心脑血管药理、食管癌放疗增敏CRF
C225心脑血管药理、食管癌放疗增敏
美国食品和药物管理局（FDA）已批准cetuximab作为治疗晚期结肠癌的药物上市。
Cetuximab 是迄今第一个获得批准治疗结肠癌的单克隆抗体药物。
瑞士已批准了MerckKgaA公司的抗癌药物Erbitux（cetuximab，西妥昔单抗）（也称C-225），用于对irinotecan（伊立替康）标准疗法不再响应的结肠癌患者。
这是Erbitux在全球的首次获批。
【作用机制】Cetuximab为IgG1单克隆抗体，是表皮生长因子受体(EGFR)阻止剂。
Cetuximab主要通过干扰癌细胞表面一种名为“表皮生长因子受体（EGFR）”的蛋白质生长，通过抑制表皮生长因子受体，减少癌细胞进入正常组织的几率，控制癌细胞的转移，达到抗癌目的。
它虽然不能延长结肠癌患者生命，但是能够部分缩减已扩散至身体其他部位的癌细胞。
临床试验结果显示，同时接受新药和另一种化疗药物治疗的患者中，有近２３％的人结肠肿瘤不同程度地缩减。
只接受新药治疗的患者中也有约１１％的人结肠肿瘤出现缩减。
Cetuximab是一种人和鼠的EGFR单克隆抗体的嵌合体，由鼠抗EGFR抗体和人IgG1的重链和轻链的恒定区域组成，Cetuximab可以竞争性的抑制EGF及其它配体的结合，阻断了受体的相关酶的磷酸化，进而抑制细胞生长，诱导调亡，减少基质金属蛋白酶和血管表皮生长因子（VEGF）的生成，体外实验和动物实验显示ERBITUX可以抑制过度表达EGFR的肿瘤细胞的生长，而对缺乏EGFR表达的人肿瘤细胞则没有抗肿瘤活性，此外还发现Cetuximab 与化疗联合应用要优于单独化疗。
【适应症】晚期结肠癌、肺癌。
【用法与用量】intravenous use only联合OXALIPLATIN的方案：Cetuximab 400 mg/m2 loading one dose week #1 of cycle #1250 mg/m2 weekly starting on week #2 and oxaliplatin 85 mg/m2 dl,LV 200 mg/m2, d1 & d2,5-FU 400 mg/m2 bolus then 600 mg/m2 CI (22 hours) d1 & d2 (FOLFOX4) every 2 weeks 。
心脑血管药理、食管癌放疗增敏研究食管癌三维适形后程加速放疗的临床研究
随访与统计方法
随访率：截止至2009年1月，随访率100%， 统计方法：SPSS11.5统计软件包
用Kaplan-Meier法计算生存率及局部控制率并用 Logrank法检验
近期疗效及副反应比较行χ2检验
1（3）
0.962 0.327
两组患者急性放射性肺炎发生情况比较
组别
放射性肺炎 例（%）
——————————————————
0级 1级
2级
3级
加速组 9（33） 9（33） 6（22） 3（11）
常规组 16（57） 8（28）
χ 2值
P值
3.143 0.146 0.076 0.702
2（7）
1.448 0.229
管病变长度≤10cm，无穿孔征象 临床检查无锁骨上淋巴结和远处转移 既往无肿瘤病史或可能影响治疗完成的疾病
临床资料
入组时间：2003年7月-2006年3月 病例数：55例 病理：鳞癌54例；腺癌1例 用随机数表分为三维适形后程加速组（加
速组）27例和三维适形常规分割放疗组 （常规组）28例
临床资料 性别 男 女 年龄（岁） 范围 中位值 病变部位 颈段 胸上段 胸中段 胸下段 钡餐长度（cm） 范围 中位值
临床资料
加速组（27例）
20 7
50-79 64
2 4 18 3
3.00-9.60 6.00
常规组（28例）
18 10
30-80 67
1 7 15 5
1.50-9.50 5.20
χ 2值 0.62 0.107 0.08
1.256b
P值 0.432 0.915 0.778
心脑血管药理、食管癌放疗增敏研究食管癌ctv外放
GXS-IJROBP-2007,67:389-396
研究结论
食管鳞癌: 近端：10.5± 13.5mm 远端：10.6± 8.1mm
胃-食管结合部腺癌： 近端：10.3± 7.2mm 远端：18.3± 16.3mm
94％within30mm 94%within50mm
1例为野外复发：中段病变，2年后镜检病理证实颈段食管癌
PTV纵轴外放3cm是否足够？
Button等报道三维适形放疗同期联合化疗，145例食管癌 PTV纵轴外放3cm边界，轴向外放1.5cm 结果：中位复发时间18月
治疗失败— 局部55例，远转13例，局部+远转15例 3例野外临界复发，其余全部为野内复发
≤0.5cm >0.5，≤1.0cm >1.0，≤1.5cm >1.5，≤2.0cm >2.0，≤2.5cm >2.5，≤3.0cm
>3.0cm 合计
下残端阳 性例数 1 1 1 1 0 1 3 8
病例总数
6 17 14 91 14 177 843 1162
下残阳性率%
16.6 5.9 7.1 1.1 0 0.6 0.4 0.7
2.0~3.0 3.0~4.0 2.0～3.0
3.0 5.0
上2～5cm,下4～5cm
3.0～5.0 2.0～3.0
1.0 0.5 0.5 0.3~0.5
1.0 0.5 0.5～1.0 0.5～1.0 -
0.5 0.5
0.5～1.0
CTV纵向外放标准探讨
病理学研究 临床疗效及复发模式 CT勾画食管癌GTV长度的偏差
王军 祝淑钗 韩春 李晓宁 高超 赵玉芹 贾敬好 中国肿瘤临床，2008,35：967－969
Iressa心脑血管药理、食管癌放疗增敏
非小细胞肺癌新药Iressa药品介绍：【药品名称】：通用名：吉非替尼片、易瑞沙英文名：Gefitinib Tablet 、Iressa、ZD1839 【性状】褐色，圆形，双凸面，薄膜衣片；一面印有“ 250”，另一面光滑。
每片含吉非替尼250mg。
【药理毒理】药物动力学特性吉非替尼是一种选择性表皮生长因子受体(EGFR)酪氨酸激酶抑制剂，该酶通常表达于上皮来源的实体瘤。
对于EGFR酪氨酸激酶活性的抑制可妨碍肿瘤的生长，转移和血管生成，并增加肿瘤细胞的凋亡。
在体内，吉非替尼广泛抑制异种移植于裸鼠的人肿瘤细胞衍生系的肿瘤生长，并提高化疗、放疗及激素治疗的抗肿瘤活性。
在临床实验中已证实吉非替尼对局部晚期或转移性非小细胞肺癌具客观的抗肿瘤反应并可改善疾病相关的症状。
药物代谢动力学特性静脉给药后，吉非替尼迅速廓清，分布广泛，平均清除半衰期为48小时。
癌症患者口服给药后，吸收较慢，平均终末半衰期为41小时吉非替尼每天给药1次出现2-8倍蓄积，经7-10天的给药后达到稳态。
24小时间隔用药，循环血浆药物浓度一般维持在2-3倍之间。
吸收口服给药后，吉非替尼的血浆峰浓度出现在给药后的3到7小时。
癌症患者的平均吸收生物利用度为59%。
进食对吉非替尼吸收的影响不明显。
在一项健康志愿者的实验中，当pH值维持在pH5以上时，吉非替尼的吸收减少47%(见4.4和4.5节)。
分布在吉非替尼稳态时的平均分布容积为1400L，表明组织分布广泛。
血浆蛋白结合率近90%。
吉非替尼与血清白蛋白及αl—酸性糖蛋白结合。
代谢体外研究数据表明参与吉非替尼氧化代谢的P450同工酶只有CYP3A4。
体外研究显示吉非替尼可能有限的抑制CYP2D6酶。
在一项临床试验中，吉非替尼与metoprolol(美多心安，一种CYP2D6酶底物)合用使该组的作用有少量的增高(35%)，其实际临床意义尚未估计。
在动物实验中吉非替尼未显示酶诱导作用，并且对其它的细胞色素P450酶也没有显著抑制作用（体外）。
肿瘤医院心脑血管药理、食管癌放疗增敏
肺癌是最常见的恶性肿瘤，2000年上海 市男性肺癌的发病率为53/10万，女性肺 癌的发病率为21/10万。[1]放疗作为一种 局部治疗手段，在占有所有肺癌75%85%的NSCLC的治疗中，发挥着重要的 作用。[2]
背景
FUDAN UNIVERSITY CANCER HOSPITAL
• 采用常规分割放疗技术时，NSCLC的根 治性放疗一般需要6周左右的时间，根据 Kupelian等[3]的研究，NSCLC在常规分 割放疗中，肿瘤体积每天以1.2%的速度 发生着退缩。就放疗过程中，肿瘤退缩 以及与之相关的肿瘤空间位置改变对靶 区剂量分布的影响这一问题，在胶质瘤、 宫颈癌和头颈部肿瘤[4、5、6]中已有详 尽的阐述。
背景
FUDAN UNIVERSITY CANCER HOSPITAL
本研究就NSCLC放疗过程中，肿瘤退缩 以及与之相关的肿瘤空间位置改变对靶 区剂量分布的影响作一的探讨。
FUDAN UNIVERSITY CANCER HOSPITAL
非小细胞肺癌放疗过程中肿瘤退 缩以及与之相关的肿瘤空间位置 改变对靶区剂量分布的影响
王艳阳 樊旼 徐志勇 傅小龙
FUDAN UNIVERSITY CANCER HOSPITAL
背景
背景
FUDAN UNIVERSITY CANCER HOSPITAL
心脑血管药理食管癌放疗增敏
心脑血管药理食管癌放疗增敏
摘要
心脑血管药物是治疗心血管疾病的药物，在放射治疗食管癌中也被发现可以增
强放疗的敏感性。
本文将介绍心脑血管药物在食管癌放疗中的增敏作用以及相关机制。
引言
食管癌是一种常见的消化道恶性肿瘤，治疗方法包括手术、放疗、化疗等。
而
心脑血管药物在放疗中的增敏作用近年来引起了研究者的关注。
这些药物在心血管疾病中的应用已经被广泛证实，而在食管癌放疗中的作用则是一块新的领域。
心脑血管药物在食管癌放疗中的增敏作用
心脑血管药物包括降压药、抗心律失常药等，已经被证实可以增强食管癌患者
对放射治疗的敏感性。
研究表明，这些药物可以通过多种途径影响肿瘤细胞的代谢、增殖等过程，从而增强放疗的疗效。
此外，心脑血管药物还可能调节肿瘤微环境，促进肿瘤细胞的凋亡。
相关机制
心脑血管药物增敏食管癌放疗的机制尚不完全清楚，但已有一些研究取得了初
步的认识。
其中，心脑血管药物对血管内皮细胞、免疫细胞等的影响被认为是一个重要的机制。
此外，一些药物还可能通过调节细胞信号通路、影响肿瘤细胞的
DNA修复等途径发挥增敏作用。
结论
心脑血管药物在食管癌放疗中的增敏作用为该疾病的治疗带来了新的可能性。
未来的研究还需要进一步探索心脑血管药物在放射治疗中的作用机制，以期为临床治疗提供更有效的策略。
以上就是本文对心脑血管药理食管癌放疗增敏的探讨，希望对相关领域的研究
工作有所启发。
新近距离心脑血管药理、食管癌放疗增敏
第一节 概述
2.近距离治疗的剂量率模式；
二 剂量率效应 按照放射生物学原理，肿瘤组织与晚反应正常组 织的生物效应对不同剂量率的响应不同。即对一给定 的总剂量水平，剂量率增加，正常组织晚期效应的增 加幅度大于肿瘤控制率的增加；剂量率降低，正常组 织晚期效应的减弱幅度大于肿瘤控制率的减少，也就 是说治疗增益比（肿瘤控制率与正常组织并发症发生 率之比）随剂量率的增加而减少。
第四节 近距离放疗的剂量学系统和施治技术
1.妇瘤腔内治疗的剂量学系统(巴黎系统、斯德哥尔摩系 统、曼彻斯特系统) ICRU系统
ICRU系统：38报告 剂量监测点： 直肠参考点为阴道容器轴线与阴道后壁交 点后0.5cm处；膀胱剂量参考点为仰位投影片造影剂集聚 的最低点；腹主动脉，骼总和外骼淋巴结参考点与 Fletcher淋巴的梯形区定义一致；
比释动能kerma 是指电离辐射在介质中释放电离粒子的功能，定义 为dEtr除以dm的商，其中dEtr为不带电粒子在质量为dm的 介质中释放的全部电离粒子的初始动能。 空气比释动能强度 是指在自由空间内空气比释动能率与剂量平方的乘 积。单位符号为U，1U＝1μGym2h－1
K = dEtr / dm
照射量率常数 与活度为A的ν射线点源相距为L，有能量大于Δ＝ 11.3KeV的光子产生的照射量率（dX/dt）Δ与L2相乘后再 被A相除所得的商，单位Ckg-1m2MBq-1。 吸收剂量 电离辐射在质量为dm的介质中沉积的平均能量; 单位：Gy，1Gy＝100cGy=100rad=100ergs/g. 吸收剂量率 单位时间内得到的吸收剂量
第三节 近距离放疗的物理量、单位制和剂量计算
2.指数衰变规律 衰变常数 半衰期 平均寿命 放射性活度 外观活度
半衰期 HVL为放射活度或放射性原子数量衰减到初始值 的一半所需要的时间。 T = 0.693 / λ
心脑血管药理、食管癌放疗增敏
