Radiation exposure and leukaemia risk among cohorts of persons exposed to low and moderate doses of external ionising radiation in childhood.

BACKGROUND: Many high-dose groups demonstrate increased leukaemia risks, with risk greatest following childhood exposure; risks at low/moderate doses are less clear. METHODS: We conducted a pooled analysis of the major radiation-associated leukaemias (acute myeloid leukaemia (AML) with/without the inclusion of myelodysplastic syndrome (MDS), chronic myeloid leukaemia (CML), acute lymphoblastic leukaemia (ALL)) in ten childhood-exposed groups, including Japanese atomic bomb survivors, four therapeutically irradiated and five diagnostically exposed cohorts, a mixture of incidence and mortality data. Relative/absolute risk Poisson regression models were fitted. RESULTS: Of 365 cases/deaths of leukaemias excluding chronic lymphocytic leukaemia, there were 272 AML/CML/ALL among 310,905 persons (7,641,362 person-years), with mean active bone marrow (ABM) dose of 0.11 Gy (range 0-5.95). We estimated significant (P < 0.005) linear excess relative risks/Gy (ERR/Gy) for: AML (n = 140) = 1.48 (95% CI 0.59-2.85), CML (n = 61) = 1.77 (95% CI 0.38-4.50), and ALL (n = 71) = 6.65 (95% CI 2.79-14.83). There is upward curvature in the dose response for ALL and AML over the full dose range, although at lower doses (<0.5 Gy) curvature for ALL is downwards. DISCUSSION: We found increased ERR/Gy for all major types of radiation-associated leukaemia after childhood exposure to ABM doses that were predominantly (for 99%) <1 Gy, and consistent with our prior analysis focusing on <100 mGy.

Lymphoma and multiple myeloma in cohorts of persons exposed to ionising radiation at a young age.

There is limited evidence that non-leukaemic lymphoid malignancies are radiogenic. As radiation-related cancer risks are generally higher after childhood exposure, we analysed pooled lymphoid neoplasm data in nine cohorts first exposed to external radiation aged <21 years using active bone marrow (ABM) and, where available, lymphoid system doses, and harmonised outcome classification. Relative and absolute risk models were fitted. Years of entry spanned 1916-1981. At the end of follow-up (mean 42.1 years) there were 593 lymphoma (422 non-Hodgkin (NHL), 107 Hodgkin (HL), 64 uncertain subtype), 66 chronic lymphocytic leukaemia (CLL) and 122 multiple myeloma (MM) deaths and incident cases among 143,136 persons, with mean ABM dose 0.14 Gy (range 0-5.95 Gy) and mean age at first exposure 6.93 years. Excess relative risk (ERR) was not significantly increased for lymphoma (ERR/Gy = -0.001; 95% CI: -0.255, 0.279), HL (ERR/Gy = -0.113; 95% CI: -0.669, 0.709), NHL + CLL (ERR/Gy = 0.099; 95% CI: -0.149, 0.433), NHL (ERR/Gy = 0.068; 95% CI: -0.253, 0.421), CLL (ERR/Gy = 0.320; 95% CI: -0.678, 1.712), or MM (ERR/Gy = 0.149; 95% CI: -0.513, 1.063) (all p-trend > 0.4). In six cohorts with estimates of lymphatic tissue dose, borderline significant increased risks (p-trend = 0.02-0.07) were observed for NHL + CLL, NHL, and CLL. Further pooled epidemiological studies are needed with longer follow-up, central outcome review by expert hematopathologists, and assessment of radiation doses to lymphoid tissues.

Evidence for Increased Susceptibility to Breast Cancer From Exposure to Ionizing Radiation Due to a Familial History of Breast Cancer: Results From the Swedish Hemangioma Cohort.

Women with a history of breast cancer among family members are at increased risk for breast cancer. However, it is unknown whether a familial breast cancer history (FBCH) also increases individual susceptibility to breast cancer from radiation exposure. In this cohort study, 17,200 female Swedish hemangioma patients with 1,079 breast cancer cases diagnosed between 1958 and 2013, exposed to ionizing radiation in infancy, were linked to their first-degree relatives. The association between FBCH and radiation-induced breast cancer risk was assessed. Further, the relevance for breast cancer radiotherapy and mammography screening was evaluated. On average, the radiation-induced excess relative risk and excess absolute risk of breast cancer at age 50 years were 0.51 Gy-1 (95% confidence interval (CI): 0.33, 0.71) and 10.8 cases/10,000 person-years/Gy (95% CI: 7.0, 14.6), respectively. Radiation risk was higher by a factor of 2.7 (95% CI: 1.0, 4.8; P = 0.05) if 1 first-degree relative was affected by breast cancer. For whole-breast standard radiotherapy at age 40 years with a contralateral breast dose of 0.72 Gy, the 20-year radiation-related excess risk of contralateral breast cancer was estimated to increase from 0.6% for women without FBCH to 1.7% for women with FBCH. In a biennial mammography screening program at ages 40-74 years, radiation risk up to age 80 years would increase from 0.11% for women without FBCH to 0.29% for women with FBCH.

