18F-FLT PET During Radiotherapy or Chemoradiotherapy in Head and Neck Squamous Cell Carcinoma Is an Early Predictor of Outcome

Bianca A.W. Hoeben; Esther G.C. Troost; Paul N. Span; Carla M.L. van Herpen; Johan Bussink; Wim J.G. Oyen; Johannes H.A.M. Kaanders

doi:10.2967/jnumed.112.105999

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FIGURE 1.
Box plots of SUV_max(9) (A), GTV_VIS (B), GTV_SBR (C), and GTV_50% (D) on consecutive ¹⁸F-FLT PET/CT scans. Bottom and top of each box are lower and upper quartiles. Black band near middle of box is median. Extremes of lower and higher whiskers represent range of minimum and maximum values. *P ≤ 0.001, Wilcoxon signed-rank test.
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FIGURE 2.
¹⁸F-FLT PET/CT before therapy (A and D), in second week of therapy (B and E), and in fourth week of therapy (C and F). First example (A–C) shows slow decrease in ¹⁸F-FLT uptake (cT4N2bM0 supraglottic laryngeal carcinoma treated with chemoradiotherapy; local recurrence after 7 mo; later distant metastases) and second one (D–F) fast decrease (cT3N1M0 supraglottic laryngeal carcinoma treated with radiotherapy only; no tumor-related event after 32 mo of follow-up). For GTV_VIS (green), 3-dimensional volume change was +8% between A and B, −35% between A and C, −60% between D and E, and −66% between D and F. For GTV_SBR (yellow), 3-dimensional volume change was +7% between A and B, +4% between A and C, −44% between D and E, and +22% between D and F. For GTV_50% (red), 3-dimensional volume change was +11% between A and B, +102% between A and C; +30% between D and E, and +247% between D and F. SUV_max(9) changed by −35% between A and B, −70% between A and C, −58% between D and E, and −69% between D and F.
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FIGURE 3.
SUV_max(9) above or below 45% decrease between scans 1 and 2 for entire group of patients. P = 0.035.
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FIGURE 4.
GTV_VIS decrease above or below median between scans 1 and 2 for all patients (A), radiotherapy group (B), and chemoradiotherapy group (C). P = 0.037, 0.203, and 0.039, respectively.

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TABLE 1

Patient Characteristics and Events

Characteristic	Data
Age at baseline PET (y)
Mean	60
Range	39–75
Sex (n = 48)
Female	10 (21)
Male	38 (79)
Smoking (n = 48)
Active	33 (69)
Former	12 (25)
Unknown	3 (6)
Alcohol use (n = 48)
Active	35 (73)
Former	4 (8)
Never	4 (8)
Unknown	5 (10)
T stage (n = 50)
1	1 (2)
2	25 (50)
3	17 (34)
4	7 (14)
N stage (n = 50)
0	22 (44)
1	6 (12)
2a	—
2b	11(22)
2c	11 (22)
International Union Against Cancer stage (n = 50)
II	12 (24)
III	13 (26)
IVA	25 (50)
Histologic grade (n = 50)
1	4 (8)
2	26 (52)
3	11 (22)
Unknown	9 (18)
Primary tumor site (n = 50)
Oral cavity	1 (2)
Oropharynx	27 (54)
Larynx	14 (28)
Hypopharynx	8 (16)
Treatment (n = 48)
Radiotherapy	33 (69)
Chemoradiotherapy	15 (31)
No. of events tumor-related (n = 48)
Locoregional recurrence	7 (15)
Distant metastases^*	4 (8)
Tumor-related death	7 (15)
No. of events not tumor-related (n = 48)
Death due to another cause	6 (13)
Second primary tumor after start of study^†	8 (17)

↵* Distant metastases (pulmonal, skeletal, cerebral, and cutaneous) were detected after 7, 9, and 11 mo.
↵† Second primary tumors were located in head and neck area, lungs, esophagus, rectum, bladder, and skin.
Data are numbers of patients, with percentages in parentheses, except for age, which is years.

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TABLE 2

Outcome as Function of (Changes in) PET/CT Parameters

		P
Parameter	Best group by cutoff level	3-y LRC	3-y DFS	3-y OS
All patients
SUV_max(9) 1	SUV_max(9) ≥ 6.1^*	0.17	0.12	0.52
GTV_CT 1	GTV_CT < 6.5 cm³	100 (80–100) vs. 76 (60–92): 0.044^†	0.27	0.13
GTV_VIS 1	GTV_VIS < 6.5 cm³	100 (75–100) vs. 79 (65–93): 0.092	0.20	0.26
Δ SUV_max(9) 1–2	Decrease ≥ 45%^‡	92 (80–100) vs. 72 (51–93): 0.066	88 (75–100) vs. 63 (41–85): 0.035^†	0.23
Δ GTV_VIS 1–2	Decrease ≥ 41%^*	0.21	91 (80–100) vs. 65 (46–84): 0.037^†	0.86
Δ GTV_VIS 1–3	Decrease ≥ 78%^*	100 (78–100) vs. 68 (41–94): 0.021^†	100 (78–100) vs. 56 (30–83): 0.005^†	80 (54–100) vs. 48 (6–89): 0.084
Radiotherapy
SUV_max(9) 1	SUV_max(9) < 6.6^‡	95 (85–100) vs. 70 (41–99): 0.075	90 (77–100) vs. 59 (31–87): 0.044^†	0.59
GTV_CT 1	GTV_CT < 6.5 cm³	100 (79–100) vs. 73 (50–96): 0.048^†	0.26	0.25
GTV_VIS 1	GTV_VIS < 6.5 cm³	0.11	0.20	0.44
Δ SUV_max(9) 1–2	Decrease ≥ 45%	0.48	0.20	0.65
Δ GTV_VIS 1–2	Decrease ≥ 47%^*	0.95	0.20	0.27
Δ GTV_VIS 1–3	Decrease > 77%^*	100 (72–100) vs. 66 (34–98): 0.05	100 (72–100) vs. 53 (23–83): 0.013^†	0.12
Chemoradiotherapy
SUV_max(9) 1	SUV_max(9) ≥ 6.6^*	100 (63–100) vs. 57 (20–94): 0.044^†	100 (63–100) vs. 57 (20–94): 0.044^†	100 (63–100) vs. 57 (8–100): 0.080
GTV_CT 1	GTV_CT < 6.5 cm³	0.63	0.63	0.66
GTV_VIS 1	GTV_VIS < 6.5 cm³	0.63	0.63	0.66
Δ SUV_max(9) 1–2	Decrease ≥ 45%	100 (54–100) vs. 57 (20–94): 0.081	100 (54–100) vs. 57 (20–94): 0.081	100 (54–100) vs. 57 (8–100): 0.10
Δ GTV_VIS 1–2	Decrease ≥ 31%^*	100 (59–100) vs. 50 (10–90): 0.039^†	100 (59–100) vs. 50 (10–90): 0.039^†	100 (59–100) vs. 56 (7–100): 0.079
Δ GTV_VIS 1–3	Not tested^§	Not tested^§	Not tested^§	Not tested^§

↵* Dichotomization by median value.
↵† P < 0.05.
↵‡ Dichotomization value found through receiver-operating-characteristic analysis.
↵§ Too few subjects for testing (n = 7).
GTV_CT = visually delineated gross tumor volume on CT; Δ = difference between baseline scans (1) and subsequent scans (2 or 3).
Numbers after PET/CT parameters refer to first, second, or third scan. For survival data with P ≤ 0.1, 3-y survival data per group are given (%), with 95% CI in parentheses; for survival differences with P > 0.1, only P value is given.