Feasibility of indocyanine green‐guided localization of pulmonary nodules in children with solid tumors

Abstract

BackgroundClearing all pulmonary metastases is essential for curing pediatric solid tumors. However, intraoperative localization of such pulmonary nodules can be challenging. Therefore, an intraoperative tool that localizes pulmonary metastases is needed to improve diagnostic and therapeutic resections. Indocyanine green (ICG) real‐time fluorescence imaging is used for this purpose in adult solid tumors, but its utility in pediatric solid tumors has not been determined.MethodsA single‐center, open‐label, nonrandomized, prospective clinical trial (NCT04084067) was conducted to assess the ability of ICG to localize pulmonary metastases of pediatric solid tumors. Patients with pulmonary lesions who required resection, either for therapeutic or diagnostic intent, were included. Patients received a 15‐minute intravenous infusion of ICG (1.5 mg/kg), and pulmonary metastasectomy was performed the following day. A near‐infrared spectroscopy iridium system was optimized to detect ICG, and all procedures were photo‐documented and recorded.ResultsICG‐guided pulmonary metastasectomies were performed in 12 patients (median age: 10.5 years). A total of 79 nodules were visualized, 13 of which were not detected by preoperative imaging. Histologic examination confirmed the following histologies: hepatoblastoma (n = 3), osteosarcoma (n = 2), and one each of rhabdomyosarcoma, Ewing sarcoma, inflammatory myofibroblastic tumor, atypical cartilaginous tumor, neuroblastoma, adrenocortical carcinoma, and papillary thyroid carcinoma. ICG guidance failed to localize pulmonary metastases in five (42%) patients who had inflammatory myofibroblastic tumor, atypical cartilaginous tumor, neuroblastoma, adrenocortical carcinoma, or papillary thyroid carcinoma.ConclusionsICG‐guided identification of pulmonary nodules is not feasible for all pediatric solid tumors. However, it may localize most metastatic hepatic tumors and high‐grade sarcomas in children.

Indocyanine Green (ICG) Fluorescence-Assisted Open Surgery Using the Rubina® Lens System in the Pediatric Population: A Single-Center Prospective Case Series

“…There is very scarce pediatric literature about use of ICG fluorescence in open surgery. The main applications have been described for oncological indications to facilitate lymph node sampling in Wilms' tumors, aid in hepatectomy for hepatoblastoma or localize pulmonary metastases of pediatric solid tumors [22][23][24][25]. Different studies have examined the feasibility of ICG-guided tumor resection in common childhood solid tumors such as neuroblastoma, sarcomas, hepatic tumors, pulmonary metastases and other rare tumors [5,24,25].…”

“…The main applications have been described for oncological indications to facilitate lymph node sampling in Wilms' tumors, aid in hepatectomy for hepatoblastoma or localize pulmonary metastases of pediatric solid tumors [22][23][24][25]. Different studies have examined the feasibility of ICG-guided tumor resection in common childhood solid tumors such as neuroblastoma, sarcomas, hepatic tumors, pulmonary metastases and other rare tumors [5,24,25]. Fluorescence-guided lymphatic mapping of Wilms tumor drainage is feasible by both intraparenchymal and peri-hilar injection techniques.…”

Children's Oncology Group's 2023 blueprint for research: Surgery

“…FGS can provide real-time tumor visualization and has demonstrated significant benefits in surgical oncology, including sentinel lymph node biopsy (SLNB), identifying occult lesions, and delineating tumor margins. [51][52][53][54][55][56] Contemporary FGS uses near-infrared (NIR) agents, which have better tissue penetration and less tissue autofluorescence than visual-spectrum fluorescent agents. 57 The most common NIR-dye is indocyanine green (ICG), which accumulates in tumors due to enhanced permeability of leaky tumor vessels F I G U R E 2 Near-infrared images of tumors following systemic administration of indocyanine green (1.5 mg/kg) given intravenously 24 hours prior to surgery.…”

“…Currently, COG surgeons are studying ICG-guided SLNB for WT tumor in collaboration with SIOP surgeons. [51][52][53][54][55][56]59,60 To overcome passive targeting by ICG, molecularly targeted fluorescent agents have been developed that specifically bind the tissue of interest and are conjugated to a fluorescent molecule. Ideally, nonspecific binding is minimal, and the tumor-to-background ratio (TBR) is maximized.…”