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Pseudoprogression
Blair A. Winegar, MD; Karen L. Salzman, MD
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KEY FACTS

  • Terminology

    • Imaging

      • Top Differential Diagnoses

        • Clinical Issues

          TERMINOLOGY

          • Abbreviations

            • Pseudoprogression (PsP)
            • Programmed death-1/Programmed death ligand-1 (PD-1/PD-L1)
          • Synonyms

            • Treatment-related enhancement
            • Treatment-related changes
          • Definitions

            • Treatment-related increase in contrast enhancement mimicking tumor progression
              • Classically described in malignant glioma after chemoradiation [temozolomide with radiotherapy (XRT)]
              • May occur in malignant glioma or metastatic disease after treatment with immunotherapy (i.e., PD-1/PD-L1 inhibitors)
            • Typically occurs within 3-6 months after conclusion of XRT or immunotherapy
            • Self-limited, enhancing lesions resolve without new treatment

          IMAGING

          • General Features

            • MR Findings

              • Imaging Recommendations

                DIFFERENTIAL DIAGNOSIS

                  PATHOLOGY

                  • General Features

                    • Gross Pathologic & Surgical Features

                      CLINICAL ISSUES

                      • Presentation

                        • Natural History & Prognosis

                          • Treatment

                            DIAGNOSTIC CHECKLIST

                            • Consider

                              Selected References

                              1. Simard JL et al: Pseudoprogression of melanoma brain metastases. Curr Oncol Rep. 20(11):91, 2018
                              2. Thust SC et al: Pseudoprogression of brain tumors. J Magn Reson Imaging. 48(3):571-89, 2018
                              3. Wang Q et al: Pseudoprogression and hyperprogression after checkpoint blockade. Int Immunopharmacol. 58:125-35, 2018
                              4. Aquino D et al: MRI in glioma immunotherapy: evidence, pitfalls, and perspectives. J Immunol Res. 2017:5813951, 2017
                              5. 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
                              6. Galldiks N et al: Diagnosis of pseudoprogression in patients with glioblastoma using O-(2-[18F]fluoroethyl)-L-tyrosine PET. Eur J Nucl Med Mol Imaging. 42(5):685-95, 2015
                              7. Melguizo-Gavilanes I et al: Characterization of pseudoprogression in patients with glioblastoma: is histology the gold standard? J Neurooncol. 123(1):141-50, 2015
                              8. Park JE et al: Pseudoprogression in patients with glioblastoma: assessment by using volume-weighted voxel-based multiparametric clustering of MR imaging data in an independent test set. Radiology. 275(3):792-802, 2015
                              9. Radbruch A et al: Pseudoprogression in patients with glioblastoma: clinical relevance despite low incidence. Neuro Oncol. 17(1):151-9, 2015
                              10. Shiroishi MS et al: Principles of T2 *-weighted dynamic susceptibility contrast MRI technique in brain tumor imaging. J Magn Reson Imaging. 41(2):296-313, 2015
                              11. Yun TJ et al: Glioblastoma treated with concurrent radiation therapy and temozolomide chemotherapy: differentiation of true progression from pseudoprogression with quantitative dynamic contrast-enhanced MR imaging. Radiology. 274(3):830-40, 2015
                              12. Boxerman JL et al: Longitudinal DSC-MRI for distinguishing tumor recurrence from pseudoprogression in patients with a high-grade glioma. Am J Clin Oncol. 40(3):228-34, 2014
                              13. Cha J et al: Differentiation of tumor progression from pseudoprogression in patients with posttreatment glioblastoma using multiparametric histogram analysis. AJNR Am J Neuroradiol. 35(7):1309-17, 2014
                              14. Gahramanov S et al: Diagnosis of pseudoprogression using MRI perfusion in patients with glioblastoma multiforme may predict improved survival. CNS Oncol. 3(6):389-400, 2014
                              15. Lin AL et al: Codeletions at 1p and 19q predict a lower risk of pseudoprogression in oligodendrogliomas and mixed oligoastrocytomas. Neuro Oncol. 16(1):123-30, 2014
                              16. Nasseri M et al: Evaluation of pseudoprogression in patients with glioblastoma multiforme using dynamic magnetic resonance imaging with ferumoxytol calls RANO criteria into question. Neuro Oncol. 16(8):1146-54, 2014
                              17. Chu HH et al: Differentiation of true progression from pseudoprogression in glioblastoma treated with radiation therapy and concomitant temozolomide: comparison study of standard and high-b-value diffusion-weighted imaging. Radiology. 269(3):831-40, 2013
                              18. Gahramanov S et al: Pseudoprogression of glioblastoma after chemo- and radiation therapy: diagnosis by using dynamic susceptibility-weighted contrast-enhanced perfusion MR imaging with ferumoxytol versus gadoteridol and correlation with survival. Radiology. 266(3):842-52, 2013
                              19. Motegi H et al: IDH1 mutation as a potential novel biomarker for distinguishing pseudoprogression from true progression in patients with glioblastoma treated with temozolomide and radiotherapy. Brain Tumor Pathol. 30(2):67-72, 2013
                              20. Suh CH et al: Prediction of pseudoprogression in patients with glioblastomas using the initial and final area under the curves ratio derived from dynamic contrast-enhanced T1-weighted perfusion MR imaging. AJNR Am J Neuroradiol. 34(12):2278-86, 2013
                              21. Jahangiri A et al: Pseudoprogression and treatment effect. Neurosurg Clin N Am. 23(2):277-87, viii-ix, 2012
                              22. 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
                              23. Brandsma D et al: Clinical features, mechanisms, and management of pseudoprogression in malignant gliomas. Lancet Oncol. 9(5):453-61, 2008
                              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

