摘要

BACKGROUND:The use of chemotherapy to manage newly diagnosed low grade glioma (LGG) was first introduced in the 1980s. One randomised trial has studied two- versus four-drug regimens with a duration of 12 months of treatment after resection.
METHODS:Within the European comprehensive treatment strategy for childhood LGG, the International Society of Paediatric Oncology-Low Grade Glioma (SIOP LGG) Committee launched a randomised trial involving 118 institutions and 11 countries to investigate the addition of etoposide (100 mg/m2, days 1, 2 & 3) to a four-course induction of vincristine (1.5 mg/m2 × 10 wkly) and carboplatin (550 mg/m2 q 3 weekly) as part of 18-month continuing treatment programme. Patients were recruited after imaging diagnosis, resection or biopsy with progressive disease/symptoms. Some 497 newly diagnosed patients (M/F 231/266; median age 4.26 years (interquartile range (IQR) 2.02-7.06)) were randomised to receive vincristine carboplatin (VC) (n = 249) or VC plus etoposide (VCE) during induction (n = 248), stratified by age and tumour site.
FINDINGS:No differences between the two arms were found in term of survival and radiological response. Response and non-progression rates at 24 weeks for VC and VCE, were 46% versus 41%, and 93% versus 91% respectively; 5-year Progression-Free Survival (PFS) and Overall Survival (OS) were 46% (StDev 3.5) versus 45% (StDev 3.5) and 89% (StDev 2.1) versus 89% (StDev 2.1) respectively. Age and diencephalic syndrome are adverse clinical risk factors for PFS and OS. 5-year OS for patients in early progression at week 24 were 46% (StDev 13.8) and 49% (StDev 16.5) in the two arms, respectively.
INTERPRETATION:The addition of etoposide to VC did not improve PFS or OS. High non-progression rates at 24 weeks justify retaining VC as standard first-line therapy. Infants with diencephalic syndrome and early progression need new treatments to be tested. Future trials should use neurological/visual and toxicity outcomes and be designed to discriminate between the impact on disease outcomes of 'duration of therapy' and 'age at stopping therapy'.

译文

背景: 使用化疗来管理新诊断的低级别胶质瘤 (LGG) 最早是在 1980 引入的。一项随机试验研究了切除后持续 12 个月治疗的两种与四种药物方案。
方法: 在欧洲儿童 LGG 综合治疗策略内，国际儿科肿瘤学会-低级别胶质瘤 (SIOP LGG) 委员会发起了一项涉及 118 个机构和 11 个国家的随机试验，以调查在长春新碱的四疗程诱导中添加依托泊苷 (100 毫克/平方米，第 1 、 2 和 3 天)(1.5 mg/m2 × 10 wkly) 和卡铂 (每周 550 mg/m2 q 3) 作为 18 个月持续治疗计划的一部分。患者在影像学诊断、切除或活检后被招募，并伴有进展性疾病/症状。大约 497 名新诊断患者 (M/F 231/266; 中位年龄 4.26 岁 (四分位数范围 (IQR) 2.02-7.06)) 被随机分配接受长春新碱卡铂 (VC) (n = 249) 或诱导过程中的 VC 加依托泊苷 (VCE) (n = 248)，按年龄和肿瘤部位分层。
结果: 两组在存活率和放射反应方面没有发现差异。VC 和 VCE 在 24 周的反应率和无进展率分别为 46% 比 41% 和 93% 比 91%; 5 年无进展生存期 (PFS) 总生存率 (OS) 分别为 46% (StDev 3.5) 对 45% (StDev 3.5) 和 89% (StDev 2.1) 对 89% (StDev 2.1)。年龄和间脑综合征是 PFS 和 OS 的不良临床危险因素。在 24 周早期进展的患者的 5 年 OS 在两组分别为 46% (StDev 13.8) 和 49% (StDev 16.5)。
解释: 在 VC 中添加依托泊苷并没有改善 PFS 或 OS。24 周时的高无进展率证明保留 VC 作为标准的一线治疗是合理的。患有间脑综合征和早期进展的婴儿需要测试新的治疗方法。未来的试验应使用神经/视觉和毒性结果，并旨在区分 “治疗持续时间” 和 “停止治疗年龄” 对疾病结果的影响。