Radiation Therapy Dose and Fractionation Schedules for Breast Angiosarcomas: An Analysis of the National Cancer Database

Abstract

Breast angiosarcoma (AS) is an uncommon malignancy that is either secondary to prior radiation therapy (RT) or can occur in the primary setting in the absence of prior RT. Since these malignancies are rare, there are scant prospective data to guide the optimal use and timing of surgery, chemotherapy and RT. Here, we set to focus on details of RT use for primary AS and secondary AS with a focus on the dose, fractionation and timing of RT relative to surgery using the National Cancer Database (NCDB). We hypothesized that RT use would be more frequent in primary AS compared to secondary AS. In addition, we hypothesized that when RT is used, hyperfractionated schedules and preoperative RT would be more common in secondary AS compared to primary AS.We identified patients with a histologic diagnosis of AS from the NCDB from 2004-2016. Patients that were coded as having a prior malignancy were used as a surrogate to denote secondary AS whereas the rest were classified as primary AS. RT use was defined as conventional fractionation (1.8-2.0 Gy/fraction given daily); hypofractionated (> 2.0 Gy/fraction given daily); accelerated hyperfractionated (≤1.5 Gy/fraction given 2-3 times/day); palliative (total dose≤30 Gy); or unknown (insufficient RT details provided). Comparisons between the primary AS and secondary AS groups were performed using the chi-square test with P < 0.05 considered significant.We identified 1,174 patients with non-metastatic AS: 864 secondary AS, 310 primary AS. Radiation was used in 211 patients (18.0%) and was significantly more common in primary AS compared to secondary AS (36.1% [N = 113] vs. 11.4% [N = 98], P < 0.0001). The majority of patients received conventional fractionation (63.5%, N = 134) followed by unknown schedule (16.1%, N = 34), hyperfractionated RT (10.4%, N = 22), palliative RT (6.6%, N = 14), and hypofractionated RT (3.3%, N = 7). Fewer than 10% of patients (N = 18) received preoperative RT but its use was more common in secondary AS vs. primary AS (13.3% vs. 4.4%, P = 0.02). Accelerated hyperfractionated RT use was also more common in secondary AS vs. primary AS (19.4% vs. 2.7%, P < 0.0001). Fractionation schedules for the 22 patients treated with accelerated hyperfractionation included: 1.5 Gy BID to 45-60 Gy in 11 patients; 1.2 Gy BID to 50.4-60 Gy in 8 patients; 1 Gy TID to 45-60 Gy in 3 patients. An additional boost dose of 7.2-15 Gy was given to 11 of these 22 patients.Radiation use for the treatment of breast AS is uncommon, even for patients with primary AS. When RT is used, conventional fractionation schedules predominate. However, accelerated hyperfractionation is used more frequently in secondary AS with 1.5 Gy BID to doses≥45 Gy as the most common regimen. Preoperative RT is rarely used for AS based on this analysis. The under-utilization of RT and wide variations in RT dose/fractionation schedules emphasize the need for more standardized consensus guidelines for this rare but aggressive malignancy.