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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 -
Journal of Neurosurgery Aug 2017
Topics: Disease Progression; Humans; Neuroma, Acoustic; Radiosurgery
PubMed: 27885955
DOI: 10.3171/2016.7.JNS161236 -
World Journal of Clinical Oncology May 2021In 2017, immune response evaluation criteria in solid tumors (iRECIST) were introduced to validate radiologic and clinical interpretations and to better analyze tumor's... (Review)
Review
In 2017, immune response evaluation criteria in solid tumors (iRECIST) were introduced to validate radiologic and clinical interpretations and to better analyze tumor's response to immunotherapy, considering the different time of following and response, between this new therapy compared to the standard one. However, even if the iRECIST are worldwide accepted, to date, different aspects should be better underlined and well reported, especially in clinical practice. Clinical experience has demonstrated that in a non-negligible percentage of patients, it is challenging to determine the correct category of response (stable disease, progression disease, partial or complete response), and consequently, to define which is the best management for those patients. Approaching radiological response in patients who underwent immunotherapy, a new uncommon kind of target lesions behavior was found. This phenomenon is mainly due to the different mechanisms of action of immunotherapeutic drug. Therefore, new groups of response have been described in clinical practice, defined as "atypical responses," and categorized into three new groups: pseudoprogression, hyperprogression, and dissociated response. This review summarizes and reports these patterns, helping clinicians and radiologists get used to atypical responses, in order to identify patients that respond best to treatment.
PubMed: 34131564
DOI: 10.5306/wjco.v12.i5.323 -
Frontiers in Immunology 2022Gliomas are tumors derived from mutations in glial brain cells. Gliomas cause significant morbidity and mortality and development of precision diagnostics and novel... (Review)
Review
Gliomas are tumors derived from mutations in glial brain cells. Gliomas cause significant morbidity and mortality and development of precision diagnostics and novel targeted immunotherapies are critically important. Radiographic imaging is the most common technique to diagnose and track response to treatment, but is an imperfect tool. Imaging does not provide molecular information, which is becoming critically important for identifying targeted immunotherapies and monitoring tumor evolution. Furthermore, immunotherapy induced inflammation can masquerade as tumor progression in images (pseudoprogression) and confound clinical decision making. More recently, circulating cell free tumor DNA (cf-tDNA) has been investigated as a promising biomarker for minimally invasive glioma diagnosis and disease monitoring. cf-tDNA is shed by gliomas into surrounding biofluids (e.g. cerebrospinal fluid and plasma) and, if precisely quantified, might provide a quantitative measure of tumor burden to help resolve pseudoprogression. cf-tDNA can also identify tumor genetic mutations to help guide targeted therapies. However, due to low concentrations of cf-tDNA, recovery and analysis remains challenging. Plasma cf-tDNA typically represents <1% of total cf-DNA due to the blood-brain barrier, limiting their usefulness in practice and motivating the development and use of highly sensitive and specific detection methods. This mini review summarizes the current and future trends of various approaches for cf-tDNA detection and analysis, including new methods that promise more rapid, lower-cost, and accessible diagnostics. We also review the most recent clinical case studies for longitudinal disease monitoring and highlight focus areas, such as novel accurate detection methodologies, as critical research priorities to enable translation to clinic.
Topics: Biomarkers, Tumor; Brain; Brain Neoplasms; Circulating Tumor DNA; Glioma; Humans; Immunotherapy; Liquid Biopsy
PubMed: 35464472
DOI: 10.3389/fimmu.2022.882452 -
Clinical Radiology Aug 2022To assess the local diagnostic accuracy and interobserver agreement of dynamic susceptibility contrast-enhanced magnetic resonance perfusion (DSC MRP) reporting in...
Assessing the diagnostic accuracy and interobserver agreement of MRI perfusion in differentiating disease progression and pseudoprogression following treatment for glioblastoma in a tertiary UK centre.
AIM
To assess the local diagnostic accuracy and interobserver agreement of dynamic susceptibility contrast-enhanced magnetic resonance perfusion (DSC MRP) reporting in differentiating between disease progression and pseudoprogression (PP) at a tertiary UK centre.
MATERIALS AND METHODS
This retrospective study included adults with histology-proven glioblastoma who underwent an index DSC MRP examination following treatment. Each index examination was evaluated by three reporters independently, including qualitative assessment and measurement of mean regional cerebral blood volume (rCBV) ratios. Consensus opinion was used as the reference standard and considered clinical, radiological and histological follow-up information. Examination reports were compared to each other and to the consensus opinion.
