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European Journal of Nuclear Medicine... Dec 2023The current clinical recommendations posit the deployment of specific approved radiolabeled prostate-specific membrane antigen-ligand positron emission tomography (PSMA... (Meta-Analysis)
Meta-Analysis Review
The diagnostic accuracy of radiolabeled PSMA-ligand PET for tumour staging in newly diagnosed prostate cancer patients compared to histopathology: a systematic review and meta-analysis.
PURPOSE
The current clinical recommendations posit the deployment of specific approved radiolabeled prostate-specific membrane antigen-ligand positron emission tomography (PSMA PET) for detecting metastatic prostate cancer during primary staging. Nevertheless, the precise efficacy of such ligands in localizing intraprostatic tumours (index tumour) and T-staging is not well established. Consequently, the objective of this inquiry is to ascertain the diagnostic accuracy of PSMA-PET in the tumour staging of newly diagnosed prostate cancer by means of a meta-analysis that integrates studies utilizing histological confirmation as the reference standard.
METHODS
In this study, we conducted a systematic literature search of the PubMed, Embase, Web of Science, and Cochrane Library databases using a predefined collection of search terms. These terms included 'PSMA PET', 'primary staging', and 'prostate cancer'. Subsequently, two independent reviewers evaluated all the studies based on predetermined inclusion criteria, extracted pertinent data, and assessed the quality of evidence. Any disparities were resolved by a third reviewer. A random effects Sidik-Jonkman model was applied to conduct a meta-analysis and estimate the diagnostic accuracy on a per-patient basis, along with 95% confidence intervals. Moreover, an appraisal regarding the likelihood of publication bias and the impact of small-study effects was performed utilizing both Egger's test and a graphical examination of the funnel plot.
RESULTS
The present analysis comprised a total of twenty-three scientific papers encompassing 969 patients and involved their analysis by both qualitative and quantitative approaches. The results of this study demonstrated that the estimated diagnostic accuracy of PSMA PET/CT and PSMA PET/MRI, for the detection of intraprostatic tumours, regardless of the type of PSMA-ligand, was 86% (95% CI: 76-96%) and 97% (95% CI: 94-100%), respectively. Furthermore, the diagnostic accuracy for the detection of extraprostatic extension (EPE) was 73% (95% CI: 64-82%) and 77% (95% CI: 69-85%), while the diagnostic accuracy for the detection of seminal vesicle involvement (SVI) was 87% (95% CI: 80-93) and 90% (95% CI: 82-99%), respectively.
CONCLUSION
The present investigation has demonstrated that PSMA PET/MRI surpasses currently recommended multiparametric magnetic resonance imaging (mpMRI) in terms of diagnostic accuracy as inferred from a notable data trajectory, whereas PSMA-PET/CT exhibited comparable diagnostic accuracy for intraprostatic tumour detection and T-staging compared to mpMRI. Nevertheless, the analysis has identified certain potential limitations, such as small-study effects and a potential for publication bias, which may impact the overall conclusions drawn from this study.
Topics: Male; Humans; Positron Emission Tomography Computed Tomography; Neoplasm Staging; Ligands; Gallium Radioisotopes; Prostatic Neoplasms; Positron-Emission Tomography
PubMed: 37597010
DOI: 10.1007/s00259-023-06392-0 -
EBioMedicine Jul 2023Various studies have reported cell-free RNAs (cfRNAs) as noninvasive biomarkers for detecting hepatocellular carcinoma (HCC). However, they have not been independently...
BACKGROUND
Various studies have reported cell-free RNAs (cfRNAs) as noninvasive biomarkers for detecting hepatocellular carcinoma (HCC). However, they have not been independently validated, and some results are contradictory. We provided a comprehensive evaluation of various types of cfRNA biomarkers and a full mining of the biomarker potential of new features of cfRNA.
METHODS
We first systematically reviewed reported cfRNA biomarkers and calculated dysregulated post-transcriptional events and cfRNA fragments. In 3 independent multicentre cohorts, we further selected 6 cfRNAs using RT-qPCR, built a panel called HCCMDP with AFP using machine learning, and internally and externally validated HCCMDP's performance.
FINDINGS
We identified 23 cfRNA biomarker candidates from a systematic review and analysis of 5 cfRNA-seq datasets. Notably, we defined the cfRNA domain to describe cfRNA fragments systematically. In the verification cohort (n = 183), cfRNA fragments were more likely to be verified, while circRNA and chimeric RNA candidates were neither abundant nor stable as qPCR-based biomarkers. In the algorithm development cohort (n = 287), we build and test the panel HCCMDP with 6 cfRNA markers and AFP. In the independent validation cohort (n = 171), HCCMDP can distinguish HCC patients from control groups (all: AUC = 0.925; CHB: AUC = 0.909; LC: AUC = 0.916), and performs well in distinguishing early-stage HCC patients (all: AUC = 0.936; CHB: AUC = 0.917; LC: AUC = 0.928).
