Hybrid volumetric modulated arc therapy for hypofractionated radiotherapy of breast cancer: a treatment planning study

The patients included in this study were selected by defining a volume-based standardized breast size (n = 200), whereby the PTV sizes were evaluated as a measure of breast size. The computed tomography (CT) scans (Canon Aquilion LB, Canon Medical Systems Europe B.V., Zoetermeer, the Netherlands) were acquired with a slice thickness of 3.0 mm. Patients were positioned in a headfirst supine position. An arm board helped to immobilize the chest and thorax with the arms positioned overhead. To minimize intrafractional movement, the CT scans were carried out in deep-inspiration breath-hold (DIBH). This method bears dosimetric advantages, especially for cardiopulmonary OAR exposure and secondary lung cancer risk [7‐10]. Of the 200 patients analyzed, 110 patients met the inclusion criteria of the study regarding PTV size and no exclusion criteria were included, such as funnel chests, pathological enlarged hearts, or anatomic variations. Out of these patients, 40 (20 per breast side) were selected randomly.

The Eclipse software (version 15.6, Varian Medical Systems, Palo Alto, CA, USA) was used for treatment planning. Treatment plans were created for a Varian TrueBeam linear accelerator, the calculation model was based on the anisotropic analytical algorithm (AAA, version 15.5.12) and a calculation grid size of 2.5 mm. Each PTV included the whole breast and was cropped 5 mm from the skin surface, resulting in a VMAT optimization where the dose is not forcibly modulated to the surface. The thoracic wall was defined as part of the PTV. Individual treatment plans were created using the H‑VMAT technique and the 3D-CRT technique as reference (Ref). The H‑VMAT plans represented sum plans: each consisted of two treatment plans including 3D-CRT and VMAT. The prescribed dose was 40.05 Gy in 15 fractions (2.67 Gy per fraction) based on the START B trail, which demonstrated the non-inferiority of this hypofractionated regime regarding locoregional control and toxicity in comparison to normofractionated treatment [11]. The reference treatment plans were planned as tangential opposing fields with mixed beam energies (6 MV and 15 MV) and HWF. All planning parameters such as gantry and wedge filter angles, collimator position, and field weightings were individually optimized. H‑VMAT plans were weighted 80/20 between 3D-CRT and VMAT, which included 3D-CRT as a base plan for VMAT optimization. The supplementary dose consisted of a single VMAT field with an identical isocenter position. Its range of rotation angle corresponded to the tangential angles from the base plan. The collimator rotation angle was set to 5° and the maximum dose rate to 600 MU/min. A standard optimization protocol was used for the inverse planning process of VMAT, which was adapted individually. Flattening-filter beams were used in all treatment plans. Within the hybrid approach, six different H‑VMAT combinations (HV1–HV6, Table 1) were used, varying beam energy and the application or omission of HWF in the 3D-CRT plans. The selection of these combinations was based on a previous evaluation by our group. This previous study was an initial assessment of 32 different combinations, 16 of which were within the weightings 60/40 and 80/20, which were evaluated based on a case number of 5 patients. To assess the optimal hybrid combination, superior combinations of this evaluation with respect to quality indices (PTV coverage, conformity, homogeneity) and OAR doses were analyzed in detail (Table 1).

PTV dose coverage had the first priority in treatment planning. The PTV dose requirements in our study were based on the recommendations of ICRU Report 83 [12]:

In order to ensure an appropriate plan comparison with regard to OAR doses, these PTV requirements should be kept as consistent as possible. For this purpose, an upper limit for PTV D_95% was set. Minimizing OAR doses was a secondary priority. The protection was implemented so that the PTV dose requirements could be guaranteed. Each of the prepared 520 treatment plans was separately optimized for individual patients.

Four different indices were used to assess PTV dose conformity and homogeneity:

The Radiation Therapy Oncology Group (RTOG) Report 1005 [17] served as a guide for dosimetric evaluations of the OAR doses (for detailed OAR constraints, see Table 2). Our previous evaluation showed clinically negligible doses to the contralateral lung and spinal cord, so that these OAR were not considered in this study.

Further evaluation criteria were the planned monitor units (MU) and beam-on time (BOT) that were observed over the total number of patients.

A volume-specific standard breast of 961 ± 346 cm³ was determined from the data of 200 patients. A Kolmogorov–Smirnov test confirmed the presence of a normal sample distribution. The analysis included only patients with a PTV or breast size within the range of the standard deviation, integrating 68% of all women, whereas anatomical variations such as funnel chests and pathological enlarged hearts were not considered.

Compared to the reference treatment plan, all analyzed H‑VMAT combinations consistently delivered significantly better values for PTV dose coverage (Fig. 1, Table 3). With the conventional radiation technique (Ref), dose coverage was consistently less successful than with H‑VMAT. Compared to Ref, all H‑VMAT combinations achieved significantly better EI values. The use of HWF in H‑VMAT was disadvantageous for the EI in left-sided breast therapy, whereby HV4 (EI = 0.012 ± 0.008) and HV5 (EI = 0.013 ± 0.009) showed worse values compared to other combinations without HWF use such as HV1 (EI = 0.008 ± 0.003). Compared to Ref (left CN = 0.391 ± 0.050, right CN = 0.395 ± 0.046), the evaluation of conformity showed better values in all H‑VMAT combinations. HV4 (left CN = 0.611 ± 0.016, right CN = 0.622 ± 0.021) and HV5 (left CN = 0.598 ± 0.025, right CN = 0.617 ± 0.020) revealed inferior results compared to other H‑VMAT combinations for both breast sides. Better dose homogeneity within the PTV (HI) was generally achieved in the H‑VMAT plans.

