Department of Radiation Oncology, University Hospital Erlangen, Erlangen.
Department of Dermatology, University Hospital Essen, Essen.
Ann Oncol. 2015 Jun;26(6):1238-1244. doi: 10.1093/annonc/mdv139. Epub 2015 Mar 11.
Recent evidence suggests that ionizing radiation may be associated with unexpected side-effects in melanoma patients treated with concomitant BRAF inhibitors. A large multicenter analysis was carried out to generate reliable safety data and elucidate the mechanism.
A total of 161 melanoma patients from 11 European skin cancer centers were evaluated for acute and late toxicity, of whom 70 consecutive patients received 86 series of radiotherapy with concomitant BRAF inhibitor therapy. To further characterize and quantify a possible radiosensitization by BRAF inhibitors, blood samples of 35 melanoma patients were used for individual radiosensitivity testing by fluorescence in situ hybridization of chromosomal breaks after ex vivo irradiation.
With radiotherapy and concomitant BRAF inhibitor therapy the rate of acute radiodermatitis ≥2° was 36% and follicular cystic proliferation was seen in 13% of all radiotherapies. Non-skin toxicities included hearing disorders (4%) and dysphagia (2%). Following whole-brain radiotherapy, rates of radiodermatitis ≥2° were 44% and 8% (P < 0.001) for patients with and without BRAF inhibitor therapy, respectively. Concomitant treatment with vemurafenib induced acute radiodermatitis ≥2° more frequently than treatment with dabrafenib (40% versus 26%, P = 0.07). In line with these findings, analysis of chromosomal breaks ex vivo indicated significantly increased radiosensitivity for patients under vemurafenib (P = 0.004) and for patients switched from vemurafenib to dabrafenib (P = 0.002), but not for patients on dabrafenib only. No toxicities were reported after stereotactic treatment.
Radiotherapy with concomitant BRAF inhibitor therapy is feasible with an acceptable increase in toxicity. Vemurafenib is a more potent radiosensitizer than dabrafenib.
最近的证据表明，电离辐射可能与同时接受 BRAF 抑制剂治疗的黑色素瘤患者出现意外的副作用有关。进行了一项大型多中心分析，以生成可靠的安全性数据并阐明其机制。
来自 11 个欧洲皮肤癌中心的 161 名黑色素瘤患者接受了急性和晚期毒性评估，其中 70 名连续患者接受了 86 系列放射治疗，并同时接受了 BRAF 抑制剂治疗。为了进一步表征和量化 BRAF 抑制剂可能产生的放射增敏作用，使用 35 名黑色素瘤患者的血液样本通过体外照射后染色体断裂的荧光原位杂交进行个体放射敏感性测试。
接受放射治疗和同时接受 BRAF 抑制剂治疗的患者中，急性放射性皮炎≥2 级的发生率为 36%，所有放射治疗中出现滤泡囊性增殖的比例为 13%。非皮肤毒性包括听力障碍（4%）和吞咽困难（2%）。全脑放疗后，接受 BRAF 抑制剂治疗的患者放射性皮炎≥2 级的发生率为 44%，而未接受 BRAF 抑制剂治疗的患者为 8%（P<0.001）。与达布拉非尼相比，维莫非尼同时治疗更易引起急性放射性皮炎≥2 级（40%对 26%，P=0.07）。与这些发现一致，体外分析染色体断裂表明，接受维莫非尼治疗的患者（P=0.004）和从维莫非尼转为达布拉非尼治疗的患者（P=0.002）的放射敏感性显著增加，但仅接受达布拉非尼治疗的患者则没有。立体定向治疗后无毒性反应报告。
同时接受 BRAF 抑制剂治疗的放射治疗是可行的，但毒性增加可接受。维莫非尼比达布拉非尼更能增强放射敏感性。
