Persistent subclinical inflammation among A-bomb survivors

PURPOSE: To investigate the associations between inflammation tests and radiation dose in A-bomb survivors. SUBJECTS AND METHODS: Subjects were A-bomb survivors who underwent inflammation tests of leukocyte counts, neutrophil counts, erythrocyte sedimentation rate, corrected erythrocyte sedimentation rate, alpha-1 globulin, alpha-2 globulin and sialic acid between 1988 and 1992. Associations with radiation dose (DS86) were analyzed by regression analysis and heterogeneity among inflammatory diseases, anaemia at examination, or history of cancer was also tested. RESULTS: The associations with radiation dose were statistically significant for leukocyte counts (71.0mm(-3) Gy(-1), p=0.015), erythrocyte sedimentation rate (1.58 mm h(-1) Gy(-1) , p = 0.0001), corrected erythrocyte sedimentation rate (1.14mm h(-1) Gy(-1), p=0.0001), alpha-1 globulin (0.0057 g dl(-1) Gy(-1), p=0.0001), alpha-2 globulin (0.0128 g dl(-1) Gy(-1), p=0.0001), and sialic acid (1.2711 mg dl(-1) Gy(-1), p=0.0001) but not for neutrophil counts (29.9 mm(-3) Gy(-1), p=0.17). Heterogeneity was not statistically significant. Among inflammatory diseases, associations were the strongest for chronic thyroiditis and chronic liver diseases. CONCLUSIONS: This study suggests statistically significant association between inflammation in A-bomb survivors and radiation dose of during 1988-1992. The association might contribute, as an epigenetic and/or bystander effect, to development of several radiation-induced disorders.     

Radiation dose-dependent increases in inflammatory response markers in A-bomb survivors

PURPOSE: The well-documented increases in malignant tumours in the A-bomb survivors have recently been supplemented by reports that non-cancer diseases, including cardiovascular disease, may also have increased in incidence with increasing radiation dose. Given that low-level inflammatory responses are widely accepted as a significant risk factor for such diseases, we undertook a detailed investigation of the long-term effects of ionizing radiation on the levels of the inflammatory markers C-reactive protein (CRP) and interleukin 6 (IL-6) in A-bomb survivors. MATERIALS AND METHODS: Blood samples were taken from 453 participants in a long-term epidemiological cohort of A-bomb survivors. Plasma levels of CRP and IL-6 were measured using standard antibody-mediated procedures. Relationships between CRP or IL-6 levels and radiation dose were then investigated by multivariate regression analysis. Blood lymphocytes from each individual were used for immunophenotyping by flow cytometry with murine monoclonal antibodies to CD3, CD4 and CD8. RESULTS: CRP levels were significantly increased by about 31% Gy(-1) of estimated A-bomb radiation (p=0.0001). Higher CRP levels also correlated with age, male gender, body mass index and a history of myocardial infarction. After adjustments for these factors, CRP levels still appeared to have increased significantly with increasing radiation dose (about 28% increase at 1Gy, p=0.0002). IL-6 levels also appeared to have increased with radiation dose by 9.3% at 1Gy (p=0.0003) and after multiple adjustments by 9.8% at 1Gy (p=0.0007). The elevated CRP and IL-6 levels were associated with decreases in the percentages of CD4(+) helper T-cells in peripheral blood lymphocyte populations. CONCLUSIONS: Our results appear to indicate that exposure to A-bomb radiation has caused significant increases in inflammatory activity that are still demonstrable in the blood of A-bomb survivors and which may lead to increased risks of cardiovascular disease and other non-cancer diseases.     

Meta-analysis of non-tumour doses for radiation-induced cancer on the basis of dose-rate

Purpose: Quantitative analysis of cancer risk of ionising radiation as a function of dose-rate. Materials and methods: Non-tumour dose, D(nt), defined as the highest dose of radiation at which no statistically significant tumour increase was observed above the control level, was analysed as a function of dose-rate of radiation. Results: An inverse correlation was found between D(nt) and dose-rate of the radiation. D(nt) increased 20-fold with decreasing dose-rate from 1-10(-8) Gy/min for whole body irradiation with low linear energy transfer (LET) radiation. Partial body radiation also showed a dose-rate dependence with a 5- to 10-fold larger D(nt) as dose rate decreased. The dose-rate effect was also found for high LET radiation but at 10-fold lower D(nt) levels. Conclusions: The cancer risk of ionising radiation varies 1000-fold depending on the dose-rate of radiation and exposure conditions. This analysis explains the discrepancy of cancer risk between A-bomb survivors and radium dial painters.     

