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1、髓母细胞瘤的放射治疗第1页，此课件共32页哦概述概述来源：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%）。第2页，此课件共32页哦临床表现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第3页，此课件共32页哦分级分级Stage Risk staging syste
2、m Stage Changs M staging systemLow-risk Localized disease at the time of diagnosis M0 No evidence of gross subarachnoid orGroup Age 3 years hematogenous metastasis Total tumor resection or subtotal with residual tumor 1.5 cm3 High-risk Disseminated disease at the time of diagnosis M1 Microscopic tum
3、or cells found inGroup cerebrospinal fluid Age 3 years M2 Gross nodule seeding seen in the cerebellar or cerebral subarachnoid space or in the third or lateral ventricles Subtotal tumor resection with a residual tumor M3 Gross nodule seeding in the spinal 1.5 cm3 subarachnoid space metastasis M4 Ext
4、raneural第4页，此课件共32页哦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(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。第5页，此课件共32页哦放疗剂量低危组：CSI 23.4Gy/13f+后颅窝加量至 54Gy高危组：CSI 36Gy/20f+后颅窝加量至54Gy第6页，此课件共32页哦放疗技术常规分割CSI+Boost to posterior fossa 超分割CSI+Boost to post
5、erior fossa SRT Boost to posterior fossa第7页，此课件共32页哦Craniospinal irradiation(CSI):methods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第8页，此课件共32页哦第9页，此课件共32页哦Craniospinal irradiation(CSI):doseradiotherapy alone（5-year EFS）Chemotherapy+（5-year EFS
6、）standard radiotherapy reduced-dose radiotherapy60%7.8%41%8%75%7%69%8%Prospective randomised trial of chemotherapy given before radiotherapy in childhood medulloblastoma:International Society of Paediatric Oncology(SIOP)and the(German)Society of Paediatric Oncology(GPO)SIOP II.Med Pediatr Oncol 25:1
7、66-178,1995 第10页，此课件共32页哦23.4GyCSI的疗效Risk-adapted craniospinal radiotherapy followed by high-dose chemotherapy and stem-cell rescue in Risk-adapted craniospinal radiotherapy followed by high-dose chemotherapy and stem-cell rescue in children with newly diagnosed medulloblastoma(St Jude Medulloblasto
8、ma-96):long-term results from a children with newly diagnosed medulloblastoma(St Jude Medulloblastoma-96):long-term results from a prospective,multicentre trialprospective,multicentre trial http:/oncology.the Vol 7 October 2006Vol 7 October 2006第11页，此课件共32页哦23.4GyCSI对智力的影响(POG-8631)Journal of Clinic
9、al Oncology,Vol 16,No 5,pp.172328,1998第12页，此课件共32页哦CSI:cranial-spinal junction site THE CRANIAL-SPINAL JUNCTION IN MEDULLOBLASTOMA:DOES IT MATTER?Int.J.Radiation Oncology Biol.Phys.,Vol.44,No.1,pp.8184,1999Organ low junction(SD)high junction(SD)Cord 40.3Gy(0.5)38.4Gy(1.3)Thyroid gland 20.3Gy(9.2)26.
