申戈的儿童胶质瘤的放疗.ppt

单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,*,*,儿童胶质瘤的放疗,北京解放军,307,医院 申戈,1,儿童低级别胶质瘤分类,PA,纤维性星形细胞瘤,(,毛细胞,),PMA,毛细胞黏液样星形细胞瘤,PXA,多形性黄色瘤型星形细胞瘤,OD,少突胶质细胞瘤,OA,少突星形细胞瘤,GG,神经节胶质瘤,DIT,多纤维性婴儿节细胞胶质瘤,DNT,胚胎发育不良性神经上皮瘤,AG,血管中心型胶质瘤,Bergthold,G,1,Bandopadhayay,P,2,Bi WL,Biochim,Biophys,Acta,.,2014 Apr;1845(2):294-307.,2,儿童低级别胶质瘤分类与年龄的关系,Bergthold,G,1,Bandopadhayay,P,2,Bi WL,Biochim,Biophys,Acta,.,2014 Apr;1845(2):294-307.,3,Interplay among BRAF,p16,p53,and MIB1 inpediatriclow-gradegliomas.(2012),BRAF,重排及,BRAF V600E,位点突变与,PLGG,复发有关,本文回顾分析,198,例,PLGG,，其中,40,例进行了辅助治疗,BRAF,重排、,BRAF V600E,p16/CDKN2A,缺失、,p53,过表达及,MIB1,增殖指数,BRAF,重排、,p16,缺失者：,PFS,短,(P=.04).,MIB1,增殖指数高者辅助治疗效果差于,BRAF,重排、,p16-,无缺失者,(P=.08).,多因素分析预后差最强相关因素：位于中线,(P=.0001),及,p16,缺失,(P=.03).,BRAF V600E,突变与疾病进展有相关的趋势,(P=.07),BRAF,重排的预后影响中等,(P=.15),Horbinski,C,1,Nikiforova,MN,Hagenkord,JM,Neuro Oncol.,2012 Jun;14(6):777-89.,4,(A)PFS,，中线,vs,小脑：,P.0001,；,0003,vs,大脑,;(B)OS,，中线,vs,小脑,P.001,；,vs,大脑,p=.17,。中线肿瘤：间脑,diencephalon,(,丘脑及下丘脑,),、中脑,midbrain,、脑干,brainstem,及脊髓,spinal,cord(DMBS,),还包括基底节区,basal ganglia,Horbinski,C,1,Nikiforova,MN,Hagenkord,JM,Neuro Oncol.,2012 Jun;14(6):777-89.,5,(A),位于小脑的肿瘤,BRAF,重排率高于大脑及,DMBS.*P.001,；,(BF)BRAF,重排对,PFS or OS,影响不明显,Horbinski,C,1,Nikiforova,MN,Hagenkord,JM,Neuro Oncol.,2012 Jun;14(6):777-89.,6,(A),大脑肿瘤,BRAF V600E,突变高,(*P.05),；,(B),BRAF V600E,对,PFS or OS,影响不大,in(CF),Horbinski,C,1,Nikiforova,MN,Hagenkord,JM,Neuro Oncol.,2012 Jun;14(6):777-89.,7,不同部位肿瘤的,p16,缺失情况区别不大,p=.64,大脑肿瘤,p16,缺失时,PFS,差,(C),所有入组的胶质瘤,p16,缺失时,PFS,也差,Horbinski,C,1,Nikiforova,MN,Hagenkord,JM,Neuro Oncol.,2012 Jun;14(6):777-89.,8,Transcriptional profiles of,pilocytic,astrocytoma,are related to their three different locations,but not to radiological tumor features.,毛细胞星型胶质瘤预后好，有时也会出现复发或脑膜播散,原发于幕上或幕下者，分子类型不同,86,例毛细胞星型胶质瘤，,55,男、,31,女，,14,个月,-17,岁，平均年龄,7,岁,40,例小脑、,23,视路,/,下丘脑、,21,例大脑、,2,例脑干,按,MRI,分为,4,个亚型：无囊壁强化；有囊壁强化；实性中心坏死；实性为主,81,例仅手术并得到根治，,5,例出现了进展,8,个亚组：大脑半球,(M1);,视路或下丘脑,(M2);,囊壁无强化,(M3R1),；囊壁有强化,(M3R2),；实性有坏死,(M3R3),；实性,(M3R4),；与,NF1,相关肿瘤,;,进展,(P2).,生物信息分析表明基因表达模式与肿瘤的部位显著相关，,The