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Journal of Neuro-oncology Nov 2017This study aimed to assess the incidence and management of pseudoprogression after radiation therapy (RT) in patients with pediatric low-grade glioma (LGG). This...
This study aimed to assess the incidence and management of pseudoprogression after radiation therapy (RT) in patients with pediatric low-grade glioma (LGG). This retrospective review included patients aged 21 years or younger with intracranial LGG treated with curative-intent RT. Pseudoprogression was defined as an increase in tumor size by ≥10% in at least two dimensions between two and three consecutive MR imaging studies. Overall survival (OS) and event-free survival (EFS) were measured from the first day of RT. EFS was defined as survival without true progression or secondary high-grade glioma. Sixty-two of 221 patients developed pseudoprogression, with a 10-year cumulative incidence of 29.0% (95% CI 23.0-35.2). Median time to pseudoprogression was 6.1 months after RT. Symptomatic pseudoprogression was managed with subtotal resection, shunt/Ommaya reservoir placement, or corticosteroids in 11 (18%), 7 (11%), and 2 patients (3%), respectively. The remaining tumors were observed (68%). Patients with pilocytic astrocytoma (PA) had 5.4-fold greater odds of developing pseudoprogression relative to tumors of other histology (odds ratio 95% CI 2.5-11.4, P < 0.0001). Among patients with PA (n = 127), the 10-year cumulative incidence of pseudoprogression was 42.9%. In this group, pseudoprogression was associated with improved 10-year EFS (84.5% vs. 58.5%, P = 0.008) and OS (98.0% vs. 91.2%, P = 0.03). Pseudoprogression after irradiation was common, especially in patients with pilocytic astrocytoma, and was associated with improved survival. Knowledge of the incidence and temporal course of pseudoprogression may help avoid unnecessary salvage therapy.
Topics: Adolescent; Brain; Brain Neoplasms; Child; Child, Preschool; Disease Management; Disease Progression; Female; Glioma; Humans; Incidence; Infant; Magnetic Resonance Imaging; Male; Neoplasm Grading; Retrospective Studies; Survival Analysis; Time Factors; Tumor Burden; Young Adult
PubMed: 28752498
DOI: 10.1007/s11060-017-2583-9 -
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 -
Translational Cancer Research Dec 2019
PubMed: 35117135
DOI: 10.21037/tcr.2019.11.16 -
Critical Reviews in Oncology/hematology Dec 2017Manipulating an individual's immune system through immune checkpoint blockade is revolutionizing the paradigms of cancer treatment. Peculiar patterns and kinetics of... (Review)
Review
Manipulating an individual's immune system through immune checkpoint blockade is revolutionizing the paradigms of cancer treatment. Peculiar patterns and kinetics of response have been observed with these new drugs, rendering the assessment of tumor burden particularly challenging in cancer immunotherapy. The mechanisms of action for immune checkpoint blockade, based upon engagement of the adaptive immune system, can generate unusual response patterns, including pseudoprogression, hyperprogression, atypical and delayed responses. In patients treated with immune checkpoint blockade and radiotherapy, a reduction in tumor burden at metastatic sites distant from the irradiation field (abscopal effect) has been observed, with synergistic systemic immune effects provoked by this combination. New toxicities have also been observed, due to excessive immune activity in several organs, including lung, colon, liver and endocrine glands. Efforts to standardize assessment of cancer immunotherapy responses include novel consensus guidelines derived by modifying World Health Organization (WHO) and Response Evaluation Criteria In Solid Tumors (RECIST) criteria. The aim of this review is to evaluate imaging techniques currently used routinely in the clinic and those being used as investigational tools in immunotherapy clinical trials.
Topics: Humans; Immunotherapy; Neoplasms
PubMed: 29198327
DOI: 10.1016/j.critrevonc.2017.09.017 -
Advanced Biosystems Dec 2020Liquid biopsy for the detection and monitoring of central nervous system tumors is of significant clinical interest. At initial diagnosis, the majority of patients with... (Review)
Review
Liquid biopsy for the detection and monitoring of central nervous system tumors is of significant clinical interest. At initial diagnosis, the majority of patients with central nervous system tumors undergo magnetic resonance imaging (MRI), followed by invasive brain biopsy to determine the molecular diagnosis of the WHO 2016 classification paradigm. Despite the importance of MRI for long-term treatment monitoring, in the majority of patients who receive chemoradiation therapy for glioblastoma, it can be challenging to distinguish between radiation treatment effects including pseudoprogression, radiation necrosis, and recurrent/progressive disease based on imaging alone. Tissue biopsy-based monitoring is high risk and not always feasible. However, distinguishing these entities is of critical importance for the management of patients and can significantly affect survival. Liquid biopsy strategies including circulating tumor cells, circulating free DNA, and extracellular vesicles have the potential to afford significant useful molecular information at both the stage of diagnosis and monitoring for these tumors. Here, current liquid biopsy-based approaches in the context of tumor monitoring to differentiate progressive disease from pseudoprogression and radiation necrosis are reviewed.
