Search

Supplemental material, ACR890087 Supplemental Material2 for Reporting and handling of equivocal imaging findings in diagnostic studies of bone metastasis in prostate cancer by Lars J Petersen, Martin N Johansen, Jesper Strandberg, Louise Stenholt and Helle D Zacho in Acta Radiologica

PURPOSE: The aim of this study was to evaluate the clinical safety profile of the Ga-PSMA-11 ligand for PET/CT imaging in prospective clinical trials.METHODS: Eighty-eight patients with newly diagnosed or recurrent prostate cancer participated in 2 prospective trials. Safety reporting was identical in the 2 trials. The Ga-PSMA-11 ligand was administered as 2 MBq/kg body weight (mean, 9.2 μg, 9.7 nmol). The reporting of clinical adverse events (AEs) and the measurement of blood pressure (BP) and heart rate (HR) were performed prior to injection (baseline); immediately after injection of Ga-PSMA-11 (postinjection); at 1, 10, and 60 minutes after injection; and after acquisition of the PET/CT scan (postscan). All hemodynamic assessments were performed in the supine position, except for the postscan measurement (sitting). The patients were interviewed regarding any AEs at baseline, postinjection, or postscan. In addition, the patients were instructed to report any AEs during the investigation and to contact the investigator if AEs occurred during the rest of the day. Adverse events were classified as mild, moderate, or severe by the patients and categorized by the investigator using the CTCAE (Common Terminology Criteria for Adverse Events) version 4.0.RESULTS: There were no reported clinical AEs. There were significant decreases in systolic BP (P < 0.001) and HR (P < 0.001) over time. In comparison, the diastolic BP increased significantly (P < 0.001). After removal of the last observation (supine position), there was no time-dependent change in systolic or diastolic BP, but the significant change in HR remained. The mean changes over the entire observation period were minimal (systolic BP, -6 to 5 mm Hg; diastolic BP, -2 to 3 mm Hg; HR, decrease of 5 beats/min). No patients developed hypotension. Fifty-five patients presented with hypertension at baseline, which increased by 1 CTCAE grade in 15 patients and by 2 grades in 2 patients. A large number of cases of asymptomatic (grade 1) bradycardia were observed, primarily in patients with preexisting bradycardia. One patient developed transient grade 1 tachycardia. No patients required medical intervention for cardiovascular perturbations.CONCLUSIONS: Ga-PSMA-11 PET/CT was very well tolerated. We consider Ga-PSMA-11 to be safe for human application.

The aim of this study was to prospectively compare planar, bone scan (BS) versus SPECT/CT and NaF PET/CT in detecting bone metastases in prostate cancer. Thirty-seven consecutive, newly diagnosed, prostate cancer patients with prostate specific antigen (PSA) levels ≥ 50 ng/mL and who were considered eligible for androgen-deprivation therapy (ADT) were included in this study. BS, SPECT/CT, and NaF PET/CT, were performed prior to treatment and were repeated after six months of ADT. Baseline images from each index test were independently read by two experienced readers. The reference standard was based on a consensus decision made by a multidisciplinary team on the basis of baseline and follow-up images of the index tests, the findings of the baseline index tests by the experienced readers, and any available imaging, biochemical, and clinical data, including the response to ADT. Twenty-seven (73%) of the 37 patients had bone metastases according to the reference standard. The sensitivities for BS, SPECT/CT and NaF PET/CT were 78%, 89%, and 89%, respectively, and the specificities were 90%, 100%, and 90%, respectively. The positive predictive values of BS, SPECT/CT and NaF PET/CT were 96%, 100%, and 96%, respectively, and the negative predictive values were 60%, 77% and 75%, respectively. No statistically significant difference among the three imaging modalities was observed. All three imaging modalities showed high sensitivity and specificity. NaF PET/CT and SPECT/CT showed numerically improved, but not statistically superior, sensitivity compared with BS in this limited and selected patient cohort.

