放射性食管炎发病相关因素的研究进展

摘 要：放射治疗是胸部肿瘤的主要治疗手段之一,放射性食管炎是胸部肿瘤患者放疗时常见的不良反应,其发生及严重程度影响患者放射治疗的依从性及疗效。目前研究发现,放射性食管炎的发生与患者临床特征、放疗物理剂量学参数、基因分子标志物等有关。根据放射性食管炎发生相关因素,识别发生放射性食管炎的高危患者,对于制定合理的治疗策略、减少放射性食管炎的发生风险、提高治疗疗效至关重要。文章就放射性食管炎发病相关因素的研究进展作一综述。     

云南白药合剂防治放射性食管炎的临床观察

目的探讨减轻胸部肿瘤患者放射治疗所致的食管黏膜反应、进食梗阻等副反应的防治方法,保证放射治疗的顺利进行.方法将120例颈胸部肿瘤需行放射治疗的患者随机分为3组,试验1组从放疗开始即口服云南白药合剂,试验2组于放疗过程中出现放射性食管炎时口服云南白药合剂,对照组于放疗过程中出现放射性食管炎时口服利氟庆合剂.结果试验1组与试验2组、对照组比较,放射性食管炎发生率明显减少,说明云南白药合剂对放射性食管炎有显著的治疗作用.结论云南白药合剂能促进食管黏膜组织的再生修复,服用方便,经济实用,药疗与食疗结合,能增加营养,提高机体免疫力,安全无任何不良影响,防治放射性食管炎效果显著,可协助患者顺利完成放疗疗程.     

放射性肺炎相关预测指标的研究进展

放射性肺损伤(radiation-induced lung toxicity,RILT)是胸部肿瘤患者放射治疗的主要副反应之一,亦是影响放射治疗疗效的主要剂量限制性因素。RILT包括放射性肺炎(radiation pneumonitis,RP)和放射性肺纤维化(radiation fibrosis,RF)。放射性肺炎通常发生于放疗开始后的1-6个月。放射性肺纤维化的发生较缓慢通常为数月到几年之间。本综述就与放射性肺炎有关的临床和剂量学等参数进行分析,旨在提供临床可行的预测指标,以指导肺癌放射治疗计划的制订,减少正常组织的放射性损伤。     

蛋珍油对放射性食管炎的防治作用

1放射性食管炎发生机制 放射治疗是肺癌，乳腺癌，食管癌以及纵隔淋巴瘤等胸部恶性肿瘤进行有效的根治或姑息性治疗的主要方法之一，在控制恶性肿瘤进展方面发挥着重要作用。然而，胸部肿瘤的放疗照射野常常或不可避免地包及食管，从而出现急性放射性食管炎。食管黏膜结构与皮肤相似，为复层鳞状上皮，其上皮细胞和血管的内皮细胞对放射线较敏感。     

放射性肺炎的临床危险因素

目前放射治疗是胸部恶性肿瘤的重要治疗手段之一,而放射性肺炎是放疗常见的不良反应。放射性肺炎的发生不利于肿瘤的治疗、影响患者的生活质量,且增加患者的经济负担。明确放射性肺炎的危险因素将有利于胸部恶性肿瘤患者放疗前的评估,可对高危个体提前预知或预防,进一步指导患者的个体化治疗。     

放射性肺损伤预测因子研究进展

摘 要：放射性肺损伤是胸部肿瘤放疗中的常见并发症,是制约放疗剂量增加及影响放疗效果的重要因素。目前严重RILI尚无有效治疗方法,早期预测RILI的发生对于疾病的治疗和预后具有重要意义。全文主要探讨生物因子、基因多态性、治疗因素、患者因素、肿瘤因素、功能影像参数等在预测RILI方面的价值。     

痰热清治疗30例胸部肿瘤放疗损伤的观察

胸部肿瘤主要包括食管癌、支气管肺癌、纵隔肿瘤等，治疗上首选手术，其次是放疗。但部分患者因年龄过大及经济条件、严重心肺疾病，不能手术，还有些患者惧怕手术，所以放疗是适合多数胸部肿瘤患者的有效治疗手段。临床上放疗在胸部肿瘤的治疗中起到了积极的作用，但足量放疗后继发放射性食管炎、放射性肺炎、气管损伤及黏膜损伤仍是个棘手的问题。痰热清有效地解决了这个问题。我科自2004年3月开始使用痰热清注射液治疗胸部肿瘤放疗后继发放射性食管炎、放射性肺炎及气管损伤共30例，结果表明：痰热清在止咳化痰、消肿、退热、修复黏膜损伤方面疗效确切。     

