化疗在儿童颅内生殖细胞肿瘤诊治中的应用

Application of chemotherapy in the diagnosis and treatment of children with intracranial gonioma

目的：探讨化疗在儿童颅内生殖细胞肿瘤（germ cell tumors,GCTs）的诊断与治疗中的意义和价值。方法：2010年1月至2013年12月我科拟诊GCTs患儿根据肿瘤标志物甲胎蛋白（alpha-fetoprotin,AFP）和β-人绒毛膜促性腺激素（human chorionic gonadotropin beta,β-HCG）检查结果分为生殖细胞瘤和非生殖细胞瘤性生殖细胞瘤（non-germinoma germ cell tumors,NGGCTs）,生殖细胞肿瘤行CE方案（卡铂＋依托铂苷）,诊断性化疗2个疗程后复查根据实体瘤疗效评价标准（response evaluation criteria in solid tumors,RECIST）判断化疗效果,肿瘤部分缓解（partial remission,PR）或完全缓解（complete remission,CR）临床确诊为GCTs后,≥3岁的患者行降低剂量的放疗及后续化疗,〈3岁的患儿继续化疗,待3岁后延期放疗,排除诊断的则行手术,根据病理检查进一步治疗;内胚窦瘤混合型生殖细胞瘤分别采用BCE（博来霉素、卡铂、依托铂苷）和ICE方案（异环磷酰胺、卡铂、依托泊苷）化疗,同时均联合足量全中枢放疗,视情况行二期探查手术。结果：25例患者获得随访,20例拟诊生殖细胞瘤患者诊断性化疗后PR19例（95%）,临床确诊为生殖细胞瘤后,≥3岁组（15例）,经后续放化疗后100%CR,随访生存率100%,平均随访时间2年,〈3岁组（3例）,1例化疗第6个疗程肿瘤发生全脑全脊髓转移,放弃治疗,2例化疗6个疗程后均顺利完成延期放疗,放化疗结束后均CR,目前随访中肿瘤稳定1例,排除生殖细胞瘤诊断,经手术后病检确诊为畸胎瘤,肿瘤全切,目前无事件生存（event free survival,EFS）2年。诊断NGGCTs（5例）,其中卵黄囊瘤（yolk sac tumor,YST）2例,1例化疗4个疗程,放疗期间复发死亡,1例手术完整切除后顺利完成化疗及放疗,目前已EFS 2年;混合性生殖细胞瘤3例,均行化疗＋放疗＋化疗的综合治疗,EFS1~3年。结论：GCTs对CE方案的化疗非常敏感,诊断性化疗是一种有效的诊断手段;但单纯化疗后复发率较高,治疗必须联合放疗,化疗联合降低剂量及范围放疗可以有效的提高生存率及生存质量,〈3岁的患者仍是治疗的难点和研究的重点。化疗对NGGCTs的治疗效果非常明显,具有很好的应用前景,化疗联合全中枢放疗是治疗NGGCTs的主要手段。

Objective：To investigate the role of chemotherapy in the diagnosis and treatment of children with intracranial gonioma.Methods：Cases to be diagnosed as intracranial gonioma in the Children’s Hospital of Chongqing Medical University from January2010 to December 2013 were divided into intracranial gonioma and non-intracranial gonioma according to tumor markers alpha-fetoprotin（AFP）and human chorionic gonadotropin beta（β-HCG）test results. Cases in intracranial gonioma group were treated by CE chemotherapy for two courses,and the curative effect including partial remission（PR）or complete remission（CR）was evaluated using solid tumor evaluation criteria-response evaluation criteria in solid tumors（RECIST）. After making a definite diagnosis,patients over 3 years old carried out radiation therapy and follow-up chemotherapy and patients less than 3 years old were administrated with chemotherapy until over the age of 3 years,and then received extended radiotherapy. Non-intracranial gonioma cases were administered with BCE or ICE chemotherapy combined with full dose of central nervous system radiotherapy. Whether carrying out the secondsurgery was decided according to the actual conditions. Results：Twenty-five patients were followed up,19 patients（95%）out of20 suspected patients with intracranial gonioma were PR after receiving chemotherapy. After being diagnosed as intracranial gonioma,15 patients（100%）in over than 3-year-old group were CR after chemotherapy,with 100% survival rate and an averagefollow-up period of 2 years. In less than 3-year-old group,one patients experienced relapse and craniospinal metastasis after six courses of chemotherapy and abandoned the treatment,the other 2 patients were successfully completed deferred radiotherapy after six courses of chemotherapy,both CR until now. During the current follow-up,one patient with stable tumor was diagnosed as teratomas by pathologic examination excluding the diagnosis of intracranial gonioma and underwent resection. There were 5 cases of non-intracranial gonioma including 2 cases of yolk sac tumor and 3 cases of mixed intracranial gonioma. One patient with yolk sac tumor died during the chemotherapy and one patient lived with event free survival for 2 years after successfully completing the resection and the chemotherapy. Three patients with mixed intracranial gonioma received comprehensive treatment of chemotherapy plus radiotherapy plus chemotherapy and lived with event free survival for 1-3 years. Conclusions：Diagnostic chemotherapy is effective since intracranial gonioma is very sensitive to the CE chemotherapy. But taking into consideration of higher recurrence rate after chemotherapy,diagnostic chemotherapy must combine with radiotherapy. Chemotherapy combined with radiotherapy（reducing the effective dose and scope）can improve the survival and quality of life. Patents with age less than 3 years old are still the difficulties in the treatment and research.Chemotherapy treatment is effective for treating non intracranial gonioma and chemotherapy combined with radiotherapy is the main therpay.