Up to 40% of breast cancer patients have a tumor-positive resection margin (TPRM) - defined as cancer cells at the surface of the resected specimen - after breast-conserving surgery (BCS), necessitating re-resection or boost radiation. To prevent these additional treatments, intraoperative near-infrared (NIR) fluorescence imaging with the topically applied, cathepsin-activatable imaging agent AKRO-6qcICG might be used to detect TPRMs and guide additional resection. Here, to validate its performance, the agent is topically applied to all surfaces of freshly resected breast cancer specimens (n = 11 patients) and to 3-5mm thick tissue slices of the specimens (n = 26 patients). NIR fluorescence images of the resection surfaces and tissue slices are acquired and correlated to final histopathology. AKRO-6qcICG detects TPRMs with a sensitivity, specificity, PVV, and NPV of 100%, 67%, 10%, and 100%, respectively. On the tissue slices, the fluorescence signal has a median tumor-to-background ratio of 1.8. These findings indicate that topically applied AKRO-6qcICG can visualize TPRMs ex vivo with a high sensitivity and NPV, with sufficient contrast to adjacent healthy breast tissue.
Ex vivo fluorescence-guided resection margin assessment in breast cancer surgery using a topically applied, cathepsin-activatable imaging agent.
CHDR
Linders DGJ, Bijlstra OD, Walker E, March TL, Pool M, Valentijn ARPM, Dijkhuis TH, Woltering JN, Pijl FR, Noordam G, van den Burg D, van der Sijp JRM, Guicherit OR, Marinelli AWKS, Burggraaf J, Rissmann R, Bogyo M, Hilling DE, Kuppen PJK, Straight B, Straver ME, Hazelbag HM, Basilion JP, Vahrmeijer AL
