Toward a consensus on radiobiology teaching to radiation oncology residents

There are approximately 82 radiation oncology residency programs in the United States, which provide training opportunities for about 400 residents. All accredited radiation oncology residency programs must have at least one basic scientist on the faculty, and it is these individuals who often assume, wholly or in part, the responsibility of teaching radiation and cancer biology to radiation oncology residents in preparation for the American College of Radiology (ACR) In-Training Examination in Radiation Oncology and the American Board of Radiology (ABR) written examinations. In response to a perceived lack of uniformity in radiation and cancer biology curricula currently being taught to residents and a perceived lack of guidance for instructors in formulating course content for this population, a special session was presented at the Forty-eighth Annual Radiation Research Society meeting on April 23, 2001. The session, entitled "Toward a Consensus on Radiobiology Teaching to Radiation Oncology Residents", was focused on issues related to teaching radiobiology to radiation oncology residents and targeted for individuals who actively teach radiation and cancer biology as well as coordinators of residency training programs. The speakers addressed current challenges and future problems facing instructors and programs. Among these were lack of feedback on resident performance on ABR and ACR written examinations and on course content, uncertainty about what topics residents must know to pass the ABR examination, and, in the near future, a reduction (due to retirement) of instructors qualified to teach radiobiology. This article provides a synopsis of the information that was presented during that session, offers a glimpse into how the ABR and ACR examinations are prepared and details of the content of past and future examinations, and summarizes the activities of the Joint Working Group on Radiobiology Teaching which was formed to educate instructors, to establish a consensus for course curricula, and to improve the overall quality of resident teaching.     

Updates to astronaut radiation limits: radiation risks for never-smokers

New epidemiology assessments of the life span study (LSS) of the atomic bomb survivors in Japan and of other exposed cohorts have been made by the U.S. National Academy of Sciences, the United Nations Committee on the Effects of Atomic Radiation, and the Radiation Research Effects Foundation in Japan. The National Aeronautics and Space Administration (NASA) uses a 3% risk of exposure-induced death (REID) as a basis for setting age- and gender-specific dose limits for astronauts. NASA's dose limits originate from the report of the National Council on Radiation Protection and Measurements (NCRP) in the year 2000 based on analysis of older epidemiology data. We compared the results of the recent analysis of the LSS to the earlier risk projections from the NCRP. Using tissue-specific, incidence-based risk transfer from the LSS data to a U.S. population to project REID values leads to higher risk and reduced dose limits for older astronauts (>40 years) compared to earlier models that were based on mortality risk transfer. Because astronauts and many other individuals should be considered as healthy workers, including never-smokers free of lifetime use of tobacco, we considered possible variations in risks and dose limits that would occur due to the reference population used for estimates. After adjusting cancer rates to remove smoking effects, radiation risks for lung and total cancer were estimated using a mixture model, with equal weights for additive and multiplicative transfer, to be 20% and 30% lower for males and females, respectively, for never-smokers compared to the average U.S. population. We recommend age- and gender-specific dose limits based on incidence-based risk transfer for never-smokers that could be used by NASA. Our analysis illustrates that gaining knowledge to improve transfer models, which entail knowledge of cancer initiation and promotion effects, could significantly reduce uncertainties in risk projections.     

Recent initiatives for radiation oncology resident education in radiation and cancer biology

Nearly all residents from accredited radiation oncology residency programs in the United States are required to take the American College of Radiology (ACR) In-Training examination each year. The test is comprised of three sections: Clinical Radiation Oncology, Radiological Physics, and Radiation (and Cancer) Biology. Here we provide an update on changes to the biology portion of the ACR exam. We also discuss the availability and use of the ACR and biology practice exams as assessment and teaching tools for both the instructors of radiation and cancer biology and the residents they teach.     

