Accuracy in the quantification of the SUV is a critical point in PET because proper quantification of tumor uptake is essential for therapy monitoring and prognosis evaluation. Recent advances such ...as time-of-flight (TOF) and point-spread-function (PSF) reconstructions have dramatically improved detectability. However, first experiences with these techniques have shown a consistent tendency to measure markedly high SUV values, bewildering nuclear medicine physicians and referring clinicians.
We investigated different reconstruction and quantification procedures to determine the optimum protocol for an accurate SUV quantification in last generation PET scanners.
Both phantom and patient images were evaluated. A complete set of experiments was performed using a body phantom containing 6 spheres with different background levels and contrasts. Whole-body FDG PET/CT of 20 patients with breast and lung cancer was evaluated. One hundred five foci were identified by 2 experienced nuclear medicine physicians.Each acquisition was reconstructed both with classical and advanced (TOF, PSF) reconstruction techniques. Each sphere and each in vivo lesion was quantified with different parameters as follows: SUV(max), SUV(mean), and SUV(50) (mean within a 50% isocontour).
This study has confirmed that quantification with SUV(max) produces important overestimation of metabolism in new generation PET scanners. This is a relevant result because, currently, SUV(max) is the standard parameter for quantification. SUV(50) has been shown as the best alternative, especially when applied to images reconstructed with PSF + TOF.
SUV(50) provides accurate quantification and should replace SUV(max) in PET tomographs incorporating advanced reconstruction techniques. PSF + TOF reconstruction is the optimum for both detection and accurate quantification.
With science, technology, engineering, and mathematics (STEM) heralded as pivotal to Australia's future prosperity, declining participation in Year 12 mathematics and science has attracted nationwide ...concern. While the national statistics certainly provide clear evidence of declining enrolments and the underrepresentation of females in STEM, we wondered if possible jurisdictional differences had been overlooked. To investigate this issue, we compiled Year 12 enrolment data from 1991 to 2017 in New South Wales, Australia's most populous state. Three complementary analyses were conducted: (1) changes in the Year 12 student cohort, (2) male and female rates of participation in Year 12 STEM courses, and (3) differences between STEM and non-STEM course enrolments. These analyses confirm declining enrolments in digital technologies and mathematics, especially for girls. In contrast, enrolments in almost all NSW science courses have been increasing since 2001, at a rate faster than many non-STEM courses. Declining enrolments in advanced mathematics were less substantial than nationally, and participation in intermediate level mathematics increased in 2017 for the first time since 1991. Despite these promising signs, our analysis also shows that students are selecting less challenging courses, while one in four girls in NSW currently undertakes no mathematics in Year 12. These results indicate the need for continued policy work on gender, mathematics, and digital technologies if key STEM targets are to be met. We argue that understanding key differences between state jurisdictions may be critical to developing interventions with greater impact. Author abstract
Dopaminergic depletion in the nigrostriatal system is the neurochemical hallmark of Parkinson's disease (PD). Although numerous efforts have been made to determine the evolution of dopaminergic ...depletion in PD, “in vivo” data concerning the stages of this process are still scarce. We evaluated 6-18F-fluoro-
l-DOPA (
18F-DOPA) and 11C-(+)-α-dihydrotetrabenazine (
11C-DTBZ) using PET in a model of chronically MPTP-induced parkinsonism in non-human primates. Methods: Sixty-seven cynomolgus monkeys (
M
acaca
fascicularis) were included in the study. Progressive parkinsonism was induced by repeated administration of small doses of MPTP (iv) over several months. Animals were classified as controls, asymptomatic, recovered (having exhibited parkinsonian features transiently) and stable parkinsonian, according to their motor status. Analysis of striatal dopaminergic activity was conducted by regions of interest (ROI) and statistical parametric mapping (SPM) over normalized parametric images. Results: A progressive loss of striatal uptake was evident among groups for both radiotracers, which correlated significantly with the clinical motor status. Changes occurred earlier, i.e. in the less affected stages, with
11C-DTBZ. Similar results were achieved by ROI and SPM analysis. Uptake was similar with both radiotracers for the asymptomatic and recovered groups. Conclusions: Serial assessment with
18F-DOPA and
11C-DTBZ PETs provides an effective approach to evaluate evolution of dopaminergic depletion in monkeys with MPTP-induced parkinsonism. This approach could be useful to perform studies aiming to test the effect of early therapeutic intervention and putative neuroprotective treatments.
