Phase 2 study of pre-excision single-dose intraoperative radiation therapy for early-stage breast cancers: six-year update with application of the ASTRO accelerated partial breast irradiation consensus statement criteria

Abstract

Background: Intraoperative radiation therapy (IORT) allows delivery of high-dose radiation at the time of lumpectomy, potentially sparing adjuvant daily radiation. A phase 2 study of pre-excision IORT was performed for early-stage breast cancer.

Methods: Patients ≥ 48 years of age with invasive ductal carcinoma, ≤ 3 cm, and clinically node-negative were eligible for this study, which was approved by institutional review board. Ultrasound was used to select electron energy and cone size to cover the tumor plus 1.5- to 2.0-cm lateral margins and 1-cm-deep margins (90% isodose). Fifteen Gy was delivered with a Mobetron irradiator, and immediate needle-localized partial mastectomy followed. Local event results were updated using the Kaplan-Meier method.

Results: A total of 53 patients received IORT alone. Median age was 63 years, and median tumor size was 1.2 cm. Of these, 81% were positive for estrogen receptor or progesterone receptor, 11% were positive for human epidermal growth factor receptor 2, and 15% were triple-negative. Also, 42%, 49%, and 9% would have fallen into the Suitable, Cautionary, and Unsuitable groups, respectively, of the American Society of Therapeutic Radiation Oncology consensus statement for accelerated partial breast irradiation. Median follow-up was 69 months. Ipsilateral events occurred in 8 of 53 patients. The 6-year actuarial rate of ipsilateral events was 15% (95% confidence interval = 7%-29%). The crude event rate for Suitable and Cautionary groups was 1 of 22 (5%) and 7 of 26 (27%), respectively. Overall survival was 94.4%, and breast cancer-specific survival was 100%.

Conclusions: The rate of local events in this study is a matter of concern, especially in the Cautionary group. On the basis of these findings, pre-excision IORT, as delivered in this study, may not provide adequate local control for less favorable early-stage breast cancers.

Copyright © 2013 American Cancer Society.

Figures

Figure 1:

Figure 1a: Ultrasound simulation was performed to aid in tumor localization and for optimal angle of approach to minimize the skin-to-tumor distance and maximize the tumor- to-lung distance. Figure 1b: The skin was retracted and the cone was placed overlying the tumor at the angle of approach per Ultrasound simulation. The tumor was centered inside the cone and visualized by both the treating radiation oncologist and surgeon. Figure 1c: The patients were positioned underneath the mobile linear accelerator which was positioned at the correct angle for delivery of 15 Gy to the 90% isodose line.

Figure 2:

Time to Local Event Graph with local recurrence % on y axis and time in months on the x-axis. The red tick marks are indicators of patient lost to follow up. The black lines at 5 years and 6 years represent the 95% confidence intervals at those times.

Figure 3:

Kaplan-Meier Local Control Rate by ASTRO APBI Consensus Groups. The Black line indicates the local control rate for ‘Suitable’ patients and tick marks indicate individual patients lost to follow up. The red line indicates the local control rate for ‘Cautionary’ patients with red tick marks indicating individual patients lost to follow up. Because there were 0 of 5 ‘Unsuitable patients’ who recurred there is no Green line, however the Green Tick marks indicate individual ‘Unsuitable’ patients lost to follow up. *Note there were no recurrences in the Unsuitable group and 7 recurrences in the Cautionary group, however these two groups were combined for clinical and statistical purposes. Green tick marks indicate last follow up for each Unsuitable patient