RESULTS
Thirty-two cases were included (19 progression, 13 pseudoprogression). Interobserver agreement was fair for qualitative opinion (κ=0.58, 95% confidence interval [CI] 0.40-0.76) and good for rCBV ratio measurement (intraclass correlation coefficient [ICC, two-way random effects model] 0.63, 95% CI=0.43-0.78). Qualitative opinion showed diagnostic accuracies of 77.1% (95% CI=67.4-85.1) for progression and 75% (95% CI=65.1-83.3) for pseudoprogression. rCBV ratios were higher for progression (6.85 ± 3.98) than pseudoprogression (3.71 ± 3.40); a 3.0 threshold value maximised the sum of sensitivity (91.1%) and specificity (69.7%) on receiver operating characteristic analysis.
CONCLUSIONS
DSC MRP and rCBV ratio measurement aid differentiation between progression and pseudoprogression following treatment for glioblastoma. Measurement of the rCBV ratio shows good interobserver agreement and can change opinion and improve confidence in DSC MRP reporting. Individual centres should validate their own threshold rCBV ratio values to optimise diagnostic accuracy.
Topics: Adult; Brain Neoplasms; Disease Progression; Glioblastoma; Humans; Magnetic Resonance Imaging; Observer Variation; Perfusion; Retrospective Studies; United Kingdom
PubMed: 35636976
DOI: 10.1016/j.crad.2022.04.011 -
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 -
Scientific Reports Apr 2022Our aim is to define the capabilities of radiomics and machine learning in predicting pseudoprogression development from pre-treatment MR images in a patient cohort...
Our aim is to define the capabilities of radiomics and machine learning in predicting pseudoprogression development from pre-treatment MR images in a patient cohort diagnosed with high grade gliomas. In this retrospective analysis, we analysed 131 patients with high grade gliomas. Segmentation of the contrast enhancing parts of the tumor before administration of radio-chemotherapy was semi-automatically performed using the 3D Slicer open-source software platform (version 4.10) on T1 post contrast MR images. Imaging data was split into training data, test data and an independent validation sample at random. We extracted a total of 107 radiomic features by hand-delineated regions of interest (ROI). Feature selection and model construction were performed using Generalized Boosted Regression Models (GBM). 131 patients were included, of which 64 patients had a histopathologically proven progressive disease and 67 were diagnosed with mixed or pure pseudoprogression after initial treatment. Our Radiomics approach is able to predict the occurrence of pseudoprogression with an AUC, mean sensitivity, mean specificity and mean accuracy of 91.49% [86.27%, 95.89%], 79.92% [73.08%, 87.55%], 88.61% [85.19%, 94.44%] and 84.35% [80.19%, 90.57%] in the full development group, 78.51% [75.27%, 82.46%], 66.26% [57.95%, 73.02%], 78.31% [70.48%, 84.19%] and 72.40% [68.06%, 76.85%] in the testing group and finally 72.87% [70.18%, 76.28%], 71.75% [62.29%, 75.00%], 80.00% [69.23%, 84.62%] and 76.04% [69.90%, 80.00%] in the independent validation sample, respectively. Our results indicate that radiomics is a promising tool to predict pseudo-progression, thus potentially allowing to reduce the use of biopsies and invasive histopathology.
Topics: Glioma; Humans; Machine Learning; Magnetic Resonance Imaging; Retrospective Studies
PubMed: 35396525
DOI: 10.1038/s41598-022-09945-9 -
Journal of Neuroimaging : Official... Mar 2020Neuroimaging plays a critical role in the management of patients with gliomas. While conventional magnetic resonance imaging (MRI) remains the standard imaging modality,... (Review)
Review
Neuroimaging plays a critical role in the management of patients with gliomas. While conventional magnetic resonance imaging (MRI) remains the standard imaging modality, it is frequently insufficient to inform clinical decision-making. There is a need for noninvasive strategies for reliably distinguishing low-grade from high-grade gliomas, identifying important molecular features of glioma, choosing an appropriate target for biopsy, delineating target area for surgery or radiosurgery, and distinguishing tumor progression (TP) from pseudoprogression (PsP). One recent advance is the identification of the T2/fluid-attenuated inversion recovery mismatch sign on standard MRI to identify isocitrate dehydrogenase mutant astrocytomas. However, to meet other challenges, neuro-oncologists are increasingly turning to advanced imaging modalities. Diffusion-weighted imaging modalities including diffusion tensor imaging and diffusion kurtosis imaging can be helpful in delineating tumor margins and better visualization of tissue architecture. Perfusion imaging including dynamic contrast-enhanced MRI using gadolinium or ferumoxytol contrast agents can be helpful for grading as well as distinguishing TP from PsP. Positron emission tomography is useful for measuring tumor metabolism, which correlates with grade and can distinguish TP/PsP in the right setting. Magnetic resonance spectroscopy can identify tissue by its chemical composition, can distinguish TP/PsP, and can identify molecular features like 2-hydroxyglutarate. Finally, amide proton transfer imaging measures intracellular protein content, which can be used to identify tumor grade/progression and distinguish TP/PsP.
