Ferumoxtran-10-enhanced MRI for pre-operative metastatic lymph node detection in pancreatic, duodenal, or periampullary adenocarcinoma

Abstract

Objectives: To assess 3-Tesla (3-T) ultra-small superparamagnetic iron oxide (USPIO)-enhanced MRI in detecting lymph node (LN) metastases for resectable adenocarcinomas of the pancreas, duodenum, or periampullary region in a node-to-node validation against histopathology.

Methods: Twenty-seven consecutive patients with a resectable pancreatic, duodenal, or periampullary adenocarcinoma were enrolled in this prospective single expert centre study. Ferumoxtran-10-enhanced 3-T MRI was performed pre-surgery. LNs found on MRI were scored for suspicion of metastasis by two expert radiologists using a dedicated scoring system. Node-to-node matching from in vivo MRI to histopathology was performed using a post-operative ex vivo 7-T MRI of the resection specimen. Sensitivity and specificity were calculated using crosstabs.

Results: Eighteen out of 27 patients (median age 65 years, 11 men) were included in the final analysis (pre-surgery withdrawal n = 4, not resected because of unexpected metastases peroperatively n = 2, and excluded because of inadequate contrast-agent uptake n = 3). On MRI 453 LNs with a median size of 4.0 mm were detected, of which 58 (13%) were classified as suspicious. At histopathology 385 LNs with a median size of 5.0 mm were found, of which 45 (12%) were metastatic. For 55 LNs node-to-node matching was possible. Analysis of these 55 matched LNs, resulted in a sensitivity and specificity of 83% (95% CI: 36-100%) and 92% (95% CI: 80-98%), respectively.

Conclusion: USPIO-enhanced MRI is a promising technique to preoperatively detect and localise LN metastases in patients with pancreatic, duodenal, or periampullary adenocarcinoma.

Clinical relevance statement: Detection of (distant) LN metastases with USPIO-enhanced MRI could be used to determine a personalised treatment strategy that could involve neoadjuvant or palliative chemotherapy, guided resection of distant LNs, or targeted radiotherapy.

Registration: The study was registered on clinicaltrials.gov NCT04311047. https://clinicaltrials.gov/ct2/show/NCT04311047?term=lymph+node&cond=Pancreatic+Cancer&cntry=NL&draw=2&rank=1 .

Key points: LN metastases of pancreatic, duodenal, or periampullary adenocarcinoma cannot be reliably detected with current imaging. This technique detected LN metastases with a sensitivity and specificity of 83% and 92%, respectively. MRI with ferumoxtran-10 is a promising technique to improve preoperative staging in these cancers.

Keywords: Duodenal cancer; Lymph node metastasis; Magnetic resonance imaging; Pancreatic cancer; Periampullary cancer.

Fig. 1

Flowchart of patient inclusion, study procedures, and analysis

Fig. 2

An example of a false negative LN from an 80-year-old female patient with cholangiocarcinoma, not suspected on USPIO-MRI, but metastatic at histopathology. a T1-VIBE in phase, axial view; b mGRE TE = 12 ms (iron sensitive), axial view; c malignant LN at histopathology, H&E staining; and (d) magnified part of malignant LN with small malignant depositions (black arrows) visible in an abundance of normal lymphatic tissue. The LN is indicated with white arrows on the MRI images and shows strong signal loss on the iron-sensitive sequence (type 7)

Fig. 3

An example of a false positive LN from an 81-year-old male patient with cholangiocarcinoma, suspect on USPIO-MRI (type 1) but negative at histopathology. a T1-VIBE in phase, axial view, LN indicated with the white arrow; b mGRE TE = 12 ms (iron sensitive), axial view, LN indicated with the white arrow, partly shows a high signal intensity, and is thus indicated as suspicious; and (c) benign LN at histopathology, H&E staining

Fig. 4

An example of a true positive LN from a 58-year-old male patient with cholangiocarcinoma, suspect on USPIO-MRI (type 1) and metastatic at histopathology. a T1-VIBE in phase, axial view, LN indicated with the white arrow; b mGRE TE = 12 ms (iron sensitive), axial view, LN indicated with the white arrow; c malignant LN at histopathology with metastatic tissue in the entire LN, H&E staining; and (d) magnified part of malignant LN with malignant cells visible

Fig. 5

An example of a true negative LN from a 55-year-old male patient with cholangiocarcinoma, not suspect on USPIO-MRI (type 7) and negative at histopathology. a T1-VIBE in phase, coronal view, LN indicated with the white arrow; b mGRE TE = 12 ms (iron sensitive), coronal view, LN indicated with the white arrow; c T1-VIBE in phase, axial view, LN indicated with the white arrow; d mGRE TE = 12 ms (iron sensitive), axial view, LN indicated with the white arrow; and (e) benign LN at histopathology, H&E staining