Semin Neurol 2017; 37(05): 589-596
DOI: 10.1055/s-0037-1608657
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Neuroimaging of Brain Tumors: Pseudoprogression, Pseudoresponse, and Delayed Effects of Chemotherapy and Radiation

Jörg Dietrich
1   Department of Neurology, Center for Neuro-Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
,
Sebastian F. Winter
1   Department of Neurology, Center for Neuro-Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
3   Department of Neurosurgery, Charité - Universitätsmedizin Berlin, Berlin, Germany
,
Joshua P. Klein
2   Departments of Neurology and Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
› Author Affiliations
Further Information

Publication History

Publication Date:
05 December 2017 (online)

Abstract

Management of patients with brain cancer critically depends on an accurate interpretation of imaging findings that will guide treatment decisions. Treatment with chemotherapy and radiation can affect the imaging characteristics of a tumor and therefore cause misinterpretation of treatment response. Specifically, radiotherapy or chemotherapy may result in distinctive imaging abnormalities that can be challenging to differentiate from tumor itself. Moreover, cancer therapy can be associated with unique adverse effects on the brain, which need to be appropriately recognized by the treating physician to guide patient management. Specific imaging findings, such as radiation-induced tissue necrosis, leukoencephalopathy, pseudoprogression, and pseudoresponse represent treatment-related phenomena that can complicate interpretation of imaging studies and clinical decision making. The aim of this review is to describe these phenomena and improve clinician familiarity as to how these appear on structural (MRI) and functional (perfusion, spectroscopy, PET) imaging studies.

