Skip to main content

Advertisement

Log in

Evaluation of MR markers that predict survival in patients with newly diagnosed GBM prior to adjuvant therapy

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

Abstract

Purpose Glioblastoma Multiforme (GBM) is the most common and lethal primary brain tumor in adults. The goal of this study was to test the predictive value of MR parameters in relation to the survival of patients with newly diagnosed GBM who were scanned prior to receiving adjuvant radiation and chemotherapy. Methods The study population comprised 68 patients who had surgical resection and were to be treated with fractionated external beam radiation therapy and chemotherapy. Imaging scans included anatomical MRI, diffusion and perfusion weighted imaging and 1H MRSI. The MR data were acquired 3–5 weeks after surgery and approximately 1 week before treatment with radiation therapy. The diffusion, perfusion and spectroscopic parameter values were quantified and subjected to proportional hazards analysis that was adjusted for age and scanner field strength. Results The patients with larger lesion burden based upon volumes of anatomic lesions, volume of CNI2 (number of voxels within the T2 lesion having choline to NAA index >2), volume of CBV3 (number of pixels within the T2 lesion having relative cerebral blood volume >3), and volume of nADC1.5 (number of pixels within the T2 lesion having normalized apparent diffusion coefficient <1.5) had a higher risk for poor outcome. High intensities of combined measures of lactate and lipid in the T2 and CNI2 regions were also associated with poor survival. Conclusions Our study indicated that several pre-treatment anatomic, physiological and metabolic MR parameters are predictive of survival. This information may be important for stratifying patients to specific treatment protocols and for planning focal therapy.

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

Access this article

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
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Aboagye EO, Kelson AB, Tracy M, Workman P (1998) Preclinical development and current status of the fluorinated 2-nitroimidazole hypoxia probe N-(2-hydroxy-3,3,3-trifluoropropyl)-2-(2-nitro-1-imidazolyl) acetamide (SR 4554, CRC 94/17): a non-invasive diagnostic probe for the measurement of tumor hypoxia by magnetic resonance spectroscopy and imaging, and by positron emission tomography. Anticancer Drug Des 13:703–730

    PubMed  CAS  Google Scholar 

  2. Alger JR, Frank JA, Bizzi A, Fulham MJ, DeSouza BX, Duhaney MO et al (1990) Metabolism of human gliomas: assessment with H-1 MR spectroscopy and F-18 flourodeoxyglucose PET. Radiology 177:633–641

    PubMed  CAS  Google Scholar 

  3. Basser PJ, Pierpaoli C (1996) Microstructural and physiological features of tissues elucidated by quantitative-diffusion-tensor MRI. J Magn Reson B 111:209–219. doi:10.1006/jmrb.1996.0086

    Article  PubMed  CAS  Google Scholar 

  4. Burger PC, Green SB (1987) Patient age, histologic features, and length of survival in patients with glioblastoma multiforme. Cancer 59:1617–1625. doi:10.1002/1097-0142(19870501)59:9<1617::AID-CNCR2820590916>3.0.CO;2-X

    Article  PubMed  CAS  Google Scholar 

  5. Burger PC, Vogel FS, Green SB, Strike TA (1985) Glioblastoma multiforme and anaplastic astrocytoma. Pathologic criteria and prognostic implications. Cancer 56:1106–1111. doi:10.1002/1097-0142(19850901)56:5<1106::AID-CNCR2820560525>3.0.CO;2-2

    Article  PubMed  CAS  Google Scholar 

  6. Catalaa I, Henry R, Dillon WP, Graves EE, McKnight TR, Lu Y et al (2006) Perfusion, diffusion and spectroscopy values in newly diagnosed cerebral gliomas. NMR Biomed 19:463–475. doi:10.1002/nbm.1059

    Article  PubMed  CAS  Google Scholar 

  7. Cha S, Lupo JM, Chen MH, Lamborn KR, McDermott MW, Berger MS et al (2007) Differentiation of glioblastoma multiforme and single brain metastasis by peak height and percentage of signal intensity recovery derived from dynamic susceptibility-weighted contrast-enhanced perfusion MR imaging. AJNR Am J Neuroradiol 28:1078–1084. doi:10.3174/ajnr.A0484

