: 177 Lu-PSMA-617 prolonged radiographic progression-free survival relative to ARPI change, with a favourable safety profile. For patients with PSMA-positive metastatic castration-resistant prostate cancer who are being considered for a change of ARPI after progression on a previous ARPI, 177 Lu-PSMA-617 may be an effective treatment alternative., Funding: Novartis., Competing Interests: Declaration of interests MJM declares receiving consulting or advisory fees from Amgen, AstraZeneca, Blue Earth Diagnostics, Clarity Pharmaceuticals, Convergent Therapeutics, Daiichi, ITM Isotope Technologies Munich, Lantheus Medical Imaging, Pfizer, POINT Biopharma, Progenics, Telix Pharmaceuticals, and Z-Alpha; stock and other ownership in Doximity; travel, accommodations, and expenses from APCCC, AstraZeneca, and Memorial Sloan-Kettering Cancer Center; institutional research funding from Astellas Pharma, Bayer, Celgene, Corcept Therapeutics, Janssen, Novartis, Progenics, and Roche/Genentech; patents pending with Novartis; and royalties from Telix. DC declares receiving payment or honorarium from Astellas, AstraZeneca, Bayer, Bristol Myers Squibb, Clovis, Eisai, Exelisis, GlaxoSmithKline, Ipsen, Janssen, Lilly, MSD, Pfizer, QED Therapeutics, and Roche; travel or other expenses from Astellas, AstraZeneca, Bristol Myers Squibb, GlaxoSmithKline, Ipsen, Janssen, MSD, Novartis, Pfizer, and Roche; participation on a data safety monitoring or advisory board for Astellas, AstraZeneca, Bristol Myers Squibb, GlaxoSmithKline, Ipsen, Janssen, MSD, Novartis, Pfizer, and Roche; and other financial or non-financial interests in Spanish Oncology Genito-Urinary Group Foundation and GUARD Consortium Spanish group. KH declares receiving grants or contracts from Boston Scientific, Janssen, and Novartis; consulting fees from Amgen, AstraZeneca, Bain Capital, Bayer, Boston Scientific, Convergent, Curium, Debiopharm, EcoR1, Fusion, GE Healthcare, Immedica, Isotopen Technologien München, Janssen, Merck, Molecular Partners, Novartis, NVision, POINT Biopharma, Pfizer, Radiopharm Theranostics, Rhine Pharma, Siemens Healthineers, Sofie Biosciences, Telix, Theragnostics, and Y-mAbs Therapeutics; and stock or other ownership in AdvanCell, Aktis Oncology, Convergent, NVision, Pharma 15, and Sofie Biosciences. JSdB declares receiving grants or contracts from Amgen, Astellas, AstraZeneca, Bayer, Bioxcel Therapeutics, Crescendo, Daiichi-Sankyo, Endocyte, Genentech/Roche, GlaxoSmithKline, ImCheck Therapeutics, Janssen, Merck Serono, Merck Sharp & Dohme, Novartis, Pfizer, and Sanofi Aventis; consulting or advisory fees from Astellas, AstraZeneca, Bayer, Daiichi-Sankyo, Genentech/Roche, GlaxoSmithKline, Janssen, Merck Serono, Merck Sharp & Dohme, Orion, Pfizer, Sanofi Aventis, and Taiho; payment or honorarium from Astellas, AstraZeneca, Bayer, Cellcentric, Crecendo, Daiichi, Genentech, Genmab, GlaxoSmithKline, Janssen, Merck Serono, Mycrix, MSD, Orion, Pfizer, Sanofi Aventis, and Taiho; being an inventor on patent 8822438 for a method for treating cancer; participating on a data safety monitoring or advisory board for Amgen, AstraZeneca, Bayer, Bioxcel Therapeutics, Crescendo, Daiichi-Sankyo, Endocyte, Genentech/Roche, GlaxoSmithKline, ImCheck Therapeutics, Janssen, Merck Serono, Merck Sharp & Dohme, Novartis, Oncternal, Pfizer, and Sanofi Aventis; and receiving institutional royalties or licences related to abiraterone, PARP inhibitor, and PI3K/AKT. NDS declares receiving support for the present manuscript from Novartis; consulting fees from AbbVie, Accord, Amgen, Antev, Arquer, Asieris, Astellas, AstraZeneca, Aura Biosciences, Bayer, Bioprotect, Bristol Myers Squibb, Clarity, Cold Genesys, Curium, Dendreon, Exact Imaging, Ferring, Fize Medical, Invitae, Janssen, Lantheus, Lilly, MDXHealth, Merck, Minomic, Myriad, Novartis, PlatformQ, Pfizer, POINT Biopharma, Preview, Promaxo, Propella, Protara, Sanofi Genzyme, Siemens, Speciality Networks, Sumitomo, Telix, Tolmar, and Urogen; having a leadership or fiduciary role for Photocure, and Alessa; and having stock or stock options with Photocure, and Alessa. KNC declares receiving grants or contracts from AstraZeneca, Bayer, Janssen, Merck, Novartis, Pfizer, POINT Biopharma, and Roche; and consulting fees from Astellas, AstraZeneca, Bayer, Janssen, Merck, Novartis, Pfizer, POINT Biopharma, and Roche. MC declares receiving support for the present manuscript from Novartis; consulting fees from Astellas, AstraZeneca, Blue Earth Diagnostics, Boston Scientific, Elekta, Johnson & Johnson, Lantheus, Macrogenics, Pfizer, Profound Medical, Sumitomo, Telix, Tolmar, and Tempus; payment or honorarium from Johnson & Johnson, Pfizer, Profound Medical, and Telix; participating on an advisory board for Telix; and having a leadership or fiduciary role for the Society of Nuclear Medical and Molecular Imaging, and the American Urological Association. JMP declares receiving grants or contracts from BeiGene, Bristol Myers Squibb, Immunocore, Mirati, MSD, and Pfizer; consulting fees from Astellas, AstraZeneca, BeiGene, Bristol Myers Squibb, Clovis, Ideaya, Immunocore, Janssen, MSD, Novartis, and Pfizer; and travel expenses from AstraZeneca, Janssen, and Pfizer. AF declares receiving payment or honorarium from Astellas, AstraZeneca, Bayer, Bristol Myers Squibb, Janssen, Merck, MSD, Novartis, and Pfizer; and travel expenses from Astellas, AstraZeneca, Bayer, Bristol Myers Squibb, Janssen, Merck, SD, Novartis, and Pfizer. XXW declares receiving institutional grants or contracts from Bristol Myers Squibb; consulting fees from Dendreon and Novartis; honorarium from Novartis; travel or other expenses from Novartis; and participating on a data safety monitoring or advisory board for Dendreon and Novartis. HM declares receiving payment or honorarium from Astellas, AstraZeneca, Bayer, Bristol Myers Squibb, Ipsen, Janssen, Merck, MSD, Novartis and Pfizer; travel or other expenses from AstraZeneca, Novartis, Pfizer, Roche; and acting on a scientific steering committee for Curium. GR declares receiving grants or contracts from Bayer; and consulting fees from Astellas, AstraZeneca, Bayer, Janssen, MSD, Novartis, and Pfizer. HŠ declares receiving consulting fees from Astellas, Bayer, Janssen, Novartis, and Pfizer. JN declares receiving contracts or grants from ABX, and Novartis; consulting fees from Curium, and POINT Biopharma; and payment or honorarium from Bayer AG, and Pfizer. BM declares receiving grants or contracts from Astellas, Bayer, Janssen, Roche, and Sanofi; payment or honorarium from Astellas, Bayer, Bristol Myers Squibb, Ipsen, Janssen, Pfizer, Roche, and Sanofi; travel or other expenses from Ipsen, Janssen Pfizer, and Roche; and other financial or non-financial interests in Astellas, Bayer, Bristol Myers Squibb, Ipsen, Janssen, Pfizer, Roche, and Sanofi. ÁM-P declares receiving personal fees from Astellas, AstraZeneca, Bayer, Bristol Myers Squibb, Ipsen, Janssen, Merck, MSD, Novartis, and Pfizer; and non-financial support from Bayer, Ipsen, Merck, and Pfizer. EK, SG, TNK, CW, and KL declare being employed by and receiving restricted stock options from Novartis. OS declares receiving support for the present manuscript from Novartis; institutional grants or contracts from Amgen, AstraZeneca, Bayer, Endocyte, Invitae, Janssen, Lantheus, Merck, Novartis, Progenics, and Tenebio; consulting fees from ARTBIO, AstraZeneca, Bayer, Blue Earth Diagnostics, Clarity Pharmaceuticals, Fusion, Isotopen Technologien Muenchen, Janssen, Merck, Myovant, Myriad, Noria Therapeutics, NorthStar, Novartis, Pfizer, POINT Biopharma, Sanofi, Telix, and Tenebio; travel and accommodation expenses from Lantheus, NorthStar, and Novartis; participation on a data safety monitoring or advisory board for AstraZeneca, Merck, and Pfizer; and stock or stock options in ARTBIO, Clarity Pharmaceuticals, Convergent, Fusion, Lilly, Pfizer, Ratio, and Telix. KF declares receiving institutional honorarium or payments to Gustave Roussy Institute from Astellas, AstraZeneca, Bayer, Janssen, MSD, Novartis, and Sanofi; institutional participation on data safety monitoring or advisory boards for Amgen, Astellas, AstraZeneca, Bayer, Clovis, Daiichi Sankyo, Janssen, MSD, Novartis, Pfizer, and Sanofi; and personal participation on a data safety monitoring or advisory board for Arvinas, CureVac, Macrogenics, Orion., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Purpose: Pre-treatment [ 99m Tc]TcMAA-based radioembolization treatment planning using multicompartment dosimetry involves the definition of the tumor and normal tissue compartments and calculation of the prescribed absorbed doses. The aim was to compare the real-world utility of anatomic and [ 99m Tc]TcMAA-based segmentation of tumor and normal tissue compartments., Materials and Methods: Included patients had HCC treated by glass [ 90 Y]yttrium microspheres, ≥ 1 tumor, ≥ 3 cm diameter and [ 99m Tc]TcMAA SPECT/CT imaging before treatment. Segmentation was performed retrospectively using dedicated dosimetry software: (1) anatomic (diagnostic CT/MRI-based), and (2) [ 99m Tc]TcMAA threshold-based (i.e., using an activity-isocontour threshold). CT/MRI was co-registered with [ 99m Tc]TcMAA SPECT/CT. Logistic regression and Cox regression, respectively, were used to evaluate relationships between total perfused tumor absorbed dose (TAD) and objective response rate (ORR) and overall survival (OS). In a subset-analysis pre- and post-treatment dosimetry were compared using Bland-Altman analysis and Pearson's correlation coefficient., Results: A total of 209 patients were enrolled. Total perfused tumor and normal tissue volumes were larger when using anatomic versus [ 99m Tc]TcMAA threshold segmentation, resulting in lower absorbed doses. mRECIST ORR was higher with increasing total perfused TAD (odds ratio per 100 Gy TAD increase was 1.22 (95% CI: 1.01-1.49; p = 0.044) for anatomic and 1.19 (95% CI: 1.04-1.37; p = 0.012) for [ 99m Tc]TcMAA threshold segmentation. Higher total perfused TAD was associated with improved OS (hazard ratio per 100 Gy TAD increase was 0.826 (95% CI: 0.714-0.954; p = 0.009) and 0.847 (95% CI: 0.765-0.936; p = 0.001) for anatomic and [ 99m Tc]TcMAA threshold segmentation, respectively). For pre- vs. post-treatment dosimetry comparison, the average bias for total perfused TAD was + 11.5 Gy (95% limits of agreement: -227.0 to 250.0) with a strong positive correlation (Pearson's correlation coefficient = 0.80)., Conclusion: Real-world data support [ 99m Tc]TcMAA imaging to estimate absorbed doses prior to treatment of HCC with glass [ 90 Y]yttrium microspheres. Both anatomic and [ 99m Tc]TcMAA threshold methods were suitable for treatment planning., Trial Registration Number: NCT03295006., (© 2024. The Author(s).)

