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Published in: Neuroradiology 10/2006

Open Access 01-10-2006 | Diagnostic Neuroradiology

Cerebral blood volume, genotype and chemosensitivity in oligodendroglial tumours

Authors: Michael D. Jenkinson, Trevor S. Smith, Kathy A. Joyce, Diane Fildes, John Broome, Daniel G. du Plessis, Brian Haylock, David J. Husband, Peter C. Warnke, Carol Walker

Published in: Neuroradiology | Issue 10/2006

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Abstract

Introduction

The biological factors responsible for differential chemoresponsiveness in oligodendroglial tumours with or without the −1p/−19q genotype are unknown, but tumour vascularity may contribute. We aimed to determine whether dynamic susceptibility contrast (DSC) magnetic resonance imaging (MRI) could distinguish molecular subtypes of oligodendroglial tumour, and examined the relationship between relative cerebral blood volume (rCBV) and outcome following procarbazine, lomustine and vincristine (PCV) chemotherapy.

Methods

Pretherapy rCBV was calculated and inter- and intraobserver variability assessed. Allelic imbalance in 1p36, 19q13, 17p13, 10p12–15, and 10q22–26 and p53 mutation (exons 5–8) were determined. rCBV was compared with genotype and clinicopathological characteristics (n=37) and outcome following PCV chemotherapy (n=33).

Results

1p/19q loss was seen in 6/9 grade II oligodendrogliomas, 6/14 grade II oligoastrocytomas, 4/4 grade III oligodendrogliomas, and 3/10 grade III oligoastrocytomas. rCBV measurements had good inter- and intraobserver variability, but did not distinguish histology subtype or grade. Tumours with 1p/19q loss had higher rCBV values (Student’s t-test P=0.001). Receiver operating characteristic analysis revealed a cut-off of 1.59 for identifying genotype (sensitivity 92%, specificity 76%). Tumours with high and low rCBV showed response to chemotherapy. The −1p/−19q genotype, but not rCBV, was strongly associated with response, progression-free and overall survival following PCV chemotherapy. Tumours with high rCBV and intact 1p/19q were associated with shorter progression-free and overall patient survival than those with intact 1p/19q and low rCBV or high rCBV and 1p/19q loss.

