Glioblastoma Pseudoprogression [Neurosurgery Wiki]

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====== Glioblastoma Pseudoprogression======

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[[Pseudoprogression]] (PsP) is a transient [[magnetic resonance imaging]] (MRI) pattern mimicking [[tumor progression]] but not necessarily accompanied by clinical deterioration. It occurs most frequently during the first 3 months after [[radiation therapy]] and improvement will usually occur within a few weeks or months. PsP is more frequent in patients treated with concomitant [[temozolomide]] than in those receiving radiation therapy alone
((Taal, W. , Brandsma D., de Bruin H. G., Bromberg J. E., Swaak‐Kragten A. T., Smitt P. A., et al. 2008. Incidence of early pseudo‐progression in a cohort of malignant glioma patients treated with chemoirradiation with temozolomide. Cancer 113:405–410.))
((Brandsma, D. , Stalpers L., Taal W., Sminia P., and van den Bent M. J.. 2008. Clinical features, mechanisms, and management of pseudoprogression in malignant gliomas. Lancet Oncol. 9:453–461.)).
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Pseudoprogression is primarily reported in patients who underwent radiotherapy for [[glioblastoma]] and was first described by Hoffman et al. in [[1979]]. In a study of 51 patients with high-grade glioma, six patients (12 %) had increased computerized tomography (CT) enhancement following radiation, which later disappeared
((Hoffman WF, Levin VA, Wilson CB. Evaluation of malignant glioma patients during the postirradiation period. J Neurosurg. 1979 May;50(5):624-8. doi: 10.3171/jns.1979.50.5.0624. PMID: 430157.))



Pseudoprogression (psPD) refers to an increase in size or appearance of new areas of MRI contrast enhancement soon after completing chemoradiation. The term is largely used in brain tumours imaging follow-up, especially for high grade gliomas (e.g. glioblastoma), when observed after chemotherapy and radiotherapy treatment (in about 30% of patients submitted to these therapy) or after just radiotherapy treatment (in about 15%). 

Brain post-radiation treatment effects can be divided into pseudoprogression and [[radiation induced necrosis]].

[[Chemoradiotherapy]] followed by monthly [[temozolomide]] (TMZ) is the standard of care for patients with [[glioblastoma multiforme]] (Glioblastoma). Case reports have identified Glioblastoma patients who experienced transient radiological deterioration after concurrent chemoradiotherapy which stabilized or resolved after additional cycles of adjuvant TMZ, a phenomenon known as radiographic pseudoprogression. Little is known about the natural history of radiographic pseudoprogression.

===== Epidemiology =====
The [[incidence]] of [[tumor]] [[pseudoprogression]] ranges from 28% to 66% in all [[glioblastoma]] patients undergoing [[chemoradiation]] and typically occurs within 3 months after the completion of concurrent [[radiation]] and [[temozolomide]]
((Fink J, Born D, Chamberlain MC: Pseudoprogression: Relevance with respect to treatment of high-grade gliomas. Curr Treat Options Oncol 12:240-252, 2011.)).

Glioblastoma patients with promoter methylation of the repair enzyme 06-methyl guanine DNA methyltransferase ([[MGMT]]) may be at a higher risk of tumor pseudoprogression, with 91% (21 of 23 patients) of such patients developing early radiographic changes in one study
((Brandes AA, Franceschi E, Tosoni A, et al: MGMT promoter methylation status can predict the incidence and outcome of pseudoprogression after concomitant radiochemotherapy in newly diagnosed glioblastoma patients. J Clin Oncol 26:2192-2197, 2008.)).

