Tumor pseudoprogression

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 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
  • spectroscopy 7
    • low choline
    • ratio Cho/NAA ratio ≤ 1.4 8
    • increased lactate peak 
    • increased lipid peak
    • the trace may also be generally flat (hypometabolic)
  • ADC
    • 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

Not only does pseudoprogression not represent disease progression, it often is a marker of longer survival, presumably because it represent a robust response to treatment 8

Astrocytic tumour
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Article information

rID: 34959
Synonyms or Alternate Spellings:
  • pseudoprogression
  • Tumor pseudoprogression
  • Pseudoprogression of a tumour

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Cases and figures

  • Case 1: GBM 6 months after treatment
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  • Case 1: 5 years later treatment
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  • Case 2: end of Stupp
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  • Case 2: 2 months later
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  • Case 3: Six months after treatment
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  • Case 3: 11 months after treatment
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  • Case 4: 1 months post Stupp
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  • Case 4: 6 month post Stupp
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  • Case 5: MRS
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  • Case 5: haemotoxylin and eosin
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  • Case 6
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  • Case 7
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