Duffner P K, Krischer J P, Horowitz M E, Cohen M E, Burger P C, Friedman H S, Kun L E
SUNY at Buffalo School of Medicine, NY, USA.
Ann Neurol. 1998 Sep;44(3):313-6. doi: 10.1002/ana.410440305.
Between 1986 and 1990, the Pediatric Oncology Group conducted a study in which 198 children younger than 3 years of age with malignant brain tumors were treated with prolonged postoperative chemotherapy in an effort to delay irradiation and reduce long-term neurotoxicity. Children younger than 2 years of age received 24 months of chemotherapy followed by irradiation, and those between 2 and 3 years of age received 12 months of chemotherapy plus irradiation. Chemotherapy was given in 28-day cycles (AAB, AAB), with cycle A = vincristine (0.065 mg/kg) intravenously on days 1 and 8 and cyclophosphamide (65 mg/kg) intravenously on day 1, and cycle B = cisplatinum (4 mg/kg) intravenously on day 1 and etoposide (6.5 mg/kg) intravenously on days 3 and 4. Five of the 198 children developed second malignancies, with a cumulative risk at 8 years of 11.3% (95% confidence interval [CI], 0-39%). Four of the five second malignancies occurred in children younger than 2 years of age at diagnosis, with a cumulative risk at 8 years of 18.9% (CI, 0-70%). Initial diagnoses were choroid plexus carcinoma (2 children), ependymoma (1 child), desmoplastic infantile ganglioglioma (2 children), and medulloblastoma (1 child). Duration from diagnosis of initial tumor to second malignancy was 33, 35, 57, 66, and 92 months. Three children younger than 2 years of age developed lymphoproliferative disease, that is, myelodysplastic syndrome (2 children), both with monosomy 7 deletions, and acute myelogenous leukemia (1 child), after 24 to 26 cycles of chemotherapy, including 8 cycles of etoposide. Two of 3 received craniospinal irradiation (2,560/3,840 cGy) and (3,520/5,320 cGy). Time to second malignancy was 7 years 8 months, 4 years 9 months, and 2 years 9 months. Two children developed solid tumors, at 5 years 6 months and 2 years 11 months, respectively, after initiation of treatment. A sarcoma developed after 26 cycles of chemotherapy and no irradiation, and a meningioma developed after 12 cycles of chemotherapy and local craniospinal irradiation. Potential causative factors for this high rate of secondary malignancies include prolonged use of alkylating agents and etoposide with or without irradiation.
1986年至1990年间，儿科肿瘤学组开展了一项研究，对198例3岁以下的恶性脑肿瘤患儿进行了术后长期化疗，以推迟放疗并降低长期神经毒性。2岁以下的儿童接受24个月的化疗后再进行放疗，2至3岁的儿童接受12个月的化疗加放疗。化疗以28天为周期（AAB，AAB）进行，A周期 = 第1天和第8天静脉注射长春新碱（0.065 mg/kg），第1天静脉注射环磷酰胺（65 mg/kg），B周期 = 第1天静脉注射顺铂（4 mg/kg），第3天和第4天静脉注射依托泊苷（6.5 mg/kg）。198名儿童中有5名发生了第二原发恶性肿瘤，8年时的累积风险为11.3%（95%置信区间[CI]，0 - 39%）。5例第二原发恶性肿瘤中有4例发生在诊断时年龄小于2岁的儿童中，8年时的累积风险为18.9%（CI，0 - 70%）。初始诊断为脉络丛癌（2例）、室管膜瘤（1例）、促结缔组织增生性婴儿型神经节胶质瘤（2例）和髓母细胞瘤（1例）。从初始肿瘤诊断到第二原发恶性肿瘤的时间为33、35、57、66和92个月。3名2岁以下的儿童在接受24至26个周期的化疗（包括8个周期的依托泊苷）后发生了淋巴增殖性疾病，即骨髓增生异常综合征（2例，均有7号染色体单体缺失）和急性髓系白血病（1例）。3名患儿中有2名接受了全脑全脊髓照射（2560/3840 cGy）和（3520/5320 cGy）。发生第二原发恶性肿瘤的时间分别为7年8个月、4年9个月和2年9个月。2名儿童在开始治疗后分别于5年6个月和2年11个月发生了实体瘤。1例在26个周期化疗且未接受放疗后发生了肉瘤，另1例在12个周期化疗及局部全脑全脊髓照射后发生了脑膜瘤。这种高比例的第二原发恶性肿瘤的潜在致病因素包括长期使用烷化剂和依托泊苷，无论是否接受放疗。
