Synapse - Noninvasive assessment of human epidermal growth factor receptor 2 (HER2) in esophagogastric cancer using (89)Zr-trastuzumab PET: A pilot study

Noninvasive assessment of human epidermal growth factor receptor 2 (HER2) in esophagogastric cancer using (89)Zr-trastuzumab PET: A pilot study Journal Article

Authors:	Lumish, M. A.; Maron, S. B.; Paroder, V.; Chou, J. F.; Capanu, M.; Philemond, S.; O'Donoghue, J. A.; Schoder, H.; Lewis, J. S.; Lyashchenko, S. K.; Pandit-Taskar, N.; Janjigian, Y. Y.
Article Title:	Noninvasive assessment of human epidermal growth factor receptor 2 (HER2) in esophagogastric cancer using (89)Zr-trastuzumab PET: A pilot study
Abstract:	Variations in human epidermal growth factor receptor 2 (HER2) expression between the primary tumor and metastases may contrib-ute to drug resistance in HER2-positive (HER2+) metastatic esopha-gogastric cancer (mEGC). 89Zr-trastuzumab PET (HER2 PET) holds promise for noninvasive assessment of variations in HER2 expression and target engagement. The aim of this study was to describe HER2 PET findings in patients with mEGC. Methods: Patients with HER2+ mEGC were imaged with HER2 PET, 18F-FDG PET, and CT. Lesions were annotated using measurements (on CT) and maximum SUVs (on HER2 PET). Correlation of visualized disease burden among imaging modalities with clinical and pathologic characteristics was performed. Results: Thirty-three patients with HER2+ mEGC were imaged with HER2 PET and CT (12% esophageal, 64% gastroesophageal junc-tion, and 24% gastric adenocarcinoma), 26 of whom were also imaged with 18F-FDG PET. More lesions were identified on 18F-FDG PET (median, 7 [range, 1-14]) than HER2 PET (median, 4 [range, 0-11]). Of the 8 lesions identified on HER2 but not on 18F-FDG PET, 3 (38%) were in bone and 1 was in the brain. Of the 68 lesions identified on 18F-FDG but not on HER2 PET, 4 (6%) were in bone and the remainder were in the lymph nodes (35, 51%) and liver (16, 24%). Of the 33 total patients, 23 (70%) were HER2 imaging-positive (& GE;50% of tumor load positive). Only 10 patients had 100% of the tumor load positive; 2 had 0% positive. When only patients receiving HER2-directed therapy as first-line treatment were considered (n = 13), median progression-free survival (PFS) therapy was not significantly different between HER2 imaging-positive and -negative patients. Median PFS for patients with at least 1 intense or very intense lesion (SUV & GE; 10) was 16 (95% CI: 11-not reached) mo (n = 7), compared with 12 (95% CI: 6.3-not reached) mo for patients without an intense or very intense lesion (n = 6) (P = 0.35). Conclusion: HER2 PET may identify heterogeneity of HER2 expression and allow assessment of lesions throughout the entire body. A potential application of HER2 PET is noninvasive evaluation of HER2 status including assessment of intrapatient disease heterogeneity not captured by standard imaging or single-site biopsies.
Keywords:	trastuzumab; esophageal adenocarcinoma; gastric adenocarcinoma; breast-cancer; gastroesophageal junction cancer; her2 heterogeneity; her2 pet
Journal Title:	Journal of Nuclear Medicine
Volume:	64
Issue:	5
ISSN:	0161-5505
Publisher:	Society of Nuclear Medicine
Date Published:	2023-05-01
Start Page:	724
End Page:	730
Language:	English
ACCESSION:	WOS:001016966900011
DOI:	10.2967/jnumed.122.264470
PROVIDER:	wos
PMCID:	PMC10152123
PUBMED:	36418168
Notes:	The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PDF. Corresponding MSK authors are Melissa A. Lumish and Neeta Pandit-Taskar -- Source: Wos