1、髓母细胞瘤的放射治疗,曹嫣娜,概述,来源：胚胎残留的未分化的原始髓样上皮细胞。部位：第四脑室顶上的小脑蚓部。发病率：2.1/10万/年，占儿童颅内恶性肿瘤的1520%。疾病特点：恶性程度高。 生长极其迅速； 手术难以完整切除； 肿瘤细胞易沿脑脊液播散（1646%）。,临床表现,颅内压增高：头痛、呕吐、视神经乳头水肿小脑损害：躯干性共济失调为主其它：复视、面瘫、强迫头位、头颅增大、病理反射阳性、呛咳、小脑危象、蛛网膜下腔出血脊髓转移灶症状：背部或双下肢痛、进行性加重的截瘫或四肢瘫,分级,治疗方案,标准治疗方案(“Philadelphia protocol”)手术放疗：术后28天内开始。化疗(VC
2、P)：放疗中VCR1.5mg/m2/w，共8周； 放疗后6周开始CCNU75mg/m2 DDP75mg/m2 VCR1.5mg/m2/w3w， 每6周一个周期，共8个周期。,放疗剂量,低危组：CSI 23.4Gy/13f+后颅窝加量至 54Gy高危组：CSI 36Gy/20f+后颅窝加量至54Gy,放疗技术,常规分割CSI+ Boost to posterior fossa 超分割CSI+ Boost to posterior fossa SRT Boost to posterior fossa,Craniospinal irradiation (CSI):methods,俯卧位，双手置于体侧
3、头部两侧对穿野照射全脑及上段颈髓单后野照射脊髓各野皮肤间隔1cm每照射10Gy移动一次射野以减少各野间交叉高剂量6MV-X线照射剂量(DT)：23.4Gy36Gy, 1.8Gy/f,Craniospinal irradiation (CSI):dose,Prospective randomised trial of chemotherapy given before radiotherapy in childhood medulloblastoma: International Society of Paediatric Oncology (SIOP) and the (German) Soc
4、iety of Paediatric Oncology (GPO)SIOP II. Med Pediatr Oncol 25:166-178, 1995,23.4GyCSI的疗效,Risk-adapted craniospinal radiotherapy followed by high-dose chemotherapy and stem-cell rescue in children with newly diagnosed medulloblastoma (St Jude Medulloblastoma-96): long-term results from a prospective
5、, multicentre trial http:/oncology.the Vol 7 October 2006,23.4GyCSI对智力的影响(POG-8631),Journal of Clinical Oncology, Vol 16, No 5, pp. 172328, 1998,CSI:cranial-spinal junction site,THE CRANIAL-SPINAL JUNCTION IN MEDULLOBLASTOMA: DOES IT MATTER? Int. J. Radiation Oncology Biol. Phys., Vol. 44, No. 1, p
6、p. 8184, 1999,超分割放疗,Twice-daily l-Gy fractions were administered separated by 4-6 h.放疗剂量和射野同常规分割,SRT Boost to posterior fossa,POSTERIOR FOSSA BOOST IN MEDULLOBLASTOMA: AN ANALYSIS OF DOSE TO SURROUNDING STRUCTURES USING 3-DIMENSIONAL (CONFORMAL) RADIOTHERAPY Int. J. Radiation Oncology Biol. Phys., V
7、ol. 46, No. 2, pp. 281286, 2000,放疗反应,急性反应：骨髓抑制、脑水肿等；远期副作用：甲低认知障碍其它：听力减退、骨骼发育障碍、周围组织损伤继发第二恶性肿瘤等。,甲低,1.HYPOTHYROIDISM IN CHILDREN WITH MEDULLOBLASTOMA: A COMPARISON OF 3600 AND 2340 cGY CRANIOSPINAL RADIOTHERAPY Int. J. Radiation Oncology Biol. Phys., Vol. 53, No. 3, pp. 543547, 20022. Thyroid Dysfunc
8、tion as a Late Effect in Survivors of Pediatric Medulloblastoma /Primitive Neuroectodermal Tumors A Comparison of Hyperfractionated versus Conventional Radiotherapy Cancer 1997;80:798804.,认知障碍,MODELING RADIATION DOSIMETRY TO PREDICT COGNITIVE OUTCOMES IN PEDIATRIC PATIENTS WITH CNS EMBRYONAL TUMORS
9、INCLUDING MEDULLOBLASTOMA Int. J. Radiation Oncology Biol. Phys., Vol. 65, No. 1, pp. 210221, 2006,影响因素包括：受照射时年龄（小于3岁差）、照射范围（全脑差于部分脑照射）、照射剂量(低剂量较好）特别是后颅窝最大剂量、肿瘤部位（幕上好于后颅窝）。,联合化疗,常用方案：VCP(VCR+CCNU+DDP);“8 in 1” (VCR+甲强龙+CCNU+羟基脲+甲基苄肼+ DDP+CTX+Ara-c);其他方案：MTX鞘内注射CTX、VCR、VP-16、CCNU、CBP等组合,Risk-adapted
