First Results of the Primary Outcome of a Phase II Prospective Clinical Trial to Assess the Feasibility of Preoperative Radiation Boost in Breast Cancer Patients

A radiation boost targeted at the tumor bed is an important component of breast-conserving therapy (BCT) and has been shown to improve outcomes in patients with early-stage breast cancer. This is a prospective phase II study (NCT04871516) to assess the feasibility of delivering the radiation boost pre-operatively. This approach allows more accurate targeting of the high radiation dose at the tumor that may spare more normal breast tissue. We hypothesize wound complication rates to be comparable to standard treatment.The study design was a prospective phase II with a planned accrual of 55 patients. Women with non-metastatic node negative breast cancer or DCIS who were eligible for BCT were included. Patients were treated with pre-operative radiation boost of 1332 cGy in 4 fractions, followed by lumpectomy and adjuvant hypofractionated whole breast radiation to 3663 cGy in 11 fractions. The primary outcome of the study was to demonstrate that the incidence of grade 3 or more wound complications was not inferior to the current standard of care with conventional lumpectomy, postoperative whole breast radiation and a postoperative boost (6- 20%). Secondary outcomes included cosmetic outcome, local-regional control, and immunologic biomarkers induced by the preoperative radiation boost. We report here the results of the primary outcome of the study.Fifty-five women were enrolled between June 2021 and October 2022. Of those, 48 patients had at least 1 month follow up and were included in the analysis. Median age was 64 years-old, (range 40-77). Median follow up time was 2 months, (range 1-15). Forty-three patients (90%) had invasive cancers and 5 (10 %) had DCIS. Median clinical tumor size was 13 mm, (range 5-26). Median pathologic tumor size was 9 mm, (range 0-27). Margins were negative in 47 patients (98%). Two patients were found to have node positive disease on final pathology. Grade 3 wound dehiscence requiring surgical revision occurred in one patient (2%). There were no other grade 3 adverse side effects reported. Three patients (6%) had grade 2 wound infections requiring antibiotics. Cosmetic outcome at 1st follow up was available for 45 patients and was very good or excellent in 39 patients (87%). No patient had a poor cosmetic outcome.The use of a pre-operative radiation boost prior to lumpectomy followed by whole breast radiation as administered in this prospective trial resulted in an acceptable primary outcome with a similar rate of post-operative wound complications as the standard of care. We are currently enrolling patients on an expansion cohort to assess longer term cosmetic outcomes and performing a panel of immunologic markers to assess immune response to the preoperative boost.