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Study design

This trial was a retrospective study on postoperative AHF IMRT (MARA-1). Preliminary positive results in terms of acute toxicity were previously published on a group of 99 patients.12 From that analysis and the evidence coming from randomized trials,8,9 the MARA-1 schedule became our institutional standard protocol for postoperative RT in low-risk early-stage BC.


The primary endpoint was to evaluate late (cutaneous and subcutaneous) toxicity. Secondary endpoints were acute toxicity, LC, and survival.


Patients at low risk of recurrence were eligible for the study. Inclusion criteria were as follows: confirmed histologic evidence of early-stage BC who underwent BCT, postmenopausal (at least 3 years) status, and patients with clear surgical margins (>3 mm). Exclusion criteria were pT4 pathologic stage, positive or close resection margins, ≥3 metastatic axillary nodes, nodal irradiation, and distant metastasis.

Treatment planning

All patients had computed tomography scans for treatment planning. An alpha cradle immobilization device was used for patient treatment reproducibility. The clinical target volume 1 (CTV1) delineation included the tumor bed, while the clinical target volume 2 (CTV2) was the entire WB tissue with the exclusion of the skin (5 mm). The planning target volumes (PTV1 and PTV2) were defined as CTV1 and CTV2 plus an isotropic 8 mm margin excluding the skin surface. In the CG patients, the WB tissue was irradiated by two conformed tangential beams with standard multileaf collimators and wedge filters while the tumor bed (boost) was irradiated by a direct electron beam. The dose was prescribed according to the ICRU 62 report. In the MARA-1 patients, the treatment planning optimization was obtained using a forward-planned IMRT technique, as previously described.12 This is a simplified form of IMRT, in which the contribution from each tangential beam was divided into two different segments. One segment was designed to include the WB using 6 MV photon beams. This configuration, in the absence of filters, results in a volume of underdosage in the thickest region of the breast. From this resulting inhomogeneous dose distribution, the second segment, usually with 15 MV photon energy, was conformed to block the dose >107% and directed to the areas of underdosage in order to increase the dose to the deepest part of the breast while sparing the most superficial part (Figure 1).