Int J Clin Oncol

DOI 10.1007/s10147-017-1155-5

REVIEW ARTICLE

Brachytherapy in the treatment of breast cancer

Xinna Deng1 · Haijiang Wu2 · Fei Gao1 · Ye Su3,4 · Qingxia Li1 · Shuzhen Liu1 ·
Jianhui Cai1 

Received: 8 July 2016 / Accepted: 14 June 2017

© Japan Society of Clinical Oncology 2017

Abstract  Brachytherapy is an important radio-therapeutic an overview of outcomes, cosmetic outcome, toxicity,

modality for a variety of malignancies, including prostate
cancer, cervix cancer, breast cancer, vagina cancer, endo-
metrium cancer, head and neck cancer, and many more.
This technique has been shown to be an effective and safe
non-pharmaceutical treatment with fewer serious complica-
tions and better outcome than other treatments for breast
cancer. Every year, hundreds of thousands of patients
around the world benefit from brachytherapy, which reli-
ably delivers a relatively higher radiation dose to the
intended target. However, the follow-up time, patient eligi-
bility criteria, treatment strategy, and radiation doses used
in published studies are somewhat inconsistent, making it
difficult to strictly compare and evaluate the performance
of the treatment. More rigorous studies are required to
confirm the safety of this technique and to make outcome
data more comparable. In this review, we focus on recent
advances in breast brachytherapy techniques and provide
Xinna Deng and Haijiang Wu have contributed equally to this
work.
* Jianhui Cai
jianhuicai2001@163.com
Xinna Deng
dengxinna@sina.com
1 to patients who should receive adjunct therapy, possibly in
Department of Oncology & Immunotherapy, Hebei General
Hospital, Shijiazhuang, China
2 appropriate radiation therapy center, indigence, and poor
Department of Pathology, Hebei Medical University,
Shijiazhuang, China
3 eral breast tumor recurrences (IBTR) after BCS have been
Mathew Mailing Centre for Translational Transplantation
Studies, Lawson Health Research Institute, London Health
Sciences Centre, London, ON, Canada
4
Department of Medicine, and Pathology, University
of Western Ontario, London, ON, Canada
complications, and limitations of brachytherapy for the
treatment of breast cancer. We also summarize the clinical
outcomes and toxicity results in patients receiving or not
receiving brachytherapy.
Keywords  Brachytherapy · Breast cancer · Radiation
therapy · Outcomes
Introduction
Breast cancer is the most frequent malignant tumor for
women, with approximately 1,677,000 newly diagnosed
cases and 522,000 deaths worldwide in 2012 alone [1].
In China, about 248,620 women were newly diagnosed
with breast cancer in 2011, and in that same year the num-
ber of female breast cancer deaths was about 60,473 [2].
Breast-conserving surgery (BCS) followed by whole-breast
irradiation (WBI) is widely accepted as the standard treat-
ment for patients with early breast cancer (stages 0, I and
II). However, it has been reported that up to 23% of female
breast cancer patients in the USA who were eligible for
lumpectomy did not receive any adjunct radiation therapy
after conservative surgery [3]. The repetitive cycles of post-
operative radiotherapy (3–7 weeks) are a major deterrent
conjunction with other hurdles, such as long distance to an
ambulatory status. In addition, the vast majority of ipsilat-
shown to localize only to the tumor bed area, rather than to
other sites of the ipsilateral breast [4, 5].
Recently, accelerated partial breast irradiation (APBI)
has quickly emerged as a potential alternative to standard

