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Psychopharmacology Nov 2022While one of the basic axioms of pharmacology postulates that there is a relationship between the concentration and effects of a drug, the value of measuring blood... (Meta-Analysis)
Meta-Analysis Review
RATIONALE
While one of the basic axioms of pharmacology postulates that there is a relationship between the concentration and effects of a drug, the value of measuring blood levels is questioned by many clinicians. This is due to the often-missing validation of therapeutic reference ranges.
OBJECTIVES
Here, we present a prototypical meta-analysis of the relationships between blood levels of aripiprazole, its target engagement in the human brain, and clinical effects and side effects in patients with schizophrenia and related disorders.
METHODS
The relevant literature was systematically searched and reviewed for aripiprazole oral and injectable formulations. Population-based concentration ranges were computed (N = 3,373) and pharmacokinetic influences investigated.
RESULTS
Fifty-three study cohorts met the eligibility criteria. Twenty-nine studies report blood level after oral, 15 after injectable formulations, and nine were positron emission tomography studies. Conflicting evidence for a relationship between concentration, efficacy, and side effects exists (assigned level of evidence low, C; and absent, D). Population-based reference ranges are well in-line with findings from neuroimaging data and individual efficacy studies. We suggest a therapeutic reference range of 120-270 ng/ml and 180-380 ng/ml, respectively, for aripiprazole and its active moiety for the treatment of schizophrenia and related disorders.
CONCLUSIONS
High interindividual variability and the influence of CYP2D6 genotypes gives a special indication for Therapeutic Drug Monitoring of oral and long-acting aripiprazole. A starting dose of 10 mg will in most patients result in effective concentrations in blood and brain. 5 mg will be sufficient for known poor metabolizers.
Topics: Humans; Aripiprazole; Schizophrenia; Reference Values; Antipsychotic Agents; Cytochrome P-450 CYP2D6
PubMed: 36195732
DOI: 10.1007/s00213-022-06233-2 -
Molecular Imaging 2022Positron emission tomography (PET) imaging with prostate-specific membrane antigen- (PSMA-) binding tracers has been found incidentally to demonstrate uptake in CNS... (Review)
Review
INTRODUCTION
Positron emission tomography (PET) imaging with prostate-specific membrane antigen- (PSMA-) binding tracers has been found incidentally to demonstrate uptake in CNS tumors. Following the encouraging findings of several such case reports, there is a growing interest in the potential application of PSMA-targeted PET imaging for diagnostics, theranostics, and monitoring of CNS tumors. This is a systematic literature review on PSMA-binding tracers in CNS tumors.
METHODS
A PubMed search was conducted, including preclinical and clinical reports. One hundred and twelve records were identified, and after screening, 56 were included in the final report.
RESULTS
Tissue studies demonstrated PSMA expression in tumor vascular endothelial cells, without expression in normal brain tissue, though the extent and intensity of staining varied by anti-PSMA antibody and methodology. Most included studies reported on gliomas, which showed strong PSMA ligand uptake and more favorable tumor to background ratios than other PET tracers. There are also case reports demonstrating PSMA ligand uptake in prostate cancer brain metastases, nonprostate cancer brain metastases, and meningiomas. We also review the properties of the various PSMA-binding radiotracers available. Therapeutic and theranostic applications of PSMA-binding tracers have been studied, including labeled alpha- and beta-ray emitting isotopes, as well as PSMA targeting in directing MRI-guided focused ultrasound.
CONCLUSIONS
There is a potential application for PSMA-targeted PET in neuro-oncology as a combination of diagnostic and therapeutic use, as a theranostic modality for managing CNS tumors. Further research is needed regarding the mechanism(s) of PSMA expression in CNS tumors and its differential performance by tumor type.
Topics: Brain Neoplasms; Endothelial Cells; Humans; Ligands; Male; Neuroimaging; Positron-Emission Tomography; Prostate; Prostatic Neoplasms; Radiopharmaceuticals
PubMed: 35517711
DOI: 10.1155/2022/5358545 -
Journal of Thoracic Disease Feb 2023Lung cancers with air lucency are poorly understood, often recognized only after substantial progression. (Review)
Review
BACKGROUND
Lung cancers with air lucency are poorly understood, often recognized only after substantial progression.