INTERPRETATION
This study comprehensively evaluated full-spectrum cfRNA biomarker types for HCC detection, highlighted the cfRNA fragment as a promising biomarker type in HCC detection, and provided a panel HCCMDP.
FUNDING
National Natural Science Foundation of China, and The National Key Basic Research Program (973 program).
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; alpha-Fetoproteins; Cell-Free Nucleic Acids; Biomarkers, Tumor; ROC Curve; MicroRNAs
PubMed: 37315449
DOI: 10.1016/j.ebiom.2023.104645 -
Clinical Genitourinary Cancer Feb 2023Adrenocortical carcinoma (ACC) is a very rare endocrine cancer and is associated with a poor prognosis. There is a paucity of randomized clinical trials for this rare... (Review)
Review
A Systematic Review of Published Clinical Trials in the Systemic Treatment of Adrenocortical Carcinoma: An Initiative Led on Behalf of the Global Society of Rare Genitourinary Tumors.
Adrenocortical carcinoma (ACC) is a very rare endocrine cancer and is associated with a poor prognosis. There is a paucity of randomized clinical trials for this rare disease. We aimed to perform a systematic review of the literature on systemic therapy options in different stages of ACC. A systematic review was performed using Pubmed and Embase databases according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. A total of 24 trials of systemic therapy in the treatment of ACC were identified and included in this review. Only one clinical trial in the adjuvant setting was identified, the negative phase III trial ADIUVO, which tested mitotane in low to intermediate-risk ACC patients. In the treatment of advanced ACC, cisplatin-based chemotherapy was evaluated in small and non-randomized phase II trials, and response rates ranged from 21% to 53.5%. The phase III trial FIRM-ACT compared etoposide, doxorubicin, cisplatin, and mitotane versus treatment with streptozotocin and mitotane and showed no difference in OS, but higher RR and PFS were reported with the multi-drug regimen. Six clinical trials of immunotherapy and seven studies of targeted therapy in advanced ACC were included, with modest activity and no phase 3 trials were identified. Treatment recommendations of ACC are based on retrospective and small studies with limited systemic therapy options. International and multi-center collaboration is essential to expand clinical research and improve outcomes.
Topics: Humans; Adrenocortical Carcinoma; Mitotane; Adrenal Cortex Neoplasms; Cisplatin; Retrospective Studies; Antineoplastic Combined Chemotherapy Protocols
PubMed: 36376169
DOI: 10.1016/j.clgc.2022.10.011 -
Radiology Mar 2022Background Contrast-enhanced mammography (CEM) is a promising technique for breast cancer detection, but conflicting results have been reported in previous... (Meta-Analysis)
Meta-Analysis
Background Contrast-enhanced mammography (CEM) is a promising technique for breast cancer detection, but conflicting results have been reported in previous meta-analyses. Purpose To perform a systematic review and meta-analysis of CEM diagnostic performance considering different interpretation methods and clinical settings. Materials and Methods The MEDLINE, EMBASE, Web of Science, and Cochrane Library databases were systematically searched up to July 15, 2021. Prospective and retrospective studies evaluating CEM diagnostic performance with histopathology and/or follow-up as the reference standard were included. Study quality was assessed with the Quality Assessment of Diagnostic Accuracy Studies 2 tool. Summary diagnostic odds ratio and area under the receiver operating characteristic curve were estimated with the hierarchical summary receiver operating characteristic (HSROC) model. Summary estimates of sensitivity and specificity were obtained with the hierarchical bivariate model, pooling studies with the same image interpretation approach or focused on the same findings. Heterogeneity was investigated through meta-regression and subgroup analysis. Results Sixty studies (67 study parts, 11 049 CEM examinations in 10 605 patients) were included. The overall area under the HSROC curve was 0.94 (95% CI: 0.91, 0.96). Pooled diagnostic odds ratio was 55.7 (95% CI: 42.7, 72.7) with high heterogeneity (τ = 0.3). At meta-regression, CEM interpretation with both low-energy and recombined images had higher sensitivity (95% vs 94%, < .001) and specificity (81% vs 71%, = .03) compared with recombined images alone. At subgroup analysis, CEM showed a 95% pooled sensitivity (95% CI: 92, 97) and a 78% pooled specificity (95% CI: 66, 87) from nine studies in patients with dense breasts, while in 10 studies on mammography-detected suspicious findings, CEM had a 92% pooled sensitivity (95% CI: 89, 94) and an 84% pooled specificity (95% CI: 73, 91). Conclusion Contrast-enhanced mammography demonstrated high performance in breast cancer detection, especially with joint interpretation of low-energy and recombined images. © RSNA, 2021 See also the editorial by Bahl in this issue.
