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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. 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. 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 conventional imaging conferred management change less frequently (23 [15%] men [10–22] vs 41 [28%] men [21–36]; p=0·008) and had more equivocal findings (23% [17–31] vs 7% [4–13]) than PSMA PET-CT did. Radiation exposure was 10·9 mSv (95% CI 9·8–12·0) higher for conventional imaging than for PSMA PET-CT (19·2 mSv vs 8·4 mSv; p<0·001). We found high reporter agreement for PSMA PET-CT (κ=0·87 for nodal and κ=0·88 for distant metastases). In patients who underwent second-line image, management change occurred in seven (5%) of 136 patients following conventional imaging, and in 39 (27%) of 146 following PSMA PET-CT. PSMA PET-CT is a suitable replacement for conventional imaging, providing superior accuracy, to the combined findings of CT and bone scanning. Movember and Prostate Cancer Foundation of Australia. [Display omitted]

After neoadjuvant chemoradiotherapy for oesophageal cancer, roughly half of the patients with squamous cell carcinoma and a quarter of those with adenocarcinoma have a pathological complete response of the primary tumour before surgery. Thus, the necessity of standard oesophagectomy after neoadjuvant chemoradiotherapy should be reconsidered for patients who respond sufficiently to neoadjuvant treatment. In this study, we aimed to establish the accuracy of detection of residual disease after neoadjuvant chemoradiotherapy with different diagnostic approaches, and the optimal combination of diagnostic techniques for clinical response evaluations. The preSANO trial was a prospective, multicentre, diagnostic cohort study at six centres in the Netherlands. Eligible patients were aged 18 years or older, had histologically proven, resectable, squamous cell carcinoma or adenocarcinoma of the oesophagus or oesophagogastric junction, and were eligible for potential curative therapy with neoadjuvant chemoradiotherapy (five weekly cycles of carboplatin [area under the curve 2 mg/mL per min] plus paclitaxel [50 mg/m2 of body-surface area] combined with 41·4 Gy radiotherapy in 23 fractions) followed by oesophagectomy. 4–6 weeks after completion of neoadjuvant chemoradiotherapy, patients had oesophagogastroduodenoscopy with biopsies and endoscopic ultrasonography with measurement of maximum tumour thickness. Patients with histologically proven locoregional residual disease or no-pass during endoscopy and without distant metastases underwent immediate surgical resection. In the remaining patients a second clinical response evaluation was done (PET–CT, oesophagogastroduodenoscopy with biopsies, endoscopic ultrasonography with measurement of maximum tumour thickness, and fine-needle aspiration of suspicious lymph nodes), followed by surgery 12–14 weeks after completion of neoadjuvant chemoradiotherapy. The primary endpoint was the correlation between clinical response during clinical response evaluations and the final pathological response in resection specimens, as shown by the proportion of tumour regression grade (TRG) 3 or 4 (>10% residual carcinoma in the resection specimen) residual tumours that was missed during clinical response evaluations. This study was registered with the Netherlands Trial Register (NTR4834), and has been completed. Between July 22, 2013, and Dec 28, 2016, 219 patients were included, 207 of whom were included in the analyses. Eight of 26 TRG3 or TRG4 tumours (31% [95% CI 17–50]) were missed by endoscopy with regular biopsies and fine-needle aspiration. Four of 41 TRG3 or TRG4 tumours (10% [95% CI 4–23]) were missed with bite-on-bite biopsies and fine-needle aspiration. Endoscopic ultrasonography with maximum tumour thickness measurement missed TRG3 or TRG4 residual tumours in 11 of 39 patients (28% [95% CI 17–44]). PET–CT missed six of 41 TRG3 or TRG4 tumours (15% [95% CI 7–28]). PET–CT detected interval distant histologically proven metastases in 18 (9%) of 190 patients (one squamous cell carcinoma, 17 adenocarcinomas). After neoadjuvant chemoradiotherapy for oesophageal cancer, clinical response evaluation with endoscopic ultrasonography, bite-on-bite biopsies, and fine-needle aspiration of suspicious lymph nodes was adequate for detection of locoregional residual disease, with PET–CT for detection of interval metastases. Active surveillance with this combination of diagnostic modalities is now being assessed in a phase 3 randomised controlled trial (SANO trial; Netherlands Trial Register NTR6803). Dutch Cancer Society.

