In the context of oncologic therapy for children, radiation therapy is frequently indicated. This study identified the frequency of and reasons for the development of high-grade acute toxicity and possible sequelae.
Irradiated children have been prospectively documented since 2001 in the Registry for the Evaluation of Side Effects After Radiation in Childhood and Adolescence (RiSK) database in Germany and since 2008 in the registry for radiation therapy toxicity (RADTOX) in Sweden. Data were collected using standardized, published forms. Toxicity classification was based on Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer criteria.
As of June 2013, 1500 children have been recruited into the RiSK database and 485 into the RADTOX registry leading to an analysis population of 1359 patients (age range 0-18). A total of 18.9% (n=257) of all investigated patients developed high-grade acute toxicity (grades 3/4). High-grade toxicity of the bone marrow was documented for 63.8% (n=201) of those patients, oral mucositis for 7.6% (n=24), and dermatitis for 7.6% (n=24). Patients with high-grade acute toxicity received concomitant chemotherapy more frequently (56%) than patients with no or lower acute toxicity (31.5%). In multivariate analyses, concomitant chemotherapy, diagnosis of Ewing sarcoma, and total radiation dose showed a statistically noticeable effect (P=.05) on acute toxicity, whereas age, concomitant chemotherapy, Hodgkin lymphoma, Ewing sarcoma, total radiation dose, and acute toxicity influenced the time until maximal late toxicity.
Generally, high-grade acute toxicity after irradiation in children and adolescence occurs in a moderate proportion of patients (18.9%). As anticipated, the probability of acute toxicity appeared to depend on the prescribed dose as well as concomitant chemotherapy. The occurrence of chronic toxicity correlates with the prior acute toxicity grade. Age seems to influence the time until maximal late toxicity but not the development of acute toxicity.
The operation of the Mayak Production Association in the Southern Urals region of Russia, resulted in releases of large amounts of radioactive effluent into the Techa River during the period 1949-1956. The residents of the riverside communities were thus exposed to both external radiation, and internal radiation following ingestion of contaminated water and foodstuffs. One of the most important radionuclides for internal exposure was 90Sr. This paper gives a brief overview of the models provided by International Commission on Radiological Protection (ICRP), which are of interest for assessing internal doses from 90Sr. The application of these models to the calculation of red bone marrow doses for the fetus and infant from 90Sr intakes by the mother and the infant is illustrated by an example. A hypothetical individual born in 1951 is used as an example for dose calculations. The following doses due to intakes of 90Sr are taken into account: received in utero due to maternal intakes during pregnancy; received after birth from 90Sr accumulated by the fetus in utero; from intakes in breast milk; from intakes in the infant's diet after weaning. It is shown that doses to the fetus following maternal ingestion and subsequent transfer to the fetus via the placenta dominate the doses received for this particular individual for the first two years of life. Doses to the infant from intakes in breast milk are substantially lower but do make significant contributions to total doses in the first two years after birth. By about the age of two years residual 90Sr from placental transfer still contributes about the same dose as do intakes by the infant, but in later years doses from intakes by the infant dominate.
It is theorized that biological responses to ionizing radiation in the low dose range are determined according to a doubly dichotomous pattern. Energy depositions fall into 2 categories: events at thermal energy levels where they may be experienced by cells as rates even at background exposure conditions, and events at energy levels of the order of 10-100 eV where damage to DNA may be caused. Variations in background exposure intensity may or may not lead preemptively to changes in the cell's capacity for response to radiation damage. High-level energy depositions lead post hoc to an initial stabilizing reaction largely leading to the fixation of the initial DNA damage, and to a subsequent restorative or palliative repair process. This model entails reinterpretation of some experimental results. The model has implications for the relationship between scientific analysis of low-dose effects and the regulatory needs for simplicity and homogeneity in risk evaluation. This represents a new challenge for the acceptability of radiation protection norms.
Comment In: Mutat Res. 1992 Dec;298(2):141-31282211
Operation of "Mayak" plutonium production complex resulted in radioactive contamination of the part of Chelyabinsk Region in 1950-60s. Significant gas-aerosol emissions of 1311 occurred since 1948; in 1957, a radiation accident resulted in 90Sr contamination of large territories. This paper presents comparison of bone mineral density of persons lived on territories with different levels of soil 90Sr-contamination with a control group. It was found that in 1970-1975 the bone mineral density, estimated from mineral content in bone samples, in residents of contaminated areas born in 1936-1952 was significantly lower compared with the control group. For persons born in 1880-1935 such differences were not found. It was shown that the decrease in bone mineral density was not related to 90Sr exposure of osteogenic cells in the dose range from 0.1 to 1300 mGy: the coefficient of correlation between individual 90Sr-doses and bone mineral contents was not significant. The decrease in bone mineral density of persons born in 1936-1952 could be associated with exposure of thyroid and parathyroid glands (systemic regulators of calcium turnover) by 131I from gas-aerosol emissions from "Mayak". Maximum gas-aerosol emissions occurred in 1948-1954 and coincided with growth and development of thyroid gland, characterizing by intensive accumulation of 131I, and with growth and maturation of the skeleton of persons born in these calendar years.