Undergraduate cancer education in Spain: The debate,the opportunities and the initiatives of the University Forum of the Spanish Society of Radiation Oncology (SEOR)

Most medical schools in Spain (80%) offer undergraduate training in oncology. This education is highly variable in terms of content (theory and practical training), number of credits, and the medical specialty and departmental affiliation of the professors. Much of this variability is due to university traditions in the configuration of credits and programmes, and also to the structure of the hospital-based practical training. Undergraduate medical students deserve a more coherent and modern approach to education with a strong emphasis on clinical practice. Oncology is an interdisciplinary science that requires the input of professors from multiple specialties to provide the primary body of knowledge and skills needed to obtain both a theoretical and clinical understanding of cancer. Clinical skills should be a key focus due to their importance in the current model of integrated medical management and care.Clinical radiation oncology is a traditional and comprehensive hospital-based platform for undergraduate education in oncology. In Spain, a significant number (n = 80) of radiation oncology specialists have a contractual relationship to teach university courses. Most Spanish universities (80%) have a radiation oncologist on staff, some of whom are department chairs and many others are full professors who have been hired and promoted under competitive conditions of evaluation as established by the National Agency for Quality Evaluation.The Spanish Society of Radiation Oncology (SEOR) has identified new opportunities to improve undergraduate education in oncology. In this article, we discuss proposals related to theoretical (20 items) and practical clinical training (9 items). We also describe the SEOR University Forum, which is an initiative to develop a strategic plan to implement and organize cancer education at the undergraduate level in an interdisciplinary teaching spirit and with a strong contribution from radiation oncologists.     

Frontiers in glycomics; bioinformatics and biomarkers in disease. September 11-13, 2006 Natcher Conference Center, NIH Campus, Bethesda, MD, USA

This is a short summary of a meeting entitled "The Frontiers in Glycomics; Bioinformatics and Biomarkers in Disease" which was jointly organized by the NIH Consortium for Functional Glycomics (CFG), Human Disease Glycomics/Proteome Initiative (HGPI), National Cancer Institute, National Institute of General Medical Sciences, Japan Society for the Promotion of Science and National Center for Research Resources held at the NIH Campus, Bethesda, MD, Natcher Conference Center in September 11-13, 2006.     

Radiation chemistry and the Radiation Research Society: a history from the beginning

Radiation chemistry studies began in the early 20th century with observations involving the decomposition of various materials by X rays and radium. Hugo Fricke recognized that the chemical effects of radiation should be studied to help understand the response of living systems to radiation, and in 1928 he established a laboratory to conduct such studies. Early radiation chemists were intimately involved in the founding of the Radiation Research Society and contributed substantially to its interdisciplinary culture. In this historical review, the highlights of research in radiation chemistry leading up to the founding of the Radiation Research Society in 1952 are discussed. The status of the field is established at that point, and a sampling of the major accomplishments from then until the present is presented, with emphasis on those scientists who have contributed substantially to the life and culture of the Radiation Research Society.     

Modifying normal tissue damage postirradiation. Report of a workshop sponsored by the Radiation Research Program, National Cancer Institute, Bethesda, Maryland, September 6-8, 2000

Late effects that develop in normal tissues adjacent to the tumor site in the months to years after radiotherapy can reduce the quality of life of cancer survivors. They can be dose-limiting and debilitating or life-threatening. There is now evidence that some late effects may be preventable or partially reversible. A workshop, "Modifying Normal Tissue Damage Postirradiation", was sponsored by the Radiation Research Program of the National Cancer Institute to identify the current status of and research needs and opportunities in this area. Mechanistic, genetic and physiological studies of the development of late effects are needed and will provide a rational basis for development of treatments. Interdisciplinary teams will be needed to carry out this research, including pathologists, physiologists, geneticists, molecular biologists, experts in functional imaging, wound healing, burn injury, molecular biology, and medical oncology, in addition to radiation biologists, physicists and oncologists. The participants emphasized the need for developing and choosing appropriate models, and for radiation dose-response studies to determine whether interventions remain effective at the radiation doses used clinically. Both preclinical and clinical studies require long-term follow-up, and easier-to-use, more objective clinical scoring systems must be developed and standardized. New developments in biomedical imaging should provide useful tools in all these endeavors. The ultimate goals are to improve the quality of life and efficacy of treatment for cancer patients treated with radiotherapy.     