Comparisons of lung tumour mortality risk in the Japanese A-bomb survivors and in the Colorado Plateau uranium miners: support for the ICRP lung model

PURPOSES: To estimate the ratio of risks for exposure to radon progeny relative to low-LET radiation based on human lung cancer data, taking account of possible time and age variations in radiation-induced lung cancer risk. MATERIALS AND METHODS: Fitting two sorts of time- and age-adjusted relative risk models to a case-control dataset nested within the Colorado Plateau uranium miner cohort and to the Japanese atomic (A)-bomb survivor mortality data. RESULTS: If all A-bomb survivors are compared with the Colorado data, there are statistically significant (two-sided p < 0.05) differences between the two datasets in the pattern of the variation of relative risk with time after exposure, age at exposure and attained age. The excess relative risk decreases much faster with time, age at exposure and attained age in the Colorado uranium miners than in the Japanese A-bomb survivors. If only male A-bomb survivors are compared with the Colorado data, there are no longer statistically significant differences between the two datasets in the pattern of variation of relative risk with time after exposure, age at exposure or attained age. There are no statistically significant differences between the male and female A-bomb survivors in the speed of reduction of relative risk with time after exposure, age at exposure or attained age, although there are indications of rather faster reduction of relative risk with time and age among male survivors than among female survivors. The implicit risk conversion factor for exposure to radon progeny relative to the A-bomb radiation in the male survivors is 1.8 x 10(-2) Sv WLM(-1) (95% CI 6.1 x10(-3), 1.1 x 10(-1)) using a model with exponential adjustments for the effects of radiation for time since exposure and age at exposure, and 1.9 x 10(-2) Sv WLM(-1) (95% CI 6.2 x 10(-3), 1.6 x 10(-1)) using a model with adjustments for the effects of radiation proportional to powers of time since exposure and attained age. Estimates of the risk conversion factor calculated using variant assumptions as to the definition of lung cancer in the Colorado data, or by excluding miners for whom exposure estimates may be less reliable, are very similar. The absence of information on cigarette smoking in the Japanese A-bomb survivors, and the possibility that this may confound the time trends in radiation-induced lung cancer risk in that cohort, imply that these findings should be interpreted with caution. CONCLUSIONS: There are no statistically significant differences between the male A-bomb survivors data and the Colorado miner data in the pattern of variation of relative risk with time after exposure and age at exposure. The risk conversion factor is very close to the value suggested by the latest ICRP lung model, albeit with substantial uncertainties.     

gamma-H2AX foci formation in peripheral blood lymphocytes of tumor patients after local radiotherapy to different sites of the body: dependence on the dose-distribution, irradiated site and time from start of treatment

PURPOSE: To evaluate the relationship between an estimated integral total body radiation dose delivered and phosphorylated histone H2AX protein (gamma-H2AX) foci formation in peripheral blood lymphocytes of cancer patients. MATERIAL AND METHODS: gamma-H2AX formation was quantified as the mean number of foci per lymphocyte (N(meanH2AX)) and the percentage of lymphocytes with > or =n foci. The integrated total body radiation dose was estimated from the dose volume histogram of patient's body corrected for the proportion of the body scanned by computed tomography for 3D treatment planning. RESULTS: There was a strong linear correlation between the mean number of gamma-H2AX foci per lymphocyte in the peripheral blood sample and integrated total body radiation dose (r = 0.83, p < 0.0001). The slope of the relationship was dependent on the site of body irradiated. In comparison to chest irradiation with a slope of 8.7 +/- 0.8 foci Gy(-1), the slopes for brain, upper leg and pelvic sites were significantly shallower by -4.7, -4.3, and -3.8 Gy(-1), respectively (p < 0.0001), while the slope for upper abdomen irradiation was significantly larger by 9.1 +/- 2.6 Gy(-1) (p = 0.0007). There was a slight time effect since the start of radiotherapy on the slopes of the in vivo dose responses leading to shallower slopes (-1.5 +/- 0.7 Gy(-1), p = 0.03) later (> or =10 day) during radiotherapy. After in vitro irradiation, lymphocytes showed 10.41 +/- 0.12 foci per Gy with no evidence of inter-individual heterogeneity. CONCLUSIONS: gamma-H2AX measurements in peripheral lymphocytes after local radiotherapy allow the estimation of the applied integral body dose. The site and time dependence have to be considered.     

