Phase II trial of hippocampal-sparing whole brain irradiation with simultaneous integrated boost for metastatic cancer
Phase II trial of hippocampal-sparing whole brain irradiation with simultaneous integrated boost for metastatic cancer
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DOI：
10.1093/neuonc/noaa092
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发表时间：
2020-12-01
期刊：
影响因子：
15.9
通讯作者：
Timmerman, Robert
中科院分区：
文献类型：
--
作者：
Westover, Kenneth D.;Mendel, J. Travis;Timmerman, Robert
背景先进的放射治疗技术通过避免海马结构限制了脑转移全脑放疗（WBRT）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。我们进行了一项单机构单臂II期临床试验，在脑转移的成人患者中对转移性沉积物进行保留脑组织的全脑照射同时进行整合加强（HSIB-WBRT）。放射治疗包括在2-2.5周内分10次向全脑提供20戈伊的调强放射治疗，同时分10次向转移性病变提供40戈伊的综合加强治疗。海马区限制为16戈伊。认知能力和癌症的结果进行了评估。共入组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，较差的生存率和临终考虑导致认知测试的高排除率。然而，在HSIB-WBRT后3个月时，霍普金斯言语学习测验修订版延迟回忆（HVLT-R DR）的平均下降仅为10.6%（95% CI：-36.5.15.3%）。1年时，局部和颅内衰竭的累积发生率（死亡作为竞争风险）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级毒性，包括恶心、呕吐和坏死或头痛。可评估患者的多维疲劳量表20评分在3个月时保持稳定。HSIB-WBRT后的HVLT-R DR与传统WBRT治疗患者的历史结局相比显著改善，同时实现了与WBRT+立体定向放射外科（SRS）治疗患者相似的颅内控制。
Background. Advanced radiotherapeutic treatment techniques limit the cognitive morbidity associated with wholebrain 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 progressionfree 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.