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Item does not contain fulltext, BACKGROUND: Innovations in imaging and molecular characterisation and the evolution of new therapies have improved outcomes in advanced prostate cancer. Nonetheless, we continue to lack high-level evidence on a variety of clinical topics that greatly impact daily practice. To supplement evidence-based guidelines, the 2022 Advanced Prostate Cancer Consensus Conference (APCCC 2022) surveyed experts about key dilemmas in clinical management. OBJECTIVE: To present consensus voting results for select questions from APCCC 2022. DESIGN, SETTING, AND PARTICIPANTS: Before the conference, a panel of 117 international prostate cancer experts used a modified Delphi process to develop 198 multiple-choice consensus questions on (1) intermediate- and high-risk and locally advanced prostate cancer, (2) biochemical recurrence after local treatment, (3) side effects from hormonal therapies, (4) metastatic hormone-sensitive prostate cancer, (5) nonmetastatic castration-resistant prostate cancer, (6) metastatic castration-resistant prostate cancer, and (7) oligometastatic and oligoprogressive prostate cancer. Before the conference, these questions were administered via a web-based survey to the 105 physician panel members ("panellists") who directly engage in prostate cancer treatment decision-making. Herein, we present results for the 82 questions on topics 1-3. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Consensus was defined as ≥75% agreement, with strong consensus defined as ≥90% agreement. RESULTS AND LIMITATIONS: The voting results reveal varying degrees of consensus, as is discussed in this article and shown in the detailed results in the Supplementary material. The findings reflect the opinions of an international panel of experts and did not incorporate a formal literature review and meta-analysis. CONCLUSIONS: These voting results by a panel of international experts in advanced prostate cancer can help physicians and patients navigate controversial areas of clinical manage

01 juli 2023, Contains fulltext : 294539.pdf (Publisher’s version ) (Open Access), Prostate-specific membrane antigen (PSMA) is expressed by the majority of clinically significant prostate adenocarcinomas, and patients with target-positive disease can easily be identified by PSMA PET imaging. Promising results with PSMA-targeted radiopharmaceutical therapy have already been obtained in early-phase studies using various combinations of targeting molecules and radiolabels. Definitive evidence of the safety and efficacy of [(177)Lu]Lu-PSMA-617 in combination with standard-of-care has been demonstrated in patients with metastatic castration-resistant prostate cancer, whose disease had progressed after or during at least one taxane regimen and at least one novel androgen-axis drug. Preliminary data suggest that (177)Lu-PSMA-radioligand therapy (RLT) also has high potential in additional clinical situations. Hence, the radiopharmaceuticals [(177)Lu]Lu-PSMA-617 and [(177)Lu]Lu-PSMA-I&T are currently being evaluated in ongoing phase 3 trials. The purpose of this guideline is to assist nuclear medicine personnel, to select patients with highest potential to benefit from (177)Lu-PSMA-RLT, to perform the procedure in accordance with current best practice, and to prepare for possible side effects and their clinical management. We also provide expert advice, to identify those clinical situations which may justify the off-label use of [(177)Lu]Lu-PSMA-617 or other emerging ligands on an individual patient basis.

Background: innovations in treatments, imaging, and molecular characterisation in advanced prostate cancer have improved outcomes, but various areas of management still lack high-level evidence to inform clinical practice. The 2021 Advanced Prostate Cancer Consensus Conference (APCCC) addressed some of these questions to supplement guidelines that are based on level 1 evidence. Objective: to present the voting results from APCCC 2021. Design, setting, and participants: the experts identified three major areas of controversy related to management of advanced prostate cancer: newly diagnosed metastatic hormone-sensitive prostate cancer (mHSPC), the use of prostate-specific membrane antigen ligands in diagnostics and therapy, and molecular characterisation of tissue and blood. A panel of 86 international prostate cancer experts developed the programme and the consensus questions. Outcome measurements and statistical analysis: The panel voted publicly but anonymously on 107 pre-defined questions, which were developed by both voting and non-voting panel members prior to the conference following a modified Delphi process. Results and limitations: the voting reflected the opinions of panellists and did not incorporate a standard literature review or formal meta-analysis. The answer options for the consensus questions received varying degrees of support from panellists, as reflected in this article and the detailed voting results reported in the Supplementary material. Conclusions: these voting results from a panel of experts in advanced prostate cancer can help clinicians and patients to navigate controversial areas of management for which high-level evidence is scant. However, diagnostic and treatment decisions should always be individualised according to patient characteristics, such as the extent and location of disease, prior treatment(s), comorbidities, patient preferences, and treatment recommendations, and should also incorporate current and emerging clinical eviden, National Health and Medical Research Council (NHMRC) Practitioner Fellowship; Prostate Cancer Foundation; Peter MacCallum Foundation; NHMRC Investigator Grant

