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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 -
Frontiers in Oncology 2020Imaging-based monitoring of disease burden in glioma patients is frequently confounded by treatment effects. Circulating biomarkers could theoretically augment...
Imaging-based monitoring of disease burden in glioma patients is frequently confounded by treatment effects. Circulating biomarkers could theoretically augment imaging-based response monitoring. This systematic review aimed to present and evaluate evidence for differential expression and diagnostic accuracy of circulating biomarkers with respect to outcomes of tumor response, progression, stable disease, and treatment effects (pseudoprogression, radionecrosis, pseudoresponse, and pseudolesions) in patients undergoing treatment for World Health Organization grades II-IV diffuse astrocytic and oligodendroglial tumors. MEDLINE, EMBASE, Web Of Science, and SCOPUS databases were searched until August 18, 2019, for observational or diagnostic studies on multiple circulating biomarker types: extracellular vesicles, circulating nucleic acids, circulating tumor cells, circulating proteins, and metabolites, angiogenesis related cells, immune cells, and other cell lines. Methodological quality of included studies was assessed using an adapted Quality Assessment of Diagnostic Accuracy Studies-2 tool, and level of evidence (IA-IVD) for individual biomarkers was evaluated using an adapted framework from the National Comprehensive Cancer Network guidelines on evaluating tumor marker utility. Of 13,202 unique records, 58 studies met the inclusion criteria. One hundred thirty-three distinct biomarkers were identified in a total of 1,853 patients across various treatment modalities. Fifteen markers for response, progression, or stable disease and five markers for pseudoprogression or radionecrosis reached level IB. No biomarkers reached level IA. Only five studies contained data for diagnostic accuracy measures. Overall methodological quality of included studies was low. While extensive data on biomarker dysregulation in varying response categories were reported, no biomarkers ready for clinical application were identified. Further assay refinement and evaluation in larger cohorts with diagnostic accuracy study designs are required. : CRD42018110658.
PubMed: 32923382
DOI: 10.3389/fonc.2020.01191 -
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 -
Neuro-oncology Advances 2022The response assessment in neuro-oncology (RANO) criteria have been the gold standard for monitoring treatment response in glioblastoma (GBM) and differentiating tumor... (Review)
Review
The response assessment in neuro-oncology (RANO) criteria have been the gold standard for monitoring treatment response in glioblastoma (GBM) and differentiating tumor progression from pseudoprogression. While the RANO criteria have played a key role in detecting early tumor progression, their ability to identify pseudoprogression is limited by post-treatment damage to the blood-brain barrier (BBB), which often leads to contrast enhancement on MRI and correlates poorly to tumor status. Amino acid positron emission tomography (AA PET) is a rapidly growing imaging modality in neuro-oncology. While contrast-enhanced MRI relies on leaky vascularity or a compromised BBB for delivery of contrast agents, amino acid tracers can cross the BBB, making AA PET particularly well-suited for monitoring treatment response and diagnosing pseudoprogression. The authors performed a systematic review of PubMed, MEDLINE, and Embase through December 2021 with the search terms "temozolomide" OR "Temodar," "glioma" OR "glioblastoma," "PET," and "amino acid." There were 19 studies meeting inclusion criteria. Thirteen studies utilized [F]FET, five utilized [C]MET, and one utilized both. All studies used static AA PET parameters to evaluate TMZ treatment in glioma patients, with nine using dynamic tracer parameters in addition. Throughout these studies, AA PET demonstrated utility in TMZ treatment monitoring and predicting patient survival.
PubMed: 35300149
DOI: 10.1093/noajnl/vdac008 -
Journal of Medical Imaging and... Sep 2022Chemotherapy and radiotherapy can produce treatment-related effects, which may mimic tumour progression. Advances in Artificial Intelligence (AI) offer the potential to... (Meta-Analysis)
Meta-Analysis Review
Machine learning imaging applications in the differentiation of true tumour progression from treatment-related effects in brain tumours: A systematic review and meta-analysis.
INTRODUCTION
Chemotherapy and radiotherapy can produce treatment-related effects, which may mimic tumour progression. Advances in Artificial Intelligence (AI) offer the potential to provide a more consistent approach of diagnosis with improved accuracy. The aim of this study was to determine the efficacy of machine learning models to differentiate treatment-related effects (TRE), consisting of pseudoprogression (PsP) and radiation necrosis (RN), and true tumour progression (TTP).
METHODS
The systematic review was conducted in accordance with PRISMA-DTA guidelines. Searches were performed on PubMed, Scopus, Embase, Medline (Ovid) and ProQuest databases. Quality was assessed according to the PROBAST and CLAIM criteria. There were 25 original full-text journal articles eligible for inclusion.
RESULTS
For gliomas: PsP versus TTP (16 studies, highest AUC = 0.98), RN versus TTP (4 studies, highest AUC = 0.9988) and TRE versus TTP (3 studies, highest AUC = 0.94). For metastasis: RN vs. TTP (2 studies, highest AUC = 0.81). A meta-analysis was performed on 9 studies in the gliomas PsP versus TTP group using STATA. The meta-analysis reported a high sensitivity of 95.2% (95%CI: 86.6-98.4%) and specificity of 82.4% (95%CI: 67.0-91.6%).
CONCLUSION
TRE can be distinguished from TTP with good performance using machine learning-based imaging models. There remain issues with the quality of articles and the integration of models into clinical practice. Future studies should focus on the external validation of models and utilize standardized criteria such as CLAIM to allow for consistency in reporting.
