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PubMed2003

Radiation-induced genomic instability and bystander effects: related inflammatory-type responses to radiation-induced stress and injury? A review.

PURPOSE: To review studies of radiation responses in the haemopoietic system in the context of radiation-induced genomic instability, bystander effects and inflammatory-type processes. RESULTS: There is considerable evidence that cells that themselves are not exposed to ionizing radiation but are the progeny of cells irradiated many cell divisions previously may express a high frequency of gene mutations, chromosomal aberrations and cell death. These effects are collectively known as radiation-induced genomic instability. A second untargeted effect results in non-irradiated cells exhibiting responses typically associated with direct radiation exposure but occurs as a consequence of contact with irradiated cells or by receiving soluble signals from irradiated cells. These effects are collectively known as radiation-induced bystander effects. Reported effects include increases or decreases in damage-inducible and stress-related proteins; increases or decreases in reactive oxygen species, cell death or cell proliferation, and induction of mutations and chromosome aberrations. This array of responses is reminiscent of effects mediated by cytokines and other similar regulatory factors that may involve, but do not necessarily require, gap junction-mediated transfer, have multiple inducers and a variety of context-dependent consequences in different cell systems. That chromosomal instability in haemopoietic cells can be induced by an indirect bystander-type mechanism both in vitro and in vivo provides a potential link between these two untargeted effects and there are radiation responses in vivo consistent with the microenvironment contributing secondary cell damage as a consequence of an inflammatory-type response to radiation-induced injury. Intercellular signalling, production of cytokines and free radicals are features of inflammatory responses that have the potential for both bystander-mediated and persisting damage as well as for conferring a predisposition to malignancy. The induction of bystander effects and instabilities may reflect interrelated aspects of a non-specific inflammatory-type response to radiation-induced stress and injury and be involved in a variety of the pathological consequences of radiation exposures.

Animals↗

PubMed2004

Radiation-blocking glasses allow vision during ophthalmic plaque radiation therapy.

PURPOSE: To evaluate the use of leaded safety glasses to block radiation and allow for vision during ophthalmic plaque radiation therapy. DESIGN: Interventional case series. METHODS: Eight patients were treated with palladium 103 ophthalmic plaque radiotherapy and measured for emitted radiation while wearing leaded glasses or a lead patch. Radiation emission was measured at 1 m so as to compare the glasses' ability to block radiation in vivo. RESULTS: In two patients the tumor was in the patients' only seeing eye, and the leaded radiation safety glasses allowed them to function (feed themselves and walk to the bathroom unassisted). In two additional patients, the glasses allowed binocularity and were preferred over the patch. Measurements revealed that both the lead patch and leaded radiation safety glasses reduced exposure to levels acceptable for discharge to home in New York City. CONCLUSIONS: Leaded radiation safety glasses improved patients' quality of life without sacrificing radiation safety.

Brachytherapy↗

PubMed2001

Inflammatory-type responses after exposure to ionizing radiation in vivo: a mechanism for radiation-induced bystander effects?

Haemopoietic tissues exposed to ionizing radiation are shown to exhibit increased macrophage activation, defined by ultrastructural characteristics and increased lysosomal and nitric oxide synthase enzyme activities. Macrophage activation post-irradiation was also associated with enhanced respiratory burst activities and an unexpected neutrophil infiltration. Examination of p53-null mice demonstrated that macrophage activation and neutrophil infiltration were not direct effects of irradiation, but were a consequence of the recognition and clearance of radiation-induced apoptotic cells. Increased phagocytic cell activity was maintained after apoptotic bodies had been removed. These findings demonstrate that, contrary to expectation, recognition and clearance of apoptotic cells after exposure to radiation produces both a persistent macrophage activation and an inflammatory-type response. We also demonstrate a complexity of macrophage activation following radiation that is genotype dependent, indicating that the in vivo macrophage responses to radiation damage are genetically modified processes. These short-term responses of macrophages to radiation-induced apoptosis and their genetic modification are likely to be important determinants of the longer-term consequences of radiation exposure. Furthermore, in addition to any effects attributable to immediate radiation-induced damage, our findings provide a mechanism for the production of damage via a 'bystander' effect which may contribute to radiation-induced genomic instability and leukaemogenesis.