Patients with advanced prostate cancer (APC) may be at greater risk for severe illness, hospitalisation, or death from coronavirus disease 2019 (COVID-19) due to male gender, older age, potential immunosuppressive treatments, or comorbidities. Thus, the optimal management of APC patients during the COVID-19 pandemic is complex. In October 2021, during the Advanced Prostate Cancer Consensus Conference (APCCC) 2021, the 73 voting members of the panel members discussed and voted on 13 questions on this topic that could help clinicians make treatment choices during the pandemic. There was a consensus for full COVID-19 vaccination and booster injection in APC patients. Furthermore, the voting results indicate that the expert's treatment recommendations are influenced by the vaccination status: the COVID-19 pandemic altered management of APC patients for 70% of the panellists before the vaccination was available but only for 25% of panellists for fully vaccinated patients. Most experts (71%) were less likely to use docetaxel and abiraterone in unvaccinated patients with metastatic hormone-sensitive prostate cancer. For fully vaccinated patients with high-risk localised prostate cancer, there was a consensus (77%) to follow the usual treatment schedule, whereas in unvaccinated patients, 55% of the panel members voted for deferring radiation therapy. Finally, there was a strong consensus for the use of telemedicine for monitoring APC patients. Patient summary: In the Advanced Prostate Cancer Consensus Conference 2021, the panellists reached a consensus regarding the recommendation of the COVID-19 vaccine in prostate cancer patients and use of telemedicine for monitoring these patients., NA

Background: Lutetium-177 [177Lu]Lu-PSMA-617 is a radiolabelled small molecule that delivers beta radiation to cells expressing prostate-specific membrane antigen (PSMA), with activity and safety in patients with metastatic castration-resistant prostate cancer. We aimed to compare [177Lu]Lu-PSMA-617 with cabazitaxel in patients with metastatic castration-resistant prostate cancer. Method(s): We did this multicentre, unblinded, randomised phase 2 trial at 11 centres in Australia. We recruited men with metastatic castration-resistant prostate cancer for whom cabazitaxel was considered the next appropriate standard treatment. Participants were required to have adequate renal, haematological, and liver function, and an Eastern Cooperative Oncology Group performance status of 0-2. Previous treatment with androgen receptor-directed therapy was allowed. Men underwent gallium-68 [68Ga]Ga-PSMA-11 and 2-flourine-18[18F]fluoro-2-deoxy-D-glucose (FDG) PET-CT scans. PET eligibility criteria for the trial were PSMA-positive disease, and no sites of metastatic disease with discordant FDG-positive and PSMA-negative findings. Men were randomly assigned (1:1) to [177Lu]Lu-PSMA-617 (6.0-8.5 GBq intravenously every 6 weeks for up to six cycles) or cabazitaxel (20 mg/m2 intravenously every 3 weeks for up to ten cycles). The primary endpoint was prostate-specific antigen (PSA) response defined by a reduction of at least 50% from baseline. This trial is registered with ClinicalTrials.gov, NCT03392428. Finding(s): Between Feb 6, 2018, and Sept 3, 2019, we screened 291 men, of whom 200 were eligible on PET imaging. Study treatment was received by 98 (99%) of 99 men randomly assigned to [177Lu]Lu-PSMA-617 versus 85 (84%) of 101 randomly assigned to cabazitaxel. PSA responses were more frequent among men in the [177Lu]Lu-PSMA-617 group than in the cabazitaxel group (65 vs 37 PSA responses; 66% vs 37% by intention to treat; difference 29% (95% CI 16-42; p<0.0001; and 66% vs 44% by treatment rec

