Short Course, Two Day Accelerated Hypofractionated Partial Breast Balloon Brachytherapy: A Phase II Multi-Institutional Trial

Abstract

Accelerated partial breast irradiation (APBI) is presently an option for post lumpectomy treatment in properly selected women. When using brachytherapy to deliver treatment, conventionally the target volume is treated to 34 Gy in 10 fractions delivered BID over 5 days. A company sponsored prospective non-randomized trial was initiated to evaluate brachytherapy based dose-escalation to further reduce the overall treatment time to 2-3 days, improving the patient experience. This study reports the local control and toxicity results of the multi-institutional trial. Patients presenting with ductal carcinoma in situ and/or invasive disease, size ≤3cm, ER or PR positive, resected with margins free of tumor and axillary node negative were eligible. Patients were treated using a multi-lumen single entry balloon device placed post lumpectomy with ultra sound guidance. The intent of the trial design was to treat 30 patients (pts) at a dose level of 7 Gy x 4 fractions (fx), 30 pts at a dose level of 8.25 Gy X 3 fx and 30 pts at a dose level of 9.5 Gy x 2 fx. All fractions were separated by at least 6 hours and delivered over 2 days. End points evaluated included in-breast disease control, toxicity rates and physician reported cosmetic outcome. Fisher’s exact two-sided probability was used. Thirty patients were enrolled and evaluable on the first dose level, 29 pts on the second dose level and the trial was closed prior to enrollment on the final dose level due to lack of sponsorship. Four institutions participated. Median age was 64 years old. Mean tumor size was 1.3 cm (±0.9 cm) with invasive ductal carcinoma in 67.8%, invasive lobular carcinoma in 8.5% and DCIS in 23.7%. All tumors were estrogen receptor positive. The most common location of these tumors was upper outer quadrant (50.9%). Balloon diameter of 4-5cm was used in 73.2% of pts and a larger balloon, 5-6 cm, in 26.8%. Median follow up time was 51 months (range 21-86 months). In-breast failures were reported in five pts (8.5%), one considered true recurrence and four considered elsewhere. There was no difference in local control recurrence based on dose level. A trend towards less toxicity in pain and seroma (p= 0.02 and 0.04) with the second dose level is appreciated but low event rates preclude conclusions. There were no statistically significant differences in terms of fibrosis, hyperpigmentation, and fat necrosis between the two dose levels. Overall good/excellent cosmetic outcome was reported in 95% of patient (n=55) with no difference seen between dose levels. Results from this prospective phase II trial suggest extreme hypo-fractionation of dose with delivery over 2 days for early stage breast cancer appears safe with acceptable toxicity, cosmetic outcome and in-breast control rates. This experience generates support for a larger trial opening opportunities for treatment time reduction and improvement in the patient experience.