Department of Radiotherapy and Radiation Oncology, University of Leipzig Medical Center, Stephanstraße 9a, 04103, Leipzig, Germany.
Division of Pediatric Hematology and Oncology, University Medical Center Goettingen, Goettingen, Germany.
Strahlenther Onkol. 2018 Mar;194(3):215-224. doi: 10.1007/s00066-017-1218-6. Epub 2017 Oct 11.
As the efficacy of all pediatric high-grade glioma (HGG) treatments is similar and still disappointing, it is essential to also investigate the toxicity of available treatments.
Prospectively recorded hematologic and nonhematologic toxicities of children treated with radiochemotherapy in the HIT GBM-C/D and HIT-HGG-2007 trials were compared. Children aged 3-18 years with histologically proven HGG (WHO grade III and IV tumors) or unequivocal radiologic diagnosis of diffuse intrinsic pontine glioma (DIPG) were included in these trials. The HIT-HGG-2007 protocol comprised concomitant radiochemotherapy with temozolomide, while cisplatinum/etoposide (PE) and PE plus ifosfamide (PEI) in combination with weekly vincristine injections were applied during radiochemotherapy in the HIT GBM-C/D protocol.
Regular blood counts and information about cellular nadirs were available from 304 patients (leukocytes) and 306 patients (thrombocytes), respectively. Grade 3-4 leukopenia was much more frequent in the HIT GBM-C/D cohort (n = 88, 52%) vs. HIT-HGG-2007 (n = 13, 10%; P <0.001). Grade 3-4 thrombopenia was also more likely in the HIT GBM-C/D cohort (n = 21, 12% vs. n = 3,2%; P <0.001). Grade 3-4 leukopenia appeared more often in children aged 3-7 years (n = 38/85, 45%) than in children aged 8-12 years (n = 39/120, 33%) and 13-18 years (24/100, 24%; P =0.034). In addition, sickness was more frequent in the HIT GBM-C/D cohort (grade 1-2: 44%, grade 3-4: 6% vs. grade 1-2: 28%, grade 3-4: 1%; P <0.001).
Radiochemotherapy involving cisplatinum-based polychemotherapy is more toxic than radiotherapy in combination with temozolomide. Without evidence of differences in therapeutic efficacy, the treatment with lower toxicity, i. e., radiotherapy with temozolomide should be used.
由于所有儿科高级别神经胶质瘤(HGG)治疗的疗效相似且仍令人失望,因此有必要调查现有治疗方法的毒性。
比较了在 HIT GBM-C/D 和 HIT-HGG-2007 试验中接受放化疗的儿童的前瞻性记录的血液学和非血液学毒性。这些试验纳入了组织学证实的 HGG(世卫组织 3 级和 4 级肿瘤)或弥漫性内在脑桥胶质瘤(DIPG)明确的影像学诊断的 3-18 岁儿童。HIT-HGG-2007 方案包括替莫唑胺联合放化疗,而 HIT GBM-C/D 方案中,在放化疗期间应用顺铂/依托泊苷(PE)和 PE 联合异环磷酰胺(PEI)联合每周长春新碱注射。
304 例患者(白细胞)和 306 例患者(血小板)分别有定期的血液计数和细胞最低点信息。HIT GBM-C/D 队列(n=88,52%)发生 3-4 级白细胞减少症的频率明显高于 HIT-HGG-2007 队列(n=13,10%;P<0.001)。HIT GBM-C/D 队列中也更可能发生 3-4 级血小板减少症(n=21,12%vs.n=3,2%;P<0.001)。3-7 岁儿童(n=38/85,45%)发生 3-4 级白细胞减少症的频率明显高于 8-12 岁儿童(n=39/120,33%)和 13-18 岁儿童(n=24/100,24%;P=0.034)。此外,HIT GBM-C/D 队列中恶心更为常见(1-2 级:44%,3-4 级:6%vs.1-2 级:28%,3-4 级:1%;P<0.001)。
含顺铂的联合化疗的放化疗比放疗联合替莫唑胺的毒性更大。在没有治疗效果差异的证据的情况下,应使用毒性较低的治疗方法,即放疗联合替莫唑胺。