
==== Front
Breast
Breast
The Breast : Official Journal of the European Society of Mastology
0960-9776
1532-3080
Elsevier

S0960-9776(24)00127-9
10.1016/j.breast.2024.103796
103796
Original Article
Stereotactic body radiotherapy using CyberKnife versus interstitial brachytherapy in accelerated partial breast irradiation on left-sided breast: A comparison of dosimetric characteristics and preliminary clinical results
Wei Ting-Na a
Lin Jia-Fu b
Cheng Mei-Chun b
Yeh Hui-Ling hlyeh@vghtc.gov.tw
a⁎
a Department of Radiation Oncology, Taichung Veterans General Hospital, Taichung, Taiwan
b Division of Radiation Physics, Department of Radiation Oncology, Taichung Veterans General Hospital, Taichung, Taiwan
⁎ Corresponding author. 1650 Taiwan Boulevard Sect. 4, Taichung, 40705, Taiwan. hlyeh@vghtc.gov.tw
04 9 2024
12 2024
04 9 2024
78 10379627 6 2024
15 8 2024
2 9 2024
© 2024 The Author(s)
2024
https://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Introduction

We compared the dosimetric characteristics of the target and organs at risk (OARs) as well as the preliminary clinical outcomes between two accelerated partial breast irradiation (APBI) techniques.

Methods

Forty-four patients diagnosed with left-sided early breast cancer who underwent APBI using either interstitial brachytherapy (IB) or stereotactic body radiation therapy (SBRT) with CyberKnife (CK) were retrospectively reviewed. The dosimetric parameters of the target and OARs were compared. Preliminary clinical outcomes, including tumor control and acute toxicity, were analyzed.

Results

Treatment plans with CK demonstrated a better cardiac dose-sparing effect. Radiation doses to the heart at V150cGy for the CK and IB groups were 24.4 % and 60.4 %, respectively (p < 0.001), while the mean heart doses for the CK and IB groups were 107.4 cGy and 204 cGy, respectively (p < 0.001). The heart D1c.c. and the ipsilateral lung received a lower dose in the IB group, without any significant differences. The median follow-up time in the CK and IB groups was 28.6 and 61.3 months, respectively. No patients died from either breast cancer or cardiac events during follow-up. A locoregional recurrence event at the neck occurred in one patient within the IB group.

Conclusions

APBI planned by CK was shown to have a better dose-sparing effect on the heart, as well as better conformity and homogeneity to the target. CK is a non-invasive treatment which showed minimal acute toxicity and promising tumor control.

Highlights

• APBI is time-saving, cost effectiveness and non-inferior to WBI for postoperative radiotherapy in early breast cancer.

• CK is a non-invasive treatment which showed minimal acute toxicity and promising tumor control.

• APBI planned by CK has a better dose-sparing effect on the heart and better conformity and homogeneity to the target.

Keywords

Accelerated partial breast irradiation
Interstitial brachytherapy
Stereotactic body radiation therapy
CyberKnife
==== Body
pmc1 Introduction

Breast conserving surgery followed by adjuvant whole breast irradiation (WBI) is a standard treatment for early breast cancer patients and has demonstrated rates of tumor control and overall survival that are comparable to those achieved through mastectomy, according to long-term clinical results [1,2]. Currently, the preferred prescribed dose scheme for adjuvant radiotherapy is hypofractionated WBI, delivering a dose of 4000 cGy in 15 fractions or 4250 cGy in 16 fractions [[3], [4], [5]]. Previous studies have identified that the tumor bed is the most prevalent site of local recurrence [6]. Based on the evidence, it is reasonable to consider reducing the irradiation volume in order to de-escalate the radiation doses and reduce the treatment period time. The target volume of accelerated partial breast irradiation (APBI) includes a 1.5–2 cm margin surrounding the tumor bed rather than the whole breast. This approach minimizes radiation exposure to adjacent organs due to the smaller irradiation volume. Previous clinical studies have demonstrated that APBI is an effective and time-saving method of postoperative radiotherapy in early breast cancer treatment, offering a much shorter treatment duration when compared to conventional WBI.

Many prospective clinical studies have shown that APBI is non-inferior to WBI in terms of local control and overall survival rate for early breast cancer patients. The NSABP B-39/RTOG 0413 trial compared conventional WBI with APBI using either brachytherapy or external beam radiotherapy(EBRT). The results showed that the absolute difference in cumulative incidence at 10 years was less than 1 % [7]. A randomized clinical trial performed by GEC-ESTRO reported in its 10-year results that there was comparable treatment efficacy between APBI using multicatheter brachytherapy and WBI, with a lower incidence of late toxicity [8]. The UK IMPORT LOW and RAPID trial demonstrated the non-inferiority of local tumor control, whether delivered through external beam radiotherapy APBI or hypofractionated WBI [9,10]. The APBI-IMRT-Florence trial treated early breast cancer with APBI using external beam irradiation with intensity modulated radiotherapy (IMRT), showing the cumulative 10-year recurrence rate to be low, with no difference being seen when compared to WBI. Meanwhile, acute toxicity, late toxicity, and cosmesis outcomes significantly favored APBI [11,12]. Additionally, several meta-analysis studies corroborated these findings, indicating similar results and a lower toxicity being associated with APBI [13,14].Hence, APBI has been widely adopted in adjuvant radiotherapy for treatment of low-risk early breast cancer.