Animals↗

PubMed2005

Reduction of treatment breaks and radiation-induced esophagitis and pneumonitis using amifostine in unresectable non-small cell lung cancer patients receiving definitive concurrent chemotherapy and radiation therapy: a prospective community-based clinical trial.

Concurrent chemotherapy with daily thoracic radiation therapy is a common regimen used in patients with non-small cell lung cancer resulting in excellent response rates but with appreciable morbidity. Radiation-induced toxicities may increase the number of treatment breaks and then may limit the use of this aggressive treatment approach for some patients. We are conducting an open-label, multicenter trial determining the incidence of radiation treatment breaks and severity of treatment-related toxicities with the concurrent use of a cytoprotective agent. Approximately 15 to 20 sites in the United States will participate with a total of 200 patients. Patients will receive one of two chemotherapy regimens and daily radiation (1.8 to 2.0 Gy daily; total dose, 60 to 70 Gy) and amifostine 500 mg subcutaneously or intravenous push daily over a 6- to 7-week period. Patients will receive amifostine (Ethyol; MedImmune Inc, Gaithersburg, MD) 500 mg daily. The route of amifostine administration chosen at the time of patient registration must be adhered to throughout the study. In addition, all patients may receive consolidation chemotherapy consisting of intravenous docetaxel 75 mg/m 2 once every 3 weeks for three courses, starting more than 30 but less than 60 days after the last dose of amifostine or thoracic radiation therapy, whichever is the last therapy discontinued. The objectives of this study are to determine the incidence of radiation treatment breaks and evaluate acute radiation esophagitis, acute radiation pneumonitis, chronic radiation pneumonitis, and pulmonary function in patients with measurable, medically inoperable non-small cell lung cancer stage II, unresectable stage IIIA, or IIIB disease receiving combined modality therapy and amifostine.

Amifostine↗

PubMed1993

Objective evaluation of 3-D radiation treatment plans: a decision-analytic tool incorporating treatment preferences of radiation oncologists.

PURPOSE: Selecting the optimal radiation treatment plan from a set of competing plans involves making trade-offs among the doses delivered to the target volumes and normal tissues by the competing plans. Evaluation of 3-dimensional radiation treatment plans is difficult because it requires the review of vast amount of graphical and numerical data. We have developed an objective plan-ranking model based on the concepts of decision analysis. METHODS AND MATERIALS: Our model ranks a set of tentative radiation treatment plans from best to worst. A figure of merit is computed for each plan based on probabilities of possible clinical complications such as non-eradication of the tumor and radiation induced damage to the nearby healthy normal tissues, and weights which indicate their clinical relevance. This figure of merit is used to rank the plans. Key issues addressed by the model include the incorporation of individual treatment preferences of the radiation oncologist and clinical features of the patient. RESULTS: A methodology has been established for eliciting the treatment preferences of radiation oncologists. Results of this elicitation, and examples of several plan evaluations are presented. An interactive computer-based tool has been developed as one of a set of tools to assist in the evaluation of 3-dimensional radiation treatment plans. CONCLUSION: The paper presents a decision-analytic model incorporating radiation oncologists' treatment preferences and an interactive computer-based tool for objectively ranking competing radiation treatment plans. The tool can be used by radiation oncologists for the evaluation of competing plans, or as part of a system which tries to automatically generate optimal treatment plans using mathematical or symbolic techniques.

Decision Support Techniques↗

PubMed1999

Desmoid tumor: prognostic factors and outcome after surgery, radiation therapy, or combined surgery and radiation therapy.