    Article  PubMed  CAS  Google Scholar 

  8. Chang L, Mc Bride D, Miller BL, Cornford M, Booth RA, Buchthal SD et al (1995) Localized in vivo 1H magnetic resonance spectroscopy and in vitro analyses of heterogeneous brain tumors. J Neuroimaging 5:157–163

    PubMed  CAS  Google Scholar 

  9. Chenevert TL, Stegman LD, Taylor JM, Robertson PL, Greenberg HS, Rehemtulla A et al (2000) Diffusion magnetic resonance imaging: an early surrogate marker of therapeutic efficacy in brain tumors. J Natl Cancer Inst 92:2029–2036. doi:10.1093/jnci/92.24.2029

    Article  PubMed  CAS  Google Scholar 

  10. Coffey RJ, Lunsford LD (1987) Factors determining survival of patients with malignant gliomas diagnosed by stereotactic biopsy. Appl Neurophysiol 50:183–187. doi:10.1159/000100707

    Article  PubMed  CAS  Google Scholar 

  11. Crawford FW, Khayal IS, McGue C, Saraswathy S, Pirzkall A, Cha S, Lamborn KR, Chang SM, Berger MS, Nelson SJ (2008) Relationship of pre-surgery metabolic and physiological MR imaging parameters to survival for patients with untreated GBM. J Neurooncol (in press)

  12. Etienne MC, Formento JL, Lebrun-Frenay C, Gioanni J, Chatel M, Paquis P et al (1998) Epidermal growth factor receptor and labeling index are independent prognostic factors in glial tumor outcome. Clin Cancer Res 4:2383–2390

    PubMed  CAS  Google Scholar 

  13. Fuss M, Wenz F, Scholdei R, Essig M, Debus J, Knopp MV et al (2000) Radiation-induced regional cerebral blood volume (rCBV) changes in normal brain and lowgrade astrocytomas: quantification and time and dose-dependent occurrence. Int J Radiat Oncol Biol Phys 48:53–58. doi:10.1016/S0360-3016(00)00590-3

    Article  PubMed  CAS  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 224:177–183. doi:10.1148/radiol.2241010637

    Article  PubMed  Google Scholar 

  15. Hamstra DA, Chenevert TL, Moffat BA, Johnson TD, Meyer CR, Mukherji SK et al (2005) Evaluation of the functional diffusion map as an early biomarker of time-to-progression and overall survival in high-grade glioma. Proc Natl Acad Sci USA 102:16759–16764. doi:10.1073/pnas.0508347102

    Article  PubMed  CAS  Google Scholar 

  16. Henry RG, Vigneron DB, Fischbein NJ, Grant PE, Day MR, Noworolski SM et al (2000) Comparison of relative cerebral blood volume and proton spectroscopy in patients with treated gliomas. AJNR Am J Neuroradiol 21:357–366

    PubMed  CAS  Google Scholar 

  17. Hohwieler SM, Freidberg SR, Heatley GJ, Lo TC (1989) Glucocorticoid dependency as a prognostic factor in radiotherapy for cerebral gliomas. Acta Oncol 28:51–55. doi:10.3109/02841868909111181

    Article  Google Scholar 

  18. Jeremic B, Grujicic D, Antunovic V, Djuric L, Stojanovic M, Shibamoto Y (1994) Influence of extent of surgery and tumor location on treatment outcome of patients with glioblastoma multiforme treated with combined modality approach. J Neurooncol 21:177–185. doi:10.1007/BF01052902

    Article  PubMed  CAS  Google Scholar 

  19. Johnson G, Wetzel SG, Cha S, Babb J, Tofts PS (2004) Measuring blood volume and vascular transfer constant from dynamic, T(2)*-weighted contrast-enhanced MRI. Magn Reson Med 51:961–968. doi:10.1002/mrm.20049

    Article  PubMed  Google Scholar 

  20. Kaplan EL, Meier P (1958) Nonparametric estimation from incomplete observations. J Am Stat Assoc 53:457–481. doi:10.2307/2281868

