BACKGROUND The current study was aimed at investigating the feasibility of hippocampus-avoidance whole-brain radiation therapy with a simultaneous integrated boost (HA-WBRT+SIB) for metastases and at assessing tumor control in comparison with conventional whole-brain radiation therapy (WBRT) in patients with multiple brain metastases. METHODS Between August 2012 and December 2016, 66 patients were treated within a monocentric feasibility trial with HA-WBRT+SIB: hippocampus-avoidance WBRT (30 Gy in 12 fractions, dose to 98% of the hippocampal volume ≤ 9 Gy) and a simultaneous integrated boost (51 or 42 Gy in 12 fractions) for metastases/resection cavities. Intracranial tumor control, hippocampal failure, and survival were subsequently compared with a retrospective cohort treated with WBRT via propensity score matching analysis. RESULTS After 1:1 propensity score matching, there were 62 HA-WBRT+SIB patients and 62 WBRT patients. Local tumor control (LTC) of existing metastases was significantly higher after HA-WBRT+SIB (98% vs 82% at 1 year; P = .007), whereas distant intracranial tumor control was significantly higher after WBRT (82% vs 69% at 1 year; P = .016); this corresponded to higher biologically effective doses. Intracranial progression-free survival (PFS; 13.5 vs 6.4 months; P = .03) and overall survival (9.9 vs 6.2 months; P = .001) were significantly better in the HA-WBRT+SIB cohort. Four patients (6.5%) developed hippocampal metastases after hippocampus avoidance. The neurologic death rate after HA-WBRT+SIB was 27.4%. CONCLUSIONS HA-WBRT+SIB can be an efficient therapeutic option for patients with multiple brain metastases and is associated with improved LTC of existing metastases, higher intracranial PFS, a reduction of the neurologic death rate, and an acceptable risk of radiation necrosis. The therapy has the potential to prevent neurocognitive adverse effects, which will be further evaluated in the multicenter, phase 2 HIPPORAD trial.

中文翻译：

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避免海马全脑放射治疗，同时进行综合性多发脑转移治疗。

背景技术目前的研究旨在调查海马回避全脑放射治疗同时进行联合增强（HA-WBRT + SIB）转移治疗的可行性，并评估与常规全脑放射治疗（WBRT）相比的肿瘤控制多发脑转移的患者。方法在2012年8月至2016年12月之间，通过HA-WBRT + SIB在单中心可行性试验中对66例患者进行了治疗：避免海马体WBRT（12馏分中30 Gy，剂量达到98％的海马体积≤9 Gy），同时集成增强（12馏分为51或42 Gy）用于转移/切除腔。随后通过倾向评分匹配分析将颅内肿瘤控制，海马衰竭和生存率与WBRT治疗的回顾性队列进行比较。结果1：倾向评分匹配为1，有62例HA-WBRT + SIB患者和62例WBRT患者。HA-WBRT + SIB后现有转移的局部肿瘤控制（LTC）显着更高（1年时为98％vs 82％； P = .007），而WBRT后远处颅内肿瘤控制显着更高（82％vs 69％） 1年； P = .016）；这对应于更高的生物学有效剂量。在HA-WBRT + SIB队列中，颅内无进展生存期（PFS； 13.5 vs 6.4个月； P = .03）和总生存期（9.9 vs 6.2个月； P = .001）明显更好。避免海马后有四名患者（6.5％）出现海马转移。HA-WBRT + SIB后的神经系统死亡率为27.4％。结论HA-WBRT + SIB可作为多发性脑转移患者的有效治疗选择，并与现有转移的LTC改善，颅内PFS升高，神经系统死亡率降低和放射坏死风险相联系。该疗法具有预防神经认知不良反应的潜力，将在多中心2期HIPPORAD试验中进一步评估。