Prognostic Significance of Dynamic 18F-FET PET in Newly Diagnosed Astrocytic High-Grade Glioma

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FIGURE 1.
Time–activity curves of ¹⁸F-FET uptake were evaluated slice by slice throughout entire tumor to assess TTP_min. (A) Example of decreasing curve with early peak after 4 min. (B) Example of late peak after 17.5 min.
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FIGURE 2.
Kaplan–Meier estimates for PFS (A) and OS (B) of patients with newly diagnosed astrocytic HGG. Plots show significantly longer PFS and OS for patients with late TTP_min > 12.5 min than for patients with short TTP_min ≤ 12.5 min (P = 0.006 for PFS and P = 0.001 for OS).
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FIGURE 3.
Kaplan–Meier estimates for PFS (A) and OS (B) of patients with newly diagnosed astrocytic HGG show significantly increased PFS and OS for WHO III astrocytoma patients with late TTP_min > 12.5 min (P < 0.001 for PFS and OS), whereas those with short TTP_min ≤ 12.5 min had outcome comparable to glioblastoma patients (P = 0.92 for PFS and P = 0.30 for OS).

TABLE 1

Overview of Clinical and FET PET Parameters According to WHO Group

Parameter	All HGG	WHO III	WHO IV	P
Patients (n)	121	51	70	NS
Age (y)	54.0	46.9	59.1	≤0.001
Sex
Male (n)	73	32	41	NS
Female (n)	48	19	29
MGMT
Methylated (n)	66	33	33	0.022
Unmethylated (n)	43	12	31
Not available (n)	12	6	6
Contrast enhancement on MR imaging
Yes (n)	95	25	70	≤0.001
No (n)	26	26	0
Surgical resection (n)	33	6	27	≤0.001
Radiochemotherapy^* (n)	82	17	65	≤0.001
Chemotherapy^† (n)	23	21	2	≤0.001
Radiotherapy (60 Gy) (n)	13	11	2	≤0.001
Brachytherapy (n)	2	2	0	NS
Palliative treatment (n)	1	0	1	NS
¹⁸F-FET PET parameters
SUV_max/BG	3.4 ± 0.1	3.0 ± 0.2	3.7 ± 0.1	0.004
SUV_mean/BG	2.2 ± 0.1	2.1 ± 0.1	2.3 ± 0.1	0.008
BTV (mL)	20.6 ± 1.9	13.1 ± 2.6	25.5 ± 2.6	0.002
TTP_min
≤12.5 min (n)	72	22	50	0.016
>12.5 min (n)	39	21	18
Not available (n)	10	8	2

NS = not statistically significant.
↵* Radiotherapy with concomitant and adjuvant temozolomide (60 Gy; 75 mg/m² of body surface area, 5 of 7 d per week, 6 wk) according to the European Organisation for Research and Treatment of Cancer and the National Cancer Institute of Canada (1,2).
↵† 19 temozolomide, 4 vincristine.

TABLE 2

P Values for Determination of Prognostic Factors Regarding OS

Parameter	P	HR	95% CI
Age (≥55 vs. <55 y)	<0.001	2.38	1.54–3.68
Sex (male vs. female)	0.16	1.35	0.89–2.06
Karnofsky performance score (<90 vs. ≥90)	0.21	1.72	0.74–4.03
WHO (IV vs. III)	<0.001	2.56	1.61–4.06
MGMT promoter methylation (no vs. yes)	<0.001	2.89	1.83–4.57
Contrast enhancement (yes vs. no)	0.01	2.32	1.23–4.36
Initial treatment (radiotherapy vs. chemotherapy vs. radiochemotherapy)	<0.001	1.87	1.38–2.53
Surgical resection (no vs. yes)	0.90	1.03	0.65–1.63
SUV_max/BG	0.27	1.12	0.92–1.35
SUV_mean/BG	0.42	1.22	0.76–1.96
BTV	0.11	1.01	1.00–1.02
TTP_min (≤12.5 min vs. >12.5 min)	0.001	2.25	1.38–3.67

HR = hazard ratio; CI = confidence interval.
P values were derived from univariate Cox regression for continuous parameters and Log rank test for categoric parameters.

TABLE 3

P Values of Prognostic Factors in Multivariate Analysis Regarding OS

Parameter	P	HR	95% CI
Age (≥55 vs. <55 y)	0.015	1.82	1.12–2.94
MGMT promoter methylation (no vs. yes)	<0.001	2.78	1.71–4.50
TTP_min (≤12.5 min vs. >12.5 min)	0.009	2.04	1.20–3.48
Age (≥55 vs. <55 y)	0.007	1.95	1.02–3.17
MGMT promoter methylation (no vs. yes)	<0.001	2.73	1.70–4.39
WHO (IV vs. III)	0.042	1.73	1.02–2.93
Age (≥55 vs. <55 y)	0.026	1.73	1.07–2.68
MGMT promoter methylation (no vs. yes)	<0.001	2.62	1.61–4.27
WHO (IV vs. III)	0.150	1.49	0.87–2.56
TTP_min (≤12.5 min vs. >12.5 min)	0.023	1.89	1.09–3.22

HR = hazard ratio; CI = confidence interval.
P values were derived from multivariate Cox regression.
The two alternative models, excluding either WHO grade or TTP_min as a factor, reached a similar fit. In the model with both factors, TTP_min remains significant.