突破肿瘤放射治疗发展瓶颈的重粒子束治疗

重粒子束的高线性能量传递射线突破了常规放射肿瘤的发展瓶颈，是肿瘤放射治疗最尖端技术。重粒子束作为难治性肿瘤治疗的重要手段，取得了令人鼓舞的疗效，尤以碳离子是这一研究领域的亮点。①碳离子是迄今最佳的治疗肿瘤用重粒子射线；②碳离子突出的特点是拥有高相对生物效应值，同时兼有比质子更好的肿瘤剂量适形性的双重优越性；③碳离子放疗对常规放疗抗拒的一些难治性肿瘤疗效好、疗程短，无明显并发症：④碳离子放疗对外科手术困难的肿瘤、邻近重要组织器官的肿瘤仍能够治疗，对老年患者组织器官功能减退及生长发育期的青少年儿童患者具有特殊的临床意义；⑤对常规放疗无效或复发患者的再程放疗仍有效。     

调强放疗降低腮腺剂量提高头颈部肿瘤生物有效剂量的可能性:治疗设计研究

头颈部肿瘤的传统放疗能取得尚可接受的局部控制率,但因对正常组织的毒性限制了进一步提高剂量.口干即为常见的并发症之一.作者研究了调强放疗(IMRT)对头颈部肿瘤提高肿瘤生物有效剂量、同时降低腮腺等正常组织剂量的可能性.     

立体定向放射治疗在妇科肿瘤中的应用进展

立体定向放射治疗（SBRT）是近年来兴起的放疗新技术,该技术的优点在于它能够在控制正常组织剂量的前提下提高肿瘤组织的剂量。SBRT在妇科肿瘤中的应用主要集中在盆腔复发灶、腹主动脉旁转移淋巴结、远处转移灶的局部治疗,可获得良好的局部控制,甚至一些患者有长期无病生存的可能。尽管SBRT有严格的剂量限制,但放疗后野内复发灶治疗后出现严重不良反应的概率较高。SBRT可以作为局部晚期宫颈癌体外放疗结束后,因某些因素而无法实施后装治疗的替代治疗。     

再程立体定向放射治疗的应用

肿瘤经放射治疗或者多种方法联合治疗后,局部复发经常出现,但局部再程放疗仅适用于少数病人,因其会引起潜在的严重并发症,特别是对大体积的肿瘤进行再程放疗时。采用立体定向放射治疗(SBRT)对复发的椎体转移瘤、头颈部肿瘤、盆腔肿瘤进行再程放疗,不仅能够提高局部控制率并减轻症状,同时还能够减少正常组织不良反应。SBRT在临床上是一种安全有效的方法,建议将SBRT作为控制局部症状的重要治疗手段。     

三维适形放疗和调强放射治疗

三维适形放疗是治疗肿瘤的一种主要的外照射治疗方式,如:前列腺癌、头颈部癌、乳腺癌和肺癌等。与传统的放疗相比,它能提高肿瘤靶区剂量,减小旁邻正常组织的剂量,降低辐射引起的急性和远期效应。调强放疗则是在常规适形放疗技术的基础上,对射束内束流强度的空间分布进行调制,得到更好的治疗效果。     

调强放疗降低腮腺剂量提高头颈部肿瘤生物有效剂量的可能性:治疗设计研究

头颈部肿瘤的传统放疗能取得尚可接受的局部控制率,但因对正常组织的毒性限制了进一步提高剂量。口干即为常见的并发症之一。作者研究了调强放疗(IMRT)对头颈部肿瘤提高肿瘤生物有效剂量、同时降低腮腺等正常组织剂量的可能性。 作者报道了4例头颈部肿瘤患者IMRT最优化系统计划的结果,对其中1例作了详细分析,并将其IMRT计划与实际应用的三维适形治疗(3DCRT)计划作比较,另3例仅总结IMRT计划数据。病例1,女,33岁,右软腭粘膜上皮癌,T_4N_0M_0;病例2,     