Background and Objective: The prognostic value of declining prostate-specific antigen (PSA) levels is under investigation in patients with prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer (mCRPC) receiving PSMA-targeted radioligand therapy with [ 177 Lu]Lu-PSMA-617 ( 177 Lu-PSMA-617). This post hoc analysis of the phase 3 VISION trial aimed to evaluate associations between PSA decline and clinical and patient-reported outcomes in patients receiving 177 Lu-PSMA-617., Methods: Of 831 enrolled patients with PSMA-positive progressive mCRPC treated previously with one or more androgen receptor pathway inhibitors and one to two taxanes, 551 were randomised to 177 Lu-PSMA-617 plus protocol-permitted standard of care (SoC). Radiographic progression-free survival, overall survival, radiographic objective response rate, and patient-reported health-related quality of life (HRQoL) and pain were analysed in subgroups of patients categorised by the magnitude of unconfirmed PSA decline from baseline., Key Findings and Limitations: Patients randomised to 177 Lu-PSMA-617 with the best PSA declines of ≥0-<50% (96/551 [17%]), ≥50-<90% (152/551 [28%]), and ≥90% (83/551 [15%]) up to and including week 12 had 61%, 72%, and 88% reduced risks of radiographic disease progression or death, and 51%, 70%, and 87% reduced risks of death, respectively, versus those with increased PSA levels (160/551 [29%]), based on hazard ratios in a multivariate Cox proportional hazard model. In patients with greater PSA declines, radiographic responses were more frequent and median time to worsening in HRQoL and pain scores were longer., Conclusions and Clinical Implications: The magnitude of PSA decline was associated with improvement in clinical and patient-reported outcomes in patients with mCRPC receiving 177 Lu-PSMA-617 plus SoC in VISION. PSA decline therefore appears to have a prognostic value during 177 Lu-PSMA-617 treatment in this population., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Prostate-specific membrane antigen (PSMA)-PET was introduced into clinical practice in 2012 and has since transformed the staging of prostate cancer. Prostate Cancer Molecular Imaging Standardized Evaluation (PROMISE) criteria were proposed to standardise PSMA-PET reporting. We aimed to compare the prognostic value of PSMA-PET by PROMISE (PPP) stage with established clinical nomograms in a large prostate cancer dataset with follow-up data for overall survival., Methods: In this multicentre retrospective study, we used data from patients of any age with histologically proven prostate cancer who underwent PSMA-PET at the University Hospitals in Essen, Münster, Freiburg, and Dresden, Germany, between Oct 30, 2014, and Dec 27, 2021. We linked a subset of patient hospital records with patient data, including mortality data, from the Cancer Registry North-Rhine Westphalia, Germany. Patients from Essen University Hospital were randomly assigned to the development or internal validation cohorts (2:1). Patients from Münster, Freiburg, and Dresden University Hospitals were included in an external validation cohort. Using the development cohort, we created quantitative and visual PPP nomograms based on Cox regression models, assessing potential PPP predictors for overall survival, with least absolute shrinkage and selection operator penalty for overall survival as the primary endpoint. Performance was measured using Harrell's C-index in the internal and external validation cohorts and compared with established clinical risk scores (International Staging Collaboration for Cancer of the Prostate [STARCAP], European Association of Urology [EAU], and National Comprehensive Cancer Network [NCCN] risk scores) and a previous nomogram defined by Gafita et al (hereafter referred to as GAFITA) using receiver operating characteristic (ROC) curves and area under the ROC curve (AUC) estimates., Findings: We analysed 2414 male patients (1110 included in the development cohort, 502 in the internal cohort, and 802 in the external validation cohort), among whom 901 (37%) had died as of data cutoff (June 30, 2023; median follow-up of 52·9 months [IQR 33·9-79·0]). Predictors in the quantitative PPP nomogram were locoregional lymph node metastases (molecular imaging N2), distant metastases (extrapelvic nodal metastases, bone metastases [disseminated or diffuse marrow involvement], and organ metastases), tumour volume (in L), and tumour mean standardised uptake value. Predictors in the visual PPP nomogram were distant metastases (extrapelvic nodal metastases, bone metastases [disseminated or diffuse marrow involvement], and organ metastases) and total tumour lesion count. In the internal and external validation cohorts, C-indices were 0·80 (95% CI 0·77-0·84) and 0·77 (0·75-0·78) for the quantitative nomogram, respectively, and 0·78 (0·75-0·82) and 0·77 (0·75-0·78) for the visual nomogram, respectively. In the combined development and internal validation cohort, the quantitative PPP nomogram was superior to STARCAP risk score for patients at initial staging (n=139 with available staging data; AUC 0·73 vs 0·54; p=0·018), EAU risk score at biochemical recurrence (n=412; 0·69 vs 0·52; p<0·0001), and NCCN pan-stage risk score (n=1534; 0·81 vs 0·74; p<0·0001) for the prediction of overall survival, but was similar to GAFITA nomogram for metastatic hormone-sensitive prostate cancer (mHSPC; n=122; 0·76 vs 0·72; p=0·49) and metastatic castration-resistant prostate cancer (mCRPC; n=270; 0·67 vs 0·75; p=0·20). The visual PPP nomogram was superior to EAU at biochemical recurrence (n=414; 0·64 vs 0·52; p=0·0004) and NCCN across all stages (n=1544; 0·79 vs 0·73; p<0·0001), but similar to STARCAP for initial staging (n=140; 0·56 vs 0·53; p=0·74) and GAFITA for mHSPC (n=122; 0·74 vs 0·72; p=0·66) and mCRPC (n=270; 0·71 vs 0·75; p=0·23)., Interpretation: Our PPP nomograms accurately stratify high-risk and low-risk groups for overall survival in early and late stages of prostate cancer and yield equal or superior prediction accuracy compared with established clinical risk tools. Validation and improvement of the nomograms with long-term follow-up is ongoing (NCT06320223)., Funding: Cancer Registry North-Rhine Westphalia., Competing Interests: Declaration of interests MJK reports ownership of stocks in Bayer. JH reports participation on a data safety monitoring board for CARP-Study (carp-studie.de). VG reports grants or contracts from Pfizer, AstraZeneca, Bristol Myers Squibb (BMS), and MSD; consulting fees from BMS, Pfizer, Novartis, MSD Oncology, Ipsen, Janssen-Cilag, Eisai, Debiopharm, PCI Biotech, Gliead, Cureteq, Oncorena, and Synthekine; payment or honoraria from BMS, Pfizer, Ipsen, Eisai, MSD Oncology, Merck Serono, AstraZeneca, Janssen-Cilag, AAA/Novartis, Apogepha, Ono Pharmaceutical, Astellas Pharma, and Amgen; ownership of stocks in MSD, BMS, AstraZeneca, Genmab, and Bicycle Therapeutics; travel support from Pfizer, AstraZeneca, Janssen, Merck Serono, and Ipsen; participation on a data safety monitoring board or advisory board for the European Organisation for Research and Treatment of Cancer; and a leadership role for Arbeitsgemeinschaft Internistische Onkologie of the German Cancer Society. MS reports patents not related to the manuscript as planned, issued, or pending. ME reports grants or contracts from Blue Earth Diagnostics and Bayer; royalties from POSLUMA (an FDA-approved radiohybrid PSMA-targeted agent for PET imaging of prostate cancer in adults); consulting fees for Blue Earth Diagnostics, Novartis/AAA, Bayer, Telix, RayzeBio, Point Biopharma, and Janssen Pharmaceuticals; payment or honoraria from Novartis/AAA, Eckert-Ziegler, ABX, and Janssen Pharmaceuticals; patent application as inventor of radiohybrid PSMA; a leadership role in the European Association of Nuclear Medicine committee meeting; ownership of stocks in Novartis, Telix, Bayer, and Point Biopharma; support for travel from Blue Earth Diagnostics and Terumo; and payment for expert testimony from Paraxel and Bioclinica. TT reports grants from DAAD Researcher Grant and speaker fees from ABX. CK reports ownership of stocks in Telix and Actinium Pharmaceuticals; grants or contracts from Novartis, Mariana Oncology, and Amgen; payment or honoraria from Novartis and Pfizer; and travel support from Bayer, Janssen, and Amgen. KH reports grants or contracts from Novartis and Sofie Biosciences; consulting fees from Advanced Accelerator Applications, a Novartis company, Amgen, AstraZeneca, Bain Capital, Bayer, Boston Scientific, Convergent, Curium, Debiopharm, EcoR1, Fusion, GE Healthcare, Immedica, Isotopen Technologien München, Janssen, Merck, Molecular Partners, NVision, POINT Biopharma, Pfizer, Radiopharm Theranostics, Rhine Pharma, Siemens Healthineers, Sofie Biosciences, Telix, Theragnostics, and ymabs; payment or honoraria for educational events from PeerVoice; support for American Society of Clinical Oncology participation from Janssen; participation on a data safety monitoring board or advisory board for Fusion and GE Healthcare; and ownership of stocks in Sofie Biosciences, Pharma15, NVision, Convergent, Aktis Oncology, and AdvanCell. KR reports consulting fees from AAA/Novartis, Bayer, ABX, ABX-CRO, UroTrials, and Pharmtrace; honoraria or payment from AAA/Novartis, Bayer, and ABX; and travel support from Bayer. PTM reports payment to their institution from Siemens Healthineers. BAH reports consulting fees from Lightpoint medical, Janssen, Bayer, ABX, Astellas, Merck, Amgen, MSD/Pfizer, Novartis, BMS, Onkowissen, POINT Biopharma, Ipsen, AstraZeneca, Lightpoint medical, Telix, and Accord Healthcare; travel support from AstraZeneca, BMS, Janssen, Bayer, and Ipsen; grants or contracts from Janssen, Deutsche Forschungsgesellschaft, Novartis, and BMS; royalties or licenses from Uromed; payment or honoraria from Janssen, Amgen, Astellas, and Monrol; participation on a data safety monitoring board or advisory board for Janssen and ABX; and a leadership role for Deutsche Gesellschaft für Urologie. WPF reports grants from SOFIE Biosciences; consulting fees from Janssen, Calyx, Bayer, Novartis, and Urotrials; payment or Honoraria from Janssen, Calyx, Bayer, Novartis, Urotrials, Amgen, ABX, Eczacıbaşı Monrol, GE Healthcare, and Telix. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Cardiovascular disease is the leading cause of morbidity and mortality worldwide. Myocardial fibrosis plays an important role in adverse outcomes such as heart failure and arrhythmias. As the pathological response and degree of scarring, and therefore clinical presentation varies from patient to patient, early detection of fibrosis is crucial for identifying the appropriate treatment approach and forecasting the progression of a disease along with the likelihood of disease-related mortality. Current imaging modalities provides information about either decreased function or extracellular signs of fibrosis. Targeting activated fibroblasts represents a burgeoning approach that could offer insights prior to observable functional alterations, presenting a promising focus for potential anti-fibrotic therapeutic interventions at cellular level. In this article, we provide an overview of imaging cardiac fibrosis and discuss the role of different advanced imaging modalities with the focus on novel non-invasive imaging of activated fibroblasts., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Tugce Telli reports speaker fee from Abx not related to current work. David Kersting reports a research grant from Pfizer and funding by the German Research Foundation (DFG, KE2933/1-1) outside of the submitted work. Ken Herrmann reports receiving consultant fees from Advanced Accelerator Applications, a Novartis company, Amgen, AstraZeneca, Bain Capital, Bayer, Boston Scientific, Convergent, Curium, Debiopharm, EcoR1, Fusion, GE Healthcare, Immedica, Isotopen Technologien München, Janssen, Merck, Molecular Partners, NVision, POINT Biopharma, Pfizer, Radiopharm Theranostics, Rhine Pharma, Siemens Healthineers, Sofie Biosciences, Telix, and Theragnostics, ymabs, receiving research grants from Advanced Accelerator Applications, a Novartis company, Boston Scientific, Janssen, having stock or other ownership interests with AdvanCell, Aktis Oncology, Convergent, NVision, Pharma 15, and Sofie Biosciences. Zohreh Varasteh received support from the German Research Foundation (VA1183/2-1). Other authors have nothing to declare related to current work. The other authors declare no conflict of interest regarding this manuscript., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: In metastatic castration-resistant prostate cancer (mCRPC), some patients show low/absent PSMA expression in tumour lesions on positron emission tomography (PET) scans, indicating heterogeneity and heightened risk of non-response to PSMA-RLT (radioligand therapy). Imaging cancer-associated fibroblasts and glucose uptake may further characterise tumour heterogeneity in mCRPC patients. Here, we aimed to evaluate tumour heterogeneity and its potential implications for management in mCRPC patients assessed for PSMA-RLT using [ 68 Ga]Ga-FAPI-46, 2-[ 18 F]FDG and [ 68 Ga]Ga-/[ 18 F]F-PSMA-11/-1007 PET., Material and Methods: Patients with advanced, progressive mCRPC underwent clinical [ 68 Ga]Ga-/[ 18 F]F-PSMA-11/-1007, 2-[ 18 F]FDG and [ 68 Ga]Ga-FAPI-46 PET/CT to evaluate treatment with PSMA-directed RLT. Tumour detection/semiquantitative parameters were compared on a per-lesion/-region basis. Two phenotypes were defined: Criteria for the mixed phenotype were: (a) PSMA-negative findings for lymph node metastases ≥ 2.5 cm, any solid organ metastases ≥ 1.0 cm, or bone metastases with soft tissue component ≥ 1.0 cm, (b) low [ 68 Ga]Ga-/[ 18 F]F-PSMA-11/-1007 uptake and/or (c) balanced tumour uptake of all radioligands. The PSMA-dominant phenotype was assigned if the criteria were not met., Results: In ten patients, 472 lesions were detected on all imaging modalities (miTNM regions: M1b: 327 (69.3%), M1a: 95 (20.1%), N1: 26 (5.5%), M1c: 18 (3.8%), T: 5 (1.1%) and Tr: 1 (0.2%). [ 68 Ga]Ga-/[ 18 F]F-PSMA-11/-1007 (n = 453 (96.0%)) demonstrates the highest detection rate, followed by [ 68 Ga]Ga-FAPI-46 (n = 268 (56.8%))/2-[ 18 F]FDG (n = 241 (51.1%)). Semiquantitative uptake was highest for [ 68 Ga]Ga-/[ 18 F]F-PSMA-11/-1007 (mean SUV max (interquartile range): 22.7 (22.5), vs. [ 68 Ga]Ga-FAPI-46 (7.7 (3.7)) and 2-[ 18 F]FDG (6.8 (4.7)). Seven/three patients were retrospectively assigned to the PSMA-dominant/mixed phenotype. Median overall survival was significantly longer for patients who underwent [ 177 Lu]Lu-PSMA-617 RLT and were retrospectively assigned to the PSMA-dominant phenotype (19.7 vs. 9.3 months)., Conclusion: Through whole-body imaging, we identify considerable inter- and intra-patient heterogeneity of mCRPC and potential imaging phenotypes. Regarding uptake and tumour detection, [ 68 Ga]Ga-/[ 18 F]F-PSMA-11/-1007 was superior to [ 68 Ga]Ga-FAPI-46 and 2-[ 18 F]FDG, while the latter two were comparable. Patients who underwent [ 177 Lu]Lu-PSMA-617 RLT based on clinical-decision making had a longer overall survival and could be assigned to the PSMA-dominant phenotype., (© 2024. The Author(s).)

