Toxicity and Cosmetic Outcomes of 28 Gy in 5 Fractions Twice per Week Ultrahypofractionated Whole-Breast Irradiation in Early-Stage Breast Cancer.

Abstract

The UK FAST and FAST-Forward trials established the non-inferiority of ultrahypofractionated whole-breast irradiation delivered in five fractions with respect to local control, toxicity, and cosmetic outcomes. The optimal regimen and technical approach for ultrahypofractionated adjuvant radiotherapy, however, remain uncertain. This retrospective, single-institution study included women with ductal carcinoma in situ (DCIS) or early-stage invasive breast cancer who underwent lumpectomy followed by adjuvant whole-breast irradiation of 28 Gy in 5 fractions, delivered twice per week. Radiation was delivered using a 3D conformal radiotherapy (3D-CRT) technique, with the prone position used as the standard setup. Acute and late radiation toxicities were graded using CTCAE version 5.0, and cosmetic outcomes were evaluated by physicians using the Harvard scale. From February 2020 to March 2025, a total of 94 patients were included. The median age was 72 years. T1 disease was the most common (69.1%), and 18.1% had pure DCIS. 92.6% of patients were estrogen receptor positive and 74.5% were progesterone receptor positive. HER2 was negative in 96.1% of invasive cases. Oncotype DX scores were available in 45.5% of invasive cases, with a median score of 16. Most patients (79.8%) received endocrine therapy. All patients were treated with 3D-CRT, and 96.8% were treated in the prone position. No grade 3 or higher acute or late toxicities were observed. The most common acute grade 1-2 toxicities included fatigue (71%), dermatitis (53.3%), hyperpigmentation (29.9%), breast pain (29.3%), breast edema (24.4%), and pruritus (17.7%). At 1 year, the most frequent late toxicities were skin induration (75.8%), fatigue (58.8%), breast atrophy (56.9%), and hyperpigmentation (54.1%). Cosmetic assessment was available in 80 patients at 1 year, with 98.8% showing excellent-to-good and 1.2% fair results. An ultrahypofractionated regimen of 28 Gy in 5 fractions delivered twice weekly in the prone position using 3D-CRT appears to be safe and feasible, with acceptable cosmetic outcomes in this retrospective cohort. Further studies with longer follow-up and larger patient populations are warranted to validate these findings and assess long-term clinical outcomes.