102 - NOVEMBER, A Phase II Trial of a 9 Day Course of Whole Breast Radiotherapy for Early Stage Breast Cancer

M. M. Poppe¹, K. Boucher¹, D. K. Gaffney¹, K. Brownson¹, G. Smith², J. Howell³, F. Ticona³, and K. E. Kokeny¹; ¹Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, ²Huntsman Cancer Institute, Salt Lake City, UT, ³Department of Radiation Oncology, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT

Purpose/Objective(s): 15-16 fraction (fx) whole breast radiation (RT) after lumpectomy has become a standard of care for early-stage breast cancer (BC). We prospectively evaluated a novel 9 fx course of daily whole breast RT with simultaneous boost to the lumpectomy cavity. Based on the UK Start B trial reporting 80% of patients (pts) having good to excellent cosmetic outcome at 24 mos., we designed a single institutional phase 2 non-inferiority trial with a hypothesis that > 70% of pts would have good to excellent overall cosmetic breast scoring 24 mos. after completing RT, assuming a baseline excellent/good cosmetic scoring of 80% with an 80% power to reject the null hypothesis, a= 0.1. Materials/

Methods: We enrolled Tis and T1-3N0 BC pts to receive 3420 cGy to the whole breast with simultaneous boost of 3960 cGy to the lumpectomy cavity over 9 daily fractions. We utilized 3D planning with tangents or intensity modulated photon RT. The primary endpoint was assessed utilizing EORTC cosmetic scoring/with bilateral photographs 24 mos. after RT, averaged from three unbiased, independent reviewers (breast surgeon, radiation oncologist and oncology nurse).
Results: From 2018-2020, under IRB approval, we prospectively enrolled 102 pts. 95% of pts had ductal histology, 74% = 2cm invasive, 14% > 2cm and 12% pure DCIS. Of invasive disease, 40% were grade 1 (G1), 38% G2 and 22% were G3. Pts age averaged 59.5 yrs. (33-82), with 5 pts < 40yrs., 20 pts between 41-50 yrs., and 14 pts > 70 yrs. With a mean follow-up of 51 mos., there were no local only recurrences and only one local + distant recurrence (brain and axilla). Without comparison to baseline, the 24 month post RT cosmetic photos were scored as 68% excellent/good, 32% fair/poor. The one-sided exact binomial p-value is 0.69. The null hypothesis was not rejected with one-sided 95% exact binomial confidence interval (CI) of 59.1%-100%. The two-sided 95% exact binomial CI was 57.4% - 77.7%. Eight pts reported a grade 3 toxicity event: RT dermatitis (4), breast infection (2), fibrosis (1), and atrophy (1). There were no late = G3 RT toxicity events which occurred or persisted > 6 months after RT with G2 only reported in 4 pts: fibrosis (2), rib fracture pain (1), and breast pain (1). Patient reported outcomes (PROs) utilizing the Breast-Q survey revealed breast satisfaction in 93% of women at 24 months with the remaining 7% unsatisfied with their breast even at their pre-RT baseline.
Conclusion: NOVEMBER demonstrates a novel 9 fx whole breast RT schedule with integrated lumpectomy cavity boost. Although we did not meet our pre-specified statistic goal of good/excellent cosmetic result in > 80% of pts, we demonstrate excellent local control and low RT toxicity, despite a significant proportion of our patient being under the age of 50. These cometic results are similar to those seen in the Canadian NCIC hypofractionation trial and patients had high breast satisfaction PROs. We hope to move this concept forward in a randomized trial against the UK Fast Forward regimen, inclusive of a lumpectomy cavity boost.