Skip to main content
SpringerLink
Log in

Assessment of Progression-Free-Survival in Glioblastomas by Intratreatment Dynamic Contrast-Enhanced MRI

  • Original Article
  • Published:
Clinical Neuroradiology Aims and scope Submit manuscript

Abstract

Purpose

The efficacy of concomitant chemoradiation in patients with glioblastomas (GBMs) cannot be reliably assessed until several weeks after therapy completion. Our aim was to evaluate dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) as an early predictive assay for the progression-free-survival.

Methods and Materials

A total of 22 patients with primary GBMs underwent DCE-MRI before, during and after completion of adjuvant chemoradiation. K trans (transfer constant between the intravascular and extravascular, extracellular space), v e (extracellular, extravascular volume) and IAUGC (initial area under the gadolinium concentration time curve) and their changes into treatment were assessed as prognostic markers (12 months of progression-free-survival (PFS)).

Results

Both responders (7 subjects) and non-responders (15 subjects) experienced a reduction in the baseline IAUGC and v e values during the early phase of the treatment. This reduction was more prominent in the responders and was statistically significant for the v e (P = 0.04). Baseline K trans values among responders demonstrated statistically significant reduction during the early phase of treatment (P = 0.001). Multivariate Cox regression analysis demonstrated significant relationship between response and the early changes in K trans values during the treatment (P = 0.04). Trend to significant prognostic value demonstrated the baseline K trans, v e and IAUGC as well as the changes of IAUGC and K trans upon therapy completion.

Conclusions

Early perfusion changes during concomitant chemoradiation in GBMs can be detected by means of DCE-MRI and have significant prognostic value for the 12-month PFS.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Provenzale JM, Mukundan S, Barboriak DP. Diffusion-weighted and perfusion MR imaging for brain tumor characterization and assessment of treatment response. Radiology. 2006;239(3):632–49. doi:10.1148/radiol.2393042031.

    Article  PubMed  Google Scholar 

  2. Galban CJ, Chenevert TL, Meyer CR, Tsien C, Lawrence TS, Hamstra DA, Junck L, Sundgren PC, Johnson TD, Galban S, Sebolt-Leopold JS, Rehemtulla A, Ross BD. Prospective analysis of parametric response map-derived MRI biomarkers: identification of early and distinct glioma response patterns not predicted by standard radiographic assessment. Clin Cancer Res. 2011;17(14):4751–60. doi:10.1158/1078-0432.CCR-10-2098.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Cao Y, Tsien CI, Nagesh V, Junck L, Ten Haken R, Ross BD, Chenevert TL, Lawrence TS. Survival prediction in high-grade gliomas by MRI perfusion before and during early stage of RT [corrected]. Int J Radiat Oncol Biol Phys. 2006;64(3):876–85. doi:10.1016/j.ijrobp.2005.09.001.

    Article  PubMed  Google Scholar 

  4. Sawlani RN, Raizer J, Horowitz SW, Shin W, Grimm SA, Chandler JP, Levy R, Getch C, Carroll TJ. Glioblastoma: a method for predicting response to antiangiogenic chemotherapy by using MR perfusion imaging–pilot study. Radiology. 2010;255(2):622–8. doi:10.1148/radiol.10091341.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Voglein J, Tuttenberg J, Weimer M, Gerigk L, Kauczor HU, Essig M, Weber MA. Treatment monitoring in gliomas: comparison of dynamic susceptibility-weighted contrast-enhanced and spectroscopic MRI techniques for identifying treatment failure. Invest Radiol. 2011;46(6):390–400. doi:10.1097/RLI.0b013e31820e1511.

    Article  PubMed  Google Scholar 

  6. Sorensen AG, Batchelor TT, Zhang WT, Chen PJ, Yeo P, Wang M, Jennings D, Wen PY, Lahdenranta J, Ancukiewicz M, di Tomaso E, Duda DG, Jain RK. A “vascular normalization index” as potential mechanistic biomarker to predict survival after a single dose of cediranib in recurrent glioblastoma patients. Cancer Res. 2009;69(13):5296–300. doi:10.1158/0008-5472.CAN-09-0814.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Sorensen AG, Emblem KE, Polaskova P, Jennings D, Kim H, Ancukiewicz M, Wang M, Wen PY, Ivy P, Batchelor TT, Jain RK. Increased survival of glioblastoma patients who respond to antiangiogenic therapy with elevated blood perfusion. Cancer Res. 2012;72(2):402–7. doi:10.1158/0008-5472.CAN-11–2464.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. 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 Research and Treatment of Cancer Brain Tumor and Radiotherapy Groups, National Cancer Institute of Canada Clinical Trials Group. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005;352(10):987–96. doi:10.1056/NEJMoa043330.

