SYRA3 COST Action – Microbeam radiation therapy: Roots and prospects

Microbeam radiation therapy (MRT) is an irradiation modality for therapeutic purposes which uses arrays of collimated quasi parallel microbeams, each up to 100 μm wide, to deliver high radiation doses. Several studies have reported the extraordinary tolerance of normal tissues to MRT irradiation; conversely, MRT has been shown to be highly efficient on tumor growth control. The original and most widely developed application of MRT, yet in the preclinical phase, consists in using spatially fractionated X-ray beams issued from a synchrotron radiation source in the treatment of brain tumors. More recently, MRT has been tested in successful pioneering assays to reduce or interrupt seizures in preclinical models of epilepsy. The MRT concept has also been extended to proton therapy. The development of MRT towards its clinical implementation is presently driven by an EU-supported consortium of laboratories from 16 countries within the COST Action TD1205 (SYRA3). The results of the first SYRA3 workshop on “Radiation Therapy with Synchrotron Radiation: Achievements and Challenges” held in Krakow (Poland) during March 25–26 2014 are summarized in this issue with an overview presented in this paper. The papers reflect the multidisciplinary international activities of SYRA3. The topics covered in this focus issue include medical physics aspects, pre-clinical studies, clinical applications, and an industrial perspective; finally an outlook towards future prospects of compact sources and proton microbeams.     

A review on photoneutrons characteristics in radiation therapy with high-energy photon beams

In radiation therapy with high-energy photon beams (E > 10 MeV) neutrons are generated mainly in linacs head thorough (γ,n) interactions of photons with nuclei of high atomic number materials that constitute the linac head and the beam collimation system. These neutrons affect the shielding requirements in radiation therapy rooms and also increase the out-of-field radiation dose of patients undergoing radiation therapy with high-energy photon beams. In the current review, the authors describe the factors influencing the neutron production for different medical linacs based on the performed measurements and Monte Carlo studies in the literature.     

Medical physics aspects of the synchrotron radiation therapies: Microbeam radiation therapy (MRT) and synchrotron stereotactic radiotherapy (SSRT)

Stereotactic Synchrotron Radiotherapy (SSRT) and Microbeam Radiation Therapy (MRT) are both novel approaches to treat brain tumor and potentially other tumors using synchrotron radiation. Although the techniques differ by their principles, SSRT and MRT share certain common aspects with the possibility of combining their advantages in the future. For MRT, the technique uses highly collimated, quasi-parallel arrays of X-ray microbeams between 50 and 600 keV. Important features of highly brilliant Synchrotron sources are a very small beam divergence and an extremely high dose rate. The minimal beam divergence allows the insertion of so called Multi Slit Collimators (MSC) to produce spatially fractionated beams of typically ∼25–75 micron-wide microplanar beams separated by wider (100–400 microns center-to-center(ctc)) spaces with a very sharp penumbra. Peak entrance doses of several hundreds of Gy are extremely well tolerated by normal tissues and at the same time provide a higher therapeutic index for various tumor models in rodents. The hypothesis of a selective radio-vulnerability of the tumor vasculature versus normal blood vessels by MRT was recently more solidified.SSRT (Synchrotron Stereotactic Radiotherapy) is based on a local drug uptake of high-Z elements in tumors followed by stereotactic irradiation with 80 keV photons to enhance the dose deposition only within the tumor. With SSRT already in its clinical trial stage at the ESRF, most medical physics problems are already solved and the implemented solutions are briefly described, while the medical physics aspects in MRT will be discussed in more detail in this paper.     

Complication of radiation therapy among patients with positive S. aureus culture from genital tract

AimThe main goal of this investigation was to evaluate the influence of positive Staphylococcus aureus culture from the genital tract on patients receiving radiation therapy, suffering from carcinoma of the uterus. The other aim was to observe radiation therapy complications.BackgroundRadiation therapy of patients suffering from cervical cancer can be connected with inflammation of the genitourinary tract.Materials and methodsIn years 2006–2010 vaginal swabs from 452 patients were examined. 39 women with positive S. aureus cultures were analysed.ResultsComplications and interruptions during radiation therapy were observed in 7 (18.9%) of 37 patients with positive vaginal S. aureus culture. One of them, a 46-year-old woman developed pelvic inflammatory disease. None of the six patients who received palliative radiotherapy showed interruption in this treatment. Isolated S. aureus strains were classified into 13 sensitivity patterns, of which 8 were represented by 1 strain, two by 2 strains and three by 13, 8 and 6 strains. One strain was diagnosed as methicillin resistant S. aureus (MRSA).ConclusionsThe results of the present study show that S. aureus may generally be isolated from the genital tract of female patients with neoplastic disease of uterus but is not often observed as inflammation factor of this tract. Comparison of species’ resistance patterns may be used in epidemiological studies in order to discover the source of infections and therefore be of profound significance in the prevention of nosocomial infections.     