13

WBI, and this strategy may compensate for the limitations
of logistical and economic constraints. APBI is defined
as radiotherapy to treat solely the adjacent breast tissue
around the surgical cavity in a drastically shortened 1-week
radiotherapy course. Four types of APBI techniques have
been described: multi-catheter interstitial brachytherapy
(MIB), intracavitary brachytherapy ­ (MammoSite®, Xoft
® ®
­Axxent , and ­ ClearPath ), three-dimensional conformal
external beam radiation therapy (EBRT), and intra-opera-
tive radiotherapy, each with its own advantages, drawbacks,
and most suitable indications—and none as yet qualifies as
a universal solution.
Of these four types of APBI techniques, only MIB and
intracavitary brachytherapy are reviewed here, excluding
intravascular brachytherapy and pulsed dose rate (PDR)
brachytherapy. We discuss the general principles and the
cutting-edge implantation techniques in the context of clin-
ical applications of brachytherapy in breast cancer. Previ-
ously published data for brachytherapy are also compared.
Overview of brachytherapy
Brachytherapy is a type of radiotherapy wherein the tiny
radioactive sources are directly implanted into or close to
the target tissue to kill cancer cells. Despite the early results
being not as good as expected, it has regained popularity
in recent years, initially due to the emerging of sophisti-
cated imaging modalities, such as transrectal ultrasound
and computerized dose planning systems. This therapy has
saved or prolonged the lives of millions of cancer patients
worldwide and changed the landscape of oncotherapy.
There are four basic types of brachytherapy: intracavi-
tary brachytherapy, interstitial brachytherapy, intralumi-
nal brachytherapy, and intravascular brachytherapy. It also
can be split into three main types according to the radia-
tion dose rate: low dose rate (LDR), high dose rate (HDR),
and PDR. Additionally, according to the duration of radio-
active isotope in the target area, brachytherapy comprises
two categories: permanent brachytherapy and temporary
brachytherapy.
Experimental results indicate that cells in mitotic divi-
sion (M phase) and ribonucleic acid (RNA) synthesis (G2
phase) are particularly sensitive to radiation. Radiation
therapy preferentially affects cancer cells that divide rap-
idly. Therefore, cancer cells are more sensitive to radiation
than normal cells. Brachytherapy delivers precise radia-
tion doses to the tumor from the inside out. According to
Newton’s inverse-square law, the radiation dose drasti-
cally reduces with distance from the center of the source.
Hence, a relatively high radiation dose is constricted to the
tumor bed, sparing even nearby healthy structures and criti-
cal organs. Both of these advantages of radiation therapy
13
Int J Clin Oncol
provide persuasive arguments for the use of brachytherapy.
At present, iodine-125 (125I) is the most commonly used
radioisotope in brachytherapy, but it can also be delivered
with an electronic brachytherapy source involving a minia-
turized X-ray tube [6]. Brachytherapy is often used to treat
tumors of the prostate, cervix, breast, vagina, endometrium,
head and neck, esophagus, lung, and several others.
Multi‑catheter interstitial brachytherapy
Multi-catheter interstitial brachytherapy was originally
administered as a boost after BCS and WBI, which initi-
ated the concept of APBI. Beginning in the 1990s, MIB, as
a monotherapy or a sole adjuvant radiotherapy after BCS,
has offered a whole new approach to treat early breast can-
cer. Typically, 10–20 catheters are continuously implanted
into the breast tissue surrounding the lumpectomy site at
10- to 20-mm intervals during or immediately after the
surgical procedure. Radioactive sources are subsequently
placed inside the catheters to deliver radiation from inside
the breast. Once treatment planning is accomplished, the
radioactive source is remotely after-loaded into the cath-
eter under computer control, providing a homogeneous
dose to the target volume. Interstitial brachytherapy can
be administered at either LDR or HDR. Unfortunately, the
early clinical results of MIB were not as encouraging as
expected, with some studies reporting a high incidence of
ipsilateral breast tumor recurrence and late complications.
For example, in 1991, Fentiman et al. reported that 27
patients with operable breast cancer were treated with HDR
iridium-192 (192Ir; 55 Gy) after tumorectomy [7]. In 1996,
their 6-year follow-up of the same population determined
that ten (37%) of the 27 patients had local recurrence, and
the authors thus considered that the treatment was a failure
[8]. These frustrating results may suggest that adherence to
appropriate patient selection criteria and proper technical
guidelines are critical to successful long-term outcome.
In the past two decades, image-based dose planning
and seed implantation have clearly improved the tumor
dose coverage and overall survival of patients receiving
brachytherapy. Computed tomography (CT) is the most
commonly used modality for MIB and has replaced the
traditional two-dimensional orthogonal-based imaging.
Some of the first retrospective CT-based interstitial brachy-
therapy studies was performed in the 1990s at the William
Beaumont Hospital in the USA [9, 10]. In these studies,
CT-based interstitial brachytherapy was originally used for
dose-volume analysis of HDR interstitial breast implants,
and promising results were obtained. Consistent with these
results, another study with CT-based treatment planning
achieved excellent visualization of the lumpectomy cavity
and normal structures, resulting in improved target volume
Int J Clin Oncol
