不同剂量X射线照射对小鼠免疫系统的影响

目的：观察不同剂量X射线照射对小鼠免疫系统的影响。方法将24只小鼠随机分为对照组（无照射）,低剂量照射组（每次2 Gy）和高剂量照射组（每次5 Gy）,每组各8只。比较不同剂量X射线对小鼠进行单次全身照射后,胸腺、脾脏变化及对外周血白细胞,淋巴细胞及血小板数量的影响。结果高剂量照射组胸腺指数较对照组降低,差异具有统计学意义（P﹤0.05）,而低剂量照射组胸腺指数与对照组比较,差异无统计学意义（P﹥0.05）;随着X线照射剂量的增大,脾脏指数降低,差异均有统计学意义（P﹤0.05）;与对照组比较,低、高剂量照射组小鼠外周血白细胞,淋巴细胞及血小板数量均减少,差异均有统计学意义（P﹤0.05）。结论不同免疫器官对X射线敏感度不同,X射线对免疫功能的损伤随着射线剂量的增加而增大,因此应该加强对放射治疗患者免疫器官的保护。     

Y射线对小鼠胸腺淋巴细胞微丝形态及丝切蛋白磷酸化的影响

目的：通过观察γ射线诱导小鼠胸腺淋巴细胞的微丝形态变化和对丝切蛋白（cofilin）磷酸化的影响,探讨cofilin及相关蛋白在辐射损伤中的作用。方法：将36只BALB/c小鼠按对照组（0 h）,照射后3、6、9、12和24 h时间点随机分为6组,每组6只,除对照组外,其余各组均给予2 Gy γ射线诱导,根据cofilin蛋白表达规律,确定取材时间。另将24只BALB/c小鼠按γ射线诱导剂量随机分为未照射（0 Gy）组、2、6和10 Gy组共4组,照射3 h后取材,观察淋巴细胞微丝形态,进行cofilin蛋白1（cofilin 1）、磷酸化cofilin蛋白（p-cofilin）、LIM激酶1（LIMK1）、TES激酶2（TESK2）和Slingshot家族的磷酸酶2（SSH2）表达检测。结果：BALB/c小鼠在2 Gy γ射线照射3 h后胸腺淋巴细胞cofilin基因的mRNA和蛋白表达均显著下调（P < 0.05）,因此后续实验选择照后3 h为取材时间。通过对cofilin及相关蛋白表达的检测,发现随着γ射线照射剂量的增加,胸腺淋巴细胞cofilin的表达逐渐增加,与对照组相比,以10 Gy组增加最为明显（P < 0.05）;而p-cofilin的表达则减少,10 Gy组减少最为明显（P < 0.05）。LIMK1、TESK2和SSH2的表达在照射后无显著变化（P > 0.05）。结论：随着照射剂量的增加,更多的SSH2使p-cofilin的Ser3位点去磷酸化,胞质内cofilin的量增多,参与到微丝骨架组装的过程中,细胞的迁移能力增强。     

宫颈癌放疗患者外周血淋巴细胞DNA损伤的研究

目的：评价宫颈癌放疗患者外周血淋巴细胞的DNA损伤。方法：取15例宫颈鳞癌放疗患者放疗前及放疗累积剂量为10、20、30、40、50、60Gy时的外周静脉血,以彗星实验检测淋巴细胞的DNA损伤。结果：各累积剂量组淋巴细胞DNA拖尾率比照射前显著升高（P〈0.01）,并且在0～60Gy之间,拖尾率与累积照射剂量之间成线性关系,回归方程为y=12.133＋0.230x,相关系数r=0.964（P〈0.05）。各累积剂量组尾长比照射前均增加（P〈0.01）,在照射剂量累积30Gy时,尾长达最大。之后随照射累积剂量的进一步增加,尾长稍有下降,但是与照射前相比仍持续在较高的水平（P〈0.01）,尾长与累积剂量间不成线性关系。结论：宫颈癌患者放疗后可造成外周血淋巴细胞DNA损伤。     