质子及重离子治疗肿瘤的现状及研究进展

质子和重离子射线治疗肿瘤,是利用质子和重离子穿过物质形成Bragg峰的物理特性和重离子优越的放射生物学特性,将高剂量区调整嵌合在肿瘤上,同时尽量避开周围正常组织器官。质子及重离子放疗剂量分布优于光子放疗,这有利于提升肿瘤剂量和降低正常组织损伤。近年来,不少研究探索了质子重离子治疗头颈部肿瘤、肺癌、食管癌、肝癌等肿瘤的有效性及安全性,而多个对比光子及质子治疗肿瘤的临床研究也正在进行中。这些研究的结果将有利于更好地了解质子及重离子治疗的特点及优势,以便筛选合适的患者,合理推广质子重离子放疗。     

三维适形放疗和调强放射治疗

三维适形放疗是治疗肿瘤的一种主要的外照射治疗方式，如：前列腺癌、头颈部癌、乳腺癌和肺癌等。与传统的放疗相比，它能提高肿瘤靶区剂量，减小旁邻正常组织的剂量，降低辐射引起的急性和远期效应。调强放疗则是在常规适形放疗技术的基础上，对射束内束流强度的空间分布进行调制，得到更好的治疗效果。     

肝脏肿瘤适形放疗新技术与放射性肝病的国外研究进展

放疗在肝脏肿瘤治疗中占有日趋重要的地位，放射诱导肝脏疾病（radiation-induced liver disease，RILD）与肝脏放疗损伤模型的研究允许给予部分肝脏更高放疗剂量，而三维适形放疗新技术如调强放射治疗（intensity modulated radiotherapy，IMRT）、自主呼吸控制（active breathe control，ABC）、影像指导放疗（image-guided radiotherapy，IGRT），立体体部放射治疗（stereotactic body radiotherapy，SBRT）的应用，提高了部分肝脏放疗剂量，同时最大程度减少了正常肝脏组织损伤，取得了令人鼓舞的治疗效果。笔者就近年来国外有关研究报道综述如下。     

头颈部肿瘤IMRT治疗后局部复发问题探讨

调强适形放疗(IMRT)能更好地提高靶区剂量,减少靶区周围正常组织的剂量,特别适宜头颈部这些比较靠近重要器官的肿瘤的治疗.在头颈部肿瘤的治疗中,IMRT比常规放疗有更好的剂量分布优势,在不影响肿瘤控制率和无瘤生存率的情况下,能够降低临近重要器官毒性,从而降低脑、脊髓损伤以及口干等副作用的发生率.IMRT显著提高了靶区的覆盖范围和避开正常组织,然而在头颈部肿瘤的治疗中局部复发依然是治疗失败的主要原因.分析了1999年以来关于头颈部肿瘤局部复发的文献资料,对使用IMRT治疗头颈部肿瘤病人的局部复发问题进行综述.     

闪速放射治疗(FLASH)技术对机房屏蔽设计带来的挑战

与常规放疗技术相比, FLASH治疗技术在保护正常组织方面具有优势, 但剂量率提升100倍以上。如果按照现有标准对机房进行屏蔽设计, 将显著提升改造成本, 且仍有可能无法满足标准要求, 导致FLASH治疗技术无法开展。通过调研国内外标准及文献, 分析了FLASH治疗技术对机房屏蔽设计带来的挑战, 并着重对比了不同国家在放疗机房屏蔽设计时采用的剂量率控制标准。部分国家屏蔽设计时采用考虑实际治疗工况下的平均剂量率;我国主要采用考虑居留因子条件下的瞬时剂量率方法进行控制。如果在我国开展FLASH治疗技术, 瞬时剂量率的要求将很难满足。为了提高FLASH等高剂量率放射治疗技术, 在管理目标限值不变的前提下, 建议考虑对现有标准进行修订, 采用一定时间内的平均剂量率限值进行控制, 或增加FLASH治疗条件下的控制标准。     

