Pseudoprogression of brain tumors

Thust, Stefanie; Bent, Martin J. van den; Smits, Marion

doi:10.1002/jmri.26171

Cited by 227 publications

(214 citation statements)

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“…Future work should be aimed at validating cutoff values and standardized quantification of perfusion images allowing identification of the best cutoff for clinical implementation. Moreover, decisions about incorporating perfusion MRI in every follow‐up protocol are to be made . Currently, the imaging follow‐up interval of treated GBM patients remains debatable and it is not known if adding perfusion MRI to every follow‐up scan improves clinical decision‐making.…”

Section: Remaining Questionsmentioning

confidence: 99%

“…This is called pseudoprogression. 3,4 Furthermore, antiangiogenic treatment can result in a decrease of enhancement on postcontrast MRI while the tumor remains stable or even increases. This is called pseudoresponse.…”

Section: Accreditationmentioning

confidence: 99%

“…Moreover, decisions about incorporating perfusion MRI in every follow-up protocol are to be made. 4,54 Currently, the imaging follow-up interval of treated GBM patients remains debatable and it is not known if adding perfusion MRI to every followup scan improves clinical decision-making. Finally, comparing perfusion parameters longitudinally in a patient is not straightforward, as the coregistration of subsequent follow-up scans remains challenging.…”

Section: Standardization Of Parametersmentioning

confidence: 99%

“…However, enhancement can also be due to a treatment‐related blood–brain barrier disruption without underlying tumor progression. This is called pseudoprogression . Furthermore, antiangiogenic treatment can result in a decrease of enhancement on postcontrast MRI while the tumor remains stable or even increases.…”

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confidence: 99%

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Perfusion MRI in treatment evaluation of glioblastomas: Clinical relevance of current and future techniques

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Smits

et al. 2018

Magnetic Resonance Imaging

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Treatment evaluation of patients with glioblastomas is important to aid in clinical decisions. Conventional MRI with contrast is currently the standard method, but unable to differentiate tumor progression from treatment‐related effects. Pseudoprogression appears as new enhancement, and thus mimics tumor progression on conventional MRI. Contrarily, a decrease in enhancement or edema on conventional MRI during antiangiogenic treatment can be due to pseudoresponse and is not necessarily reflective of a favorable outcome. Neovascularization is a hallmark of tumor progression but not for posttherapeutic effects. Perfusion‐weighted MRI provides a plethora of additional parameters that can help to identify this neovascularization. This review shows that perfusion MRI aids to identify tumor progression, pseudoprogression, and pseudoresponse. The review provides an overview of the most applicable perfusion MRI methods and their limitations. Finally, future developments and remaining challenges of perfusion MRI in treatment evaluation in neuro‐oncology are discussed. Level of Evidence: 3 Technical Efficacy: Stage 4 J. Magn. Reson. Imaging 2019;49:11–22.

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Section: Remaining Questionsmentioning

confidence: 99%

Section: Accreditationmentioning

confidence: 99%

Section: Standardization Of Parametersmentioning

confidence: 99%

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confidence: 99%

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Perfusion MRI in treatment evaluation of glioblastomas: Clinical relevance of current and future techniques

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Smits

et al. 2018

Magnetic Resonance Imaging

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“…However, differentiating tumor recurrence (TuR) from treatment effects (TrE) remains challenging due to overlapping imaging features in conventional structural MRI. For example, newly developed or increased size of enhancing lesions with surrounding edema may occur in both states . Treatment effects include early pseudoprogression and late radiation effects .…”

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Diagnostic performance of multiparametric MRI in the evaluation of treatment response in glioma patients at 3T