导读：朱庆磊等在―D-半乳糖催老大鼠氧化水平和抗氧化能力的变化‖中华老年心血管病杂志，吉瑞瑞等的―D-半乳糖诱导大鼠肺微血管内皮细胞‖，D-半乳糖和（10g/L）DMEM培养液培养大鼠肺微血管内皮细胞（PMVECs），致人衰老因素又有新发现——专家称半乳糖是人体衰老剂●阿星―情绪不良、缺少运动、肥胖等因素能导致人体过早衰老，这些，我想大家知道，但牛奶中的半乳糖同样会加速人体的衰老，是一种致衰老剂，我心脑血管药理、食管癌放疗增敏致人衰老因素又有新发现——专家称半乳糖是人体衰老剂●阿星―情绪不良、缺少运动、肥胖等因素能导致人体过早衰老，这些，我想大家知道，但牛奶中的半乳糖同样会加速人体的衰老，是一种致衰老剂，我想大家知道不多。
‖3月26日，专家严肃指出，―这是前不久研究发现的。
‖专家解答半乳糖危害健康专家首先指出，半乳糖与骨质疏松、白内障、青光眼等众多疾病有关。
它主要随奶制品摄入体内。
当然在这里强调的是，这并没颠覆牛奶―白色血液‖的美称，大家也不必谈奶色变，这主要是指糖尿病人、胃病患者、中老年三高人士和乳糖不耐受者等一些特殊人群要慎用！―那我小时候喝奶没事，咋现在就不行了呢？‖接着，专家对笔者所提出的问题予以解释：婴儿在3岁之前，人体内有一种乳糖酶，能够分解奶中的乳糖成分。
但3岁以后人体内的乳糖酶逐渐减少，一些人再喝奶时，奶中的乳糖将会很难分解或只能分解成葡萄糖和半乳糖。
葡萄糖不用说，会导致糖尿病人血糖升高，威胁健康，但关键是半乳糖不仅会使血糖升高，而且还是一种致衰老剂，过量摄入危害大！尤其是女性每天喝超过230毫升的牛奶（即早晚各一杯奶），得乳腺癌的概率将会大大增加。
接着，专家从专业角度进一步予以解释。
―新陈代谢是生命的本质，也是生命活动的基础。
糖代谢在三大物质代谢中具有很重要的意义。
糖代谢紊乱必会引起心、肝、肾、脑等重要器官代谢的异常，最终出现衰老症状。
已有数据证明若大量摄入D-半乳糖，可使机体细胞内半乳糖浓度增高，在醛糖还原酶的催化下，还原成半乳糖醇，以致不能被细胞进一步代谢而堆积在细胞内，影响正常转化，导致细胞肿胀，功能障碍，代谢紊乱。
心脑血管药理、食管癌放疗增敏-铂类药物的新进展
DDP 上市至今已超过30年，但仍是目前应用最 广泛的药物之一：
1) 现已公认含铂类方案是晚期非小细胞肺癌的首选 方案，亦是小细胞肺癌的主要组方之一
2) DDP是头颈癌单药有效率最高的药物之一，5Fu+DDP是头颈癌化疗的标准方案（Taxol、 Gemcitabine亦是非常有前途的头颈癌化疗药）
2） CBP几乎全部经由肾小球滤过，因此药物在体内 的存留与药物浓度－时间曲线下面积（AUC）密切 相关。目前国际上多是根据AUC计算CBP用量。
3） CBP、DDP存在明显的交叉耐药性。 4） CBP具有与DDP相同的抗瘤谱，两者疗效相近。
CBP已在临床广泛应用
对于非小细胞肺癌、小细胞肺癌、卵巢癌（上皮来 源）等可作为首选方案的组成部分
个氯离子，增加了化合物的水溶性。
药代动力学特点：体内过程符合三室模型，T1/2α= 0.2 ～0.4hr, T1/2β=1.3～1.7hrs,T1/2γ=22～40hrs， 药物的总体清除率与剂
量无关。
与DDP比较，CBP有以下特点：
1） 肾、耳、神经毒性明显降低，剂量限制性毒性为 骨髓抑制，毒性呈剂量依赖性；
+ 2H2O Cl
NH3
H2O+
Pt(II)
+ 2Cl-
H2O+ NRHe3 active complex
G
Pt
G
DNA Strand
铂化合物的主要作用机制（1）
由于DDP与两个结合位点，故理论上可以形成1）链内交联2） 链间交联；3）DNA-蛋白质分子间交联，使DNA链局部纽结 或解旋，阻止DNA聚合酶推进，致使DNA复制、转录失败， 造成肿瘤细胞死亡。其中链内交联占大部分，链间交联的形 成不到5％。可见铂化合物一类周期非特异性抗癌药物。
心脑血管药理、食管癌放疗增敏Pages 158-168
Cutaneous LymphomasBenjamin D.Smith,MD,*and Lynn D.Wilson,MD,MPH†The skin is the most common site of extranodal non-Hodgkin lymphoma,with a yearlyincidence approaching1per100,000individuals in the United States.Skin lymphomas areclassified broadly into cutaneous T-cell lymphoma(CTCL)and cutaneous B-cell lymphoma(CBCL).Within these broad categories,multiple unique pathologic entities exist with awide array of natural histories and treatment options.Radiotherapy plays an important rolein the curative treatment of localized CTCL and CBCL and may be used to palliatecutaneous and visceral symptoms associated with advanced disease.This review high-lights the role of radiotherapy in the multidisciplinary management of cutaneous lymphoma.Semin Radiat Oncol17:158-168©2007Elsevier Inc.All rights reserved.A pproximately 27% of all non-Hodgkin lymphomas arisein extranodal sites,such as the skin,stomach,brain, small intestine, lung, and eye.1 The skin is the most common extranodal site,with a yearly incidence approaching1case per 100,000 individuals in the United States.2 Cutaneous lymphomas present substantial diagnostic and therapeutic challenges,given their diverse clinical manifestations and ex-pansive,multidisciplinary treatment options.This article will review the natural history of the most common cutaneous lymphomas and will discuss treatment options with a special emphasis on the role of radiotherapy.World Health Organization–European Organization for the Research and Treatment of Cancer ClassificationThe pathologic classification of cutaneous lymphoma has been a subject of much debate.In1997,the European Orga-nization for the Research and Treatment of Cancer(EORTC) proposed a classification scheme for primary cutaneous lym-phoma.3 Although the EORTC classification borrowed terms previously used in the classification of nodal lymphoma,the EORTC terminology was not intended to apply to nodal lym-phoma.In contrast,the World Health Organization(WHO) classification,proposed in2001,was a unified system that applied similar terminology to both extranodal lymphoma (including primary cutaneous lymphoma)and nodal lym-phoma.4 However, grouping cutaneous and nodal lym-phoma within the same classification scheme may be inap-propriate because accumulating evidence suggests that primary cutaneous lymphomas behave differently than his-tologically similar nodal lymphomas.To address the need for a universally accepted classification solely devoted to primary cutaneous lymphoma,the WHO-EORTC published a unified classification for primary cutaneous lymphoma in 2005.5 The entities included in the WHO-EORTC classification,along with their relative frequencies and associated5-year disease-specific survivals, are reported in Table 1.Mycosis FungoidesClinical ManifestationsMycosis fungoides(MF)is a malignancy of helper(CD4ϩ) T-cells and accounts for nearly50%of all cutaneous lympho-mas,with a yearly incidence of approximately5cases per million in the United States.2,5 The EORTC classification states that the term mycosis fungoides should be reserved for those CD4ϩcutaneous lymphomas that are“characterized by the subsequent evolution of patches to more infiltrated plaques and eventually tumors.”3 The earliest phase of MF—the premycotic phase—typically begins with skin patches that are mildly erythematous,slightly scaling,annular(ring-shaped)or arcuate(arc-shaped),and classically involves sun-shielded areas (Fig. 1A). Such lesions may wax and wane for years before histologicfindings show definitive evidence of MF.As MF progresses,patches lose their predilection for sun-shielded areas and may become eczematous,hypopig-mented,or hyperpigmented.The trunk,pelvis,and proximal extremities are most commonly involved.Patches may progress to form more generalized,deeply infiltrative,scaling plaques that have well-demarcated, palpable borders (Fig. 1B). If the neoplastic cells lose their skin-homing(epidermo-*United States Air Force,Wilford Hall Medical Center,Lackland AFB,TX.