    Article  CAS  PubMed  Google Scholar 

  9. 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 () Updated response assessment criteria for high-grade gliomas: response assessment in neuro-oncology working group. J Clin Oncol. 2010;28(11):1963–72. doi:10.1200/JCO.2009.26.3541.

    Article  PubMed  Google Scholar 

  10. Tofts PS, Kermode AG. Measurement of the blood-brain barrier permeability and leakage space using dynamic MR imaging. 1. Fundamental concepts. Magn Reson Med. 1991;17(2):357–67.

    Article  CAS  PubMed  Google Scholar 

  11. Orton MR, d’Arcy JA, Walker-Samuel S, Hawkes DJ, Atkinson D, Collins DJ, Leach MO. Computationally efficient vascular input function models for quantitative kinetic modelling using DCE-MRI. Phys Med Biol. 2008;53(5):1225–39. doi:10.1088/0031-9155/53/5/005.

    Article  PubMed  Google Scholar 

  12. Parker GJ, Roberts C, Macdonald A, Buonaccorsi GA, Cheung S, Buckley DL, Jackson A, Watson Y, Davies K, Jayson GC. Experimentally-derived functional form for a population-averaged high-temporal-resolution arterial input function for dynamic contrast-enhanced MRI. Magn Reson Med. 2006;56(5):993–1000. doi:10.1002/mrm.21066.

    Article  PubMed  Google Scholar 

  13. Chen KW, Huang SC, Yu DC. The effects of measurement errors in the plasma radioactivity curve on parameter estimation in positron emission tomography. Phys Med Biol. 1991;36(9):1183–200.

    Article  CAS  PubMed  Google Scholar 

  14. Leach MO, Morgan B, Tofts PS, Buckley DL, Huang W, Horsfield MA, Chenevert TL, Collins DJ, Jackson A, Lomas D, Whitcher B, Clarke L, Plummer R, Judson I, Jones R, Alonzi R, Brunner T, Koh DM, Murphy P, Waterton JC, Parker G, Graves MJ, Scheenen TW, Redpath TW, Orton M, Karczmar G, Huisman H, Barentsz J, Padhani A, Experimental Cancer Medicine Centres Imaging Network Steering Committee. Imaging vascular function for early stage clinical trials using dynamic contrast-enhanced magnetic resonance imaging. Eur Radiol. 2012;22(7):1451–64. doi:10.1007/s00330-012-2446-x.

    Article  CAS  PubMed  Google Scholar 

  15. Bankman IN. Handbook of medical imaging: processing and analysis. Academic Press series in biomedical engineering. San Diego: Academic Press; 2000.

    Google Scholar 

  16. Bastin ME, Carpenter TK, Armitage PA, Sinha S, Wardlaw JM, Whittle IR. Effects of dexamethasone on cerebral perfusion and water diffusion in patients with high-grade glioma. AJNR Am J Neuroradiol. 2006;27(2):402–8.

    CAS  PubMed  Google Scholar 

  17. Zwick S, Brix G, Tofts PS, Strecker R, Kopp-Schneider A, Laue H, Semmler W, Kiessling F. Simulation-based comparison of two approaches frequently used for dynamic contrast-enhanced MRI. Eur Radiol. 2010;20(2):432–42. doi:10.1007/s00330-009-1556-6.

    Article  PubMed  Google Scholar 

  18. Koh TS, Bisdas S, Koh DM, Thng CH. Fundamentals of tracer kinetics for dynamic contrast-enhanced MRI. J Magn Reson Imaging. 2011;34(6):1262–76. doi:10.1002/jmri.22795.

    Article  PubMed  Google Scholar 

  19. Mills SJ, Patankar TA, Haroon HA, Baleriaux D, Swindell R, Jackson A. Do cerebral blood volume and contrast transfer coefficient predict prognosis in human glioma? AJNR Am J Neuroradiol. 2006;27(4):853–8.

    CAS  PubMed  Google Scholar 

  20. Goel S, Duda DG, Xu L, Munn LL, Boucher Y, Fukumura D, Jain RK. Normalization of the vasculature for treatment of cancer and other diseases. Physiol Rev. 2011;91(3):1071–121. doi:10.1152/physrev.00038.2010.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Yankeelov TE, Lepage M, Chakravarthy A, Broome EE, Niermann KJ, Kelley MC, Meszoely I, Mayer IA, Herman CR, McManus K, Price RR, Gore JC. Integration of quantitative DCE-MRI and ADC mapping to monitor treatment response in human breast cancer: initial results. Magn Reson Imaging. 2007;25(1):1–13. doi:10.1016/j.mri.2006.09.006.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Pickles MD, Lowry M, Manton DJ, Gibbs P, Turnbull LW. Role of dynamic contrast enhanced MRI in monitoring early response of locally advanced breast cancer to neoadjuvant chemotherapy. Breast cancer Res Treat. 2005;91(1):1–10. doi:10.1007/s10549-004-5819-2.

