For Personal Use. Only Reproduce with Permission from the Lancet Publishing Group. Review Hyperthermia in Cancer Treatment Hyperthermia in Combined Treatment of Cancer
For Personal Use. Only Reproduce with Permission from the Lancet Publishing Group. Review Hyperthermia in Cancer Treatment Hyperthermia in Combined Treatment of Cancer
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P. Wust;B. Hildebrandt;G. Sreenivasa;B. Rau;J. Gellermann;H. Riess;R. Felix;P. Schlag
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作者：
P. Wust;B. Hildebrandt;G. Sreenivasa;B. Rau;J. Gellermann;H. Riess;R. Felix;P. Schlag
热疗是将肿瘤组织的温度升高到40-43°C的过程，作为与各种已建立的癌症治疗（如放疗和化疗）一起的连续治疗。最近，通过规划系统和其他建模工具的发展，控制体内功率分布的潜力得到了显着提高。这种理解的增加导致了多天线应用程序（包括其转换网络）的设计和实施系统的监测电场（例如，电光传感器）和温度（特别是，在线磁共振断层扫描）。几项比较单独放疗或与热疗的III期试验显示，热疗（使用现有标准设备）在局部控制（例如，复发性乳腺癌和恶性黑色素瘤）和生存率（例如，头颈部淋巴结转移、胶质母细胞瘤、宫颈癌）方面具有有益效果。因此，进一步发展现有技术和阐明分子机制是合理的。在最近的分子和生物学研究中，已经出现了新的应用，例如基因治疗或免疫治疗（疫苗接种），其中温度作为增强剂，以触发或打开和关闭机制。然而，对于用于临床目的的每一个特定的温度依赖性相互作用，在空间上和时间上对身体深部区域的温度进行复杂的控制将进一步提高潜力。热疗是一种治疗程序，用于提高受癌症影响的身体区域的温度（图1）。它与其他癌症治疗方式（多模式肿瘤学策略）一起施用。可以通过各种方法来实现所需的温度升高。20世纪70年代早期，对体外细胞培养和体内实验诱导肿瘤的研究为热疗的临床应用提供了令人信服的理由。其原理是基于在41-42 °C以上的温度下直接杀死细胞的效果。1然而，热剂量-反应关系在细胞系之间变化，并且还取决于微环境因素，例如pH。2热休克后，所有细胞类型显示出24-48 h的耐热性增加（耐热性）。在临床条件下，未达到根据临床前数据得出的所需温度。因此，其他热机制可能是相关的。热和辐射剂量以及各种细胞抑制治疗之间的协同相互作用已在临床前研究中得到验证。3，4这种热敏作用甚至在41°C以下也有效。正如临床前实验所发现的，治疗之间的时间和手术顺序很重要。5对于放疗和热疗的结合，同时进行热疗的效果最好。
Hyperthermia, the procedure of raising the temperature of tumour-loaded tissue to 40–43°C, is applied as an adjunctive therapy with various established cancer treatments such as radiotherapy and chemotherapy. The potential to control power distributions in vivo has been significantly improved lately by the development of planning systems and other modelling tools. This increased understanding has led to the design of multiantenna applicators (including their transforming networks) and implementation of systems for monitoring of E-fields (eg, electro-optical sensors) and temperature (particularly, on-line magnetic resonance tomography). Several phase III trials comparing radiotherapy alone or with hyperthermia have shown a beneficial effect of hyperthermia (with existing standard equipment) in terms of local control (eg, recurrent breast cancer and malignant melanoma) and survival (eg, head and neck lymph-node metastases, glioblastoma, cervical carcinoma). Therefore, further development of existing technology and elucidation of molecular mechanisms are justified. In recent molecular and biological investigations there have been novel applications such as gene therapy or immunotherapy (vaccination) with temperature acting as an enhancer, to trigger or to switch mechanisms on and off. However, for every particular temperature-dependent interaction exploited for clinical purposes, sophisticated control of temperature, spatially as well as temporally, in deep body regions will further improve the potential. Hyperthermia is a therapeutic procedure used to raise the temperature of a region of the body affected by cancer (figure 1). It is administered together with other cancer treatment modalities (multimodal oncological strategies). The temperature increase required can be achieved by various methods. Studies on cell cultures in vitro and on experimentally induced tumours in vivo in the early 1970s provided convincing justification for the clinical application of hyperthermia. The rationale is based on a direct cell-killing effect at temperatures above 41–42 °C. 1 However, the thermal dose–response relation varies among cell lines and depends, furthermore, on microenvironmental factors such as pH. 2 After a heat shock, all cell types show increased thermoresistance for 24–48 h (thermotolerance). The required temperatures derived from the preclinical data are not achieved under clinical conditions. Therefore, other mechanisms of heat may be relevant. A synergistic interaction between heat and radiation dose as well as various cytostatic treatments has been validated in preclinical studies. 3,4 This thermosensitisation is effective even below 41°C. Here, as found in preclinical experiments, the time between treatments and the sequence of operation are important. 5 For the combination of radiotherapy and hyperthermia, the effect is greatest for simultaneous …