†Department of Therapeutic Radiology,Yale University School of Medicine, New Haven,CT.Address reprint requests to Lynn D.Wilson,MD,MPH,Department of Therapeutic Radiology,Yale University School of Medicine,HRT132,333Cedar Street,New Haven,CT06520.E-mail:Lynn.wilson@1581053-4296/07/$-see front matter©2007Elsevier Inc.All rights reserved.doi:10.1016/j.semradonc.2007.02.001tropic)properties,they enter a vertical growth phase and form cutaneous tumors (Fig. 1C). Such tumors may cause substantial morbidity because of ulceration and superinfec-tion.DiagnosisThe diagnosis of mycosis fungoides remains challenging, even for the experienced clinician and dermatopatholo-gist,because of both the absence of a diagnostic gold stan-dard and the number of benign dermatoses that may mimic MF.On skin biopsy,the most notablefinding of early MF is substantial epidermotropism,characterized by lymphocytes grouped along the epidermal basement membrane.Pautrier’s microabscesses,which are well-de-fined collections of intraepidermal lymphocytes,are con-sidered pathognomonic for MF but are seen in less than 20%of early lesions.For clinically and histologically bor-derline cases,molecular studies may help to confirm a diagnosis of MF.Typically,MF shows the following im-munophenotype:CD2ϩ(pan T-cell),CD3ϩ(pan T-cell), CD4ϩ(helper T-cell),CD5ϩ(pan T-cell),CD45ROϩ(memory T-cell),CLAϩ(cutaneous lymphoid antigen), CD8- (cytotoxic T-cell), and CD30- (activated T cell).6 An aberrant T-cell phenotype,such as loss of expression of CD2,CD3,and/or CD5,also supports the diagnosis of MF.5Use of polymerase chain reaction to identify a clonal T-cell receptor gene rearrangement may help to confirm the diagnosis of MF.For example,a clonal T-cell popula-tion can be identified in50%to80%of histologically borderline biopsies obtained from patients who subse-quently develop classic MF.7,8 Other tests recommended to complete the diagnostic work up are summarized in Table 2.Staging and PrognosisThe American Joint Committee on Cancer(AJCC)staging system for MF identifies extent and character of skin le-sions,extracutaneous disease,and leukemic transforma-tion as the major determinants of poor prognosis (Tables 3 and 4).9Patients with limited patches and plaques (stage IA,T1N0M0)experience10-year survival similar to a matched control population.10The median survival is ap-proximately11years for patients with extensive patches and plaques(T2),3.2years for patients with tumors(T3), and 4.6 years for patients with erythroderma (T4).11Pa-tients with either pathologically documented lymph node involvement or visceral involvement experience a median survival of approximately 1 year.12The AJCC also in-cluded a blood descriptor,B0versus B1,to document the absence or presence of greater than1,000Sézary cells (CD4ϩ,CD7Ϫ)perL.Among patients with erythro-derma,the presence of B1disease doubles the risk ofTable 1 The WHO-EORTC Classification for Cutaneous Lymphoma5Histology Frequency(%)5-YearDisease-SpecificSurvival(%)ClinicalBehaviorCutaneous T-cell and NK-cell lymphomasMycosis fungoides4488Indolent Variants of mycosis fungoidesFolliculotropic mycosis fungoides480Indolent Pagetiod reticulosis<1100Indolent Granulomatous slack skin<1100IndolentSézary syndrome324Aggressive Adult T-cell leukemia/lymphoma———Primary cutaneous CD30؉lymphoproliferative disordersPrimary cutaneous anaplastic large-cell lymphoma895Indolent Lymphomatoid papulosis12100Indolent Subcutaneous panniculitis-like T-cell lymphoma(␣/type)182Indolent Extranodal NK/T-cell lymphoma,nasal type<1—Aggressive Primary cutaneous peripheral T-cell lymphoma,unspecified216Aggressive Primary cutaneous aggressive epidermotropic CD8؉<118Aggressive T-cell lymphomaCutaneous␥/␦T-cell lymphoma(provisional)<1—Primary cutaneous CD4؉small-/medium-sized pleomorphic275Indolent T-cell lymphomaCutaneous B-cell lymphomasPrimary cutaneous marginal zone B-cell lymphoma799Indolent Primary cutaneous follicle center lymphoma1195Indolent Primary cutaneous diffuse large B-cell lymphoma,leg type455Intermediate Primary cutaneous diffuse large B-cell lymphoma,other<150Intermediate Intravascular large B-cell lymphoma<165Intermediate Precursor hematologic neoplasmCD4؉/CD56؉hematodermic neoplasm(blastic NK-cell lymphoma)———Cutaneous lymphomas159death.13 Other factors that may herald a poor prognosis include age Ն60,14 elevated lactate dehydrogenase (LDH),14 elevated soluble interleukin-2 receptor levels,15T-cell clonality within the cutaneous infiltrate detected by polymerase chain reaction,16,17 an identical T-cell clone in the skin and peripheral blood,18 and T-cell clonality in dermatopathic lymph nodes.19Sézary SyndromeSézary syndrome (SS)is defined as erythroderma (stage T4,Fig. 1D ) plus evidence of malignant circulating T cells that satisfy any of the 5 criteria listed in Table 5.20 For the pur-poses of these criteria,the Sézary cell is defined as “any atyp-ical lymphocyte with [a]moderately to highly infolded or grooved nucleus.”20 The pathologic link between MF andSS remains unclear.SS usually arises de novo without antecedent MF.Rarely,MF will evolve to an erythrodermic stage with concomitant hematologic findings that satisfy a diagnosis of SS.Radiotherapy for Mycosis FungoidesOverviewRadiation produces very high complete response rates and may be the single most effective modality in the treatment of MF.21 For patients with stage IA MF, localized, superficial radiotherapy,or total skin electron-beam therapy (TSEBT)may be curative.For patients with more advancedcutaneousFigure 1Clinical presentation of CTCL.