Conclusion

rCBV identifies oligodendroglial tumours with 1p/19q loss, but does not predict chemosensitivity. The prognostic significance of rCBV may differ in oligodendroglial tumours with or without the −1p/−19q genotype.
Literature
1.
go back to reference Buckner JC, Gesme D Jr, O’Fallon JR et al (2003) Phase II trial of procarbazine, lomustine, and vincristine as initial therapy for patients with low-grade oligodendroglioma or oligoastrocytoma: efficacy and associations with chromosomal abnormalities. J Clin Oncol 21:251–255PubMedCrossRef Buckner JC, Gesme D Jr, O’Fallon JR et al (2003) Phase II trial of procarbazine, lomustine, and vincristine as initial therapy for patients with low-grade oligodendroglioma or oligoastrocytoma: efficacy and associations with chromosomal abnormalities. J Clin Oncol 21:251–255PubMedCrossRef
2.
go back to reference Cairncross JG, Ueki K, Zlatescu MC et al (1998) Specific genetic predictors of chemotherapeutic response and survival in patients with anaplastic oligodendrogliomas. J Natl Cancer Inst 90:1473–1479PubMedCrossRef Cairncross JG, Ueki K, Zlatescu MC et al (1998) Specific genetic predictors of chemotherapeutic response and survival in patients with anaplastic oligodendrogliomas. J Natl Cancer Inst 90:1473–1479PubMedCrossRef
3.
go back to reference Ino Y, Betensky RA, Zlatescu MC et al (2001) Molecular subtypes of anaplastic oligodendroglioma: implications for patient management at diagnosis. Clin Cancer Res 7:839–845PubMed Ino Y, Betensky RA, Zlatescu MC et al (2001) Molecular subtypes of anaplastic oligodendroglioma: implications for patient management at diagnosis. Clin Cancer Res 7:839–845PubMed
4.
go back to reference Smith JS, Perry A, Borell TJ, et al (2000) Alterations of chromosome arms 1p and 19q as predictors of survival in oligodendrogliomas, astrocytomas, and mixed oligoastrocytomas. J Clin Oncol 18:636–645PubMed Smith JS, Perry A, Borell TJ, et al (2000) Alterations of chromosome arms 1p and 19q as predictors of survival in oligodendrogliomas, astrocytomas, and mixed oligoastrocytomas. J Clin Oncol 18:636–645PubMed
5.
go back to reference van den Bent MJ (2004) Advances in the biology and treatment of oligodendrogliomas. Curr Opin Neurol 17:675–680PubMedCrossRef van den Bent MJ (2004) Advances in the biology and treatment of oligodendrogliomas. Curr Opin Neurol 17:675–680PubMedCrossRef
6.
go back to reference Sasaki H, Zlatescu MC, Betensky RA et al (2002) Histopathological-molecular genetic correlations in referral pathologist-diagnosed low-grade “oligodendroglioma”. J Neuropathol Exp Neurol 61:58–63PubMed Sasaki H, Zlatescu MC, Betensky RA et al (2002) Histopathological-molecular genetic correlations in referral pathologist-diagnosed low-grade “oligodendroglioma”. J Neuropathol Exp Neurol 61:58–63PubMed
7.
go back to reference Walker C, Smith TS, Haylock B et al (2006) Clinical use of genotype to predict chemosensitivity in oligodendroglial tumors. Neurology 66:1661–1667PubMedCrossRef Walker C, Smith TS, Haylock B et al (2006) Clinical use of genotype to predict chemosensitivity in oligodendroglial tumors. Neurology 66:1661–1667PubMedCrossRef
8.
go back to reference Cha S, Tihan T, Crawford F et al (2005) Differentiation of low-grade oligodendrogliomas from low-grade astrocytomas by using quantitative blood-volume measurements derived from dynamic susceptibility contrast-enhanced MR imaging. AJNR Am J Neuroradiol 26:266–273PubMed Cha S, Tihan T, Crawford F et al (2005) Differentiation of low-grade oligodendrogliomas from low-grade astrocytomas by using quantitative blood-volume measurements derived from dynamic susceptibility contrast-enhanced MR imaging. AJNR Am J Neuroradiol 26:266–273PubMed
9.
go back to reference Keston P, Murray AD, Jackson A (2003) Cerebral perfusion imaging using contrast-enhanced MRI. Clin Radiol 58:505–513PubMedCrossRef Keston P, Murray AD, Jackson A (2003) Cerebral perfusion imaging using contrast-enhanced MRI. Clin Radiol 58:505–513PubMedCrossRef