Rationale: Positron Emission Tomography (PET) using the somatostatin receptor 2 (SSTR2)-antagonist satoreotide trizoxetan ( 68 Ga-SSO120) is a novel, promising imaging modality for small-cell lung cancer (SCLC), which holds potential for theranostic applications. This study aims to correlate uptake in PET imaging with SSTR2 expression in immunohistochemistry (IHC) and to assess the prognostic value of 68 Ga-SSO120 PET at initial staging of patients with SCLC. Methods: We analyzed patients who underwent 68 Ga-SSO120 PET/CT during initial diagnostic workup of SCLC as part of institutional standard-of-care. SSTR2 expression in IHC was evaluated on a 4-level scale and correlated with normalized standardized uptake values and tumor-to-liver ratios (SUV max and TLR peak ) in 68 Ga-SSO120 PET on a lesion level. Highest lesion SUV max /TLR peak per patient, SSTR2 score in IHC, M status according to TNM classification, and other parameters were analyzed for association with overall survival (OS) and time to treatment failure (TTF) by univariate, multivariate (cut-off values were identified on data for best separation), and stratified Cox regression. Results: We included 54 patients (24 men/30 women, median age 65 years, 21 M0/33 M1 according to TNM classification). In 43 patients with available surplus tumor tissue samples, hottest lesion SUV max /TLR peak showed a significant correlation with the level of SSTR2-expression by tumor cells in IHC (Spearman's rho 0.86/0.81, both p < 0.001; ANOVA p < 0.001). High SSTR2 expression in IHC, 68 Ga-SSO120 SUV max and TLR peak of the hottest lesion per patient, whole-body TLR mean , MTV, TLG, M status, and serum LDH showed a significant association with inferior TTF/OS in univariate analysis. In separate multivariate Cox regression (including sex, age, M stage, and LDH) higher hottest-lesion TLR peak showed a significant association with shorter OS (HR = 0.26, 95%CI: 0.08-0.84, p = 0.02) and SSTR2 expression in IHC with significantly shorter TTF (HR = 0.24, 95%CI: 0.08-0.71, p = 0.001) and OS (HR = 0.22, 95%CI: 0.06-0.84, p = 0.03). In total, 12 patients (22.2%) showed low (< 1), 21 (38.9%) intermediate (≥ 1 but < 2), 14 (25.9%) high (≥ 2 but < 5), and 7 (13.0%) very high (≥ 5) whole-body mean TLR mean . Conclusion: In patients with SCLC, SSTR2 expression assessed by 68 Ga-SSO120 PET and by IHC were closely correlated and associated with shorter survival. More than 75% of patients showed higher whole-body 68 Ga-SSO120 tumor uptake than liver uptake and almost 40% high or very high uptake, possibly paving the way towards theranostic applications., Competing Interests: Competing Interests: Filiz Oezkan received personal fees from Sanofi Aventis, Janssen, DeciBio, ERBE and Genentech/Roche Ltd.; program funding to the institution was received from Olympus, Astrazeneca, ERBE and Janssen, all outside the submitted work. Lale Umutlu is a Speaker / Advisory Board Member for Bayer Healthcare and Siemens Healthcare and received research grants from Siemens Healthcare outside the submitted work. Rainer Hamacher was supported by the Clinician Scientist Program of the University Medicine Essen Clinician Scientist Academy (UMEA; Faculty of Medicine and Deutsche Forschungsgemeinschaft [DFG]); reports travel grants from Lilly, Novartis, and PharmaMar; and reports personal fees from Lilly and PharmaMar outside the submitted work. Jens Siveke is supported by German Cancer Aid (grant 70112505, PIPAC; grant 70113834, PREDICT-PACA), the Wilhelm-Sander Foundation (grant 2019.008.1), the DFG through grant SI1549/3-1 (Clinical Research Unit KFO337) and SI1549/4-1, and the Federal Ministry of Education and Research (BMBF; SATURN3 consortium); receives honoraria as a consultant or for continuing medical education presentations from AstraZeneca, Bayer, Immunocore, Roche, and Servier; receives research funding (to the institution) from Bristol Myers Squibb, Celgene, and Roche; and holds ownership and serves on the board of directors of Pharma15—all outside the submitted work. Wolfgang Fendler reports fees from SOFIE Biosciences (research funding), Janssen (consultant, speaker), Calyx (consultant, image review), Bayer (consultant, speaker, research funding), Novartis (speaker, consultant), Telix (speaker), GE Healthcare (speaker), Eczacıbaşı Monrol (speaker), Abx (speaker), Amgen (speaker), and Urotrials, all outside the submitted work. Marcel Wiesweg reports honoraria and advisory role from Amgen, AstraZeneca, Daiichi Sankyo, GlaxoSmithKline, Janssen, Novartis, Pfizer, Roche, Takeda, and research funding from Bristol-Myers Squibb, Takeda outside the submitted work. Ken Herrmann reports personal fees from Bayer, personal fees and other from Sofie Biosciences, personal fees from SIRTEX, non-financial support from ABX, personal fees from Adacap, personal fees from Curium, personal fees from Endocyte, grants and personal fees from BTG, personal fees from IPSEN, personal fees from Siemens Healthineers, personal fees from GE Healthcare, personal fees from Amgen, personal fees from Novartis, personal fees from ymabs, personal fees from Aktis Oncology, personal fees from Theragnostics, personal fees from Pharma15, outside the submitted work. Martin Schuler reports personal fees as a consultant from Amgen, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, GlaxoSmithKline, Janssen, Merck Serono, Novartis, Roche, Sanofi, and Takeda; honoraria for continuing medical education presentations from Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Janssen, MSD, and Novartis; and research funding (to the institution) from AstraZeneca and Bristol Myers Squibb, all outside the submitted work. Hubertus Hautzel reports personal fees from Roche and Urenco, and other fees from Pari, Roche and Urenco, outside the submitted work. David Kersting reports speaker honoraria from Pfizer and Novartis outside the submitted work. A research grant from Pfizer outside the submitted work and funding by the German Research Foundation (DFG, KE2933/1-1), outside the submitted work., (© The author(s).)