(A)Typical early patch with erythema and mild scale.(B)Typical plaque,with raised,palpable borders,central clearing,and overlying scale.(C)Large tumor with necrosis and ulceration.(D)Generalized erythroderma.(Reprinted with permission from Smith BD,Wilson LD:Man-agement of mycosis fungoides.Part 1.Diagno-sis,staging,and prognosis.Oncology [Hun-tingt]17:1281-1288,2003.)Figure 4Clinical presentation of -mon clinical features of CBCL include scalp in-volvement (C and D),red-orange hue (A),red hue (B and C),blue-purple hue (D),grouped papules (A),combined papule and patch (B),a single papule (C),and a single tumor (D).Note the absence of scale.160 B.D.Smith and L.D.Wilsonand/or visceral disease,radiotherapy can provide meaningful and durable palliation.Localized,Superficial RadiotherapyFor treatment of an isolated lesion with localized,superficial radiotherapy,the optimal dose isՆ30Gy delivered in1.2to 2.0 Gy per fraction. For example, Cotter and coworkers22 reported an infield recurrence rate of42%for those treated to a total doseՅ10Gy,32%for10.01to20Gy,21%for20.01 to30Gy,and0%forϾ30Gy.In addition,Wilson and coworkers23reported local failure in 20% (4/20) of lesions treated withՅ20Gy compared with0%(0/10)of lesions treated withϾ20Gy.Evidence suggests that the malignant cells of MF have little ability to execute sublethal damage repair,thus supporting the use of low daily fraction sizes to minimize late toxicity without sacrificing local control.24 Approximately5%of patients with stage IA disease present with a single skin lesion or with2or3lesions in close proximity,such that all clinically apparent disease can be encompassed within a reasonable radiotherapy portal.23For patients with such limited disease, we recom-mend definitive treatment with localized,superficial ra-diotherapy because prior retrospective experiences have documented long-term disease-free survival in excess of 85% with this approach.23,25,26For example, 21 patients treated at Yale University experienced a complete response rate of97%.For those who receivedՆ20Gy,long-term disease-free survival was 91%.23Similarly, 18 patients treated to a median dose of30.6Gy at Allegheny Univer-sity Hospitals experienced a10-year disease-free survivalTable3TNM(B)Classification for Mycosis FungoidesT1–Patches and/or plaques involving<10%body surface areaT2–Patches and/or plaques involving>10%body surface areaT3–One or more cutaneous tumorsT4–Generalized erythrodermaN0–Lymph nodes clinically uninvolvedN1–Lymph nodes clinically enlarged but histologically uninvolvedN2–Lymph nodes clinically nonpalpable but histologically involvedN3–Lymph nodes clinically enlarged and histologically involvedM0–No visceral disease presentM1–Visceral disease presentB0–No circulating atypical cells(<1,000Sézary cells [CD4؉CD7-]/L)B1–Circulating atypical cells present(>1,000Sézary cells [CD4؉CD7-]/L)Adapted with permission.9Table4Staging Classification for Mycosis FungoidesIA T1N0M0 IB T2N0M0 IIA T1-2N1M0 IIB T3N0-1M0 IIIA T4N0M0 IIIB T4N1M0 IVA T1-4N2-3M0 IVB T1-4N0-3M1 The B descriptor is not considered in stage classification.Table2Diagnostic Testing for Patients With Suspected Mycosis FungoidesHistory and physical with attention to skin,lymph nodes,liver,and spleenSkin biopsy with attention toHistologyEpidermotropic lymphocytes with medium-large,extremely convoluted nucleiPautrier’s microabscessesImmunophenotypeClassically CD2؉CD3؉CD4؉CD5؉CD45RO؉CD8؊CD30؊Rarely CD4؊CD3؉CD8؉PCR for T-cell receptor gene rearrangementBiopsy of enlarged lymph nodes with attention toHistology,both number of atypical lymphocytes and disruption of nodal architectureIn dermatopathic nodes,consider PCR for T-cell clonality and immunophenotyping to rule out occult involvement Evaluation of bloodCBC with manual differential,liver function tests and serum chemistries for all patientsIn those with suspected stage IIB-IV diseaseLDH,soluble interleukin-2receptorFlow cytometry for CD2,CD3,CD4,CD5,CD7,CD8,CD20,CD45RO.Findings suggestive of blood involvement include an elevated CD4:CD8ratio(normal range0.5–3.5),or an expanded population of CD4؉CD7؊or CD45RO؉lymphocytes.PCR for T-cell receptor gene rearrangementBone marrow aspirate and biopsy is only indicated to evaluate unexplained cytopeniasImagingPosteroanterior and lateral chest radiograph for stages IA-IBComputed tomography of chest,abdomen,and pelvis for suspected stage IIA-IVCutaneous lymphomas161of 86%.25Minimal stage IA disease should be treated with a single radiationfield where possible,although abutting fields may be required at a convex surface such as the scalp,an axillary fold,breast,hand,or foot.The junction of abuttingfields should be shifted weekly during the course of treatment to improve homogeneity.Field mar-gins can be limited to only1to2cm beyond the visible(or palpable)clinical lesion.TSEBT:TechniqueConsensus guidelines for delivery of TSEBT have been pub-lished by the EORTC27 (Table 6). The EORTC recommends a total