10.
go back to reference Cha S, Knopp EA, Johnson G et al (2002) Intracranial mass lesions: dynamic contrast-enhanced susceptibility-weighted echo-planar perfusion MR imaging. Radiology 223:11–29PubMed Cha S, Knopp EA, Johnson G et al (2002) Intracranial mass lesions: dynamic contrast-enhanced susceptibility-weighted echo-planar perfusion MR imaging. Radiology 223:11–29PubMed
11.
go back to reference Law M, Oh S, Babb JS et al (2006) Low-grade gliomas: dynamic susceptibility-weighted contrast-enhanced perfusion MR imaging–prediction of patient clinical response. Radiology 238:658–667PubMed Law M, Oh S, Babb JS et al (2006) Low-grade gliomas: dynamic susceptibility-weighted contrast-enhanced perfusion MR imaging–prediction of patient clinical response. Radiology 238:658–667PubMed
12.
go back to reference Warnke PC, Berlis A, Ostertag C (1998) Physiological characterization of malignant oligodendrogliomas responding to PCV chemotherapy. J Neurosurg 88:399A Warnke PC, Berlis A, Ostertag C (1998) Physiological characterization of malignant oligodendrogliomas responding to PCV chemotherapy. J Neurosurg 88:399A
13.
go back to reference Jager HR, Waldman AD, Benton C, Fox N, Rees J (2005) Differential chemosensitivity of tumor components in a malignant oligodendroglioma: assessment with diffusion-weighted, perfusion-weighted, and serial volumetric MR imaging. AJNR Am J Neuroradiol 26:274–278PubMed Jager HR, Waldman AD, Benton C, Fox N, Rees J (2005) Differential chemosensitivity of tumor components in a malignant oligodendroglioma: assessment with diffusion-weighted, perfusion-weighted, and serial volumetric MR imaging. AJNR Am J Neuroradiol 26:274–278PubMed
14.
go back to reference Godfraind C, Rousseau E, Ruchoux MM, Scaravilli F, Vikkula M (2003) Tumour necrosis and microvascular proliferation are associated with 9p deletion and CDKN2A alterations in 1p/19q-deleted oligodendrogliomas. Neuropathol Appl Neurobiol 29:462–471PubMedCrossRef Godfraind C, Rousseau E, Ruchoux MM, Scaravilli F, Vikkula M (2003) Tumour necrosis and microvascular proliferation are associated with 9p deletion and CDKN2A alterations in 1p/19q-deleted oligodendrogliomas. Neuropathol Appl Neurobiol 29:462–471PubMedCrossRef
15.
go back to reference Jenkinson MD, Smith TS, Joyce K et al (2005) MRS of oligodendroglial tumors: correlation with histopathology and genetic subtypes. Neurology 64:2085–2089PubMedCrossRef Jenkinson MD, Smith TS, Joyce K et al (2005) MRS of oligodendroglial tumors: correlation with histopathology and genetic subtypes. Neurology 64:2085–2089PubMedCrossRef
16.
go back to reference Walker C, du Plessis DG, Fildes D et al (2004) Correlation of molecular genetics with molecular and morphological imaging in gliomas with an oligodendroglial component. Clin Cancer Res 10:7182–7191PubMedCrossRef Walker C, du Plessis DG, Fildes D et al (2004) Correlation of molecular genetics with molecular and morphological imaging in gliomas with an oligodendroglial component. Clin Cancer Res 10:7182–7191PubMedCrossRef
17.
go back to reference Walker C, du Plessis DG, Joyce KA et al (2005) Molecular pathology and clinical characteristics of oligodendroglial neoplasms. Ann Neurol 57:855–865PubMedCrossRef Walker C, du Plessis DG, Joyce KA et al (2005) Molecular pathology and clinical characteristics of oligodendroglial neoplasms. Ann Neurol 57:855–865PubMedCrossRef
18.
go back to reference Walker C, Haylock B, Husband D et al (2006) Clinical use of genotype to predict chemosensitivity in oligodendroglial tumors. Neurology 66:1661–1667PubMedCrossRef Walker C, Haylock B, Husband D et al (2006) Clinical use of genotype to predict chemosensitivity in oligodendroglial tumors. Neurology 66:1661–1667PubMedCrossRef
19.
go back to reference Kleihues P, Cavanee W (eds) (2000) Pathology and genetics of tumours of the nervous system. IARC Press, Lyon Kleihues P, Cavanee W (eds) (2000) Pathology and genetics of tumours of the nervous system. IARC Press, Lyon
