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01-11-2011 | Clinical Study - Patient Study

Proton magnetic resonance spectroscopy predicts survival in children with diffuse intrinsic pontine glioma

Authors: Emilie A. Steffen-Smith, Joanna H. Shih, Sean J. Hipp, Robyn Bent, Katherine E. Warren

Published in: Journal of Neuro-Oncology | Issue 2/2011

Abstract

Patients with diffuse intrinsic pontine glioma (DIPG) face a grim prognosis with limited treatment options. Many patients will enroll on investigational trials though the role of chemotherapy or immunotherapy is unclear. Radiographic changes on conventional MRI are used to evaluate tumor response and progression, but are not predictive of outcome in these patients. More sensitive measures of tumor biology are needed to improve patient management. We evaluated changes in magnetic resonance spectroscopy (MRS) biomarkers in patients with DIPG. Thirty-eight patients were enrolled prospectively on an IRB-approved protocol, which included standard MRI, single voxel spectroscopy (SVS) and multi-slice multi-voxel spectroscopy (MRSI). Scans were performed at multiple time points during each patient’s clinical course, with a total of 142 scans. The prognostic values of Choline:N-acetylaspartate (Cho:NAA), Cho:Creatine (Cho:Cr) and the presence of lactate and lipids (+Lac/Lip) were evaluated. Cho:NAA and variance in Cho:NAA values among different voxels within a tumor were each predictive of shorter survival. This prospective study shows that MRS can be used to identify high-risk patients and monitor changes in tumor metabolism, which may reflect changes in tumor behavior.

Central Brain Tumor Registry of the United States (CBTRUS) (2010) CBTRUS statistical report: primary and central nervous system tumors diagnosed in the United States in 2004–2006, Hindsdale, IL, pp 10–25

Ueoka DI, Nogueira J, Campos JC, Maranhao Filho P, Ferman S, Lima MA (2009) Brainstem gliomas-retrospective analysis of 86 patients. J Neurol Sci 281:20–23. doi:10.1016/j.jns.2009.03.009 PubMedCrossRef

Wolff JE, Classen CF, Wagner S, Kortmann RD, Palla SL, Pietsch T, Kuhl J, Gnekow A, Kramm CM (2008) Subpopulations of malignant gliomas in pediatric patients: analysis of the HIT-GBM database. J Neurooncol 87:155–164. doi:10.1007/s11060-007-9495-z PubMedCrossRef

Shah NC, Ray A, Bartels U, Rutka J, Bouffet E, Drake J, Hawkins CE, Huang A (2008) Diffuse intrinsic brainstem tumors in neonates. Report of two cases. J Neurosurg Pediatr 1:382–385. doi:10.3171/PED/2008/1/5/382 PubMedCrossRef

Maria BL, Rehder K, Eskin TA, Hamed LM, Fennell EB, Quisling RG, Mickle JP, Marcus RB Jr, Drane WE, Mendenhall NP et al (1993) Brainstem glioma: I. Pathology, clinical features, and therapy. J Child Neurol 8:112–128PubMedCrossRef

Hargrave D, Bartels U, Bouffet E (2006) Diffuse brainstem glioma in children: critical review of clinical trials. Lancet Oncol 7:241–248. doi:10.1016/S1470-2045(06)70615-5 PubMedCrossRef

Hargrave D, Chuang N, Bouffet E (2008) Conventional MRI cannot predict survival in childhood diffuse intrinsic pontine glioma. J Neurooncol 86:313–319. doi:10.1007/s11060-007-9473-5 PubMedCrossRef

Liu AK, Brandon J, Foreman NK, Fenton LZ (2009) Conventional MRI at presentation does not predict clinical response to radiation therapy in children with diffuse pontine glioma. Pediatr Radiol 39:1317–1320. doi:10.1007/s00247-009-1368-5 PubMedCrossRef

Kornreich L, Schwarz M, Karmazyn B, Cohen IJ, Shuper A, Michovitz S, Yaniv I, Fenig E, Horev G (2005) Role of MRI in the management of children with diffuse pontine tumors: a study of 15 patients and review of the literature. Pediatr Radiol 35:872–879. doi:10.1007/s00247-005-1502-y PubMedCrossRef

10.

