Struik Gerson M, Godart Jeremy, Verduijn Gerda M, Kolkman-Deurloo Inger-Karine, de Vries Kim C, de Boer Raymond, Koppert Linetta B, Birnie Erwin, Ghandi Ali, Klem Taco M, Pignol Jean-Philippe
Department of Surgery, Franciscus Gasthuis and Vlietland, PO Box 10900, 3004 BA, Rotterdam, The Netherlands.
Department of Radiation Oncology, Erasmus MC Cancer Institute, PO Box 5201, 3008 AE, Rotterdam, The Netherlands.
Trials. 2018 Dec 17;19(1):689. doi: 10.1186/s13063-018-3035-3.
Accelerated 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.
In 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.
In 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.
Netherlands Trial Register, NTR6549 . Registered on 27 June 2017.
加速部分乳腺照射（APBI）是部分早期乳腺癌患者的一种治疗选择。一些APBI技术会导致皮肤毒性，皮肤剂量是主要风险因素。我们假设在皮肤与靶区之间注射间隔物可降低永久性乳腺籽源植入（PBSI）患者的皮肤剂量及后续毒性。
在这项平行组、单中心、随机对照试验中，测试皮下注射间隔物对接受PBSI治疗患者皮肤毒性的影响。参与资格源自部分乳腺放疗合适患者的国际指南，例如年龄≥50岁、组织学证实为非小叶型乳腺癌和/或原位导管癌（DCIS）、肿瘤大小≤3 cm、淋巴结阴性且PBSI技术上可行的女性。排除标准包括新辅助化疗、淋巴管浸润以及对透明质酸过敏。对于分配接受间隔物的患者，在PBSI操作后，使用超声引导将4 - 10 cc可生物降解透明质酸（Barrigel™，Palette Life Sciences，美国加利福尼亚州圣巴巴拉市或Restylane SubQ®，Galderma Benelux，荷兰布雷达）直接注射到皮肤下，在治疗靶区与皮肤之间形成额外0.5 - 1 cm的间隙。主要结局是两年时的毛细血管扩张率，采用本岑4分法进行盲法评估。次要结局包括：局部复发；无病生存率和总生存率；不良事件（疼痛、发红、皮肤/皮下硬结、放射性皮炎、色素沉着、手术部位感染）；皮肤剂量；美容和功能结果；以及健康相关生活质量。将采用Fisher精确检验来测试两组在主要结局上的差异。既往研究发现两年时毛细血管扩张率为22.4%。我们预计使用间隔物可将毛细血管扩张的发生率降至7.7%。230例患者的样本量将允许有10%的失访率。
在本研究中，在保乳治疗背景下接受PBSI治疗的患者中测试皮下注射间隔物对皮肤剂量、晚期皮肤毒性和美容结局的影响。我们的结果对于大多数形式的乳腺近距离放疗以及机器人放射外科手术都将具有参考价值，因为皮肤间隔物可通过这些其他技术保护皮肤。
荷兰试验注册库，NTR6549。于2017年6月27日注册。
