Department of Radiation Oncology, University Medical Center Leipzig, Stephan-Str. 9a, 04103, Leipzig, Germany,
Strahlenther Onkol. 2014 Apr;190(4):377-81. doi: 10.1007/s00066-013-0513-0. Epub 2014 Feb 19.
High-grade (HGG) and diffuse intrinsic pontine gliomas (DIPG) with primary metastatic spread are extremely rare and have a dismal prognosis. Analogous to simultaneous radiochemotherapy in non-metastatic HGG and DIPG, concurrent craniospinal irradiation (CSI) and metronomic temozolomide (metroTMZ) may represent a reasonable therapeutic approach. However, the antitumor efficacy and toxicity of this treatment still have to be investigated.
Between March 2007 and December 2012, six children with primary metastatic HGG (n = 4) or DIPG (n = 2) received CSI and concurrent metroTMZ based on individual treatment recommendations and, in some cases, within the HIT-HGG 2007 multicenter trial. Outcome and treatment-related toxicities were evaluated.
All patients received irradiation to the entire craniospinal axis (35.2 Gy, n = 5; 36 Gy, n = 1:) and 5 received a local boost to macroscopic tumor deposits. Simultaneously, metroTMZ (75 mg/m(2)/day, n = 5; 60 mg/m(2)/day, n = 1) was administered. Additionally, 1 patient received nimotuzumab once per week. Within a median follow-up of 10.0 months (range 6.5-18.7 months), all patients experienced disease progression and 5 patients died. Median progression-free survival was 4.0 ± 0.8 months (range 2.4-10.7 months) and median overall survival was 7.6 ± 3.5 months (range 4.0-17.6 months). Acute myelosuppression most severely limited application of this aggressive treatment strategy. Severe hematotoxicities (≥ grade 3) occurred in all patients and metroTMZ had to be interrupted or discontinued in 4 out of 6 cases.
Concurrent CSI and metroTMZ might represent a feasible treatment approach for primary metastatic HGG and DIPG. On the basis of our experience, severe but manageable acute hematotoxicity has to be expected. An international effort is warranted to reassess the efficacy and toxicity of this approach within a prospective study.
高级别（HGG）和弥漫性内在脑桥胶质瘤（DIPG）伴原发性转移极为罕见，预后极差。类似于非转移性 HGG 和 DIPG 的同步放化疗，颅脊髓照射（CSI）和节拍替莫唑胺（metroTMZ）同步治疗可能是一种合理的治疗方法。然而，这种治疗的抗肿瘤疗效和毒性仍有待研究。
2007 年 3 月至 2012 年 12 月，6 例原发性转移性 HGG（n=4）或 DIPG（n=2）患儿根据个体治疗建议接受 CSI 和同步 metroTMZ 治疗，部分患儿在 HIT-HGG 2007 多中心试验中接受治疗。评估疗效和治疗相关毒性。
所有患者均接受全颅脊髓轴照射（35.2Gy，n=5；36Gy，n=1），5 例患者局部接受肿瘤靶区剂量增强。同时给予 metroTMZ（75mg/m2/天，n=5；60mg/m2/天，n=1）。此外，1 例患者每周给予尼妥珠单抗一次。中位随访时间为 10.0 个月（范围 6.5-18.7 个月），所有患者均出现疾病进展，5 例患者死亡。中位无进展生存期为 4.0±0.8 个月（范围 2.4-10.7 个月），中位总生存期为 7.6±3.5 个月（范围 4.0-17.6 个月）。急性骨髓抑制严重限制了这种强化治疗策略的应用。所有患者均发生严重的血液学毒性（≥3 级），4 例患者因 metroTMZ 中断或停药。
同步 CSI 和 metroTMZ 可能是原发性转移性 HGG 和 DIPG 的可行治疗方法。根据我们的经验，严重但可管理的急性血液学毒性是可以预料的。需要进行国际努力，在前瞻性研究中重新评估这种方法的疗效和毒性。