Technology advancement for studying gene expression and gene function: a workshop report

Society News

Technology advancement for studying gene expression and gene function: a workshop reportSponsored by National Institute of Child Health and Human Development, National Institute of General Medical Sciences, National Center for Human Genome Research, National Center for Research Resources, National Institutes of Health, Bethesda, Maryland 20892, USA     

Global radiation oncology waybill

Background/aim

Radiation oncology covers many different fields of knowledge and skills. Indeed, this medical specialty links physics, biology, research, and formation as well as surgical and clinical procedures and even rehabilitation and aesthetics. The current socio-economic situation and professional competences affect the development and future or this specialty. The aim of this article was to analyze and highlight the underlying pillars and foundations of radiation oncology, indicating the steps implicated in the future developments or competences of each.

Methods

This study has collected data from the literature and includes highlights from discussions carried out during the XVII Congress of the Spanish Society of Radiation Oncology (SEOR) held in Vigo in June, 2013. Most of the aspects and domains of radiation oncology were analyzed, achieving recommendations for the many skills and knowledge related to physics, biology, research, and formation as well as surgical and clinical procedures and even supportive care and management.

Results

Considering the data from the literature and the discussions of the XVII SEOR Meeting, the “waybill” for the forthcoming years has been described in this article including all the aspects related to the needs of radiation oncology.

Conclusions

Professional competences affect the development and future of this specialty. All the types of radio-modulation are competences of radiation oncologists. On the other hand, the pillars of Radiation Oncology are based on experience and research in every area of Radiation Oncology.     

Report on an interagency workshop on the radiobiology of nuclear terrorism. Molecular and cellular biology dose (1-10 Sv) radiation and potential mechanisms of radiation protection (Bethesda,Maryland, December 17-18, 2001)

The events of September 11, 2001 have focused attention on the possibility of nuclear terrorism, and 1-10 Sv is arguably the dose range of biological interest, since doses in this range both pose a risk of acute effects and are potentially survivable. Because of this interest, a coalition of U.S. government agencies (NCI, DOD, DOE) and the Radiation Research Society convened a workshop in December 2001 "to focus on molecular, cellular and tissue changes that occur [at doses of 1-10 Sv] and potential mechanisms of radioprotection". A draft report of this workshop was posted on the NCI website in February 2002. According to the draft, the workshop was also intended to "determine the research opportunities and resources required [and] develop a research-action plan for further discussion and implementation." Injuries after exposure to ionizing radiation are important to patients with cancer and to populations potentially subject to accidental or intentional exposure. In these populations, partial- or whole-body exposures in the range of 1-10 Sv are possible. The consequences of exposure of limited tissue volumes to doses above 10 Sv have been researched because of their applicability to cancer therapy, while exposure to doses below 1 Sv has been researched because of nuclear fallout and space exploration issues. Except for research aimed at protection of members of the armed forces, the intervening dose range has received relatively little attention. The workshop participants concluded that although we currently have only a limited ability to deal with the consequences of radiation exposures in this range, focused research would have the potential of rapidly expanding such capabilities.     

Mechanistic models for radiation carcinogenesis and the atomic bomb survivor data

Recently, Heidenreich et al. (Radiat. Res., 158, 607-617, 2002) suggested that the Radiation Effects Research Foundation (RERF) A-bomb survivor cohort study is not large enough to discriminate between various possible carcinogenic mechanisms. At least with the current follow-up, this is true to some extent, but I think the specific issues are rather different than they suggest. In particular, I do not think it is true-as they further indicate-that various models fit the data about equally well while estimating very different patterns of excess risk, which would imply that these patterns cannot be reasonably well characterized. I will point to specific criticisms of their approach to the data and offer some more general comments on mechanistic modeling approaches. Although there are important distinctions, I suggest on a very optimistic note that the two major approaches may be converging, and soon the main differences may not be in the assumptions made but in the aims of the modeling.     

The 6(th) East Midlands Proteomics Workshop supported by the BSPR and BMSS 14 November 2007, Nottingham, UK

Now in its 6(th) year, the East Midlands Proteomics workshop held in November 2007 brought together over 200 scientists with a common interest in proteomic techniques and their application to complex biological and biomedical problems. For the first time, this meeting was jointly supported by the British Society for Proteome Research (BSPR) and British Mass Spectrometry Society (BMSS).     