Multiple techniques are currently applicable for APBI, including intraoperative radiotherapy, multicatheter interstitial brachytherapy, and EBRT [15]. However, there is no consensus on which approach is superior. There are some differences in dosimetric characteristics among these treatment modalities. Multicatheter interstitial brachytherapy is the oldest and most mature technique for APBI, supported by adequate long-term clinical follow-up data. Nonetheless, CyberKnife is considered to have the highest accuracy among the numerous techniques due to its ability to track the irradiation target and adjust instantly to respiratory motion. In our hospital, we use both methods in our APBI treatment modalities.

Since the majority of patients diagnosed with early breast cancer are given a good prognosis with a long-term survival outcome, it is crucial to consider de-escalation of the radiation doses in order to avoid long-term sequelae of adjuvant radiotherapy. In left breast cancer, the major organs at risk (OARs) are the heart and lungs. According to the QUENTEC review, the probability of pericarditis is less than 15 % when the mean pericardial dose is below 26Gy; the cardiac mortality rate at 15 years is expected to be less than 1 % if the radiation dose to the heart V25Gy is below 10 %; and the mean dose–response curve indicates a 20 % risk of radiation pneumonitis for a mean lung dose of 20Gy [16]. Therefore, we should make every effort to balance the efficacy of treatment and its potential adverse effects.

The purpose of this study was to compare two APBI methods: stereotactic body radiotherapy using CyberKnife® versus multicatheter interstitial brachytherapy. The dosimetric characteristics of the OARs and the target using the two modalities were compared, with the preliminary clinical results and acute toxicity also being recorded.

2 Materials and methods

2.1 Patient selection

We retrospectively reviewed 44 left-sided breast cancer patients who underwent APBI after lumpectomy at our hospital during the period from January 2017 to December 2022. Treatment plans by two different APBI techniques were compared, namely multicatheter interstitial brachytherapy and stereotactic body radiotherapy (SBRT) by CyberKnife. The patient selection criteria for APBI were determined according to the "suitable" or "cautionary" criteria outlined in the consensus statement of the American Society for Therapeutic Radiology and Oncology (ASTRO) which was updated in 2017 [17]. Our inclusion criteria comprised patients aged ≧45 years, left-sided tumor, tumor size of the invasive carcinoma ≦3 cm/ductal carcinoma in situ <2.5 cm, positive tumor estrogen receptor (ER) status, negative resection margin, no regional lymph node metastases, and a Karnofsky performance status scale ≥80 %. Patients diagnosed with distant metastasis or bilateral breast cancer were excluded from the study. This retrospective study was approved by the Institutional Review Board of our hospital and the Research Ethical Committee (No.: CE23257C). The committee waived the requirement for informed consent. The abstract about the preliminary analysis of this paper was presented at 2023 ESMO ASIA as a poster. DOI: https://doi.org/10.1016/j.annonc.2023.10.161.

2.2 Treatment planning

(1) Multicatheter interstitial brachytherapy

After the tumor was surgically removed, catheters were inserted to cover the tumor bed at a 2 cm margin using the free hand technique during the operation. The spacing of each catheter was set at 1.5 cm with 1–2 planes, depending on the size of the patient's breast. The details of the implantation procedures have been recorded in our previous studies [18,19]. (Fig. 1) A non-contrast CT simulation with a slice thickness of 2.5 mm was acquired on the second day of surgery for target and OARs contouring. The tumor bed was identified based on the seroma and surgical clips. The clinical target volume (CTV) was created from the tumor bed with 2 cm margin. The ribs and skin were excluded from the CTV. The radiation dose was delivered by Elekta microSelectron high-dose rate after loader, using a radioisotope Iridium-192 radiation source. The total prescribed dose was 3400 cGy in 10 fractions, administered twice a day with a 6-h interval between each fraction. Dose constraints for target volume and OARs were in accordance with the dose restrictions of the ESTRO-ACROP guidelines for ipsilateral breast V90Gy<10 % and V50Gy<40 %, the ipsilateral mean lung dose<8 % and D0.1cm3<50 %, heart D0.1cm3<80 % and the mean heart dose<8 % [20].(2) CyberKnife

Fig. 1 Multicatheter interstitial brachytherapy treatment planning.

(A) Breast after multicatheter insertion.

(B) Dose distribution of multicatheter interstitial brachytherapy.