The benefit of multicompartment dosimetry in the radioembolization of neuroendocrine neoplasms is not firmly established. We retrospectively assessed its potential with patient outcome. Methods: Forty-three patients were eligible. The association of mean absorbed dose (MAD) for tumors and treatment response was tested per lesion with a receiver operating characteristic curve analysis, and the association of MAD with progression-free survival (PFS) and overall survival was tested per patient using uni- and multivariate Cox regression analyses. Results: The area under the curve for treatment response based on MAD was 0.79 (cutoff, 196.6 Gy; P < 0.0001). For global PFS, grade (grade 2 vs. 1: hazard ratio [HR], 2.51; P = 0.042; grade 3 vs. 1: HR, 62.44; P < 0.001), tumor origin (HR, 6.58; P < 0.001), and MAD (HR, 0.998; P = 0.003) were significant. For overall survival, no prognostic parameters were significant. Conclusion: In line with prior publications, a MAD of more than 200 Gy seemed to favor treatment response. MAD was also associated with PFS and may be of interest for radioembolization planning for neuroendocrine neoplasm patients., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

The fibroblast activation protein (FAP) is highly expressed in tumor and stromal cells of mesothelioma and thus is an interesting imaging and therapeutic target. Previous data on PET imaging with radiolabeled FAP inhibitors (FAPIs) suggest high potential for superior tumor detection. Here, we report the data of a large malignant pleural mesothelioma cohort within a 68 Ga-FAPI46 PET observational trial (NCT04571086). Methods: Of 43 eligible patients with suspected or proven malignant mesothelioma, 41 could be included in the data analysis of the 68 Ga-FAPI46 PET observational trial. All patients underwent 68 Ga-FAPI46 PET/CT, contrast-enhanced CT, and 18 F-FDG PET/CT. The primary study endpoint was the association of 68 Ga-FAPI46 PET uptake intensity and histopathologic FAP expression. Furthermore, secondary endpoints were detection rate and sensitivity, specificity, and positive and negative predictive values as compared with 18 F-FDG PET/CT. Datasets were interpreted by 2 masked readers. Results: The primary endpoint was met, and the association between 68 Ga-FAPI46 SUV max or SUV peak and histopathologic FAP expression was significant (SUV max : r = 0.49, P = 0.037; SUV peak : r = 0.51, P = 0.030). 68 Ga-FAPI46 and 18 F-FDG showed similar sensitivity by histopathologic validation on a per-patient (100.0% vs. 97.3%) and per region (98.0% vs. 95.9%) basis. Per-region analysis revealed higher 68 Ga-FAPI46 than 18 F-FDG specificity (81.1% vs. 36.8%) and positive predictive value (87.5% vs. 66.2%). Conclusion: We confirm an association of 68 Ga-FAPI46 uptake and histopathologic FAP expression in mesothelioma patients. Additionally, we report high sensitivity and superior specificity and positive predictive value for 68 Ga-FAPI46 versus 18 F-FDG., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

Background Lutetium 177 [ 177 Lu]Lu-PSMA-617 ( 177 Lu-PSMA-617) is a prostate-specific membrane antigen (PSMA)-targeted radioligand therapy for metastatic castration-resistant prostate cancer (mCRPC). Quantitative PSMA PET/CT analysis could provide information on 177 Lu-PSMA-617 treatment benefits. Purpose To explore the association between quantitative baseline gallium 68 [ 68 Ga]Ga-PSMA-11 ( 68 Ga-PSMA-11) PET/CT parameters and treatment response and outcomes in the VISION trial. Materials and Methods This was an exploratory secondary analysis of the VISION trial. Eligible participants were randomized (June 2018 to October 2019) in a 2:1 ratio to 177 Lu-PSMA-617 therapy (7.4 GBq every 6 weeks for up to six cycles) plus standard of care (SOC) or to SOC only. Baseline 68 Ga-PSMA-11 PET parameters, including the mean and maximum standardized uptake value (SUV mean and SUV max ), PSMA-positive tumor volume, and tumor load, were extracted from five anatomic regions and the whole body. Associations of quantitative PET parameters with radiographic progression-free survival (rPFS), overall survival (OS), objective response rate, and prostate-specific antigen response were investigated using univariable and multivariable analyses (with treatment as the only other covariate). Outcomes were assessed in subgroups based on SUV mean quartiles. Results Quantitative PET parameters were well balanced between study arms for the 826 participants included. The median whole-body tumor SUV mean was 7.6 (IQR, 5.8-9.9). Whole-body tumor SUV mean was the best predictor of 177 Lu-PSMA-617 efficacy, with a hazard ratio (HR) range of 0.86-1.43 for all outcomes (all P < .001). A 1-unit whole-body tumor SUV mean increase was associated with a 12% and 10% decrease in risk of an rPFS event and death, respectively. 177 Lu-PSMA-617 plus SOC prolonged rPFS and OS in all SUV mean quartiles versus SOC only, with no identifiable optimum among participants receiving 177 Lu-PSMA-617. Higher baseline PSMA-positive tumor volume and tumor load were associated with worse rPFS (HR range, 1.44-1.53 [ P < .05] and 1.02-1.03 [ P < .001], respectively) and OS (HR range, 1.36-2.12 [ P < .006] and 1.04 [ P < .001], respectively). Conclusion Baseline 68 Ga-PSMA-11 PET/CT whole-body tumor SUV mean was the best predictor of 177 Lu-PSMA-617 efficacy in participants in the VISION trial. Improvements in rPFS and OS with 177 Lu-PSMA-617 plus SOC were greater among participants with higher whole-body tumor SUV mean , with evidence for benefit at all SUV mean levels. ClinicalTrials.gov identifier: NCT03511664 Published under a CC BY 4.0 license. Supplemental material is available for this article.

Introduction: Granulomatosis due to immune reconstitution inflammatory syndrome (IRIS) and disseminated Mycobacterium avium-intracellulare (M. avium) infection may trigger hypercalcemia. Here, we report a rare case of hypercalcemia and acute kidney damage related to IRIS in a person living with Human Immunodeficiency Virus (HIV)., Case Presentation: A 39-year-old male person living with HIV presented with muscle weakness and unwanted weight loss of 8 kg within the last 2 weeks. Laboratory findings included serum hypercalcemia of 3.27 mmol/mL associated with elevated calcitriol and acute kidney damage. Since the first diagnosis of HIV and concomitant disseminated M. avium infection, the patient received antiretroviral therapy (ART), rifabutin, clarithromycin, and ethambutol. 18 Fluoro-D-glucose positron emission computed tomography ( 18 FDG-PET/CT) showed progressive multilocular lymphadenopathy. Biopsy specimen from the duodenum as well as retroperitoneal and mediastinal lymph nodes revealed granulomatous inflammation consistent with IRIS. Treatment with forced diuresis, bisphosphonates, and calcitonin normalized serum calcium and kidney function recovered., Conclusion: Hypercalcemia due to IRIS is a rare differential diagnosis in persons living with HIV and may lead to acute kidney damage, despite sufficient ART and antimycobacterial treatment., (© 2024. The Author(s).)

Despite their unique histologic features, gliosarcomas belong to the group of glioblastomas and are treated according to the same standards. Fibroblast activation protein (FAP) is a component of a tumor-specific subpopulation of fibroblasts that plays a critical role in tumor growth and invasion. Some case studies suggest an elevated expression of FAP in glioblastoma and a particularly strong expression in gliosarcoma attributed to traits of predominant mesenchymal differentiation. However, the prognostic impact of FAP and its diagnostic and therapeutic potential remain unclear. Here, we investigate the clinical relevance of FAP expression in gliosarcoma and glioblastoma and how it correlates with 68 Ga-FAP inhibitor (FAPI)-46 PET uptake. Methods: Patients diagnosed with gliosarcoma or glioblastoma without sarcomatous differentiation with an overall survival of less than 2.5 y were enrolled. Histologic examination included immunohistochemistry and semiquantitative scoring of FAP (0-3, with higher values indicating stronger expression). Additionally, 68 Ga-FAPI-46 PET scans were performed in a subset of glioblastomas without sarcomatous differentiation patients. The clinical SUVs were correlated with FAP expression levels in surgically derived tumor tissue and relevant prognostic factors. Results: Of the 61 patients who were enrolled, 13 of them had gliosarcoma. Immunohistochemistry revealed significantly more FAP in gliosarcomas than in glioblastomas without sarcomatous differentiation of tumor tissue ( P < 0.0001). In the latter, FAP expression was confined to the perivascular space, whereas neoplastic cells additionally expressed FAP in gliosarcoma. A significant correlation of immunohistochemical FAP with SUV mean and SUV peak of 68 Ga-FAPI-46 PET indicates that clinical tracer uptake represents FAP expression of the tumor. Although gliosarcomas express higher levels of FAP than do glioblastomas without sarcomatous differentiation, overall survival does not significantly differ between the groups. Conclusion: The analysis reveals a significant correlation between SUV mean and SUV peak in 68 Ga-FAPI-46 PET and immunohistochemical FAP expression. This study indicates that FAP expression is much more abundant in the gliosarcoma subgroup of glioblastomas. This could open not only a diagnostic but also a therapeutic gap, since FAP could be explored as a theranostic target to enhance survival in a distinct subgroup of high-risk brain tumor patients with poor survival prognosis., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

Objective. The partial-volume effect (PVE) is an important factor impairing tumour quantification in molecular imaging. The commonly used contour-volume-of-interest (contour-VOI) approach to correct for this effect employs phantom-based recovery coefficients. Applying oversize-VOIs could offer superior quantification accuracy in small lesions. The oversize-VOI approach uses a large oversize volume to determine the total tumour activity after applying a background correction. Aims of this study were to provide a procedure for the application of the oversize-VOI approach and to compare its performance to the contour-VOI approach in PET imaging. Approach. A sphere tumour model was simulated to determine the oversize diameter that contained 90%, 95%, and 98% of the total activity as a function of the tumour size. Experimental investigations involving phantom and clinical data were conducted on a digital PET/CT scanner. In the phantom investigation, 12 spherical tumour inserts (diameters ranging from 3.7 to 37.4 mm) containing 18 F-solution were used. The accuracy of the contour- and oversize-VOI approach was evaluated for different signal-to-background ratios (20-3). Clinically, both approaches were applied on PET/CT images acquired with 18 F-labelled prostate-specific membrane antigen in prostate cancer patients. Main results. From the tumour model, we deduced that an oversize-VOI of two PET spatial resolutions larger than the physical lesion diameter contains at least 98% of the total activity for lesions with diameters down to one PET spatial resolution, while minimizing the background contribution. Both approaches were robust against varying phantom and clinical imaging conditions. Performance of the oversize-VOI approach was favorable for lesions below 10 mm in diameter, whereas the contour-VOI approach was slightly more accurate for sizes above 10 mm. Significance. The oversize-VOI approach facilitates image quantification of small tumours. It is simple and effective to correct for the PVE and may be used in pre-therapeutic (small) tumour dosimetry., (Creative Commons Attribution license.)

Purpose: The Minimal Documentation System (MIDOS2) is recommended as a systematic screening tool for assessing symptom burden and patient needs in advanced cancer patients. Given the absence of an optimal weighting of individual symptoms and a corresponding cut-off value, this study aims to determine a threshold based on inpatient's subjective need for palliative support. Additionally, we investigate the correlation between symptom burden and subjective need for palliative support collected through a patient-reported outcome measure (PROM) with survival duration of less or more than one year., Methods: Inpatients diagnosed with advanced solid cancer completed an electronic PROM, which included the MIDOS2 questionnaire among other tools. Differences in symptom burden were analysed between patients expressing subjective need for palliative support and those with survival of less or more than one year using ANOVA, Mann-Whitney-U Test, logistic regression, Pearson and Spearman correlation tests. Cut-off analyses were performed using a ROC curve. Youden-Index, sensitivity, and specificity measures were used as well., Results: Between April 2020 and March 2021, 265 inpatients were included in the study. Using a ROC curve, the MIDOS2 analysis resulted in an Area under the curve (AUC) of 0.732, a corresponding cut-off value of eight points, a sensitivity of 76.36% and a specificity of 62.98% in assessing the subjective need for palliative support. The MIDOS2, with double weighting of the significant symptoms, showed a cut-off value of 14 points, achieving a sensitivity of 78.18% and a specificity of 72.38%. A total of 55 patients (20.8%) expressed a need for support from the palliative care team. This need was independent of the oncological tumour entity and increased among patients with a survival of less than one year. These patients reported significantly poorer physical (p < 0.001) or mental (p < 0.001) condition. Additionally, they reported higher intensities of pain (p = 0.002), depressive symptoms (p < 0.001), weakness (p < 0.001), anxiety (p < 0.001), and tiredness (p < 0.001)., Conclusion: Using the established MIDOS2 cut-off value with an adjusted double weighting in our study, a large proportion of inpatients may be accurately referred to SPC based on their subjective need for palliative support. Additionally, subjective reports of poor general, mental, and physical condition, as well as pain, depressive symptoms, weakness, anxiety, and tiredness, increase the subjective need for palliative support, particularly in patients with a survival prognosis of less than one year., (© 2024. The Author(s).)

