Outcomes of salvage re-irradiation in recurrent medulloblastoma correlate with age at initial diagnosis, primary risk-stratification, and molecular subgrouping
Outcomes of salvage re-irradiation in recurrent medulloblastoma correlate with age at initial diagnosis, primary risk-stratification, and molecular subgrouping
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DOI：
10.1007/s11060-019-03225-9
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发表时间：
2019-09-01
影响因子：
3.9
通讯作者：
Moiyadi, Aliasgar
中科院分区：
文献类型：
--
作者：
Gupta, Tejpal;Maitre, Madan;Moiyadi, Aliasgar
目的 报告复发性/进行性髓母细胞瘤 (MB) 挽救性再照射 (re-RT) 的结果。方法 回顾性分析 2008 年至 2018 年间接受根治性再放疗作为多模式治疗复发/进行性 MB 的患者的病历。结果 共有 28 名患者（首次诊断时中位年龄 18 岁）纳入研究。根据选定的 12 个蛋白质编码基因和 9 个 microRNA 的差异表达，使用实时逆转录酶聚合酶链反应 (RT-PCR) 进行分子亚组。 17 名声刺猬 (SHH)-MB 患者中的 15 名 (88%) 在索引瘤床内出现孤立的局部复发，而 7 名 4 组 MB 患者中的 5 名 (72%) 出现后颅窝外的局部复发。 2 名 SHH-MB 患者以及第 4 组和无翼 (WNT)-MB 各一名患者中观察到弥漫性椎管内播散。 3 名患者的分子亚型未知。 re-RT 的剂量和体积基于复发部位和模式，其中 18 名患者 (64%) 接受单灶治疗，3 名患者 (11%) 接受多灶治疗，7 名患者 (25%) 接受重复颅脊髓照射 (re-CSI)。从初次照射到再次放疗的中位间隔为 49.5 个月（范围 24-98 个月），中位累积生物有效剂量为 117 Gy（范围 78-132 Gy）。所有患者在重新放疗之前或之后均接受了以铂类为基础的挽救性化疗。一名患者在重新 CSI 后出现症状性放射性坏死。中位随访 24 个月（范围 6-84 个月）时，再放疗后 2 年无进展生存率 (PFS) 和总生存率 (OS) 分别为 46% 和 51%。指数诊断、主要风险分层（标准风险）和分子亚组（第 4 组）时年龄较小（< 18 岁）与显着更好的再 RT 结局相关。结论 挽救性再放疗为选定的复发/进行性 MB 患者提供了良好的局部控制并提高了生存结果，且毒性可接受。
Purpose To report outcomes of salvage re-irradiation (re-RT) in recurrent/progressive medulloblastoma (MB). Methods Medical records of patients treated with curative-intent re-RT as multi-modality management for recurrent/progressive MB between 2008 and 2018 were analyzed retrospectively. Results A total of 28 patients (median age 18 years at index diagnosis) were included. Molecular subgrouping was done using real-time reverse transcriptase polymerase chain reaction (RT-PCR) based on the differential expression of select set of 12 protein coding genes and 9 microRNAs. Fifteen of 17 (88%) patients with sonic hedgehog (SHH)-MB developed isolated local recurrence within the index tumor-bed, while 5 of 7 (72%) patients with Group 4 MB developed localized relapse outside the posterior fossa. Diffuse neuraxial dissemination was seen in 2 patients with SHH-MB, and one each of Group 4 and wingless (WNT)-MB. Molecular subgrouping was not known in 3 patients. The dose and volume of re-RT was based on site and patterns of relapse, comprising unifocal in 18 (64%), multi-focal in 3 (11%), and repeat craniospinal irradiation (re-CSI) in 7 (25%) patients. Median interval from primary irradiation to re-RT was 49.5 months (range 24-98 months) with median cumulative biologically effective dose of 117 Gy (range 78-132 Gy). All patients received platinum-based salvage chemotherapy either before or after re-RT. One patient developed symptomatic radiation necrosis following re-CSI. At a median follow-up of 24 months (range 6-84 months), 2-year post-re-RT progression-free survival (PFS) and overall survival (OS) was 46% and 51% respectively. Younger age (< 18 years) at index diagnosis, primary risk stratification (standard-risk) and molecular subgrouping (Group 4) were associated with significantly better post-re-RT outcomes. Conclusion Salvage re-RT provides good local control and encouraging survival outcomes with acceptable toxicity in selected patients with recurrent/progressive MB.