Long-term follow-up after near-infrared fluorescence-guided resection of colorectal liver metastases: A retrospective multicenter analysis

Abstract

Background: Several studies demonstrated that intraoperative near-infrared fluorescence (NIRF) imaging using indocyanine green (ICG) identifies (sub)capsular colorectal liver metastases (CRLM) missed by other techniques. It is unclear if this results in any survival benefit. This study evaluates long-term follow-up after NIRF-guided resection of CRLM using ICG.

Methods: First, patients undergoing resection of CRLM with or without NIRF imaging were analyzed retrospectively. Perioperative details, liver-specific recurrence-free interval and overall survival were compared. Second, the prognosis of patients in whom additional metastases were identified solely by NIRF was studied.

Results: Eighty-six patients underwent resection with NIRF imaging and 87 without. In significantly more patients of the NIRF imaging cohort additional metastases were identified during surgery (25% vs. 13%, p = 0.04). Tumors identified solely by NIRF imaging were significantly smaller compared to additional metastases identified also by inspection, palpation or intraoperative ultrasound (3.2 ± 1.8 mm vs. 7.4 ± 2.6 mm, p < 0.001). Liver-specific recurrence-free survival at 4 years was 47% with NIRF imaging and 39% without (hazard ratio at multivariate analysis 0.73, 95% CI 0.42-1.28, p = 0.28). Overall survival at 4 years was 62% and 59%, respectively (p = 0.79). No liver recurrences occurred within 3 years follow-up in 52% of patients in whom additional metastases were resected based on only NIRF imaging.

Conclusions: This study suggests that NIRF imaging identifies significantly more and smaller tumors during resection of CRLM, preventing recurrences in a subset of patients. Given its safety profile and low expense, routine use can be considered until tumor targeting fluorescent tracers are clinically available.

Keywords: Cancer; Fluorescence imaging; Indocyanine green; Liver neoplasms; Prognosis; Surgery.

Figure 1. Intraoperative near-infrared fluorescence imaging of liver metastases

A liver metastasis identified by NIRF imaging only (white arrow) in a patient that received 10 mg indocyanine green one day prior to surgery. Tumors that were already identified by preoperative imaging (dashed arrow) can be demarcated by fluorescence imaging. Imaging was performed using the Mini-FLARE^®.

Figure 2. Patient selection

NIRF: near-infrared fluorescence; LUMC: Leiden University Medical Center; SMGH: San Matteo General Hospital. Analysis 1 assesses differences in perioperative details and survival between patients from LUMC who underwent surgery with or without guidance by near-infrared fluorescence. Analysis 2 includes only patients in whom additional metastases were identified solely by near-infrared fluorescence imaging.

Figure 3. Additionally identified colorectal liver metastases (analysis 1)

Additionally identified colorectal liver metastases. The percentage of patients in whom additional metastases were identified during surgery was significantly higher in the LUMC experimental cohort compared to the LUMC control cohort. Tumors identified solely by near-infrared fluorescence imaging were significantly smaller compared to additional metastases identified using standard techniques. * In 3% (n=2) additional metastases were identified with standard techniques, but NIRF imaging identified even more unknown metastases.

Figure 4. Liver-specific recurrence-free interval and overall survival (analysis 1)

(Estimated) liver-specific recurrence-free interval and overall survival. LUMC: Leiden University Medical Center; SMGH: San Matteo General Hospital; NIRF: near-infrared fluorescence.