放射治疗对宫颈癌病人DNA损伤及hprt基因突变的初步研究

目的：评价放射治疗对宫颈癌患者造成的遗传学损伤。方法：取15例宫颈鳞癌放疗患者放疗前及放疗累积剂量为0Gy、10Gy、20Gy、30Gy、40Gy、50Gy、60Gy时的外周静脉血,以彗星实验检测淋巴细胞的DNA损伤,采用多核细胞法测hprt基因位点突变率。结果：各累积剂量组淋巴细胞DNA拖尾率比照射前显著升高（P〈0.01）,并且在0-60Gy之间,拖尾率与累积照射剂量之间成线性关系。各累积剂量组尾长比照射前均增加（P〈0.01）,在照射剂量累积30Gy时,尾长均值达最大。尾长与累积剂量间不成线性关系。hprt基因位点突变率在照射后升高,与照射前相比,在照射累积剂量为30Gy、40Gy和50Gy时,显示有统计学意义差别（P〈0.05）。hprt基因突变率与累积剂量间呈现较好的剂量-效应关系。结论：宫颈癌患者放疗后造成外周血淋巴细胞DNA损伤及hprt基因突变,hprt基因突变和彗星实验用于评价放疗造成的损伤,具有较高的敏感性。     

γ射线诱导小鼠胸腺淋巴细胞中Arp2、Arp3和cofilin基因表达的变化

目的：观察不同剂量的γ射线照射小鼠后,胸腺淋巴细胞中Arp2、Arp3和cofilin基因表达的变化。方法：BALB/c小鼠40只,随机分成4个照射组和1个非照射组,每组8只。照射组行全身γ射线照射,照射剂量分别为0.02、0.1、1和6 Gy。于照后3 h颈椎脱臼处死小鼠,取出胸腺,用PBS冲出胸腺淋巴细胞。分别采用荧光定量PCR技术和Western-blot检测各组小鼠胸腺淋巴细胞中Arp2、Arp3、cofilin mRNA和蛋白的表达。结果：与未照射组比较,各照射组小鼠胸腺淋巴细胞Arp2 mRNA表达的变化无统计学意义（P〉0.05）,1 Gy照射组Arp2蛋白表达上调（H=2.33,P〈0.05）;1 Gy照射组Arp3 mRNA表达下调（t=-12.77,P〈0.01）,6Gy照射组Arp3 mRNA表达上调（t=3.39,P〈0.05）,各照射组Arp3蛋白的表达无明显变化;0.02、0.1和1 Gy照射组cofilin mRNA的表达上调（t=6.38～9.41,P〈0.01）,各照射组cofilin蛋白的表达变化无统计学意义（P〉0.05）。结论：不同剂量的γ射线可诱导BALB/c小鼠胸腺淋巴细胞Arp2、Arp3和cofilin基因表达发生变化,其变化特点与照射剂量大小有关,该结果为研究辐射致胸腺淋巴细胞微丝骨架改变的机制提供了实验依据。     

放化疗综合治疗鼻咽癌临床观察

对21例鼻咽癌采用顺铂、平阳霉素加放疗与单纯放疗随机分组对比观察。两组照射方法、剂量相同。鼻咽部DT 65~80 Gy/6.5~8周,颈部总剂量60~70Gy/6~7.5周。综合组颈部淋巴结缩小所需照射剂量较单放组要低。疗终综合治疗组颈淋巴结退缩率较单放组差别并不显著。     