 
  • References

  • 1 Dietrich J, Monje M, Wefel J, Meyers C. Clinical patterns and biological correlates of cognitive dysfunction associated with cancer therapy. Oncologist 2008; 13 (12) 1285-1295
  • 2 Dietrich J, Klein JP. Imaging of cancer therapy-induced central nervous system toxicity. Neurol Clin 2014; 32 (01) 147-157
  • 3 Eisele SC, Dietrich J. Cerebral radiation necrosis: diagnostic challenge and clinical management. Rev Neurol 2015; 61 (05) 225-232
  • 4 Rahmathulla G, Marko NF, Weil RJ. Cerebral radiation necrosis: a review of the pathobiology, diagnosis and management considerations. J Clin Neurosci 2013; 20 (04) 485-502
  • 5 Furuse M, Nonoguchi N, Kawabata S, Miyatake S, Kuroiwa T. Delayed brain radiation necrosis: pathological review and new molecular targets for treatment. Med Mol Morphol 2015; 48 (04) 183-190
  • 6 Lee AW, Foo W, Chappell R. , et al. Effect of time, dose, and fractionation on temporal lobe necrosis following radiotherapy for nasopharyngeal carcinoma. Int J Radiat Oncol Biol Phys 1998; 40 (01) 35-42
  • 7 Tuan JK, Ha TC, Ong WS. , et al. Late toxicities after conventional radiation therapy alone for nasopharyngeal carcinoma. Radiother Oncol 2012; 104 (03) 305-311
  • 8 Giglio P, Gilbert MR. Cerebral radiation necrosis. Neurologist 2003; 9 (04) 180-188
  • 9 Marks JE, Baglan RJ, Prassad SC, Blank WF. Cerebral radionecrosis: incidence and risk in relation to dose, time, fractionation and volume. Int J Radiat Oncol Biol Phys 1981; 7 (02) 243-252
  • 10 Kumar AJ, Leeds NE, Fuller GN. , et al. Malignant gliomas: MR imaging spectrum of radiation therapy- and chemotherapy-induced necrosis of the brain after treatment. Radiology 2000; 217 (02) 377-384
  • 11 Ruben JD, Dally M, Bailey M, Smith R, McLean CA, Fedele P. Cerebral radiation necrosis: incidence, outcomes, and risk factors with emphasis on radiation parameters and chemotherapy. Int J Radiat Oncol Biol Phys 2006; 65 (02) 499-508
  • 12 Brandsma D, Stalpers L, Taal W, Sminia P, van den Bent MJ. Clinical features, mechanisms, and management of pseudoprogression in malignant gliomas. Lancet Oncol 2008; 9 (05) 453-461
  • 13 Blonigen BJ, Steinmetz RD, Levin L, Lamba MA, Warnick RE, Breneman JC. Irradiated volume as a predictor of brain radionecrosis after linear accelerator stereotactic radiosurgery. Int J Radiat Oncol Biol Phys 2010; 77 (04) 996-1001
  • 14 Minniti G, Clarke E, Lanzetta G. , et al. Stereotactic radiosurgery for brain metastases: analysis of outcome and risk of brain radionecrosis. Radiat Oncol 2011; 6: 48
  • 15 Fink J, Born D, Chamberlain MC. Radiation necrosis: relevance with respect to treatment of primary and secondary brain tumors. Curr Neurol Neurosci Rep 2012; 12 (03) 276-285
  • 16 Mullins ME, Barest GD, Schaefer PW, Hochberg FH, Gonzalez RG, Lev MH. Radiation necrosis versus glioma recurrence: conventional MR imaging clues to diagnosis. Am J Neuroradiol 2005; 26 (08) 1967-1972
  • 17 Dequesada IM, Quisling RG, Yachnis A, Friedman WA. Can standard magnetic resonance imaging reliably distinguish recurrent tumor from radiation necrosis after radiosurgery for brain metastases? A radiographic-pathological study. Neurosurgery 2008; 63 (05) 898-903 ; discussion 904
  • 18 Verma N, Cowperthwaite MC, Burnett MG, Markey MK. Differentiating tumor recurrence from treatment necrosis: a review of neuro-oncologic imaging strategies. Neuro-oncol 2013; 15 (05) 515-534
  • 19 Barajas Jr RF, Chang JS, Segal MR. , et al. Differentiation of recurrent glioblastoma multiforme from radiation necrosis after external beam radiation therapy with dynamic susceptibility-weighted contrast-enhanced perfusion MR imaging. Radiology 2009; 253 (02) 486-496
  • 20 Barajas RF, Chang JS, Sneed PK, Segal MR, McDermott MW, Cha S. Distinguishing recurrent intra-axial metastatic tumor from radiation necrosis following gamma knife radiosurgery using dynamic susceptibility-weighted contrast-enhanced perfusion MR imaging. Am J Neuroradiol 2009; 30 (02) 367-372
