Novel method of radiotherapy planning to improve the dose homogeneity at the junction region for breast cancer

This article introduces a new method to design the radiation therapy planning after radical surgery for breast cancer in order to provide a better homogeneity of the dose distribution in the junction region between the supra clavicular fossa and chest wall.


INTRODUCTION
Breast cancer is one of the most common malignant tumors in women, ranking first in female tumors. 1 Radiotherapy plays an important role in breast cancer treatment, because it is able to not only reduce the local recurrence rate, but also improve the survival rate of patients with cancer. 1 There are many radiotherapy techniques for breast cancer, such as volume intensity modulated radiotherapy, intensity-modulated radiotherapy (IMRT) and 3-D conformal radiation therapy (3D-CRT).
However, in some situations, we need to use a special technique to design the plan. For example, when the target is so large that it includes the clavicle region and whole chest wall, we usually need to use a hybrid IMRT technique to carry out the goal. To be specific, we need to design a IMRT or volume IMRT plan for the clavicle region, and also need to use two tangential intensity-modulated fields (field-in-field) combining two IMRT fields for the chest wall region. 2 In fact, although these techniques have been widely used in a variety of tumor radiotherapy treatments, when we think about breast cancer patients' breathing, hybrid IMRT and field-in-field techniques are usually preferred over volume IMRT and IMRT techniques. However, when dealing with a large target that includes the clavicle region and whole chest wall in the clinical planning process, we found that the dose distribution and the conformal index (CI) of the planning target volume (PTV) in the junction region are always poor. 4 Therefore, we designed a new method to improve the dose distribution, and evaluated the advantages and disadvantages of these two plans.

METHODS
The experimental scheme design of this study included three steps: (i) case selection; (ii) plan design; and (iii) result analysis.

Equipment and scanning parameters
All patients were placed on a positioning couch that was made up of carbon fiber in a supine position, with an appropriate headrest, and both arms above the head. A breast bracket plus fixed lower limb foam plate were used on the affected side of the patients. The crossbar was held, and the inclination angle of the breast bracket was adjusted. At the same time, the foam plate with the appropriate angle and thickness was cushioned under the limb of the affected side to keep the patients stable, and expose the axillary and breast areas. 5 In addition, functional training needs to be provided for those patients who could not keep their arms raised for a long time. 5

Target and organs at risk delineation
The doctors treating the participants contoured the target area based on computed tomography imaging. The clinical target volume (CTV) included the ipsilateral clavicle, chest wall, and lymphatic drainage area. 8 If the primary tumor is located in the center of the breast, when no adjuvant trastuzumab treatment is indicated, the breast area needs to be covered. The PTV was a clinical target area of 5-mm extension in three dimensions from the CTV no less than 3mm from the skin surface. Patients with modified radical surgery will not need to pay attention to the skin distance of the PTV, but, in genera, a 0.5-cm compensation material is required during planning. 9, 10 We also defined the target as PTV_J. PTV_J was the volume of the junction region, which was 1-cm cranial and 1-cm caudal to the isocenter in PTV. The endangered organs were the heart, lung, healthy breast, and spinal cord. 11 Contouring was carried out according to the window width and window position on the computed tomography image.

Planning design of hybrid IMRT
The target area of the breast was irradiated with an 80% dose of the prescription in the tangential fields planning and a 20% dose of the prescription in the IMRT planning. The aim was to adjust the uniformity of the target area. We could move the target position so as to use only one side of the jaw to control the tangential field planning. The upper boundary of the jaw in the mammary gland area was located in the interface of the upper and lower target areas, as shown in Figure 1. We ensured the angle of the collimator was 0 • degrees and the tangential opposing fields passed through the lung with minimal volume on the beam eye view. We also aimed to avoid the heart and contralateral breast exposure.
The jaw on the outer line of the patient's breast was opened 2 cm more to avoid underdose caused by respiratory movement. 12 We added two fields to IMRT planning based on the tangential opposite fields, which increased by 10-15 • to cover the whole target area.

New planning design
After adding the tangential opposing fields, we needed to adjust the design method to form a dose gradient at the junction, as shown in We also needed to keep the other conditions the same with the traditional method.
A comparison of the dose distribution of the penetrating fields by the two methods is shown in Figure 3. The dose distribution changed significantly such that the conventional method had no obvious dose gradient at the junction, whereas the new method formed an obvious dose gradient through MLC shielding.

Planning optimization and dose limit
Both method plans use the AAA algorithm for optimization, and the optimization parameters were based on the prescription dose, as shown in Table 1. We need to keep the parameters the same as those in the first optimization when optimizing. The optimization process also needs to be adjusted to keep the dose of the organs at risk (OAR)s as low as possible until the optimal value is reached while ensuring that the target area meets the requirements.