METHODS
From a systematic review (PubMed and EMBASE, 2000-2022, terms related to cystic, cavitary, bulla, pseudocavitary, bubble-like, date 10-30-2022) 49 studies were selected using broad inclusion criteria (case series of ≥10 cases up to trials and reviews). There was no source of funding. Primary evidence relevant to clinical management issues was assembled. Because data was available only from heterogeneous retrospective case series, meta-analysis and formal risk-of-bias assessment was omitted. A framework was developed to guide clinical management based on the available data.
RESULTS
Demographic, smoking and histologic differences suggest that cystic, cavitary and bullous lung cancers with air lucency may be distinct entities; insufficient data leaves it unclear whether this also applies to pseudocavitary (solid) or bubble-like (ground glass) cancers. Annual observation of irregular thin-walled cysts is warranted; a surgical diagnosis (and resection) is justified once a solid component appears because subsequent progression is often rapid with markedly worse outcomes. Bubble-like ground glass lesions should be managed similarly. Cavitary lesions must be distinguished from infection or vasculitis, but generally require needle or surgical biopsy. Pseudocavitary lesions are less well studied; positron emission tomography may be useful in this setting to differentiate scar from malignancy. Further research is needed because these conclusions are based on interpretation of retrospective case series.
CONCLUSIONS
The aggregate of available evidence suggests a framework for management of suspected lung cancers with air lucency. Greater awareness, earlier detection, and aggressive management once a solid component appears are needed. This review and framework should facilitate further research; questions include whether the suggested entities and proposed management are borne out and should involve clearly defined terms and outcomes related to progression and treatment. In summary, a conceptual understanding is emerging from interpretation of available data about a previously poorly understood topic; this should improve patient outcomes.
PubMed: 36910113
DOI: 10.21037/jtd-22-1199 -
The British Journal of Radiology Dec 2021Radiomics is the conversion of medical images into quantitative high-dimensional data. Laryngeal cancer, one of the most common head and neck cancers, has risen globally...
OBJECTIVES
Radiomics is the conversion of medical images into quantitative high-dimensional data. Laryngeal cancer, one of the most common head and neck cancers, has risen globally by 58.7%. CT, MRI and PET are acquired during the diagnostic process providing potential data for radiomic analysis and correlation with outcomes.This review aims to examine the applications of this technique to laryngeal cancer and the future considerations for translation into clinical practice.
METHODS
A comprehensive systematic review-informed search of the MEDLINE and EMBASE databases was undertaken. Keywords "laryngeal cancer" OR "larynx" OR "larynx cancer" OR "head and neck cancer" were combined with "radiomic" OR "signature" OR "machine learning" OR "artificial intelligence". Additional articles were obtained from bibliographies using the "snowball method".
RESULTS
The included studies ( = 15) demonstrated that radiomic features are significantly associated with various clinical outcomes (including stage, overall survival, treatment response, progression-free survival) and that predictive models incorporating radiomic features are superior to those that do not. Two studies demonstrated radiomics could improve laryngeal cancer staging whilst 12 studies affirmed its predictive capability for clinical outcomes.
CONCLUSIONS
Radiomics has potential for improving multiple aspects of laryngeal cancer care; however, the heterogeneous cohorts and lack of data on laryngeal cancer exclusively inhibits firm conclusions. Large prospective well-designed studies in laryngeal cancer are required to progress this field. Furthermore, to implement radiomics into clinical practice, a unified research effort is required to standardise radiomics practice.
ADVANCES IN KNOWLEDGE
This review has highlighted the value of radiomics in enhancing laryngeal cancer care (including staging, prognosis and predicting treatment response).