20.
go back to reference Wetzel SG, Cha S, Johnson G et al (2002) Relative cerebral blood volume measurements in intracranial mass lesions: interobserver and intraobserver reproducibility study. Radiology 224:797–803PubMed Wetzel SG, Cha S, Johnson G et al (2002) Relative cerebral blood volume measurements in intracranial mass lesions: interobserver and intraobserver reproducibility study. Radiology 224:797–803PubMed
21.
go back to reference Warmuth C, Gunther M, Zimmer C (2003) Quantification of blood flow in brain tumors: comparison of arterial spin labeling and dynamic susceptibility-weighted contrast-enhanced MR imaging. Radiology 228:523–532PubMed Warmuth C, Gunther M, Zimmer C (2003) Quantification of blood flow in brain tumors: comparison of arterial spin labeling and dynamic susceptibility-weighted contrast-enhanced MR imaging. Radiology 228:523–532PubMed
22.
go back to reference Levin VA, Edwards MS, Wright DC et al (1980) Modified procarbazine, CCNU, and vincristine (PCV 3) combination chemotherapy in the treatment of malignant brain tumors. Cancer Treat Rep 64:237–244PubMed Levin VA, Edwards MS, Wright DC et al (1980) Modified procarbazine, CCNU, and vincristine (PCV 3) combination chemotherapy in the treatment of malignant brain tumors. Cancer Treat Rep 64:237–244PubMed
23.
go back to reference Macdonald DR, Cascino TL, Schold SC Jr, Cairncross JG (1990) Response criteria for phase II studies of supratentorial malignant glioma. J Clin Oncol 8:1277–1280PubMed Macdonald DR, Cascino TL, Schold SC Jr, Cairncross JG (1990) Response criteria for phase II studies of supratentorial malignant glioma. J Clin Oncol 8:1277–1280PubMed
24.
go back to reference Bland JM, Altman DG (1986) Statistical methods for assessing agreement between two methods of clinical measurement. Lancet 1:307–310PubMed Bland JM, Altman DG (1986) Statistical methods for assessing agreement between two methods of clinical measurement. Lancet 1:307–310PubMed
25.
go back to reference Law M, Yang S, Wang H et al (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 Law M, Yang S, Wang H et al (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
26.
go back to reference Maia AC Jr, Malheiros SM da Rocha AJ, et al (2005) MR cerebral blood volume maps correlated with vascular endothelial growth factor expression and tumor grade in nonenhancing gliomas. AJNR Am J Neuroradiol 26:777–783PubMed Maia AC Jr, Malheiros SM da Rocha AJ, et al (2005) MR cerebral blood volume maps correlated with vascular endothelial growth factor expression and tumor grade in nonenhancing gliomas. AJNR Am J Neuroradiol 26:777–783PubMed
27.
go back to reference Hakyemez B, Erdogan C, Ercan I et al (2005) High-grade and low-grade gliomas: differentiation by using perfusion MR imaging. Clin Radiol 60:493–502PubMedCrossRef Hakyemez B, Erdogan C, Ercan I et al (2005) High-grade and low-grade gliomas: differentiation by using perfusion MR imaging. Clin Radiol 60:493–502PubMedCrossRef
28.
go back to reference Lev MH, Ozsunar Y, Henson JW et al (2004) Glial tumor grading and outcome prediction using dynamic spin-echo MR susceptibility mapping compared with conventional contrast-enhanced MR: confounding effect of elevated rCBV of oligodendrogliomas [corrected]. AJNR Am J Neuroradiol 25:214–221PubMed Lev MH, Ozsunar Y, Henson JW et al (2004) Glial tumor grading and outcome prediction using dynamic spin-echo MR susceptibility mapping compared with conventional contrast-enhanced MR: confounding effect of elevated rCBV of oligodendrogliomas [corrected]. AJNR Am J Neuroradiol 25:214–221PubMed
29.
go back to reference Roberts HC, Roberts TP, Bollen AW et al (2001) Correlation of microvascular permeability derived from dynamic contrast-enhanced MR imaging with histologic grade and tumor labeling index: a study in human brain tumors. Acad Radiol 8:384–391PubMedCrossRef Roberts HC, Roberts TP, Bollen AW et al (2001) Correlation of microvascular permeability derived from dynamic contrast-enhanced MR imaging with histologic grade and tumor labeling index: a study in human brain tumors. Acad Radiol 8:384–391PubMedCrossRef