PURPOSE: To evaluate the therapeutic value of resection and the potential benefits of and indications for adjuvant and definitive radiation therapy for desmoid tumors. MATERIALS AND METHODS: We performed a retrospective review of 189 consecutive cases of desmoid tumor treated with surgical resection, resection and radiation therapy, or radiation therapy alone. Treatment was surgery alone in 122 cases, surgery and radiation therapy in 46, and radiation therapy alone in 21. Median follow-up was 9.4 years. RESULTS: Overall, 5- and 10-year actuarial relapse rates were 30% and 33%, respectively. Uncorrected survival rates were 96%, 92%, and 87% at 5, 10, and 15 years, respectively. For the patients treated with surgery, the actuarial relapse rates were 34% and 38% at 5 and 10 years, respectively. Among 78 patients with negative margins, the 10-year recurrence rate was 27%, whereas 40 margin-positive patients had a 10-year relapse rate of 54% (P = .003). Tumors located in an extremity also had a poorer prognosis than did those in the trunk. For patients treated with radiation therapy for gross disease, the 10-year actuarial relapse rate was 24%. For patients treated with combined resection and radiation therapy, the 10-year actuarial relapse rate was 25%. The addition of radiation therapy offset the adverse impact of positive margins seen in the surgical group. CONCLUSION: Wide local excision with negative pathologic margins is the treatment of choice for most desmoid tumors. Function-sparing resection is appropriate because adjuvant radiation therapy can offset the adverse impact of positive margins. Unresectable disease should be treated with definitive radiation therapy.

Adolescent↗

PubMed1987

Heat potentiation of radiation damage versus radiation potentiation of heat damage.

The enhanced lethality of mammalian cells after combined treatment with hyperthermia and radiation is usually attributed to heat potentiation of radiation damage. However, it has been suggested that the situation may be reversed and that radiation may act as a modifier for heat damage. To test this hypothesis, BP-8 murine sarcoma cells were subjected to sequential radiation and heat treatments and the kinetics and extent of cell death were evaluated with the [125I]-iododeoxyuridine prelabeling assay. Cell death after heating was rapid and essentially complete within 2 days after heat exposure, whereas radiation death was slow and became apparent only after a delay period of 3 days. Combined exposure of cells to radiation and heat caused a pronounced increase in the delayed component of cell death, that is, the radiation component of death. Irradiation of cells before heating did not change the early heat component of cell death even in cells that were exposed to massive radiation doses of up to 300 Gy prior to heating. These results indicate that the increased cell death observed in hyperthermia/radiation-treated cells results from heat potentiation of radiation damage, not radiation potentiation of heat damage.

Animals↗

PubMed1993

Study of biological effects of varying mixtures of Cf-252 and gamma radiation on the acute radiation syndromes: relevance to clinical radiotherapy of radioresistant cancer.

PURPOSE: Data for the 30 day bone marrow syndrome (BM-50) and the 6-10 day gastrointestinal (GI-50) syndrome for a one and two fraction schedule and acute and low dose rate irradiation using pure and mixed Cf-252 and photon radiation are presented. METHODS AND MATERIALS: The radiations of Cf-252 is a mixture of neutrons and gamma rays. We total body irradiated Balb/c mice of both sexes with acute Co-60, low dose rate Cs-137 and Cf-252 using a 1 x and 2 x schedule. For low linear energy transfer radiations of Co-60 or Cs-137 there was expected to be an increase in the dose to produce the gastrointestinal and bone marrow syndromes with minimal change for Cf-252 neutrons. However, the radiations from Cf-252 are approximately 65% neutrons and approximately 35% photons and hence some repair may be expected. We further altered the proportion of photons in the Cf-252 radiation field by mixing Cs-137 with the Cf-252 sources and total body irradiated the mice to determine the effects on the syndromes. We determined the effects of mixing Cf-252 neutrons with different proportions of photons on the radiation syndromes. RESULTS: There was increase in BM-50 and GI-50 doses with fractionated or low dose rate photon irradiations and the dose modifying factors were 1.3-1.4 for the GI syndrome and 1.2 for the bone marrow syndrome. For Cf-252 there was minimal fractionation effect for the GI-50 syndrome, which increased by a 1.1 for x 1 vs. x 2 fractions; for the BM-50 syndrome it rose by a 1.1 factor. For LDR Cs-137 the dose for the GI-50 syndrome rose by a 2.2 fold. For mixed neutron-photon radiation of 0%, 15%, 35%, and 65% eta/gamma mixtures, the dose to produce the BM-50 and GI-50 endpoints dropped sharply from 0 to 35% neutrons and remained flat thereafter. CONCLUSION: For major tissues such as the bone marrow and G-I tract, Cf-252 behaved as high linear energy transfer for mixtures of neutrons and gamma rays of approximately 35% neutrons when the radiation were delivered simultaneously at the low dose rates studied. There was little or no additional contribution to the effectiveness of the mixed radiations if neutrons contributed 35% or more of the dose.