  • 21 Mitsuya K, Nakasu Y, Horiguchi S. , et al. Perfusion weighted magnetic resonance imaging to distinguish the recurrence of metastatic brain tumors from radiation necrosis after stereotactic radiosurgery. J Neurooncol 2010; 99 (01) 81-88
  • 22 Larsen VA, Simonsen HJ, Law I, Larsson HB, Hansen AE. Evaluation of dynamic contrast-enhanced T1-weighted perfusion MRI in the differentiation of tumor recurrence from radiation necrosis. Neuroradiology 2013; 55 (03) 361-369
  • 23 Zeng QS, Li CF, Zhang K, Liu H, Kang XS, Zhen JH. Multivoxel 3D proton MR spectroscopy in the distinction of recurrent glioma from radiation injury. J Neurooncol 2007; 84 (01) 63-69
  • 24 Smith EA, Carlos RC, Junck LR, Tsien CI, Elias A, Sundgren PC. Developing a clinical decision model: MR spectroscopy to differentiate between recurrent tumor and radiation change in patients with new contrast-enhancing lesions. AJR Am J Roentgenol 2009; 192 (02) W45-W52
  • 25 Rock JP, Scarpace L, Hearshen D. , et al. Associations among magnetic resonance spectroscopy, apparent diffusion coefficients, and image-guided histopathology with special attention to radiation necrosis. Neurosurgery 2004; 54 (05) 1111-1117 ; discussion 1117–1119
  • 26 Ricci PE, Karis JP, Heiserman JE, Fram EK, Bice AN, Drayer BP. Differentiating recurrent tumor from radiation necrosis: time for re-evaluation of positron emission tomography?. Am J Neuroradiol 1998; 19 (03) 407-413
  • 27 Chen W, Silverman DH, Delaloye S. , et al. 18F-FDOPA PET imaging of brain tumors: comparison study with 18F-FDG PET and evaluation of diagnostic accuracy. J Nucl Med 2006; 47 (06) 904-911
  • 28 Terakawa Y, Tsuyuguchi N, Iwai Y. , et al. Diagnostic accuracy of 11C-methionine PET for differentiation of recurrent brain tumors from radiation necrosis after radiotherapy. J Nucl Med 2008; 49 (05) 694-699
  • 29 Kim YH, Oh SW, Lim YJ. , et al. Differentiating radiation necrosis from tumor recurrence in high-grade gliomas: assessing the efficacy of 18F-FDG PET, 11C-methionine PET and perfusion MRI. Clin Neurol Neurosurg 2010; 112 (09) 758-765
  • 30 Lizarraga KJ, Allen-Auerbach M, Czernin J. , et al. (18)F-FDOPA PET for differentiating recurrent or progressive brain metastatic tumors from late or delayed radiation injury after radiation treatment. J Nucl Med 2014; 55 (01) 30-36
  • 31 Dietrich J, Wen P. Neurologic complications of chemotherapy. In: Schiff D, Kesari S, Wen P. , eds. Cancer Neurology in Clinical Practice, 2nd ed. Totowa, New Jersey: Humana Press Inc.; 2008: 287-326
  • 32 Arrillaga-Romany IC, Dietrich J. Imaging findings in cancer therapy-associated neurotoxicity. Semin Neurol 2012; 32 (04) 476-486
  • 33 Constine LS, Konski A, Ekholm S, McDonald S, Rubin P. Adverse effects of brain irradiation correlated with MR and CT imaging. Int J Radiat Oncol Biol Phys 1988; 15 (02) 319-330
  • 34 Perrini P, Scollato A, Cioffi F, Mouchaty H, Conti R, Di Lorenzo N. Radiation leukoencephalopathy associated with moderate hydrocephalus: intracranial pressure monitoring and results of ventriculoperitoneal shunting. Neurol Sci 2002; 23 (05) 237-241
  • 35 Lai R, Abrey LE, Rosenblum MK, DeAngelis LM. Treatment-induced leukoencephalopathy in primary CNS lymphoma: a clinical and autopsy study. Neurology 2004; 62 (03) 451-456
  • 36 DeAngelis LM, Delattre JY, Posner JB. Radiation-induced dementia in patients cured of brain metastases. Neurology 1989; 39 (06) 789-796
  • 37 Harder H, Holtel H, Bromberg JE. , et al. Cognitive status and quality of life after treatment for primary CNS lymphoma. Neurology 2004; 62 (04) 544-547
  • 38 Prust MJ, Jafari-Khouzani K, Kalpathy-Cramer J. , et al. Standard chemoradiation for glioblastoma results in progressive brain volume loss. Neurology 2015; 85 (08) 683-691