单核苷酸多态性与肺癌放射性食管炎相关性的研究

目的 探索肺癌放疗中单核苷酸多态性与放射性食管炎的相关性.方法 采用聚合酶链反应-限制性内切酶片段长度多态性(PCR-RFLP)方法分析了DNA损伤修复通路、凋亡通路和炎症因子相关的加个基因37个单核苷酸多态性位点的基因型,观察放疗中和放疗结束后3个月内发生的≥2级放射性食管炎与其相关性.170例病理证实的不可手术的肺癌患者(非小细胞肺癌127例,小细胞肺癌43例)接受了45～70 Gy(平均60 Gy)的放疗,其中三维适形放疗132例,常规放疗38例;单纯放疗41例,放化疗129例(序贯放化疗78例,同步放化疗51例).结果 170例中发生≥2放射性食管炎40例,其中2级36例,3级4例.单因素分析结果显示放疗技术、同步放化疗与放射性食管炎的发生有关(P=0.032、0.049),多因素分析结果接近统计学水平(P=0.072、0.094).相关性分析显示TGF-β1-509T和XPD 751Lys/Lys基因型为放射性食管炎的风险基因型(χ2=5.65,P=0.017,χ2=3.84 P=0.048).结论 TGF-β1-509C/T和XPD Lys751Gln多态性与肺癌放射性食管炎的发生有显著相关性.     

三维适形放射治疗胸部肿瘤致食管损伤的相关因素分析

目的:分析三维适形放射治疗胸部肿瘤时食管损伤的发生率及相关因素。方法:回顾性分析83例行三维适形放疗的胸部肿瘤患者资料,评价食管损伤并对其相关因素进行单因素和多因素分析。结果:83例患者发生急性食管炎42例(50.6%),其中1级12例(14.5%),2级25例(30.1%),3级4例(4.8%),4、5级0例;晚期食管损伤1例(1.2%)。经单因素和多因素分析显示,急性放射性食管炎与食管V50、Dmeas、是否同期放化疗有关。结论:食管放射损伤的主要原因是V50、Dmeas和同期化疗,制定放疗计划时应尽量避免食管区的高剂量照射,同时辅以放疗防护剂起一定的保护作用。     

消炎利水合剂治疗放射性食管炎临床体会

放射性食管炎是胸部肿瘤放疗中的常见并发症 ,我们应用自组方消炎利水合剂预防和治疗放射性食管炎 ,取得较好效果。本文对 1990年 8月至 1997年 7月间放射治疗中发生放射性食管炎且临床资料完整的989例进行了回顾性总结 ,以期探讨消炎利水合剂对放射性食管炎的疗效。1　材料与方法1 1　一般资料在 989例经病理学或细胞学确诊的病人中 ,男 784例 ,女 2 0 5例。年龄 2 3～ 80岁 ,平均 51 3岁。服用消炎利水合剂按开始时间分四组 :①放疗开始即口服消炎利水合剂 175例 ;②放疗ＤＴ12～ 2 0Ｇｙ出现放射反应后开始口服消炎利水合剂 4 33例 ;③放…     

Molekulare Modulation der Strahlenwirkung

Radiation-based treatment modalities are a mainstay of modern oncology. Technological improvements, i.e., CT-based planning and computer-optimized dose delivery techniques are of utmost importance for the efficacy, versatility, and quality of modern radiation treatments. However, new biological treatment strategies, which are mainly based on molecular analysis of cellular radiation responses, are being tested in clinical trials and may widen the therapeutic spectrum in radiation oncology. Unfortunately, these approaches are associated with a variety of new problems. In this regard, the high specificity of the biological modifier requires the presence of defined alterations in cellular pathways in an individual patient. Furthermore, many of the agents employed may exert complex and even ambivalent effects. Thus, for the design of new trials using biological response modulators all these characteristics of these novel drugs have to be taken into account. The aim of the present article is to introduce the principles and problems of therapies based on the molecular modulation of radiation responses.     