most prominent differences were noted for IRX2,PAX3,CXCL14,LHX2,SIX6,CNTN1 and SIX1 genes expression even within different compartments of the,supratentorial,region.,与影像学特点的关系很小,Zakrzewski,K,1,Jarzb,M,2,Pfeifer A,BMC Cancer.,2015 Oct 24;15:778.,9,Zakrzewski,K,1,Jarzb,M,2,Pfeifer A,BMC Cancer.,2015 Oct 24;15:778.,PA,的部位：,a,视路及下丘脑,b,大脑半球,.,c,小脑,.d,脑干,PA,的影像学特点：,a,囊壁有强化；,b,囊壁无强化；,C,中心有坏死,d,实体肿瘤,10,Zakrzewski,K,1,Jarzb,M,2,Pfeifer A,BMC Cancer.,2015 Oct 24;15:778.,11,Pediatriclow-grade,ganglioglioma,:epidemiology,treatments,and outcome analysis on 348 children from the surveillance,epidemiology,and end results database.(2015,美国神经节胶质瘤,),占所有,CNS,的,0.5%,占儿童,CNS,的,1-5%,年龄,0-19,岁，,low-grade,GGs,，共,348,例，,2004-2010,中位随访,37,个月，男,208,59.8%,，女,140,40.2%,，,P 10,岁，,3.5%1,岁；,50%,位于颞叶，,3.7%-3.5%,位于脑干及脊髓,91.6%,进行了手术，,68.3%,全切；,3.2%,进行了放疗,92%,，除外,1,岁以下,(43.2%),GG,年龄长些的男孩多，多数可以全切，放疗少用，多数预后良好,Dudley RW,1,Torok,MR,Gallegos DR,Neurosurgery.,2015 Mar;76(3):313-9;,12,颞叶,额叶,顶叶,小脑,重叠脑区,枕叶,脑干,脑室,NOS,脑内,NOS,脊髓,端脑,视神经,脑膜,垂体,Dudley RW,1,Torok,MR,Gallegos DR,Neurosurgery.,2015 Mar;76(3):313-9;,13,Dudley RW,1,Torok,MR,Gallegos DR,Neurosurgery.,2015 Mar;76(3):313-9;,14,Long-term outcome of centrally located low-grade,glioma,inchildren.(2013,美国德州,),1987-2008,，,47,例，中位随访,79,个月,所有患者：,5,年,OS,及,PFS,：,96%,、,53%,放疗方案：,11,例,3D-CRT,，,1,例质子,化疗方案：,21,例卡铂,+,长春新碱；,4,例卡铂,+,长春新碱,+TMZ,(ACNS0223,方案,),；,2,例,卡铂,+,长春新碱,+CTX,(POG9436,方案,),；,1,例卡铂,+Vp-16,开始进行放疗者：,12,例，中位,11,岁,(3-15),，,5,年,PFS,为,76%,开始进行化疗者：,28,例，,2,岁,(0-8),，,37%,，,P=.02,化疗进展又进行了放疗者，放疗后,5,年,PFS,为,55%,5,岁的患者更易出现内分泌异常,P20,年,Williams NL,1,Rotondo,RL,Bradley JA,et al.,Am J,Clin,Oncol,.,2016 Jan 22.,24,年龄与,FFE,Williams NL,1,Rotondo,RL,Bradley JA,et al.,Am J,Clin,Oncol,.,2016 Jan 22.,25,23,例长期生存者,2,级以上晚期毒性，,15,例,3,级以上毒性,Cognitive disturbance,例,%,Grade 2,5,(22),Grade 3,7,(30),Hearing loss,1,(4),Any endocrine deficiency6,(26),Hydrocephalus(,脑水肿,)/persistent shunt,分流,2,(9),Cerebrovascular,event,3,(13),Radionecrosis,1,(4),Secondary tumor,5,(22),1,例患者放疗后,8,年单侧听力下降需要助听器，,多数垂体周围肿瘤放疗后需要内分泌药物替代治疗，,3,例术后出现全垂体功能减退，需要甲状腺激素、,ACTH,、生长,(GH),、促性激素释放激素。