Freeman CR, Farmer JP (1998) Pediatric brain stem gliomas: a review. Int J Radiat Oncol Biol Phys 40:265–271PubMedCrossRef

11.

Broniscer A, Gajjar A (2004) Supratentorial high-grade astrocytoma and diffuse brainstem glioma: two challenges for the pediatric oncologist. Oncologist 9:197–206PubMedCrossRef

12.

Kim CY, Kim SK, Phi JH, Lee MM, Kim IA, Kim IH, Wang KC, Jung HL, Lee MJ, Cho BK (2010) A prospective study of temozolomide plus thalidomide during and after radiation therapy for pediatric diffuse pontine gliomas: preliminary results of the Korean Society for pediatric neuro-oncology study. J Neurooncol. doi:10.1007/s11060-010-0157-1

13.

Jalali R, Raut N, Arora B, Gupta T, Dutta D, Munshi A, Sarin R, Kurkure P (2010) Prospective evaluation of radiotherapy with concurrent and adjuvant temozolomide in children with newly diagnosed diffuse intrinsic pontine glioma. Int J Radiat Oncol Biol Phys 77:113–118. doi:10.1016/j.ijrobp.2009.04.031 PubMedCrossRef

14.

Korones DN, Fisher PG, Kretschmar C, Zhou T, Chen Z, Kepner J, Freeman C (2008) Treatment of children with diffuse intrinsic brain stem glioma with radiotherapy, vincristine and oral VP-16: a Children’s Oncology Group phase II study. Pediatr Blood Cancer 50:227–230. doi:10.1002/pbc.21154 PubMedCrossRef

15.

Massimino M, Spreafico F, Biassoni V, Simonetti F, Riva D, Trecate G, Giombini S, Poggi G, Pecori E, Pignoli E, Casanova M, Ferrari A, Meazza C, Luksch R, Terenziani M, Cefalo G, Podda M, Polastri D, Clerici CA, Fossati-Bellani F, Gandola L (2008) Diffuse pontine gliomas in children: changing strategies, changing results? A mono-institutional 20-year experience. J Neurooncol 87:355–361. doi:10.1007/s11060-008-9525-5 PubMedCrossRef

16.

Frazier JL, Lee J, Thomale UW, Noggle JC, Cohen KJ, Jallo GI (2009) Treatment of diffuse intrinsic brainstem gliomas: failed approaches and future strategies. J Neurosurg Pediatr 3:259–269. doi:10.3171/2008.11.PEDS08281 PubMedCrossRef

17.

Michalski A, Bouffet E, Taylor RE, Hargrave D, Walker D, Picton S, Robinson K, Pizer B, Bujkiewicz S (2010) The addition of high-dose tamoxifen to standard radiotherapy does not improve the survival of patients with diffuse intrinsic pontine glioma. J Neurooncol. doi:10.1007/s11060-010-0141-9

18.

Broniscer A, Baker JN, Tagen M, Onar-Thomas A, Gilbertson RJ, Davidoff AM, Panandiker AP, Leung W, Chin TK, Stewart CF, Kocak M, Rowland C, Merchant TE, Kaste SC, Gajjar A (2010) Phase I study of vandetanib during and after radiotherapy in children with diffuse intrinsic pontine glioma. J Clin Oncol 28:4762–4768. doi:10.1200/JCO.2010.30.3545 PubMedCrossRef

19.

Pincus DW, Richter EO, Yachnis AT, Bennett J, Bhatti MT, Smith A (2006) Brainstem stereotactic biopsy sampling in children. J Neurosurg 104:108–114. doi:10.3171/ped.2006.104.2.108 PubMed

20.