Topics: Breast Neoplasms; Contrast Media; Female; Humans; Mammography
PubMed: 34904875
DOI: 10.1148/radiol.211412 -
Oral Surgery, Oral Medicine, Oral... Nov 2022We performed a systematic review dedicated to pooling evidence for the associations of clinical features with malignant transformation (MT) and recurrence of 3 oral... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
We performed a systematic review dedicated to pooling evidence for the associations of clinical features with malignant transformation (MT) and recurrence of 3 oral potentially malignant disorders (OPMDs) (actinic cheilitis [AC], oral leukoplakia [OL], and proliferative verrucous leukoplakia [PVL]).
STUDY DESIGN
We selected studies that included clinical features and risk factors (age, sex, site, size, appearance, alcohol intake, tobacco use, and sun exposure) of OL, PVL, and AC associated with recurrence and/or MT.
RESULTS
Based on the meta-analysis results, non-homogeneous OL appears to have a 4.53 times higher chance of recurrence after treatment. We also found 6.52 higher chances of MT of non-homogeneous OL. Another clinical feature related to higher MT chances is the location (floor of the mouth and tongue has 4.48 higher chances) and the size (OL with >200 mm in size has 4.10 higher chances of MT). Regarding habits, nonsmoking patients with OL have a 3.20 higher chance of MT. The only clinical feature related to higher chances of MT in patients with PVL was sex (females have a 2.50 higher chance of MT).
CONCLUSIONS
Our study showed that some clinical features may indicate greater chances of recurrence after treatment and MT of OPMD.
Topics: Female; Humans; Leukoplakia, Oral; Precancerous Conditions; Cell Transformation, Neoplastic; Cheilitis
PubMed: 36153299
DOI: 10.1016/j.oooo.2022.07.006 -
Journal of Neuro-oncology Oct 2023Despite their precarious behavioral classification (benign and low grade on histopathology yet behaviorally malignant), great strides have been taken to improve... (Meta-Analysis)
Meta-Analysis Review
Assessing survival outcomes and complication profiles following surgical excision and radiotherapy as interventions for skull base chordoma: a systematic review of operative margins and surgical approaches.
INTRODUCTION
Despite their precarious behavioral classification (benign and low grade on histopathology yet behaviorally malignant), great strides have been taken to improve prognostication and treatment paradigms for patients with skull base chordoma. With respect to surgical techniques, lateral transcranial (TC) approaches have traditionally been used, however endoscopic endonasal approaches (EEA) have been advocated for midline lesions. Nonetheless, due to the rarity of this pathology (0.2% of all intracranial neoplasms), investigations within the literature remain limited to small retrospective series. Furthermore, radiotherapeutic treatments investigated to date have proven largely ineffective.
METHODS
Accordingly, we performed a systematic review in order to profile surgical and survival outcomes for skull base chordoma. Fixed and random-effect meta-analyses were performed for categorical variables including GTR, STR, 5-year OS, 10-year OS, 5-year PFS, and 10-year PFS. Additionally, we pooled eligible studies for formal meta-analysis to compare outcomes by surgical approach (lateral versus midline). Statistical analyses were performed using R Studio 'metafor' package or Cochrane Review Manager. Furthermore, meta-analysis of pooled mortality rates and sub-analyses of operative margin and surgical complications were used to compare midline versus lateral approaches via the Mantel-Haenszel method. We considered all p-values < 0.05 to be statistically significant.