Purpose Positron emission tomography (PET) with the first and only tau targeting radiotracer of 18 F-flortaucipir approved by FDA has been increasingly used in depicting tau pathology deposition and distribution in patients with cognitive impairment. The goal of this international consensus is to help nuclear medicine practitioners procedurally perform 18 F-flortaucipir PET imaging. Method A multidisciplinary task group formed by experts from various countries discussed and approved the consensus for 18 F-flortaucipir PET imaging in Alzheimer’s disease (AD), focusing on clinical scenarios, patient preparation, and administered activities, as well as image acquisition, processing, interpretation, and reporting. Conclusion This international consensus and practice guideline will help to promote the standardized use of 18 F-flortaucipir PET in patients with AD. It will become an international standard for this purpose in clinical practice.

Background Neoadjuvant chemoradiotherapy (nCRT) plus surgery is a standard treatment for locally advanced oesophageal cancer. With this treatment, 29% of patients have a pathologically complete response in the resection specimen. This provides the rationale for investigating an active surveillance approach. The aim of this study is to assess the (cost-)effectiveness of active surveillance vs. standard oesophagectomy after nCRT for oesophageal cancer. Methods This is a phase-III multi-centre, stepped-wedge cluster randomised controlled trial. A total of 300 patients with clinically complete response (cCR, i.e. no local or disseminated disease proven by histology) after nCRT will be randomised to show non-inferiority of active surveillance to standard oesophagectomy (non-inferiority margin 15%, intra-correlation coefficient 0.02, power 80%, 2-sided α 0.05, 12% drop-out). Patients will undergo a first clinical response evaluation (CRE-I) 4–6 weeks after nCRT, consisting of endoscopy with bite-on-bite biopsies of the primary tumour site and other suspected lesions. Clinically complete responders will undergo a second CRE (CRE-II), 6–8 weeks after CRE-I. CRE-II will include 18F–FDG-PET-CT, followed by endoscopy with bite-on-bite biopsies and ultra-endosonography plus fine needle aspiration of suspected lymph nodes and/or PET- positive lesions. Patients with cCR at CRE-II will be assigned to oesophagectomy (first phase) or active surveillance (second phase of the study). The duration of the first phase is determined randomly over the 12 centres, i.e., stepped-wedge cluster design. Patients in the active surveillance arm will undergo diagnostic evaluations similar to CRE-II at 6/9/12/16/20/24/30/36/48 and 60 months after nCRT. In this arm, oesophagectomy will be offered only to patients in whom locoregional regrowth is highly suspected or proven, without distant dissemination. The main study parameter is overall survival; secondary endpoints include percentage of patients who do not undergo surgery, quality of life, clinical irresectability (cT4b) rate, radical resection rate, postoperative complications, progression-free survival, distant dissemination rate, and cost-effectiveness. We hypothesise that active surveillance leads to non-inferior survival, improved quality of life and a reduction in costs, compared to standard oesophagectomy. Discussion If active surveillance and surgery as needed after nCRT leads to non-inferior survival compared to standard oesophagectomy, this organ-sparing approach can be implemented as a standard of care.

Background Bone biopsy is the gold standard for diagnosing bone metastases. However, there is no clinical consensus regarding the optimal imaging test for determining the puncture site. Methods We compared the performance of [ 18 F]FDG PET/CT with CT in detecting bone metastases to achieve the highest biopsy efficiency. This registered prospective study enrolled 273 patients with bone lesions who were treated between January 2020 and March 2021. Patients were randomly assigned to undergo [ 18 F]FDG PET/CT or CT to determine the puncture site before bone biopsy. The accuracy, sensitivity, specificity, second biopsy rate, diagnostic time and cost-effectiveness of the two imaging tests were compared. Results The accuracy and sensitivity of [ 18 F]FDG PET/CT group in detecting bone metastases were significantly higher than CT group(97.08% vs. 90.44%, 98.76% vs. 92.22%, P  < 0.05). The second biopsy rate was significantly lower in the [ 18 F]FDG PET/CT group (2.19% vs. 5.15%; P  < 0.05). The diagnostic time of [ 18 F]FDG PET/CT was 18.33 ± 2.08 days, which was significantly shorter than 21.28 ± 1.25 days in CT group ( P  < 0.05). The cost of [ 18 F] FDG PETCT is 11428.35 yuan, and the cost of CT is 13287.52 yuan; the incremental cost is 1859.17 yuan. SUVmax > 6.3 combined with ALP > 103 U/L showed a tendency for tumor metastases with an AUC of 0.901 (95%CI 0.839 to 0.946, P  < 0.001). Conclusion [ 18 F]FDG PET/CT has better performance and cost-effectiveness than CT in determining the bone biopsy site for suspect bone metastases. Trial registration The prospective study was registered on 2018-04-10, and the registration number is ChiCTR1800015540.