超高剂量率照射和常规照射对小鼠肝脏辐射损伤的转录组学比较研究

目的研究超高剂量率照射(FLASH-RT)和常规照射(CONV-RT)对小鼠肝脏基因表达谱的影响, 为揭示FLASH-RT的潜在作用机制提供理论依据。方法将11只C57BL/6J雄性小鼠, 按照随机数字法分为健康对照组(Ctrl组)、常规照射组(CONV-RT组)和超高剂量率照射组(FLASH-RT组)。CONV-RT组和FLASH-RT组采用相应的方式对小鼠进行腹部照射, 剂量均为12 Gy, 照后将小鼠脱颈处死, 分别收集肝脏组织, 提取总RNA。通过转录组测序技术和生物信息学分析方法, 探究小鼠受照后肝脏组织基因表达谱变化。利用实时定量PCR法对3个基因(Stat1、Irf9和Rela)表达水平进行验证分析。结果 FLASH-RT组与CONV-RT组之间共发现1 762个差异表达基因(DEGs), 其中上调基因660个, 下调基因1 102个;FLASH-RT组与Ctrl组之间共发现1 918个差异表达基因, 其中上调基因728个, 下调基因1 190个;CONV-RT组与Ctrl组之间共发现1 569个差异表达基因, 其中上调基因1 046个, 下调基因523个。基因本体论(G...     

Radioprotection of normal tissue cells

Improvements of radiotherapy in combination with surgery and systemic therapy have resulted in increased survival rates of tumor patients. However, radiation-induced normal tissue toxicity is still dose limiting. Several strategies have been pursued with the goal to develop substances which may prevent or reduce damage to normal tissue. Drugs applied before radiotherapy are called radioprotectors; those given after radiotherapy to reduce long-term effects are radiomitigators. Despite more than 50 years of research, until now only two substances, amifostine and palifermin, have overcome all obstacles of clinical approval and are applied during radiotherapy of head and neck cancer or total body irradiation, respectively. However, better understanding of the cellular pathways involved in radiation response has allowed the development of several highly promising drugs functioning as scavengers of reactive oxygen species or targeting specific molecules involved in regulation of cell death pathways or cell cycle arrest. The present review describes the major targets for radioprotectors or radiomitigators currently tested in clinical trials.     

高分子纳米材料用于肿瘤放疗增敏的研究进展

放疗是治疗恶性肿瘤的三大常规手段之一,但由于其存在高辐射剂量损伤正常组织和肿瘤细胞辐射抵抗性强等问题,导致治疗后往往达不到预期效果。为提高放疗疗效,并且减少对正常组织的不良作用,探索新型放疗增敏剂及放化疗联合的新策略已成为研究热点。高分子纳米材料凭借其良好的生物相容性和生理稳定性等优点,为提高肿瘤放疗效果开拓了广阔的应用前景。笔者就高分子纳米材料用于放疗增敏的研究进展进行综述。     

Die Bedeutung von Zytokinen für die radiogene Lungenreaktion

BACKGROUND: The radiosensitivity of the lung tissue limits the dose of radiation which can be delivered to tumors in the thoracic region. Radiation-induced lung damage implies the induction of numerous cytokines which form the basis for the multicellular interactions of the inflammatory and fibrogenic processes associated with radiation injury. It is of special clinical significance, how far local radiation induced cytokine production in the lung tissue may be reflected in increased cytokine blood levels in patients during radiotherapy and may predict the later development of radiation-induced lung damage. Another potential cause of increased cytokine levels in the blood of oncologic patients is the secretion of cytokines in the blood circulation by tumor specimens. METHODS: Published data on radiation-induced cytokine expression from experimental and clinical studies are reviewed. RESULTS AND CONCLUSION: The major pro-inflammatory cytokines in the radiation response of the lung include tumor necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1), and interleukin-6 (IL-6). Transforming growth factor-beta (TGF-beta) appears to be of particular importance in the development of lung fibrosis. First approaches with radioprotective agents and gene therapy to modify radiation-induced cytokine expression have been investigated for prevention of late effects of irradiation lung damage in animal experiments. Preliminary data of clinical studies suggest that elevated plasma TGF-beta-levels during radiotherapy may predict the development of symptomatic radiation pneumonitis. The biological impacts of endogenous radiation-induced cytokine production by tumor cells in respect of tumor behavior, potential damage to normal tissue, and clinical status of the host still need to be determined more precisely.     

