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.     

Three-dimensional visualization and measurement of conformal dose distributions using magnetic resonance imaging of bang polymer gel dosimeters

: The measurement of complex dose distributions (those created by irradiation through multiple beams, multiple sources, or multiple source dwell positions) requires a dosimeter that can integrate the dose during a complete treatment. Integrating dosimeter devices generally are capable of measuring only dose at a point (ion chamber, diode, TLD) or in a plane (film). With increasing use of conformal dose distributions requiring shaped, noncoplanar beams, there will be an increased requirement for a dosimeter that can record and display a 3D dose distribution. The use of a 3D dosimeter will be required to confirm the accuracy of treatment plans produced by the current generation of 3D treatment-planning computers.

: The use of a Fricke-infused gel and magnetic resonance imaging (MRI) to demonstrate the localization of stereotactic beams has been demonstrated (11). The recently developed BANG polymer gel dosimetry system (MGS Research, Inc., Guilford, CT), based on radiation-induced chain polymerization of acrylic monomers dispersed in a tissue-equivalent gel, surpasses ther Fricke-gel method by providing accurate, quantitative dose distribution data that do not deteriorate with time (6, 9). The improved BANG2 formulation contains 3% N,N′-methylene-bisacrylamide, 3% acrylic acid, 1% sodium hydroxide, 5% gelatin, and 88% water, where all percentage are by weight. The gel was poured into volumetric flasks, of dimensions comparable to a human head. The gels were irradiated with complex beam arrangements, similar to those used for conformal radiation therapy. Images of the gels were acquired using a Siemens 1.5T imager and a Hahn spin-echo pulse sequence (90°-τ-180°-τ-acquire, for different values of τ). The images were transferred via network to a Macintosh computer for which a data analysis and display program was written. The program calculates R2 maps on the basis of multiple TE images, using a monoexponential nonlinear least-squares fit based on the Levenberg-Marquardt algorithm. The program also creates a dose-to-R2 calibration function by fitting a polynomial to a set of dose and R2 data points, obtained from gels irradiated in test tubes to known doses. This function can then be applied to any other R2 map, so that a dose map can be computed and displayed.

: Through exposure to known doses of radiation, the gel has been shown to respond linearly with dose in the range of 0 to 10 Gy, and its response is independent of the beam energy or modality. Dose distributions have been imaged in orthogonal planes, and can be displayed in a convenient form for comparison with isodose plans. The response of the gel is stable; the gel can be irradiated at any time after its manufacture, and imaging can be conducted any time following a brief interval after irradiation.

: The polymer gel dosimeter has been shown to be a valuable device for displaying three-dimensional dose distributions. The imaged dose distribution can be compared easily with calculated dose distributions, to validate a treatment planning system. In the future, gels may be prepared in anthropomorphic phantoms, to confirm unique patient dose distributions.     

Radioenhancement by cisplatin with accelerated fractionated radiotherapy in a human tumour xenograft

The aim of the present study was to investigate whether cisplatin would enhance the radioresponse of a human tumour xenograft when given in different schedules combined with accelerated fractionated radiation therapy. A human squamous carcinoma of the hypopharynx, FaDu, was grown in the thigh of athymic nude mice. Tumours were exposed to twice-daily 2-Gy fractions, applied 6 h apart over 2 weeks, 5 days a week, alone or combined with cisplatin given at maximally tolerated doses in three different schedules: (1) i.p. as a single bolus (SB) or (2) i.p. as a daily bolus at 30 min before the first daily radiation fraction or (3) s.c. as a continuous infusion through a mini-osmotic pump over 13 days, commencing 24 h prior to the first daily radiation fraction. The end point for the study was tumour growth delay (TGD), calculated as the difference between the delay in regrowth to 200% of the initial tumour size in treated versus control mice. SB cisplatin plus radiation showed only an additive effect on TGD, whereas daily-bolus and continuous-infusion cisplatin demonstrated a greater than additive effect when combined with accelerated fractionated radiation in this human tumour model. Cisplatin appears to be especially beneficial as a radiation enhancer when given throughout the course of radiation. Received: 15 December 1996 / Accepted: 25 March 1997     

Increased risk of salivary gland tumors after low-dose irradiation

Objective: To assess the risk of neoplastic development among persons exposed to scalp irradiation. Study Design: Historical cohort study initially; prospective follow-up subsequently. Method: Two control groups—population and siblings—matched for age, sex, ethnic origin, and year of immigration. Follow-up from time of irradiation (1950s) until the end of 1991. Linkage with nationwide cancer registry. Results: A 4.5–fold incidence of cancer (P < .01) and a 2.6–fold increase of benign tumors were noted. The mean length of latency period until tumor development was 11 years for malignant tumors and 21.5 years for benign. A clear dose response effect for both cancer and benign tumors was demonstrated. Conclusions: The study confirms the role of radiation in salivary gland carcinogenesis. It indicates a need for better awareness, a comprehensive examination, and long-term follow-up of patients who have been subjected to head and neck radiation.     

放、化疗同步与非同步治疗Ⅲ期非小细胞肺癌的对比观察

目的:为比较放、化疗同步治疗与非同步治疗肺癌的临床效果.方法:选择不手术的Ⅲ期非小细胞肺癌(NSCLC)患者81例,随机分为同步治疗组(42例)和非同步组(39例).结果:治疗总有效率同步组66.7%,非同步组61.5%,前者略高于后者,两者比较无显著差异(P>0.05),但达到上述有效率所用的时间前者平均69天,后者为143天,两者比较有非常显著差异(P<0.01).结论:同步组的近期疗效似优于非同步组,且前者治疗周期、住院周期缩短,更有利于患者康复.     

61例喉癌单纯放射治疗临床分析

目的喉癌单纯放疗效果分析。方法６１例喉癌，以６０Ｃｏ外放射治疗，常规照射。结果五年生存率，声门癌６５％，声门上型癌２４．４％。结论推荐剂量，声门癌Ｔ１Ｔ２６０００ｃＧｙ，Ｔ３６８００ｃＧｙ。声门上型癌Ｔ１Ｔ２６０００～６５００ｃＧｙ，Ｔ３７０００ｃＧｙ。