Purpose This study was prospectively designed to evaluate the early dynamic organ distribution and tumor detection capability of [ 68  Ga]Ga-P16-093, which was compared with [ 68  Ga]Ga-PSMA-617 in the same group of recurrent prostate cancer patients. Methods Twenty patients with recurrent prostate cancer were enrolled. In 2 consecutive days, each patient underwent a 60-min dynamic PET/CT scan after intravenous administration of 148–185 MBq (4–5 mCi) [ 68  Ga]Ga-P16-093 and [ 68  Ga]Ga-PSMA-617, respectively. Following a low-dose CT scan, serial dynamic PET scans were performed from head to proximal thigh at 9 time points (30 s/bed at 4, 7, 10, 13, and 16 min; 1 min/bed at 20, 30, and 45 min; and 2 min/bed at 60 min). Standardized uptake values were measured for semi-quantitative comparison. Results [ 68  Ga]Ga-P16-093 PET/CT revealed a significantly higher tumor uptake at 4 min (SUVmax 7.88 ± 5.26 vs. 6.01 ± 3.88, P  < 0.001), less blood pool retention at 4 min (SUVmean 5.12 ± 1.16 vs. 6.14 ± 0.98, P  < 0.001), and lower bladder accumulation at 60 min (SUVmean 31.33 ± 27.47 vs. 48.74 ± 34.01, P  = 0.042) than [ 68  Ga]Ga-PSMA-617 scan. Significantly higher [ 68  Ga]Ga-P16-093 uptakes were also observed in the parotid gland, liver, spleen, and kidney. Besides, [ 68  Ga]Ga-P16-093 exhibited a better detectability of tumor than [ 68  Ga]Ga-PSMA-617 (366 vs. 321, P  = 0.009). Conclusions [ 68  Ga]Ga-P16-093 showed advantages over [ 68  Ga]Ga-PSMA-617 with higher tumor uptakes, tumor-to-blood pool ratio and detection capability, less blood pool, and bladder accumulation in recurrent prostate cancer patients. Trial registration: [ 68  Ga]Ga-P16-093 and [ 68  Ga]Ga-PSMA-617 PET/CT Imaging in the Same Group of Prostate Cancer Patients (NCT04796467, Registered 12 March 2021, retrospectively registered) URL of registry: https://clinicaltrials.gov/ct2/show/NCT04796467

Adjunctive rosuvastatin for rifampicin-susceptible pulmonary tuberculosis (rs-PTB) shows no effect on microbiological or radiological outcomes in a phase IIb randomised, controlled trial (NCT04504851). We explore the impact of adjunctive rosuvastatin on 18F-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET-CT) imaging in a sub-study of 24 participants. Changes in standardised uptake value (SUVmax, SUVmean), Total Metabolic Volume, (TMV), Total Lesion Glycolysis (TLG), cavity diameter and volume, between week 0 and week 8 post-randomisation, are evaluated. Here we show no evidence of difference in the reduction in TLG [median 65.8% for the rosuvastatin group (Q1, Q3 38.6, 94.5) vs 64.3% for standard tuberculosis treatment group (Q1, Q3 −20.0, 81.7), P  = 0.32], reduction in cavity volume on CT [median 3.2 cm 3 (IQR 11.1, 0.5) for rosuvastatin, 2.2 cm 3 (IQR 4.6, 0.7) for control ( p  = 0.72)], or any other PET-CT parameter measured. We show that the first 8-weeks of standard tuberculosis treatment results in a reduction in the volumetric indices (TLG and TMV), but had little change in SUVmax or SUVmean. Change in TLG and TMV holds promise as biomarkers of tuberculosis treatment response: future PET-CT studies should evaluate their role in predicting relapse-free cure, and the overall role of 18F-FDG-PET-CT as a tool for early-phase tuberculosis clinical trials. In this work, authors report on the PET-CT outcomes from the use of adjunctive statin therapy, rosuvastatin, in the intensive phase of tuberculosis (TB) treatment. Rosuvastatin had no impact on PET-CT changes when used as an adjunct to TB treatment. 8-weeks of TB treatment resulted in ~50% reduction in total lesion glycolysis (TLG), a metric that combines the volume of lung affected and metabolic activity.

