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World Neurosurgery Dec 2020On brain magnetic resonance imaging, both diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI) are used to evaluate cerebral tumors. The purpose of this... (Meta-Analysis)
Meta-Analysis
Differentiation Between True Tumor Progression of Glioblastoma and Pseudoprogression Using Diffusion-Weighted Imaging and Perfusion-Weighted Imaging: Systematic Review and Meta-analysis.
BACKGROUND
On brain magnetic resonance imaging, both diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI) are used to evaluate cerebral tumors. The purpose of this meta-analysis was to evaluate and compare the diagnostic performance of DWI and PWI in differentiating between pseudoprogression and true tumor progression of glioblastoma.
METHODS
We performed a systematic review of the PubMed database from January 2000 to December 2019 for relevant studies. After application of specific inclusion and exclusion criteria, the eligible articles were evaluated for methodologic quality and risk of bias using the updated Quality Assessment of Diagnostic Accuracy (QUADAS-2) tool. From the published study results, the pooled sensitivity, pooled specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio and their corresponding confidence intervals (% CI), and the area under the curve, were calculated individually for DWI and PWI.
RESULTS
The meta-analysis included 24 studies, with a total of 900 patients. DWI was found to be slightly superior in terms of sensitivity and specificity, 0.88 (% CI 0.83-0.92) and 0.85 (% CI 0.78-0.91), respectively, compared with the respective values of PWI, 0.85 (% CI 0.81-0.89) and 0.79 (% CI 0.74-0.84). On comparison of the overall diagnostic accuracy of the MRI modalities using their respective area under the curve values (0.9156 for DWI, 0.9072 for PWI), no significant difference was demonstrated between the 2.
CONCLUSIONS
Both DWI and PWI provided optimal diagnostic performance in differentiating pseudoprogression from true tumor progression in cerebral glioblastoma, and neither technique proved to be superior.
Topics: Brain Neoplasms; Diagnosis, Differential; Diffusion Magnetic Resonance Imaging; Disease Progression; Glioblastoma; Humans; Perfusion Imaging; Sensitivity and Specificity
PubMed: 32777397
DOI: 10.1016/j.wneu.2020.07.218 -
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 -
European Radiology Experimental Jan 2020A wide range of cancer immunotherapy approaches has been developed including non-specific immune-stimulants such as cytokines, cancer vaccines, immune checkpoint...
A wide range of cancer immunotherapy approaches has been developed including non-specific immune-stimulants such as cytokines, cancer vaccines, immune checkpoint inhibitors (ICIs), and adoptive T cell therapy. Among them, ICIs are the most commonly used and intensively studied. Since 2011, these drugs have received marketing authorisation for melanoma, lung, bladder, renal, and head and neck cancers, with remarkable and long-lasting treatment response in some patients. The novel mechanism of action of ICIs, with immune and T cell activation, leads to unusual patterns of response on imaging, with the advent of so-called pseudoprogression being more pronounced and frequently observed when compared to other anticancer therapies. Pseudoprogression, described in about 2-10% of patients treated with ICIs, corresponds to an increase of tumour burden and/or the appearance of new lesions due to infiltration by activated T cells before the disease responds to therapy. To overcome the limitation of response evaluation criteria in solid tumors (RECIST) to assess these specific changes, new imaging criteria-so-called immune-related response criteria and then immune-related RECIST (irRECIST)-were proposed. The major modification involved the inclusion of the measurements of new target lesions into disease assessments and the need for a 4-week re-assessment to confirm or not confirm progression. The RECIST working group introduced the new concept of "unconfirmed progression", into the irRECIST. This paper reviews current immunotherapeutic approaches and summarises radiologic criteria to evaluate new patterns of response to immunotherapy. Furthermore, imaging features of immunotherapy-related adverse events and available predictive biomarkers of response are presented.
