临床肿瘤学进展专家讲座.pptx

,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,临床肿瘤学进展,临床肿瘤学进展,第1页,53项突出进展,12项重大进展,临床肿瘤学进展,第2页,年临床肿瘤学重大进展,癌症发病率和死亡率下降,美国4家权威机构国立癌症研究所(NCI)、疾病控制与预防中心(CDC)、美国癌症学会(ACS)、北美肿瘤登记中心联合会(NACCR)联合汇报，,1999年间美国癌症发病率平均每年下降1%，死亡率每年下降1.6%。,难治性癌症疗效有改进,老年肺癌,惯用标准化疗方案卡铂+紫杉醇治疗普通情况很好老年患者，总生存(OS)优于吉西他滨或长春瑞滨单药治疗。,转移性胰腺癌,对于期胰腺癌患者，与标准吉西他滨单药治疗相比，FOLFIRINOX方案(5-氟尿嘧啶/亚叶酸钙+伊立替康+奥沙利铂)联合化疗显著改进有效率、无进展生存(PFS)和OS。,晚期卵巢癌,贝伐珠单抗联合卡铂+紫杉醇治疗并续以贝伐珠单抗维持治疗，与单纯化疗相比显著延长晚期卵巢癌患者中位PFS期。,黑色素瘤,一个单克隆抗体药品(ipilimumab)可使晚期黑色素瘤患者2年生存率显著提升34%。,临床肿瘤学进展,第3页,年临床肿瘤学重大进展,降低癌症复发,对于接收保乳手术后手术切缘阴性、腋淋巴结阴性,浸润性乳腺癌,患者，接收短程大剂量低分割放疗10年局部复发风险与标准放疗相近。,靶向治疗和个体化治疗,ALK 抑制剂,一项期临床试验采取间变淋巴瘤激酶(ALK)抑制剂(crizotinib)治疗,非小细胞肺癌(NSCLC),，超出2/3患者肿瘤缩小，90%以上患者治疗有效。,BRAF抑制剂,一项期临床研究显示，BRAF V600E突变,晚期黑色素瘤,患者接收新BRAF抑制剂(PLX4032)治疗，81%患者肿瘤完全或部分消退，包含骨和肝脏转移灶,。,临床肿瘤学进展,第4页,年临床肿瘤学重大进展,生活质量,化疗加姑息治疗,晚期肺癌,患者接收标准化疗并在诊疗后马上接收姑息治疗，生存期和生活质量均显著优于仅接收化疗者。,睡眠问题,超出3/4癌症患者有失眠或其它睡眠问题，发生率是普通人群3倍。中青年患者睡眠问题更常见，失眠造成患者抑郁和疲乏百分比更高。,FDA同意新药,Sipuleucel-T,去势治疗无效,转移性前列腺癌,患者接收肿瘤疫苗(sipuleucel-T)治疗，其OS优于抚慰剂组。,Cabazitaxel,对于去势治疗无效,转移性前列腺癌,，cabazitaxel联合泼尼松治疗OS优于米托蒽醌联合泼尼松。,临床肿瘤学进展,第5页,年临床肿瘤学重大进展,肺癌：3项,消化系统肿瘤：1项,泌尿生殖系统肿瘤：2项,乳腺癌：1项,妇科肿瘤：1项,黑色素瘤：2项,儿科肿瘤：1项,血液系统肿瘤,临床肿瘤学进展,第6页,肺 癌-法国III期随机,1.联合化疗可改进老年进展期肺癌患者预后,IIIIV期NSCLC,451例,70-89岁，中位77.2岁,PS：02,CBP AUC=6,4-weekly,Taxol 90mg/m2,d1,8,15,单药,GEM 1150mg/m2 or,NVB 30mg/m2,d1,8,3-weekly,结果：,NSCLC治疗选择并非主要取决于年纪，而应是患者实际体能状态。,OS：10.4m VS 6.2m PFS:6.3m VS 3.2m,级血液学毒性：联合组单药组（中性粒细胞降低症：54.3%VS 14.3%）,E.A.Quoix,et al.ASCO，Abstract ID:41167,R,PD,Erllotinib,150mg/d,临床肿瘤学进展,第7页,肺 癌-韩国I期临床研究,2.,Crizotinib对ALK阳性肺腺癌初显效,间变型淋巴瘤激酶（ALK）在肿瘤细胞生长和进展过程中起着关键性作用。ALK基因可经过与EML4(棘皮动物微管蛋白样4）基因形成融合基因（EML4-ALK)来编码产生ALK，从而促进肺癌细胞生长。,5%NSCLC患者携带EML4-ALK融合原癌基因。Crizotinib为一个选择性小分子ALK和MET/HGF受体酪氨酸激酶口服抑制剂。,临床肿瘤学进展,第8页,肺 癌-韩国I期临床研究,病例：82例：EML4-ALK融合基因（+）(FISH)、腺癌、不吸烟/曾吸烟、各种治疗后,口服Crizotinib 250 mg bid,结果：ORR：57%,8周疾病控制率：87%,PFS probability at 6months:72%,安全性：Gastrointestinal toxicities:I度,nausea(55%),vomiting(39%),结论：对于携带EML4-ALK融合基因NSCLC患者，Crizotinib治疗缓解率高，且安全性良好。