Abstract：
OBJECTIVE: To assess in patients with 1-10 brain metastases, each of which has been treated by neurosurgery or stereotactic radiosurgery, whether hippocampal sparing whole brain radiotherapy (HS-WBRT) better spares neurocognitive function (NCF) than standard WBRT. Further, to assess whether a phase III randomised trial of HS-WBRT would be feasible in the UK.
METHODS: A multicentre, randomised, open label phase II trial was undertaken, randomising patients to 30Gy in 10 fractions of WBRT or HS-WBRT. The primary endpoint was decline in Total recall using Hopkins Verbal Learning Test Revised (HVLT-R) at 4 months post treatment. To assess this, we aimed to recruit 84 patients over 3 years. Secondary endpoints included further measures of NCF, quality of life, duration of functional independence, local control of treated metastases, development of new metastases, disease control within the hippocampal regions, overall survival, steroid and antiepileptic medication requirements, and toxicity.
RESULTS: The trial closed prematurely due to slower than anticipated recruitment. From April 2016 to January 2018, 23 patients were randomised. Follow up was a median of 25 months. Fifteen patients (6 WBRT, 9 HS-WBRT) were assessed for the primary endpoint; of these, 1 in each arm experienced significant decline in the 4-month HVLT-R Total recall score (p = 0.8). Patients in the HS-WBRT arm experienced less insomnia (p < 0.01) and drowsiness (p < 0.01). There were no differences in other secondary endpoints.
CONCLUSIONS: A phase III randomised trial of HS-WBRT was shown not to be feasible at this time in the UK. As most randomised trials of HS-WBRT reported to date share common endpoints, including NCF, an individual patient data meta-analysis should be undertaken.
METHODS: A multicentre, randomised, open label phase II trial was undertaken, randomising patients to 30Gy in 10 fractions of WBRT or HS-WBRT. The primary endpoint was decline in Total recall using Hopkins Verbal Learning Test Revised (HVLT-R) at 4 months post treatment. To assess this, we aimed to recruit 84 patients over 3 years. Secondary endpoints included further measures of NCF, quality of life, duration of functional independence, local control of treated metastases, development of new metastases, disease control within the hippocampal regions, overall survival, steroid and antiepileptic medication requirements, and toxicity.
RESULTS: The trial closed prematurely due to slower than anticipated recruitment. From April 2016 to January 2018, 23 patients were randomised. Follow up was a median of 25 months. Fifteen patients (6 WBRT, 9 HS-WBRT) were assessed for the primary endpoint; of these, 1 in each arm experienced significant decline in the 4-month HVLT-R Total recall score (p = 0.8). Patients in the HS-WBRT arm experienced less insomnia (p < 0.01) and drowsiness (p < 0.01). There were no differences in other secondary endpoints.
CONCLUSIONS: A phase III randomised trial of HS-WBRT was shown not to be feasible at this time in the UK. As most randomised trials of HS-WBRT reported to date share common endpoints, including NCF, an individual patient data meta-analysis should be undertaken.
摘要：
目的：评估1-10例脑转移患者，每个都经过神经外科或立体定向放射外科治疗，海马保留全脑放疗（HS-WBRT）是否比标准WBRT更好地保留神经认知功能（NCF）。Further,评估HS-WBRT的III期随机试验在英国是否可行.
方法：多中心，随机化，进行了开放标签II期试验，在WBRT或HS-WBRT的10个部分中将患者随机分配至30Gy。主要终点是治疗后4个月使用霍普金斯言语学习测试修订版（HVLT-R）的总召回率下降。为了评估这一点，我们的目标是在3年内招募84名患者。次要终点包括NCF的进一步措施，生活质量,功能独立的持续时间，治疗转移的局部控制，发展新的转移，海马区的疾病控制，总生存率,类固醇和抗癫痫药物的要求，和毒性。
结果：由于比预期招募慢，试验提前结束。从2016年4月至2018年1月，23例患者被随机分组。随访中位数为25个月。15例患者（6例WBRT，9HS-WBRT)评估了主要终点；其中，在4个月的HVLT-R总回忆评分中,每个臂中的1经历了显著下降(p=0.8)。HS-WBRT手臂的患者经历了较少的失眠（p<0.01）和嗜睡（p<0.01）。其他次要终点没有差异。
结论：在英国，HS-WBRT的III期随机试验目前不可行。由于迄今为止报道的大多数HS-WBRT随机试验都有共同的终点，包括NCF，应进行个体患者数据荟萃分析.
方法：多中心，随机化，进行了开放标签II期试验，在WBRT或HS-WBRT的10个部分中将患者随机分配至30Gy。主要终点是治疗后4个月使用霍普金斯言语学习测试修订版（HVLT-R）的总召回率下降。为了评估这一点，我们的目标是在3年内招募84名患者。次要终点包括NCF的进一步措施，生活质量,功能独立的持续时间，治疗转移的局部控制，发展新的转移，海马区的疾病控制，总生存率,类固醇和抗癫痫药物的要求，和毒性。
结果：由于比预期招募慢，试验提前结束。从2016年4月至2018年1月，23例患者被随机分组。随访中位数为25个月。15例患者（6例WBRT，9HS-WBRT)评估了主要终点；其中，在4个月的HVLT-R总回忆评分中,每个臂中的1经历了显著下降(p=0.8)。HS-WBRT手臂的患者经历了较少的失眠（p<0.01）和嗜睡（p<0.01）。其他次要终点没有差异。
结论：在英国，HS-WBRT的III期随机试验目前不可行。由于迄今为止报道的大多数HS-WBRT随机试验都有共同的终点，包括NCF，应进行个体患者数据荟萃分析.
