Hippocampal Avoidance During Prophylactic Cranial Irradiation for Patients With Small Cell Lung Cancer: Randomized Phase II/III Trial NRG-CC003.

This trial hypothesized that HA during prophylactic cranial irradiation (PCI) in patients with small cell lung cancer (SCLC) leads to noninferior intracranial relapse (ICR) and reduction in NCF toxicity.

该试验假设在小细胞肺癌（SCLC）患者预防性颅脑放疗（PCI）期间进行海马体避免（HA）会导致非劣的颅内复发（ICR）并减少NCF毒性。

Methods

This randomized phase II/III trial enrolled patients with SCLC, no brain metastases, and response to chemotherapy.

这项随机化II/III期试验招募了小细胞肺癌患者，无脑转移，并对化疗有反应。

The primary end points were 12-month ICR (noninferiority design, randomized phase II) and 6-month Hopkins Verbal Learning Test-Revised (HVLT-R) Delayed Recall (DR) failure (phase III).

主要终点是12个月的ICR（非劣效设计，随机化II期）和6个月的霍普金斯口头学习测试-修订版（HVLT-R）延迟回忆（DR）失败（III期）。

Secondary end points were failure in any NCF test, health-related quality of life (HRQOL), overall survival(OS), and toxicity.

次要终点包括任何神经认知功能(NCF)测试的失败、与健康相关的生活质量(HRQOL)、总生存(OS)和毒性。

Results

From December 2015 to June 2022, 393 patients were randomly assigned.

从2015年12月到2022年6月，共有393名患者被随机分配。

The median age was 64 years.

中位年龄为64岁。

Stage and memantine usage were balanced.

各阶段和美金刚使用情况均衡。

The median follow-up was 17.0 months (all patients) and 30.8 months (alive patients).

中位随访时间为17.0个月（所有患者）和30.8个月（存活患者）。

HA-PCI had noninferior 12-month ICR rate (PCI 14.8% v HA-PCI 14.7%, P < .0001).

HA-PCI在12个月的ICR率上显示出非劣效性（PCI为14.8%，HA-PCI为14.7%，P < .0001）。

Six-month HVLT-R DR deterioration was not significantly different (PCI 30.0% v HA-PCI 25.5%, P = .28).

六月时HVLT-R DR恶化情况在PCI组的30.0%与HA-PCI组的25.5%之间没有显著差异（P = .28）。

Addition of HA to PCI reduced the risk of failure in any NCF test (adjusted hazard ratio[HR], 0.78; 95% CI [0.61 to 0.99]; P = .039).

加入HA到PCI后，任何神经认知功能测试失败的风险有所降低（调整后风险比[HR]，0.78；95%置信区间[0.61至0.99]；P = .039）。

Addition of HA to PCI was not associated with longitudinal change in any HRQOL domain.

将HA添加到PCI中并未与任何HRQOL领域的纵向变化相关联。

There were no differences in OS (adjusted HR, 0.88 [95% CI, 0.67 to 1.14]; P = .33) or grade ≥3 toxicity (PCI 31.4% v HA-PCI 30.7%, P = .88).

总生存期（调整后的HR，0.88 [95%置信区间，0.67至1.14]；P = .33）或3级或以上毒性（PCI 31.4%对比HA-PCI 30.7%，P = .88）之间没有差异。

Conclusions

Although the study did not meet its primary end point of DR preservation, HA during PCI reduces the risk of overall neurocognitive toxicity with noninferior ICR risk and similar survival.

尽管该研究未达到其主要终点即DR保护，但PCI期间的HA降低了总体神经认知毒性的风险，ICR风险非劣效，并且生存率相似。