Individual and population doses on Danish territory are calculated from hypothetical, severe core-melt accidents at the Swedish nuclear plant at Barsebäck. The release fractions for these accidents are taken from WASH-1400. Based on parametric studies, doses are calculated for very unfavourable, but not incredible weather conditions. The probability of such conditions in combination with wind direction towards Danish territory is estimated. Doses to bone marrow, lungs, GI-tract and thyroid are calculated using dose models developed at Risø. These doses are found to be consistent with doses calculated with the models used in WASH-1400.
Roentgen treatment for painful benign conditions in the locomotor system as arthrosis and spondylosis was in Sweden very common up to the beginning of the 1960s. The mode of treatment differed from the British ankylosing spondylitis series as smaller parts of the red bone marrow were exposed and smaller doses were applied. A cohort of 20,024 such patients treated 1950-1964 at two hospitals in northern Sweden was analysed with regard to the risk of haematological malignancies. Average factors for conversion of prescribed skin doses to mean absorbed red bone marrow doses were estimated on random samples of the different treatment sites and then applied on the cohort in its whole. The standard incidence ratio (SIR) for leukaemia was 1.18 (95% CI: 0.98-1.42) and the standard mortality ratio (SMR) 1.25 (0.99-1.45). In the highest dose group (mean absorbed red bone marrow dose > 0.5 Gy) the corresponding values were 1.40 (1.00-1.92) and 1.50 (1.08-2.04). In the mortality analysis also a slightly increased myeloma risk was noted with SMR = 1.20 (0.99-1.56). Extension of the cohort and nested case-control studies are under progress.
To investigate within the framework of a multilaboratory study the suitability of FISH chromosome painting to measure so-called stable translocations in peripheral lymphocytes of Mayak nuclear-industrial workers (from the Southern Urals) and their use for retrospective biodosimetry.
Chromosime analyses were carried out from 69 workers who had received protracted occupational radiation exposures (0.012-6.065 Gy) up to approximately 40 years before blood sampling. Twenty-one unexposed people living in the same area were controls. A multicolour FISH-painting protocol with the target chromosomes 1, 4 and 8 simultaneously with a pancentromeric probe was used to score potentially transmissible chromosome-type aberrations (reciprocal translocations 2B and related 'one-way' patterns I-III according to the S&S classification).
Individual biodosimetry estimates were obtained in terms of these potentially long-term surviving aberration types based on the linear component of a low dose-rate gamma-ray calibration curve produced using identical staining and scoring protocols. For comparison, the workers personal and total background doses were converted to red bone marrow doses. The estimated doses were mainly lower than would be predicted by the calibration curve, particularly at accumulated higher dose levels.
Owing to the limited life-time of circulating T-lymphocytes, the long-term persistence of translocations in vivo requires the assumption of a clonal repopulation of these naturally senescing cells from the haemopoietic stem cell compartments. Obviously such a replacement cannot be fully achieved, leading to a temporal decline even of the yield of transmissible aberrations types. Assuming further a highly selective capacity of stem cells against any type of chromosomal damage and the fact that one must rely on partial genome findings, the potential of FISH chromosome painting for retrospective dose reconstruction is probably limited to a decade or so after high-level protracted radiation exposure.
We examined the records of 105 patients with advanced ovarian cancer who had been treated with cisplatin combination chemotherapy followed by abdominopelvic radiotherapy. The purpose was to define the morbidity of this approach, and identify those factors predictive of toxicity. Acute toxicity resulting in delay or failure to complete treatment was most commonly due to myelosuppression. Nine of 105 patients (8.6%) required surgery for bowel obstruction that was not due to recurrent disease, 3 had an episode of bowel obstruction that settled conservatively, and a further 5 underwent surgery for obstruction due to recurrent tumor. The presence of both a dose of abdominopelvic radiotherapy over 2250 cGy, as well as a second-look laparotomy prior to radiotherapy, was associated with an increased risk of serious bowel complications. The increased frequency of late bowel morbidity seen in the combined modality group is likely explained by the presence of these two factors, rather than the exposure to chemotherapeutic agents per se. These observations are supported by the published literature.
The Mayak Production Association released large amounts of (90)Sr into the Techa River (Southern Urals, Russia) with peak amounts in 1950-1951. Techa Riverside residents ingested an average of about 3,000 kBq of (90)Sr. The (90)Sr-body burden of approximately 15,000 individuals has been measured in the Urals Research Center for Radiation Medicine in 1974-1997 with use of a special whole-body counter (WBC). Strontium-90 had mainly deposited in the cortical part of the skeleton by 25 years following intake, and (90)Sr elimination occurs as a result of cortical bone resorption. The effect of (90)Sr-radiation exposure on the rate of cortical bone resorption was studied. Data on 2,022 WBC measurements were selected for 207 adult persons, who were measured three or more times before they were 50-55 years old. The individual-resorption rates were calculated with the rate of strontium recirculation evaluated as 0.0018 year(-1). Individual absorbed doses in red bone marrow (RBM) and bone surface (BS) were also calculated. Statistically significant negative relationships of cortical bone resorption rate were discovered related to (90)Sr-body burden and dose absorbed in the RBM or the BS. The response appears to have a threshold of about 1.5-Gy RBM dose. The radiation-induced decrease in bone resorption rate may not be significant in terms of health. However, a decrease in bone remodeling rate can be among several causes of an increased level of degenerative dystrophic bone pathology in exposed persons.