Chemoradiation of Unresectable Pancreatic Carcinoma: Impact of Pretreatment Hemoglobin Level on Patterns of Failure

AIM: To evaluate, in patients with locally advanced pancreatic carcinoma undergoing concomitant chemoradiation, the impact of pretreatment hemoglobin (Hb) concentration on the outcome in terms of clinical response, local control, metastasis-free survival, disease-free survival, and overall survival. PATIENTS AND METHODS: 30 patients undergoing concomitant chemoradiation (5-fluorouracil [5-FU], 1,000 mg/m(2)/day, continuous i.v. infusion days 1-4 of radiotherapy) and external beam radiotherapy (50.4-59.4 Gy) were divided into two groups based on pretreatment median Hb value (11.5 g/dl). The potential prognostic factors examined besides Hb concentration were: tumor site (head vs body-tail), sex (female vs male), cN (cN0 vs nC1), dose of external beam radiotherapy (50.4 Gy vs 59.4 Gy), presence of jaundice at diagnosis (yes vs no), weight loss at diagnosis (> or = 5 kg vs < 5 kg), epigastric-lumbar pain at diagnosis (yes vs no), maximum tumor diameter (< 40 mm vs > or = 40 mm). RESULTS: Pretreatment Hb ranged between 9.6 and 15.0 g/dl. No statistically significant differences were observed as for clinical response and local control between patients with an Hb < or = 11.5 g/dl and those with an Hb > 11.5 g/dl. Metastasis-free survival was 5.1 months in patients with an Hb < or = 11.5 g/dl and 10.7 months in patients with an Hb > 11.5 g/dl (p = 0,010). Median actuarial disease-free survival was 5.1 and 10.2 months in patients with an Hb < or = 11.5 and > 11.5 g/dl, respectively (p = 0.026). Median actuarial overall survival was 7.5 and 10.3 months in patients with an Hb < or = 11.5 and > 11.5 g/dl; respectively (p = 0.039). On multivariate analysis, Hb concentration at diagnosis was the only factor prognostically correlated with metastasis-free survival (p = 0.026), disease-free survival (p = 0.032), and overall survival (p = 0.048). CONCLUSION: In a group of patients with locally advanced pancreatic carcinoma treated with chemoradiation, a significant correlation was observed between pretreatment Hb levels and metastasis-free survival, disease-free survival, and overall survival.     

Problems Inherent in the Assessment of Long-TermLow-Dose Radiation Carcinogenesis

Risk estimates derived from studies based on actual exposure to low dose radiation(LDR),I. E populations exposed to fallout,those living in the vicinity of nuclear reactors,scattered x- radiation. Nuclear industry and in utero exposure(1-8),vary from extrapolations coming from highdose studies. i. e A-bomb survivors and indi viduals exposed to therapeutic irradiation(9-12).     

Henry S. Kaplan Distinguished Scientist Award 2003. The crooked shall be made straight; dose-response relationships for carcinogenesis

Estimates of radiation-induced malignancies come principally from the atomic (A)-bomb survivors and show an excess incidence of carcinomas that is linearly related to dose from about 5 cGy to 2.5 Gy. Above and below this dose range there is considerable uncertainty about the shape of the dose-response relationship. Both the International Commission of Radiation Protected (ICRP) and the National Council of Radiation Protection (NCRP) suggest that cancer risks at doses lower than those at which direct epidemiological observations are possible should be obtained by a linear extrapolation from higher doses. The demonstrated bystander effect for irradiation exaggerates the consequences of small doses of radiation and implies that a linear extrapolation from high doses would underestimate low dose risks. It is possible to make estimates of the cancer risk of diagnostic radiological procedures. Helical computed tomography in children is of particular interest since it is rapidly increasing in use and the doses involved are close to the lower limit of significance in the A-bomb survivors. For example, an abdominal computed tomographic scan in a 1-year-old child can be estimated to result in a lifetime cancer risk of about 1:1000. In the context of radiotherapy, some normal tissues receive 70 Gy, while a larger volume receives a lower dose, but still far higher than the range for which data are available from the A-bomb survivors. Data are available for the risk of radiation-induced malignancies for patients who received radiotherapy, e.g. for prostate or cervical cancer. New technologies such as intensity modulated radiation therapy could result in a doubling of radiation-induced second cancers since the technique involves a larger total-body dose due to leakage radiation and the dose distribution obtained involves a larger volume of normal tissue exposed to lower radiation doses.     