X射线照射对人脐静脉内皮细胞焦亡的影响

目的：探讨X射线照射对人脐静脉内皮细胞（HUVEC）焦亡的影响。方法：单次10 Gy X射线照射HUVEC细胞,采用ELISA法检测照射后0~72 h HUVEC分泌细胞因子IL-1β、IL-6、TNF-α和IL-18的浓度,Western blot法检测照射后6~48 h HUVEC内Caspase-1的活化水平,采用透射电子显微镜检测照射后72 h HUVEC形态的变化。采用流式细胞术检测单次10 Gy以及多次小剂量（2.5 Gy/d,连续4 d）照射后HUVEC焦亡率的变化。结果：10 Gy X射线照射后0~72 h HUVEC中IL-1β、IL-6、TNF-α和IL-18浓度与对照组（0 Gy组）相比均明显升高（P<0.05）。10 Gy X射线照射后6~48 h细胞内Caspase-1活化水平升高（P<0.05）,细胞呈现体积增大肿胀状态。单次10 Gy照射组和多次小剂量照射组细胞焦亡率均明显高于空白对照组（P<0.01）;此外,单次10 Gy照射组细胞焦亡率较多次小剂量照射组细胞升高约1倍（P<0.01）。结论：X射线照射可引起人脐静脉内皮细胞HUVEC焦亡;在总剂量相同情况下,单次大剂量照射引起的HUVEC焦亡水平明显高于多次小剂量照射。     

不同辐射剂量损伤后T淋巴细胞亚群及Th1和Th2的变化

目的： 观察不同辐射剂量损伤对小鼠T淋巴细胞功能亚群的影响,探讨辐射所致的免疫系统损伤在细胞学和分子水平上的机制。方法：C57BL/6j小鼠采用60 Coγ射线照射诱导辐射损伤模型。总照射剂量分别为0、0.7、1.4、2.8和5.6 Gy。应用细胞表面标志和细胞内因子标记,流式细胞仪检测分析不同剂量组小鼠脾T淋巴细胞功能亚群CD3＋、CD4＋、CD8＋ T细胞改变及Th1和Th2的变化。结果：与空白对照组比较,小鼠脾T淋巴细胞功能亚群CD3＋、CD4＋、CD8＋ T细胞在照射后均明显降低(P＜0.01),降低幅度与受照剂量明显相关。CD4＋/CD8＋比值显示照射后均明显升高(P＜0.01)。照射后Th1水平均降低(P＜0.01),而在照射剂量≥1.4 Gy时Th2均明显降低(P＜0.01),其中Th1降低明显高于Th2。受照剂量大于2.8 Gy组Th2/Th1比值较空白对照组明显升高(P＜0.01)。结论：不同照射剂量对T淋巴细胞功能亚群CD3+、CD4+、CD8+ T细胞和CD4＋/CD8＋比值有明显影响,Th1,Th2和Th2/Th1功能亚群的失衡在辐射所致的免疫损伤中具有重要作用。     

豚鼠中耳黏膜早期辐射反应扫描电镜研究

目的：观察不同剂量放疗后中耳黏膜超微结构变化规律。方法：豚鼠左侧卧位，γ射线照射右侧耳，300cGy/F,5次／周；12只豚鼠分为照射15Gy组、30Gy组、45Gy后30天组，3只未照射作为对照，取中耳黏膜行扫描电镜观察。结果：中耳黏膜上皮在低剂量照射时无明显变化，随着剂量的增加，中耳腔内出现渗出，中耳黏膜纤毛、微纤毛可发生脱落、融合、倒伏、方向改变。结论：在实验观察时间内，放射后中耳黏膜纤毛结构随着剂量和时间的变化而改变，在放射早期、剂量较小时黏膜纤毛结构、功能可能正常，随剂量增加将会恶化。     

