Accelerated, Hypofractionated Whole-Breast Radiation Therapy In Women With Breast Cancer: A Phase 2 Trial

Breast conserving therapy has become standard of care in treating early stage breast cancer. Standard course whole breast irradiation (WBI) takes approximately 6 weeks. The promise of short-course WBI lies in the added convenience it may offer to patients. Given excellent cure rates and low morbidity with current adjuvant radiation therapy technique and fractionation, it is natural that subsequent improvements in the field take convenience and economic impact into account. We evaluated a short course of hypofractionated, accelerated whole breast irradiation (AWBI) in which the goal was to complete therapy in 3 weeks inclusive of a sequential boost. Our primary endpoint was freedom from locoregional failure; we incorporated early stopping criteria based on predefined toxicity thresholds. Cosmesis was examined as a secondary endpoint. We conducted a prospective, single arm study of patients with DCIS or early stage invasive carcinoma receiving AWBI and a tumor bed boost after lumpectomy. We delivered a whole breast dose of 36.63 Gy in 11 fractions of 3.33 Gy delivered over 11 days, 1 fraction per day (EQD2 = 45 Gy). Patients received a mandatory lumpectomy bed boost delivered in 4 fractions of 3.33 Gy delivered once daily (EQD2 = 15 Gy). We allowed treatment of regional lymph nodes if indicated, as well as treatment in the prone position. Acute toxicities were scored using CTCAE v 4. Late toxicities were scored using the RTOG/EORTC scale. Cosmesis was scored using the Harvard Cosmesis Scale. We enrolled 83 women between 2009 and 2012 with Stage 0-IIIa breast cancer. Median follow-up is 33 months. Median age at AWBI is 53.4 with a range of 33.1-79.1 years. Thirty percent of patients were less than 50 years old at AWBI. There were no grade 4 or 5 toxicities. One patient experienced grade 3 and 2 patients had grade 2 toxicity. In regards to local control, there were 2 cases of isolated ipsilateral breast tumor recurrence (IBTR) (2/83, crude rate 2.4%). One patient had simultaneous IBTR and distant metastases, while another, had an in breast secondary malignancy (angiosarcoma). Breast cosmesis evaluation revealed that 89% of patients had good/excellent cosmesis. Our phase 2 institutional study offers one of the shortest courses of AWBI--delivered in 15 fractions with a boost. We demonstrated expected low toxicity and high local control rates with this novel fractionation scheme. Patients enrolled in this study had good-excellent cosmetic outcomes. We believe our fractionation scheme is feasible and offers women WBI in a highly convenient schedule. We have opened accrual to an expanded cohort of patients to this study for a descriptive analysis of long-term cosmesis.