Cryo-Assisted Resection En Bloc, and Cryoablation In Situ, of Primary Breast Cancer Coupled With Intraoperative Ultrasound-Guided Tracer Injection: A Preliminary Clinical Study

Abstract

The aim of the study was to perform cryosurgery on a primary breast tumor, coupled with simultaneous peritumoral and intratumoral tracer injection of a blue dye, to evaluate lymphatic mapping. We explored the ability of our strategy to prevent tumor cells, but not that of injected tracers, to migrate to the lymphovascular drainage during conventional resection of frozen breast malignancies. Seventeen patients aged 51 (14) years (mean [standard deviation]), presenting primary breast cancer with stage I to IV, were randomly selected and treated in The Rudolfinerhaus Private Clinic in Vienna, Austria, and included in this preliminary clinical study. Under intraoperative ultrasound, 14 patients underwent curative cryo-assisted tumor resection en bloc, coupled with peritumoral tracer injection, which consisted of complete tumor freezing and concomitant peritumor injection with a blue dye, before resection and sentinel lymph node dissection (group A). Group B consists of 3 patients previously refused any standard therapy and had palliative tumor cryoablation in situ combined with intratumoral tracer injection. The intraoperative ultrasound facilitated needle positioning and dye injection timing. In group A, the frozen site extruded the dye that was distributed through the unfrozen tumor, the breast tissue, and the resection cavity for 12 patients. One to 4 lymph nodes were stained for 10 of 14 patients. The resection margin was evaluable. Our intraoperative ultrasound-guided performance revealed the injection and migration of a blue dye during the frozen resection en bloc and cryoablation in situ of primary breast tumors. Sentinel lymph node mapping, pathological determination of the tumor, and resection margins were achievable. The study paves the way for intraoperative cryo-assisted therapeutic strategies for breast cancer.

Intraoperative Cryosurgical Freezing Assists with Local Drug Delivery and Targeting of Tumor Fluids in VX2 Model, which Translates in Locoregional Drug Targeting of Tumor Fluids during Cryoprobe-Assisted Surgical Resection of Breast Cancer

“…We have previously demonstrated that solution of small molecular tracer alone or coformulated with cytotoxic drug injected in tumor margin migrate in tumor fluid dissemination pathways. We have shown that concurrent tumor freezing modulates the direction and spread of this migration 30,32 . However, there is a lack of demonstration that the VX2 cryoablation tumor model is translatable to cyoprobeassisted surgery, i.e.…”

“…Given the unchanged tracer distribution pattern from the first to the fifth cycle, only 2 FT cycles were used for the clinical study, a widely recognized clinical technique 38 . The full dose injection of breast tumor took place before completion of the first freeze sequence, when the F-UI reached needle 32 . During the VX2 percutaneous or BRCA surgical approach, we made every effort to minimize the risk of unwanted reflux or drug loss through track of least resistance, such as the probe, the needle tract, or the surgical wound.…”

“…The clinical study, previously published in part 32 , was conducted in a single center, The Rudolfinerhaus Private Clinic, Vienna, Austria. Twenty-six patients aged 54 (±14) years (mean, SD), presenting with primary breast tumor, stage I to III or de novo stage IV, were randomly selected and treated ( Table 2).…”

“…Following intraoperative tumor freezing with ultrasound guided marginal injection of 2ml BD, and conventional resection of the frozen mass and breast tissue, dubbed cryo-assisted resection en bloc (CR), was conducted 32 . Tumor margin of resected specimen was marked with sutures for spatial orientation.…”

“…In this work, we evaluate the translational value of a cryoprobe-assisted drug delivery technique targeting the tumor margin, first in a VX2 tumor model 30 , and then in human breast tumor 32 . We describe the distribution and tumor kill pattern of a tracer-and-therapeutic mixture (TTM) deposited under CECT imaging at the frozen edge of a tumor during cryoablation.…”