Definition of conformity index and homogeneity index
Dose Volume Histogram (DVH), dose statistics, and isodose distribu-  (1) and (2), respectively 14,15 : In formula (2), D 5% and D 95% were the doses accepted by 5% and 95% of the target volume, respectively, with better uniformity of the target for HI values closer to 1.

Statistical analysis
In the comparative analysis of the two technologies, the targets in the two planning programs were evaluated according to PTV and PTV_J.
The maximum dose, the minimum dose, and HI and CI of the PTV were also compared. OARs. Paired-sample t-tests were carried out for normal distribution.

Dosimetric comparison of targets
Among the 10 patients, the maximum PTV was 877.20 cc, the minimum was 546.00 cc, and the average was 737.91 cc. The maximum PTV_J was 53.50 cc, the minimum was 11.20 cc, and the average was 31.32 cc.
Regardless of the size of the target area, both PTV and PTV_J obtained better dose uniformity with statistical significance compared with conventional plans (PTV-CI, P = 0.04; PTV_J-CI, P = 0.01; HI = 0.02). The statistical results are shown in Table 2, and the dose distribution is shown in Figure 3.
The uniformity of the dose distribution of the target PTV_J can be directly seen in Figure 2; Fig. 2a shows the new method, and Fig. 2b shows the conventional method. The dose distribution and the 5000dose line that wrapped the target area of the new method were better than those of the conventional method, and the uniformity and adaptability of the target area were also better with the new method. The dose line 2000 was lower in the lung than that in the conventional method planning.

Dosimetric comparison of the OARs
As shown in Table 3, there was no significant difference in OAR dose distribution (P > 0.05). The reason is that only the position of the MLC changed in the junction field compared with the two planning methods.
This affected the dose gradient of the junction field, but not the dose distribution in the other areas.

DISCUSSION
Breast cancer is the most common malignant tumor in female cancer patients. Surgery combined with radiotherapy and chemotherapy is one of the main treatment methods, which can effectively improve the clinical symptoms of breast cancer patients and the survival rate. 13 For patients with early-stage breast cancer, partial resection and breast conserving treatment are often used. Compared with modified radical mastectomy, this method has a good therapeutic effect while preserving the breast shape. In China, modified radical mastectomy is still the most commonly used treatment due to the late detection and late staging of many patients. 14 In the treatment of breast cancer, changes in the target areas of the breast caused by respiratory movements should be considered. [18][19] To avoid changes in the target areas, 4DCT technique and respiratory gating technique are required for IMRT treatment alone. This improves positional accuracy and protects normal tissue, but at the expense of therapeutic efficiency. In the present study, we used tangential opposing fields planning and IMRT planning to modulate the dose distribution and ensure the target area receives 70-80% of the dose and the uniformity of the target area dose; it was a practical design scheme.
The difficulty in the design of breast and supra clavicular region irradiation is how to deal with the distribution of the dose in the junction field, where a hot dose might cause skin reactions, and too many cold spots might hinder the treatment in the traditional planning. 15 This is a problem that many therapy centers face. According to the analysis of dose distribution at the junction, a very steep dose drop occurred due to 70-80% of the prescription dose given at the chest wall and half-jaw irradiation given at the junction, which made the dose contribution of the supra clavicular field unable to reach the prescription dose in such a short distance. Therefore, we designed a new planning method to create a dose-drop gradient at the junction. In addition, if the distance between the lower boundary drawn by the breast and the treatment center is >20 cm, the treatment center point should be moved downward to ensure that the lower boundary of the jaw covers the whole target area.
We used the field-in-field technique by changing the MLC in the fields to produce the dose gradient. The method was to add two subfields in each tangent opposing field. In the subfield design, the dose gradient was formed by shielding with MLC leaves. According to the calculation, if 80% of the prescribed dose was given to the main field (∼80 MU), then approximately 10 MU would be given to each subfield.
A drop dose zone of approximately 30% dose was formed within 2 cm, so that better dose modification could be achieved when the IMRT planning was designed in the supra clavicular region.
In the present study, it was found that the new method improved the dose distribution at the junction region and did not affect the OAR dose (Tables 3,4; Figure 4). The advantage of the new method for planning the dose gradient is that it can avoid the situation where the MLC cannot be adjusted quickly and accurately due to the excessive dose drop.
As a result, the new method of planning can improve the dose distribution in the junction field and tumor control rate. It also reduces the side-effects by controlling the OAR dose and has value in the clinical setting.