Animals↗

PubMed2003

Rationale for integrating high-dose rate intraoperative radiation (HDR-IORT) and postoperative external beam radiation with subcutaneous amifostine for the management of stage III/IV head and neck cancer.

Locoregional recurrence remains a major obstacle to achieving cure of locally advanced head and neck cancers despite maximal resection and postoperative external beam radiation therapy (EBRT). Locoregional failure occurs in 30% to 40% of high-risk resected head and neck cancer patients after standard postoperative EBRT. In an effort to overcome this problem, a number of strategies have been designed to enhance the effectiveness of radiation including concurrent postoperative chemoradiation, accelerated radiation schedules, incorporation of targeted biologic therapies, and improved radiation delivery techniques such as intensity modulated radiation and high-dose rate (HDR) intraoperative radiation therapy. Intraoperative radiation therapy (IORT) represents an important approach to improve outcome in head and neck cancer patients treated with definitive surgery. High-dose rate IORT is defined as the delivery of a single, large dose of radiation at the time of surgery when the tumor bed is exposed. In conjunction with EBRT, HDR-IORT offers several advantages including: (1) conformal delivery of a large dose of radiation while the tumor bed is precisely defined, minimizing the risk of a geographic miss; (2) potential for subsequent dose reduction of EBRT; (3) shortening overall treatment time; and (4) dose-escalation. Because mucositis represents the dose-limiting acute toxicity and xerostomia ranks as the most common long-term quality-of-life complaint, a reduction of the EBRT dose may provide an important benefit in reducing toxicity, especially when combined with the radioprotectant amifostine (Ethyol, WR-2721; MedImmune, Inc, Gaithersburg, MD). The purpose of this article is to review the rationale for integrating HDR-IORT with a reduced dose of postoperative EBRT combined with amifostine to improve locoregional control and quality of life outcomes in advanced-stage resected head and neck cancer patients.

Amifostine↗

PubMed2006

Radiation-induced leukemia at doses relevant to radiation therapy: modeling mechanisms and estimating risks.

BACKGROUND: Because many cancer patients are diagnosed earlier and live longer than in the past, second cancers induced by radiation therapy have become a clinically significant issue. An earlier biologically based model that was designed to estimate risks of high-dose radiation-induced solid cancers included initiation of stem cells to a premalignant state, inactivation of stem cells at high radiation doses, and proliferation of stem cells during cellular repopulation after inactivation. This earlier model predicted the risks of solid tumors induced by radiation therapy but overestimated the corresponding leukemia risks. METHODS: To extend the model to radiation-induced leukemias, we analyzed--in addition to cellular initiation, inactivation, and proliferation--a repopulation mechanism specific to the hematopoietic system: long-range migration through the blood stream of hematopoietic stem cells (HSCs) from distant locations. Parameters for the model were derived from HSC biologic data in the literature and from leukemia risks among atomic bomb survivors who were subjected to much lower radiation doses. RESULTS: Proliferating HSCs that migrate from sites distant from the high-dose region include few preleukemic HSCs, thus decreasing the high-dose leukemia risk. The extended model for leukemia provides risk estimates that are consistent with epidemiologic data for leukemia risk associated with radiation therapy over a wide dose range. For example, when applied to an earlier case-control study of 110,000 women undergoing radiotherapy for uterine cancer, the model predicted an excess relative risk (ERR) of 1.9 for leukemia among women who received a large inhomogeneous fractionated external beam dose to the bone marrow (mean = 14.9 Gy), consistent with the measured ERR (2.0, 95% confidence interval [CI] = 0.2 to 6.4; from 3.6 cases expected and 11 cases observed). As a corresponding example for brachytherapy, the predicted ERR of 0.80 among women who received an inhomogeneous low-dose-rate dose to the bone marrow (mean = 2.5 Gy) was consistent with the measured ERR (0.62, 95% CI = -0.2 to 1.9). CONCLUSIONS: An extended, biologically based model for leukemia that includes HSC initiation, inactivation, proliferation, and, uniquely for leukemia, long-range HSC migration predicts, with reasonable accuracy, risks for radiation-induced leukemia associated with exposure to therapeutic doses of radiation.

