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Background: The TheraP study reported improved prostate-specific antigen responses with lutetium-177 [ 177 Lu]Lu-PSMA-617 versus cabazitaxel in men with metastatic castration-resistant prostate cancer progressing after docetaxel. In this Article, we report the secondary outcome of overall survival with mature follow-up, and an updated imaging biomarker analysis. We also report the outcomes of participants excluded due to ineligibility on gallium-68 [ 68 Ga]Ga-PSMA-11 and 2-[ 18 F]fluoro-2-deoxy-D-glucose (2-[ 18 F]FDG) PET-CT., Methods: TheraP was an open-label, randomised phase 2 trial at 11 centres in Australia. Eligible participants had metastatic castration-resistant prostate cancer progressing after docetaxel, and PET imaging with [ 68 Ga]Ga-PSMA-11 and 2-[ 18 F]FDG that showed prostate-specific membrane antigen (PSMA)-positive disease and no sites of metastatic disease with discordant 2-[ 18 F]FDG-positive and PSMA-negative findings. Participants were randomly assigned (1:1) to treatment with [ 177 Lu]Lu-PSMA-617 (every 6 weeks for a maximum of six cycles; starting at 8·5 GBq, decreasing by 0.5 GBq to 6·0 GBq for the sixth cycle) versus cabazitaxel (20 mg/m 2 every 3 weeks, maximum of ten cycles). Overall survival was analysed by intention-to-treat and summarised as restricted mean survival time (RMST) to account for non-proportional hazards, with a 36-month restriction time corresponding to median follow-up. This trial is registered with ClinicalTrials.gov, NCT03392428, and is complete., Findings: 291 men were registered from Feb 6, 2018, to Sept 3, 2019; after study imaging, 200 were eligible and randomly assigned to treatment with [ 177 Lu]Lu-PSMA-617 (n=99) or cabazitaxel (n=101). After completing study treatment, 20 (20%) participants assigned to cabazitaxel and 32 (32%) assigned to [ 177 Lu]Lu-PSMA-617 were subsequently treated with the alternative regimen. After a median follow-up of 35·7 months (IQR 31·1 to 39·2), 77 (78%) participants had died in the [ 177 Lu]Lu-PSMA-617 group and 70 (69%) participants had died in the cabazitaxel group. Overall survival was similar among those assigned to [ 177 Lu]Lu-PSMA-617 versus those assigned to cabazitaxel (RMST 19·1 months [95% CI 16·9 to 21·4] vs 19·6 months [17·4 to 21·8]; difference -0·5 months [95% CI -3·7 to 2·7]; p=0·77). No additional safety signals were identified with the longer follow-up in this analysis. 80 (27%) of 291 men who were registered after initial eligibility screening were excluded after [ 68 Ga]Ga-PSMA-11 and 2-[ 18 F]FDG PET. In the 61 of these men with follow-up available, RMST was 11·0 months (95% CI 9·0 to 13·1)., Interpretation: These results support the use of [ 177 Lu]Lu-PSMA-617 as an alternative to cabazitaxel for PSMA-positive metastatic castration-resistant prostate cancer progressing after docetaxel. We did not find evidence that overall survival differed between the randomised groups. Median overall survival was shorter for men who were excluded because of low PSMA expression or 2-[ 18 F]FDG-discordant disease., Funding: Australian and New Zealand Urogenital and Prostate Cancer Trials Group, Prostate Cancer Foundation of Australia, Endocyte (a Novartis company), Australian Nuclear Science and Technology Organization, Movember, It's a Bloke Thing, CAN4CANCER, and The Distinguished Gentleman's Ride., Competing Interests: Declaration of interests MSH reports research grant support (to their institution) from Novartis (including AAA and Endocyte), Australian Nuclear Science and Technology Organization (ANSTO), Bayer, Isotopia, and MIM; and consulting fees for lectures or advisory boards from Astellas and AstraZeneca in the past 2 years, and from Janssen, MSD, and Mundipharma in the past 5 years. LE reports personal fees from AstraZenca, Janssen, and Astellas, outside the submitted work. SS reports grants from AAA, AstraZeneca, MSD, and Genetech to their institution; and personal fees