Early changes in glioblastoma metabolism measured by MR spectroscopic imaging during combination of anti-angiogenic cediranib and chemoradiation therapy are associated with survival

被引：14

作者：

Andronesi, Ovidiu C. ^{[1
]}

Esmaeili, Morteza ^{[1
,8
]}

Borra, Ronald J. H. ^{[1
,3
,9
]}

Emblem, Kyrre ^{[1
,10
]}

Gerstner, Elizabeth R. ^{[2
]}

Pinho, Marco C. ^{[1
,11
]}

Plotkin, Scott R. ^{[2
]}

Chi, Andrew S. ^{[2
,12
,13
]}

Eichler, April F. ^{[2
,14
]}

Dietrich, Jorg ^{[2
]}

Ivy, S. Percy ^{[4
]}

Wen, Patrick Y. ^{[5
,6
]}

Duda, Dan G. ^{[7
]}

Jain, Rakesh ^{[7
]}

Rosen, Bruce R. ^{[1
]}

Sorensen, Gregory A. ^{[1
,15
]}

Batchelor, Tracy T. ^{[2
]}

机构：

[1] Harvard Med Sch, Massachusetts Gen Hosp, Dept Radiol, Martinos Ctr Biomed Imaging, Boston, MA 02114 USA

[2] Harvard Med Sch, Dept Neurol, Stephen E & Catherine Pappas Ctr Neurooncol, Radiat Oncol,Massachusetts Gen Hosp, Boston, MA 02114 USA

[3] Turku Univ Hosp, Dept Diagnost Radiol, Med Imaging Ctr Southwest Finland, Turku, Finland

[4] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA

[5] Dana Farber Canc Inst, Dept Med Oncol, Ctr Neurooncol, Boston, MA 02115 USA

[6] Harvard Med Sch, Boston, MA 02114 USA

[7] Harvard Med Sch, Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA

[8] Norwegian Univ Sci & Technol NTNU, Dept Circulat & Med Imaging, Trondheim, Norway

[9] Univ Groningen, Univ Med Ctr Groningen, Dept Nucl Med & Mol Imaging, Groningen, Netherlands

[10] Oslo Univ Hosp, Intervent Ctr, Clin Diagnost & Intervent, Oslo, Norway

[11] Univ Texas Southwestern Med Ctr Dallas, Dept Radiol, Dallas, TX 75235 USA

[12] NYU, Brain Tumor Ctr, Laura & Isaac Perlmutter Canc Ctr, Langone Med Ctr, New York, NY 10016 USA

[13] Sch Med, New York, NY 10016 USA

[14] Maine Med Ctr, Dept Neurol, Portland, ME 04074 USA

[15] IMRIS, Deerfield Imaging, Minnetonka, MN 55343 USA

来源：

NPJ PRECISION ONCOLOGY | 2017年 / 1卷

基金：

美国国家卫生研究院; 芬兰科学院;

关键词：

MAGNETIC-RESONANCE-SPECTROSCOPY; RESPONSE ASSESSMENT; TUMOR VASCULATURE; H-1; MRSI; CANCER; PSEUDOPROGRESSION; CLASSIFICATION; PSEUDORESPONSE; NEUROONCOLOGY; NORMALIZATION;

D O I：

10.1038/s41698-017-0020-3

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Precise assessment of treatment response in glioblastoma during combined anti-angiogenic and chemoradiation remains a challenge. In particular, early detection of treatment response by standard anatomical imaging is confounded by pseudo-response or pseudo-progression. Metabolic changes may be more specific for tumor physiology and less confounded by changes in blood-brain barrier permeability. We hypothesize that metabolic changes probed by magnetic resonance spectroscopic imaging can stratify patient response early during combination therapy. We performed a prospective longitudinal imaging study in newly diagnosed glioblastoma patients enrolled in a phase II clinical trial of the pan-vascular endothelial growth factor receptor inhibitor cediranib in combination with standard fractionated radiation and temozolomide (chemoradiation). Forty patients were imaged weekly during therapy with an imaging protocol that included magnetic resonance spectroscopic imaging, perfusion magnetic resonance imaging, and anatomical magnetic resonance imaging. Data were analyzed using receiver operator characteristics, Cox proportional hazards model, and Kaplan-Meier survival plots. We observed that the ratio of total choline to healthy creatine after 1 month of treatment was significantly associated with overall survival, and provided as single parameter: (1) the largest area under curve (0.859) in receiver operator characteristics, (2) the highest hazard ratio (HR = 85.85, P = 0.006) in Cox proportional hazards model, (3) the largest separation (P = 0.004) in Kaplan-Meier survival plots. An inverse correlation was observed between total choline/healthy creatine and cerebral blood flow, but no significant relation to tumor volumetrics was identified. Our results suggest that in vivo metabolic biomarkers obtained by magnetic resonance spectroscopic imaging may be an early indicator of response to anti-angiogenic therapy combined with standard chemoradiation in newly diagnosed glioblastoma.

