Sabel Magnus, Fleischhack Gudrun, Tippelt Stephan, Gustafsson Göran, Doz François, Kortmann Rolf, Massimino Maura, Navajas Aurora, von Hoff Katja, Rutkowski Stefan, Warmuth-Metz Monika, Clifford Steven C, Pietsch Torsten, Pizer Barry, Lannering Birgitta
Department of Paediatrics, University of Gothenburg and Queen Silvia Children's Hospital, Gothenburg, Sweden.
Paediatrics III, Division of Paediatric Haematology and Oncology, University Hospital of Essen, Essen, Germany.
J Neurooncol. 2016 Sep;129(3):515-524. doi: 10.1007/s11060-016-2202-1. Epub 2016 Jul 16.
The HIT-SIOP-PNET4 randomised trial for standard risk medulloblastoma (MB) (2001-2006) included 338 patients and compared hyperfractionated and conventional radiotherapy. We here report the long-term outcome after a median follow up of 7.8 years, including detailed information on relapse and the treatment of relapse. Data were extracted from the HIT Group Relapsed MB database and by way of a specific case report form. The event-free and overall (OS) survival at 10 years were 76 ± 2 % and 78 ± 2 % respectively with no significant difference between the treatment arms. Seventy-two relapses and three second malignant neoplasms were reported. Thirteen relapses (18 %) were isolated local relapses in the posterior fossa (PF) and 59 (82 %) were craniospinal, metastatic relapses (isolated or multiple) with or without concurrent PF disease. Isolated PF relapse vs all other relapses occurred at mean/median of 38/35 and 28/26 months respectively (p = 0.24). Late relapse, i.e. >5 years from diagnosis, occurred in six patients (8 %). Relapse treatment consisted of combinations of surgery (25 %), focal radiotherapy (RT 22 %), high dose chemotherapy with stem cell rescue (HDSCR 21 %) and conventional chemotherapy (90 %). OS at 5 years after relapse was 6.0 ± 4 %. In multivariate analysis; isolated relapse in PF, and surgery were significantly associated with prolonged survival whereas RT and HDSCR were not. Survival after relapse was not related to biological factors and was very poor despite several patients receiving intensive treatments. Exploration of new drugs is warranted, preferably based on tumour biology from biopsy of the relapsed tumour.
针对标准风险髓母细胞瘤（MB）的HIT-SIOP-PNET4随机试验（2001 - 2006年）纳入了338例患者，比较了超分割放疗和传统放疗。我们在此报告中位随访7.8年后的长期结果，包括复发及复发治疗的详细信息。数据从HIT组复发性MB数据库中提取，并通过特定病例报告表获取。10年时无事件生存率和总生存率（OS）分别为76±2%和78±2%，各治疗组之间无显著差异。报告了72例复发和3例第二原发性恶性肿瘤。13例复发（18%）为后颅窝（PF）孤立性局部复发，59例（82%）为颅脊髓转移性复发（孤立或多发），伴或不伴有并发PF疾病。孤立性PF复发与所有其他复发分别发生在平均/中位时间38/35个月和28/26个月（p = 0.2）。晚期复发，即诊断后>五年，发生在6例患者（8%）中。复发治疗包括手术（25%）、局部放疗（RT 22%）、高剂量化疗联合干细胞救援（HDSCR 21%）和传统化疗（90%）。复发后5年的OS为6.0±4%。在多变量分析中，PF孤立性复发和手术与生存期延长显著相关，而RT和HDSCR则不然。复发后的生存与生物学因素无关，尽管有几名患者接受了强化治疗，但预后仍然很差。有必要探索新药，最好基于复发肿瘤活检的肿瘤生物学。