dose of 31 to 36 Gy prescribed to the skin surface to produce a dose of at least26Gy at a depth of4mm in truncal skin along the central axis.27Several retrospective experi-ences support these recommendations.For example,analysis of176patients treated at Stanford University revealed that complete response rates increased with total dose as follows: 18%for8to9.9Gy,55%for10to19.9Gy,66%for20to 24.9 Gy, 75% for 25 to 29.9 Gy, and 94% for 30 to 36 Gy.28 For patients treated at the Hamilton Regional Cancer Center, complete response rates were64%for those who received30 Gy(all treated between1977to1980)compared with85% for those who received36Gy(all treated between1980to 1992).29The target volume for patients with patch/plaque disease should include the epidermis and dermis.30The thickness of the epidermis and dermis varies from a minimum of approx-imately2mm at the trunk to a maximum of about4.5mm at the hands and soles of the feet.30For TSEBT, the 80% isodose line should fall more than4mm deep to the skin surface to ensure that the epidermis and dermis fall with the high-dose region.Cutaneous tumors often exceed this4-mm depth, and therefore such lesions are underdosed when treated with TSEBT alone.Patients with cutaneous tumors greater than 4-mm thick may receive boost treatments either during or after TSEBT,typically10Gy delivered in2Gy fractions with an appropriate electron energy and bolus.The treatment geometry for TSEBT used at Yale is pre-sented in Fig. 2.31A total of 6 treatment positions are desig-nated:anteroposterior,right and left anterior oblique,pos-teroanterior, and right and left posterior oblique (Fig. 3). These positions maximize skin unfolding,thereby improving dose homogeneity in the lateral dimension.Each treatment position is treated with both an upper and a lowerfield to maximize dose homogeneity in the vertical dimension.On treatment day1,the anteroposterior,right posterior oblique, and left posterior oblique positions are treated.On treatment day2,the posteroanterior,right anterior oblique,and left anterior oblique positions are treated with the same dose. Over the course of a2-day treatment cycle,a patient will receive2Gy to the entire skin surface.This pattern contin-ues,with patients receiving treatment4days a week for a total of nine weeks,thereby delivering a total dose of36Gy to the skin surface.By using this TSEBT technique,the soles of feet,perineum, and scalp are underdosed and require supplemental patch treatments as outlined in Table 7. Other potentially under-dosed regions include the ventral penis,upper medial thighs, inframammary folds,folds under any pannus,and the lateral andflatter regions of the face and trunk.Supplemental patch fields,as guided by in vivo dosimetry or clinical suspicion, are appropriate for these regions to ensure that the surface dose is at least 50% of the prescribed TSEBT dose.32,33 The total supplemental dose given to these areas may be reduced as clinically indicated to enhance patient tolerance,provided such areas are uninvolved.The hands,wrists,ears,ankles,and dorsal penis may be overdosed and require shielding to limit the dose toՅ36Gy. Detailed dosimetric measurements are typically required to determine the most appropriate shielding regimen for a par-ticular treatment arrangement and patient geometry.The shielding regimen used at Yale and the resulting doses to various anatomic structures are presented in Tables 7 and 8. TSEBT:Clinical ResultsTSEBT is a reasonablefirst-line treatment option for patients with nonlocalized stage IA MF and for most patients with stage IB through III MF.However,no randomized data exist to support selection of a radiation-based strategy overTable5Proposed Hematologic Criteria for the Diagnosis ofSézary Syndrome201.Absolute Sézary cell count>1,000cells/L2.CD4/CD8ratio>10due to an increase in CD3؉orCD4؉cells byflow cytometry3.Aberrant expression of pan-T cell markers(CD2,CD3,CD4,CD5)byflow cytometry.Deficient CD7expression on T cells(or expanded CD4؉,CD7؊cells>40%)is a tentative criterion4.Increased lymphocyte count with T-cell clone in bloodidentified by Southern blot or polymerase chainreaction5.A chromosomally abnormal T-cell cloneTable6EORTC Guidelines for Total Skin Electron-Beam Ther-apy27Dose inhomogeneity in air at treatment distance should be<10%within vertical and lateral dimensions80%isodose line should be>4-mm deep to the skinsurface to ensure that the epidermis and dermis fallwithin the high dose region.80%isodose line should receive a minimum total dose of26Gy20%isodose line should be<20mm from the skin surfaceto minimize dose to underlying structures30-36fractions should be used to minimize acute sideeffectsTotal dose to bone marrow from photon contaminationshould be less than0.7GyPatch treatments should be utilized to underdosed areassuch as the perineum,scalp,and soles of feetInternal and external eye shields should be used to ensurethat the dose to the globe is not more than15%of theprescribed skin surface dose162 B.D.Smith and L.D.Wilsonother treatment strategies,and therefore initial treatment is strongly dependent on institutional and patient prefer-ences.For patients presenting with limited patches and plaques (stage IA,T1N0M0),TSEBT produces complete response rates of at least 90%10,30 and 10-year relapse-free survival of 50%.34 For patients presenting with extensive patches and plaques (stage IB,T2N0M0),TSEBT produces complete response rates of approximately 80% to 90%,27,34but 10-year relapse-free survival is only 10%.34 For patients presenting with tumors (stage IIB,T3N0-1M0),TSEBT pro-duces complete response rates ranging from 50%to 100%depending on the extent of initial skin involvement 30,35,36andFigure 2Treatment geometry for total skin electron-beam therapy.