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Biomedicines Jan 2022Glioblastoma is the most frequent malignant primitive brain tumor in adults. The treatment includes surgery, radiotherapy, and chemotherapy. During follow-up, combined... (Review)
Review
BACKGROUND
Glioblastoma is the most frequent malignant primitive brain tumor in adults. The treatment includes surgery, radiotherapy, and chemotherapy. During follow-up, combined chemoradiotherapy can induce treatment-related changes mimicking tumor progression on medical imaging, such as pseudoprogression (PsP). Differentiating PsP from true progression (TP) remains a challenge for radiologists and oncologists, who need to promptly start a second-line treatment in the case of TP. Advanced magnetic resonance imaging (MRI) techniques such as diffusion-weighted imaging, perfusion MRI, and proton magnetic resonance spectroscopic imaging are more efficient than conventional MRI in differentiating PsP from TP. None of these techniques are fully effective, but current advances in computer science and the advent of artificial intelligence are opening up new possibilities in the imaging field with radiomics (i.e., extraction of a large number of quantitative MRI features describing tumor density, texture, and geometry). These features are used to build predictive models for diagnosis, prognosis, and therapeutic response.
METHOD
Out of 7350 records for MR spectroscopy, GBM, glioma, recurrence, diffusion, perfusion, pseudoprogression, radiomics, and advanced imaging, we screened 574 papers. A total of 228 were eligible, and we analyzed 72 of them, in order to establish the role of each imaging modality and the usefulness and limitations of radiomics analysis.
PubMed: 35203493
DOI: 10.3390/biomedicines10020285 -
Scientific Reports Aug 2022High-grade gliomas remain the most common primary brain tumour with limited treatments options and early recurrence rates following adjuvant treatments. However,... (Meta-Analysis)
Meta-Analysis
High-grade gliomas remain the most common primary brain tumour with limited treatments options and early recurrence rates following adjuvant treatments. However, differentiating true tumour progression (TTP) from treatment-related effects or pseudoprogression (PsP), may critically influence subsequent management options. Structural MRI is routinely employed to evaluate treatment responses, but misdiagnosis of TTP or PsP may lead to continuation of ineffective or premature cessation of effective treatments, respectively. A systematic review and meta-analysis were conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses method. Embase, MEDLINE, Web of Science and Google Scholar were searched for methods applied to differentiate PsP and TTP, and studies were selected using pre-specified eligibility criteria. The sensitivity and specificity of included studies were summarised. Three of the identified methods were compared in a separate subgroup meta-analysis. Thirty studies assessing seven distinct neuroimaging methods in 1372 patients were included in the systematic review. The highest performing methods in the subgroup analysis were DWI (AUC = 0.93 [0.91-0.95]) and DSC-MRI (AUC = 0.93 [0.90-0.95]), compared to DCE-MRI (AUC = 0.90 [0.87-0.93]). 18F-fluoroethyltyrosine PET (18F-FET PET) and amide proton transfer-weighted MRI (APTw-MRI) also showed high diagnostic accuracy, but results were based on few low-powered studies. Both DWI and DSC-MRI performed with high sensitivity and specificity for differentiating PsP from TTP. Considering the technical parameters and feasibility of each identified method, the authors suggested that, at present, DSC-MRI technique holds the most clinical potential.
Topics: Brain Neoplasms; Glioma; Humans; Magnetic Resonance Imaging; Sensitivity and Specificity; Treatment Outcome
PubMed: 35918373
DOI: 10.1038/s41598-022-16726-x -
Journal of Clinical Medicine May 2021We evaluated the incidence of pseudoprogression and indeterminate response (IR) in patients with lymphoma treated with immune checkpoint inhibitors (ICIs). A systematic... (Review)
Review
We evaluated the incidence of pseudoprogression and indeterminate response (IR) in patients with lymphoma treated with immune checkpoint inhibitors (ICIs). A systematic search of PubMed and EMBASE was performed up to 6 February 2021, using the keywords "lymphoma," "immunotherapy," and "pseudoprogression." Random-effects models were used to calculate both pooled incidence of pseudoprogression patients with lymphoma and an IR according to LYRIC criteria, while the Higgins inconsistency index (I2) test and Cochran's Q test were used for heterogeneity. Eight original articles were included, in which the number of patients ranged from 7 to 243. Among the lymphoma patients with ICIs, the pooled incidence of pseudoprogression was 10% (95% confidence interval [CI]: 0.06-0.17). There was no publication bias in Begg's test ( = 0.14). Three articles were analyzed to determine the pooled incidence of pseudoprogression in patients with IR according to LYRIC criteria in a subgroup analysis, which was shown to be 19% (95% CI: 0.08-0.40). A significant proportion (10%) of patients with lymphoma treated with ICIs showed pseudoprogression, and 19% of patients with an IR response showed pseudoprogression and a delayed response. Immune-related response criteria such as LYRIC may be used for patients with lymphoma treated with ICIs.
