Background. Accelerated partial breast irradiation (APBI) has been introduced as an alternative treatment method for selected patients with early stage breast cancer (BC). Intensity modulated radiotherapy (IMRT) had theoretical advantage of further increase in dose conformity compared to 3D technique, with more normal tissue sparing.

We present the results of a randomized equivalence trial comparing local recurrence and survival of APBI using IMRT technique to conventional WBI in early stage BC.

Methods. This study was performed at the University of Florence (Florence, Italy). Women aged more than 40 years affected by early breast cancer, with a maximum tumor diameter of 25 mm, suitable for breast-conserving surgery, were randomly assigned in a 1:1 ratio to receive either external whole-breast irradiation (WBI) or APBI using IMRT technique.

Patients in the APBI arm received a total dose of 30 Gy in 5 fractions to the tumor bed. Those in the WBI arm received 50 Gy in 25 fractions, followed by a boost of 10 Gy in 5 fractions. For this equivalence trial the prespecified equivalence margin was local recurrence of 5% in the APBI arm. The primary endpoint was occurrence of ipsilateral breast tumor recurrences (IBTR); overall survival (OS) and treatment toxicity were secondary endpoints. Treatment tolerance was assessed using the acute and late radiation morbidity scoring scheme from Radiation Therapy Oncology Group (RTOG) and the European Organization for Research and Treatment of Cancer (EORTC). Cosmetic outcome was scored on the Harvard Breast Cosmesis scale.

This trial is registered with, number NCT02104895.

Results. 520 patients were randomized (260 to external WBI and 260 to APBI with IMRT) between 2005 and 2013.

At a median follow-up of 5 years (range 0.6-9.0), we recorded 6 IBTR: 3 sited in the quadrant index (true recurrence) and 6 in other quadrants. The mean time to IBRT was 2.9 years (range 1-4). The 5-year IBTR rate was 1.5% (3 cases) in the APBI group (95% CI 0.1-3.0), within the prespecified equivalence threshold of 5%, in comparison to that of WBI group (1.4%; 95% CI 0-2.8). No statistically significant difference emerged between two groups (log rank test p=0.86).

OS at 5 years did not significantly differ between the groups (p=0.057). We identified 8 deaths (5-year event rate: 2.1%; 95% CI 0.9-3.3), 7 in the WBI group and only 1 in the APBI group. The 5-year overall survival was 96.6% for the WBI group and 99.4% for APBI group.

Concerning acute adverse events, APBI group showed a statistically significant better safety considering any grade of skin toxicity (p=0.0001). No grade 3 toxicity was observed for APBI group. Concerning late side effects, only two cases (0.8%) experienced grade 2 toxicity in WBI group (skin fibrosis). In both treatment groups the cosmetic result was rated as excellent/good for more than 90% of patients. Overall, APBI group showed better outcome to WBI group (p=0.045).

Conclusions. To our knowledge this is the first randomized study using IMRT technique for APBI delivery. No statistical difference in terms of IBTR was shown between the two arms. APBI showed a significant better acute and late toxicity profile compared to WBI.

Citation Format: Lorenzo Livi, Icro Meattini, Livia Marrazzo, Stefania Pallotta, Gabriele Simontacchi, Calogero Saieva, Vieri Scotti, Carla De Luca Cardillo, Paolo Bastiani, Jacopo Nori, Lorenzo Orzalesi, Simonetta Bianchi. Accelerated partial breast irradiation using intensity modulated radiotherapy versus whole breast irradiation: 5-year survival results of a phase 3 randomized trial [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr S5-03.