delineation and optimal coverage [11]: specifically, the
lumpectomy cavity was covered 100% and target volume
coverage was excellent. Subsequently, in 2005, Major et al.
recommended that three-dimensional imaging should be
also used for planning the geometry of the catheter posi-
tions and performing the insertions [12]. Indeed, two-
dimensional imaging is always associated with additional
uncertainties. CT-based dosimetry systems do not take
into account the unavoidable effects of organ deformation/
movement or setup error [13]. An accurate dose-volume
analysis and treatment-planning adjustment are important
to improve the implant quality.
CT-based imaging is also regarded as an essential tech-
nique for planning target volume localization and catheter
reconstruction, as well as dose distribution optimization
after implantation. Recent studies have demonstrated three-
dimensional CT-based MIB results are associated with
excellent long-term outcomes and good to excellent cosme-
sis [14]. However, the main limitation of CT in comparison
to other imaging modalities is its relatively poor soft tis-
sue contrast. This disadvantage has led to investigations on
the utility of magnetic resonance imaging (MRI) in breast
brachytherapy. Jolicoeur et al. has reported that in com-
parison to CT MRI-based planning provides a more precise
definition of the surgical bed with a smaller inter-observer
variability, leading these authors to suggest that the com-
bination of CT and MRI allows for more accurate surgical
bed delineation [15]. Nonetheless, researchers from The
Netherlands have reported conflicting results [16]. The rea-
son for the discrepancy is currently unclear. Moreover, in a
more recent study, a novel robot-assisted integrated three-
dimensional ultrasound guidance system for real-time plan-
ning and guidance of breast interstitial HDR brachytherapy
treatment performed significantly better than MRI and CT
in terms of dosimetric indices [17] and may be a reliable
alternative.
During the past 15 years, several promising results
have been reported in stringently selected patients with
early-stage breast cancer treated with MIB. Table 1 sum-
marizes a number of the reported studies with differ-
ent techniques of MIB, with a median follow-up rang-
ing from 12 to 133 months. Most retrospective studies
and prospective randomized trials have been carried out
in Western countries. There are noteworthy consisten-
cies among these clinical outcomes in spite of varied
patient eligibility criteria and brachytherapy techniques
(HDR, PDR, or LDR). In general, the local recurrence
rate, ranging from 0 to 12.5%, is much lower than that
previously reported in inappropriately selected patients.
Most patients (37–99%) achieved good or excellent
cosmetic results. Most published results to date have
illustrated excellent results with fewer and better local
controls, fewer side effects, and good cosmetic outcomes.
The main complication of MIB after treatment is infec-
tion, especially for those patients who have underwent
open-cavity implantation. Late adverse effects, such as
breast edema, fibrosis, pain, and fat necrosis, occur only
in a minority of patients. In summary, the reported side
effects are mostly mild to moderate and similar to those
seen in WBI.
Several large randomized trials comparing MIB with
WBI, as well as other radiotherapies, have been published
recently. A comparison of treatment outcomes between
sole MIB and WBI for early breast cancer is listed in
Table 2. Despite an apparent discrepancy among the dif-
ferent studies, all trials are largely consistent in terms of
fat necrosis, disease control rates, disease-free survival
rates, and overall survival rates. MIB shows a better cos-
metic outcome, although with a slight increase in breast
fibrosis and telangiectasias. These results are consistent
with those of a recent study showing that the body image
and the fear of recurrence is similar after MIB and WBI
[41]. Moreover, three studies have compared the dosime-
try between MIB and WBI on surrounding organs at risk),
such as the left anterior descending artery, heart, lung,
and adjacent skin [42, 43]. All studies seem to converge
to the lower doses occurring in the MIB. In addition, ran-
domized studies comparing the long-term results between
patients treated with MIB or external beam radiotherapy
are now completed. For example, in 2012, Anbumani
et al. specifically analyzed the feasibility of using exter-
nal beam radiotherapy for APBI in comparison with HDR
MIB on a tumor and normal tissue dose-volume analysis
[44]. The study revealed that the brachytherapy planning
resulted in a comparable conformal dose distribution to
that of external beam planning and that the normal tis-
sue dosimetry in terms of brachytherapy planning was
comparable with that of conformal external beam plan-
ning with photon beams [44]. In 2013, Roy et al. evalu-
ated the effectiveness of external beam radiotherapy or
HDR MIB used as a boost in breast conservation patients.
The study showed no significant differences in local
control rate with both techniques, although the patients
receiving MIB had worse cosmetic results than those
receiving external beam radiotherapy [45]. However, it
is important to recognize that the substantial number of
patients treated with MIB after BCS may be much lower
than it appears to be because several study results were
reported by the same research group. Additionally, vari-
ous drawbacks, such as inhomogeneous dose distribution,
insufficient long-term follow-up, under-par cosmetic out-
come, inconsistent patient selection criteria, and radiation
technique, have greatly restricted the application of this
technology.
13