Adult↗

PubMed2002

An initial radiation safety needs assessment of Costa Rica: the South Texas Chapter of the Health Physics Society's strategic planning appraisal for participation in the "Radiation Safety Without Borders" initiative.

In response to the Health Physics Society's recent 'radiation safety without borders" initiative, the South Texas Chapter of the Health Physics Society selected Costa Rica as its partner country of choice. To develop an understanding of the radiation safety needs of this country, the fall 2001 University of Texas Health Science Center at Houston School of Public Health Environmental Radiation and Radioactivity class was tasked with the assignment of assessing the possible radiation safety needs and concerns for this country. The assignment culminated in a class presentation to the membership of the South Texas Chapter during its annual fall meeting. Using library and web based resources, tile students reviewed a number of public health and radiation-related topics. Life expectancies were found to be equivalent to the United States, even though significant differences in per capita health expenditures were noted. Costa Rica exhibited lower population mortality rates from major causes such as cardiovascular diseases, neoplasms, and external sources. Maternal and infant mortality rates were found to be much higher in Costa Rica than in the United States. Naturally occurring radiation sources such as uranium deposits were not identified as apparent major radiation issues of concern, although ultraviolet radiation exposures are consistently high. Several recent events in the country and the region involving patient overexposures suggest that concerns are likely focused on ensuring the proper use and maintenance of healing arts radiation equipment. The lack of available information on radioactive waste disposal suggests that waste handling also may be an issue warranting attention. The exercise proved to be very educational for the students, and the information gathered will serve to focus the Chapter's efforts when technical exchanges are initiated. The importance of linking this initiative to other existing programs within the country is also discussed.

Costa Rica↗

PubMed1992

Mortality and occupational exposure to radiation: first analysis of the National Registry for Radiation Workers.

OBJECTIVE: To study cause specific mortality of radiation workers with particular reference to associations between fatal neoplasms and level of exposure to radiation. DESIGN: Cohort study. SETTING: United Kingdom. SUBJECTS: 95,217 radiation workers at major sites of the nuclear industry. MAIN OUTCOME MEASURE: Cause of death. RESULTS: Most standardised mortality ratios were below 100: 83 unlagged, 85 with a 10 year lag for all causes; 84 unlagged, 86 lagged for all cancers; and 80 for all known other causes, indicating a "healthy worker effect." The deficit of lung cancer (75 unlagged, 76 lagged) was significant at the 0.1% level. Standardised mortality ratios were significantly raised (214 unlagged, 303 lagged) for thyroid cancer, but there was no evidence for any trend with external recorded radiation dose. Dose of external radiation and mortality from all cancers were weakly correlated (p = 0.10), and multiple myeloma was more strongly correlated (p = 0.06); for leukaemia, excluding chronic lymphatic, the trend was significant (p = 0.03; all tests one tailed). The central estimates of lifetime risk derived from these data were 10.0% per Sv (90% confidence interval less than 0 to 24%) for all cancers and 0.76% per Sv (0.07 to 2.4%) for leukaemia (excluding chronic lymphatic leukaemia). These are, respectively, 2.5 times and 1.9 times the risk estimates recommended by the International Commission on Radiological Protection, but 90% confidence intervals are large and the commission's risk factors fall well within the range. The positive trend with dose for all cancers, from which the risk estimate was derived, was not significant. The positive association between leukaemia (except chronic lymphatic leukaemia) was significant and robust in subsidiary analyses. This study showed no association between radiation exposure and prostatic cancer. CONCLUSION: There is evidence for an association between radiation exposure and mortality from cancer, in particular leukaemia (excluding chronic lymphatic leukaemia) and multiple myeloma, although mortality from these diseases in the study population overall was below that in the general population. The central estimates of risk from this study lie above the most recent estimates of the International Commission on Radiological Protection for leukaemia (excluding chronic lymphatic leukaemia) and for all malignancies. However, the commission's risk estimates are well within the 90% confidence intervals from this study. Analysis of combined cohorts of radiation workers in the United States indicated lower risk estimates than the commission recommends, and when the American data are combined with our analysis the overall risks are close to those estimated by the commission. This first analysis of the National Registry for Radiation Workers does not provide sufficient evidence to justify a revision in risk estimates for radiological protection purposes.

