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Dynamic contrast enhanced T1 MRI perfusion differentiates pseudoprogression from recurrent glioblastoma

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Abstract

Pseudoprogression may present as transient new or increasing enhancing lesions that mimic recurrent tumors in treated glioblastoma. The purpose of this study was to examine the utility of dynamic contrast enhanced T1 magnetic resonance imaging (DCE MRI) in differentiating between pseudoprogression and tumor progression and devise a cut-off value sensitive for pseudoprogression. We retrospectively examined 37 patients with glioblastoma treated with radiation and temozolomide after surgical resection that then developed new or increasing enhancing lesion(s) indeterminate for pseudoprogression versus progression. Volumetric plasma volume (Vp) and time-dependent leakage constant (Ktrans) maps were measured for the enhancing lesion and the mean and ninetieth percentile histogram values recorded. Lesion outcome was determined by clinical follow up with pseudoprogression defined as stable disease not requiring new treatment. Statistical analysis was performed with Wilcoxon rank-sum tests. Patients with pseudoprogression (n = 13) had Vp (mean) = 2.4 and Vp (90 %tile) = 3.2; and Ktrans (mean) = 3.5 and Ktrans (90 %tile) = 4.2. Patients with tumor progression (n = 24) had Vp (mean) = 5.3 and Vp (90 %tile) = 6.6; and Ktrans (mean) = 7.4 and Ktrans (90 %tile) = 9.1. Compared with tumor progression, pseudoprogression demonstrated lower Vp perfusion values (p = 0.0002) with a Vp (mean) cutoff <3.7 yielding 85 % sensitivity and 79 % specificity for pseudoprogression. Ktrans (mean) of >3.6 had a 69 % sensitivity and 79 % specificity for disease progression. DCE MRI shows lower plasma volume and time dependent leakage constant values in pseudoprogression than in tumor progression. A cut-off value with high sensitivity for pseudoprogression can be applied to aid in interpretation of DCE MRI.

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References

  1. Rogers LR (2012) Neurologic complications of radiation. Continuum 18(2):343–354. doi:10.1212/01.CON.0000413662.35174.a8

    PubMed  Google Scholar 

  2. Brandsma D, Stalpers L, Taal W, Sminia P, van den Bent MJ (2008) Clinical features, mechanisms, and management of pseudoprogression in malignant gliomas. Lancet Oncol 9(5):453–461. doi:10.1016/S1470-2045(08)70125-6

    Article  PubMed  Google Scholar 

  3. Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO, European Organisation for R, Treatment of Cancer Brain T, Radiotherapy G, National Cancer Institute of Canada Clinical Trials G (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352(10):987–996. doi:10.1056/NEJMoa043330

    Article  CAS  PubMed  Google Scholar 

  4. Wen PY, Macdonald DR, Reardon DA, Cloughesy TF, Sorensen AG, Galanis E, Degroot J, Wick W, Gilbert MR, Lassman AB, Tsien C, Mikkelsen T, Wong ET, Chamberlain MC, Stupp R, Lamborn KR, Vogelbaum MA, van den Bent MJ, Chang SM (2010) Updated response assessment criteria for high-grade gliomas: response assessment in neuro-oncology working group. J Clin Oncol 28(11):1963–1972. doi:10.1200/JCO.2009.26.3541

    Article  PubMed  Google Scholar 

  5. Brandes AA, Franceschi E, Tosoni A, Blatt V, Pession A, Tallini G, Bertorelle R, Bartolini S, Calbucci F, Andreoli A, Frezza G, Leonardi M, Spagnolli F, Ermani M (2008) MGMT promoter methylation status can predict the incidence and outcome of pseudoprogression after concomitant radiochemotherapy in newly diagnosed glioblastoma patients. J Clin Oncol 26(13):2192–2197. doi:10.1200/JCO.2007.14.8163

    Article  PubMed  Google Scholar 

  6. Hegi ME, Diserens AC, Gorlia T, Hamou MF, de Tribolet N, Weller M, Kros JM, Hainfellner JA, Mason W, Mariani L, Bromberg JE, Hau P, Mirimanoff RO, Cairncross JG, Janzer RC, Stupp R (2005) MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med 352(10):997–1003. doi:10.1056/NEJMoa043331