(Re-printed with permission from Smith BD,Jones G,Wilson LD:Mycosis fun-goides,in Gunderson LL,Tepper JE [eds]:Clinical Radiation Oncology [ed 2].Philadelphia,PA,Elsevier,2007.)(Color version of figure is availableonline.)Figure 3Treatment positions for total skin electron-beam therapy.Top row (from left to right):right anterior oblique,anteroposterior,and left an-terior oblique treatment positions.Bottom row (from left to right):right posterior oblique,posteroanterior,and left posterior oblique treatment positions.(Reprinted with permission from Smith BD,Wilson LD:Manage-ment of mycosis fungoides:Part 2.Treatment.Oncology [Hunting]17:1419-1428;discussion 1430,1433)(Color version of figure is available online.)Cutaneous lymphomas 163may confer very meaningful palliation.However,long-term disease-free survival after TSEBT monotherapy for tumors is rare.For patients presenting with erythroderma(stage III,T4 N0-1M0),TSEBT produces complete response rates of ap-proximately75%and may result in prolonged disease-free survival in the subset of patients without blood involve-ment.37For patients with disease that has relapsed after treat-ment with TSEBT,a second course of TSEBT,typically to a total dose of18to23Gy,yields high complete response rates with acceptable toxicity.38,39TSEBT:Adjuvant TherapyBecause the majority of patients will develop a cutaneous relapse after TSEBT monotherapy,adjuvant therapy is rec-ommended to maximize disease-free survival.Retrospective experiences suggest that adjuvant topical nitrogen mustard36 or psoralen plus ultraviolet A (PUVA)40may improve disease-free survival after TSEBT for stage IB MF.For patients with more advanced disease,many adjuvant therapies may be considered, including topical nitrogen mustard,36photo-phoresis,41interferon-␣, bexarotene, and denileukin difti-tox.42TSEBT:ToxicityCommon acute toxicities from TSEBT include pruritus, dry desquamation,erythema,alopecia,xerosis,bullae of the feet,edema of the hands and feet,hypohidrosis(di-minished perspiration),43and loss of fingernails and toe-nails.34,44 Rare acute side effects include gynecomastia in men and mild epistaxis or parotiditis.34Long-term com-plications are typically mild and may include permanent nail dystrophy,xerosis,telangiectasias,partial scalp alo-pecia, and fingertip dysesthesias.27Young patients should be thoroughly counseled regarding risks of gonadal toxic-ity.Second cutaneous malignancies including squamous cell carcinoma,basal cell carcinoma,and malignant mela-noma have been observed in patients treated with TSEBT, particularly in those exposed to multiple therapies that are themselves known to be carcinogenic,such as PUVA and nitrogen mustard.45Other Therapiesfor Mycosis FungoidesIn addition to radiation,other skin-directed therapies for MF include phototherapy(both ultraviolet B monotherapy and PUVA),nitrogen mustard,carmustine,bexarotene, and corticosteroids.Systemic treatment options include systemic chemotherapy,interferon,retinoids,bexarotene, denileukin diftitox,extracorporeal photophoresis,and agents currently under investigation.The effectiveness, toxicity,and indications for these therapies are discussed by Smith and Wilson.46Table 7 Treatment Protocol at Yale-New Haven Hospital31Treatment cycleDay1AP,RPO,LPO treatment positionsDay2PA,RAO,LAO treatment positionsDoseDose per cycle2GyCycles per week2Total cycles18Total dose36GyBoostsPerineum1Gy/d,first9and last9treatmentdaysSoles of feet1Gy/d,first7and last7daystreatment daysBlockingExternal eye shields First11cyclesInternal eye shields Last7cyclesLip shield Cycles1-4Lead mitt for hands Every other cycleFingernail shield Every other cycle,alternating withmittsFoot block Cycles1-3,5,7,9,11,13,15,17,18Testicular shield Used with perineum boost onlyAt Yale,the scalp is boosted by an electron reflector mounted abovethe patient’s head.Alternatively,the scalp may be boosted with120kV,or electrons,typically6to20Gy over1to3weeks asguided by in vivo dosimetry.AP؍anteroposterior;RPO؍right posterior oblique;LPO؍leftposterior oblique;PA؍posteroanterior;RAO؍right anterioroblique;LAO؍left anterior oblique.Table 8 Dose to Anatomic Sites Measured In Vivo31Dose perTwo-Day TSEBT Treatment Cycle*Total DoseWith Blocking and BoostsGy%Gy%Central axis 2.010036100Top of head 2.311541.4115Forehead 2.411842.5118Eye0.112 2.26Eyelid——24.568Lips——3083Posterior neck 2.110437.4104Shoulder 1.78731.387Axilla 2.210939.2109Hand 1.68215.643Mid back 2.010036100Umbilicus 2.110437.4104Flank 2.09935.699Lateral thigh 1.99534.295Perineum0.6312981Top of feet 2.311728.579Soles of feet001439*Dose using dual-field,6-treatment position setup with scalp elec-tron reflector and eye shields.164 B.D.Smith and L.D.WilsonPrimary Cutaneous CD30؉Lymphoproliferative Disorders After MF,primary cutaneous CD30ϩlymphoproliferative disorders are the next most common cutaneous T-cell lymphoma.This category includes both lymphomatoid papulosis(LyP),which is a benign,self-limited