POSTOPERATIVE CHEMOTHERAPY AND DELAYED RADIATION IN CHILDREN LESS-THAN 3 YEARS OF AGE WITH MALIGNANT BRAIN-TUMORS
POSTOPERATIVE CHEMOTHERAPY AND DELAYED RADIATION IN CHILDREN LESS-THAN 3 YEARS OF AGE WITH MALIGNANT BRAIN-TUMORS
复制标题
DOI：
10.1056/nejm199306173282401
复制
发表时间：
1993-06-17
影响因子：
158.5
通讯作者：
KUN, LE
中科院分区：
文献类型：
--
作者：
DUFFNER, PK;HOROWITZ, ME;KUN, LE
背景。在恶性脑肿瘤患者中，婴儿和幼儿预后最差，与治疗相关的神经毒性作用最严重。因此，在1986年，儿科肿瘤小组开始了一项研究，在该研究中，术后给予化疗，以允许延迟放射到发育中的大脑。36个月以下经活检证实的恶性脑肿瘤患儿术后接受环磷酰胺+长春新碱两个28天周期的治疗，随后是顺铂+依托泊苷一个28天周期的治疗。在132名诊断时24个月以下的儿童和66名诊断时24至36个月的儿童中，重复这一顺序直至疾病进展或持续两年，并持续一年。在此之后，患者接受放射治疗。对102例术后残留病变患者的前两个化疗周期的疗效进行了观察。102例可评估的患者中，39%的患者使用环磷酰胺和长春新碱的前两个疗程产生完全或部分缓解。髓母细胞瘤、恶性胶质瘤或室管膜瘤患者的反应率最高。脑干胶质瘤或胚胎肿瘤（原始神经外胚层肿瘤）的患者很少或没有反应。诊断时24 - 36个月大的儿童1年无进展生存率为41%，诊断时24个月以下的儿童2年无进展生存率为39%。多因素分析发现胚胎肿瘤是一个显著的不良预后特征（相对风险，2.2；95%可信区间，1.4 - 3.4），完全切除是一个有利的特征（相对风险，0.33；95%可信区间，0.20 - 0.54）。化疗的完全缓解与接近全切除的无进展生存率相关。基线和化疗一年后的认知评估比较显示认知功能没有恶化的迹象。化疗似乎是许多儿童恶性脑肿瘤术后有效的主要治疗方法。对大多数病人进行一到两年的疾病控制，可以推迟放射治疗的时间，根据初步结果，可以减少神经毒性。对于接受了完全手术切除或对化疗有完全反应的患者，结果足够令人鼓舞，表明在化疗至少一年后，这一亚组儿童可能不需要放射治疗。
Background. Among patients with malignant brain tumors, infants and very young children have the worst prognosis and the most severe treatment-related neurotoxic effects. Therefore, in 1986, the Pediatric Oncology Group began a study in which postoperative chemotherapy was given in order to permit a delay in the delivery of radiation to the developing brain.Methods. Children under 36 months of age with biopsy-proved malignant brain tumors were treated postoperatively with two 28-day cycles of cyclophosphamide plus vincristine, followed by one 28-day cycle of cisplatin plus etoposide. This sequence was repeated until the disease progressed or for two years in 132 children under 24 months of age at diagnosis and for one year in 66 children 24 to 36 months of age at diagnosis. After this, the patients received radiation therapy. The response to the first two cycles of chemotherapy was measured in 102 patients with residual postoperative disease.Results. The first two cycles of cyclophosphamide and vincristine produced complete or partial responses in 39 percent of the 102 patients who could be evaluated. The response rates were highest among patients with medulloblastomas, malignant gliomas, or ependymomas. Patients with brain-stem gliomas or embryonal tumors (primitive neuroectodermal tumors) had little or no response. The progression-free survival rate was 41 percent at one year for children who were 24 to 36 months old at diagnosis and 39 percent at two years for those under 24 months of age at diagnosis. Multivariate analysis identified embryonal tumors as a significant adverse prognostic feature (relative risk, 2.2; 95 percent confidence interval, 1.4 to 3.4) and complete resection as a favorable feature (relative risk, 0.33; 95 percent confidence interval, 0.20 to 0.54). Complete responses to chemotherapy were associated with a progression-free survival rate approaching that achieved with gross total resection. A comparison of cognitive evaluations obtained at base line and after one year of chemotherapy revealed no evidence of deterioration in cognitive function.Conclusions. Chemotherapy appears to be an effective primary postoperative treatment for many malignant brain tumors in young children. Disease control for one or two years in a large minority of patients permitted a delay in the delivery of radiation and, on the basis of preliminary results, a reduction in neurotoxicity. For patients who had undergone total surgical resection or who had a complete response to chemotherapy, the results are sufficiently encouraging to suggest that radiation therapy may not be needed in this subgroup of children after at least one year of chemotherapy.