RESULTS
Following the systematic search and screen, 55 studies published between 1993 and 2022 reporting data for 2453 patients remained eligible for analysis. Sex distribution was comparable between males and females, with a slight predominance of male-identifying patients (0.5625 [95% CI: 0.5418; 0.3909]). Average age at diagnosis was 42.4 ± 12.5 years, while average age of treatment initiation was 43.0 ± 10.6 years. Overall, I value indicated notable heterogeneity across the 55 studies [I = 56.3% (95%CI: 44.0%; 65.9%)]. With respect to operative margins, the rate of GTR was 0.3323 [95% CI: 0.2824; 0.3909], I = 91.9% [95% CI: 90.2%; 93.4%], while the rate of STR was significantly higher at 0.5167 [95% CI: 0.4596; 0.5808], I = 93.1% [95% CI: 91.6%; 94.4%]. The most common complication was CSF leak (5.4%). In terms of survival outcomes, 5-year OS rate was 0.7113 [95% CI: 0.6685; 0.7568], I = 91.9% [95% CI: 90.0%; 93.5%]. 10-year OS rate was 0.4957 [95% CI: 0.4230; 0.5809], I = 92.3% [95% CI: 89.2%; 94.4%], which was comparable to the 5-year PFS rate of 0.5054 [95% CI: 0.4394; 0.5813], I = 84.2% [95% CI: 77.6%; 88.8%] and 10-yr PFS rate of 0.4949 [95% CI: 0.4075; 0.6010], I = 14.9% [95% CI: 0.0%; 87.0%]. There were 55 reported deaths for a perioperative mortality rate of 2.5%. The relative risk for mortality in the midline group versus the lateral approach group did not indicate any substantial difference in survival according to laterality of approach (-0.93 [95% CI: -1.03, -0.97], I = 95%, (p < 0.001).
CONCLUSION
Overall, these results indicate good 5-year survival outcomes for patients with skull base chordoma; however, 10-year prognosis for skull base chordoma remains poor due to its radiotherapeutic resistance and high recurrence rate. Furthermore, mortality rates among patients undergoing midline versus lateral skull base approaches appear to be equivocal.
Topics: Female; Humans; Male; Adult; Middle Aged; Retrospective Studies; Chordoma; Cranial Fossa, Posterior; Prognosis; Skull Base Neoplasms; Head and Neck Neoplasms; Treatment Outcome
PubMed: 37880419
DOI: 10.1007/s11060-023-04477-2 -
Neuroradiology Aug 2022Endoscopic biopsy is recommended for diagnosis of nasopharyngeal carcinoma (NPC). A proportion of lesions are hidden from endoscopic view but detected with magnetic... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Endoscopic biopsy is recommended for diagnosis of nasopharyngeal carcinoma (NPC). A proportion of lesions are hidden from endoscopic view but detected with magnetic resonance imaging (MRI). This systematic review and meta-analysis investigated the diagnostic performance of MRI for detection of NPC.
METHODS
An electronic search of twelve databases and registries was performed. Studies were included if they compared the diagnostic accuracy of MRI to a reference standard (histopathology) in patients suspected of having NPC. The primary outcome was accuracy for detection of NPC. Random-effects models were used to pool outcomes for sensitivity, specificity, and positive and negative likelihood ratio (LR). Bias and applicability were assessed using the modified QUADAS-2 tool.
RESULTS
Nine studies were included involving 1736 patients of whom 337 were diagnosed with NPC. MRI demonstrated a pooled sensitivity of 98.1% (95% CI 95.2-99.3%), specificity of 91.7% (95% CI 88.3-94.2%), negative LR of 0.02 (95% CI 0.01-0.05), and positive LR of 11.9 (95% CI 8.35-16.81) for detection of NPC. Most studies were performed in regions where NPC is endemic, and there was a risk of selection bias due to inclusion of retrospective studies and one case-control study. There was limited reporting of study randomization strategy.
CONCLUSION
This study demonstrates that MRI has a high pooled sensitivity, specificity, and negative predictive value for detection of NPC. MRI may be useful for lesion detection prior to endoscopic biopsy and aid the decision to avoid biopsy in patients with a low post-test probability of disease.
Topics: Case-Control Studies; Humans; Magnetic Resonance Imaging; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Retrospective Studies; Sensitivity and Specificity
PubMed: 35499636
DOI: 10.1007/s00234-022-02941-w -
Oral Radiology Apr 2021Oral cancer is the eighth most common type of cancer worldwide and a significant contributor to the global burden caused by this disease. The principal parameters... (Review)
Review
OBJECTIVES
Oral cancer is the eighth most common type of cancer worldwide and a significant contributor to the global burden caused by this disease. The principal parameters considered to influence prognosis, and thus treatment selection, are size and location of the primary tumor, as well as assessment of the presence and extent of lymph node and distant metastasis (DM). However, no known report regarding the relationship between the primary site and DM has been presented. For effective treatment selection and good prognosis, the correlation of DM with anatomic site and histopathology results of the primary malignancy is important. In the present study, we performed a systematic review of published reports in an effort to determine the relationship between the anatomic site of various types of oral cavity cancer and DM.
METHODS
A systematic review of articles published until the end of 2018 was performed using PubMed/MEDLINE.
