Pan Zhenyu, Yang Guozi, He Hua, Zhao Gang, Yuan Tingting, Li Yu, Shi Weiyan, Gao Pengxiang, Dong Lihua, Li Yunqian
Department of Radiation-Oncology, The First Hospital of Jilin University, Changchun, 130021, China.
Cancer Center, The First Hospital of Jilin University, Changchun, 130021, China.
Int J Cancer. 2016 Oct 15;139(8):1864-72. doi: 10.1002/ijc.30214. Epub 2016 Jun 30.
The prognosis of leptomeningeal metastasis (LM) from solid tumors is extremely poor, especially for patients with adverse prognostic factors. In this phase II clinical trial, we evaluated the efficacy and safety of intrathecal chemotherapy (IC) combined with concomitant involved-field radiotherapy (IF-RT) for treating LM from solid tumors with adverse prognostic factors. Fifty-nine patients with LM from various solid tumors were enrolled between May 2010 and December 2014. Concurrent therapy consisted of concomitant IC (methotrexate 12.5-15 mg and dexamethasone 5 mg, weekly) and IF-RT (whole brain and/or spinal canal RT, 40 Gy/20f). For patients with low Karnofsky performance status (KPS) score and radiotherapy intolerance, induction IC (1-3 times) was given before concurrent therapy. Thirty-eight patients (64.4%) received subsequent treatments. All patients were followed up at least 6 months after LM diagnosis or until death. Primary endpoint evaluated was clinical response rate. Secondary endpoints were overall survival (OS) and safety. The pathological types included lung cancer (n = 42), breast cancer (n = 11) and others (n = 6). Median KPS score was 40 (range 20-70). Fifty-one patients (86.4%) completed concurrent therapy. The overall response rate was 86.4% (51/59). OS ranged from 0.4 to 36.7 months (median 6.5 months), and 1-year-survival rate was 21.3%. Treatment-related adverse events mainly included acute meningitis, chronic-delayed encephalopathy, radiculitis, myelosuppression and mucositis. Twelve patients (20.3%) had grade III-V toxic reactions. We concluded that IC combined with concomitant IF-RT, with significant efficacy and acceptable toxicity, may be an optimal therapeutic option for treatment of LM from solid tumors with adverse prognostic factors. LM, in which cancer cells spread to membranes enveloping the brain and spinal cord, is a devastating complication of solid cancers. Existing LM therapies center on IC. In this prospective clinical study, the authors combined intrathecal methotrexate with involved-field radiotherapy in a concomitant regimen, showing that the approach can potentially improve quality of life for patients with adverse prognostic factors. Concurrent radiotherapy-bolstered IC by contributing to prolonged remission of neurological symptoms and increasing OS. The findings suggest that the concomitant regimen could be an optimal treatment option for LM.
实体瘤软脑膜转移（LM）的预后极差，尤其是对于具有不良预后因素的患者。在这项II期临床试验中，我们评估了鞘内化疗（IC）联合同期受累野放疗（IF-RT）治疗具有不良预后因素的实体瘤LM的疗效和安全性。2010年5月至2014年12月期间，纳入了59例来自各种实体瘤的LM患者。同期治疗包括同步IC（甲氨蝶呤12.5 - 15 mg和地塞米松5 mg，每周一次）和IF-RT（全脑和/或椎管放疗，40 Gy/20次）。对于卡氏功能状态（KPS）评分低且不耐受放疗的患者，在同期治疗前给予诱导IC（1 - 3次）。38例患者（64.4%）接受了后续治疗。所有患者在LM诊断后至少随访6个月或直至死亡。评估的主要终点是临床缓解率。次要终点是总生存期（OS）和安全性。病理类型包括肺癌（n = 42）、乳腺癌（n = 11）和其他（n = 6）。KPS评分中位数为40（范围20 - 70）。51例患者（86.4%）完成了同期治疗。总缓解率为86.4%（51/59）。OS为0.4至36.7个月（中位数6.5个月），1年生存率为21.3%。治疗相关不良事件主要包括急性脑膜炎、慢性延迟性脑病、神经根炎、骨髓抑制和粘膜炎。12例患者（20.3%）出现III - V级毒性反应。我们得出结论，IC联合同期IF-RT疗效显著且毒性可接受，可能是治疗具有不良预后因素的实体瘤LM的最佳治疗选择。LM是癌细胞扩散至包裹脑和脊髓的膜的一种毁灭性实体癌并发症。现有的LM治疗以IC为中心。在这项前瞻性临床研究中，作者将鞘内甲氨蝶呤与受累野放疗以同期方案联合应用，表明该方法可能改善具有不良预后因素患者的生活质量。同期放疗通过有助于延长神经症状缓解期和提高OS来增强IC。研究结果表明同期方案可能是LM的最佳治疗选择。
