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Cryoablation Without Excision for Low-Risk Early-Stage Breast Cancer: 3-Year Interim Analysis of Ipsilateral Breast Tumor Recurrence in the ICE3 Trial

Abstract

Background

The ICE3 trial is designed to evaluate the safety and efficacy of breast cryoablation, enabling women older than 60 years with low-risk early-stage breast cancers to benefit from a nonsurgical treatment and to avoid the associated surgical risks.

Methods

The ICE3 trial is a prospective, multi-center, single-arm, non-randomized trial including women age 60 years or older with unifocal, ultrasound-visible invasive ductal carcinoma size 1.5 cm or smaller and classified as low to intermediate grade, hormone receptor (HR)-positive, and human epidermal growth factor receptor 2 (HER2)-negative. Ipsilateral breast tumor recurrence (IBTR) at 5 years was the primary outcome. A 3-year interim analysis of IBTR was performed, and the IBTR probability was estimated using the Kaplan-Meier method.

Results

Full eligibility for the study was met by 194 patients, who received successful cryoablation per protocol. The mean age was 75 years (range, 55–94 years). The mean tumor length was 8.1 mm (range, 8–14.9 mm), and the mean tumor width was 7.4 mm (range, 2.8–14 mm). During a mean follow-up period of 34.83 months, the IBTR rate was 2.06% (4/194 patients). Device-related adverse events were reported as mild in 18.4% and moderate in 2.4% of the patients. No severe device-related adverse events were reported. More than 95% of the patients and 98% of the physicians reported satisfaction with the cosmetic results at the clinical follow-up evaluation.

Conclusions

Breast cryoablation presents a promising alternative to surgery while offering the benefits of a minimally invasive procedure with minimal risks. Further study within a clinical trial or registry is needed to confirm cryoablation as a viable alternative to surgical excision for appropriately selected low-risk patients.

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Acknowledgements

Funding for this trial was provided by IceCure Medical Ltd., Caesarea, Israel. Ravit Attali, RN, MPH is the Clinical Director of IceCure Medical Ltd. NIH Trial Registration No: https://clinicaltrials.gov/ct2/show/NCT02200705.

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Correspondence to Richard E. Fine MD.

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Disclosure

Andrew Kenler was the medical Director of Icecure for approximately five years and during the time period of this study and was paid for my time as medical Director. That relationship ended approximately one year ago; Kenneth Tomkovich: Stipend received for data entry for patients enrolled in trial to CentraState medical center by IceCure medical. Probes and cryoablation unit provided by IceCure medical to conduct the trial. I received no personal funds for conducting the trial or for the preparation of this manuscript. Neither I nor my medical institution have any relevant conflict of interest in conducting this research; Richard Fine: West Cancer Center & Research Institute (Author's institution) received financial support for conducting the clinical trial. Served on the original scientific advisory board that participated in the Ice3 trial protocol design. Expenses were reimbursed for travel to Chicago, Il in 2014; Margaret Chen-Seetoo: Novian Health—research grant; Theraclion—research grant; Agendia—research grant; PreludeDx—research grant; Susan Seedman profited $280 from prior purchase and sale of publicly traded stock.

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Fine, R.E., Gilmore, R.C., Dietz, J.R. et al. Cryoablation Without Excision for Low-Risk Early-Stage Breast Cancer: 3-Year Interim Analysis of Ipsilateral Breast Tumor Recurrence in the ICE3 Trial. Ann Surg Oncol 28, 5525–5534 (2021). https://doi.org/10.1245/s10434-021-10501-4

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