13
Table 1  Outcomes of multi-catheter interstitial brachytherapy in patients with early-stage breast cancer
References Dose rate Number of Median follow-up Median age Pain Infection Fat necrosis Fibrosis Good to excellent Local recurrence
patients (years) cosmesis rate

[18] HDR 32 33 months 63 6.25% 0 25% – 90.63% 3%

[19] PDR or HDR 69 24 months 58 8.60% 1.40% 0 13.00% 92.40% 0
[20] LDR or HDR 199 5.7 years 65 6 months: 27% 11% 21% 6 months: 14% >90% 1.2%
5 years: 9% 5 years: 63%
[21] PDR or HDR 176 12 months 51 – 0.60% – 14.50% 92–95% 0
[22] 69 50.2 months – – – 2.90% 23.20% – –
[23] HDR 75 73 months 63 – 5.48% 13% – 91% –
[24] HDR 20 52 months 50 – 5% 5% – 75% 5%
[25] LDR or HDR 199 6.4 years 65 6 months: 27% 11% 6 months: 1% 6 months: 22% 95-99% –
5 years: 8% 2 years: 9% 2 years: 48%
5 years: 11% 5 years: 46%
[26] HDR 45 31 months 44 4.40% 9% 2.22% – – 4.44%
[27] PDR 50 86 months 53 2% 10% 12% 26% 56% 6%
[28] HDR 45 11.1 years 45 – – Grade 0: 62.2% Grade 0: 57.8% 78% 9.3%
Grade 1:17.8% Grade 1: 20.0%
Grade 2: 17.8% Grade 2: 20.0%
Grade 3: 0% Grade 3: 2.2%
Grade 4: 2.2%
[29] HDR 48 53 months 52 – – 10.40% – 89.60% 4.6%
[30] PDR or HDR 274 63 months 60.5 – 3.28% 5.10% 30.10% 90.10% 2.9%
[31] PDR 24 30 months – 37% – – 79% 37% 12.5%
[32] 3 3.4 years 58 – – – – – 0
[33] LDR, PDR 217 3.9 years 60.6 – – – 67% 85% 5-year: 5.6%
or HDR 10-year: 7.2%
[34] LDR or HDR 1131 6.9 years 59 – – – – 84% 5.2%

HDR High dose rate, PDR pulsed dose rate, LDR low dose rate
Int J Clin Oncol
 Table 2  Comparison of treatment outcomes between sole multi-catheter interstitial brachytherapy and whole-breast irradiation for early breast cancer
Int J Clin Oncol

