Abstract：
OBJECTIVE In 1999, the World Health Organization categorized large cell neuroendocrine carcinoma (LCNEC) of the lung as a variant of large cell carcinoma, and LCNEC now accounts for 3% of all lung cancers. Although LCNEC is categorized among the non-small cell lung cancers, its biological behavior has recently been suggested to be very similar to that of a small cell pulmonary malignancy. The clinical outcome for patients with LCNEC is generally poor, and the optimal treatment for this malignancy has not yet been established. Little information is available regarding management of LCNEC patients with brain metastases (METs). This study aimed to evaluate the efficacy of Gamma Knife radiosurgery (GKRS) for patients with brain METs from LCNEC. METHODS The Japanese Leksell Gamma Knife Society planned this retrospective study in which 21 Gamma Knife centers in Japan participated. Data from 101 patients were reviewed for this study. Most of the patients with LCNEC were men (80%), and the mean age was 67 years (range 39-84 years). Primary lung tumors were reported as well controlled in one-third of the patients. More than half of the patients had extracranial METs. Brain metastasis and lung cancer had been detected simultaneously in 25% of the patients. Before GKRS, brain METs had manifested with neurological symptoms in 37 patients. Additionally, prior to GKRS, resection was performed in 17 patients and radiation therapy in 10. A small cell lung carcinoma-based chemotherapy regimen was chosen for 48 patients. The median lesion number was 3 (range 1-33). The median cumulative tumor volume was 3.5 cm3, and the median radiation dose was 20.0 Gy. For statistical analysis, the standard Kaplan-Meier method was used to determine post-GKRS survival. Competing risk analysis was applied to estimate GKRS cumulative incidences of maintenance of neurological function and death, local recurrence, appearance of new lesions, and complications. RESULTS The overall median survival time (MST) was 9.6 months. MSTs for patients classified according to the modified recursive partitioning analysis (RPA) system were 25.7, 11.0, and 5.9 months for Class 1+2a (20 patients), Class 2b (28), and Class 3 (46), respectively. At 12 months after GKRS, neurological death-free and deterioration-free survival rates were 93% and 87%, respectively. Follow-up imaging studies were available in 78 patients. The tumor control rate was 86% at 12 months after GKRS. CONCLUSIONS The present study suggests that GKRS is an effective treatment for LCNEC patients with brain METs, particularly in terms of maintaining neurological status.
摘要：
目的1999年，世界卫生组织将肺的大细胞神经内分泌癌（LCNEC）归类为大细胞癌的变体。LCNEC现在占所有肺癌的3%。尽管LCNEC被归类为非小细胞肺癌，它的生物学行为最近被认为是非常相似的小细胞肺恶性肿瘤。LCNEC患者的临床结果通常较差，这种恶性肿瘤的最佳治疗方法尚未确定。有关LCNEC脑转移（MET）患者的管理的信息很少。本研究旨在评估伽玛刀放射外科（GKRS）对LCNEC脑MET患者的疗效。方法日本Leksell伽玛刀学会计划了这项回顾性研究，日本的21个伽玛刀中心参与了这项研究。本研究回顾了101例患者的数据。大多数LCNEC患者是男性（80％），平均年龄为67岁（范围39-84岁）。据报道，在三分之一的患者中，原发性肺肿瘤得到了良好的控制。超过一半的患者患有颅外MET。在25％的患者中同时检测到脑转移和肺癌。在GKRS之前，37例患者的脑MET表现为神经系统症状.此外,在GKRS之前,17例患者接受了切除术,10例患者接受了放射治疗.为48例患者选择了基于小细胞肺癌的化疗方案。中位病变数为3（范围1-33）。中位累积肿瘤体积为3.5cm3,中位放射剂量为20.0Gy。为了进行统计分析，采用标准Kaplan-Meier方法测定GKRS术后生存率.竞争风险分析用于估计GKRS神经功能维持和死亡的累积发生率。局部复发,出现新的病变，和并发症。结果中位生存时间(MST)为9.6个月。根据改良递归分区分析（RPA）系统分类的患者的MSTs分别为25.7、11.0和5.9个月，1+2a级（20名患者），2b类（28），第3类（46），分别。GKRS术后12个月,神经无死亡和无恶化生存率分别为93%和87%，分别。对78例患者进行了随访影像学研究。GKRS术后12个月肿瘤控制率为86%。结论本研究表明，GKRS是LCNEC脑MET患者的有效治疗方法，特别是在维持神经状态方面。