Perez-Gomez JL, Rodriguez-Alvarez CA, Marhx-Bracho A, Rueda-Franco F (2010) Stereotactic biopsy for brainstem tumors in pediatric patients. Childs Nerv Syst 26:29–34. doi:10.1007/s00381-009-1000-x PubMedCrossRef

21.

Zarghooni M, Bartels U, Lee E, Buczkowicz P, Morrison A, Huang A, Bouffet E, Hawkins C (2010) Whole-genome profiling of pediatric diffuse intrinsic pontine gliomas highlights platelet-derived growth factor receptor alpha and poly (ADP-ribose) polymerase as potential therapeutic targets. J Clin Oncol 28:1337–1344. doi:10.1200/JCO.2009.25.5463 PubMedCrossRef

22.

Gilbertson RJ, Hill DA, Hernan R, Kocak M, Geyer R, Olson J, Gajjar A, Rush L, Hamilton RL, Finkelstein SD, Pollack IF (2003) ERBB1 is amplified and overexpressed in high-grade diffusely infiltrative pediatric brain stem glioma. Clin Cancer Res 9:3620–3624PubMed

23.

Paugh BS, Qu C, Jones C, Liu Z, Adamowicz-Brice M, Zhang J, Bax DA, Coyle B, Barrow J, Hargrave D, Lowe J, Gajjar A, Zhao W, Broniscer A, Ellison DW, Grundy RG, Baker SJ (2010) Integrated molecular genetic profiling of pediatric high-grade gliomas reveals key differences with the adult disease. J Clin Oncol 28:3061–3068. doi:10.1200/JCO.2009.26.7252 PubMedCrossRef

24.

Sanai N, Prados M (2010) Brainstem gliomas. In: Gupta N, Banerjee A, Haas-Kogan DA (eds) Pediatric CNS tumors, 1st edn. Springer, Berlin, pp 49–65CrossRef

25.

Peet AC, Lateef S, MacPherson L, Natarajan K, Sgouros S, Grundy RG (2007) Short echo time 1 H magnetic resonance spectroscopy of childhood brain tumours. Childs Nerv Syst 23:163–169. doi:10.1007/s00381-006-0206-4 PubMedCrossRef

26.

Astrakas LG, Zurakowski D, Tzika AA, Zarifi MK, Anthony DC, De Girolami U, Tarbell NJ, Black PM (2004) Noninvasive magnetic resonance spectroscopic imaging biomarkers to predict the clinical grade of pediatric brain tumors. Clin Cancer Res 10:8220–8228. doi:10.1158/1078-0432.CCR-04-0603 PubMedCrossRef

27.

Tzika AA, Astrakas LG, Zarifi MK, Zurakowski D, Poussaint TY, Goumnerova L, Tarbell NJ, Black PM (2004) Spectroscopic and perfusion magnetic resonance imaging predictors of progression in pediatric brain tumors. Cancer 100:1246–1256. doi:10.1002/cncr.20096 PubMedCrossRef

28.

Warren KE, Frank JA, Black JL, Hill RS, Duyn JH, Aikin AA, Lewis BK, Adamson PC, Balis FM (2000) Proton magnetic resonance spectroscopic imaging in children with recurrent primary brain tumors. J Clin Oncol 18:1020–1026PubMed

29.

Marcus KJ, Astrakas LG, Zurakowski D, Zarifi MK, Mintzopoulos D, Poussaint TY, Anthony DC, De Girolami U, Black PM, Tarbell NJ, Tzika AA (2007) Predicting survival of children with CNS tumors using proton magnetic resonance spectroscopic imaging biomarkers. Int J Oncol 30:651–657PubMed

30.

Thakur SB, Karimi S, Dunkel IJ, Koutcher JA, Huang W (2006) Longitudinal MR spectroscopic imaging of pediatric diffuse pontine tumors to assess tumor aggression and progression. AJNR Am J Neuroradiol 27:806–809PubMed

31.

