Comparison of partial breast radiation modalities in women with early-stage breast cancer: a target trial emulation

Background Partial breast irradiation (PBI) is an effective treatment for early-stage breast cancer. However, evidence comparing different PBI modalities is limited. Methods This trial emulation uses electronic health records from a multi-state large tertiary health system. Three PBI modalities were compared proton radiation therapy, photon radiation therapy, and applicator-based brachytherapy. Inverse probability weighting (IPW) was used to balance confounders. The primary outcome was ipsilateral breast recurrence (IBR). Results Between 2013-2023, 1,041 women with early-stage breast cancer were treated with PBI. 1,026 patients were included in the analyses. The median age was 66 years; 22.51% had DCIS, and 97.56% were estrogen receptor positive. With median followup of 38.2 months, the rate of IBR in the overall group was 3.05% (95% CI 1.99-4.65%) at 3 years. After IPW, Compared to photon PBI, the hazard ratio (HR) for IBR for proton PBI was 2.11 (95% confidence interval [CI] 0.70-6.33), and for brachytherapy, 3.86 (95% CI 1.39-10.69). Compared to proton PBI, the HR for IBR for brachytherapy was 1.83 (95% CI 0.88-3.81). IBR risk was similar across PBI modalities for patients with tumor size ≤ 10 mm and in patients treated for DCIS. Among patients with tumor size >10 mm, the HR for IBR for brachytherapy was 7.64 (95% CI 1.64-35.58) and 3.59 (95% CI 1.22-10.56) relative to photons and protons, respectively. Conclusion Partial breast irradiation with applicator-based brachytherapy was associated with higher ipsilateral breast recurrence than photon or proton PBI in patients with tumor size > 10 mm, suggesting the need for more careful PBI patient selection for this modality.