Abd El-Aal Hisham H, Mokhtar Mohsen M, Habib E E, El-Kashef Amr T, Fahmy Ezzat S
The Department of Clinical Oncology, Pediatric Oncology Unit, Medical School, Cairo University.
J Egypt Natl Canc Inst. 2005 Dec;17(4):301-7.
The aim of this study is to assess treatment results of 48 pediatric high-risk medulloblastoma cases that were treated by surgery, radiotherapy with or without chemotherapy. The impact of adjuvant combination chemotherapy on treatment results will be assessed. Forty-eight cases of pediatric high-risk medulloblastoma treated from July 2001 to July 2004 were randomized into two groups. The first (group I) included 21 patients who received postoperative craniospinal radiation therapy (36Gy+boost 20Gy to the posterior fossa). The second (group II) included 27 cases who received postoperative combination cranio-spinal radiation therapy (with the same dose as the first group) and chemotherapy (vincristine, etoposide, cisplatin). Both groups were compared as regards overall survival (OS), disease free survival (DFS), response rate and treatment toxicity. In-group I, complete remission (CR) was achieved in 71.4% of the cases; partial remission (PR) in 14.3% of the patients; stationary disease (SD) in 14.3% and none of the cases suffered from progressive disease. The three-year OS was 69.5% and the three-year DFS was 61.3%. In-group II, CR was achieved in 59.3% of the cases; PR in 3.7%; SD in 3.7% and PD in 37.3% of the cases. The three-year OS was 48.4% and the 3-year DFS was 48.9%. Regarding acute treatment toxicity in group I, nine patients (31.5%) developed grade I myelo-suppression and seven cases (24.5%) developed grade II myelo-suppression with three to five days treatment interruption. Whereas in group II, 13 patients (45.5%) developed grade I myelosuppression and seven cases (24.5%) developed grade II myelo-suppression requiring interruption of treatment for a period ranging from five to seven days with spontaneous recovery. In group I no other acute toxicity was recognized, whereas in group II other toxicities related to chemotherapy were noticed. For example, three patients (11%) developed peripheral neuritis during the course of treatment and two patients (7%) developed renal impairment, which responded to medical treatment. Late treatment toxicity, manifested as reduction in intelligence quotient (IQ), was noticed, which makes conventional treatment of medulloblastoma unsatisfactory. In group I; 13 patients (62%) suffered a reduction of 8-20% in IQ in comparison to their normal siblings, whereas in Group II; 13 patients (48%) developed a reduction in IQ ranging from 12-21%.
The current treatment of medulloblasotma has a detrimental effect on long-term survivors. Whereas acute toxicity is considered mild and tolerable, late toxicity regarding diminution in IQ makes current treatment unsatisfactory because of the long-term mental disability of the cured patients. We believe that, the poorer outcome in the chemo-radiation group was due to the treatment interruption during radiation therapy caused by myelosuppression since the incidence of myelosuppression was higher in the chemo-radiation group and the recovery time was longer.
本研究旨在评估48例接受手术、放疗(联合或不联合化疗)的儿童高危髓母细胞瘤病例的治疗结果。将评估辅助联合化疗对治疗结果的影响。2001年7月至2004年7月治疗的48例儿童高危髓母细胞瘤病例被随机分为两组。第一组(I组)包括21例接受术后颅脊髓放射治疗(36Gy + 后颅窝加量20Gy)的患者。第二组(II组)包括27例接受术后联合颅脊髓放射治疗(与第一组剂量相同)及化疗(长春新碱、依托泊苷、顺铂)的病例。比较两组的总生存期(OS)、无病生存期(DFS)、缓解率及治疗毒性。I组中,71.4%的病例达到完全缓解(CR);14.3%的患者部分缓解(PR);病情稳定(SD)的占14.3%,无病例病情进展。三年总生存率为69.5%,三年无病生存率为61.3%。II组中,59.3%的病例达到CR;3.7%为PR;3.7%为SD,37.3%的病例病情进展。三年总生存率为48.4%,三年无病生存率为48.9%。关于I组的急性治疗毒性,9例患者(31.5%)出现I级骨髓抑制,7例患者(24.5%)出现II级骨髓抑制,治疗中断3至5天。而II组中,13例患者(45.5%)出现I级骨髓抑制,7例患者(24.5%)出现II级骨髓抑制,需要中断治疗5至7天,之后自行恢复。I组未发现其他急性毒性,而II组注意到与化疗相关的其他毒性。例如,3例患者(11%)在治疗过程中出现周围神经炎,2例患者(7%)出现肾功能损害,经治疗后缓解。注意到存在晚期治疗毒性,表现为智商(IQ)降低,这使得髓母细胞瘤的传统治疗并不理想。I组中,与正常同胞相比,13例患者(62%)的智商降低了8 - 20%,而II组中,13例患者(48%)的智商降低了12 - 21%。
目前髓母细胞瘤的治疗对长期存活者有不利影响。虽然急性毒性被认为较轻且可耐受,但由于治愈患者存在长期智力残疾,智商降低的晚期毒性使得目前的治疗并不理想。我们认为,放化疗组结果较差是由于骨髓抑制导致放疗期间治疗中断,因为放化疗组骨髓抑制的发生率较高且恢复时间较长。