A randomized controlled trial testing hyaluronic acid spacer injection for skin toxicity reduction of Permanent Breast Seed Implant (PBSI)

1 out of 8 women develop breast cancer. Breast conserving therapy has been
shown to be as effective as ablative therapy in the treatment of a selected
group of early stage breast cancer patients. Postoperative irradiation of the
breast is part of the breast conserving therapy. Along with the fact that local
recurrences usually occur close to the primary tumor, this stimulated worldwide
research on various forms of partial breast irradiation and cosmesis and
quality of life.With Permanent Breast Seed Implant (PBSI), a form of
brachytherapy, radioactive seeds are implanted percutaneously into the surgical
cavity. Palladium-103 seeds, with a half-life of 16.8 days, and a therapeutic
dosage after 84 days, appear to be the most appropriate for this purpose.
5-year results of several multicentre trials on Permanent Breast Seed Implant
(PBSI) were reported in 2015. In total, 134 patients with early stage invasive
breast cancer were treated with a permanent breast seed implant as the sole
adjuvant radiation treatment after breast conserving surgery. The trials
accrued patients based on the guideline for accelerated partial breast
irradiation (APBI) of the American Society for Radiation Oncology (ASTRO). The
outcomes included overall and disease-free survival and local recurrence at 5
years. The true local recurrence rate was compared using 2-tailed paired t
tests for control estimates calculated using the Tufts University ipsilateral
breast tumor recurrence and Memorial Sloan Kettering ductal carcinoma in situ
nomograms. The observed local recurrence rate at a median follow-up period of
63 months was 1.2%, similar to the estimate for whole breast irradiation (1.4%
p=0.23), The 5-year overall survival rate was 97.4% SD ± 1.9%, and the disease
free survival rate was 96.4% SD ± 2.1%.
The most common side effects of PBSI are skin-related. Acute skin toxicity
comprises a moist desquamation in 16% with PBSI, which is lower than with WBI.
Late skin toxicity leads to fibrosis and induration or telangiectasia. The
latter occurs in 25% of the patients after PBSI, slightly more than after WBI5.
Telangiectasia corresponds to the dilation of an abnormal neo-vasculature in
the skin following the destruction of normal capillaries by the radiation
treatment. Due to their prominent appearance, telangiectasia have a negative
effect on cosmesis, the patient*s body image and quality of life6-7. Therefore,
interventions to reduce the clinical appearance of telangiectasia may impact a
patient*s overall well-being or quality of life7. The use of a subcutaneously
injected spacer, to increase the distance between the radiation sources and the
skin, could reduce skin toxicity after PBSI. Studies in patients with prostate
cancer who underwent brachytherapy, show that the use of a hyaluronic acid
spacer reduced rectal dose. This spacer is reabsorbed in 6 to 12 months and is
not associated with an increased risk of infection8. Hyaluronic Acid is widely
used as a dermal filler in cosmetic industry. The use of a spacer in breast
cancer patients has never been done before. In this study the effect of a
hyaluronic acid spacer on skin toxicity after PBSI will be investigated in a
randomized controlled trial. All patients in the study will receive PBSI as
sole adjuvant radiation therapy with or without spacer injection, depending on
their treatment allocation. The primary outcome measure is the occurrence of
telangiectasia at two years.
In addition, the effect of PBSI on cosmesis, quality of life (both
patient-reported), wound infection, local recurrence and (disease free)
survival and cost effectiveness will be assessed and compared to a comparable
group of patients getting standard radiation treatment. This will be the first
study on PBSI in Europe. If the results of this study are favourable, PBSI can
be a very patient-friendly and cost-effective alternative for external whole
breast irradiation in breast conserving therapy.

The primary objective is to evaluate and report the effect of an injected
hyaluronic acid spacer on the rate of telangiectasia following PBSI.

A multicenter double blinded, parallel group randomized controlled trial
comparing the use of an injected spacer during PBSI to PBSI without spacer
injection. It is set up to investigate the superiority of the intervention.
Allocation ratio will be 1:1

for more details see study protocol

Intervention group receives PBSI treatment with spacer injection, control group
receives PBSI without spacer injection.

for more details see study protocol

Application of Barrigel or Restylane SubQ, off-label, in breast cancer patients
to reduce skin toxicity during Permanent Breast Seed Implant is expected to be
a safe and effective treatment. Previous studies with hyaluronic acid based
injections for other indications in the breast showed no significant risks for
patients.
We conclude that the benefits of the treatment when used as intended
considerably outweigh the risks.