Geyer J R, Zeltzer P M, Boyett J M, Rorke L B, Stanley P, Albright A L, Wisoff J H, Milstein J M, Allen J C, Finlay J L
Children's Hospital and Medical Center, Seattle, WA.
J Clin Oncol. 1994 Aug;12(8):1607-15. doi: 10.1200/JCO.1994.12.8.1607.
Very young children with CNS primitive neuroectodermal tumors (PNETs) and ependymomas have a poor prognosis and commonly have impairment of growth and cognitive abilities, in part resulting from radiotherapy. Thus, an intensive chemotherapeutic regimen was used to treat children less than 18 months of age at diagnosis.
Children were treated on a Childrens Cancer Group (CCG) protocol with an eight-drug chemotherapeutic regimen (vincristine, carmustine, procarbazine, hydroxyurea, cisplatin, cytarabine, prednisone, and cyclophosphamide) following surgery and postoperative staging. Delayed or reduced-volume radiotherapy was to be administered to all patients, but, in fact, was omitted in most cases.
On central review of pathology, 82 children had diagnosis concordant with study entry criteria. Of these, 46 (56%) had posterior fossa (PF) PNET, eight (10%) had pineal PNET, 11 (12%) had nonpineal supratentorial PNET, 15 (18%) had ependymoma, and two had rhabdoid tumors. Fifty percent of tumor resections were complete, as verified by postoperative computed tomographic (CT) scan, and 23% of patients had metastatic disease at the time of diagnosis. Objective tumor response was documented following two cycles of chemotherapy in 28% of assessable patients. Toxicity of chemotherapy was primarily hematopoietic. Five children died of chemotherapy-related complications. Radiotherapy was administered to only nine patients before tumor progression. The 3-year progression-free survival (PFS) rates for PF PNET, pineal PNET, supratentorial nonpineal PNET, and ependymoma are 22% (SE = 6%), 0%, 55% (16%), and 26% (11%), respectively. The 3-year PFS rate for those children without metastatic disease was 29% (6%), as compared with 11% (6%) for those with metastatic disease. The only independent predictors of PFS were metastasis stage and location of the tumor within the pineal region. The median time to progression was 6 months. Twenty-four children completed the chemotherapeutic regimen without tumor progression; 19 are event-free survivors more than 2 years from diagnosis, only three of whom received radiation therapy.
While overall survival in this group of very young patients is poor, a subset of children who have received only chemotherapy as adjuvant treatment remain free from tumor recurrence.
患有中枢神经系统原始神经外胚层肿瘤（PNETs）和室管膜瘤的幼儿预后较差，且常出现生长和认知能力受损，部分原因是放疗所致。因此，采用强化化疗方案治疗诊断时年龄小于18个月的儿童。
儿童按照儿童癌症研究组（CCG）方案接受治疗，术后分期后采用八药化疗方案（长春新碱、卡莫司汀、丙卡巴肼、羟基脲、顺铂、阿糖胞苷、泼尼松和环磷酰胺）。所有患者都应接受延迟或减量放疗，但实际上大多数情况下都未进行放疗。
经中心病理复查，82名儿童的诊断符合研究纳入标准。其中，46名（56%）患有后颅窝（PF）PNET，8名（10%）患有松果体PNET，11名（12%）患有非松果体幕上PNET，15名（18%）患有室管膜瘤，2名患有横纹肌样肿瘤。术后计算机断层扫描（CT）证实50%的肿瘤切除完整，23%的患者在诊断时已有转移性疾病。28%的可评估患者在两个化疗周期后记录到客观肿瘤反应。化疗毒性主要为血液系统毒性。5名儿童死于化疗相关并发症。仅9名患者在肿瘤进展前接受了放疗。PF PNET、松果体PNET、幕上非松果体PNET和室管膜瘤的3年无进展生存率（PFS）分别为22%（标准误=6%）、0%、55%（16%）和26%（11%）。无转移性疾病儿童的3年PFS率为29%（6%），而有转移性疾病儿童为11%（6%）。PFS的唯一独立预测因素是转移分期和肿瘤在松果体区域内的位置。中位进展时间为6个月。24名儿童在无肿瘤进展的情况下完成了化疗方案；19名是诊断后2年以上无事件生存者，其中只有3名接受了放疗。
虽然这组非常年幼患者的总体生存率较低，但一部分仅接受化疗作为辅助治疗的儿童仍无肿瘤复发。
