Erker Craig, Mynarek Martin, Simbozel Marie, Craig Brandon T, Harrod Virginia L, Cappellano Andrea M, Cohen Kenneth J, Lopez Vicente Santa-Maria, Morales-La Madrid Andres, Cacciotti Chantel, Baroni Lorena, Salloum Ralph, Margol Ashley S, Michaiel George, Aguilera Dolly, Mazewski Claire M, Kline Cassie N, Finlay Jonathan L, Abdelbaki Mohamed S, Murray Jeffrey C, Dorris Kathleen, Crooks Bruce, Ginn Kevin F, Amayiri Nisreen, Tippelt Stephan, Fleischhack Gudrun, Tonn Svenja, Gerber Nicolas U, Lassaletta Alvaro, Hansford Jordan R, Khan Sara, Gilheeney Stephen W, Hoffman Lindsey M, Zapotocky Michal, Larouche Valérie, Shah Shafqat, Ramaswamy Vijay, Gajjar Amar, Perreault Sébastien, Mueller Sabine, Hukin Juliette, Cheng Sylvia, Wang Zhihong J, Matheson Kara, Bailey Simon, Bouffet Eric, Clifford Steven C, Robinson Giles, Dufour Christelle, Rutkowski Stefan, Lafay-Cousin Lucie
Division of Hematology/Oncology, Department of Paediatrics, IWK Health Centre and Dalhousie University, Halifax, NS, Canada.
Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Neuro Oncol. 2025 Apr 4. doi: 10.1093/neuonc/noaf092.
Sonic hedgehog (SHH) medulloblastoma is the most common molecular group of infant and early childhood medulloblastoma (iMB) and has no standard of care at relapse. This work aimed to evaluate the post-relapse survival (PRS) and explore prognostic factors of patients with nodular desmoplastic (ND) and/or SHH iMB.
This international retrospective study included 147 subjects diagnosed with relapsed Nodular Desmoplastic/SHH iMB between 1995 and 2017, < 6 years old at original diagnosis, and treated without initial craniospinal irradiation (CSI). Univariable and multivariable Cox models with propensity score analyses were used to assess PRS for those in the curative intent cohort.
The 3-year PRS was 61.6% (95% CI, 52.2 to 69.6). The median age at relapse was 3.4 years (IQR, 2.6-4.1). Those with local relapse (40.8%) more often received salvage surgery (p <0.001), low-dose CSI (≤ 24 Gy; p < 0.001), or focal radiotherapy (p = 0.008). Patients not receiving CSI (40.5%) more often received salvage marrow-ablative chemotherapy (HDC+AuHCR [p <0.001]). On multivariable analysis, CSI was associated with improved survival (Hazard Ratio [HR] 0.33 [95% CI, 0.13 to 0.86], p =0.04). Salvage HDC+AuHCR, while clinically important, did not reach statistical significance (HR 0.24 [95% CI, 0.0054 to 1.025], p =0.065).
Survival of patients with relapsed SHH iMB is not satisfactory and relies on treatments associated with toxicities including CSI and/or HDC+AuHCR. Upfront cure to avoid relapse is crucial. For patients with localized relapse undergoing resection, alternative salvage regimens that avoid high-dose CSI (> 24 Gy) can be considered.
声波刺猬因子（SHH）型髓母细胞瘤是婴幼儿髓母细胞瘤（iMB）中最常见的分子亚型，复发时尚无标准治疗方案。本研究旨在评估结节性促纤维增生型（ND）和/或SHH型iMB患者复发后的生存率（PRS）并探索预后因素。
这项国际回顾性研究纳入了147例在1995年至2017年间被诊断为复发的结节性促纤维增生型/SHH型iMB的患者，初诊时年龄<6岁，且初始治疗未行全脑全脊髓放疗（CSI）。采用单变量和多变量Cox模型及倾向评分分析评估根治性治疗队列患者的PRS。
3年PRS为61.6%（95%CI，52.2至69.6）。复发时的中位年龄为3.4岁（IQR，2.6 - 4.1）。局部复发患者（40.8%）更常接受挽救性手术（p<0.001）、低剂量CSI（≤24 Gy；p<0.001）或局部放疗（p = 0.008）。未接受CSI的患者（40.5%）更常接受挽救性清髓化疗（HDC + AuHCR，p<0.001）。多变量分析显示，CSI与生存改善相关（风险比[HR] 0.33 [95%CI，0.13至0.86]，p = 0.04）。挽救性HDC + AuHCR虽然具有临床重要性，但未达到统计学意义（HR 0.24 [95%CI，0.0054至1.025]，p =
