Duffner P K, Horowitz M E, Krischer J P, Friedman H S, Burger P C, Cohen M E, Sanford R A, Mulhern R K, James H E, Freeman C R
State University of New York, Buffalo School of Medicine.
N Engl J Med. 1993 Jun 17;328(24):1725-31. doi: 10.1056/NEJM199306173282401.
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.
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 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.
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.
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.
在恶性脑肿瘤患者中，婴儿和非常年幼的儿童预后最差，且治疗相关的神经毒性作用最为严重。因此，1986年，儿科肿瘤学组开展了一项研究，术后给予化疗，以便推迟对发育中的脑部进行放疗。
对活检证实为恶性脑肿瘤的36个月以下儿童术后进行两个28天周期的环磷酰胺加长春新碱治疗，随后进行一个28天周期的顺铂加依托泊苷治疗。该疗程重复进行，直至疾病进展或在132名诊断时年龄为24个月的儿童中持续两年，在66名诊断时年龄为24至36个月的儿童中持续一年。此后，患者接受放射治疗。对102例术后有残留病灶的患者测量了前两个化疗周期的反应。
在102例可评估的患者中，前两个环磷酰胺和长春新碱周期产生完全或部分反应的比例为39%。在髓母细胞瘤、恶性胶质瘤或室管膜瘤患者中反应率最高。脑干胶质瘤或胚胎性肿瘤（原始神经外胚层肿瘤）患者几乎没有反应或无反应。诊断时年龄为24至36个月的儿童一年无进展生存率为41%，诊断时年龄在24个月以下的儿童两年无进展生存率为39%。多变量分析确定胚胎性肿瘤是一个显著的不良预后特征（相对风险，2.2；95%置信区间，1.4至3.4），而完全切除是一个有利特征（相对风险，0.33；95%置信区间，0.20至0.54）。化疗的完全反应与接近大体全切除所达到的无进展生存率相关。对基线时和化疗一年后获得的认知评估进行比较，未发现认知功能恶化的证据。
化疗似乎是许多幼儿恶性脑肿瘤有效的术后主要治疗方法。在一大部分患者中疾病控制一到两年，使得放疗得以推迟，并且根据初步结果，神经毒性有所降低。对于接受了全手术切除或对化疗有完全反应的患者，结果令人鼓舞，表明在至少一年的化疗后，这一亚组儿童可能不需要放疗。