•A reduction of 30% radiation dose was achieved in standard FDG PET/CT.•More than 300 clinical patients have been evaluated.•This procedure might be easily extrapolable to any PET facility.
To reduce ...the radiation dose to patients by optimizing oncological FDG PET/CT protocols.
The baseline PET/CT protocol in our institution for oncological PET/CT examinations consisted of the administration of 5.18 MBq/kg of FDG and a CT acquisition with a reference current–time product of 120 mAs. In 2016, FDG activity was reduced to 4.44 and 3.70 MBq/kg and reference CT current–time-product was reduced to 100 and 80 mAs. 322 patients scanned with different protocols were retrospectively evaluated. For each patient, effective dose was calculated. The overall image quality was subjectively rated by the referring physician on a 4-point scale (IQ score: 1 excellent, 2 good, 3 poor but interpretable, 4 poor not interpretable). Image quality was quantitatively evaluated measuring noise in the liver.
CT Results: Effective dose was progressively reduced from 9.5 ± 2.8 to 8.0 ± 2.3 and 6.2 ± 1.5 mSv (p < 0.001). A mean dose reduction of 34.9% was achieved. There was a significant degradation of IQ score (p < 0.05) and noise (p < 0.001). Nevertheless, the number of poor quality studies (IQ score >2) did not increase.
PET Results: Effective dose was gradually reduced from 6.5 ± 1.4 to 5.7 ± 1.3 and 5.0 ± 1.0 mSv (p < 0.001). Average dose reduction was 23.4%. IQ score (p < 0.05) and noise (p < 0.001) significantly degraded for lower activity protocols. However, all images with reduced activity were scored as interpretable (IQ score ≤ 3).
A significant radiation dose reduction of 28.7% was reached. Despite a slight reduction in image quality, the new regime was successfully implemented with readers reporting unchanged clinical confidence.
Aims
To present four examples of clonally related Epstein–Barr virus (EBV)‐associated large‐cell transformation of marginal zone lymphoma (MZL) (of nodal, extranodal and splenic types), occurring ...120, 11 and 5 months after the initial diagnosis in three instances, and concurrently in one case; and to discuss several interesting features of EBV infection.
Methods and results
Somatic mutations were detected by use of a customised panel for next‐generation sequencing and polymerase chain reaction studies of IgH in both low‐grade and high‐grade components of each case. In case 1, the initial biopsy of nodal MZL showed scattered EBV‐positive cells, which might constitute an indication of EBV‐induced progression. Case 2 showed heterogeneous EBV expression, a phenomenon attributable to loss of the EBV episomes during cell division, or to a secondary superinfection or reactivation of the virus. In case 3, p53 overexpression related to gene mutation and EBV‐encoded small RNAs were identified in the same neoplastic component. In case 4, the mucosa‐associated lymphoid tissue‐type MZL and the high‐grade component were identified concurrently in a patient previously treated with methotrexate for an autoimmune disorder.
Conclusion
These data suggest that the presence of EBV should be added to the list of potential markers to be analysed for MZL prognosis.
One key feature of pancreatic ductal adenocarcinoma (PDAC) is a dense desmoplastic reaction that has been recognized as playing important roles in metastasis and therapeutic resistance. We aim to ...study tumor-stromal interactions in an in vitro coculture model between human PDAC cells (Capan-1 or PL-45) and fibroblasts (LC5). Confocal immunofluorescence, Enzyme-Linked Immunosorbent Assay (ELISA), and Western blotting were used to evaluate the expressions of activation markers; cytokines arrays were performed to identify secretome profiles associated with migratory and invasive properties of tumor cells; extracellular vesicle production was examined by ELISA and transmission electron microscopy. Coculture conditions increased FGF-7 secretion and α-SMA expression, characterized by fibroblast activation and decreased epithelial marker E-cadherin in tumor cells. Interestingly, tumor cells and fibroblasts migrate together, with tumor cells in forming a center surrounded by fibroblasts, maximizing the contact between cells. We show a different mechanism for tumor spread through a cooperative migration between tumor cells and activated fibroblasts. Furthermore, IL-6 levels change significantly in coculture conditions, and this could affect the invasive and migratory capacities of cells. Targeting the interaction between tumor cells and the tumor microenvironment might represent a novel therapeutic approach to advanced PDAC.