Fig. 1

After the wound healed (approximately 4–6 weeks after the operation), the patients received adjuvant APBI using CyberKnife. Each patient was immobilized using a customized vacuum bag in the supine and left arm-up position. Expiration breath-hold non-contrast CT simulation (120 KVp, 400 mAs, 1.25mm/slice) was acquired from the lower neck to the whole chest at a slice thickness of 1.25 mm for contouring and treatment planning. Five skin fiducial markers (SureMark™ SL-20; The Suremark Company, Simi Valley, CA) were placed within a 50 mm distance from the tumor bed following the CyberKnife fiducial implant guidelines. Scout views at 45° and 315° were acquired during CT simulation to verify and fine-tune the location of the skin marker (Fig. 2). CTV was defined as the tumor bed according to surgical clips, seroma, and scar with an additional margin of approximately 1.5–2 cm in all directions if possible. The anterior and posterior margins were limited by the skin and ribs. The thyroid was blocked and completely excluded from CTV. The CTV plus a 3 mm margin and subtraction of 4 mm of skin layer was done in order to create the planning target volume (PTV). Treatment was performed using the CyberKnife® M6 system (Accuray Inc. Sunnyvale, CA), utilizing an InCise2™ Multileaf collimator (MLC). The prescribed tumor dose was 3000 cGy in 5 fractions over a period of 5 consecutive days [21]. A synchrony respiratory tracking system provided real-time image guidance, monitoring the respiratory motion using light emitting diodes (LEDs) placed on the patient's chest just above the diaphragm area. Treatment plans were generated using the MultiPlan® Version 5.3.0 treatment planning system with a finite size pencil beam (FSPB) dose calculation algorithm. The treatment plan aimed to ensure a 95 % total PTV covered by a 100 % prescribed dose, with the D0.03cc of PTV being less than 39Gy. The dose constraints of the normal organs according to the report generated by the AAPM Task Group 101 were as follows: ipsilateral breast V15Gy<40 % and V30Gy<20 %, contralateral breast V1Gy<7 %, ipsilateral lung V9Gy< 10 %, contralateral lung V1.5Gy<10 %, heart V1.5Gy<40 %, D0.03cc of the skin and rib<33Gy [7,16,22]. The parameters of the sequential optimization method were as follows: a maximum of 300 monitor units (MU) per segment, 450 MU per node, and a zero mm leaf margin of beam shaping segments (eroded, perimeter, random shape). The median value of the beam number, segment number, and monitor unit was 63 (range, 48–101), 105 (range, 81–163), and 3260 (range 2780–3209), respectively. The median delivery time was 29 min (range 25–40).Fig. 2 Stereotactic body radiotherapy with CyberKnife treatment planning.

(A) AP and lateral view check to confirm the distance of surgical tumor bed and skin fiducials was within 5 cm (yellow: skin fiducials; red: surgical clips).

(B) Optical markers are monitored in real-time by Synchrony camera.

(C) Images were acquired to determine target position at multiple phases of respiratory cycle.

(D) Beam delivery and dose distribution of Cyberknife treatment plan.

Fig. 2

2.3 Dosimetric evaluation

To ensure quality assurance during radiotherapy treatment of breast cancer, the European Society for Radiotherapy and Oncology (ESTRO) established an international multi-disciplinary consensus regarding the essential requirements [23]. Referring to this guideline, the OAR parameters, including ipsilateral lung V900cGy, mean lung dose, mean heart dose, heat V150cGy, heart D1c.c., skin D0.03cc, and rib D0.03cc were all recorded. To evaluate the quality of planning, the new conformity index (nCI) and homogeneity index (HI) were each calculated. CI was then performed using the following formula [24]:nCI=Prescriptionisodosevolume(PIV)Tumorisodosevolume(TIV)

The homogeneity index (HI) was calculated using the formula:HI=1−V120%V100%

2.4 Follow-up

Patients were followed up in radiation oncology clinics after the completion of APBI, with assessments being performed at 2 weeks, 3 months, and then every 6 months to monitor the acute and late toxicities. The toxicities were graded by a radiation oncologist according to the Common Terminology Criteria for Adverse Events (version 4.0). Acute toxicities such as dermatitis, fibrosis, fat necrosis, telangiectasia, breast pain, breast edema, infection, scar formation and acute pneumonitis were all recorded. Regular follow-up examinations, including chest radiographs, breast ultrasound, and abdominal ultrasound, were performed every year. An annual breast mammography was also arranged for all patients.

2.5 Statistical analysis

The Mann-Whitney U test was used to compare dosimetric parameters. A p value < 0.05 was considered statistically significant. Clinical analysis of local recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS) was calculated using the Kaplan–Meier method. All statistical analyses were conducted using SPSS software, version 22.0 (IBM Corporation, USA).

3 Results

Twenty-two patients were included in the IB and CK groups. The median follow-up period for the CK and IB groups was 28.6 and 61.3 months, respectively. The median ages of the IB and CK groups were 60 years and 61 years, respectively. The predominant histology type was infiltrating ductal carcinoma. Tumor stages comprised T1-2N0 with luminal subtype. Most of the patients did not have lymphovascular invasion (93.1 %) or perineural invasion (95.4 %) as seen in the final pathology report. After the operation, the majority of patients (97.7 %) continued to receive adjuvant hormone therapy. The characteristics of the patients are described in detail in Table 1.Table 1 Patients’ characteristics.

