A comparison study between the MammoSite radiation

therapy system and intraoperative radiation therapy as a

primary breast treatment

Megan Comer
Introduction:
According to the American Cancer Society, breast cancer is the 2nd leading cause
of cancer death in women7. In 2017, it is estimated that more than 250,000 women will
be diagnosed with breast cancer, and over 40,000 women will lose their battle against the
disease7. The classic radiotherapy treatment for breast cancer is whole breast irradiation
(WBI), using two tangential fields to treat the entire affected breast. An alternative to
WBI, however, is accelerated partial breast irradiation (APBI), which decreases the
treatment time drastically, from 4-5 weeks of treatment to possibly just one high dose
treatment. This single high dose treatment is referred to as intra-operative radiation
therapy (IORT), and is delivered directly into the breast cavity during the lumpectomy
procedure using a linear accelerator located in a specialized operating room3. Another
type of APBI is a technique using the MammoSite radiation therapy system (RTS). In
this procedure, the MammoSite applicator is placed through a stab incision using
ultrasound guidance, and is inflated so that the balloon is conformed to the surgical
cavity6. Then, a live radioactive source is inserted into the balloon for a specified amount
of time, and the surrounding cavity is irradiated6. This treatment is typically done 10-14
times over the course of 5-7 days, depending on the protocol of the hospital it is being
performed in6. These two types of APBI each have their own set of pros and cons, and
multiple studies have been done looking at the outcomes and results of each of these
APBI treatments. There have been minimal studies, though, that compare these two types
of APBI. This information could be clinically useful for a center looking to invest in an
alternative treatment to WBI, or who wants to stay on the forefront of breast cancer
treatment. There are many important considerations to take into account when comparing
the two treatments, such as recurrence rates, cost, cosmetic outcomes, and overall patient
experience.
Hypothesis:
Based on reading multiple research studies and literature pieces about both
MammoSite breast treatments and IORT breast treatments, it seems that the MammoSite
system is better overall, when looking at factors such as recurrence rates, cosmesis
outcomes and patient satisfaction. If this is true, then when new clinical sites are opening
or established clinical sites are ready to invest in new equipment, they would likely
choose to invest in the MammoSite RTS versus buying the equipment required to
perform IORT to the breast.

Literature Review:
Specific studies comparing the Mammosite RTS and IORT of the breast are
minimal. Studies that mention both types of treatments are more so ones that compare
WBI to APBI in a more general form, such as the study done by Njeh, Saunders and
Langton. The results of these comprehensive reviews state that more research still needs
to be done before any type of APBI can become a mainstay treatment, but emphasizes the
possible positive effects of these types of treatments on breast cancer radiotherapy4. All
types of APBI provide a faster treatment time than standard WBI using external beam
radiation therapy (EBRT), and have also shown better cosmetic outcomes than EBRT4. It
is also evident that regardless of the type of APBI being delivered, the method should
only be used in those with very early stage disease, and with no nodal involvement2. It is
likely that no direct comparison studies between MammoSite treatment and IORT have
been done yet because both treatment techniques are still very new and their efficacies
are still being determined. To be able to compare these two different types of treatment, it
is important to review the literature that we have so far about each.
Two large clinical trials have been completed that looked at the outcomes of those
treated with IORT, the ELIOT trial and the TARGIT trial1. The ELIOT trial uses high-
energy electrons produced by a linear accelerator to treat the lumpectomy cavity before
surgical closure1. The TARGIT trial uses an intrabeam device to deliver 50 kV x-rays
directly to the lumpectomy site1. Another technique being researched by the University of
Virginia Health System is precision breast IORT (PB-IORT), which utilizes high dose
rate brachytherapy and CT-on-rails to quickly plan a single fraction treatment that closely
conforms to the lumpectomy cavity1. In all of these IORT techniques, toxicity was
greatly reduced compared to WBI using EBRT. Also, breast related quality of life issues
such as pain, swelling, sensitivity and skin problems were reduced using the different
IORT treatments. Other studies, such as the one completed by Sedlmayer et al., show the
advantages of using IORT as a boost to conventional WBI. This aspect is important to
consider in the use of IORT, as the study found that when IORT was used as a boost to
WBI, recurrence rates dropped an outstanding amount, to less than 1% overall3. As
stopping recurrence is one of the main goals of radiation therapy, it is important to
consider using IORT as a boost treatment even if it is not used as a primary treatment
itself.
The MammoSite RTS has been used since the early 2000s, and has been the focus
of multiple prospective trials. In the past few years, MammoSite has become the focus of
phase III clinical trials, which is an important development for the implementation of this
treatment as a standard breast treatment outside of the conventional WBI5. So far, the
results have shown very good ipsilateral breast, regional lymph and distant control. The
study conducted by Vargo et al. showed control of 98%, 98% and 99% respectively for a
7 year follow up time6. The most common toxicity found in this study was telangiectasia,
which is pinpoint bruising due to widened venules in the skin, which happened to 27% of
the patients in the trial in some form6. Cosmetic outcomes were rated as “good” or
“excellent” by a physician in 93.4% of the patients in this specific trial at the first follow
up, which shows a great improvement from that of cosmetic results after WBI6. Similar
results were found in the prospective study conducted by Small, Refaat and Strauss et al.,
which had a 100% survival rate at a median follow up of 42 months. While these are just
two specific examples of studies conducted using the MammoSite RTS, many other
studies have shown very similar results. Overall, though, there needs to be more phase III
trials such as the one performed by Vargo et al. to completely confirm the efficacy of
using the MammoSite RTS as a primary treatment for breast cancer.
Methods:
Using the database “PubMed”, two separate searches would be run with the same
inclusion criteria. One would be to find studies about IORT breast treatment and one
would be to find studies about the MammoSite RTS. Keywords such as “IORT breast”
and “MammoSite breast” would be used to find studies where the treatments are used as
a primary treatment instead of WBI. Only studies would be included that followed
patients after at least 3 years, to give a valid recurrence rate. The study would also need
to give patient satisfaction rates, and cosmetic outcomes using the physician guided
grading scale. After doing statistical analysis using the Mantel-Haenszel method for each
set of studies, they can then be compared to see which type of treatment is more
statistically relevant. The data would be displayed in a diagram for easy comparison and
analysis, with an IORT row and a MammoSite row displaying all data side by side.