,另外,3,例术后不需要，放疗后才需要，,1,例,GH,、,1,例甲状腺激素、,1,例需要,3,种,(,甲状腺激素、,ACTH,及促性激素释放激素,),Williams NL,1,Rotondo,RL,Bradley JA,et al.,Am J,Clin,Oncol,.,2016 Jan 22.,26,晚期损伤,4,例因肿瘤或手术出现运动障碍，放疗后加重；,4,例中有,2,例治疗后的无力及共济失调好转；,1,例放疗前需要坐轮椅，放疗后无好转。,2,例脑水肿严重需要分流，,1,例出现有症状的脑坏死需要手术；,13,例因视路或下丘脑肿瘤出现视力下降，无患者放疗后出现视力视力下降。,3,例放疗后血管病变：,1,例下丘脑,54Gy,后多次出现小中风,(,暂时性缺血中风,),，放疗后,20,年死于脑干出血；,1,例小脑受照,55Gy,后,34,年,(52,岁,),出现多次卒中致偏瘫、生活不能自理,52,；,1,例放疗后,11,年出现基底神经节区梗塞改变，,7,年后死于肿瘤进展,4,例患者出现,5,个第二肿瘤。,3,例死于第二肿瘤，分别为治疗后,10,21,及,33,年。,2,个良性肿瘤为放疗后,21,、,34,年，手术切除了。第,1,例小脑胶质瘤放疗,50Gy,后,24,年,出现,岩斜区脑膜瘤，再放疗,50.4 Gy.3,年后出现小脑胶质肉瘤，,STR,及,TMZ,治疗,1,年后死亡,(,治疗后,33,年,),；第,2,例放疗后,21,年死于恶性实体瘤；第,3,例视路胶质瘤,7,岁时受照,50Gy,，,10,年后出现视路胶质母细胞瘤，,1年后去世；第,4,例小脑放疗,55Gy,，,34,年后出现脑膜瘤,总之，,3,例死于第二肿瘤，,4,例死于放疗并发症,Williams NL,1,Rotondo,RL,Bradley JA,et al.,Am J,Clin,Oncol,.,2016 Jan 22.,27,Clinical and treatment factors determining long-term outcomes for adult survivors of childhood low-,gradeglioma,:A population-based study.,加拿大,2016,PLGG,，,Canada,，1985 to 2012(n=1202),中位随访,12.73,年,(0.02-33),，仅,93,例,(7.7%),死亡,20,年,OS,：,90.1 1.1%,合并神经纤维瘤病,1,型者：无肿瘤相关死亡,.Adverse risk factors included,pleomorphic,xanthoastrocytoma,(P.001)and a thalamic location(P.001),肿瘤未全切者确诊后生存,5,以上时，放疗增加了近,3,倍的晚期死亡风险，,P=0.001,，肿瘤相关风险增加了,4,倍，,P=0.013,多因素分析时，放疗与所有原因晚期死亡,(p=0.012),及肿瘤相关死亡明显相关,(P=0.014),。单因素分析的情况相似,(P.001).,与早期的死亡不同，晚期死亡与,PLGG,进展相关少，更多的是与肿瘤转变为恶性及非肿瘤原因有关,Krishnatry,R,Zhukova,N,Guerreiro,Stucklin,AS,1,Cancer.,2016 Apr 15;122(8):1261-9.,28,PA,纤维性星形细胞瘤；,GG,神经节胶质瘤；,PMA,毛细胞黏液样星形细胞瘤；,PXA,多形性黄色瘤型星形细胞瘤；,OD,少突胶质细胞瘤；,OA,少突星形细胞瘤；,Krishnatry,R,Zhukova,N,Guerreiro,Stucklin,AS,1,Cancer.,2016 Apr 15;122(8):1261-9.,10.3%,7.9%,6.7%,6.5%,2.9%,6.3%,8.1%,13.9%,21.8%,6.1%,6.7%,17.6%,3.2%,11.2%,8.2%,40%,7.3%,29,Krishnatry,R,Zhukova,N,Guerreiro,Stucklin,AS,1,Cancer.,2016 Apr 15;122(8):1261-9.,30,PMA,毛细胞黏液样星形细胞瘤,PA,纤维性星形细胞瘤,(,毛细胞,),Mix,少突星形细胞瘤,GG,神经节胶质瘤,LGA,低级别星型细胞瘤,PXA,多形性黄色瘤型星形细胞瘤,Krishnatry,R,Zhukova,N,Guerreiro,Stucklin,AS,1,Cancer.,2016 