Adjuvant and neoadjuvant chemoradiation therapy for primary colorectal cancer

The management of rectal cancer presents substantial challenges. Patients with T3 and/or node-positive rectal cancers are at high risk for local failure and distant metastases (DM). Adjuvant radiation has been shown to decrease local recurrence (LR) rates; however, this local therapy has not been demonstrated to improve survival when compared to surgery alone. In several prospective randomized trials adjuvant chemoradiation with 5-fluorouracil-(5-FU)-based chemotherapy improved LR rates, DM rates, and overall survival (OS). The optimal chemotherapeutic regimen has not been determined; however, studies comparing standard IV bolus 5-FU administration with continuous infusion (CI) 5-FU demonstrated that CI administration was superior. Preoperative therapy has potential advantages over adjuvant therapy such as less acute bowel toxicity and improved sphincter preservation. Preoperative chemoradiation has been shown in several studies to improve LR rates and OS when compared to surgery alone. Our current approach to patients with resectable T3 or N1 cancer in the distal two-thirds of the rectum on preoperative staging is preoperative chemoradiation with planned postoperative chemotherapy. This regimen offers the best chance for local control and disease-free survival while potentially downstaging the tumor and improving sphincter preservation.     

Flexure dose: the low-dose limit of effective fractionation

Total radiation dose often can be increased without subsequent increases in the severity of tissue injury by using reduced doses per fraction. The flexure dose, df, is defined as the largest fractional dose for which further fractionation produces no significant change in the total dose required to reach a specified effect level. Thus, df is clinically relevant in that it represents the limit of effective dose fractionation. For those tissues in which injury reflects depletion of a critical proportion of target cells, the flexure dose is a measure of the extent of the initial, nearly linear portion of the dose-survival curve. More generally, the flexure dose is a measure of the extent of the initial, nearly linear portion of a dose-response curve in organized tissue, whatever its relationship to clonogenic target cells might be. Several quantitative expressions for df are derived. The characteristic common to these is that each defines the flexure dose as a multiple of the ratio alpha/beta of the parameters of the linear-quadratic model of cell survival or dose response, where the multiple is a measure of experimental or statistical resolution. These multiples tend to fall within a limited range, thereby defining the "region of flexure" via the inequality 0.05 (alpha/beta) less than or equal to df less than or equal to 0.15 (alpha/beta). Estimates of the region of flexure are presented for a variety of normal and neoplastic tissues.     

“Buchler”后装机在临床应用的评估(附宫颈癌135例五年疗效分析)

本文从临床角度对Buchler机的放射源和剂量学上进行初步评估,认为尚有不足之处,另总结1983年10月至1985年3月应用高剂量率Buchler机合并~(60)钴或9 Mev直线加速器对分期为Ⅱ、Ⅲ期的宫颈癌135例进行根治性放射治疗,其五年生存率分别是85.25％(52/61)和68.92％(51/74)全组五年生存率为76.03％(103/135)。     

CM治疗计划系统照射野剂量计算的验证

目的　对美国CMS公司生产的肿瘤治疗计划系统 (TPS)计算结果值与实际测量值进行比较。方法　按照测量条件下的带有Farmer型电离室的固体水模在螺旋CT下进行扫描 ,图像通过网络数字传输系统传入TPS中 ,分别进行 10cm× 10cm规则野与不规则野、均匀组织与不均匀组织(分别含骨和肺 )、源轴距 10 0cm中心轴上深度 6和 10cm、野内任意点、机架角 30°、楔形板、MLC、铅挡、源皮距 90和 12 0cm条件下 6和 15MVX线计划设计并采用卷积和叠加两种算法计算 ,再与加速器治疗机上实际测量结果进行比较。结果　对于均匀组织和含骨的不均匀组织卷积和叠加算法的计算结果值具有良好的一致性 ,两种计算方法的结果偏差在 0 .5 %以内。多数实测值与计算值偏差在2 .5 %以内 ,个别计算与实测结果偏差在 3%以内 ,含肺的不均匀组织做不均匀组织校准后卷积算法与实测偏差较大 ,6MVX线为 7.8% ,15MVX线为 4 .5 % ,而叠加算法与实测偏差在 1.5 %以内。结论　除了卷积算法不能用于含肺组织或含气空腔剂量计算以外 ,卷积和叠加算法均可用于剂量计算 ,且偏差符合临床要求。     

