Dermatology Department, University Hospital Nord Saint Etienne, 42270, St Priest en Jarez, France.
Institut de Cancérologie Lucien Neuwirth, 108 bis Avenue Albert Raimond, BP 60008, 42271, St Priest en Jarez cedex, France.
Cancer Chemother Pharmacol. 2019 May;83(5):881-892. doi: 10.1007/s00280-019-03806-5. Epub 2019 Feb 26.
To assess the safety of the association of radiotherapy (RT) and systemic treatments for patients with metastatic malignant melanoma (mMM).
A retrospective analysis included consecutive patients treated with palliative RT, and at least one line of systemic therapy for mMM between 2001 and 2016. Treatments were defined as sequential or concomitant when RT and the systemic drug were administered, respectively, at more or less than five half-lives from each other.
92 patients were included. They had 110 palliative RT treatments. RT was delivered with a "conventional" chemotherapy (mainly fotemustine and/or dacarbazine) and a "modern" systemic therapy (BRAF inhibitors, association of BRAF and MEK inhibitors, immunotherapy), respectively, in 88 (80%) and 22 (20%) cases. Systemic treatments and RT were mainly concurrently performed (n = 61, 55.5%). Regarding acute grade ≥ 3 toxicity, no difference was reported between sequential and concomitant groups either in the whole cohort (p = 1) or in the subgroup of patients receiving "modern" systemic therapies (p = 1). Acute and late grade ≥ 3 toxicities only occurred with vemurafenib. BRAF inhibitors and RT produced more severe infield adverse events than other associations (p = 0.001) with two deaths.
In our series, compared to sequential administration, concomitant association of systemic anticancer drugs and palliative RT did not increase toxicity in mMM patients. BRAF inhibitors and RT produced severe infield toxicities. Prospective studies are needed to better characterize the toxicity of each association.
评估放疗(RT)与系统治疗联合用于转移性恶性黑色素瘤(mMM)患者的安全性。
回顾性分析纳入了 2001 年至 2016 年间接受姑息性 RT 治疗且至少接受过一线 mMM 系统治疗的连续患者。当 RT 和全身药物彼此相隔至少五个半衰期时,分别将治疗定义为序贯或同时进行。
共纳入 92 例患者,110 次姑息性 RT 治疗。分别有 88 例(80%)和 22 例(20%)患者接受“传统”化疗(主要为福莫司汀和/或达卡巴嗪)和“现代”系统治疗(BRAF 抑制剂、BRAF 和 MEK 抑制剂联合治疗、免疫治疗)。61 例(55.5%)患者同时接受了系统治疗和 RT。急性≥3 级毒性方面,序贯组和同时组之间的全队列(p=1)或接受“现代”系统治疗患者亚组(p=1)均无差异。急性和迟发性≥3 级毒性仅发生于维莫非尼。BRAF 抑制剂联合 RT 比其他联合治疗(p=0.001)产生更严重的瘤内不良反应,导致 2 例死亡。
在我们的研究中,与序贯给药相比,姑息性 RT 与系统抗癌药物的同时联合并未增加 mMM 患者的毒性。BRAF 抑制剂联合 RT 产生严重的瘤内毒性。需要前瞻性研究来更好地描述每种联合治疗的毒性。