  • 39 Thiessen B, DeAngelis LM. Hydrocephalus in radiation leukoencephalopathy: results of ventriculoperitoneal shunting. Arch Neurol 1998; 55 (05) 705-710
  • 40 Douw L, Klein M, Fagel SS. , et al. Cognitive and radiological effects of radiotherapy in patients with low-grade glioma: long-term follow-up. Lancet Neurol 2009; 8 (09) 810-818
  • 41 Monaco III EA, Faraji AH, Berkowitz O. , et al. Leukoencephalopathy after whole-brain radiation therapy plus radiosurgery versus radiosurgery alone for metastatic lung cancer. Cancer 2013; 119 (01) 226-232
  • 42 Mamlouk MD, Handwerker J, Ospina J, Hasso AN. Neuroimaging findings of the post-treatment effects of radiation and chemotherapy of malignant primary glial neoplasms. Neuroradiol J 2013; 26 (04) 396-412
  • 43 Cummings M, Dougherty DW, Mohile NA, Walter KA, Usuki KY, Milano MT. Severe radiation-induced leukoencephalopathy: Case report and literature review. Adv Radiat Oncol 2016; 1 (01) 17-20
  • 44 Valk PE, Dillon WP. Radiation injury of the brain. Am J Neuroradiol 1991; 12 (01) 45-62
  • 45 Fischer CM, Neidert MC, Péus D. , et al. Hydrocephalus after resection and adjuvant radiochemotherapy in patients with glioblastoma. Clin Neurol Neurosurg 2014; 120: 27-31
  • 46 Kucharczyk MJ, Parpia S, Whitton A, Greenspoon JN. Evaluation of pseudoprogression in patients with glioblastoma. Neuro-Oncology Practice 2017; 4 (02) 128-134
  • 47 Chamberlain MC, Glantz MJ, Chalmers L, Van Horn A, Sloan AE. Early necrosis following concurrent Temodar and radiotherapy in patients with glioblastoma. J Neurooncol 2007; 82 (01) 81-83
  • 48 Gerstner ER, McNamara MB, Norden AD, Lafrankie D, Wen PY. Effect of adding temozolomide to radiation therapy on the incidence of pseudo-progression. J Neurooncol 2009; 94 (01) 97-101
  • 49 Taal W, Brandsma D, de Bruin HG. , et al. Incidence of early pseudo-progression in a cohort of malignant glioma patients treated with chemoirradiation with temozolomide. Cancer 2008; 113 (02) 405-410
  • 50 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 2008; 26 (13) 2192-2197
  • 51 Yoon RG, Kim HS, Paik W, Shim WH, Kim SJ, Kim JH. Different diagnostic values of imaging parameters to predict pseudoprogression in glioblastoma subgroups stratified by MGMT promoter methylation. Eur Radiol 2017; 27 (01) 255-266
  • 52 Tanaka S, Louis DN, Curry WT, Batchelor TT, Dietrich J. Diagnostic and therapeutic avenues for glioblastoma: no longer a dead end?. Nat Rev Clin Oncol 2013; 10 (01) 14-26
  • 53 Wan B, Wang S, Tu M, Wu B, Han P, Xu H. The diagnostic performance of perfusion MRI for differentiating glioma recurrence from pseudoprogression: A meta-analysis. Medicine (Baltimore) 2017; 96 (11) e6333
  • 54 Wang S, Martinez-Lage M, Sakai Y. , et al. Differentiating tumor progression from pseudoprogression in patients with glioblastomas using diffusion tensor imaging and dynamic susceptibility contrast MRI. Am J Neuroradiol 2016; 37 (01) 28-36
  • 55 Thomas AA, Arevalo-Perez J, Kaley T. , et al. Dynamic contrast enhanced T1 MRI perfusion differentiates pseudoprogression from recurrent glioblastoma. J Neurooncol 2015; 125 (01) 183-190
  • 56 Galldiks N, Law I, Pope WB, Arbizu J, Langen KJ. The use of amino acid PET and conventional MRI for monitoring of brain tumor therapy. Neuroimage Clin 2016; 13: 386-394
  • 57 Shiroishi MS, Boxerman JL, Pope WB. Physiologic MRI for assessment of response to therapy and prognosis in glioblastoma. Neuro Oncol 2016; 18 (04) 467-478
  • 58 Reardon DA, Ballman KV, Buckner JC, Chang SM, Ellingson BM. Impact of imaging measurements on response assessment in glioblastoma clinical trials. Neuro-oncol 2014; 16 (Suppl. 07) vii24-vii35
  • 59 Huang RY, Neagu MR, Reardon DA, Wen PY. Pitfalls in the neuroimaging of glioblastoma in the era of antiangiogenic and immuno/targeted therapy - detecting illusive disease, defining response. Front Neurol 2015; 6: 33