同步辐射在显微CT中的应用

计算机X射线断层成像技术（CT）是利用X射线的穿透能力对物体进行扫描,所得信号经过反投影的算法而得到物体二维分布的一种成像方法,已经在医学诊断、工业探伤等领域广泛应用。但是由于实验室光源的低通量,光源点大小及其单色性等限制了其向高分辨发展,通常其分辨率在0．5mm左右。利用微焦点X射线源作为光源的显微CT分辨率可以达到微米量级,但是由于其光通量低且为非单色光,对不同样品有不同程度的束线硬化,影响了其真实分辨率。同步辐射作为一种新兴的光源有高亮度、高光子通量、高准直性、高极化性、高相干性及宽的频谱范围的特点,配合高分辨的X射线探测器,可以发展同步辐射显微CT,其分辨率可达10μm以下。利用同步辐射的高空间相干性开展位相衬度显微CT的研究,对低吸收物质也可以清晰三维成像。新建的上海光源的X射线成像及生物医学应用线站开展了三维显微CT方面的研究,经过初步试验,得到了较好的结果。     

甲基纤维素辐射降解及工艺研究

介绍了^60Co γ－射线对甲基纤维素的辐射降解作用,初步研究了辐射剂量、剂量率对甲基纤维素粘的影响。评价了甲基纤维素辐照后的贮存稳定性,并对辐射降解工艺进行了探讨。     

Microbeam radiation therapy: Clinical perspectives

Microbeam radiation therapy (MRT), a novel form of spatially fractionated radiotherapy (RT), uses arrays of synchrotron-generated X-ray microbeams (MB). MRT has been identified as a promising treatment concept that might be applied to patients with malignant central nervous system (CNS) tumours for whom, at the current stage of development, no satisfactory therapy is available yet. Preclinical experimental studies have shown that the CNS of healthy rodents and piglets can tolerate much higher radiation doses delivered by spatially separated MBs than those delivered by a single, uninterrupted, macroscopically wide beam. High-dose, high-precision radiotherapies such as MRT with reduced probabilities of normal tissue complications offer prospects of improved therapeutic ratios, as extensively demonstrated by results of experiments published by many international groups in the last two decades. The significance of developing MRT as a new RT approach cannot be understated. Up to 50% of cancer patients receive conventional RT, and any new treatment that provides better tumour control whilst preserving healthy tissue is likely to significantly improve patient outcomes.     

Advances and future of Radiation Oncology

Aim

Review of recent advances and vision for future developments in clinical practice of Radiation Oncology.

Background

There have been substantial research and technological developments in Radiation Oncology over the past 40 years.

Materials and methods

The relevant literature was reviewed and the authors offer their perspective on future opportunities for advancement in Radiation Oncology.

Conclusions

Significant innovative technological developments have been introduced in the practice of Radiation Oncology, with more precise target delineation and tracking and three dimensional treatment planning, optimal delivery of radiation therapy to the target and lower doses to surrounding Organs at Risk. This dose optimization and adaptive therapy have enhanced the role of Radiation Therapy to more effectively treat patients with cancer. Further creativity and refinements will continue to advance the field into new applications of ionizing radiations in cancer therapy.     

Usefulness of the analysis of links among dream sources in therapy.

A study of the links among the memory sources of dreams can be carried out by means of an automatic analysis of text files including dream reports and associations. Heuristic criteria can provide plausible explanations for the existence of these links, which generally present a logical and at the same time emotional significance. The aim of this paper is to support the idea that the study of the link patterns among dream sources, in addition to being interesting from the cognitive viewpoint can be also useful for the therapeutic process. An interaction schema is described including four operators: the dreamer (patient), the therapist, the detector of possible links, and the proposer of plausible explanations. Two examples are given of application of this schema. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Radiation and adaptation, evolutionary biology and semantics

Radiations can be either adaptive or non-adaptive, resulting in a variety of niches occupied by sympatric species, or in hardly any niche differentiation and species showing largely mosaic distribution patterns. The terms are useful despite the fact that intermediate situations occur.     

Normoxic polymer gel dosimetry using less toxic monomer of N-isopropyl acrylamide and X-ray computed tomography for radiation therapy applications

Background

Polymer gel dosimetry has been used extensively in radiation therapy for its capability in depicting a three dimensional view of absorbed dose distribution. However, more studies are required to find less toxic and more efficient polymers for application in radiotherapy dosimetry.