Topics: Diagnostic Imaging; Humans; Immunotherapy; Neoplasms; Response Evaluation Criteria in Solid Tumors
PubMed: 31900689
DOI: 10.1186/s41747-019-0134-1 -
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 -
Molecular Neurobiology Sep 2019High-grade gliomas (HGG) are the most common malignant primary brain tumor in adults. During the course of disease, several challenges occur, like measuring tumor...
High-grade gliomas (HGG) are the most common malignant primary brain tumor in adults. During the course of disease, several challenges occur, like measuring tumor burden, monitoring of treatment response, estimating the patient's prognosis, and distinguishing between true progression and pseudo-progression. So far, no blood-based biomarker has been established in the clinical routine to address these challenges. The aim of this systematic review was to analyze the present evidence on blood-based biomarkers for HGG. We systematically searched in PubMed, Web of Sciences, Scopus, and Cochrane Library databases for publications before 30th of March 2018 reporting on associations of blood-based biomarkers in HGG patients with different endpoints as overall survival, progression-free survival, and postoperative monitoring. Quality assessment of the studies according to QUIPS and STARD guidelines was performed. In accordance with the GRADE guidelines, level of evidence (I-IV) for each of the tested biomarkers was assessed. One thousand six hundred eighty unique records were identified. Of these, 170 original articles were included to this review. Four hundred fifteen different blood-based biomarkers analyzed in 15.041 patients with HGG as also their corresponding recurrent tumors. Ten predictive biomarkers reached level II of evidence. No biomarker achieved level I of evidence. In this review, 10 blood-based biomarkers were selected as most promising biomarkers for HGG: α2-Heremans-Schmid glycoprotein (AHSG), albumin, glucose, insulin-like growth factor- binding protein 2 (IGFBP-2), macrophage inflammatory protein 1δ (MIP-1 δ), macrophage inflammatory protein 3ß (MIP-3ß), neutrophil-lymphocyte ratio (NLR), red blood cell distribution width (RDW), soluble glycoprotein 130 (Sgp130), and chitinase-3-like protein 1 (YKL-40). To further assess the clinical significance of these biomarkers, the evaluation in a larger cohort of HGG and their corresponding subgroups would be necessary.
Topics: Biomarkers, Tumor; Glioma; Humans; Magnetic Resonance Imaging; Neoplasm Grading; Prognosis; Publications
PubMed: 30719642
DOI: 10.1007/s12035-019-1509-2 -
Radiology and Oncology Oct 2018Background Uncommon response during immunotherapy is a new challenging issue in oncology practice. Recently, new criteria for evaluation of response to immunotherapy...
Background Uncommon response during immunotherapy is a new challenging issue in oncology practice. Recently, new criteria for evaluation of response to immunotherapy immune response evaluation criteria in solid tumors (iRECIST) were accepted. According to iRECIST, worsening of performance status (PS) accompanied to pseudoprogression reflects most probably the true progression of the malignant disease. Methods A systematic review of the literature was made by using several electronic database with the following search criteria: symptomatic pseudoprogression, atypical response, immunotherapy and lung cancer. Results In the literature, we identified five reports of seven patients treated with immunotherapy that met the inclusion criteria. We also report our experience of patient with pseudoprogression and almost complete response after one dose of immunotherapy. Conclusions As seen from our review, iRECIST criteria might be insufficient in distinguishing true progression from pseudoprogression in some patients with advanced NSCLC treated with immunotherapy. More precise assessment methods are urgently needed.
Topics: Carcinoma, Non-Small-Cell Lung; Disease Progression; Humans; Immunologic Factors; Immunotherapy; Lung Neoplasms; Response Evaluation Criteria in Solid Tumors
PubMed: 30367809
DOI: 10.2478/raon-2018-0037 -
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 -
European Radiology Jun 2018To evaluate the value of multiparametric MRI for determination of early treatment response following concurrent chemoradiotherapy in patients with newly diagnosed... (Meta-Analysis)
Meta-Analysis Review
Multiparametric MRI as a potential surrogate endpoint for decision-making in early treatment response following concurrent chemoradiotherapy in patients with newly diagnosed glioblastoma: a systematic review and meta-analysis.