RESULTS
A total of 150 studies were selected for this review. The percentage of all cases reported with DM was 6.3%, ranging from 0.6% to 33.1% in the individual studies. The rate of incidence of tongue occurrence was 9.3%. A frequent DM site was the lungs, with adenoid cystic carcinoma the most commonly involved histopathological factor. Malignant melanoma was most frequent (43.4%) in all histopathology findings, whereas there were no cases with an acinic cell carcinoma or cystadenocarcinoma.
CONCLUSIONS
We found that the occurrence of DM from the primary site as well as rate of incidence was dependent on histopathological factors.
Topics: Carcinoma, Adenoid Cystic; Humans; Lymph Nodes; Mouth Neoplasms; Retrospective Studies
PubMed: 32468449
DOI: 10.1007/s11282-020-00440-3 -
Histopathology Apr 2023Lymph node micrometastases could be one of the reasons for the high recurrence rate after complete surgical resection in stage I-IIIA non-small cell lung cancer (NSCLC).... (Meta-Analysis)
Meta-Analysis Review
Systematic review and meta-analysis of the prognostic impact of lymph node micrometastasis and isolated tumour cells in patients with stage I-IIIA non-small cell lung cancer.
Lymph node micrometastases could be one of the reasons for the high recurrence rate after complete surgical resection in stage I-IIIA non-small cell lung cancer (NSCLC). The standard evaluation of a single haematoxylin and eosin (H&E) slide of a paraffin-embedded section of a lymph node is insufficient for the detection of micrometastases, and there is a need for additional histopathological evaluation. The association of lymph node micrometastases with survival remains as yet unresolved. The aim of this systematic review and meta-analysis is to investigate if lymph node micrometastases and isolated tumour cells in patients with stage I-IIIA NSCLC, detected with multiple sectioning and/or immunohistochemistry (IHC) and/or reverse transcriptase polymerase chain reaction (RT-PCR), are associated with overall survival (OS) and disease-free survival (DFS) after surgical resection. We performed a meta-analysis of time-to-event outcomes based on 15 articles using ancillary techniques to detect micrometastases. We extracted the OS and DFS every 3-6 months after surgery, for patients with and without occult lymph node micrometastasis, from the survival curves published in each article. These data were used to reconstruct OS and DFS for 'micrometastasis' and 'no micrometastasis' groups. Based on all included studies that used IHC, serial sectioning, or RT-PCR, we found a 5-year OS of 55% (micrometastasis) vs. 75% (no micrometastasis), and a 5-year DFS of 53% (micrometastasis) vs. 75% (no micrometastasis). Patients with stage I-IIIA NSCLC with lymph node micrometastases detected by ancillary histopathological and molecular techniques have a significantly poorer OS and DFS compared to patients without lymph node micrometastases.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Prognosis; Lung Neoplasms; Neoplasm Micrometastasis; Neoplasm Staging; Lymph Nodes
PubMed: 36282087
DOI: 10.1111/his.14831 -
Skeletal Radiology Feb 2022Developments in artificial intelligence have the potential to improve the care of patients with musculoskeletal tumors. We performed a systematic review of the published... (Review)
Review
Developments in artificial intelligence have the potential to improve the care of patients with musculoskeletal tumors. We performed a systematic review of the published scientific literature to identify the current state of the art of artificial intelligence applied to musculoskeletal oncology, including both primary and metastatic tumors, and across the radiology, nuclear medicine, pathology, clinical research, and molecular biology literature. Through this search, we identified 252 primary research articles, of which 58 used deep learning and 194 used other machine learning techniques. Articles involving deep learning have mostly involved bone scintigraphy, histopathology, and radiologic imaging. Articles involving other machine learning techniques have mostly involved transcriptomic analyses, radiomics, and clinical outcome prediction models using medical records. These articles predominantly present proof-of-concept work, other than the automated bone scan index for bone metastasis quantification, which has translated to clinical workflows in some regions. We systematically review and discuss this literature, highlight opportunities for multidisciplinary collaboration, and identify potentially clinically useful topics with a relative paucity of research attention. Musculoskeletal oncology is an inherently multidisciplinary field, and future research will need to integrate and synthesize noisy siloed data from across clinical, imaging, and molecular datasets. Building the data infrastructure for collaboration will help to accelerate progress towards making artificial intelligence truly useful in musculoskeletal oncology.
Topics: Artificial Intelligence; Humans; Machine Learning; Medical Oncology; Musculoskeletal System; Radiology
PubMed: 34013447
DOI: 10.1007/s00256-021-03820-w