Fluorescence-guided surgery improved long-term survival in orthotopic nude mouse models of cancer

Background: Negative surgical margins are vital to achieve cure and prolong survival in patients with cancer. We inquired if fluorescence-guided surgery (FGS) compared to bright-light surgery (BLS) could improve surgical outcomes and reduce recurrence rates in orthotopic mouse models of human cancer. Methods: A randomized active-control pre-clinical trial comparing BLS to FGS was used. Orthotopic mouse models of human pancreatic cancer, colon cancer, including liver metastasis, and fibrosarcoma were established. The models were established with human cancer cell lines expressing fluorescent proteins. Pre- and postoperative images were obtained with the OV-100 Small Animal Imaging System to assess completeness of surgical resection in real time. Post-operatively, noninvasive whole-body imaging was done to assess recurrence and follow tumor progression. Results: With the pancreatic cancer model, FGS resulted in significantly longer disease-free survival (DFS) than BLS (P=.02, hazard ratio=0.39, 95% CI 0.17, 0.88). With the colon cancer model, FGS lengthened disease-free median survival from 9 to >36 weeks. The median overall survival (OS) increased from 16 weeks in the BLS group to 31 weeks in the FGS group. FGS resulted in a cure in 67% of mice compared with only 37% of mice that underwent BLS (P=.049). With the colon cancer liver-metastasis model, the FGS-treated mice had significantly prolonged disease-free survival (DFS) (P=.001) and OS (P=.027) compared to BLS-treated mice. With the fibrosarcoma model the combination of BLS+FGS significantly decreased recurrence compared to BLS-only treated mice (P<.001). Mice treated with BLS+FGS had a significantly higher DFS rate than mice treated with BLS-only. Conclusion: These results demonstrate the feasibility and efficacy of FGS of primary and metastatic cancer compared to BLS.