Acute secondary effects in the esophagus in patients undergoing radiotherapy for carcinoma of the lung

The incidence and nature of acute secondary irradiation esophagitis was studied in a series of 38 patients undergoing 60Co teletherapy for carcinoma of the lung. Thirty-four patients were male and four female, with ages ranging from 38 to 78 years. The mediastinum being irradiated in the process, all the patients underwent endoscopy for signs of esophagitis and/or gastritis after a dose of 30-40 Gy was delivered to the esophagus. Eighteen patients complained of dysphagia, but only in 12 of them did endoscopy show esophagitis. Of the remaining patients without complaints five had endoscopic signs of esophagitis. Gastritis was found in 18 cases and confirmed histologically in 14. In 17 cases, esophagitis and/or gastritis were confirmed histologically. It is believed that there is a fairly close correlation among clinical, endoscopic, and histological findings to support the claim that esophagitis in these patients is radiation induced. However, the cause of gastritis is not well understood. Data in the literature suggest that nonsteroid anti-inflammatory agents can act as prophylactic means of preventing radiation esophagitis.     

Toll-like receptor-5 agonist Entolimod broadens the therapeutic window of 5-fluorouracil by reducing its toxicity to normal tissues in mice

Myelosuppression and gastrointestinal damage are common side effects of cancer treatment limiting efficacy of DNA-damaging chemotherapeutic drugs. The Toll-like receptor 5 (TLR5) agonist Entolimod has demonstrated efficacy in mitigating damage to hematopoietic and gastrointestinal tissues caused by radiation. Here, using 5-Fluorouracil (5-FU) treated mice as a model of chemotherapy-induced side effects, we demonstrated significant reduction in the severity of 5-FU-induced morbidity and increased survival accompanied by the improved integrity of intestinal tissue and stimulated the restoration of hematopoiesis. Entolimod-stimulated IL-6 production was essential for Entolimod''s ability to rescue mice from death caused by doses of 5-FU associated with hematopoietic failure. In contrast, IL-6 induction was not necessary for protection and restoration of drug-damaged gastrointestinal tissue by Entolimod. In a syngeneic mouse CT26 colon adenocarcinoma model, Entolimod reduced the systemic toxicity of 5-FU, but did not reduce its antitumor efficacy indicating that the protective effect of Entolimod was selective for normal, non-tumor, tissues. These results suggest that Entolimod has clinical potential to broaden the therapeutic window of genotoxic anticancer drugs by reducing their associated hematopoietic and gastrointestinal toxicities.     

Therapeutic applications of histone deacetylase inhibitors in sarcoma

Sarcomas are a rare group of malignant tumors originating from mesenchymal stem cells. Surgery, radiation and chemotherapy are currently the only standard treatments for sarcoma. However, their response rates to chemotherapy are quite low. Toxic side effects and multi-drug chemoresistance make treatment even more challenging. Therefore, better drugs to treat sarcomas are needed. Histone deacetylase inhibitors (HDAC inhibitors, HDACi, HDIs) are epigenetic modifying agents that can inhibit sarcoma growth in vitro and in vivo through a variety of pathways, including inducing tumor cell apoptosis, causing cell cycle arrest, impairing tumor invasion and preventing metastasis. Importantly, preclinical studies have revealed that HDIs can not only sensitize sarcomas to chemotherapy and radiotherapy, but also increase treatment responses when combined with other chemotherapeutic drugs. Several phase I and II clinical trials have been conducted to assess the efficacy of HDIs either as monotherapy or in combination with standard chemotherapeutic agents or targeted therapeutic drugs for sarcomas. Combination regimen for sarcomas appear to be more promising than monotherapy when using HDIs. This review summarizes our current understanding and therapeutic applications of HDIs in sarcomas.     

如何减少非小细胞肺癌放疗中的肺损伤

放疗是肺癌的主要治疗方式之一,但所致肺损伤也制约生存质量和疗效;如何提高疗效又减少损伤是必须面临的挑战。然而,根据经验采取一些措施可以更好的减少胸部肿瘤放疗肺损伤。首先较全面了解病情和合并症,以及放化疗协同损伤的影响来制定个体化方案。把掌握或精通的诊断技能和肿瘤生物学特性、以及肿瘤扩散和转移复发和淋巴引流规律等用于治疗靶区的制定中,以每1 mm必争来减少不必要照射。制定和评价放疗计划时,要了解肺和肺损伤修复的生物学特性,遵循宁愿小体积肺高剂量,不要大体积肺低剂量照射的原则;用胸部肿瘤放疗思维做到每1%肺DVH相争来减少肺照射,即使牺牲一些适形度。用肿瘤同步加量技术和二程治疗计划,对正常组织以及亚临床和肿瘤从剂量和分割剂量区别,可进一步增加肿瘤控制和减少损伤。肺失去通气功能剂量在20 Gy或稍多,而且为非功能性纤维化修复,要特别注意降低低剂量肺的照射。艺术性的个体化应用精准放疗技术,点滴积累减少不必要的范围和保护肺组织功能,才能有更好疗后生存质量和肿瘤疗效。     