10、3Gy(0.6)Mandible 6.2Gy(0.6)10.9Gy(5.1)Larynx 8.3Gy(3.9)27.2Gy(0.4)Pharynx 11.9Gy(5.1)20.3Gy(4.8)Parotid gland 14.9Gy(4.2)14.1Gy(4.2)第13页，此课件共32页哦超分割放疗Twice-daily l-Gy fractions were administered separated by 4-6 h.放疗剂量和射野同常规分割第14页，此课件共32页哦SRT Boost to posterior fossaPOSTERIOR FOSSA BOOST IN MEDULLOB
11、LASTOMA:AN ANALYSIS OF DOSE TO SURROUNDING STRUCTURES USING 3-DIMENSIONAL(CONFORMAL)RADIOTHERAPY Int.J.Radiation Oncology Biol.Phys.,Vol.46,No.2,pp.281286,2000 第15页，此课件共32页哦放疗反应急性反应：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。第16页，此课件共32页哦甲低 Hypothyroid p值值年龄1 5岁 7/7(100%)10岁 2/10(20%)照射剂量1
12、23.4Gy+CT 10/12(83%)0.025 36Gy+CT 6/10(60%)36Gy 2/10(20%)照射方法2常规分割 21/34(62%)=0.02超分割 2/14(14%)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 Dysfunction as a Late E
13、ffect in Survivors of Pediatric Medulloblastoma/Primitive Neuroectodermal Tumors A Comparison of Hyperfractionated versus Conventional Radiotherapy Cancer 1997;80:798804.第17页，此课件共32页哦认知障碍 IQ(point decline per year)23.4Gy(CSI)+后颅窝加量 5.2 36Gy(CSI)+后颅窝加量 3.923.4Gy(CSI)+瘤床加量 2.4MODELING RADIATION DOSIME
14、TRY TO PREDICT COGNITIVE OUTCOMES 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）。第18页，此课件共32页哦联合化疗常用方案：VCP(VCR+CCNU+DDP);“8 in 1”(VCR+甲强龙+
15、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等组合第19页，此课件共32页哦Risk-adapted craniospinal radiotherapy followed by high-dose chemotherapy and stem-cell rescue in Risk-adapted craniospinal radiotherapy followed by high-dose chemotherapy and stem-cell rescue in children with newly diagn
16、osed medulloblastoma(St Jude Medulloblastoma-96):long-term results from a children with newly diagnosed medulloblastoma(St Jude Medulloblastoma-96):long-term results from a prospective,multicentre trialprospective,multicentre trial http:/oncology.the Vol 7 October 2006Vol 7 October 2006第20页，此课件共32页哦
17、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.Phys.,Vol.46,No.2,pp.2
18、69279,2000第21页，此课件共32页哦维持化疗对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:RESULTS OF THE GERMAN PROSP
19、ECTIVE RANDOMIZED TRIAL HIT 91Int.J.Radiation Oncology Biol.Phys.,Vol.46,No.2,pp.269279,2000第22页，此课件共32页哦手术+化疗-方案适用于低龄儿童、无手术残留、无转移病灶患者第23页，此课件共32页哦手术+化疗-结果Treatment of Early Childhood Medulloblastoma by Postoperative Chemotherapy AloneN Engl J Med 2005;352:978-86.第24页，此课件共32页哦影响预后的因素年龄临床分级术式后颅窝生物有效剂
20、量（BED）放疗持续时间第25页，此课件共32页哦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 Medulloblastoma Am J
21、Clin Oncol(CCT)26(1):5559,2003.影响因素的多变量分析第26页，此课件共32页哦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 Dura
22、tion in Medulloblastoma Am J Clin Oncol(CCT)26(1):5559,2003.影响因素的多变量分析第27页，此课件共32页哦年龄Timing of Radiation in Children With Medulloblastoma/PNET Pediatr Blood Cancer 2007;48:416422第28页，此课件共32页哦CSF cytologyTiming of Radiation in Children With Medulloblastoma/PNET Pediatr Blood Cancer 2007;48:416422第29页
23、，此课件共32页哦手术切除范围Timing of Radiation in Children With Medulloblastoma/PNET Pediatr Blood Cancer 2007;48:416422第30页，此课件共32页哦后颅窝BEDTiming of Radiation in Children With Medulloblastoma/PNET Pediatr Blood Cancer 2007;48:416422第31页，此课件共32页哦Risk-adapted craniospinal radiotherapy followed by high-dose chemot
24、herapy and stem-cell rescue in 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 children with newly diagnosed medulloblastoma(St Jude Medulloblastoma-96):long-term results from a prospective,multicentre trialprospective,multicentre trial http:/ Vol 7 October 2006Vol 7 October 2006病理及免疫组化类型第32页，此课件共32页哦