Background: Data from multiple organizations are crucial for advancing learning health systems. However, ethical, legal, and social concerns may restrict the use of standard statistical methods that rely on pooling data. Although distributed algorithms offer alternatives, they may not always be suitable for health frameworks., Objective: This paper aims to support researchers and data custodians in three ways: (1) providing a concise overview of the literature on statistical inference methods for horizontally partitioned data; (2) describing the methods applicable to generalized linear models (GLM) and assessing their underlying distributional assumptions; (3) adapting existing methods to make them fully usable in health settings., Methods: A scoping review methodology was employed for the literature mapping, from which methods presenting a methodological framework for GLM analyses with horizontally partitioned data were identified and assessed from the perspective of applicability in health settings. Statistical theory was used to adapt methods and to derive the properties of the resulting estimators., Results: From the review, 41 articles were selected, and six approaches were extracted for conducting standard GLM-based statistical analysis. However, these approaches assumed evenly and identically distributed data across nodes. Consequently, statistical procedures were derived to accommodate uneven node sample sizes and heterogeneous data distributions across nodes. Workflows and detailed algorithms were developed to highlight information-sharing requirements and operational complexity., Conclusions: This paper contributes to the field of health analytics by providing an overview of the methods that can be used with horizontally partitioned data, by adapting these methods to the context of heterogeneous health data and by clarifying the workflows and quantities exchanged by the methods discussed. Further analysis of the confidentiality preserved by these methods is needed to fully understand the risk associated with the sharing of summary statistics.

Purpose: Radiolabelled fibroblast activation protein inhibitors (FAPIs) are becoming increasingly important for imaging various tumour diseases. However, it is essential to be aware of potential pitfalls. Here, we investigate FAP expression in the thyroid gland in autoimmune thyroiditis (AIT)., Methods: AIT patients with pathological thyroid uptake on [ 68 Ga]Ga-FAPI PET were compared with glucose metabolism on 2-[ 18 F]FDG PET in terms of SUV max /SUV peak /SUV mean /tissue-to-background ratio (TBR), and with a healthy control group., Results: Between September 2019 and July 2021, 6 patients presented with a visually increased thyroid uptake and TBR on [ 68 Ga]Ga-FAPI PET. In the retrospective clinical work-up, all patients had known or newly diagnosed AIT. Compared to a matched healthy control group, FAP expression and glucose metabolism were significantly increased ([ 68 Ga]Ga-FAPI (SUV peak ): 7.0 vs. 1.7; p = 0.004/(TBR bloodpool ): 6.8 vs. 1.7; p = 0.002; 2-[ 18 F]FDG (SUV peak ): 3.9 vs. 1.4; p = 0.004/(TBR bloodpool ): 4.0 vs. 1.2; p = 0.041). However, there was no significant difference in median uptake between [ 68 Ga]Ga-FAPI and 2-[18F]FDG PET (SUV peak : 7.3 vs. 5.6; p = 0.104)., Conclusion: Patients with AIT show higher thyroid uptake on [ 68 Ga]Ga-FAPI and 2-[ 18 F]FDG PET. Incidental thyroid uptake is another pitfall in the interpretation of [ 68 Ga]Ga-FAPI PET and should prompt a clinical work-up., (© 2024. The Author(s).)

Background: The existence of socioeconomic inequalities in the prevalence of symptoms of depression and anxiety is widely acknowledged, and individuals from lower socioeconomic backgrounds tend to exhibit higher rates of symptoms. However, the direction in which the COVID-19 pandemic has influenced these disparities remains uncertain. We therefore aimed to systematically outline the available evidence on the temporal dynamics of socioeconomic inequalities in symptoms related to depression and anxiety during the COVID-19 pandemic across high-income countries., Methods: A scoping review was conducted by searching the databases Embase, Scopus and PsycINFO. According to pre-defined eligibility criteria, two reviewers independently screened titles and abstracts as well as full texts of the compiled records. Data from the included studies were extracted using a standardised data-extraction form and analysed numerically and narratively. The scoping review followed the PRISMA-ScR guidelines., Results: A total of 49 studies comprising 149 analyses of socioeconomic indicators in relation to symptoms of depression and anxiety were included. Despite heterogeneous study designs and results, there was a tendency of increasing (40.9%; n  = 61) or persistent (38.2%; n  = 57) inequality trends to the detriment of those in socially more disadvantaged positions. Increasing inequalities were most pronounced when income was used as a socioeconomic indicator. Groups with lower socioeconomic status appeared most vulnerable in the initial phase of the COVID-19 pandemic. Throughout the pandemic, dynamics were diverse, with persistent trends most frequently reported., Conclusion: Overall, to the detriment of those with lower socioeconomic status, mental-health inequalities persisted or increased in most analyses. Continually monitoring socioeconomic inequalities over time is crucial, since this makes it possible to adapt prevention and intervention strategies to specific pandemic phases. Interventions targeting job security, income security and educational attainment could reduce mental-health inequalities. The results can contribute to preparedness plans for future pandemics and crises., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Herrmann, Beese, Wollgast, Mauz, Kersjes, Hoebel and Wachtler.)

Radioligand therapy is an emerging and effective treatment option for various types of malignancies, but may be intricately linked to hematological side effects such as anemia, lymphopenia or thrombocytopenia. The safety and efficacy of novel theranostic agents, targeting increasingly complex targets, can be well served by comprehensive dosimetry. However, optimization in patient management and patient selection based on risk-factors predicting adverse events and built upon reliable dose-response relations is still an open demand. In this context, artificial intelligence methods, especially machine learning and deep learning algorithms, may play a crucial role. This review provides an overview of upcoming opportunities for integrating artificial intelligence methods into the field of dosimetry in nuclear medicine by improving bone marrow and blood dosimetry accuracy, enabling early identification of potential hematological risk-factors, and allowing for adaptive treatment planning. It will further exemplify inspirational success stories from neighboring disciplines that may be translated to nuclear medicine practices, and will provide conceptual suggestions for future directions. In the future, we expect artificial intelligence-assisted (predictive) dosimetry combined with clinical parameters to pave the way towards truly personalized theranostics in radioligand therapy., Competing Interests: Declaration of competing interest R.S. received research support from Boehringer Ingelheim Fonds and Else Kröner-Fresenius-Stiftung. K.H. reports personal fees from Bayer, personal fees and other from Sofie Biosciences, personal fees from SIRTEX, non-financial support from ABX, personal fees from Adacap, personal fees from Curium, personal fees from Endocyte, grants and personal fees from BTG, personal fees from IPSEN, personal fees from Siemens Healthineers, personal fees from GE Healthcare, personal fees from Amgen, personal fees from Novartis, personal fees from ymabs, personal fees from Aktis Oncology, personal fees from Theragnostics, personal fees from Pharma15, personal fees from Debiopharm, personal fees from AstraZeneca, and personal fees from Janssen outside of the submitted work. D.K. reports funding from the German Research Association (DFG), research funding from Pfizer and speaker honoraria from Novartis and Pfizer outside of the submitted work. The other authors have nothing to declare., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Competing Interests: Funding Support and Author Disclosures Dr Settelmeier has received support from the German Research Foundation (UMEA Junior Clinician Scientist, UMEA Clinician Scientist Academy, FU356/12-2). Dr Varasteh has received support from the German Research Foundation (VA1183/2-1). Dr Rischpler has received a research grant from Pfizer; has received consultancy fees for Adacap and Pfizer; and has received speaker honoraria from Adacap, Alnylam, BTG, Curium, GE Healthcare, Pfizer, and Siemens Healthineers outside of the submitted work. Prof Fendler has received fees from SOFIE Bioscience (research funding), Janssen (consultant and speaker), Calyx (consultant and image review), Bayer (consultant, speaker, and research funding), Novartis (speaker and consultant), Telix (speaker), GE Healthcare (speaker), Eczacıbaşı Monrol (speaker), Abx (speaker), Amgen (speaker), and Urotrials (speaker) outside of the submitted work. Prof Umutlu has served as a speaker/Advisory Board member for Bayer Healthcare and Siemens Healthcare; and has received research grants from Siemens Healthcare outside of the submitted work. Prof Herrmann has received consultant fees from Advanced Accelerator Applications (a Novartis company), Amgen, AstraZeneca, Bain Capital, Bayer, Boston Scientific, Convergent, Curium, Debiopharm, EcoR1, Fusion, GE Healthcare, Immedica, Isotopen Technologien München, Janssen, Merck, Molecular Partners, NVision, POINT Biopharma, Pfizer, Radiopharm Theranostics, Rhine Pharma, Siemens Healthineers, Sofie Biosciences, Telix, Theragnostics, and Y-mAbs; has received research grants from Advanced Accelerator Applications (a Novartis company), Boston Scientific, and Janssen; and holds stock or other ownership interests in AdvanCell, Aktis Oncology, Convergent, NVision, Pharma 15, and Sofie Biosciences outside of the submitted work. Prof Rassaf is supported by the German Research Foundation (DFG RA969/12-1), Ministry of Science and Culture REBIRTH I/II (ZN3440), and Stiftung Gerdes outside of the submitted work. Dr Kersting has received support from the German Research Foundation (UMEA Clinician Scientist Academy, FU356/12-2); has received a research grant from Pfizer; has received funding by the German Research Foundation (DFG, KE2933/1-1); and has received speaker honoraria from Pfizer outside of the submitted work. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

This multicenter randomized phase III trial (NCT04457245) evaluated the effect of performing prostate-specific membrane antigen (PSMA) PET/CT before definitive radiotherapy. Methods: Men with unfavorable intermediate- or high-risk prostate cancer were randomized 1.08:1 between receiving and not receiving a PSMA PET/CT scan before definitive radiotherapy. All other imaging modalities were allowed in the control arm. The primary endpoint was 5-y progression-free survival. Results: Fifty-four men were randomized between November 2020 and December 2021 (PSMA PET/CT, n = 25; control, n = 29). The trial closed early after approval and insurance coverage of PSMA PET/CT. In the PSMA PET/CT arm, 14 patients had localized disease (miT2b-cN0M0), 6 had locally advanced disease (miT3a-bN0M0), 3 had regional metastasis (miN1M0), and 1 had distant metastasis (miM1b). Four patients were upstaged. Conclusion: PSMA PET/CT upstaged 17% of patients, which allowed for more accurate radiotherapy planning. Unfortunately, this trial closed early before completion of target enrollment (54/316, 17%) and was underpowered to assess the effect of PSMA PET/CT on progression-free survival., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

