Tumor pseudoprogression, also known just as pseudoprogression, corresponds to an increase of lesion size related to treatment, which simulates progressive disease. The term is largely used in brain tumors imaging follow-up, especially for high grade gliomas (e.g. glioblastoma), and is observed after combined chemotherapy and radiotherapy in about 30% of patients. Radiotherapy alone is less likely to result in pseudoprogression, only observed in about 15% of patients.
Brain post-radiation treatment effects can be divided into pseudoprogression and radiation necrosis 4.
Due to a overlap between the definitions of pseudoprogression and radiation necrosis, it is not incorrect to say that pseudoprogression represents a mild and self-limiting variant of treatment-related necrosis 1,2.
In almost 60% of cases pseudoprogression occurs within the first 3 months after completing treatment, but it may occur from the first few weeks to 6 months after treatment 1-3.
Patients with methylated MGMT show pseudoprogression more frequently, particularly when treated with temozolomide 1,5,8.
Pseudoprogression can be observed in a context with or without clinical deterioration. However, it is asymptomatic in most patients 1.
It is related to endothelial damage and consequent tissue hypoxia observed after treatment and it has an early occurrence (~60%), usually in the first 3 months after the treatment, but it may occur from the first few weeks to 6 months after treatment.
The hallmark of pseudoprogression is increasing size of the enhancing component of a GBM, and this has proven challenging in the trial setting as the most widely used criteria (Macdonald criteria and Rano criteria) struggle to distinguish between pseudoprogression and true disease progression as they largely rely on only the size of the enhancing component 6. As such conventional CT and MRI are insensitive to the distinction. Advanced sequences (MRS / perfusion / ADC values) are however of significant help.
A good quality MRI including advanced sequences is essential (see MRI protocol: brain tumor). The key features pseudoprogression will demonstrate include:
- perfusion: reduced cerebral blood volume (viable tumor will usually have increased rCBV) 6
- low choline
- ratio Cho/NAA ratio ≤1.4 8
- increased lactate peak
- increased lipid peak
- the trace may also be generally flat (hypometabolic)
- tumors that respond to treatment and result in pseudoprogression will have elevated ADC values due to cell death
- ADC mean values ≥1300 x 10-6 mm2/s 8
Treatment and prognosis
Not only does pseudoprogression not represent disease progression, it often is a marker of longer survival, presumably because it represents a robust response to treatment 8.
- 1. Hygino da Cruz LC, Rodriguez I, Domingues RC et-al. Pseudoprogression and pseudoresponse: imaging challenges in the assessment of posttreatment glioma. AJNR Am J Neuroradiol. 2011;32 (11): 1978-85. doi:10.3174/ajnr.A2397 - Pubmed citation
- 2. Brandsma D, van den Bent MJ. Pseudoprogression and pseudoresponse in the treatment of gliomas. Curr. Opin. Neurol. 2009;22 (6): 633-8. doi:10.1097/WCO.0b013e328332363e - Pubmed citation
- 3. Clarke JL, Chang S. Pseudoprogression and pseudoresponse: challenges in brain tumor imaging. Curr Neurol Neurosci Rep. 2009;9 (3): 241-6. Pubmed citation
- 4. Parvez K, Parvez A, Zadeh G. The diagnosis and treatment of pseudoprogression, radiation necrosis and brain tumor recurrence. Int J Mol Sci. 2014;15 (7): 11832-46. doi:10.3390/ijms150711832 - Free text at pubmed - Pubmed citation
- 5. Brandes AA, Tosoni A, Franceschi E et-al. Recurrence pattern after temozolomide concomitant with and adjuvant to radiotherapy in newly diagnosed patients with glioblastoma: correlation With MGMT promoter methylation status. J. Clin. Oncol. 2009;27 (8): 1275-9. doi:10.1200/JCO.2008.19.4969 - Pubmed citation
- 6. Nasseri M, Gahramanov S, Netto JP et-al. Evaluation of pseudoprogression in patients with glioblastoma multiforme using dynamic magnetic resonance imaging with ferumoxytol calls RANO criteria into question. Neuro-oncology. 2014;16 (8): 1146-54. doi:10.1093/neuonc/not328 - Free text at pubmed - Pubmed citation
- 7. Sawlani V, Taylor R, Rowley K et-al. Magnetic Resonance Spectroscopy for Differentiating Pseudo-Progression from True Progression in GBM on Concurrent Chemoradiotherapy. Neuroradiol J. 2013;25 (5): 575-86. Pubmed citation
- 8. Bulik M, Kazda T, Slampa P et-al. The Diagnostic Ability of Follow-Up Imaging Biomarkers after Treatment of Glioblastoma in the Temozolomide Era: Implications from Proton MR Spectroscopy and Apparent Diffusion Coefficient Mapping. Biomed Res Int. 2015;2015: 641023. doi:10.1155/2015/641023 - Free text at pubmed - Pubmed citation
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