Rutkowski Stefan, Gerber Nicolas Ulrich, von Hoff Katja, Gnekow Astrid, Bode Udo, Graf Norbert, Berthold Frank, Henze Günter, Wolff Johannes E A, Warmuth-Metz Monika, Soerensen Niels, Emser Angela, Ottensmeier Holger, Deinlein Frank, Schlegel Paul-Gerhardt, Kortmann Rolf-Dieter, Pietsch Torsten, Kuehl Joachim
Children's University Hospital, University of Wuerzburg, Wuerzburg, Germany.
Neuro Oncol. 2009 Apr;11(2):201-10. doi: 10.1215/15228517-2008-084. Epub 2008 Sep 25.
To investigate the utility of postoperative chemotherapy in delaying radiotherapy and to identify prognostic factors in early childhood medulloblastoma, we studied children younger than 3 years of age registered to the HIT-SKK'87 (Therapieprotokoll für Säuglinge und Kleinkinder mit Hirntumoren [Brain Tumor Radiotherapy for Infants and Toddlers with Medulloblastoma] 1987) trial who received systemic interval chemotherapy until craniospinal radiotherapy was applied at 3 years of age or at relapse, from 1987 to 1993. Children with postoperative residual tumor or metastatic disease received systemic induction chemotherapy prior to interval chemotherapy. Twenty-nine children were eligible for analyses (median age, 1.7 years; median follow-up, 12.6 years). In children without macroscopic metastases, rates (+/-SEM) for 10-year progression-free survival (PFS) and overall survival (OS) were 52.9% +/- 12.1% and 58.8% +/- 11.9% (complete resection), and 55.6% +/- 16.6% and 66.7% +/- 15.7% (incomplete resection), compared with 0% and 0% in children with macroscopic metastases. Survival was superior in nine children with desmoplastic or extensive nodular histology compared with 20 children with classic medulloblastoma (10-year PFS, 88.9% +/- 10.5% and 30.0% +/- 10.3%, p = 0.003; OS, 88.9% +/- 10.5% and 40.0% +/- 11.0%, p = 0.006). Eleven of 12 children with tumor progression during chemotherapy had classic medulloblastoma. After treatment, IQ scores were inferior compared with nonirradiated children from the subsequent study, HIT-SKK'92. Classic histology, metastatic disease, and male gender were independent adverse risk factors for PFS and OS in 72 children from HIT-SKK'87 and HIT-SKK'92 combined. In terms of survival, craniospinal radiotherapy was successfully delayed especially in young children with medulloblastoma of desmoplastic/extensive nodular histology, which was a strong independent favorable prognostic factor. Because of the neurocognitive deficits of survivors, the emerging concepts to avoid craniospinal radiotherapy should rely on the histological medulloblastoma subtype.
为了研究术后化疗在延迟放疗方面的作用，并确定幼儿髓母细胞瘤的预后因素，我们对1987年至1993年期间登记参加HIT-SKK'87试验（1987年婴幼儿髓母细胞瘤脑肿瘤放疗方案）的3岁以下儿童进行了研究，这些儿童接受全身间隔化疗，直至3岁或复发时进行全脑脊髓放疗。术后有残留肿瘤或转移性疾病的儿童在间隔化疗前接受全身诱导化疗。29名儿童符合分析条件（中位年龄1.7岁；中位随访时间12.6年）。在无宏观转移的儿童中，10年无进展生存率（PFS）和总生存率（OS）（+/-SEM）在完全切除的儿童中分别为52.9% +/- 12.1%和58.8% +/- 11.9%，在不完全切除的儿童中分别为55.6% +/- 16.6%和66.7% +/- 15.7%，而有宏观转移的儿童中这两个生存率均为0%。与20例经典型髓母细胞瘤儿童相比，9例促纤维增生型或广泛结节型组织学的儿童生存率更高（10年PFS，88.9% +/- 10.5%和30.0% +/- 10.3%，p = 0.003；OS，88.9% +/- 10.5%和40.0% +/- 11.0%，p = 0.006）。化疗期间肿瘤进展的12名儿童中有11名患有经典型髓母细胞瘤。治疗后，与后续研究HIT-SKK'92中未接受放疗的儿童相比，智商得分较低。经典型组织学、转移性疾病和男性性别是HIT-SKK'87和HIT-SKK'92联合研究中72名儿童PFS和OS的独立不良风险因素。在生存方面，全脑脊髓放疗尤其在促纤维增生型/广泛结节型组织学的幼儿髓母细胞瘤中成功延迟，这是一个强有力的独立有利预后因素。由于幸存者存在神经认知缺陷，避免全脑脊髓放疗的新观念应依赖于髓母细胞瘤的组织学亚型。