Multicentre analysis of treatment planning information: Technical requirements,possible applications and a proposal

Digital data from 3‐D treatment planning computers is generally used for patient planning and then never considered again. However, such data contains enormous quantities of information regarding patient geometries, tissue outlining, treatment approaches and dose distributions. Were such data accessible from planning systems from multiple manufacturers, there would be substantial opportunities for undertaking quality assurance of radiotherapy clinical trials, prospective assessment of trial outcomes and basic treatment planning research and development. The technicalities of data exchange between planning systems are outlined, and previous attempts at producing systems capable of viewing and/or manipulating imaging and radiotherapy digital data reviewed. Development of a software system for enhancing the quality of Australasian clinical trials is proposed.     

Significance of plasma transforming growth factor-β levels in radiotherapy for non–small-cell lung cancer

PURPOSE: In dose-escalation studies of radiotherapy (RT) for non-small-cell lung cancer (NSCLC), radiation pneumonitis (RP) is the most important dose-limiting complication. Transforming growth factor-beta1 (TGF-beta1) has been reported to be associated with the incidence of RP. It has been proposed that serial measurements of plasma TGF-beta1 can be valuable to estimate the risk of RP and to decide whether additional dose-escalation can be safely applied. The aim of this study was to evaluate prospectively the time course of TGF-beta1 levels in patients irradiated for NSCLC in relation to the development of RP and dose-volume parameters. METHODS AND MATERIALS: Plasma samples were obtained in 68 patients irradiated for medically inoperable or locally advanced NSCLC (dose range, 60.8-94.5 Gy) before and 4, 6, and 18 weeks after the start of RT. Plasma TGF-beta1 levels were determined using a bioassay on the basis of TGF-beta1-induced plasminogen activator inhibitor-1 expression in mink lung cells. All patients underwent chest computed tomography scans before RT that were repeated at 18 weeks after RT. The computed tomography data were used to calculate the mean lung dose (MLD) and to score the radiation-induced radiologic changes. RP was defined on the basis of the presence of either radiographic changes or clinical symptoms. Symptomatic RP was scored according to the Common Toxicity Criteria (Grade 1 or worse) and the Southwestern Oncology Group criteria (Grade 2 or worse). Multivariate analyses were performed to investigate which factors (pre- or posttreatment TGF-beta1 level, MLD) were associated with the incidence of RP. To improve our understanding of the time course of TGF-beta1 levels, we performed a multivariate analysis to investigate which factors (pre-RT TGF-beta1 level, MLD, RP) were independently associated with the posttreatment TGF-beta1 levels. RESULTS: The pre-RT TGF-beta1 levels were increased in patients with NSCLC (median 21 ng/mL, range, 5-103 ng/mL) compared with healthy individuals (range, 4-12 ng/mL). On average, the TGF-beta1 levels normalized toward the end of treatment and remained stable until 18 weeks after RT. In 29 patients, however, TGF-beta1 was increased at the end of RT with respect to the pre-RT value. The multivariate analyses revealed that the MLD was the only variable that correlated significantly with the risk of both radiographic RP (p = 0.05) and symptomatic RP, independent of the scoring system used (p = 0.05 and 0.03 for Southwestern Oncology Group and Common Toxicity Criteria systems, respectively). The TGF-beta1 level at the end of RT was significantly associated with the MLD (p <0.001) and pre-RT TGF-beta1 level (p = 0.001). CONCLUSION: The MLD correlated significantly with the incidence of both radiographic and symptomatic RP. The results of our study did not confirm the reports that increased levels of TGF-beta1 at the end of RT are an independent additional risk factor for developing symptomatic RP. However, the TGF-beta1 level at the end of a RT was significantly associated with the MLD and the pre-RT level.     