Adult↗

PubMed1999

[Use of radiopharmaceuticals, radiation burden and radiation risks in examination procedures in nuclear medicine].

Consistent with the worldwide development of nuclear medicine, in the Czech Republic in 1987 to 1996 partly the spectrum of used radiopharmaceutical preparations and their ratio changed. In the majority of radiopharmaceutical preparations the mean administered activity increased by 20 to 80% and the range of activities administered in different departments diminished somewhat. Adherence to principles of radiation protection of patients is assisted by guidelines of administered activities of radiopharmaceutical preparations laid down in new regulations on radiation protection valid in the CR from the middle of 1997. The radiation burden associated with the majority of examinations in nuclear medicine expressed as the effective dose is comparable with the radiation burden of radiodiagnostic examinations, only after administration of preparations with 131I, 201Tl, 67Ga and 111In it is markedly higher. Based on knowledge of the effective dose it may be concluded that the lifetime extra risk of a fatal tumour due to administration of radiopharmaceutical preparations is by two to three orders lower than the lifetime risk of spontaneous development of fatal tumours. A special feature of radiation risk is its hypothetical character--it is frequently projected into the distant future of human life, contrary to immediate non-radiation risks of some medical procedures and risks in the living environment which frequently are higher. Any examination using ionising radiation can be made only if the expected health benefit for the patient is significantly greater than the radiation risk. Excessive fear of radiation risk should not lead to refusal of justified examinations with possible subsequent serious health damage for the patient.

Czech Republic↗

PubMed1975

[Radiation exposure during examination with a therapy simulator. 2. Radiation load on the examiner during radiography (measurements on the Alderson-Man phantom)].

In judging the risk incurred by persons professionally exposed to radiation, there is at present a more distinct tendency towards consideration of somatic effects - as e.g. somatic "crossing over", accidents of development, induction of cancer; thus more attention is paid to individual risk. For assessment of this radiation risk, the organ doses in question must be known; they can be estimated by means of the ascertained tissue-air-ratios, if the field of stray radiation from the X-ray equipment is known. To obtain data for statements with regard to the radiation load on the examiner during radioscopies with a therapy simulator, it was necessary to determine the stray radiation field of the X-ray apparatus. Therefore, using an Alderson-Man-phantom, the angular distribution of the local dose rate were measured at a tube voltage of 84 kV. The skin irradiation fields had dimensions of 25 cm2, 100 cm2, and 400 cm2 at the distances 50 cm, 100 cm, 150 cm, and 200 cm of the ionization chamber from the central ray. The measurements were performed on levels of 90 cm, 130 cm, and 160 cm above the floor. Some additional measurements aimed at a more exact investigation of the dependency of scattered radiation upon the tube voltage, the area of the radiation field, the distance from the central ray, and the height above the floor. The attenuation capacity of a light radioprotective apron (0.25 mm lead equivalence) was also determined. It turned out that, at a tube voltage of 84 kV, the apron still was passed by about 3.6% of the hitting stray radiation. The present measurements yield important indications of the best possible locations of the examiner during radioscopy. A practical example is given showing how to assess the radiation load on single organs; the results show that the examiner is exposed to a gonadal load of about 2 mR and to a load of about 17 mR on the crystalline lenses, while engaged in preparative roentgenologic measures for intrauterine transfusions.

Humans↗

PubMed2005

Dose build up correction for radiation monitors in high-energy bremsstrahlung photon radiation fields.

Conventional radiation monitors have been found to underestimate the personal dose equivalent in the high-energy bremsstrahlung photon radiation fields encountered near electron storage rings. Depth-dose measurements in a water phantom were carried out with a radiation survey meter in the bremsstrahlung photon radiation fields from a 450 MeV electron storage ring to find out the magnitude of the underestimation. Dose equivalent indicated by the survey meter was found to build up with increase in thickness of water placed in front of the meter up to certain depth and then reduce with further increase in thickness. A dose equivalent build up factor was estimated from the measurements. An absorbed dose build up factor in a water phantom was also estimated from calculations performed using the Monte Carlo codes, EGS-4 and EGSnrc. The calculations are found to be in very good agreement with the measurements. The studies indicate inadequacy of commercially available radiation monitors for radiation monitoring within shielded enclosures and in streaming high-energy photon radiation fields from electron storage rings, and the need for proper correction for use in such radiation fields.