30.
go back to reference Aronen HJ, Gazit IE, Louis DN et al (1994) Cerebral blood volume maps of gliomas: comparison with tumor grade and histologic findings. Radiology 191:41–51PubMed Aronen HJ, Gazit IE, Louis DN et al (1994) Cerebral blood volume maps of gliomas: comparison with tumor grade and histologic findings. Radiology 191:41–51PubMed
31.
go back to reference Aronen HJ, Pardo FS, Kennedy DN et al (2000) High microvascular blood volume is associated with high glucose uptake and tumor angiogenesis in human gliomas. Clin Cancer Res 6:2189–2200PubMed Aronen HJ, Pardo FS, Kennedy DN et al (2000) High microvascular blood volume is associated with high glucose uptake and tumor angiogenesis in human gliomas. Clin Cancer Res 6:2189–2200PubMed
32.
go back to reference Sugahara T, Korogi Y, Kochi M et al (1998) Correlation of MR imaging-determined cerebral blood volume maps with histologic and angiographic determination of vascularity of gliomas. AJR Am J Roentgenol 171:1479–1486 Sugahara T, Korogi Y, Kochi M et al (1998) Correlation of MR imaging-determined cerebral blood volume maps with histologic and angiographic determination of vascularity of gliomas. AJR Am J Roentgenol 171:1479–1486
33.
go back to reference Xu M, See SJ, Ng WH et al (2005) Comparison of magnetic resonance spectroscopy and perfusion-weighted imaging in presurgical grading of oligodendroglial tumors. Neurosurgery 56:919–926; discussion 919–926PubMed Xu M, See SJ, Ng WH et al (2005) Comparison of magnetic resonance spectroscopy and perfusion-weighted imaging in presurgical grading of oligodendroglial tumors. Neurosurgery 56:919–926; discussion 919–926PubMed
34.
go back to reference Birner P, Gatterbauer B, Oberhuber G et al (2001) Expression of hypoxia-inducible factor-1 alpha in oligodendrogliomas: its impact on prognosis and on neoangiogenesis. Cancer 92:165–171PubMedCrossRef Birner P, Gatterbauer B, Oberhuber G et al (2001) Expression of hypoxia-inducible factor-1 alpha in oligodendrogliomas: its impact on prognosis and on neoangiogenesis. Cancer 92:165–171PubMedCrossRef
35.
go back to reference Christov C, Adle-Biassette H, Le Guerinel C, Natchev S, Gherardi RK (1998) Immunohistochemical detection of vascular endothelial growth factor (VEGF) in the vasculature of oligodendrogliomas. Neuropathol Appl Neurobiol 24:29–35PubMedCrossRef Christov C, Adle-Biassette H, Le Guerinel C, Natchev S, Gherardi RK (1998) Immunohistochemical detection of vascular endothelial growth factor (VEGF) in the vasculature of oligodendrogliomas. Neuropathol Appl Neurobiol 24:29–35PubMedCrossRef
36.
go back to reference Schiffer D, Bosone I, Dutto A, Di Vito N, Chio A (1999) The prognostic role of vessel productive changes and vessel density in oligodendroglioma. J Neurooncol 44:99–107PubMedCrossRef Schiffer D, Bosone I, Dutto A, Di Vito N, Chio A (1999) The prognostic role of vessel productive changes and vessel density in oligodendroglioma. J Neurooncol 44:99–107PubMedCrossRef
37.
go back to reference Vaquero J, Zurita M, Morales C, Coca S (2002) Prognostic significance of tumor-enhancement and angiogenesis in oligodendroglioma. Acta Neurol Scand 106:19–23PubMedCrossRef Vaquero J, Zurita M, Morales C, Coca S (2002) Prognostic significance of tumor-enhancement and angiogenesis in oligodendroglioma. Acta Neurol Scand 106:19–23PubMedCrossRef
Metadata
Title
Cerebral blood volume, genotype and chemosensitivity in oligodendroglial tumours
Authors
Michael D. Jenkinson
Trevor S. Smith
Kathy A. Joyce
Diane Fildes
John Broome
Daniel G. du Plessis
Brian Haylock
David J. Husband
Peter C. Warnke
Carol Walker
Publication date
01-10-2006
Publisher
Springer-Verlag
Published in
Neuroradiology / Issue 10/2006
Print ISSN: 0028-3940
Electronic ISSN: 1432-1920
DOI
https://doi.org/10.1007/s00234-006-0122-z

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