Prediction of Pretreatment 18F-FDG-PET/CT Parameters on the Outcome of First-Line Therapy in Patients with Metastatic Breast Cancer

Figures & data

Table 1 Patients’ Characteristics at Baseline

Characteristics	MBC, n=177, n (%)
Age, years
Median (range)	53 (29–74)
Menopausal status
Postmenopausal	105 (59.3)
Premenopausal	72 (40.7)
De novo	68 (38.4)
Disease‐free interval, months
< 24	49 (27.7)
≥ 24	60 (33.9)
Subgroups
HR+/HER2-	87 (58.2)
HER2+	30 (16.9)
Triple-negative	60 (33.9)
Number of metastatic sites
1	51 (28.9)
2	62 (35.0)
≥ 3	64 (36.1)
Metastatic sites
Liver	33 (18.6)
Lung	67 (37.9)
Bone	94 (53.1)
Visceral disease	96 (54.2)
First-line treatment
Endocrine therapy	44 (24.9)
Anti-HER2 therapy	29 (16.4)
Chemotherapy	104 (58.7)

Abbreviations: HR+, hormone receptor positive; HER2-, human epidermal growth factor receptor 2 negative.

Table 2 Analysis of Risk Factors Associated with PFS in the Whole Population

Factors	n	PFS, Months (95% CI)	P value	HR (95% CI)
Clinical risk factors
Age, years
< 53	88	11.3 (9.6–13.1)	0.813	1.040 (0.749–1.444)
≥ 53	89	12.2 (9.3–12.0)
Menstruation status
Postmenopausal	105	11.9 (7.8–16.0)	0.326	1.184 (0.845–1.660)
Premenopausal	72	12.0 (9.2–14.8)
De novo
Yes	68	14.6 (10.7–18.6)	0.098	0.745 (0.525–1.056)
No	109	11.1 (9.2–13.0)
Subgroups
HR+/HER2-	87	15.6 (13.8–17.3)	0.002	Reference 1.096 (0.673–1.786) 1.808 (1.255–2.607)
HER2+	30	11.9 (8.0–15.8)
Triple-negative	60	8.3 (7.2–9.9)
Disease‐free interval, months
< 24	49	9.5 (6.5–12.6)	0.512	1.146 (0.762–1.725)
≥ 24	60	12.0 (8.6–15.4)
Number of metastatic sites
1	51	12.9 (9.6–16.2)	0.048	Reference 0.790 (0.579–1.201) 1.493 (0.996–2.237)
2	62	15.4 (10.8–20.0)
≥3	64	8.7 (6.0–11.4)
PET/CT parameters
SUVmax
< 10.35	88	14.6 (12.0–17.3)	0.028	1.446 (1.042–2.008)
≥ 10.35	89	8.3 (6.2–11.2)
SUVmean
< 4.79	88	14.9 (12.2–17.6)	0.005	1.609 (1.157–2.237)
≥ 4.79	89	8.3 (6.1–10.6)
MTV (mL)
< 53.46	88	12.9 (9.3–16.5)	0.017	1.494 (1.074–2.078)
≥ 53.46	89	11.5 (8.0–15.0)
TLG (g)
< 232.85	88	14.0 (10.6–17.5)	0.026	1.452 (1.045–2.019)
≥ 232.85	89	11.3 (8.2–14.4)
HI
< 2.04	88	12.9 (10.3–15.5)	0.035	1.424 (1.026–1.978)
≥ 2.04	89	10.1 (6.9–13.3)

Abbreviations: PFS, progression-free survival; HR, hazard ratio; CI, confidence interval; HR+, hormone receptor positive; HER2-, human epidermal growth factor receptor 2 negative; PET/CT, positron emission tomography/computed tomography; SUVmax, maximum standard uptake value; SUVmean, mean standard uptake value; MTV, metabolic volume measurements; TLG, total lesion glycolysis; HI, heterogeneity index.

Table 3 Analysis of PET Parameters Associated with PFS in Patients with De novo Stage IV

In Patients with De novo Stage IV
Factors	n	PFS, Months (95% CI)	P value	HR (95% CI)
SUVmax
< 12.79	34	17.2 (4.0–30.4)	0.177	1.475 (0.839–2.593)
≥ 12.79	34	8.2 (3.9–12.4)
SUVmean
< 5.28	34	22.7 (9.5–35.9)	0.110	1.590 (0.900–2.809)
≥ 5.28	34	10.7 (6.3–14.8)
MTV (mL)
< 109.93	34	18.4 (5.6–31.2)	0.343	1.320 (0.744–2.340)
≥ 109.93	34	13.1 (9.0–17.1)
TLG (g)
< 571.56	34	18.4 (2.7–34.1)	0.214	1.441 (0.810–2.563)
≥ 571.56	34	12.1 (9.3–14.8)
HI
< 2.67	34	25.4 (4.6–46.2)	0.001	2.821 (1.544–5.154)
≥ 2.67	34	8.2 (3.1–13.3)

Abbreviations: PET/CT, positron emission tomography/computed tomography; PFS, progression- free survival; HR, hazard ratio; CI, confidence interval; SUVmax, maximum standard uptake value; SUVmean, mean standard uptake value; MTV, metabolic volume measurements; TLG, total lesion glycolysis; HI, heterogeneity index.

Figure 1 Kaplan–Meier curve of progression-free survival for all patients stratified by SUVmax (A), SUVmean (B), MTV (C), TLG (D) and HI (E).

Abbreviations: SUVmax, maximum standardized uptake value; SUVmean, mean SUV; MTV, metabolic tumor volume; TLG, total lesion glycolysis; HI, heterogeneity index.