Topics: Brain Neoplasms; Disease Management; Glioma; Humans; Neoplasm Grading; Neuroimaging
PubMed: 31925884
DOI: 10.1111/jon.12687 -
Neuro-oncology Practice Jun 2017Management of glioblastoma is complicated by pseudoprogression, a radiological phenomenon mimicking progression. This retrospective cohort study investigated the...
BACKGROUND
Management of glioblastoma is complicated by pseudoprogression, a radiological phenomenon mimicking progression. This retrospective cohort study investigated the incidence, prognostic implications, and most clinically appropriate definition of pseudoprogression.
METHODS
Consecutive glioblastoma patients treated at the Juravinski Hospital and Cancer Centre, Hamilton, Ontario between 2004 and 2012 with temozolomide chemoradiotherapy and with contrast-enhanced MRI at standard imaging intervals were included. At each imaging interval, patient responses as per the RECIST (Response Evaluation Criteria in Solid Tumors), MacDonald, and RANO (Response Assessment in Neuro-Oncology) criteria were reported. Based on each set of criteria, subjects were classified as having disease response, stable disease, pseudoprogression, or true progression. The primary outcome was overall survival.
RESULTS
The incidence of pseudoprogression among 130 glioblastoma patients treated with chemoradiotherapy was 15%, 19%, and 23% as defined by RANO, MacDonald, and RECIST criteria, respectively. Using the RANO definition, median survival for patients with pseudoprogression was 13.0 months compared with 12.5 months for patients with stable disease (hazard ratio [HR]=0.70; 95% confidence interval [CI], 0.35-1.42). Similarly, using the MacDonald definition, median survival for the pseudoprogression group was 11.8 months compared with 12.0 months for the stable disease group (HR=0.86; 95% CI, 0.47-1.58). Furthermore, disease response compared with stable disease was also similar using the RANO (HR=0.52; 95% CI, 0.20-1.35) and MacDonald (HR=0.51: 95% CI, 0.20-1.31) definitions.
CONCLUSIONS
Of all conventional glioblastoma response criteria, the RANO criteria gave the lowest incidence of pseudoprogression. Regardless of criteria, patients with pseudoprogression did not have statistically significant difference in survival compared with patients with stable disease.
PubMed: 31386017
DOI: 10.1093/nop/npw021 -
Nederlands Tijdschrift Voor Geneeskunde Jul 2019Immune therapy is increasingly used as an effective treatment for various types of cancer. The response of tumours to immune therapy is different from conventional...
Immune therapy is increasingly used as an effective treatment for various types of cancer. The response of tumours to immune therapy is different from conventional chemotherapy. In about 10% of patients, pseudoprogression may occur. This is a phenomenon where disease progression initially appears on imaging due to inflammation, but response is seen with repeated imaging. Pseudoprogression is often accompanied by a good clinical status. We describe a 63-year-old woman with metastasized melanoma, a 53-year-old woman with metastasized lung cancer and a 77-year-old woman with metastasized renal cancer who all developed pseudoprogression upon treatment with immune therapy. Premature discontinuation of treatment should be prevented when suspecting pseudoprogression and care should be taken to avoid burdening patients with bad news. Imaging should be repeated after a minimum interval of four weeks if pseudoprogression is suspected. When in doubt, a biopsy may be performed.
Topics: Aged; Brain Neoplasms; Disease Progression; Female; Humans; Immunotherapy; Lung Neoplasms; Melanoma; Middle Aged; Treatment Outcome
PubMed: 31283128
DOI: No ID Found