Marwaha Alexander S, Liang Yun, Shepard Matthew J, Yu Alexander, Karlovits Stephen M, Wegner Rodney E
Department of Radiation Oncology, Allegheny Health Network Cancer Institute, Pittsburgh, USA.
Department of Neurosurgery, Allegheny Health Network, Pittsburgh, USA.
J Neurooncol. 2025 Mar;172(1):177-183. doi: 10.1007/s11060-024-04895-w. Epub 2024 Dec 7.
PURPOSE/OBJECTIVE(S): Small cell lung cancer (SCLC) is known to have high rates of development of brain metastases. Standard treatment has been whole brain radiation therapy (WBRT) but the role for more focused treatment and hippocampal avoidance has arisen in the past decade. In addition, with possible penetration of the central nervous system by more modern immunotherapies, the risk of distant failure may be lower. As such, we reviewed patients at our institution treated with stereotactic radiosurgery (SRS) to look at patterns, locations, and predictors of failure in the brain.
MATERIALS/METHODS: A retrospective review and analysis of charts was done on 46 patients treated with SRS (no history of prior WBRT) for their brain metastases from SCLC. Multivariate analysis was used to determine significant prognostic factors influencing survival and local/distant failure. We tracked timing and type of immunotherapy, if any, as well as if patients failed in the hippocampus or required WBRT.
There were 46 patients with 97 total brain metastases treated with SRS in this study. Median number of metastases was 2 (1-5). The median dose of radiation was 20 Gy (20-30) in 3 fractions (1-5) for all 97 tumors. 11 patients did not receive immunotherapy, whereas 35 patients had immunotherapy of some sort. Median overall survival (OS) for the entire cohort was 13 months, with a 12 month OS of 59% and 2 year OS of 30%. Cox regression did not reveal any significant predictors of OS, including age, sex, total volume, extracranial disease, KPS, immunotherapy, or number of metastases. 12 month and 24 month local control of disease was 95% and 80%, respectively. There were no significant predictors of local failure including volume, dose, or immunotherapy. 25 of the patients had distant brain failure, with a rate of distant failure of 38% and 64% for 6 and 12 months, respectively. Immunotherapy, number of metastases, total target volume, nor presence of extracranial disease was predictive of distant brain failure. WBRT free survival was also measured and found to be 73% at 1 year. There were no significant predictors for this measure. Lastly, five patients in this cohort showed failure in the hippocampus, where the rate of failure at 6 and 12 months was 16%.
Rates of distant brain failure in SCLC patients after SRS remain similar to those of NSCLC patients in the immunotherapy era. We did not show a decrease in distant failure rate based on immunotherapy use. The rate of hippocampal failure was quite low and should provide reassurance that SRS and techniques such as HA-IMRT can be reasonably used in these patients. Ongoing clinical trials will help provide more definitive answers in this arena.
已知小细胞肺癌（SCLC）发生脑转移的几率很高。标准治疗方法一直是全脑放射治疗（WBRT），但在过去十年中，更有针对性的治疗以及避免照射海马体的作用日益凸显。此外，随着更现代的免疫疗法可能穿透中枢神经系统，远处失败的风险可能会降低。因此，我们回顾了在我们机构接受立体定向放射外科治疗（SRS）的患者，以观察脑内失败的模式、位置和预测因素。
对46例因SCLC脑转移接受SRS治疗（无既往WBRT病史）的患者进行了回顾性病历分析。采用多变量分析来确定影响生存及局部/远处失败的显著预后因素。我们追踪了免疫疗法的时间和类型（若有），以及患者是否在海马体出现失败或是否需要WBRT。
本研究中有46例患者共97个脑转移灶接受了SRS治疗。转移灶的中位数为2个（1 - 5个）。所有97个肿瘤的中位放射剂量为20 Gy（20 - 30），分3次给予（1 - 5次）。11例患者未接受免疫治疗，而35例患者接受了某种免疫治疗。整个队列的中位总生存期（OS）为13个月，12个月总生存率为59%，2年总生存率为30%。Cox回归未发现任何OS的显著预测因素，包括年龄、性别、总体积、颅外疾病、KPS、免疫治疗或转移灶数量。疾病的12个月和24个月局部控制率分别为95%和80%。没有局部失败的显著预测因素，包括体积、剂量或免疫治疗。25例患者出现远处脑失败，6个月和12个月的远处失败率分别为38%和64%。免疫治疗、转移灶数量、总靶体积或颅外疾病的存在均不能预测远处脑失败。还测量了无WBRT生存期，发现1年时为73%。对此指标没有显著预测因素。最后，该队列中有5例患者在海马体出现失败，6个月和12个月的失败率为16%。
在免疫治疗时代，SCLC患者接受SRS治疗后远处脑失败率与NSCLC患者相似。我们并未显示基于免疫治疗的使用远处失败率有所降低。海马体失败率相当低，这应能让人们放心，SRS以及HA - IMRT等技术可合理用于这些患者。正在进行的临床试验将有助于在这个领域提供更明确的答案。
