Defining the Optimal Dose for 3-Dimensional Conformal Accelerated Partial Breast Irradiation: 15-Year Follow-Up of a...

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.

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.

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).

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.