Effects of low dose radiation therapy on adjuvant induced arthritis in rats

PURPOSE: Substantial clinical evidence shows the efficacy of low dose radiotherapy (RT) in the treatment of painful osteoarthritis. Experimental investigations into these empirically clinical observations remain scarce. This study investigated in vivo the effects of daily 5 x 1.0 Gy versus 5 x 0.5 Gy on adjuvant induced arthritis in rats in order to explore whether there is a dose dependence of anti-inflammatory efficacy. MATERIALS AND METHODS: Adjuvant arthritis in female Lewis rats was induced by intradermal injection of heat inactivated Mycobacterium tuberculosis on day 0. Both hind paws were X-irradiated daily from days 15 to 19 after induction according to four protocols (15 animals/group): group 1, 5 x 1.0 Gy (non-arthritic animals); group 2, sham-irradiated control; group 3, 5 x 1.0 Gy; group 4, 5 x 0.5 Gy. The clinical parameters arthritis score (AS), hind paw volume (HPV), body weight, and erythrocyte sedimentation rate (ESR) were determined. On days 21 and 30 histological sections of at least 12 ankle joints per group were analysed semi-quantitatively. RESULTS: Local irradiation of non-arthritic rats (group 1) with 5 x 1 Gy did not induce any arthritic signs. Sham-irradiated arthritic rats (group 2) showed a full-blown arthritic syndrome. Treatment of arthritic rats with 5 x 1 Gy (group 3) or 5 x 0.5 Gy (group 4) led to a reduction of mean AS from day 21 to 29 compared with group 2 (days 27-29--group 3: p=0.037; group 4: p=0.034), with no differences in efficacy between groups 3 and 4. Concurrently, following radiation treatment there was no further increase in HPV. At the end of the observation period, this effect demonstrated a dose-dependent level of significance (days 27-29--group 3: p=0.0036; group 4: p=0.039). A significant decrease in the ESR was noted in both irradiated arthritic groups on day 21 (group 3: p=0.015; group 4: p=0.006). The histopathological analysis revealed a highly significant reduction of cartilage and bone destruction on day 30 in both irradiated groups. CONCLUSIONS: This study confirms by objective criteria the anti-inflammatory efficacy of low dose RT and gives some indication for a dose dependence of its efficacy.     

Effects of low dose radiation therapy on adjuvant induced arthritis in rats

Purpose : Substantial clinical evidence shows the efficacy of low dose radiotherapy (RT) in the treatment of painful osteoarthritis. Experimental investigations into these empirically clinical observations remain scarce. This study investigated in vivo the effects of daily 5 1.0Gy versus 5 0.5Gy on adjuvant induced arthritis in rats in order to explore whether there is a dose dependence of anti-inflammatory efficacy. Materials and methods : Adjuvant arthritis in female Lewis rats was induced by intradermal injection of heat inactivated Mycobacterium tuberculosis on day 0. Both hind paws were X-irradiated daily from days 15 to 19 after induction according to four protocols (15 animals/group): group 1, 5 1.0Gy (non-arthritic animals); group 2, sham-irradiated control; group 3, 5 1.0Gy; group 4, 5 0.5Gy. The clinical parameters arthritis score (AS), hind paw volume (HPV), body weight, and erythrocyte sedimentation rate (ESR) were determined. On days 21 and 30 histological sections of at least 12 ankle joints per group were analysed semi-quantitatively. Results : Local irradiation of non-arthritic rats (group 1) with 5 1 Gy did not induce any arthritic signs. Sham-irradiated arthritic rats (group 2) showed a full-blown arthritic syndrome. Treatment of arthritic rats with 5 1 Gy (group 3) or 5 0.5Gy (group 4) led to a reduction of mean AS from day 21 to 29 compared with group 2 (days 27-29-group 3: p =0.037; group 4: p =0.034), with no differences in efficacy between groups 3 and 4. Concurrently, following radiation treatment there was no further increase in HPV. At the end of the observation period, this effect demonstrated a dose-dependent level of significance (days 27-29-group 3: p =0.0036; group 4: p =0.039). A significant decrease in the ESR was noted in both irradiated arthritic groups on day 21 (group 3: p =0.015; group 4: p =0.006). The histopathological analysis revealed a highly significant reduction of cartilage and bone destruction on day 30 in both irradiated groups. Conclusions : This study confirms by objective criteria the anti-iinflammatory efficacy of low dose RT and gives some indication for a dose dependence of its efficacy.     

Radiation therapy for painful bone metastases; aiming at optimal treatment schedules

PURPOSE: To evaluate the pain relief obtained by radiation therapy for painful bone metastases, with a special regard to general condition. MATERIALS AND METHODS: Between June 1998 and May 2000, 54 patients with 86 painful bone metastases were treated with radiation therapy whose effects could be evaluated for a minimum period of 6 months or until death. Treatment schedules were 3 Gy/fraction/day (30-36 Gy/10-12 fractions) in usual cases (61 lesions), 4-8 Gy/fraction/day (8-20 Gy/1-5 fractions) in patients with a poor general condition (9 lesions), and 2 Gy/fraction/day (40-50 Gy/20-25 fractions) in lesions with a large radiation field (16 lesions). RESULTS: Complete pain relief without medication (CR) was achieved in 40 lesions (47%). Significant predictors for CR were primary site (p = 0.0003), performance status (p = 0.0060), pain score (p = 0.0190), narcotic score (p < 0.0001), and prognosis (p < 0.0001), but no difference was found in CR among treatment schedules. No evidence of severe radiation-induced complication was seen. CONCLUSION: General condition (performance status and prognosis) has an influence on pain relief. Compared with the daily 2 Gy protocol, the daily 3 Gy protocol has the advantage of shorter treatment time. The treatment schedule should be assessed in patients with a large radiation field and/or poor general condition. Especially for the patients with poor general condition, combined pain medication should be considered.     