Panigrahy A, Nelson MD Jr, Finlay JL, Sposto R, Krieger MD, Gilles FH, Bluml S (2008) Metabolism of diffuse intrinsic brainstem gliomas in children. Neuro Oncol 10:32–44. doi:10.1215/15228517-2007-042 PubMedCrossRef

32.

Laprie A, Pirzkall A, Haas-Kogan DA, Cha S, Banerjee A, Le TP, Lu Y, Nelson S, McKnight TR (2005) Longitudinal multivoxel MR spectroscopy study of pediatric diffuse brainstem gliomas treated with radiotherapy. Int J Radiat Oncol Biol Phys 62:20–31. doi:10.1016/j.ijrobp.2004.09.027 PubMedCrossRef

33.

Duyn JH, Gillen J, Sobering G, van Zijl PC, Moonen CT (1993) Multisection proton MR spectroscopic imaging of the brain. Radiology 188:277–282PubMed

34.

Jacobs MA, Horska A, van Zijl PC, Barker PB (2001) Quantitative proton MR spectroscopic imaging of normal human cerebellum and brain stem. Magn Reson Med 46:699–705PubMedCrossRef

35.

Tedeschi G, Bertolino A, Campbell G, Barnett AS, Duyn JH, Jacob PK, Moonen CT, Alger JR, Di Chiro G (1996) Reproducibility of proton MR spectroscopic imaging findings. AJNR Am J Neuroradiol 17:1871–1879PubMed

36.

Klein JP, Moeschberger ML (2003) Survival analysis techniques for censored and truncated data. Springer Science + Business Media Inc, New York, NY

37.

McKnight TR, Lamborn KR, Love TD, Berger MS, Chang S, Dillon WP, Bollen A, Nelson SJ (2007) Correlation of magnetic resonance spectroscopic and growth characteristics within Grades II and III gliomas. J Neurosurg 106:660–666. doi:10.3171/jns.2007.106.4.660 PubMedCrossRef

38.

Law M, Yang S, Wang H, Babb JS, Johnson G, Cha S, Knopp EA, Zagzag D (2003) Glioma grading: sensitivity, specificity, and predictive values of perfusion MR imaging and proton MR spectroscopic imaging compared with conventional MR imaging. AJNR Am J Neuroradiol 24:1989–1998PubMed

39.

Ng WH, Lim T (2008) Targeting regions with highest lipid content on MR spectroscopy may improve diagnostic yield in stereotactic biopsy. J Clin Neurosci 15:502–506. doi:10.1016/j.jocn.2007.04.005 PubMedCrossRef

40.

Balmaceda C, Critchell D, Mao X, Cheung K, Pannullo S, DeLaPaz RL, Shungu DC (2006) Multisection 1H magnetic resonance spectroscopic imaging assessment of glioma response to chemotherapy. J Neurooncol 76:185–191. doi:10.1007/s11060-005-5261-2 PubMedCrossRef

41.

Hayward RM, Patronas N, Baker EH, Vezina G, Albert PS, Warren KE (2008) Inter-observer variability in the measurement of diffuse intrinsic pontine gliomas. J Neurooncol 90:57–61. doi:10.1007/s11060-008-9631-4 PubMedCrossRef

42.

Yang I, Huh NG, Smith ZA, Han SJ, Parsa AT (2010) Distinguishing glioma recurrence from treatment effect after radiochemotherapy and immunotherapy. Neurosurg Clin N Am 21:181–186. doi:10.1016/J.Nec.2009.08.003 PubMedCrossRef

43.

Nelson MD Jr, Soni D, Baram TZ (1994) Necrosis in pontine gliomas: radiation induced or natural history? Radiology 191:279–282PubMed

44.

