PURPOSE: Randomized trials have demonstrated similar local tumor control in patients treated with accelerated partial-breast irradiation (APBI) compared with whole-breast irradiation. However, the optimal APBI dose for maximizing tumor control and minimizing toxicity is uncertain. METHODS AND MATERIALS: We enrolled patients ≥18 years of age with grade 1 or 2 ductal carcinoma in situ or stage I invasive breast cancer and resection margins ≥2 mm between 2003 and 2011 to a sequential dose-escalation trial using 3-dimensional conformal external beam APBI giving twice daily 4 Gy fractions with total doses of 32 Gy, 36 Gy, and 40 Gy. Most were irradiated using mini-tangents plus en-face electrons or 3 to 4 coplanar photon beams
19 patients in the 32 Gy dose cohort were treated with protons. RESULTS: The trial accrued 324 patients (99, 101, and 124 in 32 Gy, 36 Gy, and 40 Gy cohorts, respectively). The median follow-up was 15.2 years. The 15-year cumulative incidence of local failure in each dose cohort was 6.9%, 5%, and 3.9% in the 32 Gy, 36 Gy, and 40 Gy cohorts, respectively (log-rank P = .21) The 10-year cumulative incidence of local failure in each dose cohort was 5.2%, 5.2%, and 2.2%, respectively (log-rank P = .2). Ten-year rates of moderate or severe fibrosis by physician assessment in each cohort were 40%, 58%, and 67%, respectively (log-rank P <
.01). The 10-year rates of fair or poor cosmesis by patient self-assessment were 25%, 30%, and 49% in each cohort, respectively (log-rank P <
.01)
physician assessment yielded similar 10-year rates of 21%, 39%, and 61%, respectively (log-rank P <
.01). CONCLUSIONS: There were no significant differences in local failure rates between 32 Gy, 36 Gy, or 40 Gy delivered in twice daily 4 Gy fractions, but fibrosis and cosmetic outcomes were worse for patients treated to the 2 higher doses. Hence, our study did not show the benefit of administering more than 32 Gy using this fractionation scheme.