Table 1Characteristics	Patient number (N = 44)	
IB (n = 22)	CyberKnife (n = 22)	
Follow-up(months)	61.3	28.6	
Age(year)	60(56.5–66.75)	61(55.5–67)	
Histology			
 DCIS	1	6	
 IDC	20	15	
 ILC	1	1	
Clinical stage	
 0	1	7	
 I	15	11	
 II	6	4	
Pathologic stage	
 0	2	6	
 I	19	13	
 II	1	3	
Grade (Invasive)	
 1	6	6	
 2	13	9	
 3	2	1	
Molecular subtype (Invasive)	
 Luminal A	12	12	
 Luminal B1&B2	9	4	
Lympho-vascular invasion	
 Yes	3	0	
 No	19	22	
Perineural invasion	
 Yes	1	1	
 No	21	21	
Systemic therapy	
 Neoadjuvant chemotherapy	0	0	
 Neoadjuvant hormone therapy	6	2	
 Adjuvant chemotherapy	4	0	
 Adjuvant target therapy	1	0	
 Adjuvant hormone therapy	22	21	

The median volume of the PTV was 61.8 cm3 for the IB group and 76 cm3 for the CK group, which was a significant difference (p < 0.05). Similarly, the ratio of PTV to breast volume was also lower in the IB group, with a median of 9.68 % when compared to 16.04 % in the CK group. (p < 0.001). Regarding the quality of the plan, including conformity and homogeneity, the median nCI value was 1.43 for the IB group and 1.19 for the CK group. The median HI was 0.75 and 0.88 for the IB and CK groups, respectively. Details regarding target dosimetric comparisons are provided in Table 2.Table 2 Dosimetric comparison of target.

Table 2Parameters	IB(n = 22)	CyberKnife(n = 22)		
Median(IQR)	Median(IQR)	p value*	
PTV volume(cc)	61.8(44.2–74.6)	76.0(65.1–165.0)	0.009	
Ipsilateral Breast volume(cc)	666.5(499.6–855.2)	543.1(397.7–644.7)	0.133	
PTV/Breast volume (%)	9.68(8.43–13.0)	16.04(12.0–24.4)	<0.001	
Ipsilateral Breast V50 (%)	15.4(12.6–21.9)	17.8(16.2–21.30)	0.096	
nCI	1.43(1.35–1.59)	1.19(1.13–1.22)	<0.001	
HI	0.75(0.69–0.96)	0.88(0.8–0.96)	<0.001	
* nCI=Prescriptionisodosevolume(PIV)Tumorisodosevolume(TIV)A1.

* HI=1−V120%V100%A1.

When comparing the dosimetric characteristics of OARs, the median mean heart dose for the IB and CK groups was 204.0 cGy and 107.4 cGy, respectively. The median heart V150cGy of IB and CK was 60.4 % and 24.4 %, respectively. Both parameters of radiation dose to the heart showed a significant difference (p < 0.001). The median heart D1c.c. of the IB and CK groups was 1.14 Gy and 4.24 Gy, respectively, without significant difference. The median percentage of ipsilateral lung volume receiving V900cGy was 2.21 % for the IB group and 4.8 % for the CK group. However, no differences were observed in the mean ipsilateral lung dose and skin D0.03 cc (Table 3).Table 3 Dosimetric comparison of organs at risk.

Table 3Parameters	IB(n = 22)	CyberKnife(n = 22)		
Median(IQR)	Median(IQR)	p value	
Ipsilateral lung V900cGy(%)	2.21(0.58–4.91)	4.8(2.45–7.83)	0.035	
Ipsilateral mean lung (cGy)	206(159.25–274.93)	234.5(173.75–299.5)	0.432	
Heart Dmean(cGy)	204(178.48–261.75)	107.4(91.82–124.30)	<0.001	
Heart V150 cGy(%)	60.4(50.68–69.63)	24.4(15.98–31.65)	<0.001	
Heart D 1c.c.(Gy)	1.14(0.81–8.13)	4.24(4.00–5.15)	0.071	
Skin D0.03 cc(cGy)	3166.4(2288.2–4078.7)	2936.8(2809.8–3058.2)	0.385	
Rib D0.03 cc(cGy)	2456.2(2144.4–2925.7)	3013.4(2965.2–3144.0)	<0.001	

The majority of acute toxicities recorded were grade 1 radiation dermatitis, with seven patients affected in the IB group (31.8 %) and nine affected in the CK group (40.9 %). No cases of grade 2 radiation dermatitis were observed. Furthermore, one patient in the IB group (4.5 %) experienced persistent catheter scarring two years after treatment. Skin fibrosis was recorded in one patient in the IB group (4.5 %) and in two in the CK group (9.0 %). Fat necrosis was reported in two patients who were exclusively in the CK group (Table 4).Table 4 Acute toxicity.

