Skip to main content

Advertisement

SpringerLink
Log in

Pretreatment dynamic contrast-enhanced MRI biomarkers correlate with progression-free survival in primary central nervous system lymphoma

  • Clinical Study
  • Published:
Journal of Neuro-Oncology Aims and scope Submit manuscript

Abstract

Purpose

Prediction of clinical outcomes in patients with primary central nervous system lymphoma (PCNSL) is important for optimization of treatment planning. Quantitative imaging biomarkers for PCNSL have not yet been established. This study evaluated the prognostic value of pretreatment dynamic contrast-enhanced MRI and diffusion-weighted imaging for progression-free survival (PFS) in patients with PCNSL.

Methods

Pretreatment dynamic contrast-enhanced MRI and diffusion-weighted imaging were retrospectively analyzed in 18 immunocompetent patients with PCNSL. Volumes of interest encompassing the tumors were assessed for measurements of blood plasma volume (Vp), volume transfer constant (Ktrans), and apparent diffusion coefficient. Patients were divided into short and long PFS groups based on median PFS. Imaging and clinical variables were correlated with PFS.

Results

Median PFS was 19.6 months. Lower Vpmean and Ktransmean values increased risk for rapid progression (< 19.6 months). Receiver operating characteristic curve analysis demonstrated an optimal Vpmean cutoff value of 2.29 (area under the curve [AUC] = 0.74, sensitivity and specificity = 0.78, p = 0.023) for separating patients with short and long PFS. The optimal Ktransmean cutoff was 0.08 (AUC = 0.74, sensitivity = 0.67, specificity = 0.78, p = 0.025). Kaplan–Meier survival analysis with log-rank test demonstrated significantly (p = 0.015) increased risk of rapid progression for patients with Vpmean < 2.29. Vpmean was significantly (p = 0.03) associated with PFS on univariate Cox analysis. Apparent diffusion coefficient values and clinical factors did not influence PFS.

Conclusions

Pretreatment Vp and Ktrans derived from dynamic contrast-enhanced MRI may be novel prognostic quantitative imaging biomarkers of progression-free survival in patients with PCNSL. These data should be prospectively validated in larger patient cohorts.

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
Fig. 2
Fig. 3

Similar content being viewed by others

Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

References

  1. Eloranta S, Branvall E, Celsing F, Papworth K, Ljungqvist M, Enblad G, Ekstrom-Smedby K (2018) Increasing incidence of primary central nervous system lymphoma but no improvement in survival in Sweden 2000–2013. Eur J Haematol 100(1):61–68. https://doi.org/10.1111/ejh.12980

    Article  PubMed  Google Scholar 

  2. Makino K, Nakamura H, Kino T, Takeshima H, Kuratsu J (2006) Rising incidence of primary central nervous system lymphoma in Kumamoto. Jpn Surg Neurol 66(5):503–506. https://doi.org/10.1016/j.surneu.2006.05.055

    Article  Google Scholar 

  3. Grommes C, DeAngelis LM (2017) Primary CNS lymphoma. J Clin Oncol 35(21):2410–2418. https://doi.org/10.1200/jco.2017.72.7602

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Morris PG, Abrey LE (2009) Therapeutic challenges in primary CNS lymphoma. Lancet Neurol 8(6):581–592. https://doi.org/10.1016/s1474-4422(09)70091-2

    Article  CAS  PubMed  Google Scholar 

  5. Qian L, Tomuleasa C, Florian IA, Shen J, Florian IS, Zdrenghea M, Dima D (2017) Advances in the treatment of newly diagnosed primary central nervous system lymphomas. Blood Res 52(3):159–166. https://doi.org/10.5045/br.2017.52.3.159

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Bayraktar S, Bayraktar UD, Ramos JC, Stefanovic A, Lossos IS (2011) Primary CNS lymphoma in HIV positive and negative patients: comparison of clinical characteristics, outcome and prognostic factors. J Neurooncol 101(2):257–265. https://doi.org/10.1007/s11060-010-0252-3

    Article  PubMed  Google Scholar 

  7. Omuro A, Correa DD, DeAngelis LM, Moskowitz CH, Matasar MJ, Kaley TJ, Gavrilovic IT, Nolan C, Pentsova E, Grommes CC, Panageas KS, Baser RE, Faivre G, Abrey LE, Sauter CS (2015) R-MPV followed by high-dose chemotherapy with TBC and autologous stem-cell transplant for newly diagnosed primary CNS lymphoma. Blood 125(9):1403–1410. https://doi.org/10.1182/blood-2014-10-604561

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Morris PG, Correa DD, Yahalom J, Raizer JJ, Schiff D, Grant B, Grimm S, Lai RK, Reiner AS, Panageas K, Karimi S, Curry R, Shah G, Abrey LE, DeAngelis LM, Omuro A (2013) Rituximab, methotrexate, procarbazine, and vincristine followed by consolidation reduced-dose whole-brain radiotherapy and cytarabine in newly diagnosed primary CNS lymphoma: final results and long-term outcome. J Clin Oncol 31(31):3971–3979. https://doi.org/10.1200/jco.2013.50.4910