Liu

Chen

et al. 2019

Magnetic Resonance Imaging

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Background MRI is one of the most important techniques to assess the treatment response of gliomas. However, differentiating tumor recurrence (TuR) from treatment effects (TrE) remains challenging. Purpose To compare the diagnostic performance of MR diffusion‐weighted imaging (DWI), arterial spin labeling (ASL), proton MR spectroscopy (MRS), and amide proton transfer (APT) imaging in differentiating between TuR and TrE in posttreatment glioma patients. Study Type Prospective. Population Thirty patients with suspected tumor progression. Field Strength/Sequence DWI, ASL, proton MRS, and APT imaging were performed at 3T MR. Assessment MR indices, including ADC, relative cerebral blood flow (rCBF), ratios of Cho/Cr, Cho/NAA, and NAA/Cr and APT‐weighted (APTw) effect were obtained from DWI, ASL, proton MRS, and APT imaging, respectively. Indices were measured in the contralateral normal‐appearing white matter and lesions defined on the Gd‐enhanced T1w image. TuR or TrE was either determined histologically or clinically from longitudinal MRI follow‐up for at least 6 months. Statistical Tests The diagnostic performance of the indices was evaluated using Student's t‐test, receiver operating characteristic (ROC) curve, and multivariate logistic regression analyses. Results Among the 30 patients, 16 were diagnosed as having TuR and the rest having TrE. The recurrent tumors showed a significantly higher APTw effect (1.56 ± 1.14%) and rCBF (1.44 ± 0.61) compared with lesions representing treatment effects (–0.44 ± 1.34% and 0.72 ± 0.25, respectively, with P < 0.001). The areas under the curve (AUCs) were 0.87 and 0.90 for APTw and rCBF, respectively, in differentiating between TuR and TrE. Combining APTw and rCBF achieved a higher AUC of 0.93. MRS index ratios of Cho/Cr (P = 0.25), Cho/NAA (P = 0.16), and NAA/Cr (P = 0.86) and ADC (P = 0.37) showed no significant differences between TuR and TrE lesions, with AUCs lower than 0.70. Data Conclusion Compared with DWI and MRS, ASL and APT imaging techniques showed better diagnostic capability in distinguishing TuR from TrE. Level of Evidence: 1 Technical Efficacy: Stage 4 J. Magn. Reson. Imaging 2020;51:1154–1161.

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Liquid Biopsy Strategies to Distinguish Progression from Pseudoprogression and Radiation Necrosis in Glioblastomas

et al. 2020

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despite aggressive treatment. [1] Currently, maximal resection followed by radiation therapy with concurrent temozolomide (TMZ) and adjuvant TMZ treatment is the standard of care. Post-treatment surveillance involves serial MRI. A challenge faced by clinicians is the diagnosis and management of a gadolinium enhancing lesion on a follow-up MRI post-treatment. This suspicious lesion could be progressive disease (PD) or a mere post-treatment radiation effects such as pseudoprogression or radiation necrosis (RN). Pseudoprogression and RN are distinct clinical entities, which when identified and managed appropriately result in better outcomes, while PD of the tumor is often dismal. Patients with PD have a median survival of 3-6 months, [2] and there is no standard of care. Systemic options include TMZ rechallenge, lomustine, and antiangiogenic therapy such as bevacizumab, but their effectiveness is limited. Reradiation and reresection can be considered depending on the location of the tumor and the condition of the patient. [3] Conversely, antiangiogenic drugs like bevacizumab or cediranib decrease contrast enhancement by altering permeability of tumor vasculature without actual reduction in tumor burden, referred to as pseudoresponse. Distinguishing these clinical entities from PD is crucial to avoid unnecessary reoperations, premature discontinuation of adjuvant TMZ or its substitution with second line agents. MR imaging based monitoring is the current standard of care for post-surgical monitoring. Contrast enhancement on imaging is indicative of disrupted blood brain barrier (BBB), but not tumor presence. [4] Currently, MRI-based Response Assessment in Neuro-Oncology (RANO) criteria is used to monitor treatment response in GBM patients. The criteria included T1 gadolinium enhancing disease, T2/FLAIR changes, new lesions, corticosteroid use, and clinical status. [5] Adoption of RANO criteria for monitoring response is not without limitations. There is ambiguity in identifying radiation effects, enrolling patients into clinical trials and monitoring immunotherapy response. [6] Advanced imaging modalities including diffusion-tensor imaging, perfusion imaging, MR spectroscopy (MRS), and positron emission tomography (PET) imaging 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 im...

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Pseudoprogression of brain tumors

Cited by 227 publications

References 133 publications

Perfusion MRI in treatment evaluation of glioblastomas: Clinical relevance of current and future techniques

Perfusion MRI in treatment evaluation of glioblastomas: Clinical relevance of current and future techniques

Diagnostic performance of multiparametric MRI in the evaluation of treatment response in glioma patients at 3T

Liquid Biopsy Strategies to Distinguish Progression from Pseudoprogression and Radiation Necrosis in Glioblastomas

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