PubMed: 34071024
DOI: 10.3390/jcm10112257 -
Clinical Neuroradiology Sep 2018High-grade gliomas are the most common primary brain tumours. Pseudoprogression describes the false appearance of radiation-induced progression on MRI. A distinction... (Meta-Analysis)
Meta-Analysis
BACKGROUND
High-grade gliomas are the most common primary brain tumours. Pseudoprogression describes the false appearance of radiation-induced progression on MRI. A distinction should be made from true tumour progression to correctly plan treatment. However, there is wide variation of reported pseudoprogression. We thus aimed to establish the incidence of pseudoprogression and tumour progression in high-grade glioma patients with a systematic review and meta-analysis.
METHODS
We searched PubMed, Embase and Web of Science on the incidence of pseudoprogression and tumour progression in adult high-grade glioma patients from 2005, the latest on 8 October 2014. Histology or imaging follow-up was used as reference standard. Extracted data included number of patients with worsening of imaging findings on T1 postcontrast or T2/FLAIR, pseudoprogression and tumour progression. Study quality was assessed. Heterogeneity was tested with I . Pooling of the results was done with random models using Metaprop in STATA (StataCorp. Stata Statistical Software. College Station, TX: StataCorp LP).
RESULTS
We identified 73 studies. MRI progression occurred in 2603 patients. Of these, 36% (95% confidence interval [CI] 33-40%) demonstrated pseudoprogression, 60% (95%CI 56-64%) tumour progression and unknown outcome was present in the remaining 4% of the patients (range 1-37%).
CONCLUSION
This meta-analysis demonstrated for the first time a notably high pooled incidence of pseudoprogression in patients with a form of progression across the available literature. This highlighted the full extent of the problem of the currently conventional MRI-based Response Assessment in Neuro-Oncology (RANO) criteria for treatment evaluation in high-grade gliomas. This underscores the need for more accurate treatment evaluation using advanced imaging to improve diagnostic accuracy and therapeutic approach.
Topics: Adult; Brain Neoplasms; Chemoradiotherapy; Disease Progression; Glioma; Humans; Incidence; Magnetic Resonance Imaging
PubMed: 28466127
DOI: 10.1007/s00062-017-0584-x -
World Journal of Urology Nov 2018A small subset of patients treated with immune checkpoint inhibitors manifest atypical patterns of response, the so-called pseudoprogression (PP) and hyperprogression...
OBJECTIVES
A small subset of patients treated with immune checkpoint inhibitors manifest atypical patterns of response, the so-called pseudoprogression (PP) and hyperprogression (HP). Their prevalence in urothelial (UC) and renal cancer (RCC) remains, to date, mostly uninvestigated. Therefore, we aimed to provide a summary of the current knowledge about PP and HP during immune checkpoint inhibitor therapy in UC and RCC patients.
METHODS AND MATERIALS
A systematic medline/pubmed literature search was performed. The atypical patterns of response to systemic immunotherapy were reviewed. Endpoints were PP and HP in UC and RCC.
RESULTS
Tumors respond differently to immunotherapy compared to systemic chemotherapy. To evaluate response to immunotherapy, new guidelines (iRECIST) have been developed. To date, no studies focused on PP in UC and RCC, and the only way to evaluate its role is to take patients who respond to treatment beyond progression as surrogate for pseudoprogressors. PP seems to occur in a non-negligible rate of UC and RCC (from 1.5 to 17% and from 5 to 15%, respectively). The concept of HP, defined as a rapid progression after treatment, just took the first steps, and therefore, data from ongoing trials are awaited to elucidate its impact in genitourinary cancers.
