Abstract OT2-03-01: Multicenter study to standardize and evaluate the efficacy of radiofrequency ablation therapy for early breast cancer (RAFAELO study)
Authors: Kinosita T , Takahashi M , Fujisawa T , Yamamoto N , Doihara H , Ohtani S , Futamura M , Takahashi M , Aogi K , Hojo T , Yoshida M , Shiino S , Tsuda H 
Published: May 2019

Abstract
Background: Early-stage breast cancer is increasingly detected by screening mammography, and we aim to establish radiofrequency ablation therapy (RFA) as a minimally invasive, cost-efficient, and cosmetically acceptable local treatment. In our Phase I study, localized tumors with a maximum diameter of 2 cm, preoperatively diagnosed by imaging and histopathology, were treated with RFA. A 90% complete ablation rate was confirmed histopathologically. Our phase II multicenter study of RFA without resection for early breast cancer will evaluate the long-term safety and efficacy of RFA as well as its cosmetic results, which are a perceived advantage of this technique.
Trial design: This study is a Phase III, single-arm, multicenter study being conducted with the participation of 11 hospitals. In our experimental therapy, a radiofrequency electrode needle is inserted through the skin into the breast lesion under imaging guidance, followed by thermal ablation with radiofrequency waves. RFA will be conducted under general anesthesia. The Cool-tip™ RF Ablation Single Electrode Kit (Medtronic, CO, USA) will be used to standardize the evaluation of the ablation effect. After RFA, all patients will receive radiotherapy and systemic therapy according to the ER, HER2, tumor grade, and lymph node status of the primary tumor. Residual lesions after RFA will be assessed approximately 3 months after radiotherapy using imaging and pathological studies. All patients will undergo vacuum-assisted biopsy regardless of imaging results. If specimens show viable tumor tissue, additional excision will be performed. Follow-up evaluation for residual tumor, including clinical breast examination and diagnostic imaging (ultrasound, MRI, and mammography), will be performed yearly after RFA. This trial has been registered at the UMIN Clinical Trials Registry as UMIN000012429.
Eligibility criteria: Early breast cancer patients, who are lack of prior treatment for breast cancer and histologically confirmed ductal carcinoma with a single localized tumor of 1.5 cm or less in the greatest dimension and clinically node negative on preoperative imaging.
Specific Aims: The primary endpoint is 5-year ipsilateral breast tumor recurrence(IBTR) rate, and the secondary endpoints are residual lesion rate, overall survival, DFS, and adverse events of RFA.
Statistical methods: The IBTR rate should be similar to that with standard treatment (BCS). However, the IBTR after RFA alone may be higher by up to 10% than in the NSABP-B06 study; therefore the 5-year IBTR rate is estimated to be 6.3%. We calculated the required sample size based on the following assumptions: a clinically acceptable 5-year local recurrence-free survival rate of 90%, a one-sided significance level of 5% (alpha = 0.1, 2-sided), and power of 80% (beta = 0.2). Taking into account a drop-out rate of 10%, approximately 372 patients will be enrolled in the study.
Present accrual and target accrual: The trial was activated in August 2013, with a total of 372 patients enrolled by the end of June 2018.
Citation Format: Kinosita T, Takahashi M, Fujisawa T, Yamamoto N, Doihara H, Ohtani S, Futamura M, Takahashi M, Aogi K, Hojo T, Yoshida M, Shiino S, Tsuda H. Multicenter study to standardize and evaluate the efficacy of radiofrequency ablation therapy for early breast cancer (RAFAELO study) [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr OT2-03-01.