Radiotheranostics, a combination of diagnostic and therapeutic approaches, was first utilized in cancer management using radiopharmaceuticals to both image and selectively treat specific cancer subtypes nearly a century ago. Radiotheranostic strategies rooted in nuclear medicine have revolutionized the treatment landscape for individuals diagnosed with prostate cancer and neuroendocrine tumors in the past 10 years. In specific contexts, these approaches have emerged as the prevailing standard, yielding numerous positive results. The field of radiotheranostics shows great potential for future clinical applications. This article aims to examine the key factors that will contribute to the success of radiotheranostics in the future, as well as the current challenges and potential strategies to overcome them, with insight into the global radiotheranostic market., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Ken Herrmann reports receiving consultant fees from Advanced Accelerator Applications, a Novartis company, Amgen, AstraZeneca, Bain Capital, Bayer, Boston Scientific, Convergent, Curium, Debiopharm, EcoR1, Fusion, GE Healthcare, Immedica, Isotopen Technologien München, Janssen, Merck, Molecular Partners, NVision, POINT Biopharma, Pfizer, Radiopharm Theranostics, Rhine Pharma, Siemens Healthineers, Sofie Biosciences, Telix, Theragnostics, and Y-mABs Therapeutics. Ken Herrmann reports receiving research grants from Advanced Accelerator Applications, a Novartis company, Boston Scientific, and Janssen. Ken Herrmann reports having stock or other ownership interests with AdvanCell, Aktis Oncology, Convergent, NVision, Pharma 15, and Sofie Biosciences., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The utilization of psychotherapeutic consultation at work (PT-A) has so far been investigated in large enterprises (LEs). These differ structurally from small(est) and medium-sized enterprises (SMEs). Differences in the user profiles of a PT‑A with regard to psychosomatic health, work-related self-efficacy, and work ability depending on company size have hardly been investigated. This study also examined differences in the employees' perception of the psychosocial safety climate (PSC) in the company, which represents management's efforts to promote mental health., Methods: As part of the Early Intervention in the Workplace intervention study called "friaa", employees from LEs and SMEs interested in a PT‑A were surveyed throughout Germany from September 2021 to January 2023. Using t‑ and χ 2 -tests, differences between employees in LEs (n = 439) and SMEs (n = 109) were examined with regard to the ICD-10 F diagnostic code ("International Statistical Classification of Diseases and Related Health Problems"; mental and behavioral disorders), depression (PHQ-9), anxiety (GAD-2), level of functioning (GAF), somatic symptom burden (SSS-8), health (VR-12), ability to work (WAI), self-efficacy (SOSES), and psychosocial safety climate (PSC-4). The association between these variables and especially the PSC‑4 were investigated using correlation analysis., Results: Both groups showed similar levels of stress. From the employees' perspective, psychosocial issues were addressed significantly more frequently in LEs than in SMEs with a medium effect size. The study provided initial indications that in LEs there were positive correlations of the PSC‑4 with SOSES and WAI and negative ones with PHQ‑9 and SSS‑8., Discussion: The comparable psychological strain on employees in LEs and SMEs points to the need for behavioral and structural preventive measures regardless of the company size. Mainly in SMEs, organizational communication of psychosocial health should be given greater priority., (© 2024. The Author(s).)

Introduction: Psychotherapeutic consultation at work (PT-A) offers easily accessible, short-term support for employees experiencing psychological stress. The aim of the study was to evaluate aspects of the implementation regarding announcement, access, and use of the PT‑A., Methods: The study was conducted as part of a randomized controlled trial (RCT) called "Early Intervention in the Workplace". Forty-six company actors answered a questionnaire about how the companies announced the PT‑A to their employees, the barriers in the announcement of the PT‑A, and the beneficial factors of using the PT‑A. The access routes of the 550 participating employees were used from the baseline data of the RCT. Seven company actors were qualitatively interviewed about their expectations of the PT‑A and 22 participants of the RCT were interviewed about their experiences accessing and using the PT‑A., Results: The company actors hoped that the PT‑A would have an impact on all levels of prevention. Most companies announced the PT‑A centrally (e.g., flyers and intranet) as well as through individual recommendations (e.g., through the company's social counselling and occupational health professionals). Employees appreciated the opportunity to participate anonymously in the central announcement. Advantages of the supportive access were seen in the accessibility of employees without treatment experience, employees with high levels of suffering, and employees who have not yet recognized their own need for treatment., Discussion: The results suggest that it is useful to announce the PT‑A centrally to all employees but also to recommend it personally to affected employees. By using both methods, different PT‑A target groups can be reached and the advantages of anonymous participation are retained., (© 2024. The Author(s).)

Tumoral fibroblast activation protein expression is associated with proliferation and angiogenesis and can be visualized by PET/CT. We examined the prognostic value of [ 68 Ga]Ga-fibroblast activation protein inhibitor (FAPI) ( 68 Ga-FAPI)-46 PET/CT for different tumor entities in patients enrolled in 2 prospective imaging studies (NCT05160051, n = 30; NCT04571086, n = 115). Methods: Within 4 wk, 145 patients underwent 68 Ga-FAPI-46 and [ 18 F]FDG ( 18 F-FDG) PET/CT. The association between overall survival (OS) and sex, age, tumor entity, total lesion number, highest SUV max , and the presence of each nodal, visceral, and bone metastasis was tested using univariate Cox regression analysis. Multivariate analyses were performed for prognostic factors with P values of less than 0.05. Results: In the univariate analysis, shorter OS was associated with total lesion number and the presence of nodal, visceral, and bone metastases on 68 Ga-FAPI-46 PET/CT (hazard ratio [HR], 1.06, 2.18, 1.69, and 2.05; P < 0.01, < 0.01, = 0.04, and = 0.02, respectively) and 18 F-FDG PET/CT (HR, 1.05, 2.31, 1.76, and 2.30; P < 0.01, < 0.01, = 0.03, and < 0.01, respectively) and with SUV max on 68 Ga-FAPI-46 PET/CT (HR, 1.03; P = 0.03). In the multivariate analysis, total lesion number on 68 Ga-FAPI-46 PET/CT was an independent risk factor for shorter OS (HR, 1.05; P = 0.02). In patients with pancreatic cancer, shorter OS was associated with total lesion number on 68 Ga-FAPI-46 PET/CT (HR, 1.09; P < 0.01) and bone metastases on 18 F-FDG PET/CT (HR, 31.39; P < 0.01) in the univariate analysis and with total lesion number on 68 Ga-FAPI-46 PET/CT (HR, 1.07; P = 0.04) in the multivariate analyses. In breast cancer, total lesion number on 68 Ga-FAPI-46 PET/CT (HR, 1.07; P = 0.02), as well as bone metastases on 18 F-FDG PET/CT (HR, 9.64; P = 0.04), was associated with shorter OS in the univariate analysis. The multivariate analysis did not reveal significant prognostic factors. In thoracic cancer (lung cancer and pleural mesothelioma), the univariate and multivariate analyses did not reveal significant prognostic factors. Conclusion: Disease extent on 68 Ga-FAPI-46 PET/CT is a predictor of short OS and may aid in future risk stratification by playing a supplemental role alongside 18 F-FDG PET/CT., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

Objectives: To investigate the specific strengths of MRI and PET components in 68 Ga-PSMA-11 PET/MRI for staging of patients with biochemically recurrent prostate cancer (PCa)., Methods: Patients with biochemical recurrence of PCa and contrast-enhanced whole-body 68 Ga-PSMA-11 PET/MRI including a dedicated pelvic multiparametric MRI were included in this retrospective study. Imaging datasets of MRI and PET were evaluated separately regarding local PCa recurrence (Tr), pelvic lymph node metastases (N1), distant lymph node metastases (M1a), bone metastases (M1b), and soft tissue metastases (M1c) according to PROMISE version 1. Data evaluation was performed patient- and region-/lesion-based. Cox regression revealed a PSA of 1.69 ng/mL as a cut-off for subgroup analysis. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were evaluated for each image component. Differences in staging accuracy were assessed using the Wilcoxon and McNemar test., Results: Altogether 102 patients (mean aged 68 ± 8 years, median PSA 1.33 ng/mL) were included. PCa was found in 70/102 (68%) patients. Accuracy of MRI in the detection of Tr, N1, M + , M1a, and M1b was 100%, 79%, 90%, 97%, and 95% for PSA < 1.69 ng/mL and 100%, 87%, 87%, 91%, and 96% for PSA > 1.69 ng/mL. Accuracy of 68 Ga-PSMA-11 PET was 93%, 97%, 93%, 98%, and 100% for PSA < 1.69 ng/mL and 87%, 91%, 96%, 100%, and 96% for PSA > 1.69 ng/mL., Conclusions: Combined assessment of 68 Ga-PSMA-11 PET/MRI improves tumor localization in men with biochemical recurrence. The MRI detected local recurrence of PCa more often whereas 68  Ga-PSMA-11 PET detected lymph node metastases more often, especially for PSA < 1.69 ng/mL., Clinical Relevance Statement: This study gives a scientific baseline to improve the understanding and reading of 68 Ga-PSMA-11 PET/MRI imaging in patients with biochemically recurrent PCa by showing the specific strength of each imaging component., Key Points: • Combining the individual modality strengths of 68 Ga-PSMA-11 PET/MRI improves tumor localization in men with biochemical recurrence of prostate cancer. • MRI component of 68  Ga-PSMA-11 PET/MRI shows its strength in detecting local recurrence of prostate cancer, especially at PSA < 1.69 ng/mL. • 68  Ga-PSMA-11 PET component shows its strength in detecting local and distant lymph node metastases, especially at PSA < 1.69 ng/mL., (© 2023. The Author(s).)

