Pathologic Response and Acute Toxicity: Planned Interim Analysis of the Phase 2 NeoRT Trial Evaluating Preoperative Single Fraction Partial Breast Radiation Therapy in Early Stage Breast Cancer

Abstract

Pre-operative partial breast irradiation (PBI) has been explored as an alternative to adjuvant breast radiotherapy. Practically, this approach has the potential to limit treatment volumes while simultaneously providing an avenue to study breast cancer radiation response. In this Phase II study, we hypothesized that 20% of patients would have a complete pathologic response at surgical resection six weeks after preoperative radiation. Histologically confirmed breast cancer patients with ER(+) or PR(+), Her2(-) T1N0 invasive breast cancer or Tis <2cm were enrolled in this single institution, IRB approved, Phase II study delivering 21Gy preoperatively to the intact tumor. Toxicity was scored using CTCAE version 4.0. Any toxicity possibly, probably or definitely related to radiotherapy is reported. Interim analysis was planned to assess complete pathologic response rates, defined as no residual invasive or in-situ tumor. Residual cancer burden (RCB) was also calculated. 20 of 40 planned patients have been enrolled. Three patients were subsequently ineligible on MRI but fifteen have proceeded to surgical resection. Two patients have received radiation but not surgery at the time of this analysis. The median age was 61 (range 58-77), 87% of patients were white and 87% had invasive ductal carcinoma. One patient had a post-operative wound infection and grade 3 seroma requiring drain placement. A second patient had a small area of wound dehiscence with seroma leakage. Remaining toxicities were grade 1-2 and consisted primarily of discomfort, seroma, fatigue and skin change. Pathologic complete response was noted in 1 patient (7%). Another had a pCR by RCB assessment, both with DCIS on pre-treatment biopsy. 5 patients (33%) had an RCB of I, and 8 patients (53%) an RCB of II. Fifteen women with early stage breast cancer have completed a single preoperative fraction of 21Gy followed by surgical resection at six weeks. Two (13%) grade 3 post-operative toxicities and one (7%) pathologic complete response were noted. This interim analysis suggests an increase in post-operative complications relative to our Phase I experience and a low rate of complete pathologic response in invasive disease. We plan to increase accrual in order to better define the optimal timing of surgical excision relative to operative complications and tumor response.