10、craniospinal radiotherapy followed by high-dose chemotherapy and stem-cell rescue in children with newly diagnosed medulloblastoma (St Jude Medulloblastoma-96): long-term results from a prospective, multicentre trial http:/oncology.the Vol 7 October 2006,手术+放/化疗,POSTOPERATIVE NEOADJUVANT CHEMOTHERA
11、PY BEFORE RADIOTHERAPY AS COMPARED TO IMMEDIATE RADIOTHERAPY FOLLOWED BY MAINTENANCE CHEMOTHERAPY IN THE TREATMENT OF MEDULLOBLASTOMA IN CHILDHOOD: RESULTS OF THE GERMAN PROSPECTIVE RANDOMIZED TRIAL HIT 91 Int. J. Radiation Oncology Biol. Phys., Vol. 46, No. 2, pp. 269279, 2000,维持化疗对6岁以上低危组更有效；新辅助化疗
12、增加放疗的骨髓抑制从而延长治疗时间；M分期高/低龄儿预后差；手术是否有残留对预后无明显影响。,POSTOPERATIVE NEOADJUVANT CHEMOTHERAPY BEFORE RADIOTHERAPY AS COMPARED TO IMMEDIATE RADIOTHERAPY FOLLOWED BY MAINTENANCE CHEMOTHERAPY IN THE TREATMENT OF MEDULLOBLASTOMA IN CHILDHOOD: RESULTS OF THE GERMAN PROSPECTIVE RANDOMIZED TRIAL HIT 91Int. J. Radi
13、ation Oncology Biol. Phys., Vol. 46, No. 2, pp. 269279, 2000,手术+化疗-方案,适用于低龄儿童、无手术残留、无转移病灶患者,手术+化疗-结果,Treatment of Early Childhood Medulloblastoma by Postoperative Chemotherapy AloneN Engl J Med 2005;352:978-86.,影响预后的因素,年龄临床分级术式后颅窝生物有效剂量（BED）放疗持续时间,On multivariate analysis, age 3 years, M0 status, 50
14、 Gy PFB dose, radiotherapy treatment duration 50 days, and use of chemotherapy correlated with better freedom from progression and posterior fossa control rates.Protracted Radiotherapy Treatment Duration in Medulloblastoma Am J Clin Oncol (CCT) 26(1): 5559, 2003.,影响因素的多变量分析,On multivariate analysis,
15、 age 3 years, M0 status, 50 Gy PFB dose, radiotherapy treatment duration 50 days, and use of chemotherapy correlated with better freedom from progression and posterior fossa control rates.Protracted Radiotherapy Treatment Duration in Medulloblastoma Am J Clin Oncol (CCT) 26(1): 5559, 2003.,影响因素的多变量分
16、析,年龄,Timing of Radiation in Children With Medulloblastoma/PNET Pediatr Blood Cancer 2007;48:416422,CSF cytology,Timing of Radiation in Children With Medulloblastoma/PNET Pediatr Blood Cancer 2007;48:416422,手术切除范围,Timing of Radiation in Children With Medulloblastoma/PNET Pediatr Blood Cancer 2007;48:
17、416422,后颅窝BED,Timing of Radiation in Children With Medulloblastoma/PNET Pediatr Blood Cancer 2007;48:416422,Risk-adapted craniospinal radiotherapy followed by high-dose chemotherapy and stem-cell rescue in children with newly diagnosed medulloblastoma (St Jude Medulloblastoma-96): long-term results
18、from a prospective, multicentre trial http:/ Vol 7 October 2006,病理及免疫组化类型,放疗持续时间,Protracted Radiotherapy Treatment Duration in Medulloblastoma Am J Clin Oncol (CCT) 26(1): 5559, 2003.,总结,髓母细胞瘤易沿脑脊液转移，需行全脑全脊髓放疗；年龄3岁、低危者(CSF-)、BED超过50Gy、放疗持续时间小于50天提示预后较好；低剂量CSI (23.4Gy) /低剂量CSI+化疗/HFRT有助于减轻低危患者远期并发症但并不能增加治愈率；术后应立即开始放疗，一般不推荐放疗前化疗；根据危险性分级选择放疗剂量和化疗方案。,谢谢！,