Neurotoxicity and dermatologic toxicity of cancer chemotherapy

Neurological dysfunction is a common adverse effect of many chemotherapeutic agents. Any part of the peripheral or central nervous system can be affected. Various clinical syndromes including encephalopathy, cerebellar syndrome, cranial neuropathy, seizure,myelopathy, and peripheral neuropathy commonly occur. In several drugs, neurotoxicity is a dose-limiting toxicity. Multiple factors such as cumulative dose, route of administration, drug metabolism and synergistic effects of other drugs or radiotherapy impact the incidence and severity of neurotoxicity. Much of the research in chemotherapy-induced neuropathies has been focused on the goal of ameliorating or preventing the neurotoxicity without altering the effectiveness of the medication. Various dermatologic complications of cancer chemotherapy such as extravasation, hyperpigmentation, nail change, radiation recall reaction and hypersensitivity reaction can occur. In extravasation, many cytotoxic agents are irritants or non-vesicants, however,a significant number of commonly used drugs are classified as vesicants, including the vinca alkaloids anthracyclines and taxanes. Extravasation of vesicant drugs into the subcutaneous tissue results in severe local pain and ulceration with progressive tissue destruction. Strategies to reduce the incidence of extravasation and minimize its associated morbidity are crucial to quality of life for cancer patients. The more common clinical features of chemotherapy-induced neurologic and dermatologic toxicities are discussed below.     

Toxicité œsophagienne de la radiothérapie : clinique,facteurs de risque et prise en charge

Acute radiation-induced esophagitis includes all clinical symptoms (odynophagia, dysphagia) occurring within 90 days after thoracic irradiation start. Its severity can be graded using RTOG and CTCAE scales. The clinical risk factors are: age, female gender, initial performance status, pre-therapeutic body mass index, pre-therapeutic dysphagia, tumoral and nodal stage, delivered dose, accelerated hyperfractionned radiotherapy, concomitant association of chemotherapy to radiotherapy and response to the treatment. The dosimetric parameters predictive of esophagitis are: mean dose, V_20Gy, V_30Gy, V_40Gy, V_45Gy and V_50Gy. Amifostine is the only drug to have a proven radioprotective efficacy (evidence level C, ESMO recommendation grade III). The medical management of esophagitis associates a diet excluding irritant food, medication against gastroesophageal reflux, analgesic treatment according to the WHO scale and management of dehydration and denutrition by enteral feeding.     