Nutrition education programs in schools have been effective in improving children's knowledge and behaviours related to food and nutrition. However, teachers find it challenging to implement such ...programs due to overcrowded curricula. Integrating nutrition with core subjects such as mathematics could potentially address time constraints and improve the learning of both. The primary aim of this randomized controlled trial (RCT) is to evaluate the impact of a cross-curricular nutrition and mathematics program on primary school students' portion size estimation skills. Secondary aims include impact on their nutrition knowledge, attitudes towards mathematics and evaluating the quality of the lessons. Twelve Year 3-4 classes from Catholic schools in New South Wales, Australia will be randomised to intervention (n = 6) or control (n = 6) groups. Teachers in the intervention group will receive a professional development workshop and resources to teach 4-5 lessons on portion size and measurements across 1-4 weeks. Outcome measures include portion size estimation skills, nutrition knowledge and attitudes towards mathematics, with data collected during three school visits (pre-intervention, immediately post-intervention, 4 weeks post-intervention). Additionally, teaching quality will be assessed in both intervention and control groups and process evaluation undertaken using teacher interviews and student focus groups. This RCT uses an innovative approach to improve both nutrition and mathematics related learning outcomes among primary school children. It has the potential to impact teaching practices regarding integration of nutrition into curricula and enhance the implementation of nutrition education interventions.
In recent years, there have been increasing calls for an overall transformation of the nature of engineering Ph.D. programs and the way theses are assessed. There exists a need to understand the ...examination process to ensure the best quality outcome for candidates in engineering. The work we present in this paper uses data collected between 2003 and 2010 for a total of 1220 Australian Ph.D. theses by analysing examiner reports. Our analysis indicates that Ph.D. theses in engineering, N = 106, differ considerably from those in other fields in areas such as gender of candidates and examiners and the examiners' geographical location. We also found that assessment areas such as significance and contribution of the thesis, publications arising from the thesis, breadth, depth and recency of the literature review and communication and editorial correctness are areas in which the proportion of text of engineering examiners' comments differs significantly from other fields.
Introduction
Belantamab mafodotin (BM) is a new anti-BCMA antibody–drug conjugate, recently approved for triple-class relapsed and refractory multiple myeloma (RRMM). We assessed real-world outcomes ...with BM in patients under the Spanish Expanded Access Program (EAP).
Methods
We conducted an observational, retrospective, multicenter study including RRMM patients who received ≥ 1 dose of BM (Nov 2019 to Jun 2021). The primary endpoint was overall response rate (ORR). Secondary endpoints were progression-free survival (PFS), overall survival (OS), and incidence of treatment-emergent adverse events (TEAEs).
Results
Thirty-three patients were included with a median of 70 years of age (range, 46–79 years). Median time from diagnosis was 71 months (range, 10–858 months). Median prior lines was 5 (range, 3–8 lines); 90% of patients were triple-/quad-/penta-refractory; 48% showed high-risk cytogenetics. Median BM doses was 3 (range 1–16 doses), with a median follow-up of 11 months (6–15 months). ORR was 42.2% (≥ VGPR, 18.2%).
Median PFS was 3 months (95% CI 0.92–5.08) in the overall population, and 11 months (HR 0.26; 95% CI 0.10–0.68) for patients who achieved ≥ PR. PFS was not significantly different according to age, cytogenetic risk, and prior therapy lines. OS was 424 days (95% CI 107–740). Non-hematological TEAEs (57.6% of patients; 30.3% ≥ G3) included keratopathy (51.5%; 21.2% ≥ G3) and patient-reported vision-related symptoms (45.5%). Keratopathy was resolved in 70.6% of patients. G3 hematological TEAEs was 18.2%, thrombocytopenia (21.2%). Dose reductions due to TEAEs: 30.3%; delays: 36.4%. Treatment discontinuation causes: progression (54.5%), toxicity (non-ocular; 6%/ocular; 6% /ocular + non-ocular toxicity; 3%), death (6%), and patient’s decision (3%).
Conclusions
BM showed relevant anti-myeloma activity in RRMM with a manageable safety profile. These results corroborate those observed in the BM pivotal trial.
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