Meta-analysis of non-tumour doses for radiation-induced cancer on the basis of dose-rate

Purpose:?Quantitative analysis of cancer risk of ionising radiation as a function of dose-rate.

Materials and methods:?Non-tumour dose, D_nt, defined as the highest dose of radiation at which no statistically significant tumour increase was observed above the control level, was analysed as a function of dose-rate of radiation.

Results:?An inverse correlation was found between D_nt and dose-rate of the radiation. D_nt increased 20-fold with decreasing dose-rate from 1–10^?8 Gy/min for whole body irradiation with low linear energy transfer (LET) radiation. Partial body radiation also showed a dose-rate dependence with a 5- to 10-fold larger D_nt as dose rate decreased. The dose-rate effect was also found for high LET radiation but at 10-fold lower D_nt levels.

Conclusions:?The cancer risk of ionising radiation varies 1000-fold depending on the dose-rate of radiation and exposure conditions. This analysis explains the discrepancy of cancer risk between A-bomb survivors and radium dial painters.     

Prevalence of atherosclerosis in relation to atomic bomb radiation exposure: an RERF Adult Health Study

PURPOSE: To determine whether exposure to atomic bomb radiation altered the prevalence of asymptomatic atherosclerosis. MATERIAL AND METHODS: In a cross-sectional analysis, we examined aortic arch calcification by plain chest radiography and common carotid artery intima-media thickness (IMT) by ultrasonography among 1804 survivors of the atomic bombing in Hiroshima. We evaluated the association between atherosclerotic changes and radiation exposure, while adjusting for potentially confounding factors. RESULTS: Multivariate logistic regression analysis showed that aortic arch calcification was significantly associated with radiation exposure (p < 0.05). The odds ratio at 1 Gy was 1.30 (95% confidence interval [CI]: 1.05 - 1.53) for men and 1.31 (95% CI: 1.13 - 1.51) for women. Carotid artery IMT did not vary significantly with radiation dose (p = 0.18). CONCLUSION: Radiation dose contributed to the prevalence of aortic atherosclerosis but not carotid artery atherosclerosis in atomic bomb survivors.     

Chemoradiation of Unresectable Pancreatic Carcinoma: Impact of Pretreatment Hemoglobin Level on Patterns of Failure

