Abstract

Background

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.

Methods

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.

Results

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.

Conclusions

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.

中文翻译：

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海马全脑照射同时转移联合增强（HSIB-WBRT）治疗转移性癌症的第二阶段试验。

摘要

背景

先进的放射治疗技术通过避免海马结构限制了与全脑放疗（WBRT）有关的脑转移相关的认知发病率。然而，实现持久的颅内控制仍然具有挑战性。

方法

我们进行了单机构单臂II期试验，对成年脑转移患者进行海马保护全脑照射同时同步增强（HSIB-WBRT）转移沉积。放射疗法包括强度调制放射疗法，在2–2.5周内以10分数分送20 Gy到整个大脑，同时以10分数分担40 Gy的综合增强对转移性病变的治疗。海马区仅限于16 Gy。评价认知能力和癌症结局。

结果

共有50名患者，中位年龄为60岁（四分位间距为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。不出所料，不良的生存率和寿命终止的考虑导致认知测试的高排除率。尽管如此，在HSIB-WBRT后3个月，霍普金斯语言学习测验-修订的延迟回忆（HVLT-R DR）的平均下降仅为10.6％（95％CI：-36.5％15.3％）。1年时以死亡为竞争风险的局部和颅内衰竭累积发生率分别为8.8％（95％CI：2.7‒19.6％）和21.3％（95％CI：10.7‒34.2％）。在3例患者中观察到3种3级毒性，包括恶心，呕吐，坏死或头痛。在3个月时，可评估患者的多维疲劳量表20得分保持稳定。

结论

与传统WBRT治疗的患者相比，HSIB-WBRT治疗后的HVLT-R DR明显优于历史结果，同时实现了与WBRT加立体定向放射外科手术（SRS）治疗的患者相似的颅内控制。某些患有多发性脑转移的患者如果不能以其他方式接受SRS，可以考虑使用该技术。