Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany.
Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
J Neurooncol. 2022 Mar;157(1):37-48. doi: 10.1007/s11060-021-03913-5. Epub 2022 Feb 21.
To evaluate the clinical impact of isolated spread of medulloblastoma cells into cerebrospinal fluid without additional macroscopic metastases (M1-only).
The HIT-MED database was searched for pediatric patients with M1-only medulloblastoma diagnosed from 2000 to 2019. Corresponding clinical and molecular data was evaluated. Treatment was stratified by age and changed over time for older patients.
70 patients with centrally reviewed M1-only disease were identified. Clinical data was available for all and molecular data for 45/70 cases. 91% were non-WNT/non-SHH medulloblastoma (Grp3/4). 5-year PFS for 52 patients ≥ 4 years was 59.4 (± 7.1) %, receiving either upfront craniospinal irradiation (CSI) or SKK-sandwich chemotherapy (CT). Outcomes did not differ between these strategies (5-year PFS: CSI 61.7 ± 9.9%, SKK-CT 56.7 ± 6.1%). For patients < 4 years (n = 18), 5-year PFS was 50.0 (± 13.2) %. M1-persistence occurred exclusively using postoperative CT and was a strong negative predictive factor (p < 0.01). Patients with additional clinical or molecular high-risk (HR) characteristics had worse outcomes (5-year PFS 42.7 ± 10.6% vs. 64.0 ± 7.0%, p = 0.03). In n = 22 patients ≥ 4 years with full molecular information and without additional HR characteristics, risk classification by molecular subtyping had an effect on 5-year PFS (HR 16.7 ± 15.2%, SR 77.8 ± 13.9%; p = 0.01).
Our results confirm that M1-only is a high-risk condition, and further underline the importance of CSF staging. Specific risk stratification of affected patients needs attention in future discussions for trials and treatment recommendations. Future patients without contraindications may benefit from upfront CSI by sparing risks related to higher cumulative CT applied in sandwich regimen.
评估孤立性髓母细胞瘤细胞扩散至脑脊液而无其他肉眼转移（M1 期）的临床影响。
在 HIT-MED 数据库中搜索了 2000 年至 2019 年诊断为 M1 期孤立性髓母细胞瘤的儿科患者。评估了相应的临床和分子数据。对于年龄较大的患者，根据年龄进行治疗分层，并随着时间的推移进行治疗改变。
共确定了 70 例经中心审查的 M1 期疾病患者。所有患者均提供了临床数据，45/70 例患者提供了分子数据。91%为非 WNT/非 SHH 髓母细胞瘤（Grp3/4）。52 例年龄≥4 岁患者的 5 年 PFS 为 59.4（±7.1）%，接受了 upfront 颅脊髓照射（CSI）或 SKK-三明治化疗（CT）。这两种策略的结果没有差异（5 年 PFS：CSI 61.7±9.9%，SKK-CT 56.7±6.1%）。对于年龄＜4 岁（n=18）的患者，5 年 PFS 为 50.0（±13.2）%。M1 持续存在仅发生在术后 CT 后，是一个强烈的阴性预测因素（p＜0.01）。具有其他临床或分子高危（HR）特征的患者预后较差（5 年 PFS 42.7±10.6% vs. 64.0±7.0%，p=0.03）。在 n=22 例年龄≥4 岁且具有完整分子信息且无其他 HR 特征的患者中，基于分子亚型的危险度分类对 5 年 PFS 有影响（HR 16.7±15.2%，SR 77.8±13.9%；p=0.01）。
我们的结果证实 M1 期是一种高危情况，进一步强调了 CSF 分期的重要性。在未来的试验和治疗建议讨论中，需要特别注意受影响患者的风险分层。未来无禁忌症的患者可能受益于 upfront CSI，避免因在三明治方案中应用更高累积 CT 而带来的风险。
