Multi-center study on patient selection for and the oncologic safety of intraoperative radiotherapy (IORT) with the Xoft Axxent® eBx® System for the management of early stage breast cancer in Taiwan

Abstract

Background: In this multi-center study, we report the patient selection criteria for and preliminary oncologic outcomes associated with intraoperative radiotherapy (IORT) delivered by the Xoft Axxent® eBx® system for early-stage breast cancer in Taiwan.

Methods: Patients with early breast cancer in Taiwan received breast conserving surgery and received IORT with Xoft Axxent® eBx® System during 2013-2015 was search from database of Taiwan IORT study cooperative group (T-IORTSCG). Patients' clinicopathologic characteristics and early post-operative results were collected and reported.

Results: During the study period, 26 hospitals in Taiwan performed a total of 261 Xoft IORT procedures for breast cancer. The mean age of them was 52.9 ± 9.8 years (37-72), and tumor size was 1.5 ± 0.8 cm (0.1-4.2 cm) for invasive cancer and 1.2 ± 0.8 cm (range, 0.2-3.0 cm) for ductal carcinoma in situ (DCIS) lesions. Lymph node metastasis was found in 6 (2.3%) patients. The patients received IORT in Taiwan differed markedly from those used in the ELIOT and TARGIT-A studies. Specifically, patients selected for IORT in Taiwan tended to be younger, their tumors tended to be larger and the prevalence of lymph node metastasis tended to be lower. Among these 261 patients, 8 (3.1%) patients required whole breast radiotherapy. During a mean follow up of 15.6 months, locoregional recurrence was observed in 2 (0.8%) patients.

Conclusion: In real world experience, patients received IORT differed quite significantly with criteria formulated by trials. The preliminary results of IORT in Taiwan showed it is well acceptable by patients and clinicians.

Fig 1. Procedures for patients received intra-operative radiotherapy with the Xoft Axxent® eBx® delivery system.

(a) The eBX system consists of a balloon applicator, a 50-kV source, and a mobile, highly portable controller unit that can be easily transported to any treatment room or standard operating room. (b) The chest wall shield was placed temporarily into the cavity for the duration of radiation treatment to protect the underlying heart, ribs, and lungs from scattered radiation. (c) A balloon-like cavity evaluation device was then placed through a lateral stab wound incision or directly into the wound and filled to a desired volume of 30–75 cc, based on the radiation treatment plan. (d) Once the cavity volume was determined, an appropriate size of eBX balloon was opened up and inserted into the cavity. Multiple retention-type sutures were used to maintain the balloon-to-tissue apposition and to temporarily close the lumpectomy cavity around the balloon. (e) Balloon-to-tissue conformity was assessed by intraoperative ultrasonography to ensure that the target volume did not contain air or fluid. Intraoperative ultrasonography was then used to confirm that there was a distance of at least 1 cm between the balloon and skin to reduce the risk of radionecrosis. (f) A FlexiShieldTM (FS; Xoft, Inc., San Jose, CA) was placed over the breast to minimize transmission of radiation to the patient and hospital staff. (g) The radiation source was inserted into the balloon and radiation therapy was initiated. A planned dose of 20 Gy to the balloon surface was delivered over an average of 8–15 mins. (h) During treatment, the surgeon, radiation oncologists, anesthesiologist, and other essential operating room personnel wore standard lead aprons and /or stood behind a portable radiation shield in the operating suite. The medical staffs could also leave the operation room and observe the monitors during the Xoft IORT treatment.

Fig 2. Flow chart of patients received intraoperative radiotherapy with the Xoft Axxent® eBx® delivery system.

*case summary for recurrence after IORT. Case 1: 51 y/o female with right breast cancer, which was located at upper outer quadrant of breast. She received breast conserving surgery, sentinel lymph node biopsy (SLNB), and IORT. SLNB: negative for lymph node metastasis (0/2). Pathology showed DCIS, tumor size: 3 cm, ER(+, 90%), PR(+, 40%), and HER-2(+). She received adjuvant endocrine therapy with tamoxifen. Local recurrence was found at the same quadrant (right upper outer) of operated breast (tumor size: 0.6 cm, CNB: infiltrating ductal carcinoma) 1 year post surgery. Salvage simple mastectomy and SLNB were performed. Adjuvant endocrine therapy was shifted to letrozole due to hormone positive breast cancer. Case 2: 65 y/o female diagnosed with right breast cancer (CNB: DCIS (tumor size: 2.3 cm), high grade, ER(-), PR(-), HER-2(+) over upper outer quadrant. She received BCS + SLNB + IORT. Pathology showed: DCIS with microinvasion (0.1 cm), lymp node negative. She received adjuvant therapy with letrozole. Locoregional recurrence was found over right axilla (lymph node size 1 cm, CNB: IDC) 1 year post surgery. Axillary lymph node dissection was performed, and she received adjuvant chemotherapy with 4 cycles of 5-FU, lipodoxorubicin, and cyclophosphamide. Then another 4 cycles of docetaxel were given. She also received whole-breast external beam radiotherapy (WBRT) and letrozole treatment.

Fig 3. The development and application of Xoft IORT system in Taiwan.

(a) The development and application of Xoft IORT system in Taiwan from 2013–2015. The T-IORTSCG comprises members from major IORT centers in Taiwan, and included 5 centers in 2013, 18 in 2014, and 26 in 2015. The number of IORT performed per year and the cumulative number of IORT performed in the past 3 years were provided. (b) Illustration of pre- and post-operative breast appearance of patients received conventional radiotherapy. (c) Illustration of pre- and post-operative breast appearance of patients received intra-operative radiotherapy.