Radiation and third-generation chemotherapy

All of the third-generation chemotherapeutic agents reviewed in this article are independently active against NSCLC, although the agents differ significantly in their cellular and molecular mechanisms of cytotoxicity. All have also been shown to potentiate radiation effects, and thus are promising in exerting further cytotoxicity when used in combination chemoradiation therapy for locally advanced NSCLC. Although the toxicity to normal tissue varies among these agents when used alone, phase I/II clinical results consistently demonstrated higher risk and severity of esophagitis and pneumonitis when these agents were administered concurrently with thoracic radiation. These results were consistent with the radiosensitization properties of all these agents. Nonetheless, most chemoradiation combinations have been made feasible through careful phase I studies that establish safe doses of these agents given concurrently with radiation. Indeed, phase I outcomes consistently have demonstrated the need for dose reduction compared with doses applied in the stage IV, metastatic disease setting (see Tables 1 and 2). There have been many different dose schedules in phase I/II studies for stage III NSCLC, and most have yielded improved response rates with these agents. For all these agents discussed, multiagent chemoradiation increased toxicity when compared with single agent chemoradiation, particularly in the risk of neutropenia, and the tumor response rates were no better than single-agent chemoradiation. Most studies have not reached an adequate interval for survival endpoint to assess the impact on survival using multiagent chemoradiation. A few earlier studies using paclitaxel chemoradiation, in fact, showed that the significant improvement in tumor response rate resulted in only a small gain in survival outcome. Despite much preclinical research conducted with these agents, the optimal sequence and dose of drug and the optimal schedule for combining the two modalities remain unknown. Optimal sequencing of the chemoradiation regimens may improve distant disease control and primary tumor control, as was seen in studies that administered both full-dose induction chemotherapy and concurrent chemoradiation at reduced drug dose and in studies that administered consolidative, full-dose chemotherapy after chemoradiation. Strategically altering the treatment schedule may also enhance the radiosensitizing effects while keeping toxicity low, such as was seen in the pulsed low-dose paclitaxel chemoradiation reported by Chen et al . This pulsed low-dose schedule resulted in superior tumor response (100%) and durable primary tumor control while keeping the toxicity low. Other methods to minimize normal tissue injury and to deliver higher radiation doses, such as conformal three-dimensional radiotherapy that excludes nontarget tissues from the radiation field, are under investigation. Marks and colleagues were able to deliver radiation to 80 Gy using accelerated hyperfractionation radiation after induction chemotherapy. Intensity-modulated radiotherapy is expected to revolutionize the targeting of tumor and exclusion of normal tissues from the high-dose radiation volume in the future. Integrating biologic response modifiers, radioprotectors, and molecular targeting strategies also are being investigated. It remains unclear which agent among the third-generation drugs performs better for combination chemoradiation. The CALGB 9431 study reported by Vokes et al provided some preliminary information, in that it was a randomized phase II study of a three-arm comparison of cisplatin-containing, two-drug combination chemoradiation with one of the third-generation agents. Although direct statistical comparison between the treatment arms was not valid for a phase II setting, such an analysis did indeed reveal similar overall response rates for these three arms. Chemoradiation using third-generation chemotherapeutic agents has improved local tumor response rates, with enhanced radiation toxicity such as esophagitis and pneumonitis. The challenge of targeting distant disease control for locally advanced NSCLC continues.     

Radiation esophagitis: Predictive factors and preventive strategies

Radiation esophagitis remains the primary dose-limiting acute toxicity in the radiotherapeutic management of thoracic neoplasms. Improved understanding of this toxicity will facilitate dose escalation and enhancement of the therapeutic ratio. This article reviews the predictive factors and preventive strategies for radiation esophagitis. In particular, clinical and dosimetric studies predicting the risk of radiation esophagitis are analyzed. The critical impact of chemotherapy on radiation esophagitis is characterized. Preventive strategies to minimize this toxicity also are explored. Overall, this article reviews the current understanding of radiation toxicity for the esophagus.     

老年食管鳞癌患者单纯放疗和同步放化疗的有效性和安全性比较

目的比较老年食管鳞癌患者(年龄≥65岁)单纯放疗(RT)和同步放化疗(CCRT)的有效性和安全性。方法收集2010年1月至2016年12月于本院首程接受根治性放疗的122例老年食管鳞癌患者,根据治疗情况分为RT组81例和CCRT组41例(替吉奥单药23例、奈达铂单药2例、雷替曲塞联合奈达铂7例和多西他赛联合奈达铂5例),采用实体瘤疗效评价标准RECIST 1.1版评价近期疗效,药物毒性反应标准NCI-CTC 4.0版评价药物毒副反应,急性放射反应评分标准(RTOG/EORTC)评价放疗毒副反应,根据随访数据进行预后分析并采用Cox比例风险回归模型进行多因素分析。结果RT组的总有效率和疾病控制率分别为84.0%和98.8%,与CCRT组92.7%和100.0%的差异无统计学意义(P>0.05)。RT组的中位无进展生存期(PFS)和总生存期(OS)分别为16.1个月和23.8个月,与CCRT组19.7个月和27.1个月的差异无统计学意义(P>0.05)。单因素分析显示影响PFS的因素包括ECOG评分、T分期和放疗剂量,影响OS的因素包括ECOG评分、T分期、N分期、临床分期和放疗剂量,多因素分析显示ECOG评分和放疗剂量是影响PFS的独立预后因素,而ECOG评分和N分期是影响OS的独立预后因素。最常见急性不良反应为放射性食管炎和骨髓抑制(多为1~2级),RT组未发生3~4级不良反应,CCRT组3~4级急性放射性食管炎、放射性肺炎和骨髓抑制的发生率升高至7.3%(3/41)、9.6%(4/41)和7.3%(3/41),差异均有统计学意义(P<0.05)。结论老年食管鳞癌行根治性放疗,放疗剂量提高至60~65 Gy,患者耐受性良好,可延长生存并提高生活质量。是否同步放化疗应综合评估后慎重选择。