CONCLUSIONS
PP and HP are not uncommon entities in UC and RCC patients, treated with PD-1/PD-L1 inhibitors. Further investigation is warranted to define which patients are likely to experience PP and could benefit from treatment beyond progression and which ones will instead rapidly experience progression despite treatment and should, therefore, avoid systemic immunotherapy.
Topics: Antibodies, Monoclonal; Carcinoma, Renal Cell; Carcinoma, Transitional Cell; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Disease Progression; Disease-Free Survival; Female; Humans; Immunotherapy; Kidney Neoplasms; Male; Prognosis; Randomized Controlled Trials as Topic; Risk Assessment; Survival Rate; Treatment Outcome
PubMed: 29549485
DOI: 10.1007/s00345-018-2264-0 -
Radiology Oct 2020BackgroundImmune checkpoint inhibitors (ICIs) have been increasingly used in cancer treatment, and a subset of patients undergo pseudoprogression. Recognizing the... (Meta-Analysis)
Meta-Analysis
BackgroundImmune checkpoint inhibitors (ICIs) have been increasingly used in cancer treatment, and a subset of patients undergo pseudoprogression. Recognizing the incidence of pseudoprogression is critical for clinical practice.PurposeTo evaluate by systematic review and meta-analysis the incidence of pseudoprogression in cancer treatment with ICIs, and compare the incidence according to response criteria, tumor types, and immunotherapeutic agents.Materials and MethodsMedline and Embase were searched to identify relevant studies published before December 31, 2018. Clinical trials, post hoc analysis of clinical trials, and prospective studies on ICI treatment in patients with malignant solid tumors were included. Pooled incidence of pseudoprogression for all included studies, per definition of pseudoprogression, cancer type, and drug type, was obtained by random-effects models with inverse variance weighting model.ResultsSeventeen studies with 3402 patients were analyzed. The pooled incidence of pseudoprogression was 6.0% (95% confidence interval: 5.0%, 7.0%). The definition of pseudoprogression were divided into four categories: progressive disease followed by partial response (PR) or complete response (CR) but not stable disease (SD) with Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 (six studies); progressive disease followed by SD or PR or CR with RECIST 1.1 (five studies); progressive disease followed by SD or PR or CR with RECIST 1.0 (three studies); and progressive disease followed by SD or PR or CR with immune-related response criteria (irRC) (three studies). Incidence of pseudoprogression varied from 4.5% to 8.0% per definition, ranged from 5.0% to 7.0% per cancer type, and was 5.6% with the monotherapy of programmed cell death-1 inhibitor.ConclusionThe overall incidence of pseudoprogression was 6.0% and was less than 10% in subgroup analyses according to the definitions of pseudoprogression, cancer type, and immune checkpoint inhibitor type. Varying definitions across trials and studies indicates the need for uniform criteria of pseudoprogression for solid tumors.© RSNA, 2020See also the article by Dodd and MacDermott in this issue.
Topics: Disease Progression; Humans; Immune Checkpoint Inhibitors; Neoplasms; Response Evaluation Criteria in Solid Tumors
PubMed: 32749204
DOI: 10.1148/radiol.2020200443 -
Quantitative Imaging in Medicine and... Oct 2022Tumor recurrence and pseudoprogression (PsP) have similar imaging manifestations in conventional magnetic resonance imaging (MRI), although the subsequent treatments are...
BACKGROUND
Tumor recurrence and pseudoprogression (PsP) have similar imaging manifestations in conventional magnetic resonance imaging (MRI), although the subsequent treatments are completely different. This study aimed to evaluate the value of perfusion-weighted imaging (PWI) in differentiating PsP from glioma recurrence.