                                        • Pseudoprogression (PsP)
                                        • Programmed death-1/Programmed death ligand-1 (PD-1/PD-L1)
                                      • Synonyms

                                        • Treatment-related enhancement
                                        • Treatment-related changes
                                      • Definitions

                                        • Treatment-related increase in contrast enhancement mimicking tumor progression
                                          • Classically described in malignant glioma after chemoradiation [temozolomide with radiotherapy (XRT)]
                                          • May occur in malignant glioma or metastatic disease after treatment with immunotherapy (i.e., PD-1/PD-L1 inhibitors)
                                        • Typically occurs within 3-6 months after conclusion of XRT or immunotherapy
                                        • Self-limited, enhancing lesions resolve without new treatment

                                      IMAGING

                                      • General Features

                                        • MR Findings

                                          • Imaging Recommendations

                                            DIFFERENTIAL DIAGNOSIS

                                              PATHOLOGY

                                              • General Features

                                                • Gross Pathologic & Surgical Features

                                                  CLINICAL ISSUES

                                                  • Presentation

                                                    • Natural History & Prognosis

                                                      • Treatment

                                                        DIAGNOSTIC CHECKLIST

                                                        • Consider

                                                          Selected References

                                                          1. Simard JL et al: Pseudoprogression of melanoma brain metastases. Curr Oncol Rep. 20(11):91, 2018
                                                          2. Thust SC et al: Pseudoprogression of brain tumors. J Magn Reson Imaging. 48(3):571-89, 2018
                                                          3. Wang Q et al: Pseudoprogression and hyperprogression after checkpoint blockade. Int Immunopharmacol. 58:125-35, 2018
                                                          4. Aquino D et al: MRI in glioma immunotherapy: evidence, pitfalls, and perspectives. J Immunol Res. 2017:5813951, 2017
                                                          5. 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
                                                          6. Galldiks N et al: Diagnosis of pseudoprogression in patients with glioblastoma using O-(2-[18F]fluoroethyl)-L-tyrosine PET. Eur J Nucl Med Mol Imaging. 42(5):685-95, 2015
                                                          7. Melguizo-Gavilanes I et al: Characterization of pseudoprogression in patients with glioblastoma: is histology the gold standard? J Neurooncol. 123(1):141-50, 2015
                                                          8. Park JE et al: Pseudoprogression in patients with glioblastoma: assessment by using volume-weighted voxel-based multiparametric clustering of MR imaging data in an independent test set. Radiology. 275(3):792-802, 2015
                                                          9. Radbruch A et al: Pseudoprogression in patients with glioblastoma: clinical relevance despite low incidence. Neuro Oncol. 17(1):151-9, 2015
                                                          10. Shiroishi MS et al: Principles of T2 *-weighted dynamic susceptibility contrast MRI technique in brain tumor imaging. J Magn Reson Imaging. 41(2):296-313, 2015
                                                          11. Yun TJ et al: Glioblastoma treated with concurrent radiation therapy and temozolomide chemotherapy: differentiation of true progression from pseudoprogression with quantitative dynamic contrast-enhanced MR imaging. Radiology. 274(3):830-40, 2015
                                                          12. Boxerman JL et al: Longitudinal DSC-MRI for distinguishing tumor recurrence from pseudoprogression in patients with a high-grade glioma. Am J Clin Oncol. 40(3):228-34, 2014
                                                          13. Cha J et al: Differentiation of tumor progression from pseudoprogression in patients with posttreatment glioblastoma using multiparametric histogram analysis. AJNR Am J Neuroradiol. 35(7):1309-17, 2014
                                                          14. Gahramanov S et al: Diagnosis of pseudoprogression using MRI perfusion in patients with glioblastoma multiforme may predict improved survival. CNS Oncol. 3(6):389-400, 2014
                                                          15. Lin AL et al: Codeletions at 1p and 19q predict a lower risk of pseudoprogression in oligodendrogliomas and mixed oligoastrocytomas. Neuro Oncol. 16(1):123-30, 2014
                                                          16. Nasseri M et al: Evaluation of pseudoprogression in patients with glioblastoma multiforme using dynamic magnetic resonance imaging with ferumoxytol calls RANO criteria into question. Neuro Oncol. 16(8):1146-54, 2014
                                                          17. Chu HH et al: Differentiation of true progression from pseudoprogression in glioblastoma treated with radiation therapy and concomitant temozolomide: comparison study of standard and high-b-value diffusion-weighted imaging. Radiology. 269(3):831-40, 2013
                                                          18. Gahramanov S et al: Pseudoprogression of glioblastoma after chemo- and radiation therapy: diagnosis by using dynamic susceptibility-weighted contrast-enhanced perfusion MR imaging with ferumoxytol versus gadoteridol and correlation with survival. Radiology. 266(3):842-52, 2013
                                                          19. Motegi H et al: IDH1 mutation as a potential novel biomarker for distinguishing pseudoprogression from true progression in patients with glioblastoma treated with temozolomide and radiotherapy. Brain Tumor Pathol. 30(2):67-72, 2013
                                                          20. Suh CH et al: Prediction of pseudoprogression in patients with glioblastomas using the initial and final area under the curves ratio derived from dynamic contrast-enhanced T1-weighted perfusion MR imaging. AJNR Am J Neuroradiol. 34(12):2278-86, 2013
                                                          21. Jahangiri A et al: Pseudoprogression and treatment effect. Neurosurg Clin N Am. 23(2):277-87, viii-ix, 2012
                                                          22. 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
                                                          23. Brandsma D et al: Clinical features, mechanisms, and management of pseudoprogression in malignant gliomas. Lancet Oncol. 9(5):453-61, 2008