附子提取物对肺癌A549细胞增殖抑制及放射增敏作用的研究

目的: 观察附子提取物对人肺癌A549细胞增殖及放射敏感性的影响,并探讨其可能的机制。方法: 体外培养肺癌A549细胞,采用CCK-8法检测不同浓度附子提取物作用后细胞增殖情况,并选择IC₂₀(30μg/mL)作为后续实验浓度。集落形成实验检测A549细胞的存活分数,单机多靶模型拟合细胞存活曲线计算平均致死剂量(D₀)及放射增敏比(SER)。将细胞分为对照组、附子组、X射线照射组和附子处理后X射线照射组。对照组给予培养基,附子组给予30μg/mL附子提取物处理24 h,X射线照射组采用10 Gy的X射线照射,附子处理后X射线照射组先采用30μg/mL附子提取物处理24 h后,再给予10 Gy的X射线照射。流式细胞术检测细胞凋亡率,Western blot法检测细胞中Bax、Bcl-2蛋白表达水平。结果: CCK-8法检测结果显示,小于20μg/mL的附子提取物对A549细胞存活率有增强作用,但随着附子提取物浓度到达30μg/mL,开始对人肺癌A549细胞生长具有抑制作用,且与附子提取物浓度相关。集落形成实验结果提示附子处理后X射线照射组存活曲线起始处肩部稍窄,表明联用附子提取物后,引起细胞死亡所需的放疗剂量逐渐减小,X射线照射组和附子处理后X射线照射组D₀值分别为1.83和1.48 Gy,SER为1.24。流式细胞术检测结果提示附子处理后X射线照射组细胞凋亡率显著增加,高于附子组和X线照射组(P<0.05)。Western blot检测结果显示,附子组与X射线照射组较对照组细胞Bax蛋白表达水平升高,Bcl-2蛋白表达水平下降。附子处理后X射线照射组较对照组细胞Bax、Bcl-2蛋白含量变化更加显著(P<0.01)。结论: 30μg/mL的附子提取物对人肺癌A549细胞具有增殖抑制作用和放射增敏作用,其机制可能与诱导细胞凋亡有关。     

How Much Radiation is the Chemotherapy Worth in Advanced Head and Neck Cancer?

PURPOSE: To estimate the radiotherapeutic dose equivalence of chemoradiotherapy in head and neck cancer. METHODS: The biologic equivalent dose (BED) of radiotherapy in nine trials of standard and five trials of modified fractionated radiotherapy with or without chemotherapy was calculated using the linear-quadratic formulation. Data from Radiation Therapy Oncology Group (RTOG) study 90-03 were used to calculate the relationship (S) between increase in locoregional control (LRC) and increase in BED with modified vs. standard fractionated radiotherapy. The increase in LRC with chemoradiotherapy vs. radiotherapy alone, the BED of the radiotherapy-alone arms, and the "S" value were used to calculate the BED contribution from chemotherapy and the total BED of chemoradiotherapy from each study. RESULTS: From RTOG 90-03, a 1% increase in BED yields a 1.1% increase in LRC. The mean BED of standard fractioned radiotherapy was 60.2 Gy(10) and 66 Gy(10) for modified fractionation. The mean BED of standard fractionated chemoradiotherapy was 71 Gy(10) (10.8 Gy(10) contributed by chemotherapy). The mean BED of modified fractionated chemoradiotherapy was 76 Gy(10) (10.4 Gy(10) contributed by chemotherapy). CONCLUSIONS: Chemotherapy increases BED by approximately 10 Gy(10) in standard and modified fractionated radiotherapy, equivalent to a dose escalation of 12 Gy in 2 Gy daily or 1.2 Gy twice daily. Such an escalation could not be safely achieved by increasing radiation dose alone.     

原发于上颌窦非霍奇金淋巴瘤15例临床分析

目的对原发于上颌窦非霍奇金淋巴瘤的临床、病理、治疗及预后结合文献进行分析。方法经手术后病理确诊为原发于上颌窦非霍奇金淋巴瘤15例在本院行放疗和化疗的综合治疗。放疗采用60Co-γ线或6MV~8MV高能X线,原发灶放疗中位剂量为56Gy,颈部放疗剂量为50Gy,颈部预防放疗剂量为44Gy。放射治疗前后行CHOP、COPP、COMP、BACOP等方案化疗2个~6个周期。结果5年生存率为53.4%。死亡8例,均死于远处转移。结论上颌窦非霍奇金淋巴瘤需行放射治疗和全身化疗,有条件时给予鞘内预防化疗。     

Cardiac toxicity after radiation therapy for 52 patients with malignant thymic tumors