Table 4Toxicity and grade	Patient number (N = 44)	
IB (n = 22)	CyberKnife(n = 22)	
Gr1 Acute Dermatitis	7	9	
Gr2 Acute Dermatitis	0	0	
Fibrosis	1	2	
Fat necrosis	0	2	
Telangiectasia	0	0	
Breast pain	0	0	
Edema	0	0	
Infection	0	0	
Scar formation	1	0	
Acute pneumonitis	0	0	
*Grading according to Common Terminology Criteria for Adverse Events (version 4.0).

Regarding preliminary clinical outcomes, only one patient in the IB group experienced local regional lymph node recurrence in the supraclavicular fossa of the left side and left internal mammary chain lymph nodes, which were diagnosed by positron emission tomography (PET) scan. This patient received salvage radiotherapy to the regional lymph node, including the left supraclavicular fossa, infraclavicular fossa and internal mammary chain lymph nodes, with the state of her disease currently being stable. No patient died from either breast cancer or cardiac disease during the follow-up period. The median follow-up duration was 28.6 months in the CK group. The 3-year LRFS, DMFS, DFS and OS were all 100 %. In the IB group, the median follow-up period was 61.3 months. The 5-year LRFS, DMFS, DFS and OS was 95 %, 100 %, 95 %, and 100 %, respectively.

4 Discussion

Few studies have conducted dosimetric comparisons of different APBI techniques. Major et al. compared multicatheter interstitial brachytherapy and IMRT for APBI, and found that interstitial brachytherapy generally showed a better sparing effect on OARs [25]. Weed et al. conducted a review of the dosimetric comparison seen among three different APBI techniques: interstitial brachytherapy, the MammoSite balloon apparatus, and 3D conformal external beam quadrant irradiation (3D-CRT). Their results demonstrated that 3D-CRT provided better PTV coverage. However, this improved PTV coverage with 3D-CRT was accompanied by a higher integral dose to the remaining normal breast tissue [26]. Herein et al. compared multicatheter interstitial brachytherapy (MIBT) with CyberKnife, with the results showing that both techniques achieved appropriate target irradiation with high conformity, but MIBT offered more advantages in terms of OARs doses [27,28]. The results of our study revealed that CyberKnife treatment demonstrated a better cardiac dose-sparing effect than interstitial brachytherapy and also had better conformity and homogeneity. This particular treatment plan is generated by using multiple non-coplanar, non-isocentric beams, which may potentially come from a greater number of angles when compared with planning using the LINAC treatment planning system, and may therefore produce better conformity and homogeneity to the target. These beams effectively concentrate the radiation doses on the tumor, while minimizing the doses to the OARs. On the contrary, the planned implantation positions of the catheters determine the distribution of the dose to the target or OARs in the IB treatment plan. In the current study, the reason why the mean heart dose was higher when using IB than it was with CK may be attributed, at least in part, to the position of the catheter being near the chest wall.

APBI offers a significantly shorter treatment duration as well as less toxicity exposure to normal tissue for selected early breast cancer patients, according to several prospective clinical trials. However, in clinical practice, different APBI modalities exhibit various advantages and disadvantages which must be considered (Table 5). In CyberKnife planning, we used skin fiducials for target tracking, which is a non-invasive procedure, because the distance between the skin fiducials and the tumor bed was within 5 cm. Conversely, multicatheter interstitial brachytherapy involves catheter insertion, leading to more breast pain and a higher possibility of wound infection after treatment. Additionally, the position of the catheter implantation may affect the quality of the treatment plan. One of the main drawbacks of brachytherapy is that it requires significant expertise and training in order to ensure that the catheters are properly placed [29,30]. Another major difference between the two methods is that patients undergoing CyberKnife treatment typically have their final pathological report available, while this may not be the case for those undergoing interstitial brachytherapy with intraoperative catheter implantation. This discrepancy can lead to unexpected findings, such as negative frozen section results with subsequent positive lymph node metastases in the final pathology report, or a positive surgical margin. Thus, it then becomes necessary for patients to receive subsequent whole breast irradiation or re-excision. Moreover, the treatment time for each fraction was different between the IB and CK groups in our study. CyberKnife treatment requires a longer dose delivery time per fraction (approximately 20–30 min), so patient cooperation is essential throughout the procedure. In the IB group, only 5–8 min was required in each fraction. In terms of cost effectiveness, APBI is more cost-saving when compared to WBI [31,32]. However, amongst the different APBI techniques, MIBT is covered by national health insurance, whereas APBI using CK is not covered by Taiwan's health plan, resulting in a heavier economic burden for patients who choose CK.Table 5 Clinical advantages and disadvantages between CyberKnife and interstitial brachytherapy.

