Perfusion MRI-Based Fractional Tumor Burden Differentiates between Tumor and Treatment Effect in Recurrent Glioblastomas and Informs Clinical Decision-Making

M. Iv; X. Liu; J. Lavezo; A.J. Gentles; R. Ghanem; S. Lummus; D.E. Born; S.G. Soltys; S. Nagpal; R. Thomas; L. Recht; N. Fischbein

doi:10.3174/ajnr.A6211

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Fig 1.
Representative examples of treatment effect (upper row) and recurrent tumor (lower row) in 2 patients with previously resected and irradiated glioblastomas. Contrast-enhancing lesions on postcontrast T1-weighted (A and E) and ΔT1 (B and F) images. Output FTB maps superimposed on the contrast-enhanced T1-weighted images (C and G). Blue represents areas of low blood volume (FTB_low), and red represents areas of high blood volume (FTB_high). Histograms (D and H) show all voxels of the contrast-enhancing volume classified into the respective FTB_low, FTB_mid (yellow), and FTB_high classes, which is based on the rCBV thresholds of 1.0 and 1.75.
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Fig 2.
Boxplots of the relationship between FTB and normalized rCBV in 2 histopathologically defined groups: treatment effect and recurrent tumor. Open circles and squares represent individual measurements. The upper and lower limits of the whiskers represent the minimum and maximum of all of the data. Double asterisks indicate P < .01; triple asterisks, P < .001.
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Fig 3.
Receiver operating characteristic curves for the use of fractional tumor burden classes and normalized rCBV to differentiate tumor from treatment effect.
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Fig 4.
Agreement between the consensus (among 5 physician raters) qualitative interpretation of imaging and the actual histopathologic diagnosis (A). Agreement between the hypothetic consensus decision to change treatment plans and the actual (real-time) management plans (B and C).

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Table 1:

Patient demographics and clinicopathologic information^{^a}

	TE (n = 17)	Tumor (n = 30)	Total (n = 47)
Age (yr)
Mean (SD)	56 (10)	55 (13)	55 (12)
Range	38-77	20-80	20-80
Sex
Male	11 (65%)	18 (60%)	29 (62%)
Female	6 (35%)	12 (40%)	18 (38%)
Interval time between end or radiation therapy and surgery (mo)
Median (range)	11.4 (0.6-60.4)	10.7 (1.3-101.5)	10.9 (0.6-101.5)
Bevacizumab at time of surgery^{^b}	2 (12%)	3 (10%)	5 (11%)
Surgical procedure
Biopsy	3 (18%)	4 (13%)	7 (15%)
>90% resection	3 (18%)	9 (30%)	12 (25%)
Gross total resection	11 (64%)	17 (57%)	28 (60%)
HGG histopathology
Anaplastic astrocytoma, WHO grade III	2 (12%)	0	2 (4%)
Glioblastoma, WHO grade IV	15 (88%)	29 (97%)	44 (94%)
Gliosarcoma, WHO grade IV	0	1 (3%)	1 (2%)
HGG molecular features
IDH wild type	11 (65%)	11 (37%)	22 (47%)
IDH mutant	0	2 (7%)	2 (4%)
Unknown IDH status	6 (35%)	17 (56%)	23 (49%)
MGMT-unmethylated	6 (35%)	15 (50%)	21 (45%)
MGMT-methylated	6 (35%)	8 (27%)	14 (30%)
Unknown MGMT status	5 (30%)	7 (23%)	12 (25%)

Note:—IDH indicates isocitrate dehydrogenase; MGMT, O-6-methylguanine-DNA methyltransferase; WHO, World Health Organization.
↵a Percentage values in parentheses for sex, bevacizumab at time of the operation, surgical procedure, HGG histopathology, and HGG molecular features are percentages relative to the number of patients in each column.
↵b Patient received a dose of bevacizumab within 1 month of the surgical procedure for suspected recurrence.

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Table 2:
Mean values of FTB classes and normalized rCBV in histopathologically defined treatment effect and tumor groups^{^a}
TE Tumor P Values
FTB_low 54.8 (22.3) 33.1 (20.8) .002
FTB_mid 27.0 (15.4) 21.3 (11.3) .16
FTB_high 18.2 (14.4) 45.5 (22.6) <.001
rCBV 1.2 (0.6) 2.1 (1.0) <.001
↵a Values are reported as mean (SD), except for P values.