Article Figures & Data
Figures
- FIGURE 1.
Disease sites captured by HER2 and 18F-FDG PET. (A) 18F-FDG PET, MRI, and HER2 PET images from a patient with cerebellar metastasis. The images shown are from a patient with de novo metastatic HER2+ GEJ poorly differentiated carcinoma with mixed adeno and squamous differentiation. HER2 PET (right) demonstrated a right cerebellar metastasis (SUV 2.6) without corresponding uptake on 18F-FDG PET (left) and confirmed on brain MRI (middle). (B) Number of lesions identified by HER2 PET and 18F-FDG PET among all patients. Total number of lesions avid on HER2 PET (red) and 18F-FDG PET (blue) is shown. Total numbers of lesions better identified only on HER2 (orange) or 18F-FDG PET (green) are also shown.
- FIGURE 2.
HER2 disease heterogeneity illustrated by 89Zr-trastuzumab PET (HER2 PET). (A) 18F-FDG PET and HER2 PET images from a patient with metastatic HER2+ gastric adenocarcinoma with heterogeneous HER2 expression in the liver. Heterogeneous 89Zr-trastuzumab uptake on imaging is shown (blue arrows demonstrate positive lesions, upper figure). Liver biopsy at a site of 89Zr-trastuzumab uptake demonstrates HER2 positivity with immunohistochemistry 3+ in 60% of cells (lower). (B) The percentage of tumor load with 89Zr-trastuzumab uptake. Patients were stratified into 4 groups by percentage of tumor load showing tracer uptake. Total patients in groups A–D are shown in gray. Number of patients receiving first-line HER2-directed therapy in each group is represented in blue. Patients with at least 1 intense or very intense lesion on HER2 PET (SUV ≥ 10) are represented in red. Of the 15 patients with at least 1 intense or very intense lesion (15/33 [45%]), 6 were in group A (6/33 [18%]) and 7 were in group B (7/33 [21%]). (C) PFS stratified by percentage of tumor load positive in patients receiving first-line HER2-directed therapy (P = 0.353, using permutated log-rank test comparing the 2 groups). (D) PFS stratified by presence of at least 1 lesion with intense or very intense 89Zr-trastuzumab uptake (SUV ≥ 10) in patients receiving first-line HER2-directed therapy (P = 0.159, using permutated log-rank test comparing the 2 groups). IHC = immunohistochemistry.
- FIGURE 3.
89Zr-trastuzumab PET (HER2 PET) and early assessment of response to HER2-directed therapy. (A) 18F-FDG PET, HER2 PET, and HER2 immunohistochemistry (IHC) in a patient with metastatic HER2+ esophagogastric cancer with a long response to first-line HER2-directed therapy. Patient had > 50% of tumor load with 89Zr-trastuzumab uptake on baseline imaging (group B) and at least 1 lesion with SUV ≥ 10. Although primary tumor was avid on baseline HER2 and 18F-FDG PET, less than 3 wk after initiation of trastuzumab-based treatment, primary tumor remained 18F-FDG PET avid but was no longer avid on HER2 PET, likely indicating HER2 saturation by trastuzumab. This patient had a PFS of 13 mo on first-line HER2-directed therapy. (B) 18F-FDG PET and HER2 PET in a patient metastatic HER2+ esophageal adenocarcinoma with a short response to first-line HER2-directed therapy. Patient had > 50% of the tumor load with 89Zr-trastuzumab uptake on baseline imaging (group B) but no lesions with SUV ≥ 10; patient had no change in primary tumor 89Zr-trastuzumab uptake (SUV 8.1 from 6.6, blue arrows) or in posterior left paraaortic node 89Zr-trastuzumab uptake (green arrows) after initiation of first-line HER2-directed treatment. Patient had a relatively short PFS of 6 mo on treatment. 1 L = first-line.
Tables
Characteristic Prior trastuzumab (n = 19) No prior trastuzumab (n = 14) Total (n = 33) Median age at diagnosis (y) 59 (range, 40–76) 59 (range, 34–79) 59 (range, 34–79) Patients with metastasis at diagnosis (n) 17 (89) 10 (71) 27 (82) Primary tumor site (n) Esophageal 2 (11) 2 (14) 4 (12) GEJ (Siewert I-II) 14 (74) 7 (50) 21 (64) Gastric 3 (16) 5 (36) 8 (24) Method used to confirm sample is HER2+ (n) FISH 3 (16) 3 (21) 6 (18) IHC 15 (79) 11 (79) 26 (79) NGS 1 (5) 0 (0) 1 (3) Patients with HER2 heterogeneity across samples (n) 3 (16) 6 (43) 9 (27) Patients receiving HER2-directed therapy at the time of scan (n) 16 (84) 14 (100) 30 (91) Median no. of lines of treatment at the time of HER2 PET 3 (range, 2–6) 1 (range, 1–2) 2 (range, 1–6) Median total lines of treatment received 3 (range, 2–7) 3 (range, 1–9) 3 (range, 1–9) Median time on treatment at the time of HER2 PET (d) 93 (range, 0–212) 394 (range, 7–1,410) 126 (range, 0–1,410) Total lesions detected on imaging (all patients) Median, CT 5 (range, 1–11) 5.5 (range, 1–15) 5 (range, 1–15) Median, HER2 4 (range, 1–7) 3.5 (range, 0–11) 4 (range, 0–11) Median, 18F-FDG PET 6.5 (range, 1–13) 7 (range, 1–14) 7 (range, 1–14) Patients with ≥ 1 lesion intense or very intense on HER2 PET (n) 8 (42) 7 (50) 15 (45) Median SUVmax per patient on HER2 PET 7.8 (range, 3.20–23.8) 9.8 (range, 0–22.2) 9.2 (range, 0–23.8) Median SUVmean per lesion on HER2 PET 6.5 (range, 2.8–14.2) 7.8 (range, 0–15.9) 7.0 (range, 0–15.9) Data are number, with percentages in parentheses, or median, with the minimum to maximum in parentheses.
IHC = immunohistochemistry; NGS = next-generation sequencing.
Supplemental Data
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