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1、髓母细胞瘤的放射治疗,1,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(1646,2,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,3,分级,4,治疗方案,标准治疗方案(“Philadelphia protocol”) 手术 放疗:术后28天
2、内开始。 化疗(VCP):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,5,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,6,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,7,Craniospinal irradiation (CSI):me
3、thods,俯卧位,双手置于体侧 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,8,9,Craniospinal irradiation (CSI):dose,Prospective randomised trial of chemotherapy given before radiotherapy in childhood medulloblastoma: International Society of Paediatric Oncology (
4、SIOP) and the (German) Society of Paediatric Oncology (GPO)SIOP II. Med Pediatr Oncol 25:166-178, 1995,10,23.4GyCSI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-te
5、rm results from a prospective, multicentre trial http:/oncology.the Vol 7 October 2006,11,23.4GyCSI对智力的影响(POG-8631,Journal of Clinical Oncology, Vol 16, No 5, pp. 172328, 1998,12,CSI:cranial-spinal junction site,THE CRANIAL-SPINAL JUNCTION IN MEDULLOBLASTOMA: DOES IT MATTER? Int. J. Radiation Oncolo
6、gy Biol. Phys., Vol. 44, No. 1, pp. 8184, 1999,13,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,14,SRT Boost to posterior fossa,POSTERIOR FOSSA BOOST IN MEDULLOBLASTOMA: AN ANALYSIS OF DOSE TO SURROUNDING STRUCTURES USING 3-DIMENSIONAL (CONFORMAL) RADIOTHERAPY I
7、nt. J. Radiation Oncology Biol. Phys., Vol. 46, No. 2, pp. 281286, 2000,15,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,16,甲低,1.HYPOTHYROIDISM IN CHILDREN WITH MEDULLOBLASTOMA: A COMPARISON OF 3600 AND 2340 cGY CRANIOSPINAL RADIOTHERAPY Int. J. Radiation Oncology Biol. Phys., V
8、ol. 53, No. 3, pp. 543547, 2002 2. Thyroid Dysfunction as a Late Effect in Survivors of Pediatric Medulloblastoma /Primitive Neuroectodermal Tumors A Comparison of Hyperfractionated versus Conventional Radiotherapy Cancer 1997;80:798804,17,认知障碍,MODELING RADIATION DOSIMETRY TO PREDICT COGNITIVE OUTCO
9、MES IN PEDIATRIC PATIENTS WITH CNS EMBRYONAL TUMORS 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,18,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
10、-c); 其他方案: MTX鞘内注射 CTX、VCR、VP-16、CCNU、CBP等组合,19,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, multicentre trial http:/oncology.the Vol
11、 7 October 2006,20,手术+放/化疗,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 91 Int. J. Radiation Oncology Biol
12、. Phys., Vol. 46, No. 2, pp. 269279, 2000,21,维持化疗对6岁以上低危组更有效; 新辅助化疗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: R
13、ESULTS OF THE GERMAN PROSPECTIVE RANDOMIZED TRIAL HIT 91 Int. J. Radiation Oncology Biol. Phys., Vol. 46, No. 2, pp. 269279, 2000,22,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,23,手术+化疗-结果,Treatment of Early Childhood Medulloblastoma by Postoperative Chemotherapy Alone N Engl J Med 2005;352:978-86,24,影响预后的因素,年龄
14、临床分级 术式 后颅窝生物有效剂量(BED) 放疗持续时间,25,On multivariate analysis, 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 Medullob
15、lastoma Am J Clin Oncol (CCT) 26(1): 5559, 2003,影响因素的多变量分析,26,On multivariate analysis, 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 T
16、reatment Duration in Medulloblastoma Am J Clin Oncol (CCT) 26(1): 5559, 2003,影响因素的多变量分析,27,年龄,Timing of Radiation in Children With Medulloblastoma/PNET Pediatr Blood Cancer 2007;48:416422,28,CSF cytology,Timing of Radiation in Children With Medulloblastoma/PNET Pediatr Blood Cancer 2007;48:416422,29
17、,手术切除范围,Timing of Radiation in Children With Medulloblastoma/PNET Pediatr Blood Cancer 2007;48:416422,30,后颅窝BED,Timing of Radiation in Children With Medulloblastoma/PNET Pediatr Blood Cancer 2007;48:416422,31,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, multicentre trial http:/ Vol 7 October 2006,病理及免疫组化类型,32,放疗持续时间,Pro
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