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Abrey LE, Ben-Porat L, Panageas KS, Yahalom J, Berkey B, Curran W, Schultz C, Leibel S, Nelson D, Mehta M, DeAngelis LM (2006) Primary central nervous system lymphoma: the Memorial Sloan-Kettering Cancer Center prognostic model. J Clin Oncol 24(36):5711–5715. https://doi.org/10.1200/jco.2006.08.2941

    Article  PubMed  Google Scholar 

  10. Barajas RF Jr, Rubenstein JL, Chang JS, Hwang J, Cha S (2010) Diffusion-weighted MR imaging derived apparent diffusion coefficient is predictive of clinical outcome in primary central nervous system lymphoma. AJNR Am J Neuroradiol 31(1):60–66. https://doi.org/10.3174/ajnr.A1750

    Article  PubMed  Google Scholar 

  11. Valles FE, Perez-Valles CL, Regalado S, Barajas RF, Rubenstein JL, Cha S (2013) Combined diffusion and perfusion MR imaging as biomarkers of prognosis in immunocompetent patients with primary central nervous system lymphoma. AJNR Am J Neuroradiol 34(1):35–40. https://doi.org/10.3174/ajnr.A3165

    Article  CAS  PubMed  Google Scholar 

  12. Chung SR, Choi YJ, Kim HS, Park JE, Shim WH, Kim SJ (2016) Tumor vascular permeability pattern is associated with complete response in immunocompetent patients with newly diagnosed primary central nervous system lymphoma: retrospective cohort study. Medicine 95(6):e2624. https://doi.org/10.1097/md.0000000000002624

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Tabouret E, Houillier C, Martin-Duverneuil N, Blonski M, Soussain C, Ghesquieres H, Houot R, Larrieu D, Soubeyran P, Gressin R, Gyan E, Chinot O, Taillandier L, Choquet S, Alentorn A, Leclercq D, Omuro A, Tanguy ML, Hoang-Xuan K (2017) Patterns of response and relapse in primary CNS lymphomas after first-line chemotherapy: imaging analysis of the ANOCEF-GOELAMS prospective randomized trial. Neuro-oncology 19(3):422–429. https://doi.org/10.1093/neuonc/now238

    Article  CAS  PubMed  Google Scholar 

  14. Guo AC, Cummings TJ, Dash RC, Provenzale JM (2002) Lymphomas and high-grade astrocytomas: comparison of water diffusibility and histologic characteristics. Radiology 224(1):177–183. https://doi.org/10.1148/radiol.2241010637

    Article  PubMed  Google Scholar 

  15. Ellingson BM, Malkin MG, Rand SD, Connelly JM, Quinsey C, LaViolette PS, Bedekar DP, Schmainda KM (2010) Validation of functional diffusion maps (fDMs) as a biomarker for human glioma cellularity. J Magn Reson Imaging 31(3):538–548. https://doi.org/10.1002/jmri.22068

    Article  PubMed  PubMed Central  Google Scholar 

  16. Spampinato MV, Schiarelli C, Cianfoni A, Giglio P, Welsh CT, Bisdas S, Rumboldt Z (2013) Correlation between cerebral blood volume measurements by perfusion-weighted magnetic resonance imaging and two-year progression-free survival in gliomas. Neuroradiol J 26(4):385–395. https://doi.org/10.1177/197140091302600404

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Law M, Oh S, Babb JS, Wang E, Inglese M, Zagzag D, Knopp EA, Johnson G (2006) Low-grade gliomas: dynamic susceptibility-weighted contrast-enhanced perfusion MR imaging–prediction of patient clinical response. Radiology 238(2):658–667. https://doi.org/10.1148/radiol.2382042180

    Article  PubMed  Google Scholar 

  18. Haacke EM, Filleti CL, Gattu R, Ciulla C, Al-Bashir A, Suryanarayanan K, Li M, Latif Z, DelProposto Z, Sehgal V, Li T, Torquato V, Kanaparti R, Jiang J, Neelavalli J (2007) New algorithm for quantifying vascular changes in dynamic contrast-enhanced MRI independent of absolute T1 values. Magn Reson Med 58(3):463–472. https://doi.org/10.1002/mrm.21358

    Article  PubMed  Google Scholar 

  19. 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. https://doi.org/10.3174/ajnr.A3825

    Article  CAS  PubMed  Google Scholar 

  20. Lin X, Lee M, Buck O, Woo KM, Zhang Z, Hatzoglou V, Omuro A, Arevalo-Perez J, Thomas AA, Huse J, Peck K, Holodny AI, Young RJ (2017) Diagnostic accuracy of T1-weighted dynamic contrast-enhanced-MRI and DWI-ADC for differentiation of glioblastoma and primary CNS lymphoma. AJNR Am J Neuroradiol 38(3):485–491. https://doi.org/10.3174/ajnr.A5023