from AstraZeneca, MSD, Bristol Myers Squibb, and AstraZeneca to their institution, outside the submitted work. DAP reports personal fees from Ipsen and Eisai, outside the submitted work. RJF reports institution funding and consulting fees from AIQ Solutions, outside of the submitted work; and committee involvement in the Australasian Radiopharmaceutical Trials Network (unpaid). CG donated personal fees from Astellas, Janssen, AstraZeneca, Bristol Myers Squibb, EMD Serono, Ipsen, Astellas, and MSD, direct and complete, to a third party not-for-profit. AMS reports trial or research funding from EMD Serono, ITM, AVID, Medimmune, Telix, Adalta, Fusion, Antengene, Earli, Curis, and Cyclotek; grants from the Australian National Health and Medical Research Council (NHMRC) and Medical Research Future Fund (MRFF), including an NHMRC Investigator Grant; and board and advisory committee involvement for the Australian and New Zealand Society of Nuclear Medicine and Australian and New Zealand Urogenital and Prostate (ANZUP) Cancer Trials Group (unpaid); all outside the submitted work. EMK reports personal fees from Astellas Pharma, Janssen, Pfizer, Ipsen, and Roche, all outside the submitted work; and is supported by a Prostate Cancer Foundation Young Investigator Award and University of British Columbia Killam Postdoctoral Fellowship. AAA reports grants or personal fees from Janssen, Astellas, Novartis, Merck Serono, Tolmar, Amgen, Pfizer, Bayer, Telix Pharmaceuticals, Bristol Myers Squibb, Sanofi, Noxopharm, AstraZeneca, Ipsen, MSD, Aculeus Therapeutics, and Daiichi Sankyo; and grants from Astellas (investigator), Merck Serono (investigator), AstraZeneca (investigator), Bristol Myers Squibb (institutional), AstraZeneca (institutional), Aptevo Therapeutics (institutional), GlaxoSmithKline (institutional), Pfizer (institutional), MedImmune (institutional), Astellas (institutional), Synthorx (institutional), Bionomics (institutional), Sanofi Aventis (institutional), Novartis (institutional), Ipsen (institutional), Exelixis (institutional), MSD (institutional), Janssen (institutional), Eli Lilly (institutional), Gilead Sciences (institutional), Merck Serono (institutional), and Hinova (institutional), all outside the submitted work. MRS reports grants to his institution from the NHMRC, Cancer Australia, Astellas, Amgen, AstraZeneca, Bayer, Bionomics, Bristol Myers Squibb, Celgene, Medivation, MSD, Pfizer, Roche, Sanofi, and Tilray, all outside the submitted work. IDD reports grants from the NHMRC, during the conduct of the study; and institutional payments to support prostate cancer trials from Pfizer, the ANZUP Cancer Trials Group, Bayer, Astellas, Janssen, Movember Foundation, and MSD, outside the submitted work. IDD is also unremunerated Chair of the ANZUP Cancer Trials Group, and is supported in part by an NHMRC Investigator Grant (grant number 2016274). AMJ reports consulting or advisory roles (to their institution) from Janssen Oncology, Ipsen, AstraZeneca, Sanofi, Pfizer, Novartis, Bristol Myers Squibb, Merck Serono, Eisai, Bayer, and Astellas Pharma; and research funding (to their institution) from Bristol Myers Squibb, Janssen Oncology, MSD, Mayne Pharma, Genentech, Bayer, Lilly, Pfizer, and AstraZeneca. AI reports personal fees for a consulting role for Curium Pharma and payment to their institution for a consulting role from Ambrx Pharma, all outside the submitted work. AJW reports a consulting role for and travel support from Bayer. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Purpose: The O-(2-[ 18 F]-fluoroethyl)-L-tyrosine (FET) PET in Glioblastoma (FIG) trial is an Australian prospective, multi-centre study evaluating FET PET for glioblastoma patient management. FET PET imaging timepoints are pre-chemoradiotherapy (FET1), 1-month post-chemoradiotherapy (FET2), and at suspected progression (FET3). Before participant recruitment, site nuclear medicine physicians (NMPs) underwent credentialing of FET PET delineation and image interpretation., Methods: Sites were required to complete contouring and dynamic analysis by ≥ 2 NMPs on benchmarking cases (n = 6) assessing biological tumour volume (BTV) delineation (3 × FET1) and image interpretation (3 × FET3). Data was reviewed by experts and violations noted. BTV definition includes tumour-to-background ratio (TBR) threshold of 1.6 with crescent-shaped background contour in the contralateral normal brain. Recurrence/pseudoprogression interpretation (FET3) required assessment of maximum TBR (TBR max ), dynamic analysis (time activity curve [TAC] type, time to peak), and qualitative assessment. Intraclass correlation coefficient (ICC) assessed volume agreement, coefficient of variation (CoV) compared maximum/mean TBR (TBR max /TBR mean ) across cases, and pairwise analysis assessed spatial (Dice similarity coefficient [DSC]) and boundary agreement (Hausdorff distance [HD], mean absolute surface distance [MASD])., Results: Data was accrued from 21 NMPs (10 centres, n ≥ 2 each) and 20 underwent review. The initial pass rate was 93/119 (78.2%) and 27/30 requested resubmissions were completed. Violations were found in 25/72 (34.7%; 13/12 minor/major) of FET1 and 22/74 (29.7%; 14/8 minor/major) of FET3 reports. The primary reasons for resubmission were as follows: BTV over-contour (15/30, 50.0%), background placement (8/30, 26.7%), TAC classification (9/30, 30.0%), and image interpretation (7/30, 23.3%). CoV median and range for BTV, TBR max , and TBR mean were 21.53% (12.00-30.10%), 5.89% (5.01-6.68%), and 5.01% (3.37-6.34%), respectively. BTV agreement was moderate to excellent (ICC = 0.82; 95% CI, 0.63-0.97) with good spatial (DSC = 0.84 ± 0.09) and boundary (HD = 15.78 ± 8.30 mm; MASD = 1.47 ± 1.36 mm) agreement., Conclusion: The FIG study credentialing program has increased expertise across study sites. TBR max and TBR mean were robust, with considerable variability in BTV delineation and image interpretation observed., (© 2023. The Author(s).)

Hormonal crises are a rare but increasingly recognized phenomenon following peptide receptor radionuclide therapy (PRRT) in patients with neuroendocrine neoplasms (NENs). Due to the paucity of published studies, approaches to the identification, prevention, and management of risk factors are inconsistent between different institutions. This consensus statement aimed to provide guidance for NEN patients undergoing PRRT. Our statement has been created on the basis of clinical demand and concerns regarding the precipitation of hormonal crises. A formal literature review was conducted to identify available studies. A total of 19 Australian and New Zealand experts in the fields of medical oncology, nuclear medicine, anaesthetics, and endocrinology collaborated on this consensus statement. The main focus is on carcinoid crises. Other hormonal crises seen in patients with functional pancreatic NENs are addressed briefly. These recommendations are relevant to PRRT centres internationally and should be tailored to local experience and available resources., (© 2022 S. Karger AG, Basel.)

In nuclear medicine, theranostics is a burgeoning development that is rapidly being implemented worldwide. There is an increasing need to provide a multidisciplinary framework to the practice of theranostics, ensuring that patients receive this treatment safely and are secure in the knowledge that their health-care practitioners are adequately trained. Nuclear medicine experts in Australia have taken the initiative of producing a set of theranostic guidelines relevant to Australian medical practice. These guidelines encompass specialist qualifications, patient care, radiopharmaceutical production, radiation safety, and dosimetry. We propose adaptation of these guidelines by other countries, and we promote standards of practice leading to optimal clinical outcomes for patients receiving theranostic treatments., (© 2022 by the Society of Nuclear Medicine and Molecular Imaging.)