Apr 15;122(8):1261-9.,31,后颅窝,大脑,视路,脊髓,中线,脑干,丘脑,Krishnatry,R,Zhukova,N,Guerreiro,Stucklin,AS,1,Cancer.,2016 Apr 15;122(8):1261-9.,32,Krishnatry,R,Zhukova,N,Guerreiro,Stucklin,AS,1,Cancer.,2016 Apr 15;122(8):1261-9.,33,Krishnatry,R,Zhukova,N,Guerreiro,Stucklin,AS,1,Cancer.,2016 Apr 15;122(8):1261-9.,Tumor transformation,：转为恶性胶质瘤,34,Effect of radiation therapy on long-term survival for patients with pediatric low-grade,glioma,:(A)Ontario cohortincluding all deaths,(B)independent SEER reference cohort including all deaths,(C)Hospital for Sick Children cohort including tumor-related deaths,and(D)independent SEER cohort including tumor-related deaths.OS indicates overall survival;SEER,Surveillance,Epidemiology,and End Results.,Krishnatry,R,Zhukova,N,Guerreiro,Stucklin,AS,1,Cancer.,2016 Apr 15;122(8):1261-9.,35,进行放疗者生存时间短的原因分析,早期放疗是预后差的,PLGG,患者重要的治疗手段,早期放疗较单用化疗更能延长生存,需要放疗者常部位深，仅能活检，取样有限，一些可能混有高级别成分而未能取到标本，也可以解释数年内即转化为高级别的情况,另外，只有分析存活,5,年以上的患者才能有机会看到放疗相关的死亡,Krishnatry,R,Zhukova,N,Guerreiro,Stucklin,AS,1,Cancer.,2016 Apr 15;122(8):1261-9.,36,Opticpathway,glioma,in children:10years of experience in a single institution.(2016,希腊,),视路胶质瘤占儿童脑瘤的,46%,；,65%,年龄,5,岁，多数发病在,15,岁以下，累及视交叉者占,80%,，累及视神经者,20%,；,OPGs,常为毛细胞星型细胞瘤，但生长方式多种多样，从很惰性到快速生长型都有；一线化疗常有效，但,60%,以上的患者,5,年后都会进展；需要进一步化放疗,视路胶质瘤,(OPG),常与,NF1,伴发,本文回顾分析,2003-2013,，,20,例，,11,男、,9,女，中位年龄,5,岁,(3-12),3,例进行了活检，其他依据,MRI,诊断，,7/20,因视力下降就诊，,10/20,有,NF1,，随诊时发现,OPG,。其中,15/20,伴有,NF1,14,例的核磁发现视神经和,/,或视交叉受侵，其中,5,例视交叉后部结构也受破坏,16/20,接受了卡铂为基础的化疗，,4/20,观察,(,均伴有,NF1,，,3,例无症状，,1,例症状轻,),6,例在随诊时视力下降，和,/,或影像学表现，其中,2/6,手术、,1/6,伽马刀，,1/6,接受常规放疗，,2/6,化疗,其余,14,例随诊中症状改善或稳定，其中,12,例伴有,NF1,Doganis,D,1,Pourtsidis,A,1,Tsakiris,K,Pediatr Hematol Oncol.,2016 Mar;33(2):102-8.,37,Visual outcomes in pediatricopticpathway,glioma,after conformal radiation therapy.