Background Internal mammary lymphadenopathy (IML) plays a role in breast cancer stage and prognosis. We aimed to evaluate method of IML detection, how IML impacts response to neoadjuvant chemotherapy (NAC), and oncologic outcomes. Methods We evaluated patients enrolled in the I-SPY-2 clinical trial from 2010 to 2022. We captured the radiographic method of IML detection (magnetic resonance imaging [MRI], positron emission tomography/computed tomography [PET/CT], or both) and compared patients with IML with those without. Rates of locoregional recurrence (LRR), distant recurrence (DR) and event-free survival (EFS) were compared by bivariate analysis. Results Of 2095 patients, 198 (9.5%) had IML reported on pretreatment imaging. The method of IML detection was 154 (77.8%) MRI only, 11 (5.6%) PET/CT only, and 33 (16.7%) both. Factors associated with IML were younger age ( p  = 0.001), larger tumors ( p  < 0.001), and higher tumor grade ( p  = 0.027). Pathologic complete response (pCR) was slightly higher in the IML group (41.4% vs. 34.0%; p  = 0.03). There was no difference in breast or axillary surgery ( p  = 0.41 and p  = 0.16), however IML patients were more likely to undergo radiation (68.2% vs. 54.1%; p  < 0.001). With a median follow up of 3.72 years (range 0.4–10.2), there was no difference between IM+ versus IM− in LRR (5.6% vs. 3.8%; p  = 0.25), DR (9.1% vs. 7.9%; p  = 0.58), or EFS (61.6% vs. 57.2%; p  = 0.48). This was true for patients with and without pCR. Conclusions In this large cohort of patients treated with NAC, outcomes were not negatively impacted by IML. We demonstrated that IML influences treatment selection but is not a poor prognostic indicator when treated with modern NAC and multidisciplinary disease management.

Background Current studies indicate that fluorine-18-fluorodeoxyglucose positron emission tomography/ computed tomography ([ 18 F]FDG PET/CT) is the most accurate imaging modality for the detection of relapsed locally advanced non-small cell lung cancer (NSCLC) after curatively intended chemoradiotherapy. To this day, there is no objective and reproducible definition for the diagnosis of disease recurrence in PET/CT, the reading of which is relevantly influenced by post radiation inflammatory processes. The aim of this study was to evaluate and compare visual and threshold-based semi-automated evaluation criteria for the assessment of suspected tumor recurrence in a well-defined study population investigated during the randomized clinical PET-Plan trial. Methods This retrospective analysis comprises 114 PET/CT data sets of 82 patients from the PET-Plan multi-center study cohort who underwent [ 18 F]FDG PET/CT imaging at different timepoints for relapse, as suspected by CT. Scans were first analyzed visually by four blinded readers using a binary scoring system for each possible localization and the associated reader certainty of the evaluation. Visual evaluations were conducted repeatedly without and with additional knowledge of the initial staging PET and radiotherapy delineation volumes. In a second step, uptake was measured quantitatively using maximum standardized uptake value (SUVmax), peak standardized uptake value corrected for lean body mass (SULpeak), and a liver threshold-based quantitative assessment model. Resulting sensitivity and specificity for relapse detection were compared to the findings in the visual assessment. The gold standard of recurrence was independently defined by prospective study routine including external reviewers using CT, PET, biopsies and clinical course of the disease. Results Overall interobserver agreement (IOA) of the visual assessment was moderate with a high difference between secure (ĸ = 0.66) and insecure (ĸ = 0.24) evaluations. Additional knowledge of the initial staging PET and radiotherapy delineation volumes improved the sensitivity (0.85 vs 0.92) but did not show significant impact on the specificity (0.86 vs 0.89). PET parameters SUVmax and SULpeak showed lower accuracy compared to the visual assessment, whereas threshold-based reading showed similar sensitivity (0.86) and higher specificity (0.97). Conclusion Visual assessment especially if associated with high reader certainty shows very high interobserver agreement and high accuracy that can be further increased by baseline PET/CT information. The implementation of a patient individual liver threshold value definition, similar to the threshold definition in PERCIST, offers a more standardized method matching the accuracy of experienced readers albeit not providing further improvement of accuracy.