    Article  Google Scholar 

  21. Keles GE, Anderson B, Berger MS (1999) The effect of extent of resection on time to tumor progression and survival in patients with glioblastoma multiforme of the cerebral hemisphere. Surg Neurol 52:371–379. doi:10.1016/S0090-3019(99)00103-2

    Article  PubMed  CAS  Google Scholar 

  22. Keles GE, Lamborn KR, Chang SM, Prados MD, Berger MS (2004) Volume of residual disease as a predictor of outcome in adult patients with recurrent supratentorial glioblastomas multiforme who are undergoing chemotherapy. J Neurosurg 100:41–46

    Article  PubMed  Google Scholar 

  23. Kono K, Inoue Y, Nakayama K, Shakudo M, Morino M, Ohata K et al (2001) The role of diffusion-weighted imaging in patients with brain tumors. AJNR Am J Neuroradiol 22:1081–1088

    PubMed  CAS  Google Scholar 

  24. Lacroix M, Abi-Said D, Fourney DR, Gokaslan ZL, Shi W, DeMonte F et al (2001) A multivariate analysis of 416 patients with glioblastoma multiforme: prognosis, extent of resection, and survival. J Neurosurg 95:190–198

    PubMed  CAS  Google Scholar 

  25. Lamborn KR, Chang SM, Prados MD (2004) Prognostic factors for survival of patients with glioblastoma: recursive partitioning analysis. Neuro-oncology 6:227–235. doi:10.1215/S1152851703000620

    Article  PubMed  Google Scholar 

  26. Lee MC, Cha S, Chang SM, Nelson SJ (2005) Dynamic susceptibility contrast perfusion imaging of radiation effects in normal-appearing brain tissue: changes in the first-pass and recirculation phases. J Magn Reson Imaging 21:683–693. doi:10.1002/jmri.20298

    Article  PubMed  Google Scholar 

  27. Leon SP, Folkerth RD, Black PM (1996) Microvessel density is a prognostic indicator for patients with astroglial brain tumors. Cancer 77:362–372. doi:10.1002/(SICI)1097-0142(19960115)77:2<362::AID-CNCR20>3.0.CO;2-Z

    Article  PubMed  CAS  Google Scholar 

  28. Li X, Jin H, Lu Y, Oh J, Chang S, Nelson SJ (2004) Identification of MRI and 1H MRSI parameters that may predict survival for patients with malignant gliomas. NMR Biomed 17:10–20. doi:10.1002/nbm.858

    Article  PubMed  Google Scholar 

  29. Li Y, Osorio JA, Ozturk-Isik E, Chen AP, Xu D, Crane JC et al (2006) Considerations in applying 3D PRESS H-1 brain MRSI with an eight-channel phased-array coil at 3T. Magn Reson Imaging 24:1295–1302. doi:10.1016/j.mri.2006.07.012

    Article  PubMed  Google Scholar 

  30. Lupo JM, Cha S, Chang SM, Nelson SJ (2005) Dynamic susceptibility-weighted perfusion imaging of high-grade gliomas: characterization of spatial heterogeneity. AJNR Am J Neuroradiol 26:1446–1454

    PubMed  Google Scholar 

  31. Lupo JM, Lee MC, Han ET, Cha S, Chang SM, Berger MS et al (2006) Feasibility of dynamic susceptibility contrast perfusion MR imaging at 3T using a standard quadrature head coil and eight-channel phased-array coil with and without SENSE reconstruction. J Magn Reson Imaging 24:520–529. doi:10.1002/jmri.20673

    Article  PubMed  Google Scholar 

  32. McBride DQ, Miller BL, Nikas DL, Buchthal S, Chang L, Chiang F et al (1995) Analysis of brain tumors using 1H magnetic resonance spectroscopy. Surg Neurol 44:137–144. doi:10.1016/0090-3019(95)00139-5

    Article  PubMed  CAS  Google Scholar 

  33. McKnight TR, Noworolski SM, Vigneron DB, Nelson SJ (2001) An automated technique for the quantitative assessment of 3D-MRSI data from patients with glioma. J Magn Reson Imaging 13:167–177. doi:10.1002/1522-2586(200102)13:2<167::AID-JMRI1026>3.0.CO;2-K