Aim: To evaluate, in patients with locally advanced pancreatic carcinoma undergoing concomitant chemoradiation, the impact of pretreatment hemoglobin (Hb) concentration on the outcome in terms of clinical response, local control, metastasis-free survival, disease-free survival, and overall survival. Patients and Methods: 30 patients undergoing concomitant chemoradiation (5-fluorouracil [5-FU], 1,000 mg/m²/day, continuous i. v. infusion days 1-4 of radiotherapy) and external beam radiotherapy (50.4-59.4 Gy) were divided into two groups based on pretreatment median Hb value (11.5 g/dl). The potential prognostic factors examined besides Hb concentration were: tumor site (head vs body-tail), sex (female vs male), cN (cN0 vs nC1), dose of external beam radiotherapy (50.4 Gy vs 59.4 Gy), presence of jaundice at diagnosis (yes vs no), weight loss at diagnosis (S 5 kg vs < 5 kg), epigastric-lumbar pain at diagnosis (yes vs no), maximum tumor diameter (< 40 mm vs S 40 mm). Results: Pretreatment Hb ranged between 9.6 and 15.0 g/dl. No statistically significant differences were observed as for clinical response and local control between patients with an Hb h 11.5 g/dl and those with an Hb > 11.5 g/dl. Metastasis-free survival was 5.1 months in patients with an Hb h 11.5 g/dl and 10.7 months in patients with an Hb > 11.5 g/dl (p = 0,010). Median actuarial disease-free survival was 5.1 and 10.2 months in patients with an Hb h 11.5 and > 11.5 g/dl, respectively (p = 0.026). Median actuarial overall survival was 7.5 and 10.3 months in patients with an Hb h 11.5 and > 11.5 g/dl; respectively (p = 0.039). On multivariate analysis, Hb concentration at diagnosis was the only factor prognostically correlated with metastasis-free survival (p = 0.026), disease-free survival (p = 0.032), and overall survival (p = 0.048). Conclusion: In a group of patients with locally advanced pancreatic carcinoma treated with chemoradiation, a significant correlation was observed between pretreatment Hb levels and metastasis-free survival, disease-free survival, and overall survival. Ziel: Ermittlung des Einflusses der Hämoglobinkonzentration vor Beginn einer Radiochemotherapie bei Patienten mit lokal fortgeschrittenem Pankreaskarzinom auf den Therapieerfolg anhand von klinischem Ansprechen, lokaler Kontrolle, metastasenfreiem Überleben, krankheitsfreiem Überleben und Gesamtüberleben. Patienten und Methoden: 30 Patienten, die Radiochemotherapie (5-FU, 1000 mg/m²/d, i. v. Dauerinfusion an den Tagen 1-4 der Strahlentherapie) und externe Strahlentherapie (50,4-59,4 Gy) erhielten, wurden, abhängig vom medianen Hämoglobinwert (11,5) in zwei Gruppen eingeteilt. Als weitere potentielle prognostische Faktoren wurden, neben der Hämoglobinkonzentration (Hb), Tumorlokalisation (Kopf/Korpus), Geschlecht (weiblich/männlich), Lymphknotenstatus (cN0/cN1), Dosierung der externen Strahlentherapie (50,4 Gy/59,4 Gy), Ikterus bei Diagnosestellung (ja/nein), Gewichtsverlust bei Diagnosestellung (S 5 kg/< 5 kg), epigastrisch-lumbaler Schmerz bei Diagnosestellung (ja/nein), maximaler Tumordurchmesser (< 40 mm/S 40 mm) geprüft. Ergebnisse: Die Hämoglobinkonzentration vor Therapiebeginn lag zwischen 9,6 and 15,0 g/dl. Es zeigten sich keine statistisch signifikanten Unterschiede hinsichtlich klinischem Ansprechen und lokaler Kontrolle zwischen Patienten mit Hb h 11,5 mit Hb > 11,5. Das metastasenfreie Überleben betrug 5,1 Monate bei Patienten mit Hb h 11,5 und 10,7 Monate bei Patienten mit Hb > 11,5 (p = 0,010). Das mediane krankheitsfreie Überleben betrug 5,1 und 10,2 Monate bei Patienten mit Hb h 11,5 bzw. Hb > 11,5 (p = 0,029: Das mediane Gesamtüberleben war 7,5 Monate und 10,3 Monate bei Patienten mit Hb h 11,5 bzw. > 11,5 (p = 0,039). Bei der multivariaten Analyse erwies sich die Hämoglobinkonzentration zum Diagnosezeitpunkt als der einzige prognostische Faktor, der mit dem metastasenfreien Überleben (p = 0,026), dem krankheitsfreien Überleben (p = 0,032) und dem Gesamtüberleben (p = 0,048) korrelierte. Schlussfolgerungen: In einer Patientengruppe, die wegen lokal fortgeschrittener Pankreaskarzinome Radiochemotherapie erhielt, wurde eine signifikante Korrelation zwischen dem Hämoglobinspiegel vor Therapiebeginn und metastasenfreiem Überleben, krankheitsfreiem Überleben und Gesamtüberleben beobachtet.     

Memory CD4 T-cell subsets discriminated by CD43 expression level in A-bomb survivors

Purpose:?Our previous study showed that radiation exposure reduced the diversity of repertoires of memory thymus-derived cells (T cells) with cluster of differentiation (CD)- 4 among atomic-bomb (A-bomb) survivors. To evaluate the maintenance of T-cell memory within A-bomb survivors 60 years after radiation exposure, we examined functionally distinct memory CD4 T-cell subsets in the peripheral blood lymphocytes of the survivors.

Methods:?Three functionally different subsets of memory CD4 T cells were identified by differential CD43 expression levels and measured using flow cytometry. These subsets consist of functionally mature memory cells, cells weakly responsive to antigenic stimulation, and those cells functionally anergic and prone to spontaneous apoptosis.

Results:?The percentages of these subsets within the peripheral blood CD4 T-cell pool all significantly increased with age. Percentages of functionally weak and anergic subsets were also found to increase with radiation dose, fitting to a log linear model. Within the memory CD4 T-cell pool, however, there was an inverse association between radiation dose and the percentage of functionally mature memory cells.

Conclusion:?These results suggest that the steady state of T cell memory, which is regulated by cell activation and/or cell survival processes in subsets, may have been perturbed by prior radiation exposure among A-bomb survivors.     

