The heart has traditionally been considered a radio-resistant organ that would be unaffected by cardiac doses below about 30 Gray. During the last few years, however, evidence that radiation-related heart disease can occur following lower doses has emerged from several sources. These include studies of breast cancer patients, who received mean cardiac doses of 3–17 Gray when given radiotherapy following surgery, and studies of survivors of the atomic bombings of Japan who received doses of up to 4 Gray. At doses above 30 Gray, radiation-related heart disease may occur within a year or two of exposure and risk increases with higher radiotherapy dose, younger age at irradiation, and the presence of conventional risk factors. At lower doses the typical latent period is much longer and is often more than a decade. However, the nature and magnitude of the risk following lower doses is not well characterized, and it is not yet clear whether there is a threshold dose below which there is no risk. The evidence regarding radiation-related heart disease comes from several different disciplines. The present review brings together information from pathology, radiobiology, cardiology, radiation oncology and epidemiology. It summarises current knowledge, identifies gaps in that knowledge, and outlines some potential strategies for filling them. Further knowledge about the nature and magnitude of radiation-related heart disease would have immediate application in radiation oncology. It would also provide a basis for radiation protection policies for use in diagnostic radiology and occupational exposure.

This study indicates a key role for the EGFR receptor in determining the proliferative cellular response to fractionated radiotherapy in HNSCC. It also shows that we can select the dose-fractionation regime that has the greatest chance of benefiting the patient. These results also encourage further development of EGFR targeting combined with fractionated radiotherapy in HNSCC.

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In radiooncology, cancer stem cells have been an important research field for five decades. Quantitative transplantation assays with evaluation of the take dose 50% (TD50) remain the gold standard to verify the stemness of the selected cells. New technologies allow sorting of tumour cells according to their surface marker expression and thereby selecting subpopulations that are enriched in cancer stem cells (e.g., CD133, CD44, CD29). While development of surface-marker-based assays is a highly important step in cancer-stem-cell research, to date there are still problems to be solved, e.g., the specifity of markers, adequate animal models, and optimised in vitro assays. Of special concern for radiobiology is that clonogenic in vitro assays do not necessarily measure stemness of cancer cells. This hampers investigations into the important question of whether cancer stem cells are more radioresistant than non-stem cells. The most extensive of the limited data on this topic relate to glioma stem cells identified by the surface marker CD133. These do not provide firm evidence for difference of radiosensitivity between stem and non stem cells. In spite of many problems to be solved, the combination of stem cell markers with radiobiological assays bears considerable promise for advancing translational research in radiation oncology.

Other investigators have demonstrated by transfer of medium from irradiated cells and by irradiation with low-fluence alpha particles or microbeams that cells do not have to be directly exposed to ionizing radiation to be detrimentally affected, i.e. bystander effects. In this study, we demonstrate by transfer of medium from X-irradiated human CGL1 hybrid cells that the killing of bystander cells reduces the plating efficiency of the nonirradiated CGL1 cells by 33 +/- 6%. In addition, we show that the amount of cell death induced by bystander effects is not dependent on X-ray dose, and that the induction of apoptosis does not appear to be responsible for the cell death. Furthermore, we found that the reduction in plating efficiency in bystander cells is evident for over 18 days, or 22 cell population doublings, after medium transfer, despite repeated refeeding of the cell cultures. Finally, we report the novel observation that bystander effects induced by the transfer of medium from irradiated cells can induce neoplastic transformation. Exposing unirradiated CGL1 cells to medium from cells irradiated with 5 or 7 Gy increased the frequency of neoplastic transformation significantly from 6.3 x 10(-6) in unirradiated controls to 2.3 x 10(-5) (a factor of nearly four). We conclude that the bystander effect induces persistent, long-term, transmissible changes in the progeny of CGL1 cells that result in delayed death and neoplastic transformation. The data suggest that neoplastic transformation in bystander cells may play a significant role in radiation-induced neoplastic transformation at lower doses of X rays.

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Recent experimental evidence has challenged the paradigm according to which radiation traversal through the nucleus of a cell is a prerequisite for producing genetic changes or biological responses. Thus, unexposed cells in the vicinity of directly irradiated cells or recipient cells of medium from irradiated cultures can also be affected. The aim of the present study was to evaluate, by means of the medium transfer technique, whether interleukin-8 and its receptor (CXCR1) may play a role in the bystander effect after gamma irradiation of T98G cells in vitro. In fact the cell specificity in inducing the bystander effect and in receiving the secreted signals that has been described suggests that not only the ability to release the cytokines but also the receptor profiles are likely to modulate the cell responses and the final outcome. The dose and time dependence of the cytokine release into the medium, quantified using an enzyme linked immunosorbent assay, showed that radiation causes alteration in the release of interleukin-8 from exposed cells in a dose-independent but time-dependent manner. The relative receptor expression was also affected in exposed and bystander cells.

The US nuclear weapons testing program in the Pacific conducted between 1946 and 1958 resulted in radiation exposure in the Marshall Islands. The potentially widespread radiation exposure from radioiodines of fallout has raised concerns about the risk of thyroid cancer in the Marshallese population . The most serious exposures and its health hazards resulted from the hydrogen-thermonuclear bomb test, the Castle BRAVO, on March 1, 1954. Between 1993 and 1997, we screened 3,709 Marshallese for thyroid disease who were born before the BRAVO test. It was 60% of the entire population at risk and who were still alive at the time of our examinations. We diagnosed 30 thyroid cancers and found 27 other study participants who had been operated for thyroid cancer before our screening in this group. Fifty-seven Marshallese born before 1954 (1.5%) had thyroid cancer or had been operated for thyroid cancer. Nearly all (92%) of these cancers were papillary carcinoma. We derived estimates of individual thyroid dose proxy from the BRAVO test in 1954 on the basis of published age-specific doses estimated on Utirik atoll and 137Cs deposition levels on the atolls where the participants came from. There was suggestive evidence that the prevalence of thyroid cancer increased with category of estimated dose to the thyroid. J Epidemiol2003;13:99-107. An estimated average thyroid dose from the Bravo test in a oneyear-old child was 52 Gy (5,200cGy) on the downwind atoll Rongelap and 6.8 Gy (680 cGy) on Utirik an atoll further downwind.1 These exposed communities of these two atolls were evacuated about 72 hours after the detonation and then provided with follow-up medical care over the decades since by the United States .2 The most frequent long-term health effect in the exposed population appeared to be an increased frequency of nodular thyroid disease including thyroid cancer.3 Twenty-three Japanese fishermen of Fukuryu Maru (Lucky Dragon) were also exposed to radioactive fallout from the BRAVO test nearby these two atolls.