免疫检查点在肿瘤放疗中的应用进展

放射治疗诱导DNA损伤与细胞死亡,并且通过改变肿瘤表型、肿瘤微环境,参与内源性免疫反应的调节。免疫检查点信号途径在抗微生物免疫反应中参与维持自身耐受,限制组织损伤,但其在抗肿瘤免疫中抑制细胞毒T细胞活化与功能,增强免疫抑制细胞作用,导致免疫逃逸。阻断免疫检查点信号能够恢复抗肿瘤免疫,延缓肿瘤进程。近年来,放疗与免疫治疗联合应用已成为基础与临床研究的热点。在此就放疗对机体免疫系统的作用、免疫检查点的负性调控机制以及放疗联合阻断免疫检查点用于肿瘤治疗的研究进展进行总结,以期为拓展肿瘤综合治疗提供新思路。     

超高剂量率照射诱导质粒DNA链断裂损伤的研究

目的 对比分析超高剂量率（FLASH）和常规剂量率电子线照射在诱导DNA链断裂损伤中的作用,探讨FLASH效应是否与照射诱导的DNA链断裂损伤减少有关。方法 在生理氧含量（4%）和空气氧含量（21%）条件下,对置于超纯水的pBR322质粒DNA分别实施FLASH （125 Gy/s）和常规（0.05 Gy/s）照射。通过琼脂糖凝胶电泳实验检测开环带DNA和线性带DNA发生情况。进一步应用自由基清除剂Samwirin A （SW）清除电离辐射产生的自由基,分析清除自由基对开环带DNA和线性带DNA形成的影响。最后,量化质粒DNA损伤并采用数学模型计算FLASH照射后产生开环带DNA和线性带DNA的相对生物效应（RBE）。结果 生理氧含量下,FLASH和常规照射所诱导DNA链断裂损伤呈现出剂量依赖性。其中,超纯水中,FLASH照射诱导的线性带DNA生成率较常规照射显著降低（t=5.28、5.79、7.01、7.66,P<0.05）。采用SW预处理后,FLASH和常规照射后质粒DNA链断裂损伤差异无统计学意义（P>0.05）。当氧含量为21%时,FLASH照射与常规照射导致DNA损伤效应无差别,且均较生理氧含量时明显增加。此外,FLASH照射每Gy诱导线性带DNA和开环带DNA的损伤速率分别为常规照射的（2.78±0.03）和（1.85±0.17）倍。结论 FLASH照射较常规照射减轻正常组织放射损伤主要与电离辐射后自由基产生有关,FLASH效应受氧含量的影响。     

Mechanisms of inflammatory responses to radiation and normal tissues toxicity: clinical implications

Purpose: Cancer treatment is one of the most challenging diseases in the present era. Among a few modalities for cancer therapy, radiotherapy plays a pivotal role in more than half of all treatments alone or combined with other cancer treatment modalities. Management of normal tissue toxicity induced by radiation is one of the most important limiting factors for an appropriate radiation treatment course. The evaluation of mechanisms of normal tissue toxicity has shown that immune responses especially inflammatory responses play a key role in both early and late side effects of exposure to ionizing radiation (IR). DNA damage and cell death, as well as damage to some organelles such as mitochondria initiate several signaling pathways that result in the response of immune cells. Massive cell damage which is a common phenomenon following exposure to a high dose of IR cause secretion of a lot of inflammatory mediators including cytokines and chemokines. These mediators initiate different changes in normal tissues that may continue for a long time after irradiation. In this study, we reviewed the mechanisms of inflammatory responses to IR that are involved in normal tissue toxicity and considered as the most important limiting factors in radiotherapy. Also, we introduced some agents that have been proposed for management of these responses.

