23例原发中枢神经系统生殖细胞瘤综合治疗的疗效分析

背景与目的:原发中枢神经系统生殖细胞瘤(primary central nervoussystem germ cell tumors,CNS GCTs)是较罕见的恶性肿瘤,病理类型多样。除纯生殖细胞瘤和成熟畸胎瘤外,其它类型预后较差。目前的研究多联合包括化疗在内的综合治疗以改善生存。本文分析PEB方案化疗联合放疗/手术的综合治疗的疗效及不良反应。方法:2002年5月至2006年6月期间中山大学肿瘤防治中心收治的23例CNS GCTs患者入组,中位年龄16岁,82.6%的患者AFP和/或β-HCG升高。所有患者均采用PEB方案化疗结合手术/放射治疗。PEB方案:顺铂20mg/m2d1～5或80～100mg/m2d1,足叶乙甙或替尼泊甙60～100mg/m2d1～5,博来霉素10mg/m2,d1,d5,每3周重复。结果:17例初治患者采用诱导化疗后放射治疗或手术/放疗后辅助化疗;6例复发患者行挽救化疗,其中3例肿瘤播散的患者挽救化疗后补充全中枢放疗。23例患者共完成61个周期的PEB方案化疗,中位化疗3周期,单纯化疗的客观有效率为87.0%,完全缓解率为30.4%。全中枢放疗14例,局部放疗8例,1例未放疗。13例接受过手术治疗但均未能完全切除肿瘤。综合治疗后60.9%(14/23)的患者持续完全缓解至今生存未复发。中位随访24个月,死亡6例,均死于肿瘤进展。全组2年生存率为67.4%。主要不良反应为迟发性放射性损伤:继发性再生障碍性贫血并下丘脑综合征1例,放射性脑病1例,垂体功能减退2例。结论:对CNS GCTs特别是伴有肿瘤标记物升高的患者,PEB方案化疗联合放疗/手术的综合治疗可获得较好的疗效和生存率,但全中枢放疗的远期副作用不容忽视。

Treatment outcome of primary central nervous system germ cell tumors after combined therapy: a report of 23 cases

BACKGROUND & OBJECTIVE: Primary central nervous system (CNS) germ cell tumors (GCTs) are rare malignant neoplasms with various histological types. Excluding pure germinoma and mature teratoma, other types carry a poor prognosis. Previous investigations focused on combined modality treatment including chemotherapy to improve survival. This study was to analyze the efficacy and toxicity of chemotherapy combined with surgery and/or radiotherapy on CNS GCTs. METHODS: A total of 23 patients with CNS GCTs were treated in Cancer Center of Sun Yat-sen University from May 2002 to Jun. 2006. The median age at diagnosis was 16 years. Alpha-fetoprotein (AFP) and/or beta-human chorionic gonadotropin (beta-HCG) levels were elevated in 19 patients (82.6%). All patients were treated with chemotherapy of PEB regimen combined with surgery and/or radiotherapy. PEB regimen was administered every 3 weeks with 20 mg/m(2) cisplatin (DDP) at Days 1-5 or 80-100 mg/m(2) at Day 1, 60-100 mg/m(2) etoposide (VP-16) or teniposide (VM-26) at Days 1-5, 10 mg/m(2) bleomycin (BLM) at Days 1 and 5. RESULTS: Of the 23 patients, 17 newly diagnosed patients received induction chemotherapy followed by radiotherapy or surgery/radiotherapy followed by adjuvant chemotherapy; 6 recurrent patients received salvage chemotherapy, of which 3 patients with disseminated tumor received salvage chemotherapy followed by craniospinal irradiation. The 23 patients completed a total of 61 cycles of PEB regimen with a median of 3 cycles. Chemotherapy alone gained a response rate of 87.0% and a complete remission rate of 30.4%. Craniospinal irradiation was performed in 14 patients and focal irradiation in 8 patients. One patient did not receive irradiation. Incomplete tumor resection or biopsy was performed in 13 patients. Fourteen patients (60.9%) were alive without evidence of diseases after combined modality treatment. With a median follow-up of 24 months, the 2-year survival rate was 67.4%. Main adverse events were late irradiation injury including aplastic anemia and hypothalamus syndrome (1 case), irradiation encephalopathy (1 case), and hypopituitarism (2 cases). CONCLUSIONS: The combined modality treatment including PEB regimen is highly effective in treating CNS GCTs patients, especially in the patients with elevated tumor markers. However, the long-term toxicities which related with craniospinal irradiation should not be ignored.