Jazmati Danny, Butzer Sarina, Hero Barbara, Ahmad Khalil Dalia, Merta Julien, Bäumer Christian, Plum Gina, Fuchs Jörg, Koerber Friederike, Steinmeier Theresa, Peters Sarah, Doyen Jerome, Thole Theresa, Schmidt Matthias, Blase Christoph, Tippelt Stephan, Eggert Angelika, Schwarz Rudolf, Simon Thorsten, Timmermann Beate
Department of Particle Therapy, University Hospital Essen, West German Proton Therapy Centre Essen (WPE), West German Cancer Center (WTZ), Essen, Germany.
Children's Hospital, University of Cologne, Cologne, Germany.
Front Oncol. 2021 Jan 20;10:617506. doi: 10.3389/fonc.2020.617506. eCollection 2020.
Radiotherapy (RT) is an integral part of the interdisciplinary treatment of patients with high-risk neuroblastoma (NB). With the continuous improvements of outcome, the interest in local treatment strategies that reduce treatment-related side effects while achieving optimal oncological results is growing. Proton beam therapy (PBT) represents a promising alternative to conventional photon irradiation with regard to the reduction of treatment burden.
Retrospective analysis of children with high or intermediate risk NB receiving PBT of the primary tumor site during first-line therapy between 2015 and 2020 was performed. Data from the prospective in-house registry Standard Protonentherapie WPE - Kinder- (KiProReg) with respect to tumor control and treatment toxicity were analyzed. Adverse events were classified according to CTCAE Version 4 (V4.0) before, during, and after PBT.
In total, 44 patients (24 male, 20 female) with high (n = 39) or intermediate risk NB (n = 5) were included in the analysis. Median age was 3.4 years (range, 1.4-9.9 years). PBT doses ranged from 21.0 to 39.6 Gray (Gy) (median 36.0 Gy). Five patients received PBT to the MIBG-avid residual at the primary tumor site at time of PBT according to the NB-2004 protocol. In 39 patients radiation was given to the pre-operative tumor bed with or without an additional boost in case of residual tumor. After a median follow-up (FU) of 27.6 months, eight patients developed progression, either local recurrence (n = 1) or distant metastases (n = 7). Four patients died due to tumor progression. At three years, the estimated local control, distant metastatic free survival, progression free survival, and overall survival was 97.7, 84.1, 81.8, and 90.9%, respectively. During radiation, seven patients experienced higher-grade (CTCAE ≥ °3) hematologic toxicity. No other higher grade acute toxicity occurred. After PBT, one patient developed transient myelitis while receiving immunotherapy. No higher grade long-term toxicity was observed up to date.
PBT was a well tolerated and effective local treatment in children with high and intermediate risk NB. The role of RT in an intensive multidisciplinary treatment regimen remains to be studied in the future in order to better define timing, doses, target volumes, and general need for RT in a particularly sensitive cohort of patients.
放射治疗（RT）是高危神经母细胞瘤（NB）患者多学科治疗的重要组成部分。随着治疗效果的不断改善，人们越来越关注在实现最佳肿瘤学效果的同时减少治疗相关副作用的局部治疗策略。质子束治疗（PBT）在减轻治疗负担方面是传统光子照射的一种有前景的替代方法。
对2015年至2020年一线治疗期间接受原发肿瘤部位PBT的高危或中危NB儿童进行回顾性分析。分析了来自前瞻性内部登记处标准质子治疗WPE - 儿童（KiProReg）中关于肿瘤控制和治疗毒性的数据。根据PBT前、期间和之后的CTCAE第4版（V4.0）对不良事件进行分类。
总共44例患者（24例男性，20例女性）纳入分析，其中高危NB患者39例，中危NB患者5例。中位年龄为3.4岁（范围1.4 - 9.9岁）。PBT剂量范围为21.0至39.6格雷（Gy）（中位剂量36.0 Gy）。根据NB - 2004方案，5例患者在PBT时对原发肿瘤部位的MIBG摄取残留病灶进行了PBT。39例患者对术前肿瘤床进行了放疗，如有残留肿瘤则额外增加剂量。中位随访（FU）27.6个月后，8例患者出现进展，包括局部复发（1例）或远处转移（7例）。4例患者因肿瘤进展死亡。三年时，估计的局部控制率、无远处转移生存率、无进展生存率和总生存率分别为97.7%、84.1%、81.8%和90.9%。放疗期间，7例患者出现高级别（CTCAE≥3级）血液学毒性。未发生其他高级别急性毒性反应。PBT后，1例患者在接受免疫治疗时发生短暂性脊髓炎。迄今为止，未观察到高级别长期毒性反应。
PBT是高危和中危NB儿童耐受性良好且有效的局部治疗方法。RT在强化多学科治疗方案中的作用，未来仍有待进一步研究以便更好地确定在这类特别敏感的患者群体中RT的时机、剂量、靶区体积以及总体需求。