Conclusions: The early inflammation during the radiation treatment is often a limiting factor in radiotherapy. In addition to the limiting factors, chronic inflammatory responses may increase the risk of second primary cancers through continuous free radical production, attenuation of tumor suppressor genes, and activation of oncogenes. Moreover, these effects may influence non-irradiated tissues through a mechanism named bystander effect.     

Comparison of Traditional and Simultaneous IMRT Boost Technique Basing on Therapeutic Gain Calculation

Two different radiotherapy techniques, a traditional one (CRT) - based on consecutive decreasing of irradiation fields during treatment, and intensity modulated radiation therapy technique (IMRT) with concomitant boost, deliver different doses to treated volumes, increasing the dose in regions of interest. The fractionation schedule differs depending on the applied technique of irradiation. The aim of this study was to compare different fractionation schedules considering tumor control and normal tissue complications. The analysis of tumor control probability (TCP) and normal tissue complication probability (NTCP) were based on the linear quadratic (LQ) model of biologically equivalent dose. A therapeutic gain (TG) formula that combines NTCP and TCP for selected irradiated volumes was introduced to compare CRT and simultaneous boost (SIB) methods. TG refers to the different doses per fraction, overall treatment time (OTT), and selected biological factors such as tumor cell and repopulation time. Therapeutic gain increases with the dose per fraction and reaches the maximum for the doses at about 3 Gy. Further increase in dose per fraction results in decrease of TG, mainly because of the escalation of NTCP. The presented TG formula allows the optimization of radiotherapy planning by comparing different treatment plans for individual patients and by selecting optimal fraction dose.     

Positron emission tomography in the study of human tumors

To increase our understanding of cancer and improve cancer treatment on a rational basis we need to identify both qualitative and quantitative differences between normal and neoplastic tissue. The multimodality approach to cancer treatment includes radiotherapy, chemotherapy, hyperthermia, and immunotherapy. Most of the data on which we base our therapeutic strategies have been derived from in vitro studies or animal tumor models. More information is required on the physiology of in vivo human tumors and their response to therapy. Positron emission tomography allows the regional tissue concentration of a positron emitting radionuclide to be measured in absolute units. If valid tracer models can be formulated that accurately describe the fate of an administered "biological" tracer then the physiological process under investigation can be measured quantitatively. The sequential inhalation of C15O2, 15O2, and 11CO allows regional tissue blood flow, oxygen utilization and blood volume to be measured in absolute units. Tissue perfusion, a measure of nutrient (eg, oxygen) supply, drug delivery, or a means of heat dissipation, is of immense importance to oncologists. The oxygen-15 technique has been used not only to study regional blood flow and oxygen utilization in both tumor and normal tissue but also their response to therapeutic intervention. In those studies were tracer models are thought to be less than complete (eg, due to insufficient biological data) then only a semiquantitative or qualitative assessment of the pathophysiological state may be possible. In this respect, tumor function has been characterized by the rate of uptake of 18F-2-deoxyglucose. This technique has provided a means of tumor grading and differentiating between radiation-induced tissue necrosis and tumor recurrence. Metabolic imaging with labeled amino acids appears particularly useful in the delineation of tumor extent. Blood brain barrier integrity and the pharmacokinetics of cytotoxic drugs have also been studied quantitatively. In the future, receptor studies are likely to play an increasing role. In this review dealing with the positron emission tomography oncologic work to date, emphasis has been placed on the physiological information obtainable and how it may further our understanding of cancer and its treatment.