Aim

The purpose of this work was to evaluate the N-isopropyl acrylamide (NIPAM) gel dosimetric characteristics and optimize the protocol for X-ray computed tomography (CT) imaging of gel dosimeters for radiation therapy application.

Material and methods

A polymer gel dosimeter based on NIPAM monomer was prepared and irradiated with ⁶⁰Co photons. The CT number changes following irradiation were extracted from CT images obtained with different sets of imaging parameters.

Results

The results showed the dose sensitivity of ΔN_CT (H) = 0.282 ± 0.018 (H Gy⁻¹) for NIPAM gel dosimeter. The optimized set of imaging exposure parameters was 120 kV_p and 200 mA with the 10 mm slice thickness. Results of the depth dose measurement with gel dosimeter showed a great discrepancy with the actual depth dose data.

Conclusion

According to the current study, NIPAM-based gel dosimetry with X-ray CT imaging needs more technical development and formulation refinement to be used for radiation therapy application.     

Radiation exposure limits for Japanese astronauts

Starting in 2001, Japanese astronauts will live aboard the International Space Station (ISS) for 3 to 6 months a year. For astronauts, space radiation is primarily hazardous. Therefore, the National Space Development Agency of Japan (NASDA) is developing a system for Space Radiation Safety Operations. This report describes our overall image of Space Radiation Safety Operations aboard the ISS, especially our proceedings in drafting the "Space Radiation Exposure Limits for Japanese ISS Astronauts."     

A review on gold nanoparticles radiosensitization effect in radiation therapy of cancer

In the recent years, application of nanoparticles in diagnosis and treatment of cancer has been the issue of extensive research. Among these studies some have focused on the dose enhancement effect of gold nanoparticles (GNPs) in radiation therapy of cancer. On the other hand, some studies indicated energy dependency of dose enhancement effect, and the others have studied the GNP size effect in association with photon energy. However, in some aspects of GNP-based radiotherapy the results of recent studies do not seem very conclusive in spite of relative agreement on the basic physical interaction of photoelectric between GNPs and low energy photons. The main idea behind the GNP dose enhancement in some studies is not able to explain the results especially in recent investigation on cell lines and animal models radiation therapy using GNPs. In the present article the results of the available reports and articles were analyzed and compared and the final status of the GNP-RT was discussed.     

放射治疗联合血管内皮抑制素对大鼠移植性肝癌的治疗作用

目的:探讨放射治疗联合血管内皮抑制素对大鼠移植性肝癌的治疗作用。方法:SD大鼠随机分为5组:假手术组,模型组,血管内皮抑素组,放疗组,联合组,血管内皮抑素组和联合组每日尾静脉注射浓度为10%重组人血管内皮抑素0.1 ml(20μg),共12天,联合组在第5天～10天时给予放射治疗,1次/2天。各组动物于移植术后12d处死,分离肿瘤组织备用。结果:血管内皮抑素组、放疗组、联合组均能显著抑制肿瘤生长,抑制VEGF表达,其中联合组抑制效果更为明显。结论:放射治疗联合血管内皮抑制素有明显肿瘤抑制作用,其机制可能与下调VEGF的表达有关。     

Context-dependent role of ATG4B as target for autophagy inhibition in prostate cancer therapy

ATG4B belongs to the autophagin family of cysteine proteases required for autophagy, an emerging target of cancer therapy. Developing pharmacological ATG4B inhibitors is a very active area of research. However, detailed studies on the role of ATG4B during anticancer therapy are lacking. By analyzing PC-3 and C4-2 prostate cancer cells overexpressing dominant negative ATG4B^C74Ain vitro and in vivo, we show that the effects of ATG4B^C74A are cell type, treatment, and context-dependent. ATG4B^C74A expression can either amplify the effects of cytotoxic therapies or contribute to treatment resistance. Thus, the successful clinical application of ATG4B inhibitors will depend on finding predictive markers of response.     

Challenges of Radiation Oncology in Spain Today

The increasing cost of health care delivery, coupled with reduced investments and budget cuts in European health care systems, has had a severe negative impact on health care delivery in Spain. This reduction in spending has had particularly negative effects on specialties that are heavily reliant on large capital investments to purchase the latest technologies needed to deliver optimal radiotherapy treatments. The Spanish Society of Radiation Oncology has been proactively working to mitigate the negative impact of budget cuts in Spain. In this paper, the authors describe a variety of solutions and proposals to overcome these challenges.