Leukaemia and myeloid malignancy among people exposed to low doses (<100 mSv) of ionising radiation during childhood: a pooled analysis of nine historical cohort studies.

BACKGROUND: Substantial evidence links exposure to moderate or high doses of ionising radiation, particularly in childhood, with increased risk of leukaemia. The association of leukaemia with exposure to low-dose (<100 mSv) radiation is less certain, although this is the dose range most relevant to the general population. We aimed to estimate the risk of leukaemia associated with low-dose radiation exposure in childhood (age <21 years). METHODS: In this analysis of historical cohort studies, we pooled eligible cohorts reported up to June 30, 2014. We evaluated leukaemia and myeloid malignancy outcomes in these cohorts with the relevant International Classification of Diseases and International Classification of Diseases for Oncology definitions. The cohorts included had not been treated for malignant disease, had reported at least five cases of the relevant haematopoietic neoplasms, and estimated individual active bone marrow (ABM) doses. We restricted analysis to individuals who were younger than 21 years at first irradiation who had mean cumulative ABM doses of less than 100 mSv. Dose-response models were fitted by use of Poisson regression. The data were received in fully anonymised form by the statistical analyst. FINDINGS: We identified nine eligible cohorts from Canada, France, Japan, Sweden, the UK, and the USA, including 262 573 people who had been exposed to less than 100 mSv enrolled between June 4, 1915, and Dec 31, 2004. Mean follow-up was 19·63 years (SD 17·75) and mean cumulative ABM dose was 19·6 mSv (SD 22·7). 154 myeloid malignancies were identified (which included 79 acute myeloid leukaemias, eight myelodysplastic syndromes, and 36 chronic myeloid leukaemias, in addition to other unspecified myeloid malignancies) and 40 acute lymphoblastic leukaemias, with 221 leukaemias (including otherwise unclassified leukaemias but excluding chronic lymphocytic leukaemia) identified overall. The fitted relative risks at 100 mSv were 3·09 (95% CI 1·41-5·92; ptrend=0·008) for acute myeloid leukaemia and myelodysplastic syndromes combined, 2·56 (1·09-5·06; ptrend=0·033) for acute myeloid leukaemia, and 5·66 (1·35-19·71; ptrend=0·023) for acute lymphoblastic leukaemia. There was no clear dose-response for chronic myeloid leukaemia, which had a relative risk at 100 mSv of 0·36 (0·00-2·36; ptrend=0·394). There were few indications of between-cohort heterogeneity or departure from linearity. For acute myeloid leukaemia and myelodysplastic syndromes combined and for acute lymphoblastic leukaemia, the dose-responses remained significant for doses of less than 50 mSv. Excess absolute risks at 100 mSv were in the range of 0·1-0·4 cases or deaths per 10 000 person-years. INTERPRETATION: The risks of acute myeloid leukaemia and acute lymphoblastic leukaemia were significantly increased after cumulative doses of ionising radiation of less than 100 mSv in childhood or adolescence, with an excess risk also apparent for cumulative radiation doses of less than 50 mSv for some endpoints. These findings support an increased risk of leukaemia associated with low-dose exposure to radiation and imply that the current system of radiological protection is prudent and not overly protective. FUNDING: National Cancer Institute Intramural Research Program, National Cancer Institute, and US National Institutes for Health.

Thyroid Cancer Following Childhood Low-Dose Radiation Exposure: A Pooled Analysis of Nine Cohorts.