===== Treatment =====


Approximately one-third of patients are symptomatic from tumor pseudoprogression and may require treatment with [[corticosteroid]]s. [[Bevacizumab]] ([[Avastin]]), a humanized, monoclonal antibody against the vascular endothelial growth factor ([[VEGF]])-A ligand might be efficacious in the treatment of radiation-related brain necrosis but has not been adequately studied or established as an effective therapy for symptomatic tumor pseudoprogression
((Levin VA, Bidaut L, Hou P, et al: Randomized double-blind placebo-controlled trial of bevacizumab therapy for radiation necrosis of the central nervous system. Int J Radiat Oncol Biol Phys 79:1487-1495, 2011.)).

Although preliminary evidence suggests that concurrent treatment of newly diagnosed glioblastoma patients with chemoradiation and an inhibitor of VEGF may reduce the incidence of pseudoprogression, no VEGF inhibitor is yet approved for newly diagnosed glioblastoma, and follow-up studies are required
((Pinho MC, Polaskova P, Jennings D, et al: Impact of adjuvant anti-VEGF therapy on treatment-related pseudoprogression in patients with newly diagnosed glioblastoma receiving chemoradiation with or without anti-VEGF therapy. 2012 ASCO Annual Meeting. Abstract 2025. Presented June 1, 2012.)).

Diagnosis of [[progression]] is complex given the possibility of [[pseudoprogression]] in [[glioblastoma]]. The [[Response Assessment in Neurooncology criteria]] increase the [[sensitivity]] for detecting progression. 

[[Radiation necrosis]] and other normal responses associated with surgical treatment may lead to mimicking [[recurrent glioblastoma]].
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Kim et al. from the University of Ulsan College of Medicine, Asan Medical Center, [[Seoul]], [[Korea]], therefore developed and validated a [[radiomic]]s [[model]] using multiparametric [[MRI]] to differentiate pseudoprogression from early [[tumor progression]] in patients with glioblastoma.

The [[model]] was developed from the enlarging [[contrast]]-enhancing portions of 61 glioblastomas within 3 months after standard treatment with 6472 radiomic features being obtained from contrast-enhanced [[T1]]-weighted imaging, [[fluid attenuated inversion recovery]] imaging, and [[apparent diffusion coefficient]] (ADC), and [[cerebral blood volume]] (CBV) maps. [[Imaging]] features were selected using a least absolute shrinkage and selection operator ([[LASSO]]) [[logistic regression]] model with 10-fold cross-validation. Diagnostic performance for [[pseudoprogression]] was compared with that for single parameters (mean and minimum [[ADC]] and mean and maximum [[CBV]]) and single imaging radiomics models using the area under the receiver-operating-characteristics curve (AUC). The model was validated with an external cohort (n = 34) imaged on a different scanner and an internal prospective registry data (n = 23).

Twelve significant radiomic features (3 from conventional, 2 from [[diffusion]] and 7 from [[perfusion]] MRI) were selected for model construction. The multiparametric radiomics model (AUC 0.90) showed significantly better performance than any single ADC or CBV parameter (AUC 0.57-0.79, P<.05), and better than single radiomics model using conventional MRI (AUC 0.76, P =.012), ADC (AUC 0.78, P =.014), or CBV (AUC 0.80, P=.43). The multiparametric radiomics showed higher performance in the external validation (AUC 0.85) and internal validation (AUC 0.96) than any single approach, thus demonstrating robustness.

Incorporating diffusion- and [[perfusion weighted imaging]] into a radiomics model improved diagnostic performance for identifying pseudoprogression and showed robustness in a multicenter setting
((Kim JY, Park JE, Jo Y, Shim WH, Nam SJ, Kim JH, Yoo RE, Choi SH, Kim HS.
Incorporating diffusion- and perfusion-weighted MRI into a radiomics model
improves diagnostic performance for pseudoprogression in glioblastoma patients.
Neuro Oncol. 2018 Aug 11. doi: 10.1093/neuonc/noy133. [Epub ahead of print]
PubMed PMID: 30107606.
)).


===== Diagnosis =====

[[Glioblastoma Pseudoprogression Diagnosis]].



===== Differential diagnosis =====

[[Glioblastoma Pseudoprogression Differential diagnosis]].