Clinical and Preclinical Outcomes of Combining Targeted Therapy With Radiotherapy

In the era of precision medicine, radiation medicine is currently focused on the precise delivery of highly conformal radiation treatments. However, the tremendous developments in targeted therapy are yet to fulfill their full promise and arguably have the potential to dramatically enhance the radiation therapeutic ratio. The increased ability to molecularly profile tumors both at diagnosis and at relapse and the co-incident progress in the field of radiogenomics could potentially pave the way for a more personalized approach to radiation treatment in contrast to the current ‘‘one size fits all’’ paradigm. Few clinical trials to date have shown an improved clinical outcome when combining targeted agents with radiation therapy, however, most have failed to show benefit, which is arguably due to limited preclinical data. Several key molecular pathways could theoretically enhance therapeutic effect of radiation when rationally targeted either by directly enhancing tumor cell kill or indirectly through the abscopal effect of radiation when combined with novel immunotherapies. The timing of combining molecular targeted therapy with radiation is also important to determine and could greatly affect the outcome depending on which pathway is being inhibited.

RADIOECOLOGICAL SITUATION ON THE TERRITORY OF BORODULIKHA VILLAGE OF BORODULIKHA DISTRICT, EAST KAZAKHSTAN REGION

As part of the research work on the topic «Development of scientific and methodological foundations for minimizing the environmental burden, medical support, social protection and health improvement of the population of environmentally unfavorable territories of the Republic of Kazakhstan», the Research Institute of Radiation Medicine and Ecology carried out radioecological studies on the territory of Borodulikha village of Borodulikha district of East Kazakhstan region in May 2018. Radiation parameters of the environmental situation (MED, radon concentration, alpha and beta particle flux densities, the content of radioactive elements in environmental objects).

Preventive measures for labor protection in the field of radiation medicine

Labor productivity depends on various factors, including appropriate working conditions. Work in the field of radiation medicine can have both harmful working conditions associated with equipment, drugs that must be used in the work, and psychological factors associated with the need to communicate with patients with complex diagnoses, psychological fatigue, which can become chronic if preventive measures are not taken in time. Statistical data from the official websites of the State Labor Service of Ukraine and the Ministry of Health of Ukraine were used in the work, students were interviewed using the Google survey form. Methods of rational criticism, dialectical, comparative-legal and formal-legal methods are used. It has been established that the inclusion of a special course on labor protection in educational programs will be an urgent preventive measure. To reduce the risk of burnout, it is necessary to conduct training, it is also necessary to conduct surveys of medical practitioners to identify problematic factors that need to be addressed. To improve the culture of a healthy lifestyle, to protect workers in the field of radiation medicine from the effects of hazardous production factors, it is necessary to strengthen preventive measures to prevent accidents at work and occupational diseases, as well as other exposure to hazardous production factors. To do this, it is proposed to improve two areas of preventive work. The first is to strengthen information work among students who obtain the profession of a medical worker in the field of radiation medicine, by introducing a special course on labor protection. Thus, the special course should be developed under features of work in the field of radiation medicine. In order to provide effective information, narrow specialists should be involved in lecturing. The second is to conduct simulation and psychological trainings for medical practitioners. The Social Insurance Fund of Ukraine should be involved in financing preventive measures. It is also advisable for the Foundation to submit its proposals to the methodological developments of new preventive measures.

Approaches to training and supply of qualified personnel for radiation medicine facilities

The report presents the results of a review and discussion on providing qualified personnel for radiation medicine facilities and suggests approaches to personnel training. Qualified personnel availability comes first among the principles of quality control of radiopharmaceuticals (RP), supply of modern equipment, access to up-to-date regulatory documents, validated control methods and the organization of internal audit system. Also, radiation medicine facilities workers are inevitably exposed to harmful hygienic factors of the working environment throughout the entire life cycle of RP: the development, testing, production and civil circulation. Nuclear and radiation medicine facilities place the environment at risk of negative impact. Highly qualified specialists (responsible parties) should have knowledge, skills and abilities provided by special basic education are required to assess sanitary, hygienic and environmental risks and to comply with the quality management system requirements for the stable operation of radiation medicine facilities.