References Technique Number of Median follow- Median age Disease-free Overall survival Cosmetic result Breast fibrosis Fat necrosis Breast pain
patients up (years) survival

[35] MIB 87 50 months 59 – – Good/excellent: – No FN: 63.2% –

No fat necrosis: Asymptomatic
62% FN: 25.3%
Asymptomatic Symptomatic FN:
FN: 68% 11.5%
Symptomatic FN:
22%
WBI 129 48 months 58 Good/excellent: – No FN: 71.3% –
No FN: 94% Asymptomatic
Asymptomatic FN: 20.2%
FN: 85% Symptomatic FN:
Symptomatic FN: 8.5%
60%
[36] MIB 199 9.4 years 65.2 68% 72% – – – –
WBI 199 13.7 years 63.5 77% 82% – – – –
[37] MIB 27 43.05 months 52.41 100% 93.8% Excellent: 18.5% None: 48.1% None: 88.9% –
Good: 70.4% Mild: 44.4% Asymptomatic: –
Fair: 11.1% Moderate: – Symptomatic:
Poor: – Severe: – 3.7%
Unknown: – NK/NR: 7.4% NK/NR: 7.4%
WBI 67 51.08 months 52.42 100% 92.3% Excellent: 10.4% None: 83.6% None: 89.6% –
Good: 31.3% Mild: 9.0% Asymptomatic: –
Fair: 28.4% Moderate/severe: Symptomatic:
Poor: 4.5% 1.5% 3.0%
Unknown: 25.4% NK/NR: 6.0% NK/NR: 6.0%
[38] MIB 199 10.4 years 65.1 91% 71% – – – –
WBI 199 14.0 years 63.5 87% 78% – – – –
[39] MIB 202 64.3 months 60.0 94.3% 91.90% – – – –
WBI 94 64.1 months 56.9 93.4% 96.70% – – – –
[40] MIB 633 5 years 62 95.03% 95.55% – 0 – 1.14%
WBI 551 5 years 62 94.45% 97.27% – 0.23% – 3.17%

MIB Multi-catheter interstitial brachytherapy, WBI whole-breast irradiation, FN fat necrosis, NK/NR not known/not reported

