Interim Analysis of Dose-Escalated Preoperative Breast Irradiation: A Phase Ib study

Breast irradiation (RT) is often recommended as part of breast conservative therapy (BCT) and is often delivered daily over multiple weeks after breast conserving surgery (BCS). Information regarding tumor response is lost when BCS is performed before oncologic treatment. Short course partial breast irradiation delivered preoperatively (PRT) is a potential solution.

Following informed consent, ten participants enrolled in one of four cohorts of HCC 22-003 ( NCT05464667 ). Each of the first three cohorts enrolled three participants, and one enrolled in the fourth cohort, with dose-escalation to the gross tumor volume (GTV) by 5 Gy (from 30 to 45 Gy). Participants underwent BCS within five to ten days following PRT. Pre- and post-RT contrast-enhanced breast MRI and blood work was obtained for those who consented and were able to undergo such procedures. Magee Equation 3 was calculated on all core biopsy specimens and genomic oncotype testing performed as indicated per medical oncology expert opinion.

No patients experienced ≥ grade 2 or higher acute toxicity. No pathologic complete response (pCR) occurred following PRT on interim analysis of cohorts one to three. Three patients (two of which were in cohort three, 40 Gy to GTV) had decrease in tumor size noted from pre-to post-PRT MRI. Further, two of the three patients in cohort three had substantial pathologic tumoral response to PRT. Significant increase in TNFa and INFb serum levels were seen post-RT for cohort three compared to cohorts one and two.

Dose-escalated PRT is safe, feasible, and well tolerated. There appears to be a tumoral response noted on MRI and final pathology with dose escalation to 40 Gy to the GTV. Continuation of dose-escalation to cohort four is planned with final analysis reported following completion.