Figure 2 Kaplan–Meier curve of progression-free survival for patients with De novo stage IV stratified by HI.

Abbreviation: HI, heterogeneity index.

Table 4 Analysis of PET Parameters Associated with PFS in Patients with Different Molecular Subtypes

Factors	n	PFS, Months (95% CI)	P value	HR (95% CI)
In HR+/HER2- patients
SUVmax
< 9.08	43	16.4 (13.7–19.0)	0.293	1.282 (0.806–2.038)
≥ 9.08	44	14.9 (10.9–18.9)
SUVmean
< 4.56	43	17.2 (8.1–26.3)	0.070	1.539 (0.966–2.453_
≥ 4.56	44	14.5 (10.6–18.4)
MTV (mL)
< 53.46	43	16.5 (8.1–24.9)	0.203	1.355 (0.848–2.164)
≥ 53.46	44	14.9 (12.1–17.8)
TLG (g)
< 244.83	43	17.2 (8.7–25.7)	0.277	1.296 (0.812–2.069)
≥ 244.83	44	14.9 (11.7–18.2)
HI
< 2.24	43	21.7 (12.0–31.4)	0.025	1.711 (1.070–2.734)
≥ 2.24	44	13.0 (7.2–18.9)
In HER2+ patients
SUVmax
< 12.29	15	11.3 (4.7–14.9)	0.520	0.753 (0.318–1.784)
≥ 12.29	15	14.0 (8.3–19.8)
SUVmean
< 5.09	15	17.3 (6.4–28.3)	0.410	1.439 (0.606–3.419)
≥ 5.09	15	11.3 (9.3–13.3)
MTV (mL)
< 69.42	15	14.0 (1.5–35.4)	0.151	1.956 (0.783–4.884)
≥ 69.42	15	11.3 (9.3–13.4)
TLG(g)
< 353.85	15	14.0 (1.5–35.4)	0.151	1.956 (0.783–4.884)
≥ 353.85	15	11.3 (9.3–13.4)
HI
< 2.52	15	24.7 (2.0–61.3)	0.049	2.555 (1.006–6.493)
≥ 2.52	15	11.3 (6.7–16.0)
In triple-negative patients
SUVmax
< 11.17	30	10.2 (8.0–12.4)	0.030	1.862(1.061–3.267)
≥ 11.17	30	6.9 (3.8–10.0)
SUVmean
< 5.13	30	10.1 (8.0–12.1)	0.201	1.434 (0.825–2.494)
≥ 5.13	30	7.0 (4.7–9.3)
MTV (mL)
< 45.64	30	10.2 (7.8–12.5)	0.011	2.053 (1.177–3.579)
≥ 45.64	30	5.8 (2.7–8.8)
TLG (g)
< 232.85	30	9.5 (7.4–11.6)	0.023	1.901 (1.091–3.311)
≥ 232.85	30	6.9 (3.3–10.5)
HI
< 1.76	30	9.3 (8.2–10.4)	0.126	1.540 (0.886–2.675)
≥ 1.76	30	6.9(3.8–10.0)

Abbreviations: PET/CT, positron emission tomography/computed tomography; PFS, progression- free survival; HR, hazard ratio; CI, confidence interval; HR+, hormone receptor positive; HER2, human epidermal growth factor receptor 2 negative; SUVmax, maximum standard uptake value; SUVmean, mean standard uptake value; MTV, metabolic volume measurements; TLG, total lesion glycolysis; HI, heterogeneity index.

Figure 3 Kaplan–Meier curve of progression-free survival for HR+/HER2- patients stratified by HI.

Abbreviations: HR, hormone receptor, HER2, human epidermal growth factor receptor 2; HI, heterogeneity index.

Figure 4 Kaplan–Meier curve of progression-free survival for HER2+ patients stratified by HI.

Abbreviations: HER2, human epidermal growth factor receptor 2; HI, heterogeneity index.

Figure 5 Kaplan–Meier curve of progression-free survival for triple-negative patients stratified by SUVmax (A), MTV (B) and TLG (C).

Abbreviations: SUVmax, maximum standardized uptake value; MTV, metabolic tumor volume; TLG, total lesion glycolysis.

Figure 6 Representative images. (A–E): A 31‐year‐old female patient with HR+/HER2- MBC underwent PET/CT scan (A, maximum intensity projection image). We detected that the first lumbar vertebra lesion had the highest 18F‐FDG uptake in all metastatic lesions (B, CT image; C, PET image, SUVmax were 5.43), whereas the right axillary lymph node lesion had the lowest uptake (D, CT image; E, PET image, minimum FDG uptake across all lesions = 3.58). Therefore, HI of this patient was 1.52, and she had a median PFS of 57.4 months. (F–J): A 30‐year‐old female patient with HR+/HER2- MBC underwent 18F‐FDG PET/CT scan (F, maximum intensity projection image). We detected that the chest wall lesion had the highest 18F‐FDG uptake in all metastatic lesions (G, CT image; H, PET image, SUVmax = 15.71), whereas right axillary lymph node lesion had the lowest uptake (I, CT image; J, PET image, minimum FDG uptake = 3.79); Therefore, HI of this patient was 4.15, and she had a PFS of 5.2 months.

Abbreviations: HR, hormone receptor, HER2, human epidermal growth factor receptor 2; MBC, metastatic breast cancer; PET/CT; positron emission tomography/computed tomography; 18F‐FDG, 18F-fluorodeoxyglucose; SUVmax, maximum standardized uptake value; HI, heterogeneity index, PFS, progression-free survival.