The Benefits of High Relaxivity for Brain Tumor Imaging: Results of a Multicenter Intraindividual Crossover Comparison of Gadobenate Dimeglumine with Gadoterate Meglumine (The BENEFIT Study)

M. Vaneckova; M. Herman; M.P. Smith; M. Mechl; K.R. Maravilla; J. Weichet; M.V. Spampinato; J. Žižka; F.J. Wippold; J.J. Baima; R. Babbel; E. Bültmann; R.Y. Huang; J.-H. Buhk; A. Bonafé; C. Colosimo; S. Lui; M.A. Kirchin; N. Shen; G. Pirovano; A. Spinazzi

doi:10.3174/ajnr.A4468

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Fig 1.
A 53-year-old man with left parietal glioblastoma. Images acquired before (unenhanced T1SE, A) and after (T1SE, B; T1GRE, C) administration of 0.1-mmol/kg gadobenate. Images acquired before (unenhanced T1SE, D) and after (T1SE, E; T1GRE, F) administration of 0.1-mmol/kg gadoterate. Aggressive-appearing mass with inhomogeneous enhancement shows greater lesion enhancement on images obtained with gadobenate. All blinded readers scored gadobenate images significantly higher for global preference, internal morphology, and contrast enhancement.
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Fig 2.
A 77-year-old man with a left occipital anaplastic astrocytoma. Images acquired before (unenhanced T1SE, A) and after (T1SE, B; T1GRE, C) administration of 0.05-mmol/kg gadobenate. Images acquired before (unenhanced T1SE, D) and after (T1SE, E; T1GRE, F) administration of 0.1-mmol/kg gadoterate. A single irregular ring-enhancing mass is clearly seen in both examinations; similar appearances and lesion definition and size are seen in both. All blinded readers gave similar scores for global preference, border delineation, internal morphology, and contrast enhancement, indicating equivalence for 0.05-mmol/kg gadobenate versus 0.1-mmol/kg gadoterate.
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Fig 3.
Blinded reader comparison of percentage lesion enhancement (A) and LBR (B) after administration of gadobenate and gadoterate. Highly significant increases in quantitative enhancement were noted by all readers for patients receiving 0.1-mmol/kg gadobenate compared with 0.1-mmol/kg gadoterate (Arm 1), while no differences in enhancement were noted for patients receiving 0.05-mmol/kg gadobenate compared with 0.1-mmol/kg gadoterate (Arm 2).

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Table 1:

Final lesion diagnoses

Lesion Diagnosis	Arm 1: 0.1-mmol/kg Gadobenate vs 0.1-mmol/kg Gadoterate (n = 63)	Arm 2: 0.05-mmol/kg Gadobenate vs 0.1-mmol/kg Gadoterate (n = 96)
Anaplastic astrocytoma	1	1
Pilocytic astrocytoma	–	2
Low-grade astrocytoma	3	1
Oligoastrocytoma	1	3
High-grade glioma	1	1
Glioblastoma multiforme	10	18
Oligodendroglioma	2	–
Malignant lymphoma	1	3
Metastatic tumors, total	26	47
Lung	13	23
Breast	6	4
Melanoma	4	2
Ovarian	–	2
Kidney	1	3
Other	1	7
Unknown	1	6
Tumor (unknown origin)	–	3
Ependymoma	2	–
Meningioma	11	7
Schwannoma	2	1
Hemangioblastoma	1	5
Cystic craniopharyngioma	1	1
Acute disseminate encephalomyelitis	1	–
Neurofibromatosis	–	1
Capillary telangiectasia	–	1
Subdural hematoma	–	1

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Table 2:

Qualitative assessment of patients with brain tumors: intraindividual comparison of 0.1-mmol/kg gadobenate and 0.1-mmol/kg gadoterate^{^a}

