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Brain
Diagnosis
Pathology-Based Diagnoses
Acquired Toxic/Metabolic/Degenerative Disorders
Toxic, Metabolic, Nutritional, Systemic Diseases With CNS Manifestations
Pseudoresponse
Pseudoresponse
Blair A. Winegar, MD; Karen L. Salzman, MD
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KEY FACTS

  • Terminology

    • Imaging

      • Top Differential Diagnoses

        • Clinical Issues

          TERMINOLOGY

          • Abbreviations

            • Vascular endothelial growth factor (VEGF)

          • Synonyms

            • Treatment effect, Avastin effect

          • Definitions

            • Antiangiogenic agents may substantially reduce contrast enhancement in glioblastoma (GBM) related to reduced vascular permeability rather than actual tumor response
              • Bevacizumab (Avastin): Anti-VEGF antibody is main antiangiogenic agent currently used for treatment of recurrent malignant gliomas
              • Cediranib: VEGF receptor tyrosine kinase inhibitor; has been tested in recent high-grade glioma treatment trials with similar effects
              • Enzastaurin: Inhibits protein kinase C-β; non-VEGF antiangiogenic agent

          IMAGING

          • General Features

            • MR Findings

              • Imaging Recommendations

                DIFFERENTIAL DIAGNOSIS

                  PATHOLOGY

                  • General Features

                    CLINICAL ISSUES

                    • Presentation

                      • Natural History & Prognosis

                        DIAGNOSTIC CHECKLIST

                        • Consider

                          • Image Interpretation Pearls

                            Selected References

                            1. Auer TA et al: Evaluation of the apparent diffusion coefficient in patients with recurrent glioblastoma under treatment with bevacizumab with radiographic pseudoresponse. J Neuroradiol. 46(1):36-43, 2019
                            2. Strauss SB et al: Imaging glioblastoma posttreatment: progression, pseudoprogression, pseudoresponse, radiation necrosis. Radiol Clin North Am. 57(6):1199-216, 2019
                            3. van Dijken BRJ et al: Perfusion MRI in treatment evaluation of glioblastomas: clinical relevance of current and future techniques. J Magn Reson Imaging. 49(1):11-22, 2019
                            4. Kong Z et al: Imaging biomarkers guided anti-angiogenic therapy for malignant gliomas. Neuroimage Clin. 20:51-60, 2018
                            5. Barajas RF Jr et al: Assessing biological response to bevacizumab using 18F-fluoromisonidazole PET/MR imaging in a patient with recurrent anaplastic astrocytoma. Case Rep Radiol. 2015:731361, 2015
                            6. Boxerman JL et al: Response assessment and magnetic resonance imaging issues for clinical trials involving high-grade gliomas. Top Magn Reson Imaging. 24(3):127-36, 2015
                            7. Ellingson BM et al: Diffusion MRI quality control and functional diffusion map results in ACRIN 6677/RTOG 0625: a multicenter, randomized, phase II trial of bevacizumab and chemotherapy in recurrent glioblastoma. Int J Oncol. 46(5):1883-92, 2015
                            8. Hygino da Cruz LC Jr et al: Neuroimaging and genetic influence in treating brain neoplasms. Neuroimaging Clin N Am. 25(1):121-40, 2015
                            9. Stadlbauer A et al: Quantification of serial changes in cerebral blood volume and metabolism in patients with recurrent glioblastoma undergoing antiangiogenic therapy. Eur J Radiol. 84(6):1128-36, 2015
                            10. Telles BA et al: Imaging of the posttherapeutic brain. Top Magn Reson Imaging. 24(3):147-54, 2015
                            11. Furuta T et al: Molecular analysis of a recurrent glioblastoma treated with bevacizumab. Brain Tumor Pathol. 31(1):32-9, 2014
                            12. Shim H et al: Use of high-resolution volumetric MR spectroscopic imaging in assessing treatment response of glioblastoma to an HDAC inhibitor. AJR Am J Roentgenol. 203(2):W158-65, 2014
                            13. Kothari PD et al: Longitudinal restriction spectrum imaging is resistant to pseudoresponse in patients with high-grade gliomas treated with bevacizumab. AJNR Am J Neuroradiol. 34(9):1752-7, 2013
                            14. Fatterpekar GM et al: Treatment-related change versus tumor recurrence in high-grade gliomas: a diagnostic conundrum--use of dynamic susceptibility contrast-enhanced (DSC) perfusion MRI. AJR Am J Roentgenol. 198(1):19-26, 2012
                            15. Yamasaki F et al: Advantages of high b-value diffusion-weighted imaging to diagnose pseudo-responses in patients with recurrent glioma after bevacizumab treatment. Eur J Radiol. 81(10):2805-10, 2012
                            16. Gupta A et al: Isolated diffusion restriction precedes the development of enhancing tumor in a subset of patients with glioblastoma. AJNR Am J Neuroradiol. 32(7):1301-6, 2011
                            17. Hygino da Cruz LC Jr et al: Pseudoprogression and pseudoresponse: imaging challenges in the assessment of posttreatment glioma. AJNR Am J Neuroradiol. 32(11):1978-85, 2011
                            18. Sorensen AG et al: A "vascular normalization index" as potential mechanistic biomarker to predict survival after a single dose of cediranib in recurrent glioblastoma patients. Cancer Res. 69(13):5296-300, 2009
                            Related Anatomy
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                            Related Differential Diagnoses
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                            References
                            Tables