引用

页数：9

共 42 条

[31]

Nelson SJ, 2003, MOL CANCER THER, V2, P497

[32] Post-Treatment Imaging Changes in Primary Brain Tumors [J].

O'Brien, Barbara J. ;

Colen, Rivka R. .

CURRENT ONCOLOGY REPORTS, 2014, 16 (08)

[33] WET, A T-1-INSENSITIVE AND B-1-INSENSITIVE WATER-SUPPRESSION METHOD FOR IN-VIVO LOCALIZED H-1-NMR SPECTROSCOPY [J].

OGG, RJ ;

KINGSLEY, PB ;

TAYLOR, JS .

JOURNAL OF MAGNETIC RESONANCE SERIES B, 1994, 104 (01) :1-10

[34]

Ostrom QT, 2014, NEURO-ONCOLOGY, V16, P1, DOI [10.1093/neuonc/nou327, 10.1093/neuonc/nou223, 10.1093/neuonc/nox158, 10.1093/neuonc/nov189]

[35] Clinical Proton MR Spectroscopy in Central Nervous System Disorders [J].

OZ, Gulin ;

Alger, Jeffry R. ;

Barker, Peter B. ;

Bartha, Robert ;

Bizzi, Alberto ;

Boesch, Chris ;

Bolan, Patrick J. ;

Brindle, Kevin M. ;

Cudalbu, Cristina ;

Dincer, Alp ;

Dydak, Ulrike ;

Emir, Uzay E. ;

Frahm, Jens ;

Gonzalez, Ramon Gilberto ;

Gruber, Stephan ;

Gruetter, Rolf ;

Gupta, Rakesh K. ;

Heerschap, Arend ;

Henning, Anke ;

Hetherington, Hoby P. ;

Howe, Franklyn A. ;

Hueppi, Petra S. ;

Hurd, Ralph E. ;

Kantarci, Kejal ;

Klomp, Dennis W. J. ;

Kreis, Roland ;

Kruiskamp, Marijn J. ;

Leach, Martin O. ;

Lin, Alexander P. ;

Luijten, Peter R. ;

Marjanska, Malgorzata ;

Maudsley, Andrew A. ;

Meyerhoff, Dieter J. ;

Mountford, Carolyn E. ;

Nelson, Sarah J. ;

Pamir, M. Necmettin ;

Pan, Jullie W. ;

Peet, Andrew C. ;

Poptani, Harish ;

Posse, Stefan ;

Pouwels, Petra J. W. ;

Ratai, Eva-Maria ;

Ross, Brian D. ;

Scheenen, Tom W. J. ;

Schuster, Christian ;

Smith, Ian C. P. ;

Soher, Brian J. ;

Tkac, Ivan ;

Vigneron, Daniel B. ;

Kauppinen, Risto A. .

RADIOLOGY, 2014, 270 (03) :658-679

[36] Automatic quantitation of localized in vivo 1H spectra with LCModel [J].

Provencher, SW .

NMR IN BIOMEDICINE, 2001, 14 (04) :260-264

[37] Impact of imaging measurements on response assessment in glioblastoma clinical trials [J].

Reardon, David A. ;

Ballman, Karla V. ;

Buckner, Jan C. ;

Chang, Susan M. ;

Ellingson, Benjamin M. .

NEURO-ONCOLOGY, 2014, 16 :24-35

[38] Anti-VEGF/VEGFR Therapy for Cancer: Reassessing the Target [J].

Sitohy, Basel ;

Nagy, Janice A. ;

Dvorak, Harold F. .

CANCER RESEARCH, 2012, 72 (08) :1909-1914

[39] Response criteria for glioma [J].

Sorensen, A. Gregory ;

Batchelor, Tracy T. ;

Wen, PatrickY ;

Zhang, Wei-Ting ;

Jain, Rakesh K. .

NATURE CLINICAL PRACTICE ONCOLOGY, 2008, 5 (11) :634-644

[40] A "Vascular Normalization Index" as Potential Mechanistic Biomarker to Predict Survival after a Single Dose of Cediranib in Recurrent Glioblastoma Patients [J].

Sorensen, A. Gregory ;

Batchelor, Tracy T. ;

Zhang, Wei-Ting ;

Chen, Poe-Jou ;

Yeo, Priscilla ;

Wang, Meiyun ;

Jennings, Dominique ;

Wen, Patrick Y. ;

Lahdenranta, Johanna ;

Ancukiewicz, Marek ;

di Tomaso, Emmanuelle ;

Duda, Dan G. ;

Jain, Rakesh K. .

CANCER RESEARCH, 2009, 69 (13) :5296-5300

← 1 2 3 4 5 →