Increased body weight in C57BL/6 female mice after exposure to ionizing radiation or 60Hz magnetic fields

PURPOSE: The purpose of this investigation was to determine whether early treatment with ionizing radiation and/or chronic magnetic field (MF) exposure affected body weight in female mice. MATERIALS AND METHODS: Weanling C57BL/6 female mice were irradiated with four equal weekly cobalt-60 exposures (total cumulative doses: 3.0, 4.0, 5.1Gy) and/or received chronic lifetime exposure to 1.4 mT 60 Hz circularly polarized MF or ambient MF. The body weights of 2280 mice were recorded at 35 age intervals, and analysis of variance was used to compare the mean differences from baseline weights between treatment groups and sham-exposed controls. RESULTS: A highly statistically significant effect of ionizing radiation on body weight was observed at 28 age intervals (p < or = 0.001), and for MF exposure at 10 age intervals (p < or = 0.001). During the young adult growth phase, mice exposed only to MF exhibited < or =0.5 g greater weight gain relative to sham-exposed controls (p = 0.0001). The effect of ionizing radiation alone was inversely related to dose, with the largest weight increases observed in all of the irradiated groups after 9-12 months (p = 0.0001). CONCLUSIONS: Treatment with split-dose ionizing radiation at an early age and chronic exposure to a residential power frequency MF were found to produce small but significant increases in body weight.     

Potential of iodine-123 metaiodobenzylguanidine single-photon emission tomography to detect abnormal functional status of the pulmonary neuroadrenergic system in irradiated lung.

The potential of iodine-123 metaiodobenzylguanidine (MIBG) to detect functional abnormalities of the pulmonary neuroadrenergic system (PNS) in irradiated lung areas (ILAS) was preliminarily explored using single-photon emission tomography (SPET). The subjects included five healthy subjects and a total of 31 patients with peripheral-type lung cancer treated by radiation; 15 patients (group A) had received a dose of less than 36 Gy (mean +/- SD: 28.2 +/-6.2 Gy), and 16 patients (group B) had received a higher dose (mean +/- SD: 51.2 +/- 3.5 Gy) at the time of examination. MIBG SPET scans acquired 15 min and 3 h after injection were used to measure the MIBG uptake ratio (count ratio of the ILA to the contralateral non-ILA) and the clearance rate [percentage of (early counts - delayed counts)/early counts] from the ILAs without noticeable abnormal opacities on chest computed tomography scan. Lung perfusion changes were also assessed by technetium-99m macroaggregated albumin SPET. By contrast to the homogeneous MIBG uptake in the lungs of the healthy subjects, MIBG uptake was folcally decreased in correspondence with the ILAs in all patients, including 11 patients (73.3%) of group A with relatively preserved lung perfusion. The reduction MIBG uptake was significant (P<0.0001), and the MIBG clearance rate from the ILAs was also significantly faster than the clearance rates from the normal lungs and contralateral non-ILAs (both P<0.01). Group B patients showed significantly lower MIBG uptake and faster clearance from the ILAs than group A patients (P<0. 001 and P<0.05, respectively), although there was no significant difference in the clearance from the non-ILAs. Overall, MIBG uptake/clearance from the ILAs correlated significantly with the radiation dose in the 31 patients (r = -0.656; P<0.0001 and r = 0. 387; P<0.05, respectively). Perfusion changes were inversely correlated with the clearance from the ILAs (r = -0.432, P<0.05), but did not correlate with MIBG uptake. These preliminary results suggest that MIBG may have the potential to be a marker of abnormal functional status of the PNS produced by irradiation and may facilitate investigation of irradiation lung injury independently of morphological or lung perfusion changes.     

Effektivität und Toxizität einer Re-Bestrahlung (Re-RT) bei metastatisch bedingter Rückenmarkkompression (MBRK)