,Y.Bang,et al.ASCO,Abstract ID:50854,临床肿瘤学进展,第9页,肺 癌,3.早期姑息治疗可延长肺癌患者生存期,姑息治疗应在治疗一开始即给予,评价：1.Functional Assessment of Cancer TherapyLung(FACT-L),2.Quality of life and mood,3.OS,151 patients with,newly diagnosed,metastatic,NSCLC,standard oncologic,care alone,early palliative care,+standard,oncologic care,团体：professionals from,medicine,nursing,chaplains,psychologists,pharmacists,dietitians,art,music,N Engl J Med,363(8);733,R,A,N,D,O,M,I,Z,E,D,临床肿瘤学进展,第10页,结 果,a better quality of life：mFACT-L scale 98.0 vs.91.5，P=0.03,临床肿瘤学进展,第11页,结 果,Fewer depressive symptoms：16%vs.38%,P=0.01,临床肿瘤学进展,第12页,结 果,Fewer,aggressive end-of-life care 33%vs.54%,P=0.05,临床肿瘤学进展,第13页,结 果,OS：11.6 months vs.8.9 months,P=0.02,临床肿瘤学进展,第14页,消化系统肿瘤,联合化疗方案显著改进转移性胰腺癌患者生存(PRODIGE 4/ACCORD 11临床试验),胆红素水平正常,PS:01分,Conroy,et al.ASCO,Abstract ID:4010,R,5-FU 400 mg/m2,iv,OXA 85 mg/m2,CPT-11 180 mg/m2,CF 400 mg/m2，,5-FU 2400 mg/m2 CIV46 h,GEM 1000 mg/m2 每七天1次,共7周给药，休息1周,342例,转移性胰腺癌,III期,临床肿瘤学进展,第15页,结 果,PFS：6.4m vs 3.3 m(HR 0.47，,P,0.0001),OS：11.1m vs 6.8m(HR 0.57，,P,0.05）,临床肿瘤学进展,第20页,结 果,OS：84.6%vs 84.4%,临床肿瘤学进展,第21页,结 果,At 10 years,71.3%of women in the control group as compared with 69.8%of women in the hypofractionated-radiation group,had an excellent or good,cosmetic outcome,(absolute difference,1.5 percentage points;95%CI,-6.9 to 9.8).,临床肿瘤学进展,第22页,妇科肿瘤,贝伐珠单抗延长进展期卵巢癌患者PFS期（GOG-0218),R,A组：TC+抚慰剂,B组：TC+贝伐珠单抗,C组：TC+贝伐珠单抗,抚慰剂,维持治疗,抚慰剂,贝伐珠单抗,1873例,III或IV期,卵巢上皮癌、,输卵管癌、,原发性腹膜癌,1:1:1,RA.Burger,et al.ASCO，Abstract ID:52788,临床肿瘤学进展,第23页,PFS,A组,（TC),B组,(TC+BEV),C组,(TC+BEVBEC),mPFS(m),10.3,11.2,14.1,HR,95%CI,0.906,(0.759-1.040),0.717,(0.625-0.834),P-value,0.080,0.0001,临床肿瘤学进展,第24页,OS,A组,（TC),B组,(TC+BEV),C组,(TC+BEVBEC),mOS(m),39.3,38.7,39.7,HR,95%CI,1.036,(0.827-1.297),0.915,(0.727-1.152),P-value,0.361,0.252,临床肿瘤学进展,第25页,GOG-0218:Conclusions,GOG-0218 met the primary