A randomized controlled trial testing a hyaluronic acid spacer injection for skin toxicity reduction of brachytherapy accelerated partial breast irradiation (APBI): a study protocol

Abstract

BackgroundAccelerated partial breast irradiation (APBI) is a treatment option for selected early stage breast cancer patients. Some APBI techniques lead to skin toxicity with the skin dose as main risk factor. We hypothesize that a spacer injected between the skin and target volume reduces the skin dose and subsequent toxicity in permanent breast seed implant (PBSI) patients.MethodsIn this parallel-group, single-center, randomized controlled trial, the effect of a subcutaneous spacer injection on skin toxicity among patients treated with PBSI is tested. Eligibility for participation is derived from international guidelines for suitable patients for partial breast radiotherapy, e.g. women aged ≥ 50 years with a histologically proven non-lobular breast carcinoma and/or ductal carcinoma in situ (DCIS), tumor size ≤ 3 cm, node-negative, and PBSI technically feasible. Among exclusion criteria are neoadjuvant chemotherapy, lymphovascular invasion, and allergy for hyaluronic acid. For the patients allocated to receive spacer, after the PBSI procedure, 4–10 cc of biodegradable hyaluronic acid (Barrigel™, Palette Life Sciences, Santa Barbara, CA, USA or Restylane SubQ®, Galderma Benelux, Breda, the Netherlands) is injected directly under the skin using ultrasound guidance to create an extra 0.5–1 cm space between the treatment volume and the skin. The primary outcome is the rate of telangiectasia at two years, blindly assessed using Bentzen’s 4-point scale. Secondary outcomes include: local recurrence; disease-free and overall survival rates; adverse events (pain, redness, skin/subcutaneous induration, radiation dermatitis, pigmentation, surgical site infection); skin dose; cosmetic and functional results; and health-related quality of life.A Fisher’s exact test will be used to test differences between groups on the primary outcome.Previous studies found 22.4% telangiectasia at two years. We expect the use of a spacer could reduce the occurrence of telangiectasia to 7.7%. A sample size of 230 patients will allow for a 10% lost to follow-up rate.DiscussionIn this study, the effect of a subcutaneous spacer injection on the skin dose, late skin toxicity, and cosmetic outcome is tested in patients treated with PBSI in the setting of breast-conserving therapy. Our results will be relevant for most forms of breast brachytherapy as well as robotic radiosurgery, as skin spacers could protect the skin with these other techniques.Trial registrationNetherlands Trial Register, NTR6549. Registered on 27 June 2017.Electronic supplementary materialThe online version of this article (10.1186/s13063-018-3035-3) contains supplementary material, which is available to authorized users.

Aesthetic Treatments in Cancer Patients

“…14 Moreover, the use of fillers is approved in cancer patients to prevent skin toxicity, secondary to some therapies such as radiotherapy, and have also been implied as a reconstructive technique, particularly for breast cancer. 15 Although generally safe, filler injections can sometimes cause adverse events which can be distinguished as reactions at the site of injection or an inflammatory, vascular reaction. Injection site reactions include erythema, oedema, pain and bruising.…”

Radiochromic film in vivo dosimetry predicts early the risk of acute skin toxicity for brachytherapy partial breast irradiation

“…Patients included in this study were participating in a clinical trial evaluating the benefit of a skin spacer to reduce skin toxicity for low dose rate (LDR) seed brachytherapy APBI (Struik et al 2018). An ancillary study was performed to measure the skin dose, and to correlate those measurements to dose calculations and acute toxicity in 18 consecutive patients.…”

“…Patients were excluded from the study if they had neo-adjuvant chemotherapy, lymphovascular invasion, or an allergy for hyaluronic acid. The trial details have been described elsewhere (Struik et al 2018). The trial was approved by the Erasmus MC research ethic board (MEC-2016-400) and registered at the Netherlands Trial Register (NTR6549).…”

“…The implantation procedure, including a 5-10 mm skin spacer injection (Barrigel, Palette Life Sciences) for the patients randomized to the experimental arm, has been described elsewhere (Struik et al 2018(Struik et al , 2019, and involved the placement of the seeds under light sedation using the Breast Microseed device (Concure Oncology, Seattle, WA).…”

Technologies to reduce radiation toxicity in prostate cancer patients: spacers - a simple and effective solution

“…Эффективность и целесообразность этого подхода наглядно демонстрируются существенным ростом числа публикаций, описывающих различные аспекты клинического применения БДС не только в рамках онкоурологической практики, но и при лечении многих других солидных неоплазий (гинекология, абдоминальная онкология, маммология и др.) [4][5][6][7].…”