Complete surgical resection is the first choice for all malignant thymic tumors and has a better prognosis. Myojin[1] reported 5-year survival rates for Masaoka Stage III thymoma of 86%. Radical or adjuvant radiotherapy is recommended when surgery is impossible or thymomas could not be completely resected. The results of radiation therapy for invasive thymomas are also satisfactory[2, 3]. However, late side effects of radiation therapy, such as second malignant tumors and radiation-induced h…     

Improved long-term survival with combined modality therapy for pediatric nasopharynx cancer

PURPOSE: Nasopharynx cancer is a rare malignancy in childhood. This study aims to determine the role of chemotherapy, the optimal dose of radiation, and the long-term outcome for children with locoregional disease. METHODS AND MATERIALS: Thirty-three patients [median age 14 (range: 12-20) years] were treated for Stage I-IVB nasopharynx cancer. Thirteen patients (39%) received radiotherapy alone and 20 patients (61%) had chemotherapy and radiotherapy. The median radiation dose to the primary tumor was 66 Gy (range: 54-72 Gy). The median follow-up time for surviving patients was 8.4 years (range: 0.5-23.6 years). RESUL TS: The actuarial 10-year locoregional relapse-free survival, distant metastases-free survival, and overall survival rates were 77%, 68%, and 58% , respectively. Locoregional control was improved for patients treated with radiation doses > 60 Gy compared to those receiving < or = 60 Gy (93% vs. 60%, p < 0.03). The addition of chemotherapy had no significant effect on locoregional control but did reduce the development of distant metastases (16% vs. 57%, p = 0.01). Combined modality therapy improved 10-year disease-free survival (84% vs. 35%, p < 0.01) and survival (78% vs. 33%, p < 0.05) over radiation alone. The 10-year actuarial rate of severe complications was 24%.60 Gy are used for gross disease. The addition of chemotherapy decreases the risk of distant metastases and increases survival.     

肺癌患者急性放射性肺损伤发生的相关因素分析

[目的]分析肺癌患者放射治疗后急性放射性肺损伤发生的影响因素。[方法]选取171例肺癌放射治疗的患者,采用Logistic回归分析研究性别、年龄、是否化疗、放疗剂量、V5、V20、平均肺剂量(MLD)等因素与患者3级及以上急性放射性肺损伤发生率的相关性。[结果]171例肺癌放射治疗的患者中,发生3级及以上急性放射性肺损伤50例(29.3%)。单因素分析发现,吸烟、放疗前化疗周期数多、同期放化疗、V5>40%、V20>25%、V20>28%、MLD>10Gy、MLD>13Gy均可导致肺癌患者3级及以上放射性肺损伤发生率的升高。多因素分析显示,吸烟、放疗前化疗周期数多、V20>28%、MLD>13Gy与3级及以上放射性肺损伤发生率有关。[结论]在肺癌放疗计划设计中,应针对中国肺癌患者的特点,设定适合的物理参数;此外,还需考虑患者的吸烟史、化疗史等个体化因素,尽可能降低急性放射性肺损伤的发生率。     

鼻咽癌面颈联合野放疗对唾液腺功能影响的临床分析

目的 :利用放射性核素99mTcO4-动态显像唾液腺定量测定鼻咽癌面颈联合野放疗前、中、后唾液腺功能的变化并探讨与放疗剂量之间的关系。方法 :2 0 0 3年 2月 1日～ 2 0 0 3年 10月 3 1日 ,分别对 2 0例鼻咽癌面颈联合野放疗患者于放疗前、放疗至 10、3 6～ 40、70Gy时进行99mTcO4-动态显像定量测定其唾液腺(腮腺、颌下腺 )摄锝率 (UR)、泌锝率 (ER)变化 ,同时观察其口干程度进行临床分级。结果 :2 0例鼻咽癌面颈联合野放疗剂量为 10和3 6～ 40Gy时 ,其泌锝率明显低于放疗前 ,P <0 0 5 ,在放疗 70Gy时降到最低 ,P <0 0 1。与临床观察到的口干严重程度一致 ,而其摄锝率在 3 6～ 40Gy照射以前变化不明显 ,无统计学意义。结论 :鼻咽癌面颈联合野照射患者放疗前无明显唾液腺功能障碍 ,随着放疗剂量的增加 ,唾液腺功能明显下降 ,其ER较UR下降明显 ,在确保患者放疗疗效的同时 ,应尽可能提高放疗技术 ,减少唾液腺照射剂量和放疗体积 ,保护唾液腺功能 ,以提高患者的生活质量。     