    Article  CAS  PubMed  Google Scholar 

  7. Tran DK, Jensen RL (2013) Treatment-related brain tumor imaging changes: so-called “pseudoprogression” vs. tumor progression: review and future research opportunities. Surg Neurol Int 4(Suppl 3):S129–S135. doi:10.4103/2152-7806.110661

    PubMed Central  PubMed  Google Scholar 

  8. Viallon M, Cuvinciuc V, Delattre B, Merlini L, Barnaure-Nachbar I, Toso-Patel S, Becker M, Lovblad KO, Haller S (2015) State-of-the-art MRI techniques in neuroradiology: principles, pitfalls, and clinical applications. Neuroradiology 57(5):441–467. doi:10.1007/s00234-015-1500-1

    Article  PubMed  Google Scholar 

  9. Yeo DM, Oh SN, Jung CK, Lee MA, Oh ST, Rha SE, Jung SE, Byun JY, Gall P, Son Y, Son Y (2013) Correlation of dynamic contrast-enhanced MRI perfusion parameters with angiogenesis and biologic aggressiveness of rectal cancer: preliminary results. J Magn Reson Imaging: JMRI 41:474–480. doi:10.1002/jmri.24541

    Article  PubMed  Google Scholar 

  10. Chung WJ, Kim HS, Kim N, Choi CG, Kim SJ (2013) Recurrent glioblastoma: optimum area under the curve method derived from dynamic contrast-enhanced T1-weighted perfusion MR imaging. Radiology 269(2):561–568. doi:10.1148/radiol.13130016

    Article  PubMed  Google Scholar 

  11. Jung SC, Yeom JA, Kim JH, Ryoo I, Kim SC, Shin H, Lee AL, Yun TJ, Park CK, Sohn CH, Park SH, Choi SH (2014) Glioma: application of histogram analysis of pharmacokinetic parameters from T1-weighted dynamic contrast-enhanced MR imaging to tumor grading. AJNR Am J Neuroradiol 35(6):1103–1110. doi:10.3174/ajnr.A3825

    Article  CAS  PubMed  Google Scholar 

  12. Tofts PS, Brix G, Buckley DL, Evelhoch JL, Henderson E, Knopp MV, Larsson HB, Lee TY, Mayr NA, Parker GJ, Port RE, Taylor J, Weisskoff RM (1999) Estimating kinetic parameters from dynamic contrast-enhanced T(1)-weighted MRI of a diffusable tracer: standardized quantities and symbols. J Magn Reson Imaging: JMRI 10(3):223–232

    Article  CAS  PubMed  Google Scholar 

  13. Hopewell JW, Calvo W, Jaenke R, Reinhold HS, Robbins ME, Whitehouse EM (1993) Microvasculature and radiation damage. Recent Results Cancer Res 130:1–16

    Article  CAS  PubMed  Google Scholar 

  14. Young RJ, Gupta A, Shah AD, Graber JJ, Zhang Z, Shi W, Holodny AI, Omuro AM (2011) Potential utility of conventional MRI signs in diagnosing pseudoprogression in glioblastoma. Neurology 76(22):1918–1924. doi:10.1212/WNL.0b013e31821d74e7

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  15. Nasseri M, Gahramanov S, Netto JP, Fu R, Muldoon LL, Varallyay C, Hamilton BE, Neuwelt EA (2014) Evaluation of pseudoprogression in patients with glioblastoma multiforme using dynamic magnetic resonance imaging with ferumoxytol calls RANO criteria into question. Neuro-oncology 16(8):1146–1154. doi:10.1093/neuonc/not328

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  16. Song YS, Choi SH, Park CK, Yi KS, Lee WJ, Yun TJ, Kim TM, Lee SH, Kim JH, Sohn CH, Park SH, Kim IH, Jahng GH, Chang KH (2013) True progression versus pseudoprogression in the treatment of glioblastomas: a comparison study of normalized cerebral blood volume and apparent diffusion coefficient by histogram analysis. Korean J Radiol 14(4):662–672. doi:10.3348/kjr.2013.14.4.662

