Response Monitoring in Metastatic Breast Cancer: A Prospective Study Comparing 18F-FDG PET/CT with Conventional CT

Marianne Vogsen; Frederik Harbo; Nick M. Jakobsen; Henriette J. Nissen; Sara E. Dahlsgaard-Wallenius; Oke Gerke; Jeanette D. Jensen; Jon T. Asmussen; Anne Marie B. Jylling; Poul-Erik Braad; Werner Vach; Marianne Ewertz; Malene G. Hildebrandt

doi:10.2967/jnumed.121.263358

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FIGURE 1.
Flowchart of 87 women monitored by ¹⁸F-FDG PET/CT and CE-CT during first-line treatment for MBC. ^aCombined ¹⁸F-FDG PET/CT and CE-CT every 9–12 wk. ¹⁸F-FDG PET images not available during study period.
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FIGURE 2.
Illustration of progression detected by CE-CT and ¹⁸F-FDG PET/CT but seen first on ¹⁸F-FDG PET/CT. Shown are maximum-intensity projection images and percentage change in sum of diameters for CE-CT and RECIST 1.1 (blue line) and SUL_peak for ¹⁸F-FDG PET/CT and PERCIST (red line). New lesions are shown as yellow dots. CDK4/6 = cyclin-dependent kinase 4/6; PMD = progressive metabolic disease; PMR = partial metabolic response; PR = partial response; SLD = sum of lesion diameter.
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FIGURE 3.
Illustration of progression detected by CE-CT and ¹⁸F-FDG PET/CT simultaneously. Shown are maximum-intensity projection images and percentage change in sum of diameters for CE-CT and RECIST 1.1 (blue line) and SUL_peak for ¹⁸F-FDG PET/CT and PERCIST (red line). New lesions are shown as yellow dots. PMD = progressive metabolic disease; PMR = partial metabolic response; PR = partial response; SLD = sum of lesion diameter.
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FIGURE 4.
Illustration of progression detected by ¹⁸F-FDG PET/CT only. Shown are maximum-intensity projection images and percentage change in sum of diameters for CE-CT and RECIST 1.1 (blue line) and SUL_peak for ¹⁸F-FDG PET/CT and PERCIST (red line). New lesions are shown as yellow dots. CDK4/6 = cyclin-dependent kinase 4/6; PMD = progressive metabolic disease; PMR = partial metabolic response; PR = partial response; SLD = sum of lesion diameter.
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FIGURE 5.
Illustration of progression detected by CE-CT only. Shown are maximum-intensity projection images and percentage change in sum of diameters for CE-CT and RECIST 1.1 (blue line) and SUL_peak for ¹⁸F-FDG PET/CT and PERCIST (red line). New lesions are shown as yellow dots. CDK4/6 = cyclin-dependent kinase 4/6; PMR = partial metabolic response; SLD = sum of lesion diameter.
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FIGURE 6.
Kaplan–Meier estimates of time to detection of progression by CE-CT and ¹⁸F-FDG PET/CT (n = 87) (A) and from detection of progression by ¹⁸F-FDG PET/CT to detection by CE-CT (n = 43) (B).
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FIGURE 7.
Response categories for CE-CT and ¹⁸F-FDG PET/CT for 517 follow-up scans. Response categories from visual assessments are in gray. CR = complete (metabolic) response; NM = not measurable; PR = partial (metabolic) response; SD = stable (metabolic) disease.

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TABLE 1.

Time-Related Detection of Progression by CE-CT and ¹⁸F-FDG PET/CT for 87 Patients

Distribution of progression	n	Difference
Progression seen first on ¹⁸F-FDG PET/CT	43 (49.4%)	48%; 95% CI, 36%–60%; P < 0.0001
Progression on both modalities, seen first on ¹⁸F-FDG PET/CT	26 (29.9%)
Progression on ¹⁸F-FDG PET/CT only	17 (19.5%)
Progression seen first on CE-CT	1 (1.15%)	48%; 95% CI, 36%–60%; P < 0.0001
Progression on both modalities, seen first on CE-CT	0 (0.00%)
Progression on CE-CT only	1 (1.15%)
Progression on both modalities simultaneously	11 (12.6%)
No progression on any modality	32 (36.8%)

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TABLE 2.

Baseline Characteristics of 87 Patients with MBC

Characteristic	Data
Age at diagnosis of MBC (y)	72.7 (41.1–89.4)
Time from primary breast cancer to MBC (y)	5.13 (0.00–38.1)
MBC diagnosis
De novo MBC	27 (31.0%)
First distant relapse of MBC	60 (69.0)
ER status^*
Negative, 0%	12 (13.8)
Positive, 1%–100%	75 (86.2)
HER2 status^*
Normal	80 (92.0)
Positive	5 (5.75)
Unknown	2 (2.30)
Molecular subtype^*
ER+/HER2−	71 (81.6)
ER+/HER2 unknown	2 (2.30)
HER2+ (ER±)	5 (5.75)
Triple-negative	9 (10.3)
First-line treatment
Endocrine therapy^†	10 (11.5)
Endocrine therapy^† + cyclin-dependent kinase 4/6^‡	60 (69.0)
Chemotherapy^§	12 (13.8)
Chemotherapy^§ + trastuzumab + pertuzumab	4 (4.60)
Chemotherapy + pembrolizumab	1 (1.15)
Number of metastases^∥
1	1 (1.15)
2–4	7 (8.05)
≥5	79 (90.8)
Organs involved^∥
Bone only^¶	23 (26.4)
Lymph node only	4 (4.60)
Visceral involvement	22 (25.3)
Mixed (not visceral)^#	38 (43.7)

↵* Biomarker profile of metastatic lesion or concurrent local recurrence.
↵^† Aromatase inhibitor or fulvestrant.
↵^‡ Palbociclib, ribociclib, or abemaciclib.
↵^§ Epirubicin, cyclophosphamide, taxanes, carboplatin, gemcitabine, vinorelbine, or capecitabine.
↵^∥ Combined CE-CT and ¹⁸F-FDG PET/CT assessment.
↵^¶ Bone-only metastasis ± breast ± axillary lymph nodes.
↵^# Mixed bone, lymph node, lung, skin, or other metastases.
ER = estrogen receptor; HER2 = human epidermal growth receptor 2. Qualitative data are number and percentage; continuous data are median and range.

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TABLE 3.

Reasons for First Progression Detected by CE-CT and ¹⁸F-FDG PET/CT in Patients with Measurable Disease

Reason for first progression	CE-CT (n)	¹⁸F-FDG PET/CT (n)
New lesions only	13 (48.1%)	24 (55.8%)
Increase in SLD^* or SUL_peak^† only	7 (25.9%)	10 (23.3%)
New lesions and increase in SLD^* or SUL_peak^† (combined)	5 (18.5%)	6 (14.0%)
Unequivocal progression of nontarget lesions	2 (7.40%)	3 (6.98%)
Total	27 (100%)	43 (100%)