Background: There are currently no standard first-line treatment options for patients with higher grade 2-3, well-differentiated, advanced, gastroenteropancreatic neuroendocrine tumours. We aimed to investigate the efficacy and safety of first-line [ 177 Lu]Lu-DOTA-TATE ( 177 Lu-Dotatate) treatment., Methods: NETTER-2 was an open-label, randomised, parallel-group, superiority, phase 3 trial. We enrolled patients (aged ≥15 years) with newly diagnosed higher grade 2 (Ki67 ≥10% and ≤20%) and grade 3 (Ki67 >20% and ≤55%), somatostatin receptor-positive (in all target lesions), advanced gastroenteropancreatic neuroendocrine tumours from 45 centres across nine countries in North America, Europe, and Asia. We used interactive response technologies to randomly assign (2:1) patients to receive four cycles (cycle interval was 8 weeks ± 1 week) of intravenous 177 Lu-Dotatate plus intramuscular octreotide 30 mg long-acting repeatable (LAR) then octreotide 30 mg LAR every 4 weeks ( 177 Lu-Dotatate group) or high-dose octreotide 60 mg LAR every 4 weeks (control group), stratified by neuroendocrine tumour grade (2 vs 3) and origin (pancreas vs other). Tumour assessments were done at baseline, week 16, and week 24, and then every 12 weeks until disease progression or death. The primary endpoint was progression-free survival by blinded, independent, central radiology assessment. We did the primary analysis at 101 progression-free survival events as the final progression-free survival analysis. NETTER-2 is registered with ClinicalTrials.gov, NCT03972488, and is active and not recruiting., Findings: Between Jan 22, 2020, and Oct 13, 2022, we screened 261 patients, 35 (13%) of whom were excluded. We randomly assigned 226 (87%) patients (121 [54%] male and 105 [46%] female) to the 177 Lu-Dotatate group (n=151 [67%]) and control group (n=75 [33%]). Median progression-free survival was 8·5 months (95% CI 7·7-13·8) in the control group and 22·8 months (19·4-not estimated) in the 177 Lu-Dotatate group (stratified hazard ratio 0·276 [0·182-0·418]; p<0·0001). During the treatment period, adverse events (of any grade) occurred in 136 (93%) of 147 treated patients in the 177 Lu-Dotatate group and 69 (95%) of 73 treated patients in the control group. There were no study drug-related deaths during the treatment period., Interpretation: First-line 177 Lu-Dotatate plus octreotide LAR significantly extended median progression-free survival (by 14 months) in patients with grade 2 or 3 advanced gastroenteropancreatic neuroendocrine tumours. 177 Lu-Dotatate should be considered a new standard of care in first-line therapy in this population., Funding: Advanced Accelerator Applications, a Novartis Company., Competing Interests: Declaration of interests SS reports support for the present work from Novartis; grants or contracts from Novartis; consulting fees from Ipsen, Novartis, and Camurus; and meeting attendance support from Ipsen and Novartis. DH reports support for the present work from Novartis; grants or contracts from Novartis, ITM, RayzeBio, Thermo Fisher Scientific, Camurus, and Genentech/Roche; consulting fees from Novartis, TerSera, ITM, Crinetics, Amryt, Camurus, Chimeric Therapeutics, Harpoon Therapeutics, HarbourBioMed, Lantheus, Exelixis, and Ipsen; and participation on a data safety monitoring board for Alphamedix. SM reports advisory board participation for Novartis Oncology and Ipsen. KH reports payment for steering committee participation from Novartis; grants or contracts from Novartis and SOFIE Biosciences; consulting fees from Advanced Accelerator Applications (a Novartis company), Amgen, AstraZeneca, Bain Capital, Bayer, Boston Scientific, Convergent, Curium, Debiopharm, EcoR1, Fusion, GE Healthcare, Immedica, ITM, Janssen, Merck, Molecular Partners, NVision, Pfizer, POINT Biopharma, Radiopharm Theranostics, Rhine Pharma, Siemens Healthineers, SOFIE Biosciences, Telix, Theragnostics, and Y-mAbs; honoraria from PeerVoice; meeting support from Janssen; advisory board participation for Fusion and GE Healthcare; and stock or stock options for SOFIE Biosciences, Pharma15, NVision, Convergent, Aktis Oncology, and AdvanCell. MP reports grants or contracts from Advanced Accelerator Applications (a Novartis company), Novartis, Ipsen, ITM, Camurus, and Boehringer Ingelheim; consulting fees from Advanced Accelerator Applications (a Novartis company), Novartis, Ipsen, Riemser, and HUTCHMED; honoraria from Ipsen, Advanced Accelerator Applications (a Novartis company), Novartis, Boehringer Ingelheim, MSD, Lilly, Recordati, Sanofi, and Serb; advisory board participation for Crinetics and Advanced Accelerator Applications (a Novartis company); and unpaid roles as ENETS committee member and President, on the ESMO education committee, and on the INCA advisory board. PLK reports grants or contracts from RayzeBio and Novartis; honoraria from Natera, ITM, BMS, and Foundation Medicine; steering committee participation (uncompensated) for RayzeBio and Exelixis; and advisory board participation and honoraria from Amgen, Genentech, Crinetics, HUTCHMED, and Ipsen. BC reports advisory board participation and honoraria from Advanced Accelerator Applications (a Novartis company). SL reports advisory board participation for Advanced Accelerator Applications (a Novartis company). JC reports grants or contracts from Novartis, Pfizer, AstraZeneca, Advanced Accelerator Applications (a Novartis company), Eisai, Amgen, and Bayer; and consulting fees and honoraria from Novartis, Pfizer, Ipsen, Exelixis, Bayer, Eisai, Advanced Accelerator Applications (a Novartis company), Amgen, Sanofi, Lilly, Hutchinson Pharma, ITM, Advanz, Merck, Esteve, and Roche. AG-B reports consulting fees from Advanced Accelerator Applications (a Novartis company), Bayer, and Sanofi; and speaker fees and meeting support from Novartis. D-YO reports grants or contracts from AstraZeneca, Novartis, Array, Eli Lilly, Servier, BeiGene, MSD, and Handok; and advisory board participation for AstraZeneca, Novartis, Genentech/Roche, Merck, Bayer, Taiho, ASLAN, Halozyme, Zymeworks, BMS/Celgene, BeiGene, Basilea, Turning Point, Yuhan, Arcus Biosciences, IQVIA, MSD, LG Chem, Astellas, AbbVie, J-Pharma, Mirati Therapeutics, Eutilex, Moderna, and Idience. CY reports grants or contracts from Bayer, Ipsen, AstraZeneca, Boehringer Ingelheim, Servier, and Eisai; and honoraria from Bayer, Ipsen, MSD, Merck, Celgene, AstraZeneca, GSK, Eisai, Roche, Genentech, and Novartis. TRH reports consulting fees from TerSera; advisory board participation and research support from Camurus, ITM, Advanced Accelerator Applications (a Novartis company), Crinetics, and Perspective Therapeutics; research support from Thermo Fisher Scientific; and an unpaid role as President of NANETS. IF, YZ, and PA report employment by Novartis and stock or stock options for Novartis. WWdH reports consulting fees and honoraria from Ipsen, Novartis, and Advanced Accelerator Applications (a Novartis company); and consulting fees from ITM. DF reports grants or contracts from Camurus and Pfizer; honoraria from Novartis and Recordati Rare Diseases; and advisory board participation for Camurus, Ipsen, Novartis, Recordati Rare Diseases, and Pfizer. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Objective: The management of thyroid nodules with indeterminate cytology (ITN) is still a challenge. To evaluate the performance of commercial molecular tests for ITN, we performed this comprehensive meta-analysis., Methods: We performed an electronic search using PubMed/Medline, Embase, and the Cochrane Library. Studies assessing the diagnostic accuracy of Afirma gene expression classifier (GEC), Afirma gene sequencing classifier (GSC), ThyroSeq v2 (TSv2), or ThyroSeq v3 (TSv3) in patients with ITN (only Bethesda category III or IV) were selected; Statistical analyses were performed by using Stata., Results: Seventy-one samples (GEC, n = 38; GSC, n = 16; TSv2, n = 9; TSv3, n = 8) in 53 studies, involving 6490 fine needle aspirations (FNAs) with ITN cytology with molecular diagnostics (GEC, GSC, TSv2, or TSv3), were included in the study. The meta-analysis showed the following pooled estimates: sensitivity 0.95 (95% CI: 0.94-0.97), specificity 0.35 (0.28-0.43), positive likelihood ratio (LR+) 1.5 (1.3-1.6), and negative likelihood ratio (LR-) 0.13 (0.09-0.19), with the best performance for TSv3 (area under the ROC curve 0.95 (0.93-0.96), followed by TSv2 (0.90 (0.87-0.92)), GSC (0.86 (0.82-0.88)), and GEC (0.82 (0.78-0.85)); the best rule-out property was observed for GSC (LR-, 0.07 (0.02-0.19)), followed by TSv3 (0.11 (0.05-0.24)) and GEC (0.16 (0.10-0.28), and the best rule-in was observed for TSv2 (LR+, 2,9 (1.4-4.6)), followed by GSC (1.9 (1.6-2.4)). A meta-regression analysis revealed that study design, Bethesda category, and type of molecular test were independent factors., Conclusion: We showed that in patients with ITN, TSv3 has the best molecular diagnostic performance, followed by TSv2, GSC, and GEC. As regards rule-out malignancy, GSC, and rule-in, TSV2 is superior to other tests.

Introduction: Prostate Specific Membrane Antigen Positron Emission Tomography (PSMA-PET) is routinely used for the staging of patients with prostate cancer, but data on response assessment are sparse and primarily stem from metastatic castration-resistant prostate cancer (mCRPC) patients treated with PSMA radioligand therapy. Still, follow-up PSMA-PET is employed in earlier disease stages in case of clinical suspicion of disease persistence, recurrence or progression to decide if localized or systemic treatment is indicated. Therefore, the prognostic value of PSMA-PET derived tumor volumes in earlier disease stages (i.e., hormone-sensitive prostate cancer (HSPC) and non-[ 177 Lu]Lu-PSMA-617 (LuPSMA) therapy castration resistant prostate cancer (CRPC)) are evaluated in this manuscript. Methods: A total number of 73 patients (6 primary staging, 42 HSPC, 25 CRPC) underwent two (i.e., baseline and follow-up, median interval: 379 days) whole-body [ 68 Ga]Ga-PSMA-11 PET/CT scans between Nov 2014 and Dec 2018. Analysis was restricted to non-LuPSMA therapy patients. PSMA-PETs were retrospectively analyzed and primary tumor, lymph node-, visceral-, and bone metastases were segmented. Body weight-adjusted organ-specific and total tumor volumes (PSMAvol: sum of PET volumes of all lesions) were measured for baseline and follow-up. PSMAvol response was calculated as the absolute difference of whole-body tumor volumes. High metastatic burden (>5 metastases), RECIP 1.0 and PSMA-PET Progression Criteria (PPP) were determined. Survival data were sourced from the cancer registry. Results: The average number of tumor lesions per patient on the initial PET examination was 10.3 (SD 28.4). At baseline, PSMAvol was strongly associated with OS (HR 3.92, p <0.001; n = 73). Likewise, response in PSMAvol was significantly associated with OS (HR 10.48, p < 0.005; n = 73). PPP achieved significance as well (HR 2.19, p <0.05, n = 73). Patients with hormone sensitive disease and poor PSMAvol response (upper quartile of PSMAvol change) in follow-up had shorter outcome (p < 0.05; n = 42). PSMAvol in bones was the most relevant parameter for OS prognostication at baseline and for response assessment (HR 31.11 p < 0.001; HR 32.27, p < 0.001; n = 73). Conclusion: PPP and response in PSMAvol were significantly associated with OS in the present heterogeneous cohort. Bone tumor volume was the relevant miTNM region for OS prognostication. Future prospective evaluation of the performance of organ specific PSMAvol in more homogeneous cohorts seems warranted., Competing Interests: Competing Interests: David Kersting reports fees from Pfizer (research funding, speaker honoraria), Novartis (speaker honoraria), and funding by the German Research Foundation (DFG, KE2933/1-1) outside of the submitted work. Tugce Telli reports speaker fee from Abx not related to current work. Ken Herrmann, Amgen, AstraZeneca, Bain Capital, Bayer, Boston Scientific, Convergent, Curium, Debiopharm reports receiving consultant fees from Advanced Accelerator Applications, a Novartis company, EcoR1, Fusion, GE Healthcare, Immedica, Isotopen Technologien München, Janssen, Merck, Molecular Partners, NVision, POINT Biopharma, Pfizer, Radiopharm Theranostics, Rhine Pharma, Siemens Healthineers, Sofie Biosciences, Telix, and Theragnostics, ymabs, travel fees from Janssen, payment for educational events from PeerVoice, receiving research grants from Novartis and Sofie Biosciences, having stock or stock option interests with AdvanCell, Aktis Oncology, Convergent, NVision, Pharma 15, and Sofie Biosciences, reports serving on advisory boards for Fusion, GE Healthcare. Axel Rominger has received research support and speaker honoraria from Siemens Healthineers. Wolfgang P. Fendler reports fees from SOFIE Bioscience (research funding), Janssen (consultant, speaker), Calyx (consultant, image review), Bayer (consultant, speaker, research funding), Novartis (speaker, consultant), Telix (speaker), GE Healthcare (speaker), Eczacıbaşı Monrol (speaker), Abx (speaker), Amgen (speaker), Urotrials (speaker) outside of the submitted work. Boris Hadaschik reports serving on advisory boards for Janssen, Bayer, ABX, Lightpoint, Amgen, MSD, Pfizer, and Novartis; being an invited speaker for Accord, Astellas, and Janssen; receiving institutional royalties from Uromed; receiving institutional funding from AAA/Novartis, Bristol Myers Squibb, MS, and German Research Foundation; holding an advisory role for German Cancer Aid; and holding a leadership role/speaker for DKG AUO and DGU. Christopher Darr reports personal fees from Janssen-Cilag and Bayer, travel fees from Janssen-Cilag and Ipsen. Lale Umutlu is a Speaker/Advisory Board Member for Bayer Healthcare and Siemens Healthcare and received research grants from Siemens Healthcare outside of the submitted work. Ken Herrmann reports personal fees from Bayer SIRTEX Adacap Curium Endocyte IPSEN Siemens Healthineers GE Healthcare Amgen Novartis and ymabs personal fees and other from Sofie Biosciences non-financial support from ABX grants and personal fees from BTG outside the submitted work. Robert Seifert has received research support from Boehringer Ingelheim Fonds and Else Kröner-Fresenius-Stiftung. All other authors have no conflicts of interest to declare., (© The author(s).)

