Dr Rahimi on Escalating Preoperative, Single-Fraction Ablative Radiation in HR-Positive Breast Cancer

Asal Rahimi, MD, MS, chief, Breast Radiation Oncology Service, medical director, Clinical Research Office, Associate Vice Chair of Diversity, Equity, and Inclusion, Harold C. Simmons Comprehensive Cancer Center, associate professor, Radiation Oncology, UT Southwestern Medical Center, discusses initial efficacy results from the expanded cohort of a phase 1 dose-escalation study (NCT04040569) evaluating pre-operative, single fraction stereotactic ablative radiation in early-stage, hormone receptor (HR)–positive breast cancer.

The study was designed to explore whether escalating stereotactic partial breast irradiation (SPBI) to an ablative dose improves tumor responses without creating more intense toxicities for patients with early-stage HR-positive breast cancer in an interim analysis of an expanded cohort phase I dose escalation study (NCT04040569). S-PBI was administered at doses of 30, 34, or 38 Gy in a single fraction.

Results from the interim analysis of the study demonstrated that the combined pathologic complete response (pCR) and near complete response (nCR) rate was significantly higher in patients treated with the 34 Gy dose (n = 15; 93.3%) vs the 30 Gy dose (n = 8; 37.5%), demonstrating the dose-dependent effectiveness of this approach (P = 0.01). Among the patients who received 30Gy, 73% underwent surgery with a median interval of 4.3 months. However, none achieved a pCR, and 37.5% achieved a nCR. Conversely, 93% of patients at the 34Gy dose level underwent surgery with a median interval of 7.3 months, resulting in 46.6% achieving a pCR and 46.6% achieving a nCR. Notably, 50% of those with nCR had only minimal residual disease (1-3mm).

Additionally, there was a significant reduction of Ki67 from a mean of 12.2% at diagnosis to 1.9% after surgery and single-fraction pre-operative radiation. Moreover, 87.5% of patients with residual disease had a Ki67 level below 3% after treatment.

This study establishes that pre-operative single-fraction radiation, particularly at the 34Gy dose, is both safe and highly effective in early-stage HR-positive breast cancer. This study is ongoing, and the 38 Gy group is still accruing patients.