鞘内化学治疗同步放射治疗对恶性实体肿瘤脑膜转移的临床疗效观察

Clinical observation of intrathecal chemotherapy combined with concurrent radiotherapy for leptomeningeal metastases from malignant solid tumors

目的 观察恶性实体肿瘤脑膜转移应用鞘内化学治疗（简称化疗）同步放射治疗（简称放疗）的疗效及安全性.方法 回顾性分析29例恶性实体瘤脑膜转移患者的诊疗及随访资料.治疗方案：鞘内注射甲氨蝶呤12.5 ～15.0 mg,每周1次,连续8周;同时行全脑或节段性椎管放射治疗,每次剂量40～ 50 Gy,照射20 ～ 25次.结果 症状完全缓解9例,明显缓解11例,症状减轻6例,无缓解3例;共19例患者完成同步治疗;19例患者死亡.随访期0.4 ～15.0个月;全组患者中位生存期5个月;去除随访期不足6个月的患者4例,及非肿瘤死亡患者2例,6个月生存率为48％ （11/23）.毒性反应主要为：骨髓抑制、甲氨蝶呤所致黏膜反应、化学性神经根反应、化学性脑膜炎、慢性神经系统毒性、一过性癫痫发作、放射性皮肤黏膜反应;严重毒性反应发生率为17％ （5/29）.结论 鞘内化疗同步放疗,可以有效缓解恶性实体肿瘤脑膜转移患者症状,改善生存质量;严重毒性反应发生率低,患者耐受良好;具有延长中位生存期的趋势.

Objective To investigate the efficacy and safety of intrathecal chemotherapy combined with concurrent radiotherapy in patients with leptomeningeal metastases from solid tumors. Methods The clinical and follow-up data of 29 patients with leptomeningeal metastases from malignant solid tumor who had intrathecal chemotherapy combined with concurrent radiotherapy were retrospectively analyzed. The treatment regimen was that 12. 5--15.0 mg of methotrexate intrathecal injection once a week for 8 successive weeks combined with whole brain irradiation to a total dose of 40 Gy,20 fractious or with lumbosacral spinal canal irradiation to a total dose of 50 Gy, 20--25 fractions. Results Nineteen patients completed the concurrent therapy and 19 patients were dead. There were 9 patients with complete remission of symptoms, 11 with obvious improved symptoms, 6 with alleviated symptoms, and 3 with no relief. All of the 29 patients, were followed up for 0. 4--15.0 months. The median survival was 5 months. The 6-month survival rate was 48% （11/23 ） , excluding 4 patients with follow-up time less than 6 months and 2 patients noncancer deaths. The main toxicities were myelosuppression, methotrexate-related mucositis, chemical nerve root injuries, chemical meningitis ,chronic ueurotoxicity, seizures, and radiation-related mucositis. The incidence of severe toxicity was 17% （5/29）. Conclusions Combination of intrathecal methotrexate with concurrent radiotherapy can effectively alleviate the symptoms and improve the life quality of patients. The therapy with low incidence of severe toxicity and good tolerance has the trendency to prolong the median survival.