Description
BackgroundComplete surgical resection remains one of the hallmarks of cancer therapy, with clean surgical margins positively impacting the patient's survival. Nevertheless, up to 26% of patients that underwent surgery for head and neck cancer (HNC) are left with positive surgical margins. Due to anatomical constraints, revision surgeries are often impossible and adjuvant therapies, such as radiotherapy or systemic therapies, result in a tremendous impact on the patient’s quality of life. Fluorescence-guided surgery (FGS) has recently revolutionized the field of surgical oncology but the currently used tracers show low specificity or suboptimal biokinetic profiles. We here propose a fluorescently labeled nanobody targeting the epidermal growth factor receptor (EGFR) for its use in FGS. To evaluate its clinical potential, we first performed a trial in dogs with spontaneous HNC.
Material and methods
A clinical 3+3 dose-escalation study was designed with the dog-human cross-reactive EGFR-targeting Nb 7D12 labeled with the near-infrared (NIR) fluorophore s775z. Canine patients diagnosed with HNC, scheduled for tumor resection were eligible for inclusion. The dogs received 7D12-s775z intravenously one hour before surgery. Then, an open-field NIR imaging device was used to image uptake in the malignancy in situ, followed by surgical resection of the tumor and imaging of the tumor bed. Back-table ex vivo imaging was performed using the same camera as well as a flatbed fluorescence scanner, followed by standard histopathological processing and EGFR immunohistochemistry to correlate fluorescent signal and EGFR overexpression on the target tissue.
Results (For Surgical Trial Proposals fill in 'the Feasibility', for Surgical Trial in Progress fill in the 'Current status')
Five canine patients with squamous cell carcinomas (n=3), follicular thyroid carcinoma (n=1) and salivary adenoma (n=1) were included. The first group of three patients received 1.74mg/m² and two patients included in the second group received 3.49mg/m² of 7D12-s775z. In situ fluorescence imaging allowed identification of the neoplastic tissue in all patients but was relatively weak in the lowest dose whereas adequate signal was observed in the highest dose. Histopathology displayed increased fluorescence in the regions with increased EGFR expression, confirming its high specificity.
Conclusions (For Surgical Trial in Progress and Surgical Trial Proposals fill in 'NA')
We here display the first results of a fluorescent Nb targeting EGFR in canine patients undergoing surgery for HNC. Specific fluorescent signal was observed as early as one hour after injection, even in the lowest dose group. The results obtained in this spontaneous cancer model display the high potential for future clinical translation of fluorescently labeled EGFR-targeting nanobodies to improve intraoperative margin assessment in EGFR-expressing malignancies in humans.
| Period | 3 Oct 2024 |
|---|---|
| Event title | ESSO 2024: 43rd Congress of the European Society of Surgical Oncology |
| Event type | Conference |
| Location | Antwerpen, Belgium |
| Degree of Recognition | International |