Objective: To compare the accuracy of 68gallium prostate-specific membrane antigen positron emission tomography/computed tomography (68Ga-PSMA PET/CT) with multiparametric MRI (mpMRI) in detecting and localising primary prostate cancer when compared with radical prostatectomy (RP) specimen pathology. Patients and Methods: Retrospective review of men who underwent 68Ga-PSMA PET/CT and mpMRI for primary prostate cancer before RP across four centres between 2015 and 2018. Patients undergoing imaging for recurrent disease or before non-surgical treatment were excluded. We defined pathological index tumour as the lesion with highest International Society of Urological Pathology Grade Group (GG) on RP specimen pathology. Our primary outcomes were rates of accurate detection and localisation of RP specimen pathology index tumour using 68Ga-PSMA PET/CT or mpMRI. We defined tumour detection as imaging lesion corresponding with RP specimen tumour on any imaging plane, and localisation as imaging lesion matching RP specimen index tumour in all sagittal, axial, and coronal planes. Secondary outcomes included localisation of clinically significant and transition zone (TZ) index tumours. We defined clinically significant disease as GG 3-5. We used descriptive statistics and the Mann-Whitney U-test to define and compare demographic and pathological characteristics between detected, missed and localised tumours using either imaging modality. We used the McNemar test to compare detection and localisation rates using 68Ga-PSMA PET/CT and mpMRI. Result(s): In all, 205 men were included in our analysis, including 133 with clinically significant disease. There was no significant difference between 68Ga-PSMA PET/CT and mpMRI in the detection of any tumour (94% vs 95%, P > 0.9). There was also no significant difference between localisation of all index tumours (91% vs 89%, P = 0.47), clinically significant index tumours (96% vs 91%, P = 0.15) or TZ tumours (85% vs 80%, P > 0.9) using 68Ga

Background: Conventional imaging using CT and bone scan has insufficient sensitivity when staging men with high-risk localised prostate cancer. We aimed to investigate whether novel imaging using prostate-specific membrane antigen (PSMA) PET-CT might improve accuracy and affect management. Method(s): In this multicentre, two-arm, randomised study, we recruited men with biopsy-proven prostate cancer and high-risk features at ten hospitals in Australia. Patients were randomly assigned to conventional imaging with CT and bone scanning or gallium-68 PSMA-11 PET-CT. First-line imaging was done within 21 days following randomisation. Patients crossed over unless three or more distant metastases were identified. The primary outcome was accuracy of first-line imaging for identifying either pelvic nodal or distant-metastatic disease defined by the receiver-operating curve using a predefined reference-standard including histopathology, imaging, and biochemistry at 6-month follow-up. This trial is registered with the Australian New Zealand Clinical Trials Registry, ANZCTR12617000005358. Finding(s): From March 22, 2017 to Nov 02, 2018, 339 men were assessed for eligibility and 302 men were randomly assigned. 152 (50%) men were randomly assigned to conventional imaging and 150 (50%) to PSMA PET-CT. Of 295 (98%) men with follow-up, 87 (30%) had pelvic nodal or distant metastatic disease. PSMA PET-CT had a 27% (95% CI 23-31) greater accuracy than that of conventional imaging (92% [88-95] vs 65% [60-69]; p<0.0001). We found a lower sensitivity (38% [24-52] vs 85% [74-96]) and specificity (91% [85-97] vs 98% [95-100]) for conventional imaging compared with PSMA PET-CT. Subgroup analyses also showed the superiority of PSMA PET-CT (area under the curve of the receiver operating characteristic curve 91% vs 59% [32% absolute difference; 28-35] for patients with pelvic nodal metastases, and 95% vs 74% [22% absolute difference; 18-26] for patients with distant metastases). First-line conv