Liu AK, Macy ME, Foreman NK (2009) Bevacizumab as therapy for radiation necrosis in four children with pontine gliomas. Int J Radiat Oncol Biol Phys 75:1148–1154. doi:10.1016/j.ijrobp.2008.12.032 PubMedCrossRef

45.

Castillo M, Kwock L (1998) Proton MR spectroscopy of common brain tumors. Neuroimaging Clin N Am 8:733–752PubMed

46.

Tzika AA, Zarifi MK, Goumnerova L, Astrakas LG, Zurakowski D, Young-Poussaint T, Anthony DC, Scott RM, Black PM (2002) Neuroimaging in pediatric brain tumors: Gd-DTPA-enhanced, hemodynamic, and diffusion MR imaging compared with MR spectroscopic imaging. AJNR Am J Neuroradiol 23:322–333PubMed

47.

Nelson SJ (2003) Multivoxel magnetic resonance spectroscopy of brain tumors. Mol Cancer Ther 2:497–507PubMed

48.

Senft C, Hattingen E, Pilatus U, Franz K, Schanzer A, Lanfermann H, Seifert V, Gasser T (2009) Diagnostic value of proton magnetic resonance spectroscopy in the noninvasive grading of solid gliomas: comparison of maximum and mean choline values. Neurosurgery 65:908–913. doi:10.1227/01.NEU.0000356982.82378.BA (discussion 913)PubMedCrossRef

49.

Wagner M, Nafe R, Jurcoane A, Pilatus U, Franz K, Rieger J, Steinbach JP, Hattingen E (2010) Heterogeneity in malignant gliomas: a magnetic resonance analysis of spatial distribution of metabolite changes and regional blood volume. J Neurooncol. doi:10.1007/s11060-010-0443-y

50.

Chen CY, Lirng JF, Chan WP, Fang CL (2004) Proton magnetic resonance spectroscopy-guided biopsy for cerebral glial tumors. J Formos Med Assoc 103:448–458PubMed

51.

Lupo JM, Cha S, Chang SM, Nelson SJ (2007) Analysis of metabolic indices in regions of abnormal perfusion in patients with high-grade glioma. AJNR Am J Neuroradiol 28:1455–1461. doi:10.3174/ajnr.A0586 PubMedCrossRef

52.

Krieger MD, Bluml S, McComb JG (2003) Magnetic resonance spectroscopy of atypical diffuse pontine masses. Neurosurg Focus 15:E5PubMedCrossRef

53.

Barker PB, Lin DDM (2006) In vivo proton MR spectroscopy of the human brain. Prog Nucl Magn Reson Spectrosc 49:99–128CrossRef

54.

de Graff R (2007) In vivo NMR spectroscopy: principles and techniques. Wiley, West SussexCrossRef

55.

Mascalchi M, Brugnoli R, Guerrini L, Belli G, Nistri M, Politi LS, Gavazzi C, Lolli F, Argenti G, Villari N (2002) Single-voxel long TE 1H-MR spectroscopy of the normal brainstem and cerebellum. J Magn Reson Imaging 16:532–537. doi:10.1002/jmri.10189 PubMedCrossRef

56.

McLean MA, Cross JJ (2009) Magnetic resonance spectroscopy: principles and applications in neurosurgery. Br J Neurosurg 23:5–13. doi:10.1080/02688690802491673 PubMedCrossRef

Title: Proton magnetic resonance spectroscopy predicts survival in children with diffuse intrinsic pontine glioma
Authors: Emilie A. Steffen-Smith
Joanna H. Shih
Sean J. Hipp
Robyn Bent
Katherine E. Warren
Publication date: 01-11-2011
Publisher: Springer US
Published in: Journal of Neuro-Oncology / Issue 2/2011
Print ISSN: 0167-594X
Electronic ISSN: 1573-7373
DOI: https://doi.org/10.1007/s11060-011-0601-x

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Proton magnetic resonance spectroscopy predicts survival in children with diffuse intrinsic pontine glioma

Abstract

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Abstract

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