局限期小细胞肺癌脑预防照射中海马保护技术的应用

Application of optimized hippocampus-avoidance prophylactic cranial irradiation in limited-stage small cell lung cancer

目的分析海马保护技术下的脑预防照射在局限期小细胞肺癌中的疗效、安全性,探索缩小海马外扩范围(2 mm,三维)条件下相应的剂量学参数。方法回顾性分析2014年8月—2020年6月在中国医学科学院肿瘤医院行脑预防照射的局限期小细胞肺癌患者。患者均使用缩小海马外扩范围(2 mm,三维)的海马保护技术。对脑预防照射计划相关剂量参数、不良反应进行描述性统计分析。神经认知功能变化,如简易精神状态检查(MMSE)及霍普金斯语言学习测验修订版(HVLT-R)评分使用方差分析或Kruskal-WallisH检验。Kaplan-Meier法计算总生存(OS)、无进展生存(PFS)、颅内无进展生存。竞争风险法计算累积颅内复发率、累积颅外远处转移率和累积局部区域复发率。结果共纳入112例患者,中位随访时间达50个月(95%CI为45.61~54.38)。中位海马体积为4.85 ml(范围为2.65~8.34 ml),106例(94.6%)患者的海马平均剂量≤9 Gy,92例(82.1%)患者的海马平均剂量≤8 Gy;中位海马回避区体积为15.00 ml(范围为8.61~28.06 ml),109例(97.3%)患者的海马回避区平均剂量≤12 Gy,101例(90.2%)患者的海马回避区平均剂量≤10 Gy。2年累积颅内复发、累积颅外远处转移和累积局部区域复发率分别为16.9%、23.2%、28.5%,5年累积颅内复发、累积颅外远处转移和累积局部区域复发率分别为23.2%、26.9%、33.3%。2年颅内无进展生存率、PFS率、OS率分别为66.1%(95%CI为57.9%~75.4%)、53.6%(95%CI为45.1%~63.7%)、80.4%(95%CI为73.3%~88.1%)。最常见的Ⅰ-Ⅱ度不良反应为恶心(33.9%)和头晕(31.3%),1例(0.9%)患者出现Ⅲ度恶心及头晕。部分患者进行了MMSE评分(57例)及HVLT-R评分(56例),无显著下降。结论全脑预防放疗中运用海马保护技术,海马回避区由海马区三维外扩2 mm可达到既往(5 mm)的剂量限制要求。缩小海马外扩条件下的脑预防放疗在局限期小细胞肺癌中的疗效可靠且不良反应轻,在可评估的患者中未发现明显的短期神经认知功能降低。

Objective To analyze the treatment efficacy,safety and dose parameters of optimized hippocampus-avoidance prophylactic cranial irradiation(HA-PCI)in limited-stage small cell lung cancer(LS-SCLC)and explore the corresponding dosimetric parameters under the condition of narrowing the hippocampus avoidance region as hippocampus region plus 2 mm in three dimensions.Methods Clinical data of patients with LS-SCLC receiving HA-PCI(hippocampus avoidance region defined as hippocampus region plus 2 mm in three dimensions)in Cancer Hospital Chinese Academy of Medical Sciences from August 2014 to June 2020 were retrospectively analyzed.Dose parameters of HA-PCI and adverse events were analyzed using descriptive statistics analysis.Changes of neurocognitive function,such as mini-mental state examination(MMSE)and Hopkins verbal learning test-revised(HVLT-R)scores,were evaluated by analysis of variance and Kruskal-Wallis H test.Overall survival(OS),progression-free survival(PFS)and intracranial PFS(iPFS)were calculated using Kaplan-Meier method.The cumulative incidence of local-regional recurrence(LRR),extracranial distant metastases(EDM),and locoregional recurrence(LR)were investigated under competing risk analysis.Results A total of 112 patients were included,the median follow-up time was 50 months(95%CI:45.61-54.38).The median volume of hippocampus was 4.85 ml(range:2.65-8.34 ml),with the average dose≤9 Gy in 106 patients(94.6%),≤8 Gy in 92 patients(82.1%).The median volume of hippocampus avoidance area was 15.00 ml(range:8.61-28.06 ml),with the average dose≤12 Gy in 109 patients(97.3%),≤10 Gy in 101 patients(90.2%).The 2-year cumulative LRR,EDM,LR rates were 16.9%,23.2%and 28.5%,respectively.The 5-year cumulative LRR,EDM,LR rates were 23.2%,26.9%and 33.3%,respectively.The 2-year iPFS,PFS and OS rates were 66.1%(95%CI:57.9%-75.4%),53.6%(95%CI:45.1%-63.7%)and 80.4%(95%CI:73.3%-88.1%),respectively.The most common grade I-Ⅱadverse events were nausea(33.9%)and dizziness(31.3%),and only 1 patient developed gradeⅢnausea and dizziness.MMSE(n=57)and HVLT-R tests(n=56)showed no significant decline.Conclusions Optimized HA-PCI can achieve similar dose limitation with favorable efficacy and light toxicity.No significant decline is observed in short-term neurocognitive function in evaluable patients.