    Article  PubMed  CAS  Google Scholar 

  34. McKnight TR, von dem Bussche MH, Vigneron DB, Lu Y, Berger MS, McDermott MW et al (2002) Histopathological validation of a three-dimensional magnetic resonance spectroscopy index as a predictor of tumor presence. J Neurosurg 97:794–802

    PubMed  Google Scholar 

  35. Miller PJ, Hassanein RS, Girim PG, Kimler BF, O’Boynick P, Evans RG (1990) Univariate and multivariate statistical analysis of high-grade gliomas: the relationship of radiation dose and other prognostic factors. Int J Radiat Oncol Biol Phys 1:275–280

    Google Scholar 

  36. Nelson SJ (2001) Analysis of volume MRI and MR spectroscopic imaging data for the evaluation of patients with brain tumors. Magn Reson Med 46:228–239. doi:10.1002/mrm.1183

    Article  PubMed  CAS  Google Scholar 

  37. Nelson SJ, Nalbandian AB, Proctor E, Vigneron DB (1994) Registration of images from sequential MR studies of the brain. J Magn Reson Imaging 4:877–883. doi:10.1002/jmri.1880040621

    Article  PubMed  CAS  Google Scholar 

  38. Nelson SJ, Huhn S, Vigneron DB, Day MR, Lawrence LW, Prados M et al (1997) Volume MRI and MRSI techniques for the quantitation of treatment response in brain tumors: presentation of a detailed case study. J Magn Reson Imaging 7:1146–1152. doi:10.1002/jmri.1880070630

    Article  PubMed  CAS  Google Scholar 

  39. Nelson SJ, Vigneron DB, Dillon WP (1999) Serial evaluation of patients with brain tumors using volume MRI and 3D 1H MRSI. NMR Biomed 12:123–138. doi:10.1002/(SICI)1099-1492(199905)12:3<123::AID-NBM541>3.0.CO;2-Y

    Article  PubMed  CAS  Google Scholar 

  40. Oh J, Henry RG, Pirzkall A, Lu Y, Li X, Catalaa I et al (2004) Survival analysis in patients with glioblastoma multiforme: predictive value of choline-to-N-acetylaspartate index, apparent diffusion coefficient, and relative cerebral blood volume. J Magn Reson Imaging 19:546–554. doi:10.1002/jmri.20039

    Article  PubMed  Google Scholar 

  41. Peeling J, Sutherland G (1992) High-resolution 1H NMR spectroscopy studies of extracts of human cerebral neoplasms. Magn Reson Med 24:123–136. doi:10.1002/mrm.1910240113

    Article  PubMed  CAS  Google Scholar 

  42. Perkio J, Aronen HJ, Kangasmaki A, Liu Y, Karonen K, Salvolainen S et al (2002) Evaluation of four postprocessing methods for determination of cerebral blood volume and mean transit time by dynamic susceptibility contrast imaging. Magn Reson Med 47:973–981. doi:10.1002/mrm.10126

    Article  PubMed  Google Scholar 

  43. Pirzkall A, McKnight TR, Graves EE, Carol MP, Sneed PK, Wara WW et al (2001) MR-spectroscopy guided target delineation for high-grade gliomas. Int J Radiat Oncol Biol Phys 50:915–928. doi:10.1016/S0360-3016(01)01548-6

    Article  PubMed  CAS  Google Scholar 

  44. Pirzkall A, Li X, Oh J, Chang S, Berger MS, Larson DA et al (2004) 3D MRSI for resected high-grade gliomas before RT: tumor extent according to metabolic activity in relation to MRI. Int J Radiat Oncol Biol Phys 59:126–137. doi:10.1016/j.ijrobp.2003.08.023

    PubMed  Google Scholar 

  45. Prichard JW (1991) What the clinician can learn from MRS lactate measurement. NMR Biomed 4:99–102. doi:10.1002/nbm.1940040212

    Article  PubMed  CAS  Google Scholar 

  46. Saraswathy S, Crawford F, Nelson SJ (2006) Semi-automated segmentation of brain tumor lesions in MR Images. Proceedings of 13th ISMRM meeting (abstract), Seattle, WA, USA