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Balloon intracavitary brachytherapy
The balloon intracavitary brachytherapy, mainly known
as the Mammosite brachytherapy (MSB), has been used
extensively in the curative or adjuvant treatment of breast
cancer for more than 10 years. As an alternative to inter-
stitial brachytherapy, MSB can be used a sole radiotherapy
adjuvant after BCS or a boost in conjunction with EBRT.
One of the advantages of the technique is that the patho-
logic diagnosis can be made before placement of the cath-
eter. MSB is generally safe and usually associated with
only very mild side effects. Although the incidence varies
in published studies, seroma and fat necrosis are the more
commonly reported side effects [46–48]. In addition, the
outcomes of 1440 patients enrolled in the American Soci-
ety of Breast Surgeons (ASBS) large MammoSite breast
brachytherapy registry trial have been sequentially pub-
lished in recent years (Table 3). With the increased use
of MSB over the past decade, several institutions have
reported studies which compared outcomes between MSB
and WBI, leading to the suggestion that MSB is compa-
rable or superior to WBI in terms of overall survival, dis-
ease-free survival, time to local failure, tumor bed failure,
regional recurrence, fatigue, perceived stress, and quality of
life [55–57]. However, even though these results are prom-
ising, the cost effectiveness must be taken into account to
avoid possible over-interpretation of the conclusions [58].
Several other important clinical and pathologic fac-
tors essential for successful outcomes are summarized as
follows:
(1) Patient selection: Several international and national
societies have independently published patient selec-
tion criteria, including the ASBS, the American Soci-
ety of Therapeutic Radiation Oncology (ASTRO), the
American Brachytherapy Society, and the European
Society for Radiotherapy & Oncology [59]. However,
the optimal patient selection criterion remains contro-
versial [60].
(2) Receptor phenotype: Estrogen receptor (ER) negativ-
ity was reported to be the only variable associated with
the 5-year rate of IBTR [50, 61]. However, another
study found that patients with triple negative disease,
a subtype of breast cancer that does not express genes
for ER and progesterone receptor (PR) or overex-
presses the gene for human epidermal growth factor
receptor 2 (HER-2/neu), demonstrated significantly
worse prognosis [62]. The discrepancy among stud-
ies may be attributable to ethnic, genetic, and environ-
mental differences, as well as varied sample sizes.
(3) Age: Published studies have confirmed that age is a
significant factor associated with toxicity and IBTR
for patients undergoing MSB, especially for women
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Int J Clin Oncol
younger than 50 years [49, 63], although not in all
studies [64].
(4) Infection prevention: Breast wound infection is sig-
nificantly associated with inferior cosmetic results
[65, 66]. Furthermore, post-MSB infection is signifi-
cantly associated with clinically significant seroma
development [67].
(5) Tumor size: Tumor size: Larger tumor size is signifi-
cantly associated with a greater risk of distant metas-
tasis and worse long-term cosmetic results [49, 68].
(6) Margin status: A margin of ≥1.0 mm appears to be
responsible for a 35% risk of microscopically detect-
able residual tumor [64]. However, a conflicting
result has been reported by the ASBS MammoSite
Breast Brachytherapy Registry Trial [69].
(7) Surrounding tissue: The inadequate distance from the
balloon surface to the surrounding normal tissues,
such as skin, chest wall, heart, and lung, is always
coupled to an increased rate of toxicity in patients
treated with breast brachytherapy [70].
(8) Chemotherapy: The ASBS showed that the use of
chemotherapy is one of most important predictors of
cosmesis at 36 months, regardless of the status of the
breast infection [66, 71].
Xoft Axxent® brachytherapy
To overcome the drawback of MSB that inadequate balloon-
to-skin distance may result in late skin toxicity, several other
methods are also being exploited to treat early-stage breast
cancer, such as Axxent electronic brachytherapy, Monte
Carlo, Contura, and hybrid brachytherapy devices. Xoft
Axxent® electronic brachytherapy (Xoft, Inc., Sunnyvale,
CA) is one of the fastest growing therapies in recent years.
It has been introduced as a novel method of balloon-based
APBI and received the U.S. Food and Drug Administration
approval in January 2006. Similar to the above-mentioned
MammoSite system, this device features a dual-lumen cathe-
ter. The crucial difference is that the Xoft Axxent® electronic
brachytherapy system uses a 50-kV electronic source, not
­thenn192 Inr HDR source seen in MammoSite treatments, to
produce X-rays, and it does not need the specifically shielded
radiation vault due to its the limited range of the low-energy
photon emission. The source of the Xoft Axxent® device has
a pronounced anisotropy, which minimizes excessive skin
dose and maintains optimal tumor cavity coverage when the
cavity-to-skin distance is small [72]. To date, published data
on the Xoft Axxent® electronic brachytherapy system are
rather limited. Rivard and colleagues [73] carried out a pre-
liminary dosimetric comparison between MammoSitennn192
Ir HDR brachytherapy and Xoft Axxent® electronic brachy-
therapy. The mean ipsilateral breast  %V50 (the planning
 Table 3  Outcomes of patients enrolled in the American Society of Breast Surgeons MammoSite breast brachytherapy registry trial
References Median follow- Groups Number of Ipsilateral breast 5-year actuarial 5-year overall Disease-free Cause-specific Overall survival Good to excellent
up patients tumor recurrence rate of axillary survival rate in survival rate survival rate rate cosmesis
failure patients with an
axillary failure
Int J Clin Oncol

[49] 53.5 months Suitable group 419 2.59%

Cautionary 430 5.43%
group
Unsuitable group 176 5.28%
[50] 53.6 months All patients 1449 3.89%
Unsuitable 176 5.25%
patients
All 1449 1273 3.60%
patients,
excluding
unsuitable
patients
Invasive only 1255 3.86%
patients
Invasive only 1105 3.89%
patients,
excluding
unsuit-
able invasive
patients
[51] 59 months 1440 0.79% 77.80%
[52] 60 months 1440 3.61% 58.7%a 92.1%a 80.5%a
[53] 7 years Women 537 92.00%
>70 years old
Women aged 195 87.00% 97.50% 89.30%
>70 years with
hormone-sen-
sitive tumors
with a diameter
of ≤2 cm who
received hor-
monal therapy
[54] 63.1 months 1449 3.80% 60 months: 91.3%
72 months: 90.5%
84 months: 90.6%
a
  3-year rate after ipsilateral breast tumor recurrence