    Article  CAS  PubMed  Google Scholar 

  21. Bergamino M, Bonzano L, Levrero F, Mancardi GL, Roccatagliata L (2014) A review of technical aspects of T1-weighted dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in human brain tumors. Phys Med 30(6):635–643. https://doi.org/10.1016/j.ejmp.2014.04.005

    Article  CAS  PubMed  Google Scholar 

  22. Abrey LE, Batchelor TT, Ferreri AJ, Gospodarowicz M, Pulczynski EJ, Zucca E, Smith JR, Korfel A, Soussain C, DeAngelis LM, Neuwelt EA, O’Neill BP, Thiel E, Shenkier T, Graus F, van den Bent M, Seymour JF, Poortmans P, Armitage JO, Cavalli F (2005) Report of an international workshop to standardize baseline evaluation and response criteria for primary CNS lymphoma. J Clin Oncol 23(22):5034–5043. https://doi.org/10.1200/jco.2005.13.524

    Article  PubMed  Google Scholar 

  23. Aronen HJ, Pardo FS, Kennedy DN, Belliveau JW, Packard SD, Hsu DW, Hochberg FH, Fischman AJ, Rosen BR (2000) High microvascular blood volume is associated with high glucose uptake and tumor angiogenesis in human gliomas. Clin Cancer Res 6(6):2189–2200

    CAS  PubMed  Google Scholar 

  24. Aronen HJ, Gazit IE, Louis DN, Buchbinder BR, Pardo FS, Weisskoff RM, Harsh GR, Cosgrove GR, Halpern EF, Hochberg FH et al (1994) Cerebral blood volume maps of gliomas: comparison with tumor grade and histologic findings. Radiology 191(1):41–51. https://doi.org/10.1148/radiology.191.1.8134596

    Article  CAS  PubMed  Google Scholar 

  25. Ulyte A, Katsaros VK, Liouta E, Stranjalis G, Boskos C, Papanikolaou N, Usinskiene J, Bisdas S (2016) Prognostic value of preoperative dynamic contrast-enhanced MRI perfusion parameters for high-grade glioma patients. Neuroradiology 58(12):1197–1208. https://doi.org/10.1007/s00234-016-1741-7

    Article  PubMed  PubMed Central  Google Scholar 

  26. Monteiro AR, Hill R, Pilkington GJ, Madureira PA (2017) The role of hypoxia in glioblastoma invasion. Cells 6 (4). https://doi.org/10.3390/cells6040045

  27. Mahase S, Rattenni RN, Wesseling P, Leenders W, Baldotto C, Jain R, Zagzag D (2017) Hypoxia-mediated mechanisms associated with antiangiogenic treatment resistance in glioblastomas. Am J Pathol 187(5):940–953. https://doi.org/10.1016/j.ajpath.2017.01.010

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Huang WY, Wen JB, Wu G, Yin B, Li JJ, Geng DY (2016) Diffusion-weighted imaging for predicting and monitoring primary central nervous system lymphoma treatment response. AJNR Am J Neuroradiol. https://doi.org/10.3174/ajnr.A4867

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

The authors thank Joanne Chin who provided editorial support.

Funding

National Institutes of Health/National Cancer Institute (Cancer Center Support Grant P30 CA008748).

Author information

Authors and Affiliations

  1. Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA

    Vaios Hatzoglou, Olivia Buck, Michelle Lee, Amita Shukla-Dave, Robert J. Young, Kyung K. Peck, Behroze Vachha & Andrei I. Holodny

  2. Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Jung Hun Oh, Amita Shukla-Dave & Kyung K. Peck

  3. Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Xuling Lin & Christian Grommes

  4. Brain Tumor Center, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Vaios Hatzoglou, Robert J. Young, Andrei I. Holodny & Christian Grommes

  5. Department of Neurology, Weill Cornell Medical School, New York, NY, USA

    Christian Grommes

Authors
  1. Vaios Hatzoglou
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jung Hun Oh
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Olivia Buck
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Xuling Lin
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Michelle Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Amita Shukla-Dave
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Robert J. Young
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Kyung K. Peck
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Behroze Vachha
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Andrei I. Holodny
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Christian Grommes
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Vaios Hatzoglou.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

For this type of study formal consent is not required.

Research involving human and animal rights

This article does not contain any studies with animals performed by any of the authors.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hatzoglou, V., Oh, J.H., Buck, O. et al. Pretreatment dynamic contrast-enhanced MRI biomarkers correlate with progression-free survival in primary central nervous system lymphoma. J Neurooncol 140, 351–358 (2018). https://doi.org/10.1007/s11060-018-2960-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11060-018-2960-z

Keywords

Search

Navigation