objective in the front-line treatment of advanced ovarian(epithelial OV,PP and FT)cancer,PFS with TC+BEVBEV maintenance(Arm III)statistically superior to TC alone(Arm I),-,PFS with CP+BEV(Arm II)not statistically superior to CP(Arm I),Interpretation of,survival analysis limited,Treatment regimen generally,well tolerated;,adverse events,(including GI perforation)similar to previous BEV studies,BEV first molecular targeted and first anti-angiogenic agent to demonstrate benefit in this population,CP+BEVBEV maintenance should be considered one,standard option,.,临床肿瘤学进展,第26页,恶性黑色素瘤,单克隆抗体ipilimumab改进晚期黑色素瘤患者总生存,N Engl J Med,363;711,676例,经治、不可切除,III或IV期,黑色素瘤,R,A组：ipilimumab plus,gp100(403 patients),B组：ipilimumab alone(137),C组：gp100 alone(136,),3:1:1,Ipilimumab：,T细胞活化路径，间接活化抗肿瘤免疫反应,临床肿瘤学进展,第27页,结 果,OS,ipi-plus-gp100,ipi-alone,gp100-alone,12m,43.6%,45.6%,25.3,18m,30.0%,33.2%,16.3%,24m,21.6%,23.5%,13.7%,临床肿瘤学进展,第28页,OS,Ipi-plus-gp100:10.0m(95%CI,8.5 to 11.5);ipi alone:10.1m(95%CI,8.0 to 13.8);gp100-alone:6.4m(95%CI,5.5 to 8.7).,临床肿瘤学进展,第29页,PFS,ipi-plus-gp100:2.76 months(95%CI,2.73 to 2.79),ipil-alone:2.86 months(95%CI,2.76 to 3.02),gp100-alone:2.76 months(95%CI,2.73 to 2.83),临床肿瘤学进展,第30页,恶性黑色素瘤,靶向药品治疗基因突变晚期黑色素瘤显曙光,BRAF基因编码一个丝/苏氨酸特异性激酶(a serine/theroninespecific kinases)，是RAS/RAF/MEK/ERK/MAPK通路主要转导因子，参加调控细胞内各种生物学事件，如细胞生长、分化和凋亡等。,年，Davies等发觉，约66%恶性黑色素瘤和15结肠癌中BRAF基因存在体细胞错义突变。,临床肿瘤学进展,第31页,恶性黑色素瘤,I期研究,BRAF V600E突变晚期黑色素瘤,inhibitor of mutated BRAF：PLX4032,49 of whom had melanoma,N Engl J Med,362;809,临床肿瘤学进展,第32页,结 果,240 mg or more of PLX4032 twice daily：16 patients,10 PR and 1 CR,ORR 68.75%.,960 mg twice daily:32 patients 2 CR and 24 PR,ORR 81%,The estimated median progression-free survival among all patients was more than 7 months.,临床肿瘤学进展,第33页,儿童肿瘤,儿童及青少年癌症生存者存在长久心脏病风险,BMJ,339:b4606,临床肿瘤学进展,第34页,研究结果,14358例儿童及青少年癌症长久生存者回顾性研究提醒：这些生存者发生充血性心力衰竭风险增高6倍，心肌梗死及心脏瓣膜病风险增高5倍,临床肿瘤学进展,第35页,临床肿瘤学进展,第36页,谢谢！,临床肿瘤学进展,第37页,