心脑血管药理食管癌放疗增敏研究translationVGRTCHChina

化学药物与放射治疗结合:生物学基础,Prof. Vincent GREGOIREUniversit Catholique de Louvain,Cliniques Universitaires St-Luc,高危宫颈癌患者盆腔放疗结合同期化疗与盆腔及腹主动脉旁淋巴引流区放疗的比较M. Morris et al, NEJM, 340:1137-1143, 1999.,高危宫颈癌患者盆腔放疗结合同期化疗与盆腔及腹主动脉旁淋巴引流区放疗的比较M. Morris et al, NEJM, 340:1137-1143, 1999.,放疗 放疗+化疗(n=193) (n=195)5年总生存率58%73 (p=0.004)局部复发率 35%19% (p0.001)远处复发转移33%14% (p0.001),放疗: 45 Gy + 腔内治疗 (total dose 85 Gy)化疗: cddp (75mg/m2, d1), 5Fu (1g/m2/d, d1-4), x3,放化疗综合治疗,空间协同作用 (e.g. 乳腺癌)独立的细胞杀伤作用 (e.g. 霍奇金淋巴瘤)相互作用 (e.g. 头颈, 宫颈, 非小细胞肺癌)“稀释” 毒性 (e.g.霍奇金淋巴瘤),绝经前高危乳腺癌患者术后放疗和辅助化疗 Danish Breast Cancer Cooperative Group 82b TrialM. Overgaard et al., N. Engl. J. Med., 337: 949-955, 1997,放化疗综合治疗,空间协同作用 (e.g. 乳腺癌)独立的细胞杀伤作用 (e.g. 霍奇金淋巴瘤)相互作用 (e.g. 头颈, 宫颈, 非小细胞肺癌)“稀释” 毒性 (e.g.霍奇金淋巴瘤),放疗化疗化疗+放疗(EF, 40 Gy) (MOPP/ABVD)(IF, 40 Gy)10 年总生存80-90%80-90%90%并发症 (RR)-白血病11.070.0?-淋巴瘤21.022.0?-实体肿瘤2.81.1?-心脏2.2-3.11.0?,I 期和II期 霍奇金淋巴瘤(病理类型好和较好),放化疗综合治疗,空间协同作用 (e.g. 乳腺癌)独立的细胞杀伤作用 (e.g. 霍奇金淋巴瘤)相互作用 (e.g. 头颈, 宫颈, 非小细胞肺癌)“稀释” 毒性 (e.g.霍奇金淋巴瘤),头颈鳞癌：对照-无化疗,Pignon et al., Lancet 355: 949-955, 2000,头颈鳞癌：对照-无化疗,Pignon et al., Lancet 355: 949-955, 2000,放化疗综合治疗,Dose,Effect,RT,RT+CH,Additivity,Dose,Effect,RT,Dose,Effect,RT,RT+CH,Supra-additivity,在SA-NH肿瘤中单次放疗合并氟脲嘧啶(800 mg/kg)的剂量修饰因素,RADIATION DOSE (Gy),GROWTH DELAY SE (days),6,8,10,12,14,16,18,20,22,24,19,20,21,22,23,24,25,26,27,28,29,Absolute Growth Delay,DMF = 1.57,Normalized Growth Delay,DMF = 1.2,RT alone,Dose (Gy),S.F.,1.0E-03,1.0E-02,1.0E-01,1.0E+00,0,5,10,15,20,RT,RT+CH,放化疗综合治疗,Redrawn from Steel,增强,无相互作用,抑制,放化疗综合治疗,在人类鳞癌细胞株(SQD9)中dFdC对放射的增强作用,放化疗合理的综合应用,调整DNA/染色体的修复调节肿瘤细胞增殖增加肿瘤细胞丢失加强放疗导致的核苷类似物诱导的凋亡作用增加肿瘤细胞再充氧,放化疗综合治疗：细胞水平/分子水平相互作用,抗代谢药,放化疗综合治疗： 细胞水平/分子水平相互作用,放化疗综合治疗： 细胞水平/分子水平相互作用,放化疗综合治疗： 细胞水平/分子水平相互作用,放化疗综合治疗,细胞水平 / 分子水平相互作用或组织水平相互作用 ?,在SA-NH 肿瘤中通过分割放疗和氟脲嘧啶注射对再增殖延缓进行调节,治疗增益比的概念,Acute effectLate effectAntimetabolites5-Fu+ (GI, skin)MTX+ (GI)HU+ (GI)dFdC+ (GI) (lung)F-ara-A+ (GI) (SNC)Alkylating agentscis-platinum+ (GI)+ (kidney)BCNU+ (GI)+ (lung)cyclophosphamide+ (GI, skin)+ (lung, bladder, SNC)Antimetabolitesadriamycine+ (GI, skin)+ (heart, lung)mitomycin-C+ (GI, BM)+ (lung)bleomycin+ (skin, GI)+ (skin, lung)actinomycine-D+ (GI, BM, skin)+ (lung)Plant derivativesVinca-alcaloides- (GI, BM)?Etoposide?Taxanes+ (GI)?,放化疗综合治疗：正常组织毒副作用,高危宫颈癌患者盆腔放疗结合同期化疗与盆腔及腹主动脉旁淋巴引流区放疗的比较M. Morris et al, NEJM, 340:1137-1143, 1999.,放疗 放疗+化疗(n=193) (n=195)Early toxicity (G3-5)10 (5%)88 (45%)Early toxicity* (G3-5)4 (2%)20 (10%)Late toxicity (G3-5)22 (11%)24 (12%)* non hematologic only,RT: 45 Gy + brachytherapy (total dose 85 Gy)Chemo: cddp (75mg/m2, d1), 5Fu (1g/m2/d, d1-4), x3,高危宫颈癌患者盆腔放疗结合同期化疗与盆腔及腹主动脉旁淋巴引流区放疗的比较M. Morris et al, NEJM, 340:1137-1143, 1999.,Enhancement factor,Effect on tumor control,Effect on normaltissue toxicity,5,4,3,2,1,2,3,4,5,Early,Late,Localrelapse,局部晚期头颈鳞癌采用放化疗交替治疗M. Merlano et al, NEJM, 327:1115-1121, 1992.,Enhancement factor,Effect on tumor control,Effect on normaltissue toxicity,Early,Late,2,1,2,Localrelapse,?,RT: 70 Gy, 7 weeksRT+CH:3 x 20 Gy, 9 weeks;