Topics: Biomarkers, Tumor; Brain; Brain Neoplasms; Circulating Tumor DNA; Disease Progression; Extracellular Vesicles; Glioblastoma; Humans; Liquid Biopsy; Necrosis; Neoplastic Cells, Circulating; Radiation Injuries; Radiotherapy
PubMed: 32484293
DOI: 10.1002/adbi.202000029 -
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 -
Liver Cancer Jun 2023
PubMed: 37325496
DOI: 10.1159/000527250 -
Current Treatment Options in Neurology Mar 2017With advances in treatments and survival of patients with glioblastoma (GBM), it has become apparent that conventional imaging sequences have significant limitations... (Review)
Review
With advances in treatments and survival of patients with glioblastoma (GBM), it has become apparent that conventional imaging sequences have significant limitations both in terms of assessing response to treatment and monitoring disease progression. Both 'pseudoprogression' after chemoradiation for newly diagnosed GBM and 'pseudoresponse' after anti-angiogenesis treatment for relapsed GBM are well-recognised radiological entities. This in turn has led to revision of response criteria away from the standard MacDonald criteria, which depend on the two-dimensional measurement of contrast-enhancing tumour, and which have been the primary measure of radiological response for over three decades. A working party of experts published RANO (Response Assessment in Neuro-oncology Working Group) criteria in 2010 which take into account signal change on T2/FLAIR sequences as well as the contrast-enhancing component of the tumour. These have recently been modified for immune therapies, which are associated with specific issues related to the timing of radiological response. There has been increasing interest in quantification and validation of physiological and metabolic parameters in GBM over the last 10 years utilising the wide range of advanced imaging techniques available on standard MRI platforms. Previously, MRI would provide structural information only on the anatomical location of the tumour and the presence or absence of a disrupted blood-brain barrier. Advanced MRI sequences include proton magnetic resonance spectroscopy (MRS), vascular imaging (perfusion/permeability) and diffusion imaging (diffusion weighted imaging/diffusion tensor imaging) and are now routinely available. They provide biologically relevant functional, haemodynamic, cellular, metabolic and cytoarchitectural information and are being evaluated in clinical trials to determine whether they offer superior biomarkers of early treatment response than conventional imaging, when correlated with hard survival endpoints. Multiparametric imaging, incorporating different combinations of these modalities, improves accuracy over single imaging modalities but has not been widely adopted due to the amount of post-processing analysis required, lack of clinical trial data, lack of radiology training and wide variations in threshold values. New techniques including diffusion kurtosis and radiomics will offer a higher level of quantification but will require validation in clinical trial settings. Given all these considerations, it is clear that there is an urgent need to incorporate advanced techniques into clinical trial design to avoid the problems of under or over assessment of treatment response.
PubMed: 28349351
DOI: 10.1007/s11940-017-0445-6 -
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 Personalized Medicine Mar 2021Immunotherapy is a promising therapeutic strategy both for solid and hematologic tumors, such as in Hodgkin (HL) and non-Hodgkin lymphoma (NHL). In particular,... (Review)
Review
Immunotherapy is a promising therapeutic strategy both for solid and hematologic tumors, such as in Hodgkin (HL) and non-Hodgkin lymphoma (NHL). In particular, immune-checkpoint inhibitors, such as nivolumab and pembrolizumab, are increasingly used for the treatment of refractory/relapsed HL. At the same time, evidence of chimeric antigen receptor (CAR)-T-cell immunotherapy efficacy mostly in NHL is growing. In this setting, the challenge is to identify an appropriate imaging method to evaluate immunotherapy response. The role of 18F-Fluorodeoxyglucose (18F-FDG) positron-emission tomography/computed tomography (PET/CT), especially in early evaluation, is under investigation in order to guide therapeutic strategies, taking into account the possible atypical responses (hyperprogression and pseudoprogression) and immune-related adverse events that could appear on PET images. Herein, we aimed to present a critical overview about the role of 18F-FDG PET/CT in evaluating treatment response to immunotherapy in lymphoma patients.
PubMed: 33803667
DOI: 10.3390/jpm11030217