Table 5CyberKnife	Interstitial Brachytherapy	
Skin fiducial markers (Non-invasive)	Scar of catheters (Invasive)	
Available final pathology report	No available final pathology report	
Less pain	Pain	
Less infection possibility	Infection	
Longer treatment time per fraction(20–30 min)	Shorter treatment time per fraction (5–8 min)	

The predominant acute toxicity in both groups was grade 1 radiation dermatitis. There was no grade 2 or higher acute toxicities seen in the IB or CK groups. In previous study, it was clear that when comparing the toxicity of WBI and APBI, the side effects of APBI were minimal [33]. Byun et al. prospectively evaluated the toxicity outcome between WBI and APBI using CyberKnife, with their APBI group exhibiting significantly lower skin toxicity at 12 months (p = 0.027) when compared to the WBI group. Additionally, fibrosis measured in the uninvolved quadrants was significantly lower in the APBI group than in the WBI group [34]. Due to the long-term survival which many early breast cancer patients experience, focusing on quality of life (QoL) after adjuvant radiotherapy is also of importance. The GEC-ESTRO study showed that APBI using multicatheter brachytherapy offers a similar quality of life when compared to WBI [35]. When Jacobs DH et al. compared intraoperative radiotherapy and external beam APBI using the EORTC-QLQ C30/BR23 questionnaires, both postoperative fatigue and role functioning were found to be significantly worse in the intraoperative radiotherapy group, although no significant difference in quality of life was observed one year after treatment [36]. To date, there is no available literature which directly compares the different APBI modalities of SBRT by CK and MIBT in terms of QoL. According to our clinical experience, patient satisfaction was good in both the CK and IB groups, and better than what was seen in those who underwent WBI.

The preliminary outcomes of tumor control were promising in both groups. Only one patient experienced regional lymph node recurrence, which occurred at 36.8 months, after undergoing APBI by interstitial brachytherapy. Upon reviewing the patient's history, she was diagnosed with breast cancer and lung cancer simultaneously and had received lung cancer treatment prior to breast cancer treatment, so therefore her treatment for breast cancer was delayed. In the CK group, no patient experienced local recurrence during this short-term follow-up period. However, it is important to note that the median follow-up time for the CK group was only 28.3 months, and therefore a longer follow-up period is necessary in order to fully assess tumor control outcomes for these patients. Jaysing et al. conducted a retrospective analysis of approximately 50 patients diagnosed with early breast cancer who had been treated with APBI by CyberKnife. The median follow-up time in that study was 4.68 years, with only one patient experiencing local recurrence [37].

In this study, it is important to note that the contouring of the target and OARs was conducted by the same experienced radiation oncologist who was following the same rules. The purpose of our study was to compare actual dosimetric results, side effects, and tumor control outcomes following the currently available treatment methods, thereby reflecting real-world scenarios. We believe that it is crucial to accurately describe the standard treatments in order to ensure the validity and relevance of our findings.

A limitation of our study was the retrospective nature of the investigation. Despite consistent inclusion criteria for both groups, this approach introduced potential biases due to inherent differences between the two groups of patients, including fewer patients, as well as different follow-up periods and time to undergo APBI. Additionally, this was a single institution study, which can also introduce potential biases. Further multicenter cohort studies should be conducted in order to validate our findings and ensure that they can be applied more appropriately in clinical practice.

5 Conclusion

The results of our study show that APBI delivered by SBRT using CK offers a better dose-sparing effect on the heart. CyberKnife provides a number of benefits, including less acute toxicities, more promising tumor control, and lower risks of wound infection or a delay in wound healing, when compared to treatment by multicatheter interstitial brachytherapy.

Funding

This research received no external funding.

Institutional Review Board statement

The study was conducted in accordance with the Declaration of Helsinki, and was approved by the Institutional Review Board I & II of Taichung Veterans General Hospital. The Clinical trial registration number is TCVGH-IRB No. CE23257C.

Informed consent statement

This was a retrospective study and thus the Institutional Review Board waived the requirement for informed consent. We ensured the anonymity of the patients’ data in the analysis.

Data availability statement

Due to privacy and ethical concerns, the data are not publicly available. The details of the original data are available upon request to the corresponding author.

CRediT authorship contribution statement

Ting-Na Wei: Writing – original draft, Methodology, Formal analysis, Data curation. Jia-Fu Lin: Formal analysis, Data curation. Mei-Chun Cheng: Formal analysis, Data curation. Hui-Ling Yeh: Writing – review & editing, Methodology, Conceptualization.
==== Refs
References

