Postoperative Single-Fraction Partial-Breast Irradiation for Stage 0 and I Breast Carcinoma: Results of a Prospective Single Institution Phase I/II Clinical Trial

Abstract

To assess tolerability, efficacy, quality of life and cosmetic outcomes of a prospective phase I/II trial of single fraction high gradient partial breast irradiation (SFHGPBI) given postoperatively after partial mastectomy in select patients with stage 0/I breast cancers. Postmenopausal women aged ≥50 years with hormone receptor positive, HER2/neu nonamplified pathologic T1N0 or Tis (=< 2cm) N0 breast cancer treated with partial mastectomy with negative histologic margins by at least 2 mm were treated with postoperative SFHGPBI, 20 Gy to the cavity surface while simultaneously prescribing 7 Gy to a planning target volume (PTV) defined as the surgical bed plus 1 cm of surrounding breast tissue. Co-primary endpoints were grade 3+ toxicity per CTCAE v4.0 and ipsilateral breast tumor recurrence (IBTR). Between 2014 and 2018, 50 patients were enrolled and received SFHGPBI. Patients had either stage I (n=40) or stage 0 (n=10) breast carcinomas. Mean heart dose was 0.43 Gy (range, 0.07 – 1.52 Gy), and maximum skin rind dose was 17.87 Gy (range, 8.43 – 28.53 Gy).With a median follow-up of 21 months, one patient developed a non-invasive IBTR in a separate untreated quadrant 18 months after HGPBI. One other patient developed an ipsilateral axillary recurrence 30 months after HGPBI. There have been no recurrences in the treated quadrant or distantly, with no intercurrent deaths observed. No grade 3-5 toxicities have been observed. All but 3 toxicities have been grade 1, with 17 patients (34%) having small areas of hyperpigmentation in the treatment region, 9 patients having grade 1 fibrosis, and 9 patients having transient breast pain. Grade 2 fibrosis and grade 2 chest wall pain was observed in 2 and 1 patients, respectively. Patient-reported quality of life (QOL) data per EORTC QLQ-30 and QLQ-BR23 collected at baseline and at each follow-up revealed that SFHGPBI had no detrimental effect on overall QOL as well as each of the sub-domains evaluated. Quantitative cosmetic evaluation using the percentage of breast retraction assessment (pBRA) revealed that there was a trend toward improvement in pBRA at 8 weeks (mean, 7.25%) and 12 months (6.97%) post-RT, compared to pretreatment pBRA (8.26%). The rates of good-to-excellent cosmesis reported by patients and the treating physician were 98% and 100% pretreatment, 98% and 100% at 8 weeks, and 100% and 100% at 1 year, respectively. SFHGPBI is a feasible, convenient, and well-tolerated method for delivering adjuvant radiation in patients with low-risk stage 0 and I breast cancers. No grade 3+ toxicity was observed, with low rates of acute adverse events. SFHGPBI had no detrimental effect on patient-reported quality of life, and both patient and physician-reported qualitative and quantitative cosmesis was preserved. Initial local, regional, and distant control rates were excellent.