  47. Smith JS, Cha S, Mayo MC, McDermott MW, Parsa AT, Chang SM et al (2005) Serial diffusion-weighted magnetic resonance imaging in cases of glioma: distinguishing tumor recurrence from postresection injury. J Neurosurg 103:428–438

    PubMed  Google Scholar 

  48. Star-Lack J, Spielman D, Adalsteinsson E, Kurhanewicz J, Terris DJ, Vigneron DB (1998) In vivo lactate editing with simultaneous detection of choline, creatine, NAA, and lipid singlets at 1.5T using PRESS excitation with applications to the study of brain and head and neck tumors. J Magn Reson 133:243–254. doi:10.1006/jmre.1998.1458

    Article  PubMed  CAS  Google Scholar 

  49. Steltzer KJ, Sauve KI, Spence AM, Griffin TW, Berger MS (1997) Corpus callosum involvement as a prognostic factor for patients with highgrade astrocytoma. Int J Radiat Oncol Biol Phys 38:27–30. doi:10.1016/S0360-3016(96)00632-3

    PubMed  CAS  Google Scholar 

  50. Stone HB, Brown JM, Phillips TL, Sutherland RM (1993) Oxygen in human tumors: correlations between methods of measurement, response to therapy. Summary of a workshop held November 19–20, 1992, at the National Cancer Institute, Bethesda, Maryland. Radiat Res 136:422–434. doi:10.2307/3578556

    Article  PubMed  CAS  Google Scholar 

  51. Sugahara T, Korogi Y, Kochi M, Ikushima I, Shigematu Y, Hirai T et al (1999) Usefulness of diffusion weighted MRI with echo-planar technique in the evaluation of cellularity in gliomas. J Magn Reson Imaging 9:53–60. doi:10.1002/(SICI)1522-2586(199901)9:1<53::AID-JMRI7>3.0.CO;2-2

    Article  PubMed  CAS  Google Scholar 

  52. Tien RD, Felsberg GJ, Friedman H, Brown M, MacFall J (1994) MR imaging of high-grade cerebral gliomas: value of diffusion-weighted echoplanar pulse sequences. AJR Am J Roentgenol 162:671–677

    PubMed  CAS  Google Scholar 

  53. Tran TK, Vigneron DB, Sailasuta N, Tropp J, Le Roux P, Kurhanewicz J et al (2000) Very selective suppression pulses for clinical MRSI studies of brain and prostate cancer. Magn Reson Med 43:23–33. doi:10.1002/(SICI)1522-2594(200001)43:1<23::AID-MRM4>3.0.CO;2-E

    Article  PubMed  CAS  Google Scholar 

  54. Usenius JP, Vaino P, Hernesniemi J, Kauppinen RA (1994) Choline-containing compounds in human astrocytomas studied by 1H NMR spectroscopy in vivo and in vitro. J Neurochem 63:1538–1543

    Article  PubMed  CAS  Google Scholar 

  55. Vigneron DB, Bollen A, McDermott M, Wald LL, May MR, Noworolski SM et al (2001) Three-dimensional magnetic resonance spectroscopic imaging of histologically confirmed brain tumors. Magn Reson Imaging 19:89–101. doi:10.1016/S0730-725X(01)00225-9

    Article  PubMed  CAS  Google Scholar 

  56. Warburg O (1930) The metabolism of tumors. Constable, New York

    Google Scholar 

  57. Winger MJ, Macdonald DR, Cairncross JG (1989) Supratentorial anaplastic gliomas in adults. The prognostic importance of extent of resection and prior low-grade glioma. J Neurosurg 71:487–493

    PubMed  CAS  Google Scholar 

Download references

Acknowledgements

This study was financially supported by UC Discovery Grants LSIT01-10107 and ITL-BIO04-10148 funded in conjunction with GE Healthcare, and NIH Grants R01 CA059880 and P50 CA97257.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Sarah J. Nelson.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Saraswathy, S., Crawford, F.W., Lamborn, K.R. et al. Evaluation of MR markers that predict survival in patients with newly diagnosed GBM prior to adjuvant therapy. J Neurooncol 91, 69–81 (2009). https://doi.org/10.1007/s11060-008-9685-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11060-008-9685-3

Keywords

Navigation