13

target volume that received 50% of the prescription dose) for
the MammoSite and Xoft Axxent® methods were 19.8 and
13.0%, the mean ipsilateral lung %V30 (the planning target
volume that received 30% of the prescription dose) were
3.7 and 1.1%, and the mean heart %V5 (the planning target
volume that received 5% of the prescription dose) were 59.2
and 9.4%, respectively. The authors concluded that the two
methods of balloon-based PBI offered comparable target
volume coverage, with the Xoft Axxent® method showing
an increased volume of breast tissue in the high dose regions
and a decreased dose to the adjacent normal tissues. In addi-
tion, it has also been suggested that significant dose enhance-
ment can be achieved to residual tumor cells targeted with
gold nanoparticles during APBI with Xoft brachytherapy
[74]. However, Chen et al. showed that the equivalent skin
dose from Xoft Axxent® electronic brachytherapy (537 cGy
per fraction) was significantly higher than that ­fromnn192Ir
(470 cGy per fraction) [75]. In 2010, Hepel et al. simulated
three different balloon-insertion orientations to optimize skin
surface dose: perpendicular to the surface, oblique to the sur-
face (45°), and parallel to the surface. The perpendicular ori-
entation had the lowest surface dose at 99% of the prescrip-
tion; the surface dose was the highest for the perpendicular
orientation (164%) and intermediate for the oblique orienta-
tion (117%) [72]. The authors of this study concluded that
optimized Xoft Axxent® balloon catheter orientation could
be used to decrease skin late effects and improve cosmetic
outcome [72]. Further research will be needed to define the
potential of Xoft Axxent® brachytherapy as an alternative
therapeutic approach in breast cancer.
Prospect and problems
The advantage of brachytherapy is that the radiation dose
delivered to the tumor and adjacent tissues is highly con-
formal, thereby minimizing normal surrounding structure/
organ exposure. Hence this therapy is preferable in terms
of tumor local control and cosmetic results. The develop-
ment and improvement of imaging technologies, such as
ultrasound, CT, MRI, and positron emission tomogra-
phy scans, together with the use of the highly sophisti-
cated treatment planning system, have further improved
the accuracy of seed localization and the life quality of
patients. For the appropriate patients, this technique can
be a pragmatic and effective treatment, with fewer seri-
ous complications and a better outcome than those with
other cancer treatments, including hormone therapy and
chemotherapy.
However, several issues remain to be tackled:
(1) Radiation dose: To explain the qualitative discrepancy
between different studies, future studies will be neces-
13
Int J Clin Oncol
sary to ascertain the optimal dose rates and fractiona-
tion-dose for a given individual.
(2) Long-term efficacy: There is currently little long-term
follow-up data available, especially for periods of
>10 years after therapy, to support the long-term effi-
cacy of brachytherapy, despite the promising short-term
clinical trial results.
(3) Safety: Radioactive seed implants will unavoidably
cause collateral radiation exposure to healthy tissue,
medical staff, and even family. Further rigorous studies
are required to confirm the long-term safety.
(4) Proper patient selection: there is a noteworthy inconsist-
ency in the patient selection criteria and the treatment
schedule between different countries and even between
different studies, making it difficult to compare the data
stringently from these trials or to set standards. As such,
morphological examinations, image fusion and molecu-
lar imaging technique will be increasingly used to bet-
ter define the target volumes and organs.
Funding  This study was supported by the Program of Hebei Admin-
istration of Traditional Chinese Medicine (2013031).
Compliance with ethical standards 
Conflict of interest  All authors declare that they have no conflicts of
interest.
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