Possible Results:
If the stated hypothesis were true, then it would mean that the results of the
MammoSite RTS trials were more statistically significant than the IORT breast treatment
trials. There would be values found for significance in patient recurrence rates, patient
satisfaction, and good cosmesis rates. If the hypothesis was completely true, than the
MammoSite RTS would be statistically significant more so than IORT breast treatment in
all three categories. If the hypothesis were completely wrong, then the IORT breast
treatment would be superior to the MammoSite RTS in all three categories. It may be,
though, that not one type of treatment has better results than the other in all three
categories. In this case, it would be important to examine which system excels more than
the other in each aspect, as the clinicians reading the study may be looking for a product
that has certain characteristics that are more important to them than others. Since this is
most likely to happen, the results section would analyze the recurrence rates, patient
satisfaction rates, and cosmetic outcomes separately and talk about the possibilities of
why the results were this way. It could be due to things such as different patient
populations, different approaches by clinicians, or slight differences in treatment protocol
between sites. Regardless of which approach is deemed better by statistical significance
testing, the results would be analyzed in a straight forward manner that allowed for easy
comparison between the two breast treatment techniques.
 Works Cited
1. Dutta SW, Showalter SL, Showalter TN, Libby B, Trifiletti DM. Intraoperative
radiation therapy for breast cancer patients: current perspectives. Breast Cancer – Targets
and Therapy. 2017;9 257-263.
2. Njeh CF, Saunders MW, Langton CM. Accelerated partial breast irradiation (APBI): a
review of available techniques. Radiation Oncology. 2010;5(90).
3. Sedlmayer F, Reitsamer R, Wenz F, Sperk E, et al. Intraoperative radiotherapy (IORT)
as boost in breast cancer. Radiation Oncology. 2017;12(23).
4. Skowronek J, Chichel A. Brachytherapy in breast cancer: an effective alternative.
Menopause Review. 2014;13(1):48-55.
5. Small W, Refaat T, Strauss JB, Gopalakrishnan M, et al. Clinical outcomes with the
MammoSite radiation therapy system: results of a prospective trial. 2015;4(4):395-400
6. Vargo JA, Verma V, Kim H, Kalash R, et al. Extended (5-year) outcomes of
accelerated partial breast irradiation using Mammosite ballon brachytherapy: patterns of
failure, patient selection, and dosimetric correlates for late toxicity. International Jounal
of Radiation Oncology. 2014:88(2):285-291.
7. Breast cancer resources page: American Cancer Society website. Available at:
https://www.cancer.org/cancer/breast-cancer/about.html. Accessed July 18, 2017.
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