Department of Radiation Oncology, Fairfax, Virginia.
Department of Biochemistry, Fairfax, Virginia.
Neuro Oncol. 2020 Dec 18;22(12):1831-1839. doi: 10.1093/neuonc/noaa092.
Advanced radiotherapeutic treatment techniques limit the cognitive morbidity associated with whole-brain radiotherapy (WBRT) for brain metastasis through avoidance of hippocampal structures. However, achieving durable intracranial control remains challenging.
We conducted a single-institution single-arm phase II trial of hippocampal-sparing whole brain irradiation with simultaneous integrated boost (HSIB-WBRT) to metastatic deposits in adult patients with brain metastasis. Radiation therapy consisted of intensity-modulated radiation therapy delivering 20 Gy in 10 fractions over 2-2.5 weeks to the whole brain with a simultaneous integrated boost of 40 Gy in 10 fractions to metastatic lesions. Hippocampal regions were limited to 16 Gy. Cognitive performance and cancer outcomes were evaluated.
A total of 50 patients, median age 60 years (interquartile range, 54-65), were enrolled. Median progression-free survival was 2.9 months (95% CI: 1.5-4.0) and overall survival was 9 months. As expected, poor survival and end-of-life considerations resulted in a high exclusion rate from cognitive testing. Nevertheless, mean decline in Hopkins Verbal Learning Test-Revised delayed recall (HVLT-R DR) at 3 months after HSIB-WBRT was only 10.6% (95% CI: -36.5‒15.3%). Cumulative incidence of local and intracranial failure with death as a competing risk was 8.8% (95% CI: 2.7‒19.6%) and 21.3% (95% CI: 10.7‒34.2%) at 1 year, respectively. Three grade 3 toxicities consisting of nausea, vomiting, and necrosis or headache were observed in 3 patients. Scores on the Multidimensional Fatigue Inventory 20 remained stable for evaluable patients at 3 months.
HVLT-R DR after HSIB-WBRT was significantly improved compared with historical outcomes in patients treated with traditional WBRT, while achieving intracranial control similar to patients treated with WBRT plus stereotactic radiosurgery (SRS). This technique can be considered in select patients with multiple brain metastases who cannot otherwise receive SRS.
通过避免海马结构，先进的放射治疗技术限制了全脑放疗（WBRT）治疗脑转移瘤引起的认知发病率。然而，实现持久的颅内控制仍然具有挑战性。
我们在一家机构进行了一项单臂 II 期临床试验，对患有脑转移瘤的成年患者的脑转移灶进行海马保护全脑放疗联合同步整合推量（HSIB-WBRT）。放射治疗采用调强放疗，在 2-2.5 周内将全脑照射 20Gy，10 个分次，同时将 40Gy 10 个分次的同步整合推量到转移病灶。海马区限制在 16Gy。评估认知功能和癌症结局。
共纳入 50 例患者，中位年龄 60 岁（四分位距 54-65）。中位无进展生存期为 2.9 个月（95%CI：1.5-4.0），总生存期为 9 个月。正如预期的那样，由于生存状况不佳和临终考虑，认知测试的排除率很高。然而，HSIB-WBRT 后 3 个月时 Hopkins 言语学习测试修订版延迟回忆（HVLT-R DR）的平均下降仅为 10.6%（95%CI：-36.5-15.3%）。以死亡为竞争风险的局部和颅内失败的累积发生率分别为 8.8%（95%CI：2.7-19.6%）和 21.3%（95%CI：10.7-34.2%），分别在 1 年时。3 例患者出现 3 级毒性反应，包括恶心、呕吐、坏死或头痛。在可评估的患者中，多维疲劳量表 20 的评分在 3 个月时保持稳定。
与接受传统 WBRT 治疗的患者相比，HSIB-WBRT 后的 HVLT-R DR 明显改善，而颅内控制与接受 WBRT 加立体定向放射外科（SRS）治疗的患者相似。对于不能接受 SRS 的多发脑转移患者，可以考虑使用该技术。
