Supplemental radiation doses delivered concomitantly with hypofractionated whole breast irradiation in 15 fractions demonstrated non-inferior ipsilateral breast recurrence and similar toxicity compared with sequential boosts following whole breast irradiation in high-risk early-stage breast cancer.
Radiation boosts administered concomitantly with hypofractionated whole breast irradiation (H-WBI) was found to yield non-inferior ipsilateral breast recurrence (IBR) and decreased treatment time vs sequential boosts following standard WBI for patients with high-risk early-stage breast cancer post-lumpectomy, according to data from a trial presented at the 2022 American Society for Radiation Oncology (ASTRO) Annual Meeting.
With a median follow-up of 7.4 years, the 5-year estimated IBR was 2.0% (90% CI, 1.4%-2.9%) for the WBI with sequential boost cohort and 1.9% (90% CI, 1.3%-2.7%) for the H-WBI with concurrent boost cohort. Moreover, the estimated 7-year rate was 2.2% (90% CI, 1.5%-3.0%) for the WBI cohort and 2.6% (90% CI, 1.9%-3.5%) for the H-WBI cohort (HR, 1.32; 90% CI, 0.84-2.05; non-inferiority test P =.039).
The investigators enrolled a protocol-specified population at high risk following lumpectomy with stages 0, I, and II disease. Patients were randomly assigned to 1 of 2 treatment arms. In arm 1, 1124 patients received WBI at 50 Gy in 25 fractions or 42.7 Gy in 16 fractions along with a sequential boost of 12 Gy in 6 fractions or 14 Gy in 7 fractions. In the second cohort, patients received H-WBI at 40 Gy in 15 fractions equaling 2.67 Gy daily along with a concurrent boost of 48.0 Gy equaling 3.2 Gy daily. Additionally, investigators stratified patients based on age, whether they received chemotherapy prior to randomization, histologic disease grade, and estrogen receptor (ER) status.
The primary end point of the trial was to determine if IBR for a boost administered concomitantly with H-WBI was no worse than boosts delivered sequentially following WBI. Secondary end points included the cosmetic results and determining whether it was feasible to use intensity-modulated radiation therapy (IMRT) and three-dimensional conformal radiation therapy (3DCRT) in a multi-institutional, post-lumpectomy setting for patients with early-stage breast cancer.
The median patient age in the WBI and H-WBI cohorts, respectively, were 50.5 and 55.0 years. Across both respective cohorts, 36% and 35% of patients were younger than 50 years, 35% and 33% had pathologic stage II disease, 52% and 52% had grade 3 histology, and 30% and 31% had ER-negative breast cancer. Additionally, 16% and 17% of patients had close surgery margins, 8% and 11% had an oncotype higher than 25, 3% and 3% had grade 3 ductal carcinoma in situ and were younger than 50 years, 60% and 61% had received chemotherapy prior to randomization, and 11% and 10% received endocrine therapy at the time of study entry, respectively.
Among 199 evaluable patients in the WBI cohort and 216 patients in the H-WBI cohort, respectively, 3-year global cosmesis scores (GCS) of excellent/good were reported in 86% and 82% of patients, and fair/poor scores were reported in 14% and 18% of patients (P = .33) There was no difference in the mean or mean change of GCS from baseline to 3 years between treatment arms. Moreover, investigators concluded that the use of volume-based radiation planning for 3DCRT and IMRT WBI was feasible and resulted in low toxicity for both treatment arms regardless of fractionation or boost delivery.
In terms of adverse effects (AEs) that were described as being definitely, probably, or possibly related to protocol treatment, grade 3 or higher AEs were seen in 3.3% of those in the WBI sequential boost cohort and 3.5% of those in the H-WBI concurrent boost cohort (P = .79) No grade 5 AEs were observed in either cohort. A total of 39 patients were excluded from the safety population, 35 of whom did not receive radiotherapy and 4 had no AE data submitted. Trial investigators concluded that there was no significant difference in toxicity between arms.
Vicini FA, Winter K, Freedman GM, et al. A phase III trial of hypofractionated whole breast irradiation with concurrent boost versus conventional whole breast irradiation plus sequential boost following lumpectomy for high risk early-stage breast cancer. Presented at 2022 American Society for Radiation Oncology (ASTRO) Annual Meeting; October 23-26, 2022; San Antonio, TX. Abstract 1. Accessed October 28, 2022.