entity,and cutaneous anaplastic large-cell lymphoma(C-ALCL), which is a malignant entity that may spread to extracuta-neous sites.LyPLyP presents with grouped erythematous or violaceous papules and/or nodules at different stages of development. Individual skin lesions typically resolve spontaneously within 3 to 12 weeks, but scarring is common.47Three different histologic subtypes have been described,with types A and C consisting of malignant CD30ϩT cells, often with an extensive inflammatory infiltrate,and type B–simulating classical plaque-stage MF.For type C le-sions,discrimination between LyP and C-ALCL may be difficult on histologic grounds,and assessment of the clin-ical context may be required to ensure the proper diagno-sis.3 Although cytologically malignant, LyP is clinically benign with a 5-year survival of 100%.3,48Thus, neither aggressive chemotherapy nor radiotherapy is indicated.49 Treatment options include PUVA or low-dose methotrex-ate,but neither is curative.In the long term,15%to20% of patients with LyP will develop a second malignancy, most commonly MF, C-ALCL, or Hodgkin’s disease.49,50 Cutaneous AnaplasticLarge-Cell LymphomaC-ALCL typically presents as a red-orflesh-colored nodule or tumor that may ulcerate.On biopsy,sheets of large CD30ϩ,nonepidermotropic lymphocytes are noted in the dermis.In contrast to systemic CD30ϩanaplastic large-cell lymphoma,overexpression of anaplastic lymphoma kinase is not found in C-ALCL.Patients with localized disease may be treated with radiotherapy alone,and5-year disease-specific survival is approximately 95%.3,48Cutaneous B-Cell Lymphoma Clinical ManifestationsThe term cutaneous B-cell lymphoma(CBCL)refers to a spectrum of B-cell lymphoproliferative disorders that are ex-clusively confined to the skin at diagnosis.Since the early 1990s,the reported incidence of CBCL has increased rapidly, approaching 4 cases per million in the United States.2 Risk factors for developing CBCL include advanced age,male sex, and white race.2 CBCL most commonly presents in the head and neck region2 as a unilesional or oligolesional patch, pap-ule,plaque,or tumor,with coloration varying from red to orange to blue-purple. (Fig. 4) In contrast to CTCL, CBCLs rarely produce scale.ClassificationThe pathologic classification,and correspondingly the op-timal treatment of CBCL,has been a source of much con-fusion.One important source of confusion has been dif-ferences in the original EORTC and WHO classification schemes for CBCL.For example,the most common sub-type of CBCL according to the original EORTC classifica-tion scheme was“follicle center cell lymphoma,”a low-grade B-cell neoplasm for which definitive radiation therapy without chemotherapy was recommended.How-ever,many lesions classified as“follicle center cell lym-phoma”in the EORTC classification scheme may be clas-sified as“diffuse large B-cell lymphoma”in the WHO classification.51Unlike their nodal counterparts, the ma-jority of CBCLs classified as“diffuse large B-cell lym-phoma”according to WHO criteria exhibit clinically indo-lent behavior and may potentially be treated with definitive radiotherapy without systemic chemotherapy.51 Another source of confusion has been the EORTC category termed“large B-cell lymphoma of the leg,”defined as CBCL with a preponderance of large B cells arising in the lower extremities.Based on the original EORTC criteria, histologically identical lesions would be classified as“large B-cell lymphoma of the leg”if located on the lower extrem-ities and“follicle center cell lymphoma”if located else-where.The combined WHO-EORTC pathologic classification (Table 1), published by Willemze and coworkers in 2005, has made great strides in addressing the deficiencies of the original WHO and EORTC classification schemes.5 Under this classification scheme,the category“primary cutane-ous follicle center lymphoma”includes B-cell neoplasms with both follicular and diffuse architecture,thus encom-passing the majority of“follicle center cell lymphomas”from the EORTC classification and“diffuse large B-cell lymphomas”from the WHO classification.Such CBCLs may be treated with definitive radiotherapy without che-Table 9 CBCL-Prognostic Index(CBCL-PI)2CBCL-PI Group Histology*Skin Site IA Follicular,marginal zone,or lymphoplasmacytic AnyIB Diffuse large B cell Head,neck,or armII Diffuse large B cell Trunk,leg,disseminated II Immunoblastic diffuse large B cell Head,neck,or armIII Immunoblastic diffuse large B cell Trunk,leg,disseminated *Histology is based on the WHO classification.Cutaneous lymphomas165。
总论心脑血管药理、食管癌放疗增敏
指数衰减定律（explonential
attenuation law）
有关名词
放射源（Source） 射线束（Beam） 射野中心轴（Beam Axis） 照射野（Field） 参考点 (reference point) 校准点（Calibration Point） 源皮距（SSD） 源轴距（SAD） 源瘤距（STD）
反散因子BSF（Back
Scatter Factor）
反向散射因子定义为射野中心轴上最大剂量 深度处的组织空气比，是TAR的一个特例：
D BSF＝TAR（d m , FSZ d m） = m D ma
式中FSZdm 为深度dm 处的射野大小；和分别为射 野中心轴上最大剂量深度处模体内和空气中的 吸收剂量率。反向散射因子决定于患者身体的 厚度、射线的能量及射野面积和形状。
原射线和散射线
模体中的任一点的剂量为原射线和散射线剂量 贡献之和。 原射线是指放射源发射的原始光子。 散射线按来源包括准直器系统（包括一级准直 器、均整器、治疗准直器和射线挡块等）的份额和 源于模体的份额。 源于准直器系统的散射线与原射线很难严格的 分开，并且对输出剂量的影响与原射线类似，因此 将这两者合称为有效原射线（Effective primary ray），由它们产生的剂量之和成为有效原射线剂 量，而将模体产生的剂量成为散射线剂量。
照射野大小和形状对PDD的影响
3. 不同照射野形状转换
Sterling的长方野和方野的等效转换：两 种野的面积和周长之比相等，就认为两野相 互等效。假定长方野的边长为a，b；方野的 边长为S。则： 2a × b S= a+b 圆形野和方野的等效转换：对半径为r的 圆形野，只要其面积与某一方形野的近似相 同，就可认为等效：
心脑血管药理、食管癌放疗增敏
心脑血管药物增强食管癌放疗 的临床研究结果