Radiation scientists and homeland security

Radiation scientists represent an important resource in homeland defense. Security analysts worry that a crude but deadly radiological bomb might be fashioned from stolen nuclear material and a few sticks of dynamite. Such a device could kill dozens, hundreds, and possibly thousands and could contaminate a square mile or more. Emergency workers may call upon radiation scientists to aid the injured. Educational materials are available on the ACR, ASTRO, and RRS websites, linked to the Armed Forces Radiobiology Research Institute and the Oak Ridge National Laboratory, to provide radiation workers material that they can use to help emergency room and civil defense personnel after a terrorist attack. Radiation scientists are urged to obtain these materials and contact their local hospital and public health authorities to volunteer their services and expertise.     

Specific ATM-mediated phosphorylation dependent on radiation quality

Whalen, M. K., Gurai, S. K., Zahed-Kargaran, H. and Pluth, J. M. Specific ATM-Mediated Phosphorylation Dependent on Radiation Quality. Radiat. Res. 170, 353-364 (2008).To determine whether the physical differences between high- and low-LET radiation are reflected in the biological responses of exposed cells, we detailed phospho-protein profiles of three proteins functional in radiation repair and signal transduction. Detailing gamma-H2AX, pATF2 Ser(490/498) and pSMC1 Ser(957) kinetics after X-ray and iron-ion exposure also provides a window into understanding the underlying cellular responses. Phosphorylated forms of these proteins have been documented to co-localize at sites of double-strand breaks (DSBs) after low-LET radiation exposures, and two of these phosphorylations, pATF2 and pSMC1, are specifically dependent on ATM. Flow cytometry-based methods were used to quantify total levels of each phospho-protein at various times after irradiation. As expected, we observed a greater induction and persistence in gamma-H2AX after iron-ion (high-LET) exposure compared to X-ray (low-LET) exposure. In contrast, pATF2 and pSMC1 showed markedly lower induction levels after iron-ion exposure compared to equivalent doses of X rays. Quantification of pATF2 and pSMC1 foci revealed fewer cells containing foci and fewer foci per cell after iron-ion compared to X-ray exposure. These findings suggest that ATM responds to DSBs induced by high-LET radiation differently from DSBs induced by low-LET radiation.     

Medical countermeasures for radiation combined injury: radiation with burn, blast, trauma and/or sepsis. report of an NIAID Workshop, March 26-27, 2007

Non-clinical human radiation exposure events such as the Hiroshima and Nagasaki bombings or the Chernobyl accident are often coupled with other forms of injury, such as wounds, burns, blunt trauma, and infection. Radiation combined injury would also be expected after a radiological or nuclear attack. Few animal models of radiation combined injury exist, and mechanisms underlying the high mortality associated with complex radiation injuries are poorly understood. Medical countermeasures are currently available for management of the non-radiation components of radiation combined injury, but it is not known whether treatments for other insults will be effective when the injury is combined with radiation exposure. Further research is needed to elucidate mechanisms behind the synergistic lethality of radiation combined injury and to identify targets for medical countermeasures. To address these issues, the National Institute of Allergy and Infectious Diseases convened a workshop to make recommendations on the development of animal models of radiation combined injury, possible mechanisms of radiation combined injury, and future directions for countermeasure research, including target identification and end points to evaluate treatment efficacy.     

A systematic review of epidemiological associations between low and moderate doses of ionizing radiation and late cardiovascular effects, and their possible mechanisms

Little, M. P., Tawn, E. J., Tzoulaki, I., Wakeford, R., Hildebrandt, G., Paris, F., Tapio, S. and Elliott, P. A Systematic Review of Epidemiological Associations Between Low and Moderate Doses of Ionizing Radiation and Late Cardiovascular Effects, and Their Possible Mechanisms. Radiat. Res. 169, 99-109 (2008). The link between high doses of ionizing radiation and damage to the heart and coronary arteries is established. In this paper, we systematically review the epidemiological evidence for associations between low and moderate doses (<5 Gy) of ionizing radiation and late-occurring cardiovascular disease. Risks per unit dose in epidemiological studies vary over at least two orders of magnitude, possibly a result of confounding factors. An examination of possible biological mechanisms indicates that the most likely causative effect of radiation exposure is damage to endothelial cells and subsequent induction of an inflammatory response, although it seems unlikely that this would extend to low-dose and low-dose-rate exposure. However, a role for somatic mutation has been proposed that would indicate a stochastic effect. In the absence of a convincing mechanistic explanation of epidemiological evidence that is less than persuasive at present, a cause-and-effect interpretation of the reported statistical associations cannot be reliably inferred, although neither can it be reliably excluded. Further epidemiological and biological evidence will allow a firmer conclusion to be drawn.     