BACKGROUND AND PURPOSE: Radiation myelopathy is a serious late toxicity after radiotherapy (RT) of metastatic spinal cord compression (MSCC). The risk of myelopathy depends on the equivalent dose in 2-Gy fractions (EQD2). Many radiation oncologists are concerned about spinal Re-RT, because it may result in a high cumulative EQD2. This study investigates effectiveness and feasibility of Re-RT for in-field recurrence of MSCC. PATIENTS AND METHODS: 74 patients, irradiated between 01/1995 and 12/2003 for MSCC, were reirradiated for in-field recurrence of MSCC (Table 1). Primary RT was performed with 1 x 8 Gy (n = 34), 5 x 4 Gy (n = 28), 10 x 3 Gy (n = 4), 15 x 2.5 Gy (n = 4), or 20 x 2 Gy (n = 4). Recurrence occurred after median 6 months (2-40 months). Re-RT was performed with 1 x 8 Gy (n = 35), 5 x 3 Gy (n = 16), 5 x 4 Gy (n = 13), 10 x 2 Gy (n = 4), 12 x 2 Gy (n = 3), or 17 x 1.8 Gy (n = 3). Cumulative EQD2 (alpha/beta = 2 Gy) was 39-40 Gy (n = 21), 49-50 Gy (n = 41), 56-60 Gy (n = 6), or > 60 Gy (n = 6). Follow-up after Re-RT was median 9 months (2-52 months). RESULTS: Re-RT led to an improvement of motor function in 29/74 patients (39%; Figures 1 to 3). On multivariate analysis, outcome was significantly influenced by type of primary tumor (p = 0.013) and by the time of developing motor deficits before Re-RT (p = 0.037), but not by radiation schedule (p = 0.560), by ambulatory status before Re-RT (p = 0.471), by cumulative EQD2 (p = 0.795), nor by the interval between primary RT and Re-RT (p = 0.420; Table 2). Radiation myelopathy was not observed in the whole series. CONCLUSION: Re-RT is an effective treatment for an in-field recurrence of MSCC. After a cumulative EQD2 < or = 50 Gy, radiation myelopathy appears unlikely.     

Temporal correlation of the erythrocyte sedimentation rate with Tc-99m WBC uptake on children with inflammatory bowel diseases

The goal of this study was to evaluate the temporal correlation of Tc-99m WBC studies with the erythrocyte sedimentation rate, a commonly used index of intensity of inflammation, in a large population of children with inflammatory bowel diseases. Over a 6-year period, 313 Tc-99m WBC studies were performed and the hospital charts of these consecutive children were reviewed. In each set of scans (0.5-1 hour and 2-3 hours) from the 313 patients, the bowel was divided into 8 segments resulting in 5008 bowel segments for scoring. The intensity of uptake on the planar images was graded on a scale of 0 to 6 and compared with the erythrocyte sedimentation rate obtained within 3 days, 1 week, 2 weeks, 1 month, 3 months, 6 months, or 1 year of the Tc-99m WBC scan, when available. A dataset of 508 erythrocyte sedimentation rates was available for computation. In children with Crohn's disease, when erythrocyte sedimentation rate is obtained within 3 days of the Tc-99m WBC scan, the correlation coefficient is R=0.314 (P<0.005), within 1 week R=0.358 (P<0.05), within 2 weeks R=0.254 (P=0.129), within 1 month R=-0.029 (P=0.84), within 3 months R=-0.002 (P=0.989), within 6 months R=0.241 (P=0.145), and within 1 year R=0.068 (P=0.759). In children with Crohn's disease, the uptake of Tc-99m WBC correlates well with the erythrocyte sedimentation rate during the flare of inflammation, and the correlation progressively subsides after a few weeks. No such correlation was noted in children with ulcerative colitis.     

The utility of SPECT in determining the relationship between radiation dose and salivary gland dysfunction after radiotherapy

Salivary gland scintigraphy (SGS) is used to depict salivary gland dysfunction after radiotherapy (RT). The aim of this study was to investigate the utility of SGS combined with single photon emission computed tomography (SPECT). Twenty-one patients with a carcinoma of head and neck underwent SGS before and 1 month after RT. After injection of 370 MBq 99Tcm-pertechnetate, a biplanar dynamic acquisition (12 x 1 min) was started, followed by a SPECT acquisition during 4 min. Carbachol was then injected and a second dynamic study (16 x 1 min) was performed, again followed by a SPECT acquisition. The salivary excretion fraction (SEF) was calculated both from the geometric mean planar image for each parotid and from the SPECT data for each transverse plane through the parotids. The RT-induced changes in the SEF (dSEF) were correlated with the mean radiation dose calculated using tomography-based dosimetry. The mean radiation dose to the parotids was 44 Gy (range 4.4-68.1 Gy). The mean range of the variation in radiation dose to the transverse slices within the parotids of a patient was 24 Gy (range 6.2-51.9 Gy). Considering all transverse planes through the parotids in all patients, a linear correlation was found between the dSEF calculated using SGS-SPECT and the radiation dose (r=0.45, P=0.0001). Thirteen patients had a variation in radiation dose within the parotids of more than 20 Gy. In nine of these a significant intra-individual correlation between radiation dose and the dSEF of the transverse parotid slices was found (r range 0.55-0.97; P value range 0.037-0.0001). In conclusion, SGS-SPECT can be used for monitoring radiation-induced parotid gland dysfunction. It offers the unique possibility for the assessment of intra-individual dose-dysfunction curves in patients with large variations in the radiation dose within the parotids.