Topics: Humans; Image Interpretation, Computer-Assisted; Laryngeal Neoplasms; Larynx; Machine Learning; Magnetic Resonance Imaging; Positron-Emission Tomography; Tomography, X-Ray Computed
PubMed: 34586899
DOI: 10.1259/bjr.20210499 -
Diagnostics (Basel, Switzerland) Jul 2021The purpose of this paper is to investigate the prognostic value of fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) parameters in... (Review)
Review
A Systematic Review and Meta-Analysis of the Prognostic Impact of Pretreatment Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography Parameters in Patients with Locally Advanced Cervical Cancer Treated with Concomitant Chemoradiotherapy.
BACKGROUNDS
The purpose of this paper is to investigate the prognostic value of fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) parameters in patients treated with concurrent chemoradiotherapy (CCRT) for locally advanced cervical cancer (LACC).
METHODS
Studies that met the following criteria were retrieved from PubMed and Embase: patients treated with CCRT for LACC; FDG PET/CT scans performed before CCRT treatment; and a detected relationship between the parameters of FDG PET/CT and the prognosis of patients. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were used to estimate the overall survival (OS) or event-free survival (EFS).
RESULTS
In total, 14 eligible studies with 1313 patients were included in this meta-analysis. Patients with a high maximum standardized uptake value (SUVmax) have a shorter OS than those with a low SUV (HR = 2.582, 95% = CI 1.936-3.443, < 0.001). Primary tumor SUV values (HR = 1.938, 95% CI = 1.203-3.054, = 0.004) were significantly correlated with EFS, with a relatively high heterogeneity ( = 84% and = 69.4%, respectively). Based on the limited data, the combined HR for EFS with the highest primary tumor total lesion glycolysis (TLG) and metabolic tumor volume (MTV) was 1.843 (95% CI = 1.100-3.086, = 0.02) and 2.06 (95% CI = 1.21-3.51, = 0.007), respectively. Besides, the combined HR for OS with the highest nodal SUV was 2.095 (95% CI = 2.027-2.166, < 0.001).
CONCLUSION
A high primary SUVmax has a significant correlation with the OS and EFS of patients treated with CCRT for LACC and may therefore serve as a prognostic predictor. Due to the limited data, to explore the correlation between survival and TLG, MTV, and nodal SUVmax, further large-scale prospective studies are needed.
PubMed: 34359345
DOI: 10.3390/diagnostics11071258 -
Journal of Korean Medical Science Nov 2021We conducted a pooled analysis of the diagnostic accuracy of F-18 fluoroestradiol (F-18 FES) positron emission tomography/computed tomography (PET/CT) assessing estrogen... (Meta-Analysis)
Meta-Analysis
BACKGROUND
We conducted a pooled analysis of the diagnostic accuracy of F-18 fluoroestradiol (F-18 FES) positron emission tomography/computed tomography (PET/CT) assessing estrogen receptor expression of patients who have recurrent or metastatic breast cancer.
METHODS
Two investigators and seven related experts (from the departments of nuclear medicine, hematological oncology, surgery, and evidence-based medicine) evaluated the effectiveness of F-18 FES PET/CT according to diagnostic accuracy and correlation with immunohistochemistry tests via systematic literature review, and safety according to test-related side effects. The present study was conducted in accordance with the Scottish Intercollegiate Guidelines (SIGN), and the Cochrane, and Preferred Reporting Items for Systematic Reviews and Meta Analyses guidelines. The SIGN tools were used for quality assessment.
RESULTS
Of the 512 articles retrieved in the literature search, 8 were deemed to be eligible for inclusion. Results of the evaluation indicated that the F-18 FES PET/CT test was safe because patients who reported pain in the injection site in the analyzed articles are most likely to be caused by mechanical injury from needle injection not by administration of radioactive materials. Assessment of diagnostic accuracy based on data from seven studies revealed a pooled sensitivity and specificity of 0.86 and 0.85, respectively.
CONCLUSION
As such, the test was evaluated to be a safe and effective and, considering the anatomical site where only invasive tests are possible, the test was deemed to have high clinical utility.