Background: Neuroendocrine carcinomas (NECWHOgrade 3) are aggressive cancers that are rapidly fatal. There have been no randomised trials to date to establish standard therapy for advanced gastrointestinal (GI) NECs. Etoposide and carboplatin are used by extrapolation from small cell lung cancer data. Paclitaxel is also active in NECs but there is no data on the role of nab-paclitaxel. This randomised study aims to establish if carboplatin and nab-paclitaxel combination is an effective and tolerable treatment for advanced GI NECs. Trial design: NABNEC has commenced as a randomised phase II multicentre trial enrolling adults with advanced and/or metastatic non-resectable GI NECs. Patients are randomised to: Arm A (n=47) IV nab-paclitaxel 100 mg/m2 on Day 1 every week and IV carboplatin AUC= 5 on Day 1 every 3 weeks OR: Arm B (n=23) IV etoposide 100mg/m2on Days 1-3 every 3 weeks and IV carboplatin AUC =5 on Day 1 every 3 weeks. Treatment will continue until disease progression or unmanageable toxicity. The primary endpoint is objective response rate (RR) by RECIST 1.1. At 6 months, the RR in the intervention group would need to be at least 50% to justify further investigation. A total sample size of 70 patients with a 2:1 randomisation (intervention to control) will have 80% power with 95% confidence to rule out a 30% objective RR in favour of a more clinically relevant RR of 50% at 6months. Secondary endpoints include progression free survival, overall survival, safety as measured by NCI-CTCAE V4.03, and quality of life using EORTC QLQC30 and QLQ-GINET21 questionnaires. Translational research endpoints include (1) blood and tissue biomarkers (prognostic and/or predictive) correlated with clinical endpoints including (a) circulating tumour cells, (b) mutation profile by whole exome sequencing, (c) DNA methylation profile and (2) utility of 18-fluoro-deoxyglucose positron emission tomography (FDG-PET) imaging as an early predictor of response and association of SUV max

Dilation of lymphatic vessels may contribute to iatrogenic dissemination of cancer cells during surgery. We sought to determine whether neuraxial anesthesia reduces regional lymphatic flow. Using nuclear lymphoscintigraphy, 5 participants receiving spinal anesthesia for brachytherapy had lower extremity lymph flow at rest compared with flow under conditions of spinal anesthesia. Six limbs were analyzed. Four limbs were excluded because of failure to demonstrate lymph flow (1 patient, 2 limbs), colloid injection error (1 limb), and undiagnosed deep vein thrombosis (1 limb). All analyzed limbs showed reduced lymph flow washout from the pedal injection site (range 62%-100%) due to neuraxial anesthesia. Lymph flow was abolished in 3 limbs. We report proof-of-concept that neuraxial anesthesia reduces lymphatic flow through a likely mechanism of sympathectomy.Copyright © 2016 International Anesthesia Research Society.

Rationale: Pediatric patients with refractory neuroblastoma have limited therapeutic options. Neuroblastoma may express somatostatin receptors (SSTRs) allowing imaging with 68Ga-DOTA-Octreotate (GaTATE) positron emission tomography/computed tomography (PET/CT) and peptide receptor radionuclide therapy (PRRT). We reviewed our experience with this theranostic combination. Material(s) and Method(s): GaTATE studies (8 patients; 2 to 9 years old) were reviewed and compared with 123I-MIBG or posttreatment 131I-MIBG studies. Immunohistochemistry (IHC) for SSTR subtype 2 was performed in 5 patients. Four patients received PRRT. Result(s): GaTATE PET showed additional disease in 38% (3/8 patients), and upstaged 1 patient by detecting marrow involvement. IHC detected SSTR 2 in all patients assessed. Six patients were deemed suitable for PRRT on imaging. Four patients received 17 cycles of palliative PRRT (10 111In-DOTATATE; 5 177Lu-DOTATATE; 1 combined 111In and 177Lu-DOTATATE; 1 combined 177Lu and 90Y-DOTATATE) with no significant toxicity attributed to PRRT. All had objective responses. Two survivors are now 40 and 56 months from PRRT commencement. Conclusion(s): GaTATE PET was positive in a high proportion of patients with refractory neuroblastoma, correlating with SSTR 2 on IHC, with additional disease identified compared with MIBG imaging. PRRT seems safe, feasible, with responses observed in patients with progression despite multimodality treatment. These data support ongoing clinical trials in such patients.Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.