总结心脑血管药物增强食管癌放疗的临床研究结果，为进一步的研究提供参 考。
食管癌放疗增敏的概念
介绍食管癌放疗增敏的概念与意义，为进一步的研究奠定基础。
心脑血管药物增强食管癌放疗 效果的理论基础
探讨心脑血管药物如何作用于放疗，提高放疗治疗食癌的疗效。
心脑血管药物增强食管癌放疗的机制分 析
详细分析心脑血管药物在食管癌放疗过程中的作用机制和影响因素。
心脑血管药物在食管癌放疗中 的应用
心脑血管药理、食管癌放 疗增敏
本报告将介绍心脑血管药理及其对食管癌放疗的增敏作用，探讨心脑血管药 物在食管癌治疗中的应用与临床研究结果。
心脑血管药理介绍
通过了解心脑血管药物的工作机制和作用方式，为之后的食管癌放疗增敏研 究打下基础。
放疗对食管癌治疗的作用
深入探究放疗对食管癌的治疗效果，为增加放疗敏感性提供背景。
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****治疗癫痫的II期临床试验（随机、双盲、安慰剂对照、添加治疗多中心试验）病例记录表****药业值签署本病例报告表之首页，我声明已获得患者签字的知情同意书并且此报告所附之信息与该患者情况一致。
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5．吃药 1 2 3 4 ______ 6．吃饭 1 2 3 4 ______ 7．穿衣服、脱衣服 1 2 3 4 ______ 8．梳头、刷牙等等 1 2 3 4 ______ 9．洗自己的衣服 1 2 3 4 ______ 10．在平坦的室内走 1 2 3 4 ______ 11．上下楼梯 1 2 3 4 ______ 12．上下床，坐下或站起 1 2 3 4 ______ 13．提水煮饭，洗澡 1 2 3 4 ______ 14．洗澡（水己放好） 1 2 3 4 ______ 15．剪脚趾甲 1 2 3 4 ______ 16．逛街、购物 1 2 3 4 ______ 17．定时去厕所 1 2 3 4 ______ 18．打电话 1 2 3 4 ______ 19．处理自己钱财 1 2 3 4 ______ 20．独自在家 1 2 3 4 ______得分：评定医师签名：实验室检查注：尿常规检查中除了填写实验室原始数值外，请填写医生判断结果，统一为：阴性（-）弱阳性（±）其余则分别为（+）（++）（+++）等目前抗癫痫药物服用情况（选择相应状况打×）（1）一种药□（2）二种药□（3）三种药□（4）三种以上□*：用药途径请填写：1-口服2-肌注3-静滴4-静推5-含服6-其它特殊实验室检查脑电图1-正常2-异常□如异常请具体描述：头颅CT/MRI 1-正常2-异常□如异常请具体描述：心电图1-正常2-异常□如异常请具体描述：入组、排除标准入组标准：（请在相应框中打×）1-是2-否1、年龄≥14岁，≤75岁□□2、癫痫病程≥2年□□3、近三月每月发作次数平均2次及以上□□4、目前服用抗癫痫药物1种及以上□□5、无肯定活动性神经系统器质损伤，如脑肿瘤、脑外伤等□□6、愿意参加并良好合作者□□排除标准（请在相应框中打×）1-是2-否1、不符合上述入组标准者□□2、妊娠或哺乳期妇女□□3、严重肝、肾功能损害，特别是肾功能损害者（肌酐超过正常范围）□□4、全血贫血，白细胞小于3.5 109者□□5、血压大于200/100mmHg者□□6、严重认知功能障碍而无家属照料者□□7、合作不良者□□药物分发情况给药日期（月/日/年）_ _ / _ _ / _ _ _ _此次分发药物应为84片，实发______片使用方法：第一天：每次1片，每天3次第二天：每次2片，每天3次第三天：每次3片，每天3次第四天：每次4片，每天3次第五天~：每次4片，每天3次一般情况及疗效一、生命体征体重（Kg）Kg 血压（坐位，mmHg）：收缩压：mmHg 舒张压：mmHg 心率：次/分呼吸：次/分二、癫痫发作状况（请填写发作次数，没有发作的请填0）一周内癫痫发作次数：次1、单纯部分发作（1）<1分钟/次□次（2）1-2分钟/次□次（3）3-5分钟/次□次（4）>5分钟/次□次2、复杂部分发作（1）<1分钟/次□次（2）1-2分钟/次□次（3）3-5分钟/次□次（4）>5分钟/次□次3、原发强直阵挛（1）<1分钟/次□次（2）1-2分钟/次□次（3）3-5分钟/次□次（4）>5分钟/次□次4、部分至强直阵挛（1）<1分钟/次□次（2）1-2分钟/次□次（3）3-5分钟/次□次（4）>5分钟/次□次其它抗癫痫药物服用情况*：用药途径请填写：1-口服2-肌注3-静滴4-静推5-含服6-其它不良事件有无不良事件1-有2-无□如有不良事件请补充填写第31-32页不良事件记录表（包括实验室检查中的AE）药物回收情况上次来访时共分发药物______片此次随访应该归还的药片数______片此次随访实际归还的药片数______片药物分发情况给药日期（月/日/年）_ _ / _ _ / _ _ _ _此次分发药物应为276片，实际______片使用方法：每次4片，每天3次一般情况及疗效一、生命体征体重（Kg）Kg 血压（坐位，mmHg）：收缩压：mmHg 舒张压：mmHg 心率：次/分呼吸：次/分二、癫痫发作状况（请填写发作次数，没有发作的请填0）三周内癫痫发作次数：次1、单纯部分发作（1）<1分钟/次□次（2）1-2分钟/次□次（3）3-5分钟/次□次（4）>5分钟/次□次2、复杂部分发作（1）<1分钟/次□次（2）1-2分钟/次□次（3）3-5分钟/次□次（4）>5分钟/次□次3、原发强直阵挛（1）<1分钟/次□次（2）1-2分钟/次□次（3）3-5分钟/次□次（4）>5分钟/次□次4、部分至强直阵挛（1）<1分钟/次□次（2）1-2分钟/次□次（3）3-5分钟/次□次（4）>5分钟/次□次实验室检查注：尿常规检查中除了填写实验室原始数值外，请填写医生判断结果，统一为：阴性（-）弱阳性（±）其余则分别为（+）（++）（+++）等另：如果实验室检查出现AE请补充填写第32页的不良事件记录表（3）脑电图1-正常2-异常□如异常请描述：神经系统检查1-正常2-异常□如异常请描述：其它抗癫痫药物服用情况*：用药途径请填写：1-口服2-肌注3-静滴4-静推5-含服6-其它不良事件有无不良事件1-有2-无□如有不良事件请补充填写第31-32页不良事件记录表（包括实验室检查中的AE）药物回收情况上次来访时共分发药物______片此次随访应该归还的药片数______片此次随访实际归还的药片数______片药物分发情况给药日期（月/日/年）_ _ / _ _ / _ _ _ _此次分发药物应为372片，实际______片使用方法：每次4片，每天3次一般情况及疗效一、生命体征体重（Kg）Kg 血压（坐位，mmHg）：收缩压：mmHg 舒张压：mmHg 心率：次/分呼吸：次/分三、癫痫发作状况（请填写发作次数，没有发作的请填0）四周内癫痫发作次数：次1、单纯部分发作（1）<1分钟/次□次（2）1-2分钟/次□次（3）3-5分钟/次□次（4）>5分钟/次□次2、复杂部分发作（1）<1分钟/次□次（2）1-2分钟/次□次（3）3-5分钟/次□次（4）>5分钟/次□次3、原发强直阵挛（1）<1分钟/次□次（2）1-2分钟/次□次（3）3-5分钟/次□次（4）>5分钟/次□次4、部分至强直阵挛（1）<1分钟/次□次（2）1-2分钟/次□次（3）3-5分钟/次□次（4）>5分钟/次□次中文版简易智能状态检查（MMSE）日常生活活动量表（ADL）现在我想问些有关您平常每天需要做的事情，我想知道您可以自己做这些事情，需要人家帮助，或者您根本没办法做这些事？（1）自己可以做（2）有些困难（3）需要帮助（4）根本没法做圈上最适合的情况1．自己搭公共车辆 1 2 3 4 ______ 2．到家附近的地方去（步行范围） 1 2 3 4 ______ 3．自己做饭（包括生火） 1 2 3 4 ______ 4．做家务 1 2 3 4 ______ 5．吃药 1 2 3 4 ______ 6．吃饭 1 2 3 4 ______ 7．穿衣服、脱衣服 1 2 3 4 ______ 8．梳头、刷牙等等 1 2 3 4 ______ 9．洗自己的衣服 1 2 3 4 ______10在平坦的室内走 1 2 3 4 ______ 11．上下楼梯 1 2 3 4 ______ 12．上下床，坐下或站起 1 2 3 4 ______ 13．提水煮饭，洗澡 1 2 3 4 ______ 14．洗澡（水己放好） 1 2 3 4 ______ 15．剪脚趾甲 1 2 3 4 ______ 16．逛街、购物 1 2 3 4 ______ 17．定时去厕所 1 2 3 4 ______ 18．打电话 1 2 3 4 ______ 19．处理自己钱财 1 2 3 4 ______ 20．独自在家 1 2 3 4 ______得分：评定医师签名：其它抗癫痫药物服用情况*：用药途径请填写：1-口服2-肌注3-静滴4-静推5-含服6-其它不良事件有无不良事件1-有2-无□如有不良事件请补充填写第31-32页不良事件记录表（包括实验室检查中的AE）药物回收情况上次来访时共分发药物______片此次随访应该归还的药片数______片此次随访实际归还的药片数______片药物分发情况给药日期（月/日/年）_ _ / _ _ / _ _ _ _此次分发药物应为372片，实际______片使用方法：每次4片，每天3次一般情况及疗效一、生命体征体重（Kg）Kg 血压（坐位，mmHg）：收缩压：mmHg 舒张压：mmHg 心率：次/分呼吸：次/分二、癫痫发作状况（请填写发作次数，没有发作的请填0）四周内癫痫发作次数：次1、单纯部分发作（1）<1分钟/次□次（2）1-2分钟/次□次（3）3-5分钟/次□次（4）>5分钟/次□次2、复杂部分发作（1）<1分钟/次□次（2）1-2分钟/次□次（3）3-5分钟/次□次（4）>5分钟/次□次3、原发强直阵挛（1）<1分钟/次□次（2）1-2分钟/次□次（3）3-5分钟/次□次（4）>5分钟/次□次4、部分至强直阵挛（1）<1分钟/次□次（2）1-2分钟/次□次（3）3-5分钟/次□次（4）>5分钟/次□次实验室检查注：尿常规检查中除了填写实验室原始数值外，请填写医生判断结果，统一为：阴性（-）弱阳性（±）其余则分别为（+）（++）（+++）等另：如果实验室检查出现AE请补充填写第32页的不良事件记录表（3）其它抗癫痫药物服用情况*：用药途径请填写：1-口服2-肌注3-静滴4-静推5-含服6-其它脑电图1-正常2-异常□如异常请具体描述：心电图1-正常2-异常□如异常请具体描述：神经系统检查1-正常2-异常□如异常请具体描述：中文版简易智能状态检查（MMSE）日常生活活动量表（ADL）现在我想问些有关您平常每天需要做的事情，我想知道您可以自己做这些事情，需要人家帮助，或者您根本没办法做这些事？（1）自己可以做（2）有些困难（3）需要帮助（4）根本没法做圈上最适合的情况1．自己搭公共车辆 1 2 3 4 ______ 2．到家附近的地方去（步行范围） 1 2 3 4 ______ 3．自己做饭（包括生火） 1 2 3 4 ______ 4．做家务 1 2 3 4 ______ 5．吃药 1 2 3 4 ______ 6．吃饭 1 2 3 4 ______ 7．穿衣服、脱衣服 1 2 3 4 ______ 8．梳头、刷牙等等 1 2 3 4 ______ 9．洗自己的衣服 1 2 3 4 ______ 10．在平坦的室内走 1 2 3 4 ______ 11．上下楼梯 1 2 3 4 ______ 12．上下床，坐下或站起 1 2 3 4 ______ 13．提水煮饭，洗澡 1 2 3 4 ______ 14．洗澡（水己放好） 1 2 3 4 ______ 15．剪脚趾甲 1 2 3 4 ______ 16．逛街、购物 1 2 3 4 ______ 17．定时去厕所 1 2 3 4 ______ 18．打电话 1 2 3 4 ______ 19．处理自己钱财 1 2 3 4 ______ 20．独自在家 1 2 3 4 ______得分：评定医师签名：不良事件有无不良事件1-有2-无□如有不良事件请补充填写第31-32页不良事件记录表（包括实验室检查中的AE）药物回收情况上次来访时共分发药物______片此次随访应该归还的药片数______片此次随访实际归还的药片数______片结束日期（月/日/年）_ _ / _ _ / _ _ _ _不良事件记录表(1)（请医生不要提示）不良事件记录表(2) （请医生不要提示）不良事件记录表(3) （请医生不要提示）中断情况记录表。