Diagnostic Information End Point	Reader	Gadobenate Preferred	No Difference	Gadoterate Preferred	Significance (P Value)^{^b}	3-Reader Agreement κ Value (% Agreement)
Global diagnostic preference	1	31 (49.2%)	31 (49.2%)	1 (1.6%)	<.0001	0.273 (50.8%)
	2	51 (82.3%)	9 (14.5%)	2 (3.2%)	<.0001
	3	43 (69.4%)	17 (27.4%)	2 (3.2%)	<.0001
Lesion-border delineation	1	29 (46.0%)	33 (52.4%)	1 (1.6%)	<.0001	0.271 (44.3%)
	2	34 (54.8%)	27 (43.5%)	1 (1.6%)	<.0001
	3	25 (40.3%)	35 (56.5%)	2 (3.2%)	<.0001
Definition of disease extent	1	15 (23.8%)	48 (76.2%)	0	<.0001	0.286 (57.4%)
	2	18 (29.0%)	43 (69.4%)	1 (1.6%)	<.0001
	3	15 (24.2%)	45 (72.6%)	2 (3.2%)	.0023
Visualization of lesion internal morphology	1	10 (15.9%)	53 (84.2%)	0	.002	0.215 (54.1%)
	2	14 (22.6%)	48 (77.4%)	0	.0001
	3	23 (37.1%)	38 (61.3%)	1 (1.6%)	<.0001
Lesion contrast enhancement	1	31 (49.2%)	31 (49.2%)	1 (1.6%)	<.0001	0.249 (49.2%)
	2	51 (82.3%)	9 (14.5%)	2 (3.2%)	<.0001
	3	43 (69.4%)	17 (27.4%)	2 (3.2%)	<.0001

↵a Comparisons based on the number of patients with both postdose T1SE images assessed and technically adequate: n = 63 for reader 1, n = 62 for readers 2 and 3. Numbers in parentheses, except where noted, represent proportions of patients.
↵b Wilcoxon signed rank test.

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Table 3:

Qualitative assessment of patients with brain tumors: intraindividual comparison of 0.05-mmol/kg gadobenate and 0.1-mmol/kg gadoterate^{^a}

Diagnostic Information End Point	Reader	Gadobenate Preferred	No Difference	Gadoterate Preferred	Significance (P Value)^{^b}	3-Reader Agreement κ Value (% Agreement)
Global diagnostic preference	1	14 (14.6%)	75 (78.1%)	7 (7.3%)	.13	0.505 (63.4%)
	2	18 (19.2%)	56 (59.6%)	20 (21.3%)	.75
	3	15 (15.8%)	63 (66.3%)	17 (17.9%)	.73
Lesion-border delineation	1	11 (11.4%)	76 (79.2%)	9 (9.4%)	.824	0.493 (71.0%)
	2	12 (12.8%)	66 (70.2%)	16 (17.0%)	.46
	3	8 (8.4%)	77 (81.1%)	10 (10.5%)	.815
Definition of disease extent	1	6 (6.3%)	84 (87.5%)	6 (6.3%)	1.00	0.443 (79.6%)
	2	5 (5.3%)	83 (88.3%)	6 (6.4%)	1.00
	3	7 (7.4%)	80 (84.2%)	8 (8.4%)	1.00
Visualization of lesion internal morphology	1	4 (4.2%)	88 (91.7%)	4 (4.2%)	1.00	0.459 (84.9%)
	2	3 (3.2%)	87 (92.6%)	4 (4.3%)	1.00
	3	5 (5.3%)	82 (86.3%)	8 (8.4%)	.581
Lesion contrast enhancement	1	10 (10.4%)	77 (80.2%)	9 (9.4%)	1.00	0.531 (66.7%)
	2	18 (19.2%)	56 (59.6%)	20 (21.3%)	.75
	3	14 (14.7%)	64 (67.4%)	17 (17.9%)	.598

↵a Comparisons based on the number of patients with both postdose T1SE images assessed and technically adequate: n = 96 for reader 1, n = 94 for reader 2, and n = 95 for reader 3. Numbers in parentheses, except where noted, represent proportions of patients.
↵b Wilcoxon signed rank test.