Quantitative parameters derived from gallium-68 [68Ga]Ga-prostate-specific membrane antigen (PSMA)-11 PET-CT (PSMA-PET-CT) such as whole-body standardised uptake value (SUV)mean and total tumour volume (PSMA-TTV) have shown prognostic value for response to lutetium-177 [177Lu]Lu-PSMA-617 monotherapy in patients with prostate cancer. Adding [177Lu]Lu-PSMA-617 to enzalutamide improved overall survival compared with enzalutamide in patients with metastatic castration-resistant prostate cancer in the ENZA-p trial. This prespecified substudy of ENZA-p evaluated baseline PSMA-PET quantitative parameters as predictive and prognostic biomarkers for enzalutamide plus [177Lu]Lu-PSMA-617 and enzalutamide monotherapy. ENZA-p was an open-label, randomised, phase 2 trial done in 15 hospitals in Australia. Participants were aged 18 years or older with progressive metastatic castration-resistant prostate cancer who had not previously been treated with docetaxel or androgen receptor pathway inhibitors (abiraterone permitted) for metastatic castration-resistant prostate cancer, had [68Ga]Ga PSMA-PET-CT-positive disease, an Eastern Cooperative Oncology Group performance status of 0–2, and at least two risk factors for early progression on enzalutamide. Patients were randomly assigned (1:1) by a centralised, web-based system using minimisation with a random component to either enzalutamide 160 mg daily (oral) or enzalutamide 160 mg daily plus adaptive-dosed (two or four doses) intravenous [177Lu]Lu-PSMA-617 7·5 GBq every 6–8 weeks. The primary endpoint was prostate-specific antigen (PSA) progression-free survival, which has been reported previously. All participants underwent baseline [68Ga]Ga-PSMA-11 PET-CT to assess eligibility (SUVmax >15 at a single site and SUVmax >10 at all larger tumour sites). PSMA-PET parameters were quantified with semi-automated software to derive PSMA-TTV and SUVmean and correlated with overall and PSA progression-free survival in a prespecified analysis, with the primary endpoint of this substudy being overall survival. Thresholds were based on SUVmean highest quartile (Q4 vs Q1–3) and PSMA-TTV median at baseline. We used the Kaplan–Meier method and Cox regression models and analysed patients on a treatment received basis. The trial is registered with ClinicalTrials.gov, NCT04419402, and follow-up is complete. Between Aug 17, 2020, and July 26, 2022, 162 participants were randomly assigned to enzalutamide (n=79) or enzalutamide plus [177Lu]Lu-PSMA-617 (n=83). This substudy included the 160 of the 162 randomly assigned patients who received study treatment (79 in the enzalutamide group and 81 in the enzalutamide plus [177Lu]Lu-PSMA-617 group). Median follow-up at the final data cutoff (July 31, 2024) was 34 months (IQR 29–39), with 96 overall survival events (53 with enzalutamide and 43 with enzalutamide plus [177Lu]Lu-PSMA-617). Baseline median SUVmean was 7·7 (IQR 6·5–9·8) and median PSMA-TTV was 234 mL (76–687). Median overall survival for PSMA-TTV below or above the median in the enzalutamide group was 39 months (95% CI 31–not estimable) versus 20 months (13–24; HR 0·23 [95% CI 0·13–0·42], log-rank p<0·0001). The corresponding median overall survival for PSMA-TTV below or above the median in the enzalutamide plus [177Lu]Lu-PSMA-617 group was 35 months (95% CI 32–37) versus 28 months (26–34; HR 0·66 [0·36–1·21], log-rank p=0·18). The test for interaction between PSMA-TTV and treatment group for overall survival was p=0·0078. Median overall survival for SUVmean Q4 versus Q1–3 in the enzalutamide group was 29 months (95% CI 17–39) versus 25 months (21–31; HR 0·84 [0·44–1·60], log-rank p=0·59). For enzalutamide plus [177Lu]Lu-PSMA-617, median overall survival for SUVmean Q4 versus Q1–3 was 32 months (95% CI 21–not estimable) versus 34 months (27–35; HR 0·80 [0·38–1·68], log-rank p=0·56). The test for interaction between SUVmean (Q4 vs Q1–3) and treatment group for overall survival was p=0·88. Baseline PSMA-TTV is prognostic for overall survival and predictive for a beneficial effect on overall survival with the addition of [177Lu]Lu-PSMA-617 to enzalutamide as first-line treatment for high-risk metastatic castration-resistant prostate cancer. By contrast, PSMA SUVmean was not prognostic for PSA progression-free survival or overall survival when [177Lu]Lu-PSMA-617 was administered with enzalutamide. The Prostate Cancer Research Alliance initiative (Movember and Australian Federal Government), Prostate Cancer Foundation Challenge Award, St Vincent's Clinic Foundation, GenesisCare, RoyMorgan, Endocyte (a Novartis company), and Astellas.