非小细胞肺癌吉西他滨诱导化疗+放疗后放射性肺炎危险因素及剂量学分析

目的 对非小细胞肺癌(NSCLC)吉西他滨化疗后急性放射性肺炎(ARP)的发生情况进行总结,阐明吉西他滨诱导化疗后发生急性放射性肺炎的高危因素及剂量学限制。方法 回顾性分析2010-2017年间浙江省肿瘤医院放疗科收治的接受吉西他滨化疗+胸部放疗的NSCLC患者191例,收集患者的基本信息、放化疗情况以及ARP情况。Logistic法单因素和多因素分析影响ARP发生的因素。结果 共49例患者发生≥2级ARP,占25.7%。单因素分析显示吉西他滨累积剂量≥9.0g发生ARP概率是<9.0g的3.45倍(P=0.015),放疗剂量≥50Gy与ARP发生有关(P=0.008),放化疗间隔时间在10周内ARP发生风险增加7.69倍(P=0.047);双肺V5Gy、V20Gy、V30Gy和平均肺剂量(MLD)均能有效预测ARP发生(P≤0.001)。多因素分析仅有放疗剂量(P=0.044)和V5Gy(P=0.02)是ARP发生的预测因素。结论 对于接受吉西他滨化疗的NSCLC患者来说,吉西他滨累积剂量、化放疗间隔时间以及放疗剂量均与ARP的发生有关,同时应当限制双肺V5Gy、V20Gy、V30Gy和MLD,以减少ARP的发生。     

Dose-response analysis for radiotherapy delivered to patients with intermediate-grade and large-cell immunoblastic lymphomas that have completely responded to CHOP-based induction chemotherapy

PURPOSE: To test the hypothesis that prechemotherapy tumor size affects the dose of radiation that should be delivered to intermediate-grade and large-cell immunoblastic lymphomas that have completely responded to cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP)-based induction chemotherapy. METHODS AND MATERIALS: From September 1988 through December 1996, 294 patients with newly diagnosed, Stage I-IV, intermediate-grade or large-cell immunoblastic lymphomas were enrolled on 2 prospective protocols at the M. D. Anderson Cancer Center. Treatment consisted of CHOP-based chemotherapy with or without involved field radiotherapy. One hundred seventy-two patients, with 178 nodal sites and 87 nonbony, extranodal sites of disease achieved a complete response to 2-6 cycles of chemotherapy and underwent involved field radiotherapy. Total radiation doses ranged from 30.0 to 50.4 Gy (mean +/- standard deviation: 39.7 +/- 2.5 Gy) over 22-49 days using a daily fraction size of 1.3-2.3 Gy. Because various fraction sizes were delivered, the linear-quadratic model was used to convert total radiation doses to biologically equivalent doses given at 1.8 Gy per fraction (D1.8). An alpha/beta ratio of 10 Gy was used for the lymphomas, resulting in D1.8 ranging from 29.1 to 50.8 Gy. Regression tree analysis was performed on nodal sites of disease to determine which of the following factors were predictive of local control: age, tumor size, D1.8, total radiation dose, and duration of radiotherapy. Based on the results of the regression tree analysis, Kaplan-Meier analysis was used to determine the probability of local control per site as a function of tumor size and D1.8. Regression tree analysis was also performed on patients with nonbony disease who received D1.8 = 29.1-39.1 Gy to determine if small lymphomas could be locally controlled with relatively low doses of radiation. The log-rank test was used to compare local control curves. RESULTS: The median length of follow-up among survivors was 63 months. Regression tree analysis of nodal sites identified 3 distinct groups: (a) lymphomas < or = 10 cm and D1.8 = 29.1-39.1 Gy; (b) lymphomas < or = 10 cm and D1.8 = 39.2-50.8 Gy; and (c) lymphomas > 10 cm. For nonbony lymphomas that measured < 3.5 cm, low doses of radiation resulted in excellent local control (5-year rates: 96% vs. 97% for D1.8 = 29.1-39.1 Gy vs. D1.8 = 39.2-50.8 Gy; p = 0.610). For 3.5-10.0 cm lymphomas, higher doses of radiation resulted in better local control (5-year rates: 40% versus 98% for D1.8 = 29.1-39.1 Gy versus D1.8 = 39.2-50.8 Gy, p < 0.0001). A narrow dose range (D1.8 = 39.2-40.7 Gy) was delivered to the 8 lymphomas measuring > 10 cm that completely responded to 6 cycles of chemotherapy, resulting in a 5-year local control rate of only 70%. There was no difference in local control for nodal versus nonbony, extranodal sites of disease. CONCLUSION: D1.8 ranging from 29.1 to 39.1 Gy yielded excellent local control for nonbony lymphomas measuring < 3.5 cm that had completely responded to a median of 3 cycles of CHOP-based chemotherapy. D1.8 ranging from 39.2 to 50.8 Gy yielded excellent local control for nonbony lymphomas measuring 3.5-10.0 cm that completely responded to either 3 or 6 cycles of chemotherapy. For nonbony lymphomas measuring > 10 cm that completely responded to 6 cycles of chemotherapy, D1.8 ranging from 39.2 to 40.7 Gy yielded suboptimal local control, suggesting that higher doses of radiation are indicated.     

