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

Summary

In a prospective 3D-CRT APBI dose-escalation trial (4 Gy BID; 32, 36, 40 Gy) with 324 patients and 15.2-year median follow-up, local failure did not differ significantly across doses, but 10-year moderate/severe fibrosis and fair/poor cosmesis increased with higher doses. The data support avoiding >32 Gy in this fractionation scheme.

Key Findings

• Local failure rates at 15 years: 6.9% (32 Gy), 5% (36 Gy), 3.9% (40 Gy); no significant differences (P=.21).
• 10-year moderate/severe fibrosis increased with dose: 40% (32 Gy), 58% (36 Gy), 67% (40 Gy) (P<.01).
• 10-year fair/poor cosmesis rates were higher at higher doses by both patient and physician assessments (patient: 25%, 30%, 49%; physician: 21%, 39%, 61%; both P<.01).
• No demonstrated benefit to delivering >32 Gy with 4 Gy BID APBI in this design.

Clinical Implications

For 3D-CRT APBI using 4 Gy BID, select 32 Gy to minimize fibrosis and poor cosmesis without compromising local control; incorporate patient-reported outcomes in counseling.

Limitations

• Non-randomized sequential cohorts; potential selection and temporal biases
• Generalizability to modern techniques (e.g., IMRT, prone setups) and other fractionations may be limited

Future Directions

Randomized comparisons of dose/fractionation with contemporary APBI techniques; mechanistic studies linking dose and fibrosis; integrate advanced imaging and PROs in prospective registries.