METHODS
A comprehensive literature search was performed to evaluate clinical studies focused on differentiating recurrent glioma from PsP using PWI, including dynamic susceptibility contrast MRI (DSC-MRI), dynamic contrast enhanced MRI (DCE-MRI), and arterial spin labeling (ASL). Study selection and data extraction were independently completed by two reviewers. The Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool was applied to evaluate the quality of the included studies. The software Stata 16.0 and Meta-Disc 1.4 were used for the meta-analysis. Meta-regression and subgroup analyses were applied to identify the sources of heterogeneity in the studies. This study was registered in the International Prospective Register of Systematic Reviews (PROSPERO) prior to initiation (CRD42022304404).
RESULTS
A total of 40 studies were included, including 27 English studies and 13 Chinese studies. There were 1,341 patients with glioma recurrence and 876 patients with PsP. The pooled sensitivity and specificity of DSC-MRI for differentiating glioma recurrence from PsP were 0.82 [95% confidence interval (CI): 0.78 to 0.86] and 0.87 (95% CI: 0.80 to 0.92), respectively. The pooled sensitivity and specificity of DCE-MRI were 0.83 (95% CI: 0.76 to 0.89) and 0.83 (95% CI: 0.78 to 0.87), respectively. The pooled sensitivity and specificity of ASL were 0.80 (95% CI: 0.73 to 0.86) and 0.86 (95% CI: 0.76 to 0.92), respectively.
DISCUSSION
The DSC-MRI, DCE-MRI, and ASL perfusion techniques displayed high accuracy in distinguishing glioma recurrence from PsP, and DSC-MRI had a higher diagnostic performance than the other two techniques. However, due to the diversity of the parameters and threshold differences, further investigation and standardization are needed.
PubMed: 36185045
DOI: 10.21037/qims-22-32 -
Quantitative Imaging in Medicine and... Aug 2023Positron emission tomography (PET) imaging is a promising molecular neuroimaging technique and has been proposed as one of the criteria for glioma management. However,...
BACKGROUND
Positron emission tomography (PET) imaging is a promising molecular neuroimaging technique and has been proposed as one of the criteria for glioma management. However, there is some controversy concerning the diagnostic accuracy of PET using different radiotracers to differentiate between glioma pseudoprogression (PsP) and true progression (TPR). The purpose of this meta-analysis was to systematically evaluate the methodological quality and clinical value of original studies for distinguishing PsP from TPR in glioma.
METHODS
The Medline, Web of Science, Embase, Cochrane Library, and ClinicalTrials.gov were searched from inception until September 1, 2022. Retrieved clinical studies only investigated the PsP cases but did not include the cases of radiation necrosis or other treatment-related changes. Eligible studies were screened for data extraction and evaluated by 2 independent reviewers using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool. A random effects model was used to describe summary receiver operating characteristics. Meta-regression and subgroup analyses were applied to identify any sources of heterogeneity.
RESULTS
The meta-analysis included 20 studies, comprising 317 (30.9%) patients with PsP and 708 (69.1%) with TPR. The summary sensitivity and specificity of general PET for identifying PsP were 0.86 [95% confidence interval (CI): 0.77-0.91] and 0.84 (95% CI: 0.79-0.88), respectively. The statistical heterogeneity was explained by sample size, study design, World Health Organization (WHO) grade, gold standard, and radiotracer type. The summary sensitivity and specificity of O-(2-F-fluoroethyl)-L-tyrosine (F-FET PET) were 0.80 (95% CI: 0.68-0.88) and 0.81 (95% CI: 0.75-0.85), respectively. The maximum tumor-to-brain ratio (TBRmax) and the mean tumor-to-brain ratio (TBRmean) both showed excellent diagnostic performance in F-FET studies, the summary sensitivity was 0.83 (95% CI: 0.72-0.91) and 0.79 (95% CI: 0.65-0.98), respectively, and the specificity was 0.76 (95% CI: 0.68-0.84) and 0.78 (95% CI: 0.64-0.88), respectively.
CONCLUSIONS
PET imaging is generally accurate in identifying glioma PsP. Considering the credibility of meta-evidence and the practicability of using radiotracer, F-FET PET holds the highest clinical value, while TBRmax and TBRmean should be regarded as reliable parameters. PET used with the radiotracers and multiple-parameter combinations of PET with magnetic resonance imaging (MRI) and radiomics analysis have broad research and application prospects, whose diagnostic values for identifying glioma PsP warrant further investigation.
