Innovative Surgical System for Breast Cancer Based on Real-time Excising of Hypoxic Lesions Significantly Reduced the Positive Cavity Side Margin

Abstract Background: For most people, the first step in treatment is to take out the tumor (surgery), so precise and fast diagnosis of any sign of high-risk cells in surgical cavity margins is significant. The frozen pathology method is the conventional standard of intraoperative diagnosis, but the low number of slides prepared from non-fixed tissues prevents us to achieve a perfect diagnosis. Although many improvements in intraoperative margin detection were achieved, still no clinically approved intra-operative technique has been reported for the detection of surgical margins with pathologically approved classification in breast cancer.Methods: From November 2018 to April 2020, 227 patients were registered and 213 with different types of breast tumors (IDC: n=151 (70.9%), ILC: n=6 (2.8%), DCIS: n=38 (17.8%), Atypia: n=8 (3.8%), Benign tumors: n=10 (%4.7)) were randomly assigned for CDP clinical trials. Men made up 2 (1%) of the patients; 211 (99%) were women. Functionalized carbon nanotubes grown on the electrode needles lively and selectively determine the H2O2 released from cancer/atypical cells, through reverse Warburg effect and hypoxia assisted glycolysis pathways, in a quantitative electrochemical manner. The study is registered at Iran National Committee for Ethics in Biomedical Research (IR.TUMS.VCR.REC.1397.355).Result: A real-time electrotechnical system, named cancer diagnostic probe (CDP) (Patent Pub. No.: US 2018/0299401A1), has been developed and clinically approved for breast cancer surgery (National Certificate ID:14006918495) to find the presence of pre-neoplastic/neoplastic cells in-vivo. Here, Functionalized carbon nanotubes grown on the electrode needles lively and selectively determine the H2O2 released from cancer or atypical cells, through reverse Warburg effect and hypoxia assisted glycolysis pathways, in quantitative electrochemical manner. A matched clinical diagnostic categorization between the pathological results and response peaks of CDP was proposed based on pathological classifications of WHO. Conclusion: The clinical ability of CDP was verified on more than 1300 human in-vivo breast samples with sensitivity and specificity of 93%, and 97%, respectively. After passing many trials and standard examinations, the system received production and clinical use certifications as a surgeon assistant system for usage in the operating room.