Topics: Breast Neoplasms; Estradiol; Female; Fluorine Radioisotopes; Humans; Positron Emission Tomography Computed Tomography; Radiopharmaceuticals; Sensitivity and Specificity
PubMed: 34725978
DOI: 10.3346/jkms.2021.36.e271 -
European Urology Open Science Nov 2021In December 2020, the US Food and Drug Administration approved a Ga-labeled prostate-specific membrane antigen ligand (Ga-PSMA-11) for positron emission tomography (PET)... (Review)
Review
Comparison of Ga-labeled Prostate-specific Membrane Antigen Ligand Positron Emission Tomography/Magnetic Resonance Imaging and Positron Emission Tomography/Computed Tomography for Primary Staging of Prostate Cancer: A Systematic Review and Meta-analysis.
CONTEXT
In December 2020, the US Food and Drug Administration approved a Ga-labeled prostate-specific membrane antigen ligand (Ga-PSMA-11) for positron emission tomography (PET) in patients with suspected prostate cancer (PCa) metastasis who are candidates for initial definitive therapy. Ga-PSMA PET is increasingly performed for these patients and is usually combined with computed tomography (CT). In recent years, Ga-PSMA PET has been combined with high-resolution magnetic resonance imaging (MRI), which is beneficial for T staging and may further enhance the staging of primary PCa.
OBJECTIVE
To compare the diagnostic accuracy of Ga-PSMA PET/MRI with Ga-PSMA PET/CT for staging of primary PCa.
EVIDENCE ACQUISITION
A comprehensive literature search was performed using Embase, PubMed/Medline, Web of Science, Cochrane Library, and Google Scholar up to June 24, 2021 in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Risk of bias was assessed using the QUADAS-2 tool.
EVIDENCE SYNTHESIS
The search identified 2632 articles, of which 27 were included. The diagnostic accuracy of Ga-PSMA PET/MRI, measured as the pooled natural logarithm of diagnostic odds ratio (lnDOR), was 2.27 (95% confidence interval [CI] 1.21-3.32) for detection of extracapsular extension (ECE), 3.50 (95% CI 2.14-4.86) for seminal vesicle invasion (SVI), and 4.73 (95% CI 2.93-6.52) for lymph node metastasis (LNM). For Ga-PSMA PET/CT, the analysis showed lnDOR of 2.45 (95% CI 0.75-4.14), 2.94 (95% CI 2.26-3.63), and 2.42 (95% CI 2.07-2.78) for detection of ECE, SVI, and LNM, respectively. The overall risk of bias and applicability concerns were assessed as moderate and low, respectively.
CONCLUSIONS
Ga-PSMA PET/MRI shows high diagnostic accuracy equivalent to that of Ga-PSMA PET/CT for detection of ECE, SVI, and LNM in staging of PCa. There is an urgent need for direct comparison of the two diagnostic tests in future research.
PATIENT SUMMARY
The use of radioactively labeled molecules that bind to prostate-specific membrane antigen (Ga-PSMA) for positron emission tomography (PET) scans combined with either computed tomography (CT) or magnetic resonance imaging (MRI) is increasing for prostate cancer diagnosis. There is a need for direct comparison of the two tests to demonstrate the benefit of Ga-PSMA PET/MRI for determining tumor stage in prostate cancer.
TAKE HOME MESSAGE
After the recent US Food and Drug Administration approval of Ga-labeled prostate-specific membrane antigen ligand (Ga-PSMA) positron emission tomography (PET) for staging of primary prostate cancer (PCa), it is expected that the use of this imaging modality will increase rapidly. Our review of the literature shows that Ga-PSMA PET/magnetic resonance imaging has high diagnostic accuracy equivalent to that of Ga-PSMA PET/computed tomography in primary PCa staging. There is an urgent need for direct head-to-head comparison of the two diagnostic tests in future research.