Algorithms↗

PubMedDate not supplied

[Evaluation of the radiation risk of determinate effects from space radiation in a piloted mission to Mars].

Solar cosmic rays (SCR) are one of the sources of radiation risk specific to space flights. On Earth, occupational exposure has a regular character and radiation risk is an attribute of nothing else but stochasticity of radiobiological effects. In space flight, SCR impart stochasticity to the radiation environment and, therefore, probability to all, including determinate, radiobiological effects. The most dangerous effect is radiation disease the dosimetric functional of which is an equivalent dose to the blood-forming organs. In addition, this radiation pathology is modulated by reparative processes in the blood-forming tissue which must be also taken into account during radiation risk evaluation. Using the speculated mission to Mars as an example, it was shown that radiation risk of determinate effects defined as probability of death by radiation disease in consequence of exposure to SCR can be comparable in value to the risk from stochastic effects.

Cosmic Radiation↗

PubMed1995

Simultaneous adjuvant radiation therapy and chemotherapy in high-risk breast cancer--toxicity and dose modification: a Transtasman Radiation Oncology Group Multi-Institution study.

PURPOSE: To establish the toxicity profile of simultaneously administered postoperative radiation therapy and CMF chemotherapy as a prelude to a randomized controlled study addressing the sequencing of the two modalities. METHODS AND MATERIALS: One hundred and thirty eight breast cancer patients at high risk of locoregional, as well as systemic relapse, who were referred to three centers in Australia and New Zealand were treated with postoperative radiation therapy and chemotherapy simultaneously. Acute toxicity and dose modifications in these patients were compared with 83 patients treated over the same time frame with chemotherapy alone. In a separate study the long-term radiation and surgical effects in 24 patients treated simultaneously with radiation therapy and chemotherapy at Newcastle (Australia) following conservative surgery were compared with 23 matched patients treated at Newcastle with radiation therapy alone. RESULTS: Myelotoxicity was increased in patients treated simultaneously with radiation therapy and chemotherapy. The effect was not great, but may have contributed to chemotherapy dose reductions. Lymphopenia was observed to be the largest factor in total white cell depressions caused by the simultaneous administration of radiation therapy. Postsurgical appearances were found to so dominate long-term treatment effects on the treated breast that the effect of radiation therapy dose and additional chemotherapy was difficult to detect. CONCLUSION: Studies addressing the sequencing of radiation therapy and chemotherapy will necessarily be large because adverse effects from administering the two modalities simultaneously are not great. The present study has endorsed the importance in future studies of stratification according to the extent and type of surgery and adherence to a single strict policy of chemotherapy dose modification.

Adult↗

PubMed2006

Radiation therapy-induced mucositis: relationships between fractionated radiation, NF-kappaB, COX-1, and COX-2.

Radiation therapy is one of the three major treatment modalities used in eradicating malignant tumours. When ionising radiation is used to treat abdominal tumours, severe side effects largely due to mucosal damage in the alimentary tract are common, particularly when it is combined with chemotherapy. Radiation-induced mucositis may not only limit the therapeutic doses of combined treatment but also adversely affect the quality of life of the patient. Treatment strategies to treat and prevent radiation-induced mucositis have been reviewed and published in the Clinical Practice Guidelines, 2004. However evidence supporting an effective treatment approach is tenuous, probably because the mechanistic evolution of radiation-induced mucositis is poorly understood. Several animal models have been used to examine the various effects of radiation but no single animal model has been able to effectively capture the effects of radiation on the alimentary tract at the molecular level before symptoms begin. This review will outline the events which occur following radiation exposure; from chromosomal aberrations in the mucosal cells leading to apoptotic and mitotic death, to the evolution of mucositis involving changes in gene activations and signaling. A better understanding of the mechanisms of radiation therapy-induced mucositis is necessary as it will allow for future pharmaceutical interventions to alleviate if not eliminate the debilitating side effects.

Cyclooxygenase 1↗