Topics: Artificial Intelligence; Brain Neoplasms; Diagnostic Imaging; Glioma; Humans; Machine Learning
PubMed: 35599360
DOI: 10.1111/1754-9485.13436 -
Neuro-oncology Jan 2017Distinction between tumor and treatment related changes is crucial for clinical management of patients with high-grade gliomas. Our purpose was to evaluate whether... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Distinction between tumor and treatment related changes is crucial for clinical management of patients with high-grade gliomas. Our purpose was to evaluate whether dynamic susceptibility contrast-enhanced (DSC) and dynamic contrast enhanced (DCE) perfusion-weighted imaging (PWI) metrics can effectively differentiate between recurrent tumor and posttreatment changes within the enhancing signal abnormality on conventional MRI.
METHODS
A comprehensive literature search was performed for studies evaluating PWI-based differentiation of recurrent tumor and posttreatment changes in patients with high-grade gliomas (World Health Organization grades III and IV). Only studies published in the "temozolomide era" beginning in 2005 were included. Summary estimates of diagnostic accuracy were obtained by using a random-effects model.
RESULTS
Of 1581 abstracts screened, 28 articles were included. The pooled sensitivities and specificities of each study's best performing parameter were 90% and 88% (95% CI: 0.85-0.94; 0.83-0.92) and 89% and 85% (95% CI: 0.78-0.96; 0.77-0.91) for DSC and DCE, respectively. The pooled sensitivities and specificities for detecting tumor recurrence using the 2 most commonly evaluated parameters, mean relative cerebral blood volume (rCBV) (threshold range, 0.9-2.15) and maximum rCBV (threshold range, 1.49-3.1), were 88% and 88% (95% CI: 0.81-0.94; 0.78-0.95) and 93% and 76% (95% CI: 0.86-0.98; 0.66-0.85), respectively.
CONCLUSIONS
PWI-derived thresholds separating viable tumor from treatment changes demonstrate relatively good accuracy in individual studies. However, because of significant variability in optimal reported thresholds and other limitations in the existing body of literature, further investigation and standardization is needed before implementing any particular quantitative PWI strategy across institutions.
Topics: Brain Neoplasms; Combined Modality Therapy; Contrast Media; Glioma; Humans; Magnetic Resonance Angiography; Neoplasm Grading; Prognosis
PubMed: 27502247
DOI: 10.1093/neuonc/now148 -
Frontiers in Oncology 2022Amide proton transfer (APT) imaging as an emerging MRI approach has been used for distinguishing tumor recurrence (TR) and treatment effects (TEs) in glioma patients,...
BACKGROUND
Amide proton transfer (APT) imaging as an emerging MRI approach has been used for distinguishing tumor recurrence (TR) and treatment effects (TEs) in glioma patients, but the initial results from recent studies are different.
AIM
The aim of this study is to systematically review and quantify the diagnostic performance of APT in assessing treatment response in patients with post-treatment gliomas.
METHODS
A systematic search in PubMed, EMBASE, and the Web of Science was performed to retrieve related original studies. For the single and added value of APT imaging in distinguishing TR from TEs, we calculated pooled sensitivity and specificity by using Bayesian bivariate meta-analyses.
RESULTS
Six studies were included, five of which reported on single APT imaging parameters and four of which reported on multiparametric MRI combined with APT imaging parameters. For single APT imaging parameters, the pooled sensitivity and specificity were 0.85 (95% CI: 0.75-0.92) and 0.88 (95% CI: 0.74-0.97). For multiparametric MRI including APT, the pooled sensitivity and specificity were 0.92 (95% CI: 0.85-0.97) and 0.83 (95% CI: 0.55-0.97), respectively. In addition, in the three studies reported on both single and added value of APT imaging parameters, the combined imaging parameters further improved diagnostic performance, yielding pooled sensitivity and specificity of 0.91 (95% CI: 0.80-0.97) and 0.92 (95% CI: 0.79-0.98), respectively, but the pooled sensitivity was 0.81 (95% CI: 0.65-0.93) and specificity was 0.82 (95% CI: 0.61-0.94) for single APT imaging parameters.
CONCLUSION
APT imaging showed high diagnostic performance in assessing treatment response in patients with post-treatment gliomas, and the addition of APT imaging to other advanced MRI techniques can improve the diagnostic accuracy for distinguishing TR from TE.
PubMed: 35978813
DOI: 10.3389/fonc.2022.852076 -
Cancers May 2022Pediatric brain tumors are the most common solid tumor in children. Traditionally, tumor diagnosis and molecular analysis were carried out on tumor tissue harvested... (Review)
Review
BACKGROUND
Pediatric brain tumors are the most common solid tumor in children. Traditionally, tumor diagnosis and molecular analysis were carried out on tumor tissue harvested either via biopsy or resection. However, liquid biopsy allows analysis of circulating tumor DNA in corporeal fluids such as cerebrospinal fluid or blood.
METHODS
We performed a systematic review in Pubmed and Embase regarding the role of liquid biopsy in pediatric brain tumors.
RESULTS
Nine studies with a total of 570 patients were included. The preferred corporeal fluid for analysis with a relatively high yield of ct-DNA was cerebrospinal fluid (CSF). For high-grade glioma, liquid biopsy can successfully characterize H3K27mutations and predict tumor progression before it is radiographically detected. Moreover, liquid biopsy has the potential to distinguish between pseudo-progression and actual progression. In medulloblastoma, ct-DNA in the CSF can be used as a surrogate marker of measurable residual disease and correlates with response to therapy and progression of the tumor up to three months before radiographic detection.
CONCLUSION
Liquid biopsy is primarily useful in high-grade pediatric brain tumors such as diffuse midline glioma or medulloblastoma. Disease detection and monitoring is feasible for both tumor entities. More trials to standardize its use for pediatric brain tumors are necessary.
PubMed: 35681663
DOI: 10.3390/cancers14112683 -
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 -
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