Northwestern Medicine Cancer Center Warrenville and Northwestern Medicine Proton Center, Department of Radiation Oncology, Warrenville, Illinois.
NRG Oncology Statistics and Data Management Center, Philadelphia, Pennsylvania.
Int J Radiat Oncol Biol Phys. 2023 Nov 1;117(3):571-580. doi: 10.1016/j.ijrobp.2023.04.030. Epub 2023 May 6.
Initial report of NRG Oncology CC001, a phase 3 trial of whole-brain radiation therapy plus memantine (WBRT + memantine) with or without hippocampal avoidance (HA), demonstrated neuroprotective effects of HA with a median follow-up of fewer than 8 months. Herein, we report the final results with complete cognition, patient-reported outcomes, and longer-term follow-up exceeding 1 year.
Adult patients with brain metastases were randomized to HA-WBRT + memantine or WBRT + memantine. The primary endpoint was time to cognitive function failure, defined as decline using the reliable change index on the Hopkins Verbal Learning Test-Revised (HVLT-R), Controlled Oral Word Association, or the Trail Making Tests (TMT) A and B. Patient-reported symptom burden was assessed using the MD Anderson Symptom Inventory with Brain Tumor Module and EQ-5D-5L.
Between July 2015 and March 2018, 518 patients were randomized. The median follow-up for living patients was 12.1 months. The addition of HA to WBRT + memantine prevented cognitive failure (adjusted hazard ratio, 0.74, P = .016) and was associated with less deterioration in TMT-B at 4 months (P = .012) and HVLT-R recognition at 4 (P = .055) and 6 months (P = .011). Longitudinal modeling of imputed data showed better preservation of all HVLT-R domains (P < .005). Patients who received HA-WBRT + Memantine reported less symptom burden at 6 (P < .001 using imputed data) and 12 months (P = .026 using complete-case data; P < .001 using imputed data), less symptom interference at 6 (P = .003 using complete-case data; P = .0016 using imputed data) and 12 months (P = .0027 using complete-case data; P = .0014 using imputed data), and fewer cognitive symptoms over time (P = .043 using imputed data). Treatment arms did not differ significantly in overall survival, intracranial progression-free survival, or toxicity.
With median follow-up exceeding 1 year, HA during WBRT + memantine for brain metastases leads to sustained preservation of cognitive function and continued prevention of patient-reported neurologic symptoms, symptom interference, and cognitive symptoms with no difference in survival or toxicity.
NRG 肿瘤学 CC001 的初步报告是一项全脑放射治疗加美金刚（WBRT+美金刚）联合或不联合海马回避（HA）的 3 期试验，中位随访时间不足 8 个月，显示了 HA 的神经保护作用。在此，我们报告最终结果，包括完整的认知、患者报告的结局以及超过 1 年的长期随访。
患有脑转移的成年患者被随机分配到 HA-WBRT+美金刚或 WBRT+美金刚。主要终点是认知功能衰竭的时间，定义为使用 Hopkins 词语学习测试修订版（HVLT-R）、受控口头词语联想或 Trail Making Tests（TMT）A 和 B 的可靠变化指数下降。使用 MD Anderson 症状量表-脑肿瘤模块和 EQ-5D-5L 评估患者的症状负担。
2015 年 7 月至 2018 年 3 月，共 518 例患者被随机分组。存活患者的中位随访时间为 12.1 个月。与 WBRT+美金刚相比，HA 的加入可预防认知失败（调整后的危险比，0.74，P=0.016），并且在 4 个月时 TMT-B 恶化较少（P=0.012），在 4、6 个月时 HVLT-R 识别能力较好（P=0.055，P=0.011）。对缺失数据的纵向建模显示，所有 HVLT-R 域的保存情况均较好（P<0.005）。接受 HA-WBRT+美金刚治疗的患者在 6 个月（使用缺失数据，P<0.001）和 12 个月（使用完整病例数据，P=0.026；使用缺失数据，P<0.001）时报告的症状负担较少，在 6 个月（使用完整病例数据，P=0.003；使用缺失数据，P=0.0016）和 12 个月（使用完整病例数据，P=0.0027；使用缺失数据，P=0.0014）时报告的症状干扰较少，并且随着时间的推移认知症状较少（使用缺失数据，P=0.043）。治疗组在总生存、颅内无进展生存或毒性方面无显著差异。
中位随访时间超过 1 年，WBRT+美金刚治疗脑转移时联合 HA 可持续保持认知功能的保存，并持续预防患者报告的神经症状、症状干扰和认知症状，且生存或毒性无差异。