PubMed: 34632423
DOI: 10.1016/j.euros.2021.09.006 -
Autoimmunity Reviews Feb 2024Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating condition characterized by an elusive etiology and pathophysiology. This study aims to... (Meta-Analysis)
Meta-Analysis
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating condition characterized by an elusive etiology and pathophysiology. This study aims to evaluate the pathological role of neuroinflammation in ME/CFS by conducting an exhaustive analysis of 65 observational studies. Four neuroimaging techniques, including magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), electroencephalography (EEG), and positron emission tomography (PET), were employed to comparatively assess brain regional structure, metabolite profiles, electrical activity, and glial activity in 1529 ME/CFS patients (277 males, 1252 females) and 1715 controls (469 males, 1246 females). Clinical characteristics, including sex, age, and fatigue severity, were consistent with established epidemiological patterns. Regional alterations were most frequently identified in the cerebral cortex, with a notable focus on the frontal cortex. However, our meta-analysis data revealed a significant hypoactivity in the insular and thalamic regions, contrary to observed frequencies. These abnormalities, occurring in pivotal network hubs bridging reason and emotion, disrupt connections with the limbic system, contributing to the hallmark symptoms of ME/CFS. Furthermore, we discuss the regions where neuroinflammatory features are frequently observed and address critical neuroimaging limitations, including issues related to inter-rater reliability. This systematic review serves as a valuable guide for defining regions of interest (ROI) in future neuroimaging investigations of ME/CFS.
Topics: Female; Humans; Male; Brain; Electroencephalography; Fatigue Syndrome, Chronic; Magnetic Resonance Imaging; Neuroimaging; Neuroinflammatory Diseases; Positron-Emission Tomography
PubMed: 38016575
DOI: 10.1016/j.autrev.2023.103484 -
Cancer Medicine Aug 2023Positron emission tomography (PET) images of head and neck squamous cell carcinoma (HNSCC) patients can assess the functional and biochemical processes at cellular... (Meta-Analysis)
Meta-Analysis Review
A systematic review and meta-analysis of predictive and prognostic models for outcome prediction using positron emission tomography radiomics in head and neck squamous cell carcinoma patients.
BACKGROUND
Positron emission tomography (PET) images of head and neck squamous cell carcinoma (HNSCC) patients can assess the functional and biochemical processes at cellular levels. Therefore, PET radiomics-based prediction and prognostic models have the potentials to understand tumour heterogeneity and assist clinicians with diagnosis, prognosis and management of the disease. We conducted a systematic review of published modelling information to evaluate the usefulness of PET radiomics in the prediction and prognosis of HNSCC patients.
METHODS
We searched bibliographic databases (MEDLINE, Embase, Web of Science) from 2010 to 2021 and considered 31 studies with pre-defined inclusion criteria. We followed the CHARMS checklist for data extraction and performed quality assessment using the PROBAST tool. We conducted a meta-analysis to estimate the accuracy of the prediction and prognostic models using the diagnostic odds ratio (DOR) and average C-statistic, respectively.
RESULTS
Manual segmentation method followed by 40% of the maximum standardised uptake value (SUV ) thresholding is a commonly used approach. The area under the receiver operating curves of externally validated prediction models ranged between 0.60-0.87, 0.65-0.86 and 0.62-0.75 for overall survival, distant metastasis and recurrence, respectively. Most studies highlighted an overall high risk of bias (outcome definition, statistical methodologies and external validation of models) and high unclear concern in terms of applicability. The meta-analysis showed the estimated pooled DOR of 6.75 (95% CI: 4.45, 10.23) for prediction models and the C-statistic of 0.71 (95% CI: 0.67, 0.74) for prognostic models.
CONCLUSIONS
Both prediction and prognostic models using clinical variables and PET radiomics demonstrated reliable accuracy for detecting adverse outcomes in HNSCC, suggesting the prospect of PET radiomics in clinical settings for diagnosis, prognosis and management of HNSCC patients. Future studies of prediction and prognostic models should emphasise the quality of reporting, external model validation, generalisability to real clinical scenarios and enhanced reproducibility of results.
Topics: Humans; Squamous Cell Carcinoma of Head and Neck; Prognosis; Reproducibility of Results; Positron-Emission Tomography; Head and Neck Neoplasms; Fluorodeoxyglucose F18
PubMed: 37353996
DOI: 10.1002/cam4.6278