    Article  PubMed Central  PubMed  Google Scholar 

  17. Sourbron S, Ingrisch M, Siefert A, Reiser M, Herrmann K (2009) Quantification of cerebral blood flow, cerebral blood volume, and blood-brain-barrier leakage with DCE-MRI. Magn Reson Med 62(1):205–217. doi:10.1002/mrm.22005

    Article  PubMed  Google Scholar 

  18. Yun TJ, Park CK, Kim TM, Lee SH, Kim JH, Sohn CH, Park SH, Kim IH, Choi SH (2015) 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):830–840. doi:10.1148/radiol.14132632

    Article  PubMed  Google Scholar 

  19. Boxerman JL, Ellingson BM, Jeyapalan S, Elinzano H, Harris RJ, Rogg JM, Pope WB, Safran H (2014) Longitudinal DSC-MRI for distinguishing tumor recurrence from pseudoprogression in patients with a high-grade glioma. Am J Clin Oncol. doi:10.1097/COC.0000000000000156

    Google Scholar 

  20. Arvinda HR, Kesavadas C, Sarma PS, Thomas B, Radhakrishnan VV, Gupta AK, Kapilamoorthy TR, Nair S (2009) Glioma grading: sensitivity, specificity, positive and negative predictive values of diffusion and perfusion imaging. J Neurooncol 94(1):87–96. doi:10.1007/s11060-009-9807-6

    Article  CAS  PubMed  Google Scholar 

  21. Linhares P, Carvalho B, Figueiredo R, Reis RM, Vaz R (2013) Early pseudoprogression following chemoradiotherapy in glioblastoma patients: the value of RANO evaluation. J Oncol 2013:690585. doi:10.1155/2013/690585

    Article  PubMed Central  PubMed  Google Scholar 

  22. Taal W, Brandsma D, de Bruin HG, Bromberg JE, Swaak-Kragten AT, Smitt PA, van Es CA, van den Bent MJ (2008) Incidence of early pseudo-progression in a cohort of malignant glioma patients treated with chemoirradiation with temozolomide. Cancer 113(2):405–410. doi:10.1002/cncr.23562

    Article  CAS  PubMed  Google Scholar 

  23. Sanghera P, Perry J, Sahgal A, Symons S, Aviv R, Morrison M, Lam K, Davey P, Tsao MN (2010) Pseudoprogression following chemoradiotherapy for glioblastoma multiforme. Can J Neurol Sci 37(1):36–42

    Article  PubMed  Google Scholar 

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Acknowledgments

Julio Arevalo-Perez was supported by a grant from the Spanish foundation “Fundación Alfonso Martín Escudero”. Weiji Shi and Zhigang Zhang’s research was partly supported by an NIH Core Grant P30 CA008748.

Author contributions

Drs. Thomas, Arevalo-Perez, Kaley, and Young participated in the design the study. Drs. Thomas, Arevalo-Perez, Peck, Shi, Zhang, and Young participated in the study conduct and gathered and interpreted the data. All authors were involved in the preparation of the report, and reviewed both the draft and final versions.

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Correspondence to Robert J. Young.

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Alissa A. Thomas and Julio Arevalo-Perez have contributed equally.

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11060_2015_1893_MOESM1_ESM.jpg

Supplementary material 1 (JPEG 165 kb) Supplemental Fig. 1: MRI examples pseudoprogression (top) and progression (bottom) in patients with glioblastoma following standard radiation and temozolomide. From left to right, the images demonstrate the baseline axial T1-post contrast MRI scan after surgical resection, a T1-post contrast MRI scan suggestive of progression versus pseudoprogression, the corresponding DCE-MRI blood plasma volume (Vp) parametric map, the corresponding DCE-MRI time dependent leakage constant (Ktrans) parametric map, and an axial FLAIR image

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Thomas, A.A., Arevalo-Perez, J., Kaley, T. et al. Dynamic contrast enhanced T1 MRI perfusion differentiates pseudoprogression from recurrent glioblastoma. J Neurooncol 125, 183–190 (2015). https://doi.org/10.1007/s11060-015-1893-z

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  • DOI: https://doi.org/10.1007/s11060-015-1893-z

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