Purpose: Error and variation in reporting remains one of the weakest features of clinical imaging despite enormous technological advances in nuclear medicine and radiology. The aim of this study was to evaluate agreement amongst experienced readers in staging non-small-cell lung cancer (NSCLC) with PET-CT. Method(s): A series of 18F-FDG PET-CT scans from 100 consecutive patients were reviewed independently by three experienced readers, with two readers reviewing each scan series a second time. Individual mediastinal lymph node stations were assessed as benign/inflammatory, equivocal or malignant, and AJCC N and M stage were also assigned. Kappa (kappa) was used to compare ratings from two categories and weighted kappa (kappaw) for three or more categories, and kappa values were interpreted according to the Landis-Koch benchmarks. Result(s): Both intra- and interobserver agreement for N and M staging were high. For M staging there was almost perfect intra- and interobserver agreement (kappa=0.90-0.93). For N staging, agreement was either almost perfect or substantial (intraobserver kappaw=0.79, 0.91; interobserver kappaw=0.75-0.81). Importantly, there was almost perfect agreement for N0/1 vs N2/3 disease (kappa=0.80-0.97). Agreement for inferior and superior mediastinal nodes (stations 1, 2, 3, 7, 8, 9) was either almost perfect or substantial (kappaw=0.71-0.88), but lower for hilar nodes (10; kappaw=0.56-0.71). Interreporter variability was greatest for aortopulmonary nodes (5, 6; kappaw=0.48-0.55). Conclusion(s): Amongst experienced reporters in a single centre, there was a very high level of agreement for both mediastinal nodal stage and detection of distant metastases with PET-CT. This supports the use of PET-CT as a robust imaging modality for staging NSCLC. © 2008 Springer-Verlag.

Background: A-37-year old female presented for a 123-meta-iodobenzyl-guanidine (MIBG) scan. She was initially diagnosed with bilateral phaeo-chromocytoma three years prior after presenting with a hypertensive crisis during an emergency caesarean section. She now presents for a restaging scan with suspicion of recurrence in the setting of symptoms, increasing urinary catecholamines and a 11 mm adrenal soft tissue lesion on CT. Method and Result: A whole body MIBG scan was performed followed by SPECT/CT of the chest and abdomen. Low dose multi-slice CT was performed for attenuation correction and anatomic correlation. This identifed increased activity in bone including T5, right clavicle and left humerus. In addition, activity was identifed in two soft tissue nodules in the left breast measuring up to 13 mm. Ultrasound and fne needle aspirate (FNA) con-firmed metastatic left breast phaeochromocytoma. Conclusion(s): MIBG SPECT-CT was pivotal in confrming phaeochromo-cytoma recurrence. Contemporaneous CT allowed precise localisation of abnormal MIBG activity.

Objective: New reconstructive methods employing resolution recovery and noise reduction techniques are now available with the potential to reduce imaging time. This study was designed to assess image quality of established and new reconstruction algorithms, with respect to varying acquisition time and factors including motion and adjacent infra-diaphragmatic activity. Method(s): A Kyoto cardiac phantom, with 15 MBq cardiac and 50 MBq background activity was scanned using a Philips CardioMD fxed 90 degree dual detector camera. SPECT scanning was performed, varying times per acquisition angle of 20 sec, 15 sec, 10 sec and 5 sec. This was repeated with the introduction of a small cardiac defect, addition of infra-diaphragmatic activity and motion artifact. The resulting images were processed with flter back projection, 3D-ordered subset expectation maximization (OSEM), and Astonish (a Philips algorithm incorporating OSEM and resolution recovery). Result(s): All images were successfully acquired utilizing the cardiac phantom and the various parameters described. Images will be evaluated for defect size and image quality by two nuclear medicine physicians blinded to the processing algorithm used. Conclusion(s): It is feasible to assess new reconstruction methods with a phantom model. Results of image analysis are awaited prior to considering potential protocol changes in our centre.