(2012,美国,),既往视路胶质瘤首选放疗，多数患者视力无变化；有报道放疗相关内分泌、血管病变及认知方面等不良反应；有学者尝试先化疗、观察或先手术,本文用,CRT 54Gy,治疗,20,例儿童视路胶质瘤，中位年龄,9.3,岁，,1997.07-2002.01,；中位随访,24,个月,视力检查中位,11,次,(2-17),，放疗前有,8,例进行过化疗，,9,例进行过手术,手术决定了放疗前视力情况,放疗前进行了化疗视力会下降,P=.0726,放疗前疾病进展，视力下降明显,P=.0220,没有进行化疗直接放疗的患者视力恢复好于先化疗的患者,P=.0289.,先做化疗后放疗的患者视力差于先做放疗的患者，放疗前姑息手术对保护视力有一定作用,Awdeh,RM,1,Kiehna,EN,Drewry,RD,Int,J,Radiat,Oncol,Biol,Phys.,2012 Sep 1;84(1):46-51.,38,Gamma Knife surgery foroptic,glioma,.Report of 2 cases.(2010,台湾,),2,例，,a boy and a girl,，,2005,年,3,月,-8,月；年龄,10,岁，,16,岁；,病理：均为,Pas,1,例视交叉胶质瘤剂量,11,Gy,；,1,例右侧视神经肿瘤剂量,15,Gy,随访,60,、,55,个月，均,CR,Liang CL,1,Lu K,Liliang PC,J,Neurosurg,.,2010 Dec;113 Suppl:44-7.,39,赵梓成，男，,2,岁,6,月，,2012,年,4,月被家长发现斜视、视力下降，,2013,年,6,月头颅核磁发现颅内占位，考虑视神经胶质瘤，,20130710,于行,CK,治疗，剂量：,Dt2900cGy/5f,40,41,Treatment of children with diffuse intrinsic,pontine,gliomas,with,chemoradiotherapy,followed by a combination of,temozolomide,irinotecan,andbevacizumab.(2013 MD,安德森,),DIPG,对手术及放疗都不敏感，预后差，多数,6-18,个月内死亡,回顾,6,例,DIPG,同步放化疗，,5,例每天卡铂并口服,VP-16,，,1,例口服,TMZ,；之后持续用,irinotecan,temozolomide,bevacizumab,Event-free survival(EFS),及,OS,分别：,10.4 3.08,、,14.6 3.55,月,不良反应：,2,例高血压，,4,例腹部痉挛，,5,例粒细胞减少,此方案较其他文献的,EFS and OS of 6.1 and 9.6,长,Zaky,W,1,Wellner,M,Brown RJ,Pediatr,Hematol,Oncol,.,2013 Oct;30(7):623-32.,42,Zaky,W,1,Wellner,M,Brown RJ,Pediatr,Hematol,Oncol,.,2013 Oct;30(7):623-32.,CBDCA,carboplatin,;VP-16,etoposide,;IRN,irinotecan,;BVZ,bevacizumab,;(1)TMZ at 90mg/M2/day for 6 weeks,(2)CBDCA 35mg/M2 and VP-16 50mg/M2 for 21 days every 28 days,(3)IRN 125 mg/M2 weekly,2 weeks on 1 week off,TMZ 75 mg/M2/day,POMon,Fri,BVZ 15mg/kg every 3 weeks.,43,吴*，男，,17,岁，脑干胶质瘤，,2013-10-01,无明显诱因头痛头晕，视物模糊，左下肢无力，,20131014,再次发病后，遗留视物模糊、视物重影、右下肢无力、行走不稳症状，,201310,在当地医院就诊，行头颅,CT,示“脑积水”,20131114,于我院行放疗，剂量：,Dt,54Gy/30f,。,2014-04-22,、,2014-08-18,、,2014-10-16,复查，年底进展去世。,没用,TMZ,44,Treatment of recurrent diffuse intrinsic,pontine,glioma,:the MD Anderson Cancer Center experience.(2012MD,安德森,),复发,DIPG,一般只进行姑息治疗,1998-2010,，共,31,例患者，进行,61,次治疗,常用的药物包括,Vp-16(14),贝伐,(13),伊立替康,(13),尼妥珠单抗,(13),丙戊酸钠13),7,例患者在原发肿瘤区进行了再次放疗：,首次放疗剂量,54Gy/30,次，再次放疗剂量,20Gy/10,次,7,例,PR,，,20,例,SD,，,31,例,PD,治疗后中位,PFS 2,个月，与之前的进展快慢有关，与治疗的次数无关,再放疗者,4/7,有效，,PFS,也较长,Wolff JE,1,Rytting ME,Vats TS,J Neurooncol.,2012 Jan;106(2):391-7.,45,Impact of tumor location and pathological discordance on survival of children with midline high-grade,gliomas,treated on Childrens Cancer Group high-grade,glioma,studyCCG-945.