                            Tables

                            KEY FACTS

                            • Terminology

                              • Imaging

                                • Top Differential Diagnoses

                                  • Clinical Issues

                                    TERMINOLOGY

                                    • Abbreviations

                                      • Vascular endothelial growth factor (VEGF)

                                    • Synonyms

                                      • Treatment effect, Avastin effect

                                    • Definitions

                                      • Antiangiogenic agents may substantially reduce contrast enhancement in glioblastoma (GBM) related to reduced vascular permeability rather than actual tumor response
                                        • Bevacizumab (Avastin): Anti-VEGF antibody is main antiangiogenic agent currently used for treatment of recurrent malignant gliomas
                                        • Cediranib: VEGF receptor tyrosine kinase inhibitor; has been tested in recent high-grade glioma treatment trials with similar effects
                                        • Enzastaurin: Inhibits protein kinase C-β; non-VEGF antiangiogenic agent

                                    IMAGING

                                    • General Features

                                      • MR Findings

                                        • Imaging Recommendations

                                          DIFFERENTIAL DIAGNOSIS

                                            PATHOLOGY

                                            • General Features

                                              CLINICAL ISSUES

                                              • Presentation

                                                • Natural History & Prognosis

                                                  DIAGNOSTIC CHECKLIST

                                                  • Consider

                                                    • Image Interpretation Pearls

                                                      Selected References

                                                      1. Auer TA et al: Evaluation of the apparent diffusion coefficient in patients with recurrent glioblastoma under treatment with bevacizumab with radiographic pseudoresponse. J Neuroradiol. 46(1):36-43, 2019
                                                      2. Strauss SB et al: Imaging glioblastoma posttreatment: progression, pseudoprogression, pseudoresponse, radiation necrosis. Radiol Clin North Am. 57(6):1199-216, 2019
                                                      3. van Dijken BRJ et al: Perfusion MRI in treatment evaluation of glioblastomas: clinical relevance of current and future techniques. J Magn Reson Imaging. 49(1):11-22, 2019
                                                      4. Kong Z et al: Imaging biomarkers guided anti-angiogenic therapy for malignant gliomas. Neuroimage Clin. 20:51-60, 2018
                                                      5. Barajas RF Jr et al: Assessing biological response to bevacizumab using 18F-fluoromisonidazole PET/MR imaging in a patient with recurrent anaplastic astrocytoma. Case Rep Radiol. 2015:731361, 2015
                                                      6. Boxerman JL et al: Response assessment and magnetic resonance imaging issues for clinical trials involving high-grade gliomas. Top Magn Reson Imaging. 24(3):127-36, 2015
                                                      7. Ellingson BM et al: Diffusion MRI quality control and functional diffusion map results in ACRIN 6677/RTOG 0625: a multicenter, randomized, phase II trial of bevacizumab and chemotherapy in recurrent glioblastoma. Int J Oncol. 46(5):1883-92, 2015
                                                      8. Hygino da Cruz LC Jr et al: Neuroimaging and genetic influence in treating brain neoplasms. Neuroimaging Clin N Am. 25(1):121-40, 2015
                                                      9. Stadlbauer A et al: Quantification of serial changes in cerebral blood volume and metabolism in patients with recurrent glioblastoma undergoing antiangiogenic therapy. Eur J Radiol. 84(6):1128-36, 2015
                                                      10. Telles BA et al: Imaging of the posttherapeutic brain. Top Magn Reson Imaging. 24(3):147-54, 2015
                                                      11. Furuta T et al: Molecular analysis of a recurrent glioblastoma treated with bevacizumab. Brain Tumor Pathol. 31(1):32-9, 2014
                                                      12. Shim H et al: Use of high-resolution volumetric MR spectroscopic imaging in assessing treatment response of glioblastoma to an HDAC inhibitor. AJR Am J Roentgenol. 203(2):W158-65, 2014
                                                      13. Kothari PD et al: Longitudinal restriction spectrum imaging is resistant to pseudoresponse in patients with high-grade gliomas treated with bevacizumab. AJNR Am J Neuroradiol. 34(9):1752-7, 2013
                                                      14. Fatterpekar GM et al: Treatment-related change versus tumor recurrence in high-grade gliomas: a diagnostic conundrum--use of dynamic susceptibility contrast-enhanced (DSC) perfusion MRI. AJR Am J Roentgenol. 198(1):19-26, 2012
                                                      15. Yamasaki F et al: Advantages of high b-value diffusion-weighted imaging to diagnose pseudo-responses in patients with recurrent glioma after bevacizumab treatment. Eur J Radiol. 81(10):2805-10, 2012
                                                      16. Gupta A et al: Isolated diffusion restriction precedes the development of enhancing tumor in a subset of patients with glioblastoma. AJNR Am J Neuroradiol. 32(7):1301-6, 2011
                                                      17. Hygino da Cruz LC Jr et al: Pseudoprogression and pseudoresponse: imaging challenges in the assessment of posttreatment glioma. AJNR Am J Neuroradiol. 32(11):1978-85, 2011
                                                      18. Sorensen AG et al: A "vascular normalization index" as potential mechanistic biomarker to predict survival after a single dose of cediranib in recurrent glioblastoma patients. Cancer Res. 69(13):5296-300, 2009