鼻咽癌放射治疗后颅神经损伤的临床分析

目的　探讨鼻咽癌放射治疗后颅神经损伤的临床特点、诊断、治疗及预后因素。方法　对 1990年 4月至 2 0 0 3年 2月收治的 86例鼻咽癌放射治疗后颅神经损伤患者的临床资料进行回顾性分析。结果　首程放疗患者颅神经损伤的潜伏期为 0 .5～2 1.0年 ,中位潜伏期为 4.5年。以舌下神经损伤最为多见 ( 68.6% )。 63例早期使用激素、抗生素、大量维生素等药物治疗的患者中 ,18例症状轻微改善 ,3 3例无明显变化 ,12例病情进展。随访 77例 ,死亡 2 8例 ,49例生存 ,出现神经症状者生存期 0 .6～ 13 .0年 ,3 2例生活不便 ,17例生活困难。结论　放射性颅神经损伤缺乏有效的治疗手段 ,它的发生与照射剂量、照射技术及分次剂量等因素有关 ,放射性颅神经损伤严重影响患者生存质量 ,应尽量减少其发生     

全盆四野加速超分割放射治疗Ⅲb期子宫颈鳞癌的临床研究

探讨全盆四野加速超分割放射治疗晚期子宫颈癌的临床价值。方法:于1998年1月至1999年10月分别采用全盆二野常规分割标准方案(CF组,18例)和全盆四野加速超分割方案(AHF组,17例),治疗Ⅲb期子宫颈鳞癌,对放射不良反应和治疗效果进行临床比较研究。结果:1)AHF组全疗程平均40.1天完成,CF组平均57.3天完成,AHF组疗程显著短于CF组(P<0.01);2)AHF组2、3年生存率分别为88.2%、82.4%,CF组分别为83.3%、72.2%,前者有提高生存率的趋势,但差异无统计学意义(P>0.05);3)AHF组3年局部控制率(94.1%)高于CF组(77.8%),AHF组有提高肿瘤局部控制率的趋势,但两组差异无统计学意义(P>0.05);4)近期放疗反应两组第一位均为直肠反应,其次是膀胱反应,差异无统计学意义(P>0.05);远期放疗反应第一位为照射野皮下纤维化,AHF组发生率(5.9%)显著低于CF组(72.2%)(P<0.01),两组直肠、膀胱反应发生率差异均无统计学意义(P>0.05)。结论:当采用60Co体外照射时,全盆四野加速超分割方案与常规分割标准方案比较,有提高ⅢΒ期子宫颈鳞癌生存率及局部控制率的趋势,具有总疗程明显缩短,不增加近期放疗不良反应,可显著减少远期照射野皮下纤维化的发生等优点,值得推广。     

Radiation tolerance of the cochlear nerve at the γ-knife in rabbits

Since the first treatment of acoustic neurinoma using the γ-knife by Leksell, a series of cases have been reported with good control rates. However, the most frequent complication is delayed hearing loss which occurs in more than 50% of patients. The purpose of this study was to define a safe dose by analyzing the radiosurgical dose-response relationship and histological effects on the normal cochlear nerve in rabbit. The rabbits had computed tomography (CT)-guided stereotactic radiosurgery on their cochlear nerves in the internal auditory canal with a 4 mm collimator focusing of a γ-unit. Maximum doses of 10, 20, 30, 40, 60, 80, 100, 200 and 500 Gy were administered. After the radiosurgery, auditory brain stem responses (ABR) and the behavior of the rabbits were evaluated periodically. At the conclusion, histological investigations were performed. No physiological or histological findings were observed from doses of 30 Gy or below during the 12 month period after the radiosurgery. A dose of 100 Gy caused a severe ABR threshold elevation, vestibular dysfunction and facial palsy. Necrosis and demyelination of nerves were observed pathologically. In this study, we determined that the safe dose to the normal cochlear nerve during radiosurgery was under 40 Gy in rabbits, and complications seemed to vary due to individual differences in radiation tolerance.     

异基因造血干细胞移植并发致死性间质性肺炎

目的探讨小儿异基因造血于细胞移植并发间质性肺炎（IP）的发病病因、临床特点、危险因素及防治措施。方法根据尸解病理检查及聚合酶键反应技术对病毒病原学检测结果，结合临床移植资料综合分析。结果14例移植患儿中并发IP3例（3／14），分别死于十19天、＋76天、＋150天;3例IP中2例移植前后外周血及尸解肺组织直到CMV包涵体;4例3～4应急性GVHD患儿中3例并发IP，10例0～2度急性GVHD无1例并发IP。结论IP是移植早期死亡的重要原因之一，巨细胞病毒感染是IP的主要病原，GVHD严重程度与移植后并发IP密切相关.