5-Year Results from a Prospective Phase II Trial of Ten-Fractions Hypofractionated Radiotherapy in Locally Advanced Breast Cancer

Abstract

There is a growing interest for adjuvant loco-regional hypofractionated radiotherapy (Hypo-RT) regimens in patients (pts) undergoing surgery for locally advanced breast cancer (LABC). We report the 5-year results of a phase II study on Hypo-RT targeting the primary and regional lymph nodes in ten fractions (fxs). A schedule of 34 Gy/10 fxs/2 wks to the whole breast/chest wall and to the draining lymph nodes was used; an optional single fraction 8 Gy boost was administered with electrons to the tumor bed in patients who had undergone conservative surgery. Both acute (CTCAE 4.0) and late (LENT/SOMA) toxicities were collected. All pts but those who underwent mastectomy without reconstruction or with temporary expander were also asked to rate their cosmetic outcome according to the Harvard scale. Toxicity was assessed weekly during RT and then at each follow-up (fup) examination (1, 3, 6 months and then yearly). Late toxicity was assessed starting from 3 months after the end of Hypo-RT and loco-regional toxicity was prospectively collected. Cancer related endpoints in terms of loco-regional (LR) recurrence, distant metastasis, specific disease- free survival and overall survival (OS) were evaluated from the date of RT start to the diagnosis of local relapse/distant metastases or the last fup respectively. From February 2015 to March 2019, 59 women (median age 60 yrs, IQR: 48.3-68.8 yrs) with stage II to IIIA breast cancer who underwent axillary dissection and conservative surgery (83%) or mastectomy (17%) were accrued. One patient was lost to fup immediately after the end of RT. Of the 58 evaluable pts, 56 underwent neo-adjuvant (27.5%) or adjuvant (57%) chemotherapy and 15.5% exclusive hormone therapy as well. Trastuzumab was administered concomitant to RT in HER2 positive pts (25%). All pts completed treatment as planned. No grade 2+ acute toxicity was recorded. At the median fup of 63 months (range: 25-92 mths), the cumulative incidence of any grade locoregional late toxicity estimated with the Kaplan-Meier method is 43.4% (95% CI) (30.0% and 46.1% for patients undergone mastectomy and lumpectomy, respectively). Peak 2 events have been observed for fibrosis (1 pt, 1.7%), telangiectasia (1 pts, 1.7%) and lymphoedema (1 pt, 1.7%). One patient (1.7%) experienced grade 3 breast retraction. Of all eligible patients (N = 51), patient reported cosmetic outcome was excellent, good, fair and poor in 51.7%, 22.4%, 10.3% and 3.4%, respectively. No late lung toxicity was observed. The actuarial LR control rate at 5 years is 98%; for distant metastasis-free survival, specific disease-free survival and OS rates are 89.2%, 80.8% and 93.7% respectively. Our results support the activity of a 10-fxs Hypo-RT schedule targeting the primary site as well as the draining lymph node stations after surgery for LABC.