A total of 24 female patients who required post-mastectomy regional irradiation in the Department of Oncology, Xinqiao Hospital (Third Military Medical University, Chongqing, China) between May and October 2013 were selected for enrolment. Patients aged between 18 and 75 years, with an Eastern Cooperative Oncology Group score of 0–2 (21) and adequate function of the liver, kidney, heart and hematopoietic system were considered eligible for the study. Patients that had undergone radiotherapy of the axillary or supraclavicular lymph nodes were excluded from the study. Among the 24 enrolled patients, there were 11 cases of right-sided breast cancer and 13 cases of left-sided breast cancer. The median age of the patients was 54 years (range, 21–74 years). All cases involved ductal or lobular carcinoma in different quadrants and underwent mastectomy. The stages ranged from pT3N2M0 to pT4N3M0, and required post-mastectomy regional radiotherapy according to National Comprehensive Cancer Network guidelines (2013, V1) (22). Following immobilization of the patients with a thermoplastic body-fix frame in a supine on the treatment bed, the patients were scanned using a helical computed tomography (CT) scanner with a 5-mm slice thickness. Scan extension included the underside of the chin to the upper abdomen. The CT data were transferred to the commercial treatment planning system (TPS), Oncentra MasterPlan V4.1 (OMP; Nucletron BV, Veenendaal, The Netherlands), for contouring of targets and plan design. Written informed consent was obtained from all patients and the study was approved by the Medical Ethics Committee of Xinqiao Hospital, Third Military Medical University.

The radiotherapy physicians and planners used a standardized set of contouring guidelines (23). Target volumes and OARs were delineated and confirmed by three different qualified radiotherapy physicians. The clinical target volume (CTV) encompassed the post-operated chest wall, supraclavicular lymph nodes and internal mammary nodes. CTV was defined medially at the lateral edge of the sternum, including the sternal-rib junction, laterally at the preexisting breast tissue, including the mid axillary line, inferiorly at the inframammary fold and superiorly at the inferior edge of the cricoid cartilage. The medial extent of the mastectomy scar was typically included. Plan target volume (PTV) was obtained by expanding 3 mm in all directions except toward the skin. The border of the PTV on the skin side was at least 1 mm from the skin surface. The surrounding critical healthy tissues, including the contralateral breast, ipsilateral lung, spinal cord and heart, were contoured. An extra 3-mm margin was added to the spinal cord as the planning organ-at-risk volume (PRV).

All subsequent plans were conducted on OMP. For all patients, the prescribed dose was set to deliver 50 Gy normalized to 100% in 25 fractions encompassing at least 95% of the PTV, i.e., V_100%>95%, while ≤2% of any PTV would receive >110% of its prescribed dose; the PTV ranged from 269.00 to 783.00 cm³ (mean±standard deviation, 519.80±173.39 cm³). Other planning objectives for the OARs were as follows: Point dose of PRV of spinal cord, <10 Gy; percentage volume of ipsilateral lung receiving >20 Gy (V₂₀), <20% and 30 Gy (V₃₀), <10%; percentage volume of humerus receiving >50 Gy (V₅₀), <5%; and percentage volume of heart receiving >40 Gy (V₄₀), <20%. For the T4 patients with skin involvement, a bolus material with a thickness of 1 cm was added during the whole course, including immobilization, plan optimization, dosimetric calculation and radiation delivery.

Using identical CT datasets and the exact same contours, all VMAT and IMRT plans were created using 6-MV photon beams commissioned for a Varian Trilogy Linac, equipped with a 120-leaf Multileaf Collimator (MLC; Varian Medical Systems, Palo Alto, CA, USA), with a maximal leaf speed of 2.5 cm/sec, a maximal jaw speed of 1.5 cm/sec, a maximal gantry speed of 6 cm/sec and a variable dose rate of up to 600 MUs/min. The optimization constraints and relative priorities were the same for the IMRT, and 1ARC and 2ARC VMAT plans. IMRT beams were equally spaced through the 200 sector angle in the axial plane, with fixed five gantry angles delivered in a step-and-shoot mode. 1ARC VMAT consisted of a single 200° rotation, while 2ARC VMAT consisted of two coplanar arcs of 200°, optimized simultaneously and delivered with opposite rotation (clockwise and anticlockwise). The isocenter was placed at the center of the PTV. For the two VMAT plans, the couch angle was set as 0° and at the same time, the collimator was set at 10°. The collapse cone photon dose calculation algorithm was used for all cases. The dose calculation grid was set at 2.5 mm. Each plan was formulated by three different radiotherapy physicists and confirmed by three different radiotherapy physicians.

The dose to the OARs, including the contralateral breast, ipsilateral lung, double lungs, spinal cord and heart, was measured and compared among the three planning techniques. The plans were evaluated according to dose-volume histogram (DVH) analysis, and plan quality was assessed by calculating the mean dose to the contralateral breast, ipsilateral lung, double lungs and heart, and the maximum dose to the spinal cord. The CI and HI were calculated according to the Radiation Therapy Oncology Group definition (24,25) as follows: CI = V_RI / TV and HI = I_max / RI, with V_RI representing the volume (V) of the prescribed dose for the PTV, TV as the total volume of the PTV, I_max representing the maximum dose and RI as the prescribed dose of the PTV. These two formulae were therefore changed to CI = V_Dprescribed / V_PTV and HI = D_max / D_prescribed. A CI and HI tendency towards a value of 1 demonstrated that the plan could be improved. Delivery parameters were recorded in terms of MU per fraction, mean dose rate, beam-on time, treatment time and TTT (defined as beam-on plus machine programming and setting time, but excluding patient positioning and imaging procedures).

All data presented in the text, tables and figures are presented as the mean ± standard deviation. For statistical analysis, exact Wilcoxon signed rank tests were used to assess any differences between the treatment parameters. Differences were considered statistically significant at P<0.05. All computations were performed using the IBM SPSS statistics program (version 19; SPSS Inc., Chicago, IL, USA). All statistical tests were two-sided.

The typical axial, coronal and sagittal dose distributions produced by each of the three techniques in one representative case are displayed in Fig. 1. Fig. 2A demonstrates the mean DVH of the PTVs, comparing the three techniques for the entire cohort. Fig. 2B–D reports the average DVH computed for OARs, including the heart, contralateral breast and ipsilateral lung. The mean values of the study parameters among the three different techniques are tabulated in Table I, with their corresponding standard deviation.

All the plans were considered acceptable for at least the 95% PTV volume that received 100% of the prescribed dose. The 1ARC and 2ARC VMAT plans resulted in a better dose HI compared with IMRT, with a relative improvement of 7.8 and 3.3%, respectively. This difference was significant (P<0.05). Similarly, the 1ARC and 2ARC VMAT plans exhibited a significantly higher CI than the IMRT (both P<0.05) (Table I). As expected, the 2ARC VMAT plan produced the best dose CI compared with 1ARC VMAT and IMRT, with a relative improvement of 6.6% (P<0.01) and 15.7% (P<0.01), respectively. Similarly, the 2ARC VMAT plan demonstrated a significantly higher HI than the other two techniques (both P<0.01) (Table II).