Systematic overview of preoperative (neoadjuvant) chemoradiotherapy trials in oesophageal cancer: evidence of a radiation and chemotherapy dose response.

BACKGROUND AND PURPOSE: Numerous trials have shown that pathological complete response (pCR) following preoperative chemoradiotherapy (CRT) and surgery for oesophageal cancer is associated with improved survival. However, different radiotherapy doses and fractionations and chemotherapy drugs, doses and scheduling were used, which may account for the differences in observed pCR and survival rates. A dose-response relationship may exist between radiotherapy and chemotherapy dose and pCR. PATIENTS AND METHODS: Trials using a single radiotherapy and chemotherapy regimen (5FU, cisplatin or mitomycin C-based) and providing information on patient numbers, age, resection and pCR rates were eligible. The endpoint used was pCR and the covariates analysed were prescribed radiotherapy dose, radiotherapy dosexdose per fraction, radiotherapy treatment time, prescribed chemotherapy (5FU, cisplatin and mitomycin C) dose and median age of patients within the trial. The model used was a multivariate logistic regression. RESULTS: Twenty-six trials were included (1335 patients) in which 311 patients (24%) achieved pCR. The probability of pCR improved with increasing dose of radiotherapy (P=0.006), 5FU (P=0.003) and cisplatin (P=0.018). Increasing radiotherapy treatment time (P=0.035) and increasing median age (P=0.019) reduced the probability of pCR. The estimated alpha/beta ratio of oesophageal cancer was 4.9 Gy (95% confidence interval (CI) 1.5-17 Gy) and the estimated radiotherapy dose lost per day was 0.59 Gy (95% CI 0.18-0.99 Gy). One gram per square metre of 5FU was estimated to be equivalent to 1.9 Gy (95% CI 0.8-5.2 Gy) of radiation and 100mg/m2 of cisplatin was estimated to be equivalent to 7.2 Gy (95% CI 2.1-28 Gy). Mitomycin C dose did not appear to influence pCR rates (P=0.60). CONCLUSIONS: There was evidence of a dose-response relationship between increasing protocol prescribed radiotherapy, 5FU and cisplatin dose and pCR. Additional significant factors were radiotherapy treatment time and median age of patients within the trial.