The analysis within the hybrid combinations showed potential for improvement with regard to the quality indices (Table 4). The inclusion of HWF in the base plan (HV2/HV4 and HV3/HV5) resulted in significant disadvantages regarding COV and CN. The omission of HWF resulted in a significantly better homogeneity index in left-sided, but not in right-sided breast therapy (HV3/HV5). By using higher beam energies in the VMAT supplementary dose (HV2/HV3 and HV4/HV5), better CN values could be achieved. In addition, advantages in PTV dose coverage and conformity only in left-sided therapy (HV4/HV5) were observed.

Evaluation of the ipsilateral lung (IL) dose value V16 displayed significantly better values in almost all H‑VMAT combinations on both breast sides (Fig. 2, Table 3). Only for HV1 (V16 = 15.3 ± 3.6%) and HV6 (V16 = 15.1 ± 3.6%) in the case of right-sided breast irradiation was there no significant difference to the reference treatment plan (Ref V16 = 15.3 ± 3.7%). The IL V8 doses in left-sided breast irradiation were equivalent across all RT combinations, with only HV2 (V8 = 21.7 ± 6.5%) showing statistical benefit over Ref (V8 = 22.7 ± 6.4%). In right-sided breast irradiation, most hybrid combinations, HV1, HV4, HV5, and HV6, provided disadvantages. Overall, the tolerable dose values of the RTOG Report 1005 (V8 = 35–40%) were met in most used techniques (except for one patient HV1, HV5, and HV6 for the right breast). When considering the IL dose V4, only HV2 (V4 = 41.1 ± 9.9%) and HV3 (V4 = 42.0 ± 10.3%) were superior to Ref (V4 = 44.4 ± 9.4%) in left-sided therapy. HV4 (V4 = 46.4 ± 9.4%) and HV5 (V4 = 47.3 ± 10.4%) delivered significantly worse values as well as HV1, HV4, and HV5 on right-sided therapy. All other H‑VMAT combinations were equivalent to Ref regarding IL V4. The analysis of the mean ipsilateral lung dose showed advantages of the hybrid technique on left breast therapy, with significantly better values for H‑VMAT. In right-sided therapy, only H‑VMAT combinations HV2 (D_mean = 7.5 ± 1.2 Gy) and HV3 (D_mean = 7.6 ± 1.3 Gy) offered statistically significant advantages over the reference (D_mean = 8.1 ± 1.2 Gy).

All dose values of the heart complied with the dose specification of RTOG Report 1005 regarding D_mean = 320–400 cGy (Fig. 3, Table 3). Especially in left-sided breast therapy, the heart was better protected with all H‑VMAT combinations considered. HV1 (D_mean = 128 ± 37 cGy), HV2 (D_mean = 121 ± 34 cGy), HV3 (D_mean = 123 ± 35 cGy), and HV6 (D_mean = 137 ± 39 cGy) showed the best values and thus the most pronounced advantages over Ref (D_mean = 216 ± 42 cGy). In right-sided breast irradiation, the same trend could be observed (HV1 D_mean = 71 ± 26 cGy, HV2 D_mean = 63 ± 17 cGy, HV3 D_mean = 65 ± 20 cGy, HV6 D_mean = 78 ± 27 cGy, and Ref D_mean = 132 ± 19 cGy). The combinations HV4 and HV5 consistently achieved the highest heart exposure in H‑VMAT. In general, higher heart dose values were evaluated in left-sided breast therapy.

Some treatment techniques could not fulfill the dose constraints D₅ = 144–240 cGy of the contralateral breast according to the guidelines of RTOG Report 1005 (Fig. 3, Table 3). All considered hybrid combinations showed advantages over the 3D-CRT treatment plan (left D₅ = 200 ± 33 cGy, right D₅ = 233 ± 45 cGy). The lowest dose values with the greatest advantages were achieved with H‑VMAT combinations without the inclusion of HWF. HV2 (left D₅ = 70 ± 23 cGy, right D₅ = 96 ± 35 cGy) and HV3 (left D₅ = 84 ± 29 cGy, right D₅ = 111 ± 40 cGy) provided the best values on both breast sides.

The comparison of hybrid combinations showed a possibility to reduce the OAR doses (Table 4). Significant advantages of combinations without the use of HWF in the base plan were found for all OAR. Regarding the VMAT supplementary dose, there is a tendency that the choice of higher beam energy (15 MV instead of 6 MV) is disadvantageous for OAR exposure. For IL V4, IL D_mean, and CB D₅, significant advantages could be observed using a lower VMAT energy.

Increased MU were required when using HWF (Table 3). Therefore, Ref and the combinations HV4 and HV5 in hybrid planning showed the highest values. Compared to Ref, the H‑VMAT plans showed consistently higher values for beam-on times. The longest BOT were observed using HWF (HV4 and HV5).