NASA Radiation Biomarker Workshop, September 27-28, 2007

A summary is provided of presentations and discussions at the NASA Radiation Biomarker Workshop held September 27-28, 2007 at NASA Ames Research Center in Mountain View, CA. Invited speakers were distinguished scientists representing key sectors of the radiation research community. Speakers addressed recent developments in the biomarker and biotechnology fields that may provide new opportunities for health-related assessment of radiation-exposed individuals, including those exposed during long-duration space travel. Topics discussed included the space radiation environment, biomarkers of radiation sensitivity and individual susceptibility, molecular signatures of low-dose responses, multivariate analysis of gene expression, biomarkers in biodefense, biomarkers in radiation oncology, biomarkers and triage after large-scale radiological incidents, integrated and multiple biomarker approaches, advances in whole-genome tiling arrays, advances in mass spectrometry proteomics, radiation biodosimetry for estimation of cancer risk in a rat skin model, and confounding factors. A summary of conclusions is provided at the end of the report.     

New perspectives in radiation oncology: Young radiation oncologist point of view and challenges

AimTo assess the role of the young radiation oncologist in the context of important recent advancements in the field of radiation oncology, and to explore new perspectives and competencies of the young radiation oncologist.BackgroundRadiation oncology is a field that has rapidly advanced over the last century. It holds a rich tradition of clinical care and evidence-based practice, and more recently has advanced with revolutionary innovations in technology and computer science, as well as pharmacology and molecular biology.Materials and methodsSeveral young radiation oncologists from different countries evaluated the current status and future directions of radiation oncology.ResultsFor young radiation oncologists, it is important to reflect on the current practice and future directions of the specialty as it relates to the role of the radiation oncologist in the comprehensive management of cancer patients. Radiation oncologists are responsible for the radiation treatment provided to patients and its subsequent impact on patients’ quality of life. Young radiation oncologists must proactively master new clinical, biological and technical information, as well as lead radiation oncology teams consisting of physicists, dosimetrists, nurses and technicians.ConclusionsThe role of the young radiation oncologist in the field of oncology should be proactive in developing new competencies. Above all, it is important to remember that we are dealing with the family members and loved ones of many individuals during the most difficult part of their lives.     

Sustained metaphase arrest in response to ionizing radiation in a non-small cell lung cancer cell line

Kodym, E., Kodym, R., Choy, H. and Saha, D. Sustained Metaphase Arrest in Response to Ionizing Radiation in a Non-small Cell Lung Cancer Cell Line. Radiat. Res. 169, 46-58 (2008). In solid tumors, non-apoptotic forms of tumor cell inactivation such as mitotic catastrophe appear to be predominant in the response to DNA-damaging agents. Despite its importance, the underlying molecular mechanisms of mitotic catastrophe have been only partially elucidated. We found that a large fraction of HCC2279 non-small cell lung cancer cells underwent mitotic catastrophe after irradiation. Cells were arrested in metaphase with chromosomal damage indicated by DNA fragments displaced from the metaphase plate and considerable numbers of residual gamma-H2AX foci. Although TP53 was nonfunctional, we detected a prompt radiation response on the level of checkpoint kinases. In contrast, CDC25A was the only checkpoint phosphatase that was responsive to radiation. CDC25B was not detectable, and CDC25C was constitutively phosphorylated at serine 216, leading to its cytoplasmic sequestration and functional inactivation. Therefore, radiation-induced mitotic catastrophe in HCC2279 cells appears to be induced by a combination of relative insufficiencies in the p53-mediated and checkpoint kinase-mediated pathways leading to premature entry into mitosis. Displaced chromosome fragments triggering an intra-M checkpoint in cells entering mitosis presumably result in a sustained metaphase arrest. The phenomenon found in these cells, which were derived directly from a human patient, might be responsible for therapy-induced genetic instability of tumors.