OBJECTIVE
To evaluate the value of multiparametric MRI for determination of early treatment response following concurrent chemoradiotherapy in patients with newly diagnosed glioblastoma.
METHODS
A computerized search of Ovid-MEDLINE and EMBASE up to 1 October 2017 was performed to find studies on the diagnostic performance of multiparametric MRI for differentiating true progression from pseudoprogression. The beginning search date was not specified. Pooled estimates of sensitivity and specificity were obtained using hierarchical logistic regression modeling. We performed meta-regression and sensitivity analyses to explain the effects of the study heterogeneity.
RESULTS
Nine studies including 456 patients were included. Pooled sensitivity and specificity were 84 % (95 % CI 74-91) and 95 % (95 % CI 83-99), respectively. Area under the hierarchical summary receiver operating characteristic curve was 0.95 (95 % CI 0.92-0.96). Meta-regression showed true progression in the study population, the mean age and the reference standard were significant factors affecting heterogeneity.
CONCLUSION
Multiparametric MRI may be used as a potential surrogate endpoint for assessment of early treatment response, especially in the differentiation of true progression from pseudoprogression. However, based on the current evidence, monoparametric and multiparametric MRI perform equally in the clinical context. Further evaluation will be needed.
KEY POINTS
• Multiparametric MRI shows high diagnostic performance for early treatment response in glioblastoma. • Multiparametric MRI could differentiate true progression from pseudoprogression in newly diagnosed glioblastoma. • The normalized rCBV derived from DSC was the most commonly used parameter.
Topics: Adult; Aged; Biomarkers; Brain Neoplasms; Chemoradiotherapy; Clinical Decision-Making; Disease Progression; Female; Glioblastoma; Humans; Magnetic Resonance Imaging; Male; Middle Aged; ROC Curve; Sensitivity and Specificity
PubMed: 29374321
DOI: 10.1007/s00330-017-5262-5 -
Clinical and Translational Imaging 2017Improvement of the therapeutic approaches in gastrointestinal stromal tumors (GIST) by the introduction of targeted therapies requires appropriate diagnostic tools,... (Review)
Review
PURPOSE
Improvement of the therapeutic approaches in gastrointestinal stromal tumors (GIST) by the introduction of targeted therapies requires appropriate diagnostic tools, which allow sufficient assessment of therapeutic response, including differentiation of true progression from pseudoprogression due to myxoid degeneration or intratumoral hemorrhage. In this literature review the impact and limitations of different imaging modalities used in GIST therapy monitoring are discussed.
METHODS
PubMed and Cochrane library search were performed using appropriate keywords. Overall, 39 original papers fulfilled the defined criteria and were included in this systematic review.
RESULTS
Morphological imaging modalities like computed tomography (CT) are primarily used for both diagnosis and therapy monitoring. However, therapy with tyrosine kinase inhibitors and other targeted therapies in GIST may lead only to a minor tumor volume reduction even in cases of response. Therefore, the use of Response Evaluation Criteria in Solid Tumors (RECIST) has limitations. To overcome those limitations, modified response criteria have been introduced for the CT-based therapy assessment, like the Choi criteria as well as criteria based on dual energy CT studies. Functional imaging techniques, mostly based on FDG PET-CT are in use, in particular for the assessment of early treatment response.
CONCLUSIONS
The impact and the limitations of PET-based therapy monitoring, as well as its comparison with CT, MRI and survival data are discussed in this review. CT is still the standard method for the evaluation of therapy response despite its several limitations. FDG PET-CT is helpful for the assessment of early therapy response; however, more prospective data are needed to define its role as well as the appropriate time intervals for therapy monitoring. A multiparametric evaluation based on changes in both morphological and functional data has to be assessed in further prospective studies.
PubMed: 29104864
DOI: 10.1007/s40336-017-0229-8 -
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