Breast/Soft TissueAccelerated partial-breast irradiation with high-dose-rate brachytherapy: Mature results of a Phase II trial
Introduction
Breast-conserving surgery (BCS) followed by whole-breast irradiation (WBI) became the standard treatment for early-stage breast cancer after publication of Phase III randomized trials [1], [2]. Although WBI is effective, it is a long-lasting treatment involving about 6 weeks in conventional schedules (3) and 3 weeks in hypofractionated ones [4], [5], [6], [7], [8]. Moreover, WBI could expose skin, lungs and heart to risk of radiation-related toxicity (9).
After BCS, most local recurrences occur inside or close to tumor bed (10). Accelerated partial-breast irradiation (APBI) is a form of radiation therapy which treats in few days only the breast area where the tumor has been removed (11). Reducing treatment time and sparing healthy tissues, APBI can be as effective as WBI in local control and cancer-specific survival (CSS) for selected patients with early-stage breast cancer [12], [13], [14].
The APBI has been the object of investigation for several years [15], [16], [17], [18] and, to date, several Phase III trials comparing various APBI techniques to WBI have been published.
TARGIT-A (19) and ELIOT (20) trials using intraoperative radiotherapy failed because they found a significantly increased risk of local breast recurrence after intraoperative radiotherapy vs. WBI. While in Florence trial (21), in IMPORT-LOW trial (22), and in Barcelona trial (23), investigating the role of external beam APBI vs. WBI, the 5-year risk of local breast recurrence was similar in both arms.
Interstitial multicatheter irradiation, provided with a low-dose-rate brachytherapy (LDR-BRT) or high-dose-rate brachytherapy (HDR-BRT), is the earliest form of APBI developed [24], [25]. In parallel to fractionation schedule of WBI, the optimal total dose and fractionation schedule for APBI continues to evolve (26). Currently, techniques using HDR-BRT typically utilize eight or 10 fractions delivered twice daily over 4–5 days [27], [28], [29], [30]. Fractionations recommended in clinical practice should correspond to a biologically equivalent total dose EQD2 (α/β = 4–5 Gy) in the range of 42–45 Gy (28).
Two Phase III trials comparing brachytherapy vs. WBI established the noninferiority of APBI in local control, disease-free survival (DFS) and overall survival (OS) [31], [32]. Moreover, in GEC-ESTRO randomized trial, the 5-year toxicity profile and cosmetic result were similar in both arms [33], [34].
Although the APBI with brachytherapy has been investigated in thousands of patients, at this time, there are few data reporting clinical outcomes and toxicity with at least 10 years of followup [18], [31], [35], [36], [37]. The goal of this analysis is to describe long-term clinical and cosmetic outcomes of our patients with early-stage breast cancer submitted to APBI with interstitial HDR-BRT in a Phase II prospective trial.
Section snippets
Methods and materials
From May 2005 to November 2013, both Perugia University Radiotherapy and our Centre have recruited in a Phase II trial of adjuvant APBI with interstitial HDR-BRT patients with early-stage breast cancer who had undergone BCS. Results with a median followup of 96 months have been already described (38). In the present article, we report an update of outcomes with a longer followup (median, 110 months) of patients treated in our center.
Patient characteristics
Median age of our 133 patients was 67 years (range, 42–85). Most patients were postmenopausal and had an excellent performance status. The median tumor size was 1.2 cm (range, 0.3–3 cm). Most (90%) patients were pT1b-pT1c. All patients were axillary node negative; of these, 36/133 (27%) and 97/133 (73%) patients underwent axillary node dissection and axillary node sampling or sentinel analysis, respectively. All patients had invasive not lobular cancer and most (61%) had Grade 2 histologic
Discussion
Our trial confirmed that in selected patients with early-stage breast cancer, APBI with HDR-BRT allows excellent 10- and 13-year local control (98% and 95%, respectively) and CSS (100%).
Recently, results of GEC-ESTRO trial (32), the largest randomized trial comparing APBI with HDR-BRT and WBI, have been published. In this trial, the 5-year cumulative incidence of LR was 1.44% in APBI vs. 0.92% in WBI (p = 0.42). As in the GEC-ESTRO trial, we had a very low 5- and 10-year LR rate (0% and 1.5%,
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Cited by (2)
Financial disclosure: This study was not funded.
Conflict of interest: All Authors declare that they have no conflict of interest.
Ethical approval: All procedures performed in this study involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Informed consent: Informed consent was obtained from all individual participants included in the study.