小儿及青少年非转移性髓母细胞瘤预后因素评估及参与随机试验或前瞻性注册研究的作用——来自HIT 2000试验的报告
Evaluation of Prognostic Factors and Role of Participation in a Randomized Trial or a Prospective Registry in Pediatric and Adolescent Nonmetastatic Medulloblastoma - A Report From the HIT 2000 Trial.
作者信息
Dietzsch Stefan, Placzek Felix, Pietschmann Klaus, von Bueren André O, Matuschek Christiane, Glück Albrecht, Guckenberger Matthias, Budach Volker, Welzel Jutta, Pöttgen Christoph, Schmidberger Heinz, Heinzelmann Frank, Paulsen Frank, Escudero Montserrat Pazos, Schwarz Rudolf, Hornung Dagmar, Martini Carmen, Grosu Anca Ligia, Stueben Georg, Jablonska Karolina, Dunst Juergen, Stranzl-Lawatsch Heidi, Dieckmann Karin, Timmermann Beate, Pietsch Torsten, Warmuth-Metz Monika, Bison Brigitte, Kwiecien Robert, Benesch Martin, Gerber Nicolas U, Grotzer Michael A, Pfister Stefan M, Clifford Steven C, von Hoff Katja, Klagges Sabine, Rutkowski Stefan, Kortmann Rolf-Dieter, Mynarek Martin
机构信息
Department for Radiation Oncology, University of Leipzig Medical Center, Leipzig, Germany.
Department of Radiation Oncology, Chemnitz Municipal Hospital, Chemnitz, Germany.
出版信息
Adv Radiat Oncol. 2020 Oct 7;5(6):1158-1169. doi: 10.1016/j.adro.2020.09.018. eCollection 2020 Nov-Dec.
PURPOSE
We aimed to compare treatment results in and outside of a randomized trial and to confirm factors influencing outcome in a large retrospective cohort of nonmetastatic medulloblastoma treated in Austria, Switzerland and Germany.
METHODS AND MATERIALS
Patients with nonmetastatic medulloblastoma (n = 382) aged 4 to 21 years and primary neurosurgical resection between 2001 and 2011 were assessed. Between 2001 and 2006, 176 of these patients (46.1%) were included in the randomized HIT SIOP PNET 4 trial. From 2001 to 2011 an additional 206 patients were registered to the HIT 2000 study center and underwent the identical central review program. Three different radiation therapy protocols were applied. Genetically defined tumor entity (former molecular subgroup) was available for 157 patients.
RESULTS
Median follow-up time was 7.3 (range, 0.09-13.86) years. There was no difference between HIT SIOP PNET 4 trial patients and observational patients outside the randomized trial, with 7 years progression-free survival rates (PFS) of 79.5% ± 3.1% versus 78.7% ± 3.1% ( = .62). On univariate analysis, the time interval between surgery and irradiation (≤ 48 days vs ≥ 49 days) showed a strong trend to affect PFS (80.4% ± 2.2% vs 64.6% ± 9.1%; = .052). Furthermore, histologically and genetically defined tumor entities and the extent of postoperative residual tumor influenced PFS. On multivariate analyses, a genetically defined tumor entity wingless-related integration site-activated vs non-wingless-related integration site/non-SHH, group 3 hazard ratio, 5.49; = .014) and time interval between surgery and irradiation (hazard ratio, 2.2; = .018) were confirmed as independent risk factors.
CONCLUSIONS
Using a centralized review program and risk-stratified therapy for all patients registered to the study center, outcome was identical for patients with nonmetastatic medulloblastoma treated on and off the randomized HIT SIOP PNET 4 trial. The prognostic values of prolonged time to RT and genetically defined tumor entity were confirmed.
目的
我们旨在比较随机试验内和试验外的治疗结果，并确定在奥地利、瑞士和德国接受治疗的非转移性髓母细胞瘤大型回顾性队列中影响预后的因素。
方法和材料
评估了年龄在4至21岁之间、2001年至2011年间接受原发性神经外科手术切除的非转移性髓母细胞瘤患者（n = 382）。2001年至2006年期间，这些患者中有176例（46.1%）被纳入随机化的HIT SIOP PNET 4试验。2001年至2011年期间，另有206例患者在HIT 2000研究中心登记，并接受了相同的中心审查程序。应用了三种不同的放射治疗方案。157例患者可获得基因定义的肿瘤实体（原分子亚组）。
结果
中位随访时间为7.3（范围，0.09 - 13.86）年。HIT SIOP PNET 4试验患者与随机试验外的观察性患者之间无差异，7年无进展生存率（PFS）分别为79.5% ± 3.1%和78.7% ± 3.1%（P = 0.62）。单因素分析显示，手术与放疗之间的时间间隔（≤ 48天与≥ 49天）对PFS有显著影响趋势（80.4% ± 2.2%与64.6% ± 9.1%；P = 0.052）。此外，组织学和基因定义的肿瘤实体以及术后残留肿瘤的范围影响PFS。多因素分析确定，基因定义的肿瘤实体无翅相关整合位点激活型与非无翅相关整合位点/非SHH，3组风险比为5.49；P = 0.014）以及手术与放疗之间的时间间隔（风险比为2.2；P = 0.018）是独立危险因素。
结论
通过对研究中心登记的所有患者采用集中审查程序和风险分层治疗，随机化的HIT SIOP PNET 4试验内外治疗的非转移性髓母细胞瘤患者的预后相同。放疗时间延长和基因定义的肿瘤实体的预后价值得到证实。
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