PubMed: 37581048
DOI: 10.21037/qims-22-1340 -
Radiotherapy and Oncology : Journal of... Jan 2020Pseudoprogression (PsP) following radiation therapy (RT) for low grade glioma (LGG, WHO grade I and II), including both photon-based intensity-modulated RT (IMRT) and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Pseudoprogression (PsP) following radiation therapy (RT) for low grade glioma (LGG, WHO grade I and II), including both photon-based intensity-modulated RT (IMRT) and proton beam therapy (PBT), has been described. However, its incidence has yet to be consolidated. The aim of this systematic review and meta-analysis was to pool the current literature and establish the incidence of PsP in these groups to better inform surveillance protocols in the future.
METHODS
Searches of 4 electronic databases from inception to April 2019 were conducted following PRISMA guidelines. Articles were screened against pre-specified criteria. The incidence of outcomes was then extracted and pooled by random-effects meta-analysis of proportions.
RESULTS
A total of 5 pediatric and 4 adult cohort studies describing 517 and 424 LGG subjects respectively satisfied all selection criteria. The estimated incidences of PsP in pediatric subjects following IMRT and PBT were 33% (95% CI, 20-47%) and 34% (95% CI, 23-45%) respectively, with no difference between modalities. The estimated incidences of PsP in adult subjects following IMRT and PBT were 18% (95% CI, 12-25%) and 30% (95% CI, 21-39%) respectively, with PsP significantly less common following IMRT than PBT (P-heterogeneity = 0.04). Median time from radiation initiation to first detection of PsP ranged from 6 to 12 months across all modalities and age groups.
CONCLUSIONS
The incidence of PsP following both IMRT and PBT in the management of pediatric and adult LGG is not negligible, and should therefore be recognized as a pertinent sequala within the first year at least following treatment. However, a lack of accountability in the current literature for the differences in PsP interpretation, radiation modality, radiobiology and molecular biology of LGGs precludes any firm surveillance recommendations at this time.
Topics: Adult; Brain Neoplasms; Child; Disease Progression; Glioma; Humans; Proton Therapy; Radiotherapy, Intensity-Modulated
PubMed: 31431375
DOI: 10.1016/j.radonc.2019.07.013 -
Frontiers in Oncology 2022Several studies have confirmed the impact of 5-aminolevulinic acid (5-ALA) on the extent of resection in newly diagnosed glioblastoma (GBM). However, there are...
BACKGROUND
Several studies have confirmed the impact of 5-aminolevulinic acid (5-ALA) on the extent of resection in newly diagnosed glioblastoma (GBM). However, there are controversies on the 5-ALA fluorescence status in recurrent GBM surgery, with specific reference to pseudoprogression or radionecrosis; therefore, the safety and accuracy of surgical planning in 5-ALA-assisted procedures in the recurrent context are still unclear.
MATERIALS AND METHODS
This is a systematic review and meta-analysis of comparative studies on the use of 5-ALA in newly diagnosed and recurrent GBM, consistently conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Data on fluorescence status and correlation between fluorescence and histological findings were collected. We performed a meta-analysis of proportions to estimate the pooled rates of each outcome.
RESULTS
Three online medical databases (PubMed, Scopus, Cochrane Library) were screened, 448 articles were evaluated, and 3 papers were finally included for data analysis. Fluorescence rate was not different between newly diagnosed and recurrent GBM [p = 0.45; odds ratio (OR): 1.23; 95% CI: 0.72-2.09; I = 0%], while the rate of 5-ALA fluorescence-positive areas not associated with histological findings of GBM cells was higher in recurrent GBM (p = 0.04; OR: 0.24; 95% CI: 0.06-0.91; I = 19%). Furthermore, there were no cases of radionecrosis in false-positive samples, while inflammation and signs of pseudoprogression were found in 81.4% of the cases.
DISCUSSION AND CONCLUSIONS
Therefore, a robust awareness of 5-ALA potentialities and pitfalls in recurrent GBM surgery should be considered for a cognizant surgical strategy. Further clinical trials could confirm the results of the present meta-analysis.
PubMed: 35252015
DOI: 10.3389/fonc.2022.848036