    Article  CAS  PubMed  Google Scholar 

  23. Evelhoch JL. Key factors in the acquisition of contrast kinetic data for oncology. J Magn Reson Imaging. 1999;10(3):254–9.

    Article  CAS  PubMed  Google Scholar 

  24. Larcombe-McDouall JB, Mattiello J, McCoy CL, Simpson NE, Seyedsadr M, Evelhoch JL. Size dependence of regional blood flow in murine tumours using deuterium magnetic resonance imaging. Int J Radiat Biol. 1991;60(1–2):109–13.

    Article  CAS  PubMed  Google Scholar 

  25. Leach MO, Brindle KM, Evelhoch JL, Griffiths JR, Horsman MR, Jackson A, Jayson GC, Judson IR, Knopp MV, Maxwell RJ, McIntyre D, Padhani AR, Price P, Rathbone R, Rustin GJ, Tofts PS, Tozer GM, Vennart W, Waterton JC, Williams SR, Workman P, Pharmacodynamic/Pharmacokinetic Technologies Advisory Committee, Drug Development Office Cancer Research UK. The assessment of antiangiogenic and antivascular therapies in early-stage clinical trials using magnetic resonance imaging: issues and recommendations. Br J Cancer. 2005;92(9):1599–610. doi:10.1038/sj.bjc.6602550.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Jackson A, Buckley D, Parker GJM. Dynamic contrast-enhanced magnetic resonance imaging in oncology. Medical radiology. Berlin: Springer; 2003.

    Google Scholar 

  27. Wesolowski JR, Rajdev P, Mukherji SK. Temozolomide (Temodar). AJNR Am J Neuroradiol. 2010;31(8):1383–4. doi:10.3174/ajnr.A2170.

    Article  CAS  PubMed  Google Scholar 

  28. Suh CH, Kim HS, Choi YJ, Kim N, Kim SJ. 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. 2013;34(12):2278–86. doi:10.3174/ajnr.A3634.

    Article  CAS  PubMed  Google Scholar 

  29. 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. Estimating kinetic parameters from dynamic contrast-enhanced T(1)-weighted MRI of a diffusable tracer: standardized quantities and symbols. J Magn Reson Imaging. 1999;10(3):223–32.

    Article  CAS  PubMed  Google Scholar 

  30. Sourbron SP, Buckley DL. Classic models for dynamic contrast-enhanced MRI. NMR Biomed. 2013;26:1004–27. doi:10.1002/nbm.2940.

    Article  PubMed  Google Scholar 

  31. Patriarche J, Erickson B. A review of the automated detection of change in serial imaging studies of the brain. J Digit Imaging. 2004;17(3):158–74. doi:10.1007/s10278-004-1010-x.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Lamborn KR, Yung WK, Chang SM, Wen PY, Cloughesy TF, DeAngelis LM, Robins HI, Lieberman FS, Fine HA, Fink KL, Junck L, Abrey L, Gilbert MR, Mehta M, Kuhn JG, Aldape KD, Hibberts J, Peterson PM, Prados MD, North American Brain Tumor Consortium. Progression-free survival: an important end point in evaluating therapy for recurrent high-grade gliomas. Neuro Oncol. 2008;10(2):162–70. doi:10.1215/15228517-2007-062.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Neuroradiology, Eberhard Karls University, Hoppe-Seyler-Str. 3, 72076, Tübingen, Germany

    S. Bisdas MD, MSc

  2. Department of Radiation Therapy, Oncology Institute Ljubljana, Zaloska 2, 1000, Ljubljana, Slovenia

    U. Smrdel MD

  3. Department of Neurology, University Medical Center, Zaloska 7, 1000, Ljubljana, Slovenia

    F. F. Bajrovic MD

  4. Department of Neuroradiology, University Medical Center, Zaloska 7, 1000, Ljubljana, Slovenia

    K. Surlan-Popovic MD

Authors
  1. S. Bisdas MD, MSc
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. U. Smrdel MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. F. F. Bajrovic MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. K. Surlan-Popovic MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to S. Bisdas MD, MSc.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bisdas, S., Smrdel, U., Bajrovic, F.F. et al. Assessment of Progression-Free-Survival in Glioblastomas by Intratreatment Dynamic Contrast-Enhanced MRI. Clin Neuroradiol 26, 39–45 (2016). https://doi.org/10.1007/s00062-014-0328-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00062-014-0328-0

Keywords

Search

Navigation