首次进展时行再放疗的弥漫性内在脑桥胶质瘤（DIPG）患者的生存获益：代表 SIOP-E-HGG/DIPG 工作组的匹配队列分析。
Survival benefit for patients with diffuse intrinsic pontine glioma (DIPG) undergoing re-irradiation at first progression: A matched-cohort analysis on behalf of the SIOP-E-HGG/DIPG working group.
机构信息
Department of Radiation Oncology, University Medical Center Utrecht and Princess Maxima Center for Pediatric Oncology, Utrecht, The Netherlands.
Pediatric Radiotherapy Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy.
出版信息
Eur J Cancer. 2017 Mar;73:38-47. doi: 10.1016/j.ejca.2016.12.007. Epub 2017 Feb 3.
BACKGROUND
Overall survival (OS) of patients with diffuse intrinsic pontine glioma (DIPG) is poor. The purpose of this study is to analyse benefit and toxicity of re-irradiation at first progression.
METHODS
At first progression, 31 children with DIPG, aged 2-16 years, underwent re-irradiation (dose 19.8-30.0 Gy) alone (n = 16) or combined with systemic therapy (n = 15). At initial presentation, all patients had typical symptoms and characteristic MRI features of DIPG, or biopsy-proven high-grade glioma. An interval of ≥3 months after upfront radiotherapy was required before re-irradiation. Thirty-nine patients fulfilling the same criteria receiving radiotherapy at diagnosis, followed by best supportive care (n = 20) or systemic therapy (n = 19) at progression but no re-irradiation, were eligible for a matched-cohort analysis.
RESULTS
Median OS for patients undergoing re-irradiation was 13.7 months. For a similar median progression-free survival after upfront radiotherapy (8.2 versus 7.7 months; P = .58), a significant benefit in median OS (13.7 versus 10.3 months; P = .04) was observed in favour of patients undergoing re-irradiation. Survival benefit of re-irradiation increased with a longer interval between end-of-radiotherapy and first progression (3-6 months: 4.0 versus 2.7; P < .01; 6-12 months: 6.4 versus 3.3; P = .04). Clinical improvement with re-irradiation was observed in 24/31 (77%) patients. No grade 4-5 toxicity was recorded. On multivariable analysis, interval to progression (corrected hazard ratio = .27-.54; P < .01) and re-irradiation (corrected hazard ratio = .18-.22; P < .01) remained prognostic for survival. A risk score (RS), comprising 5 categories, was developed to predict survival from first progression (ROC: .79). Median survival ranges from 1.0 month (RS-1) to 6.7 months (RS-5).
CONCLUSIONS
The majority of patients with DIPG, responding to upfront radiotherapy, do benefit of re-irradiation with acceptable tolerability.
背景
弥漫内生型脑桥胶质瘤（DIPG）患者的总体生存率（OS）较差。本研究旨在分析首次进展时再放疗的获益和毒性。
方法
在首次进展时，31 名年龄在 2-16 岁的 DIPG 患儿接受了再放疗（剂量为 19.8-30.0Gy），单独放疗（n=16）或联合系统治疗（n=15）。在初次就诊时，所有患者均有 DIPG 的典型症状和特征性 MRI 特征，或活检证实为高级别胶质瘤。在再放疗前需要有≥3 个月的初次放疗间隔。符合同样标准的 39 名患者在诊断时接受放疗，随后在进展时接受最佳支持治疗（n=20）或系统治疗（n=19），但不接受再放疗，可进行匹配队列分析。
结果
接受再放疗的患者中位 OS 为 13.7 个月。尽管初次放疗后的中位无进展生存期相似（8.2 与 7.7 个月；P=0.58），但接受再放疗的患者中位 OS 有显著获益（13.7 与 10.3 个月；P=0.04）。再放疗的生存获益随着放疗结束与首次进展之间的间隔时间延长而增加（3-6 个月：4.0 与 2.7；P<0.01；6-12 个月：6.4 与 3.3；P=0.04）。再放疗后 24/31（77%）患者的临床症状得到改善。未发生 4-5 级毒性。多变量分析显示，进展时间（校正危险比=0.27-0.54；P<0.01）和再放疗（校正危险比=0.18-0.22；P<0.01）仍是生存的预后因素。建立了一个包含 5 个类别的风险评分（RS），以预测首次进展后的生存情况（ROC：0.79）。中位生存范围从 RS-1 的 1.0 个月到 RS-5 的 6.7 个月。
结论
大多数对初次放疗有反应的 DIPG 患者都能从再放疗中获益，且具有可接受的耐受性。
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