1 Veronesi U. Cascinelli N. Mariani L. Greco M. Saccozzi R. Luini A. Twenty-year follow-up of a randomized study comparing breast-conserving surgery with radical mastectomy for early breast cancer N Engl J Med 347 2002 1227 1232 12393819
2 Darby S. Davies C. McGale P. Davison A. Dodge Y. Wermuth N. The early breast cancer trialists' collaborative group: a brief history of results to date Oxf Stat Sci 33 2005 185
3 Group S.T. The UK Standardisation of Breast Radiotherapy (START) Trial B of radiotherapy hypofractionation for treatment of early breast cancer: a randomised trial Lancet 371 2008 1098 1107 18355913
4 Group S.T. The UK Standardisation of Breast Radiotherapy (START) Trial A of radiotherapy hypofractionation for treatment of early breast cancer: a randomised trial Lancet Oncol 9 2008 331 341 18356109
5 Whelan T.J. Pignol J.-P. Levine M.N. Julian J.A. MacKenzie R. Parpia S. Long-term results of hypofractionated radiation therapy for breast cancer N Engl J Med 362 2010 513 520 20147717
6 Fisher E, Anderson S, Redmond C, Fisher B. Ipsilateral breast tumor recurrence and survival following lumpectomy and irradiation: pathological findings from NSABP protocol B-06. Seminars in surgical oncology1992 p. 161-166..
7 Vicini F.A. Cecchini R.S. White J.R. Arthur D.W. Julian T.B. Rabinovitch R.A. Long-term primary results of accelerated partial breast irradiation after breast-conserving surgery for early-stage breast cancer: a randomised, phase 3, equivalence trial Lancet 394 2019 2155 2164 31813636
8 Strnad V. Polgár C. Ott O.J. Hildebrandt G. Kauer-Dorner D. Knauerhase H. Accelerated partial breast irradiation using sole interstitial multicatheter brachytherapy compared with whole-breast irradiation with boost for early breast cancer: 10-year results of a GEC-ESTRO randomised, phase 3, non-inferiority trial Lancet Oncol 24 2023 262 272 36738756
9 Coles C.E. Griffin C.L. Kirby A.M. Titley J. Agrawal R.K. Alhasso A. Partial-breast radiotherapy after breast conservation surgery for patients with early breast cancer (UK IMPORT LOW trial): 5-year results from a multicentre, randomised, controlled, phase 3, non-inferiority trial Lancet 390 2017 1048 1060 28779963
10 Whelan T.J. Julian J.A. Berrang T.S. Kim D.-H. Germain I. Nichol A.M. External beam accelerated partial breast irradiation versus whole breast irradiation after breast conserving surgery in women with ductal carcinoma in situ and node-negative breast cancer (RAPID): a randomised controlled trial Lancet 394 2019 2165 2172 31813635
11 Meattini I. Marrazzo L. Saieva C. Desideri I. Scotti V. Simontacchi G. Accelerated partial-breast irradiation compared with whole-breast irradiation for early breast cancer: long-term results of the randomized phase III APBI-IMRT-Florence trial J Clin Oncol 38 2020 4175 4183 32840419
12 Marrazzo L. Meattini I. Simontacchi G. Livi L. Pallotta S. Updates on the APBI-IMRT-Florence trial (NCT02104895) technique: from the intensity modulated radiation therapy trial to the volumetric modulated arc therapy clinical practice Practical Radiation Oncology 13 2023 e28 e34 35659597
13 Viani G.A. Arruda C.V. Faustino A.C. De Fendi L.I. Partial-breast irradiation versus whole-breast radiotherapy for early breast cancer: a systematic review and update meta-analysis Brachytherapy 19 2020 491 498 32340902
14 Valachis A. Mauri D. Polyzos N.P. Mavroudis D. Georgoulias V. Casazza G. Partial breast irradiation or whole breast radiotherapy for early breast cancer: a meta‐analysis of randomized controlled trials Breast J 16 2010 245 251 20210799
15 Forster T. Köhler C.V.K. Debus J. Hörner-Rieber J. Accelerated partial breast irradiation: a new standard of care? Breast Care 15 2020 136 147 32398982
16 Emami B. Tolerance of normal tissue to therapeutic radiation Rep Radiother Oncol 1 2013 123 127
17 Correa C. Harris E.E. Leonardi M.C. Smith B.D. Taghian A.G. Thompson A.M. Accelerated partial breast irradiation: executive summary for the update of an ASTRO evidence-based consensus statement Practical radiation oncology 7 2017 73 79 27866865
18 Cheng H.-S. Hung C.-C. Wang K.-C. Tsai I.-C. Lin J.-F. Yeh H.-L. Preliminary outcomes of accelerated partial breast irradiation by interstitial multicatheter brachytherapy with intraoperative free-hand catheter implantation in early breast cancer J Chin Med Assoc 86 2023 381 387 36854132
19 Li C. Lin J.F. Yeh H.L. Dosimetric characteristics of accelerated partial breast irradiation by interstitial multicatheter brachytherapy with intraoperative free‐hand implantation in the treatment of early breast cancer J Appl Clin Med Phys 22 2021 27 34
