Whole-Skeleton SUVmean Measured on 18F-NaF PET/CT Studies as a Prognostic Indicator in Patients with Breast Cancer Metastatic to Bone

José Flávio Gomes Marin; Paulo Schiavom Duarte; Monique Beraldo Ordones; Heitor Naoki Sado; Marcelo Tatit Sapienza; Carlos Alberto Buchpiguel

doi:10.2967/jnmt.121.262907

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FIGURE 1.
wsVOI (A) and coronal maximum-intensity-projection ¹⁸F-NaF PET/CT image (B) of patient with a few metastatic sites in skeleton (double arrowheads). Patient presented with whole-skeleton SUV_mean of 2.20 and was still alive 1,974 d after study.
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FIGURE 2.
wsVOI (A) and coronal maximum-intensity-projection ¹⁸F-NaF PET/CT image (B) of patient with multiple metastatic sites in skeleton. Patient presented with whole-skeleton SUV_mean of 3.58 and died 153 d after study.
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FIGURE 3.
wsVOI (A) and coronal maximum-intensity-projection ¹⁸F-NaF PET/CT image (B) of patient with widespread metastatic bone disease characterized by diffuse and heterogeneous uptake of radiopharmaceutical in axial and proximal appendicular skeleton. Patient presented with whole-skeleton SUV_mean of 4.78 and died 66 d after study. In this case, wsVOI was not able to detect right hand and some fingers of left hand.
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FIGURE 4.
Kaplan–Meier curves for whole-skeleton SUV_mean (A) and SUV_max (B), estrogen receptor status (C), and alkaline phosphatase level (D). y-axis displays OS probability, and x-axis displays OS time in days. Cutoffs for division of variables into 2 comparison groups are presented in Table 3 and in figure. Statistical significance of OS differences between groups are presented in Table 4 and in figure. + = censored patients; ALP = alkaline phosphatase level.

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TABLE 1.

Patient Characteristics

Characteristic	Mean	SD	Minimum	Maximum
Follow-up time (d)	941.9	578.4	21	2,711
wsSUV_max	48.5	22.6	6.2	144.2
wsSUV_mean	3.2	0.9	0.3	6.1
Age (y)	56.9	13.4	27.4	88.2
Creatinine level (mg/dL)	0.7	0.3	0.3	2.7
CA15-3 level (units/mL)	438.1	1,412.4	7.0	12,000.0
ALP level (units/L)	142.1	133.8	21.1	955.0
Diagnosis to PET (d)	1,194.7	1,451.9	−1*	6,794

*¹⁸F-NaF PET/CT was performed before result of pathologic study confirmed cancer diagnosis.
wsSUV_max = whole-skeleton SUV_max; wsSUV_mean = whole-skeleton SUV_mean; ALP = alkaline phosphatase.

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TABLE 2.

Visceral Metastasis Status, Hormone Status, and Histologic Subtype

Characteristic	Data
VM
Absent	131 (74)
Present	45 (26)
Missing	0 (0)
Estrogen receptor
Absent	18 (10)
Present	156 (89)
Missing	2 (1)
Progesterone receptor
Absent	41 (23)
Present	130 (74)
Missing	5 (3)
HER-2 expression
Absent	139 (79)
Present	35 (20)
Missing	2 (1)
Histologic subtype
IDC	153 (87)
ILC	14 (8)
Other	4 (2.3)
Missing	5 (2.8)

VM = visceral metastases; IDC = invasive ductal carcinoma; ILC = invasive lobular carcinoma.
Data are number followed by percentage in parentheses.

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TABLE 3.

Results of Univariate Analyses

Variable	Group 1	Group 2	n in group 1	P
wsSUV_max	≤32.8	>32.8	42 (24%)	0.02*^§
wsSUV_mean	≤3.13	>3.13	97 (55%)	<0.01*^§
Age (y)	≤56	>56	91 (52%)	0.48*
Creatinine (mg/dL)	≤0.83	>0.83	135 (77%)	0.57*
CA15-3 (units/mL)	≤19.0	>19.0	20 (11%)	0.02*^§
ALP (units/L)	≤131	>131	118 (67%)	<0.01*^§
VM	Absent	Present	131 (74%)	0.15^†
Estrogen receptor	Absent	Present	18 (10%)^‡	0.01^†§
Progesterone receptor	Absent	Present	41 (24%)^‡	0.77^†
HER-2 expression	Absent	Present	139 (80%)^‡	0.24^†
Histologic subtype	IDC	ILC	153 (92%)^‡	0.40^†

wsSUVmax = whole-skeleton SUV_max; wsSUVmean = whole-skeleton SUV_mean; ALP = alkaline phosphatase; VM = visceral metastases; IDC = invasive ductal carcinoma; ILC = invasive lobular carcinoma.
* Calculated using Lausen test.
↵^†Calculated using log rank test.
↵^‡In relation to 2 groups compared (excluding missing data and other groups).
^§Variables selected for multivariate analysis (P ≤ 0.1).
Variables were divided into 2 groups for OS comparison. Numbers of individuals in group 1, and P values of difference in OS between 2 groups, are also presented.

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TABLE 4.

Results of Cox Regression Evaluating Association of Variables Selected in Univariate Analyses with OS

Variable	Group	HR	95% CI	P
wsSUV_max	>32.8	1.60	1.00–2.57	0.05*
wsSUV_mean	>3.13	1.57	1.10–2.24	0.01*
CA15-3 level (units/mL)	>19.0	1.26	0.66–2.42	0.48
ALP level (units/L)	>131	2.14	1.47–3.12	<0.01*
Estrogen receptor	Present	0.59	0.35–1.01	0.05*

* Independent variables on Cox regression (P ≤ 0.05).
wsSUV_max = whole-skeleton SUV_max; wsSUV_mean = whole-skeleton SUV_mean; ALP = alkaline phosphatase; HR = hazard ratio.