Hauswald Henrik, Bernhardt Denise, Krug David, Katayama Sonja, Habl Gregor, Lorenzo Bermejo Justo, Debus Jürgen, Sterzing Florian
Department of Radiation Oncology, Heidelberg University Hospital, 69120 Heidelberg, Germany.
National Center for Radiation Research in Oncology (NCRO), Heidelberg Institute for Radiation Oncology (HIRO), 69120 Heidelberg, Germany.
Cancer Manag Res. 2019 May 24;11:4669-4676. doi: 10.2147/CMAR.S204729. eCollection 2019.
Patients with multiple brain metastases (BMs) from malignant melanoma have a poor prognosis. Recent developments in radiation techniques allow simultaneous integrated boost (SIB) concepts while sparing organs at risk. Data on conventional versus dose-escalated radiation approaches in multiple BMs from malignant melanoma are warranted. In this prospective, single-center, randomized two-armed study (trial ID: DRKS00005127), patients with multiple BMs from malignant melanoma were treated with either conventional whole-brain radiotherapy (WBRT) applying 30 Gy in 10 fractions (standard arm) or helical tomotherapy applying 30 Gy to the whole brain with an integrated boost to metastases of 50 Gy in 10 fractions and sparing of the hippocampus (HA-WBRT, experimental arm). The primary endpoint was treatment-related toxicity, while secondary endpoints were imaging response, intracerebral progression-free survival (PFS), overall survival (OS) and quality of life. The study was stopped early due to slow patient recruitment. A total number of 7 patients were enrolled (standard arm n=3, experimental arm n=4), and were followed-up for a median time of 5 months between August 2013 and July 2017. All patients were treated according to protocol. The median OS, intracerebral PFS and follow-up time were 5 months, 2 months and 5 months, respectively. The local control in every individual BM was significantly longer in the experimental versus the standard arm. No patient developed radiation-related high-grade toxicities. HA-WBRT with SIB results in improved local control in the individual melanoma BMs without radiation-associated high-grade toxicities. Survival times were comparable to published data.
患有恶性黑色素瘤多发性脑转移（BMs）的患者预后较差。放射技术的最新进展使得在保护危及器官的同时可采用同步整合加量（SIB）概念。有必要获取关于恶性黑色素瘤多发性BMs采用传统放疗与剂量递增放疗方法的数据。在这项前瞻性、单中心、随机双臂研究（试验编号：DRKS00005127）中，患有恶性黑色素瘤多发性BMs的患者接受以下两种治疗之一：一是采用常规全脑放疗（WBRT），分10次给予30 Gy（标准组）；二是采用螺旋断层放疗，全脑给予30 Gy，同时对转移灶分10次整合加量至50 Gy，并保护海马体（HA-WBRT，试验组）。主要终点是治疗相关毒性，次要终点是影像反应、脑内无进展生存期（PFS）、总生存期（OS）和生活质量。由于患者招募缓慢，该研究提前终止。总共纳入7例患者（标准组n = 3，试验组n = 4），在2013年8月至2017年7月期间进行了中位时间为5个月的随访。所有患者均按方案接受治疗。中位OS、脑内PFS和随访时间分别为5个月、2个月和5个月。与标准组相比，试验组中每个单独BM的局部控制时间显著更长。没有患者出现与放疗相关的高级别毒性。采用SIB的HA-WBRT可改善单个黑色素瘤BM的局部控制，且无放疗相关的高级别毒性。生存时间与已发表数据相当。