20 Strnad V. Major T. Polgar C. Lotter M. Guinot J.-L. Gutierrez-Miguelez C. ESTRO-ACROP guideline: interstitial multi-catheter breast brachytherapy as accelerated partial breast irradiation alone or as boost–GEC-ESTRO breast cancer working group practical recommendations Radiother Oncol 128 2018 411 420 29691075
21 Obayomi-Davies O. Kole T.P. Oppong B. Rudra S. Makariou E.V. Campbell L.D. Stereotactic accelerated partial breast irradiation for early-stage breast cancer: rationale, feasibility, and early experience using the cyberknife radiosurgery delivery platform Front Oncol 6 2016 129 27242967
22 Benedict S.H. Yenice K.M. Followill D. Galvin J.M. Hinson W. Kavanagh B. Stereotactic body radiation therapy: the report of AAPM Task Group 101 Med Phys 37 2010 4078 4101 20879569
23 Kaidar-Person O. Meattini I. Boersma L.J. Becherini C. Cortes J. Curigliano G. Essential requirements for reporting radiation therapy in breast cancer clinical trials: an international multi-disciplinary consensus endorsed by the European SocieTy for Radiotherapy and Oncology (ESTRO) Radiother Oncol 2023 110060
24 Paddick I. A simple scoring ratio to index the conformity of radiosurgical treatment plans J Neurosurg 93 2000 219 222 11143252
25 Major T. Stelczer G. Pesznyák C. Mészáros N. Polgár C. Multicatheter interstitial brachytherapy versus intensity modulated external beam therapy for accelerated partial breast irradiation: a comparative treatment planning study with respect to dosimetry of organs at risk Radiother Oncol 122 2017 17 23 27544819
26 Weed D.W. Edmundson G.K. Vicini F.A. Chen P.Y. Martinez A.A. Accelerated partial breast irradiation: a dosimetric comparison of three different techniques Brachytherapy 4 2005 121 129 15893265
27 Herein A. Stelczer G. Pesznyák C. Fröhlich G. Smanykó V. Mészáros N. Multicatheter interstitial brachytherapy versus stereotactic radiotherapy with CyberKnife for accelerated partial breast irradiation: a comparative treatment planning study with respect to dosimetry of organs at risk Radiol Oncol 55 2021 229 239 33768766
28 Herein A. Stelczer G. Pesznyák C. Fröhlich G. Smanykó V. Mészáros N. CyberKnife versus multicatheter interstitial brachytherapy for accelerated partial breast irradiation: a dosimetrical assessment with focus on organs at risk Rep Practical Oncol Radiother 27 2022 152 160
29 Cozzi S. Augugliaro M. Ciammella P. Botti A. Trojani V. Najafi M. The role of interstitial brachytherapy for breast cancer treatment: an overview of indications, applications, and technical notes Cancers 14 2022 2564 35626168
30 Bruand M. Renard S. Salleron J. Meknaci E. Charra-Brunaud C. Peiffert D. Interstitial multi-catheter breast brachytherapy: technical aspects and experience feedback in a comprehensive cancer center Cancer Radiother 26 2022 450 457 34147341
31 Shah C. Ward M.C. Tendulkar R.D. Cherian S. Vicini F. Singer M.E. Cost and cost-effectiveness of image guided partial breast irradiation in comparison to hypofractionated whole breast irradiation Int J Radiat Oncol Biol Phys 103 2019 397 402 30253236
32 Greenup R.A. Camp M.S. Taghian A.G. Buckley J. Coopey S.B. Gadd M. Cost comparison of radiation treatment options after lumpectomy for breast cancer Ann Surg Oncol 19 2012 3275 3281 22851048
33 Shumway D.A. Corbin K.S. Farah M.H. Viola K.E. Nayfeh T. Saadi S. Partial breast irradiation compared with whole breast irradiation: a systematic review and meta-analysis JNCI: J Natl Cancer Inst 115 2023 1011 1019 37289549
34 Byun H.K. Chang J.S. Kim H. Kim J. Han M.C. Kim S.Y. Cosmetic outcome and toxicity after stereotactic accelerated partial breast irradiation in early breast cancer: a prospective observational cohort study Int J Radiat Oncol Biol Phys 117 2023 690 700 37201757
35 Schäfer R. Strnad V. Polgár C. Uter W. Hildebrandt G. Ott O.J. Quality-of-life results for accelerated partial breast irradiation with interstitial brachytherapy versus whole-breast irradiation in early breast cancer after breast-conserving surgery (GEC-ESTRO): 5-year results of a randomised, phase 3 trial Lancet Oncol 19 2018 834 844 29695348
36 Jacobs D.H. Horeweg N. Straver M. Roeloffzen E.M. Speijer G. Merkus J. Health-related quality of life of breast cancer patients after accelerated partial breast irradiation using intraoperative or external beam radiotherapy technique Breast 46 2019 32 39 31075670
37 Jaysing A. Lischalk J.W. Sanchez A. Mendez C. May P. Solan A. Robotic stereotactic body radiation therapy for the adjuvant treatment of early-stage breast cancer: outcomes of a large single-institution study Advances in Radiation Oncology 8 2023 101095