(2015),儿童,HGG,预后差，术后放化疗有用，中线,HGG,预后差于其他亚组,1985-1990,年,172,例中有,60,例是中线肿瘤：位于丘脑、下丘脑、基底节区,方案,A,：先用洛莫司汀、长春新碱、强的松后，进行受累野照射,54Gy,，,1.8Gy/,次，同步每周长春新碱,8,“8-in-1”,方案,B,：洛莫司汀、长春新碱、,羟基脲、甲基苄肼、顺铂、阿糖胞苷、氮烯咪胺、甲强龙。术后先,2,周期化疗，之后再放疗54,Gy,，,1.8,Gy,/,次，之后不再用每周的长春新碱,36%,、,MGMT,及,p53,过表达者均预后差,病理中心的再会诊及多中心研究很有意义,Eisenstat,DD,1,Pollack IF,Demers A,J,Neurooncol,.,2015 Feb;121(3):573-81.,46,a,PFS(p=0.26)and,b,OS(p=0.55).,c,PFS(p=0.48)and,d,OS(p=0.49).,Eisenstat,DD,1,Pollack IF,Demers A,J,Neurooncol,.,2015 Feb;121(3):573-81.,47,a,PFS(p=0.59)or,b,OS(p=0.39).,c,PFS(p=0.0013)or,d,OS(p=0.0084),Eisenstat,DD,1,Pollack IF,Demers A,J,Neurooncol,.,2015 Feb;121(3):573-81.,48,Treatment of children with,glioblastoma,with conformal radiation,temozolomide,and,bevacizumab,as adjuncts to surgical resection(2013,美国,),回顾,3,例胶母的治疗，,2,例巨细胞胶母；,2008.08-2009.08,近全切手术,29,天后，放疗,60Gy/30,次，同步,TMZ 90mg/m2,，,42,天，贝伐,5 mg/kg,，,14,天,1,次，术后,29,、,43,天。,放化疗后休息,4,周，开始维持治疗,12,周期，,28,天,1,周期，,TMZ 200 mg/m2 d1-5,，贝伐,10 mg/kg,，,d1,15 after 5 mg/kg,。治疗毒性小，均完成计划的治疗,2,例无复发，,38,、,49,个月,1,例,14,个月时复发，接受再次手术，之后用贝伐,+,伊立替康,4,周期解救治疗，目前,48,个月,Friedman GK,1,Spiller SE,Harrison DK,J,Pediatr,Hematol,Oncol,.,2013 Apr;35(3):e123-6.,doi,:,49,Friedman GK,1,Spiller SE,Harrison DK,J,Pediatr,Hematol,Oncol,.,2013 Apr;35(3):e123-6.,doi,:,50,A,：疗前；,B:,近期,Friedman GK,1,Spiller SE,Harrison DK,J,Pediatr,Hematol,Oncol,.,2013 Apr;35(3):e123-6.,doi,:,51,2012.11.28,男，,62,岁,2012.8.3,右顶枕开颅肿瘤切除术，病理：胶母细胞瘤,2012.8.31-10.11,术后瘤床,IMRT,，,剂量,60Gy/30f,，同时,TMZ,2012.12.3,头颅,MRI,及,MRS,示：瘤床周围肿瘤复发,2012.12.5-12.7,复发灶,CK 12Gy/3f,；,4,次贝伐珠单抗治疗,52,2012-11-28,复发,2013-1-22RT,后,2,月,2013-2-28RT,后,3,月,2013-1-8,放疗后,1,月,53,2012-11-27,2013-01-08,2013-01-22,2012-02-28,54,小 结,低级别：分类不同，慎重选择放疗,高级别：放疗,+TMZ,化疗等,DIPG,：切除困难，放疗,+TMZ,等,放疗：首程、再程；,CRT,、,IMRT,；,设备：加速器、射波刀、伽马刀、质子、重离子,55,谢谢！,56,