心脑血管药理食管癌放疗增敏

Click to edit Master title style,Click to edit Master text styles,Second Level,Third Level,Fourth Level,Fifth Level,Di Yan, DSc,William Beaumont Hospital,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,*,*,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,*,*,心脑血管药理食管癌放疗增敏,Radiotherapy Modalities,Fractionation,Normal, hyper, hypo, and simultaneous boost,Conformality,CRT, IMRT, CTV-to-PTV margin, dose distribution,High LET radiation,10 (n), 100 KeV/,m,m (p,a,),Sensitizers or biological modifiers,O,2, chemo, gene drug,Classic Radiobiology Framework,The biological basis for fractionation & total treatment time,Radiosensitivity of cell survival,Cell cycle kinetics (proliferation),DNA damage/repair (incomplete repair),The biological basis for conformality,Dose/volume effect,Molecular targeting,Radiocurability of 8-mm A431 tumor xenografts in nude mice. Radiation dose-response curves were generated for local tumor control at 120 days after treatment with radiation alone (open circle), a single dose of C225 plus radiation (open triangle), or three doses of C225 plus radiation (filled square). Error bars are 95% confidence intervals on the TCD,50.,Tumor or early reaction normal cell =,a/b,= 10,Late reaction normal cell =,a/b,= 3,Cell Survival During RT,Cell survival fraction (log) after one and n times dose delivery,Example: Tumor (,a/b,= 10),If,a,0.62 = TCP(35x2Gy) = 0% not curable,If,a,0.4, then,SF, TCP =100% always curable,Biologically Effective Dose (BED),The relationship between log cell killing and BED is always linear.,For a given dose per fraction, the BED is larger for late reacting tissue than tumor or early reacting tissue,To remain BED = constant:,Without considering cell proliferation and damage/repair,small fraction dose with large number of fractions seems,always good for normal tissues , meanwhile it remains,similar effect for tumor.,Rapid Repopulation of Tumor During RT,Tumor Cell Proliferation During RT,Tumor cell survival with consideration of tumor cell proliferation during the RT,Example: t,lag,= 21 days, t,pot,= 3 days and,a,= 0.3,a/b,= 10,After the first 21 days of treatment, the dose loss for one extra day is equals to 0.77 Gy,It implies that in the conventional RT (60 Gy = 30x2Gy week days), the equivalent dose is only 44 Gy,Biologically Effective Dose for Tumor with consideration of tumor cell proliferation during the RT,Incomplete Repair of Normal Tissue During RT,Incomplete Repair of Normal Tissue During RT,Example: t,rep,= 4 hrs, DT = 6 hrs,a,= 0.3,a/b,= 3,It implies that in the hyper-fractionation RT (60 Gy = 30x2Gy, two fractions per days), the equivalent dose will be 66.5 Gy,Biologically Effective Dose for a normal tissue with consideration of incomplete repair,Biological Equivalence:,Two dose fractionation regimens,(n,1, d,1,),and,(n,2, d,2,),are biologically equivalent with respect to tumor control or normal tissue complication if and only if,Normalized Total Dose (NTD): convert dose to NTD before applying conventional RT dose response for treatment evaluation,H&N: 3DCRT vs. 9 Beam IMRT (Dose-Volume Criteria),Cord,Tumor,Nodes,Parotids,Brainstem,3DCRT,IMRT,Lung: 3DCRT vs. 5 Beam IMRT,Heart,Esophagus,Lung,Spinal Cord,A specified dose- volume constraint can lead to an infinite number of dose responses,An infinite number of dose-volume histograms lead to the same response,Limitations of Dose-Volume-Based Treatment Planning Evaluation,Constraint: V(d 50 Gy) D - D,0,= (1/,)ln,/,0,.,Dose is relatively insensitive to the cells density.,Effect of Tumor Cells Density,(,= 0.4; D,0,= 60 Gy).,r,/,r,0,Density%,Dose%,0,D,0,= 60 Gy,TCP for Heterogeneous Dose Distribution,Tumor volume V =,N,0,; Considering V = V,1,+ V,2, and V,1,was irradiated with dose D,1,and V,2,with dose D,2,:TCP = exp(- N,s,),N,s,=,V,1,exp (-,D,1,) +,V,2,exp (-,D,2,),=,V,1,/ V) N,0,exp (-,D,1,) +,V,2,/ V) N,0,exp (-,D,2,),= ln(TCP) =,V,1,/V) lnTCP(V,D,1,) + (V,2,/V) lnTCP(V, D,2,),Therefore,85%of tumor volume has full dose, and the other 15% has dose deficiency of 0%, 10%, 15% or 20% respectively,TCP,Gy,dose deficiency in,15% of volume,- 0%,- 10%,- 15%,- 20%,Calculate TCP for 3D Treatment Planning Evaluation,Tumor volume has,DVH =(V,1, D,1,), (V,2, D,2,), ,In the practice, TCP(V, D,i,) is determined from,clinical dose response fitting,TCP for Adenocarcinoma of Prostate,Gy,TCP,TCD,50,g,50,Calculate TCP for 3D Treatment Planning Evaluation,Example (Prostate cancer):,V = V,1,+ V,2,; V,1,/V = 85%, V,2,/V = 15% ; V,1,with dose D,1,= 80 Gy and V,2,with dose D,2,= 72 Gy.,(TCP(V, 80 Gy) = 78% and TCP(V, 72 Gy) = 55%),Then,Summary,Two dose fractionation regimens or two dose distributions are equivalent if and only if the corresponding biological/clinical outcomes are equivalent,It is a mistake to believe that there is a simple “true model” in the biological sciences,However, they are all useful and necessary to guide us in clinical study and routine practice,谢谢观赏,