Purpose: To compare personalized dosimetry with yttrium-90 ( 90 Y)-loaded glass microspheres (SIRT) vs atezolizumab and bevacizumab (A+B) in hepatocellular carcinoma (HCC) treatment in terms of cost-effectiveness and budget impact from a German statutory health insurance (SHI) perspective., Patients and Methods: Cost-effectiveness analysis (CEA) and budget impact analysis (BIA) models were developed in MS Excel. The available key studies (IMbrave150 and DOSISPHERE-01) suggest that both strategies are comparable in terms of progression-free survival and overall survival in HCC, but a difference in severe adverse events (SAE) in favor of SIRT was observed. Accordingly, the CEA model investigates the endpoints "cost per SAE avoided" and "cost per quality-adjusted life year (QALY) gained", whereas the BIA simulates the impact of a stepwise re-allocation of current market share to the option which emerges as more cost-effective from the CEA., Results: The model suite estimated a mean annual total per-patient costs of € 29,984 for SIRT, compared to € 75,725 for A+B. SIRT was associated with a lower number of SAE and a higher number of QALYs compared to A+B. Switching additionally 25% of the eligible patients (≈500) from systemic therapy to SIRT could generate annual savings of approximately € 22.6 million Euros to the SHI., Conclusion: SIRT was identified as dominant treatment strategy. SIRT use not only saves SHI expenditure compared to systemic immunotherapy but also yields extra QALYs. This positions SIRT as the dominant and more cost-effective treatment strategy for patients with HCC. The savings to the SHI system, derived from the BIA conducted, become increasingly significant with rising adoption rates of SIRT., Competing Interests: The authors report no conflicts of interest in this work. This study was funded by Boston Scientific Medizintechnik GmbH. Dr Bjoern Schwander, Mrs Katharina Klesper, and Prof. Dr. York Zoellner report personal fees from Boston Scientific Medizintechnik GmbH, during the conduct of the study. This paper was presented at the ISPOR Europe 2022 (Vienna, Austria) as a poster presentation with interim findings. The poster and abstract were published in “Poster Abstracts” in Value in Health, Volume 25, Issue 12S (December 2022): https://doi.org/10.1016/j.jval.2022.09.806., (© 2024 Schwander et al.)

Prospective results have demonstrated favorable safety and efficacy of [ 177 Lu]Lu-PSMA radiopharmaceutical therapy for up to 6 cycles in men with metastatic castration-resistant prostate cancer. However, no systematic data are available outlining the feasibility of extended therapy beyond 6 cycles. We aim to evaluate the safety and efficacy of extended [ 177 Lu]Lu-PSMA radiopharmaceutical therapy in patients who have received more than 6 cycles. Methods: In total, 111 patients were included in this multicenter retrospective analysis. Based on individual decisions, patients underwent uninterrupted continuation of therapy (continuous treatment) or reexposure after a therapy break (rechallenge treatment) between 2014 and 2023. Overall survival, 50% prostate-specific antigen (PSA) decline (measured 8-12 wk after treatment initiation or rechallenge), PSMA PET response, and grades per Common Terminology Criteria for Adverse Events were assessed. χ 2 tests, multivariable Cox regression analysis, and log-rank tests were applied for statistical analyses. Results: Patients received extended treatment with [ 177 Lu]Lu-PSMA, either as a continuous treatment (43/111, 38.7%) or as a rechallenge (68/111, 61.3%) treatment, with median cumulative doses of 57.4 or 60.8 GBq, respectively. Overall survival from the initiation of [ 177 Lu]Lu-PSMA was 31.3, 23.2, and 40.2 mo for the entire cohort, the continuous treatment group, and the rechallenge treatment group, respectively. The initial 50% PSA decline was significantly higher in the retreated group than in the continuous group (57/63 [90.4%] vs. 26/42 [61.9%]; P = 0.006). A 50% PSA decline was observed in 23 of 62 patients (37.1%) after the first rechallenge. The rate of grades 3-4 toxicity was comparable between continuous and rechallenge treatments (anemia, 7/43 [16.3%] vs. 13/68 [19.1%)], P = 0.6; leukocytopenia, 1/43 [2.3%] vs. 2/67 [3.0%], P = 0.3; thrombocytopenia, 3/43 [7.0%] vs. 3/68 [4.4%], P = 0.3; renal, 2/43 [4.7%] vs. 5/68 [7.4%], P = 0.2). Conclusion: Extended therapy with [ 177 Lu]Lu-PSMA is safe and has not been associated with increased grades 3-4 toxicity. Patient candidates for extended treatment experienced a favorable median survival of 31.3 mo from the first administration. Response under [ 177 Lu]Lu-PSMA rechallenge demonstrated preserved efficacy of [ 177 Lu]Lu-PSMA after a treatment break., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

Fibroblast activation protein-α (FAP) is often highly expressed by sarcoma cells and by sarcoma-associated fibroblasts in the tumor microenvironment. This makes it a promising target for imaging and therapy. The level of FAP expression and the diagnostic value of 68 Ga-FAP inhibitor (FAPI) PET for sarcoma subtypes are unknown. We assessed the diagnostic performance and accuracy of 68 Ga-FAPI PET in various bone and soft-tissue sarcomas. Potential eligibility for FAP-targeted radiopharmaceutical therapy (FAP-RPT) was evaluated. Methods: This prospective observational trial enrolled 200 patients with bone and soft-tissue sarcoma who underwent 68 Ga-FAPI PET/CT and 18 F-FDG PET/CT (186/200, or 93%) for staging or restaging. The number of lesions detected and the uptake (SUV max ) of the primary tumor, lymph nodes, and visceral and bone metastases were analyzed. The Wilcoxon test was used for semiquantitative assessment. The association of 68 Ga-FAPI uptake intensity, histopathologic grade, and FAP expression in sarcoma biopsy samples was analyzed using Spearman r correlation. The impact of 68 Ga-FAPI PET on clinical management was investigated using questionnaires before and after PET/CT. Eligibility for FAP-RPT was defined by an SUV max greater than 10 for all tumor regions. Results: 68 Ga-FAPI uptake was heterogeneous among sarcoma subtypes. The 3 sarcoma entities with the highest uptake (mean SUV max ± SD) were solitary fibrous tumor (24.7 ± 11.9), undifferentiated pleomorphic sarcoma (18.8 ± 13.1), and leiomyosarcoma (15.2 ± 10.2). Uptake of 68 Ga-FAPI versus 18 F-FDG was significantly higher in low-grade sarcomas (10.4 ± 8.5 vs. 7.0 ± 4.5, P = 0.01) and in potentially malignant intermediate or unpredictable sarcomas without a World Health Organization grade (not applicable [NA]; 22.3 ± 12.5 vs. 8.5 ± 10.0, P = 0.0004), including solitary fibrous tumor. The accuracy, as well as the detection rates, of 68 Ga-FAPI was higher than that of 18 F-FDG in low-grade sarcomas (accuracy, 92.2 vs. 80.0) and NA sarcomas (accuracy, 96.9 vs. 81.9). 68 Ga-FAPI uptake and the histopathologic FAP expression score ( n = 89) were moderately correlated (Spearman r = 0.43, P < 0.0002). Of 138 patients, 62 (45%) with metastatic sarcoma were eligible for FAP-RPT. Conclusion: In patients with low-grade and NA sarcomas, 68 Ga-FAPI PET demonstrates uptake, detection rates, and accuracy superior to those of 18 F-FDG PET. 68 Ga-FAPI PET criteria identified eligibility for FAP-RPT in about half of sarcoma patients., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

Targeted therapy with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) has established the precision oncology paradigm in lung cancer. Most patients with EGFR -mutated lung cancer respond but eventually acquire resistance. Methods: Patients exhibiting the EGFR p.T790M resistance biomarker benefit from sequenced targeted therapy with osimertinib. We hypothesized that metabolic response as detected by 18 F-FDG PET after short-course osimertinib identifies additional patients susceptible to sequenced therapy. Results: Fourteen patients with EGFR -mutated lung cancer and resistance to first- or second-generation EGFR TKI testing negatively for EGFR p.T790M were enrolled in a phase II study. Five patients (36%) achieved a metabolic 18 F-FDG PET response and continued osimertinib. In those, the median duration of treatment was not reached (95% CI, 24 mo to not estimable), median progression-free survival was 18.7 mo (95% CI, 14.6 mo to not estimable), and median overall survival was 41.5 mo. Conclusion: Connecting theranostic osimertinib treatment with early metabolic response assessment by PET enables early identification of patients with unknown mechanisms of TKI resistance who derive dramatic clinical benefit from sequenced osimertinib. This defines a novel paradigm for personalization of targeted therapies in patients with lung cancer dependent on a tractable driver oncogene., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

Response Evaluation Criteria in Prostate-Specific Membrane Antigen Imaging (RECIP) 1.0 is an evidence-based framework to evaluate therapeutic efficacy in metastatic prostate cancer using prostate-specific membrane antigen (PSMA) PET/CT. This study aimed to evaluate the associations of interim PSMA PET/CT by RECIP 1.0 with short-term outcome after radiopharmaceutical treatment. Methods: This multicenter retrospective study included patients with metastatic castration-resistant prostate cancer who underwent [ 177 Lu]Lu-PSMA radiopharmaceutical therapy at 3 academic centers and received PSMA PET/CT at baseline and at 12 wk. Pairs of PSMA PET/CT images were assessed by 5 readers for visual RECIP 1.0. The primary outcome was the association of RECIP with prostate-specific antigen progression-free survival (PSA-PFS) by Kaplan-Meier analysis. Results: In total, 124 of 287 screened patients met the inclusion criteria, with 0 (0%), 29 (23%), 54 (44%), and 41 (33%) of those 124 patients having complete response, partial response, stable disease, or progressive disease (PD) by visual RECIP 1.0, respectively. Patients with visual RECIP PD had a significantly shorter PSA-PFS than those with RECIP stable disease or with RECIP partial response (2.6 vs. 6.4 vs. 8.4 mo; P < 0.001). The median PSA-PFS among patients with RECIP PD versus those with non-RECIP PD was 2.6 versus 7.2 mo (hazard ratio, 13.0; 95% CI, 7.0-24.1; P < 0.001). Conclusion: PSMA PET/CT by RECIP 1.0 after 2 cycles of [ 177 Lu]Lu-PSMA is prognostic for PSA-PFS. PSMA PET/CT by RECIP 1.0 may be used in earlier stages of prostate cancer to evaluate drug efficacy and to predict progression-free survival., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)