In horses pathological healing with formation of exuberant granulation tissue (EGT) is a particular problem in limb wounds, whereas body wounds tend to heal without complications. Chronic inflammation has been proposed to be central to the pathogenesis of EGT. This study aimed to investigate levels of inflammatory acute phase proteins (APPs) in interstitial fluid from wounds in horses. A novel approach for absolute quantification of proteins, selected reaction monitoring (SRM)-based mass spectrometry in combination with a quantification concatamer (QconCAT), was used for the quantification of five established equine APPs (fibrinogen, serum amyloid A, ceruloplasmin, haptoglobin, and plasminogen) and three proposed equine APPs (prothrombin, α-2-macroglobulin, and α-1-antitrypsin). Wound interstitial fluid was recovered by large pore microdialysis from experimental body and limb wounds from five horses at days 1, 2, 7, and 14 after wounding and healing without (body) and with (limb) the formation of EGT. The QconCAT included proteotypic peptides representing each of the protein targets and was used to direct the design of a gene, which was expressed in Escherichia coli in a media supplemented with stable isotopes for metabolically labeling of standard peptides. Co-analysis of wound interstitial fluid samples with the stable isotope-labelled QconCAT tryptic peptides in known amounts enabled quantification of the APPs in absolute terms. The concentrations of fibrinogen, haptoglobin, ceruloplasmin, prothrombin, and α-1-antitrypsin in dialysate from limb wounds were significantly higher than in dialysate from body wounds. This is the first report of simultaneous analysis of a panel of APPs using the QconCAT-SRM technology. The microdialysis technique in combination with the QconCAT-SRM based approach proved useful for quantification of the investigated proteins in the wound interstitial fluid, and the results indicated that there is a state of sustained inflammation in equine wounds healing with formation of EGT. This article is protected by copyright. All rights reserved.

PURPOSE: The aim of this study was to assess observer agreement on the evaluation of treatment responses of bone metastases by bone scintigraphy (BS) using different scoring methods in prostate cancer patients.PATIENTS AND METHODS: Sixty-three paired BS from 55 patients were included. BS was performed before and after more than 12 weeks of anticancer treatment. A panel of experienced nuclear medicine physicians from several institutions evaluated treatment response using three different methods: (a) standard clinical assessment, (b) MD Anderson criteria, and (c) Prostate Cancer Working Group 2 (PCWG-2) criteria. All methods were based on the evaluation of paired before-after bone scans.RESULTS: Readers were able to classify the presence of bone metastases at baseline with a high level of agreement [Cohen's κ=0.94, 95% confidence interval (CI) 0.82-1.00]. Observer agreement on bone response by PCWG-2 criteria showed considerable agreement (Cohen's κ=0.84, 95% CI: 0.69-0.99). Evaluation using standard clinical assessment and MD Anderson criteria showed moderate agreement (0.52, 95% CI: 0.36-0.69 and 0.64, 95% CI: 0.48-0.79, respectively). There was considerable variation among readers for regional lesion count on individual scans, with limits of agreement of -10 to 10 lesions or more for the majority of anatomical regions, including the thorax, spine, and pelvis.CONCLUSION: Observer agreement on treatment response by BS varied notably across methods. Optimal agreement was achieved by the PCWG-2 criteria. Variation in the classification of treatment response of bone metastases may have a significant impact on clinical decision-making, emphasizing the need for a uniform approach, including during clinical practice. Response assessment by lesion counting on repeated BS without access to previous scans cannot be recommended.

As in other fibroproliferative disorders, hypoxia has been suggested to play a key role in the pathogenesis of exuberant granulation tissue (EGT). The purpose of this study was to investigate metabolism and blood flow locally in full-thickness wounds healing with (limb wounds) and without (body wounds) formation of EGT.Microdialysis was used to recover endogenous metabolites from the wounds, and laser Doppler flowmetry was used to measure blood flow. Measurements were performed before wounding and 1-28 days after wounding.Blood flow was consistently lower in limb wounds than in body wounds throughout the study period with no change over time. After wounding and throughout the study period theglucose concentration wassignificantly lower in limb wounds than in body woundswhereas the lactate level showed a significantly higher concentration in limb wounds. The lactate/glucose ratio displayed a significant difference between body and limb wounds.In conclusion, the metabolic disturbances may suggest inadequate oxygen supply during the wound healing process in equine limb wounds healing with EGT. This may be related to the inherently decreased perfusion in the wound bed of limb wounds.

BackgroundAmong the current translational inflammatory pain models, the ultraviolet (UV) irradiation is of rapidly growing interest. The development of primary thermal and mechanical hyperalgesia has been observed in humans and rodents. The pig as a translational animal model might be advantageous due to its great homology with humans.MethodsThe skin in the flank of awake pigs was irradiated by a UV-B light source (1 J/cm2) and changes in thermal and mechanical sensitivity 24 and 48 h following irradiation were measured via assessment of nociceptive behaviours.ResultsThermal sensitivity increased significantly within the inflamed site 24 h after irradiation as indicated by the reduction of latency to respond to thermal stimulation from baseline to 24 h (P ConclusionsOur study shows that behavioural recordings are a valid tool for the assessment of thermal hyperalgesia following UV-B inflammation in porcine skin, but they were not capable of providing a clear indication of the development of mechanical hyperalgesia.