Prospective directions and problems of ensuring Radiation Safety in Radiation Medicine

The development of Radiation Medicine in the Russian Federation has resulted in the necessity to improve the regulatory and methodological support for ensuring Radiation Safety. Following the introduction of new diagnostics and therapy methods into practice, as well as the use of new radiopharmaceuticals, the actualization of radiation monitoring methods and the provision of radiological protection for patients, personnel and the public have become the most urgent tasks. Radionuclide therapy with new radiopharmaceuticals, which can be used in the day patient departments, is one of the promising directions in the development of Russian Radiation Medicine. The main tasks of ensuring Radiation Safety in the departments of radionuclide therapy are the regulation of radioactive waste management, the development of discharge criteria after the administration of radiopharmaceuticals and methods for Internal Dosimetry.

Methods of biological waste management generated by patients

The development of radiation medicine in the Russian Federation has resulted in the improvement of the regulatory and methodological framework for radiation safety regulation. The main obstacle for the development of radionuclide therapy in the Russian Federation is the liquid radioactive waste management (mainly urine and faeces of patients) generated during radionuclide therapy on an ambulatory basis (day patient department). The paper presents a brief analysis of the current domestic and international regulatory liquid radionuclide waste management documents. It has been shown that there is no strategy for solving the problem of utilizing biological waste from patients during radionuclide therapy. Long-term task for ensuring the sanitary and epidemiological well-being of the population of the Russian Federation could be the solution for the problem.

Lessons from the Fukushima Daiichi nuclear power plant accident –from a research perspective

Since the accident at Fukushima Daiichi nuclear power plant, there has been a focus on the impact of low-dose radiation exposure due to nuclear disasters and radiology on human bodies. In order to study very low levels of impact on the human body from low-dose radiation exposure, a system with high detection sensitivity is needed. Until now, the most well-established biological radiation effect detection system in the field of emergency radiation medicine has been chromosomal analysis. However, chromosomal analysis requires advanced skills, and it is necessary to perform chromosomal analysis of a large number of cells in order to detect slight effects on the human body due to low-dose radiation exposure. Therefore, in order to study the effects of low-dose radiation exposure on the human body, it is necessary to develop high-throughput chromosome analysis technology. We have established the PNA-FISH method, which is a fluorescence in-situ hybridisation method using a PNA probe, as a high-throughput chromosome analysis technique. Using this method, the detection of dicentrics and ring chromosomes has become very efficient. Using this technology, chromosomal analysis was performed on peripheral blood before and after computed tomography (CT) examination of patients at Hiroshima University Hospital, and it was possible to detect chromosomal abnormalities due to low-dose radiation exposure in the CT examination. Furthermore, it was shown that there may be individual differences in the increase in chromosomal abnormalities due to low-dose radiation exposure, suggesting the need to build a next-generation medical radiation exposure management system based on individual differences in radiation sensitivity. If techniques such as chromosomal analysis, which have been used for biological dose evaluation in emergency radiation medicine, can be used for general radiology, such as radiodiagnosis and treatment, that will be a contribution to radiology from an unprecedented angle. This article will discuss the clinical application of new biological dose evaluation methods that have been developed in the field of emergency radiation medicine.

An ionising radiation-induced specific transcriptional signature of inflammation-associated genes in whole blood from radiotherapy patients: a pilot study

Background This communication reports the identification of a new panel of transcriptional changes in inflammation-associated genes observed in response to ionising radiation received by radiotherapy patients. Methods Peripheral blood samples were taken with ethical approval and informed consent from a total of 20 patients undergoing external beam radiotherapy for breast, lung, gastrointestinal or genitourinary tumours. Nanostring nCounter analysis of transcriptional changes was carried out in samples prior and 24 h post-delivery of the 1st radiotherapy fraction, just prior to the 5th or 6th fraction, and just before the last fraction. Results Statistical analysis with BRB-ArrayTools, GLM MANOVA and nSolver, revealed a radiation responsive panel of genes which varied by patient group (type of cancer) and with time since exposure (as an analogue for dose received), which may be useful as a biomarker of radiation response. Conclusion Further validation in a wider group of patients is ongoing, together with work towards a full understanding of patient specific responses in support of personalised approaches to radiation medicine.