Context: The increased use of diagnostic and therapeutic procedures that involve radiation raises concerns about radiation effects, particularly in children and the radiosensitive thyroid gland. Objectives: Evaluation of relative risk (RR) trends for thyroid radiation doses <0.2 gray (Gy); evidence of a threshold dose; and possible modifiers of the dose-response, e.g., sex, age at exposure, time since exposure. Design and Setting: Pooled data from nine cohort studies of childhood external radiation exposure and thyroid cancer with individualized dose estimates, ≥1000 irradiated subjects or ≥10 thyroid cancer cases, with data limited to individuals receiving doses <0.2 Gy. Participants: Cohorts included the following: childhood cancer survivors (n = 2); children treated for benign diseases (n = 6); and children who survived the atomic bombings in Japan (n = 1). There were 252 cases and 2,588,559 person-years in irradiated individuals and 142 cases and 1,865,957 person-years in nonirradiated individuals. Intervention: There were no interventions. Main Outcome Measure: Incident thyroid cancers. Results: For both <0.2 and <0.1 Gy, RRs increased with thyroid dose (P < 0.01), without significant departure from linearity (P = 0.77 and P = 0.66, respectively). Estimates of threshold dose ranged from 0.0 to 0.03 Gy, with an upper 95% confidence bound of 0.04 Gy. The increasing dose-response trend persisted >45 years after exposure, was greater at younger age at exposure and younger attained age, and was similar by sex and number of treatments. Conclusions: Our analyses reaffirmed linearity of the dose response as the most plausible relationship for "as low as reasonably achievable" assessments for pediatric low-dose radiation-associated thyroid cancer risk.

Thyroid Cancer after Childhood Exposure to External Radiation: An Updated Pooled Analysis of 12 Studies.

Studies have causally linked external thyroid radiation exposure in childhood with thyroid cancer. In 1995, investigators conducted relative risk analyses of pooled data from seven epidemiologic studies. Doses were mostly <10 Gy, although childhood cancer therapies can result in thyroid doses >50 Gy. We pooled data from 12 studies of thyroid cancer patients who were exposed to radiation in childhood (ages <20 years), more than doubling the data, including 1,070 (927 exposed) thyroid cancers and 5.3 million (3.4 million exposed) person-years. Relative risks increased supralinearly through 2-4 Gy, leveled off between 10-30 Gy and declined thereafter, remaining significantly elevated above 50 Gy. There was a significant relative risk trend for doses <0.10 Gy (P < 0.01), with no departure from linearity (P = 0.36). We observed radiogenic effects for both papillary and nonpapillary tumors. Estimates of excess relative risk per Gy (ERR/Gy) were homogeneous by sex (P = 0.35) and number of radiation treatments (P = 0.84) and increased with decreasing age at the time of exposure. The ERR/Gy estimate was significant within ten years of radiation exposure, 2.76 (95% CI, 0.94-4.98), based on 42 exposed cases, and remained elevated 50 years and more after exposure. Finally, exposure to chemotherapy was significantly associated with thyroid cancer, with results supporting a nonsynergistic (additive) association with radiation.

New dosimetry for childhood skin hemangioma treatments with (226)Ra needles or tubes.

BACKGROUND: The Stockholm Hemangioma Cohort is important for evaluation of late effects after exposure to ionizing radiation during childhood. Dose estimates in this cohort were based on both measurements and calculations using an old treatment planning system. METHODS: We compare previously published and calculated dose estimates with new ones, obtained by Monte Carlo simulations, which mimic the hemangioma treatments with (226)Ra needles and tubes. The distances between the (226)Ra sources and the thyroid and breasts, respectively, were reassessed. RESULT: The Monte Carlo calculations showed significantly lower dose values than those obtained earlier. The differences depended both on the modeling of the sources and on further individualized distances from the sources. The mean value of the new calculated doses was 25% of the old breast doses and 46% of the old thyroid doses. CONCLUSION: New dosimetry for hemangioma treatments gives significantly lower organ doses for the few cases receiving the highest absorbed dose values. This implies that radiation risk estimates will increase and have to be recalculated. For retrospective studies it is now possible to calculate organ doses from radium treatments using modern treatment planning systems by modeling the source geometry carefully and apply the TG-43 formalism. It is important to be aware of the large uncertainties in calculated absorbed dose values.

Breast cancer risk and possible mechanisms of radiation-induced genomic instability in the Swedish hemangioma cohort after reanalyzed dosimetry.

The cohort of 17,200 female Swedish hemangioma patients, who had been exposed to ionizing radiation because of skin hemangioma, was analyzed for breast cancer incidence with descriptive excess relative risk models and mechanistic models of carcinogenesis. The dosimetry system has recently been updated, leading to substantially reduced doses for the most highly exposed part of the Stockholm cohort. The follow-up includes persons until December 2009 with 877 breast cancer cases. All models agree on the risk estimates. The excess relative and excess absolute risk at the age of 50 years are 0.48 Gy(-1) (95% CI 0.28; 0.69) and 10.4 (10(4)PYR Gy)(-1) (95% CI 6.1; 14.4) (95% CI 6.1; 14.4), respectively. These risk estimates are about a factor of 2 higher than previous analyses of this cohort as a consequence of the re-evaluation of the dosimetry system. Explicit models incorporating effects of genomic instability were developed and applied to the hemangioma cohort. It was found that a radiation-induced transition towards genomic instability was highly significant. The models indicate that the main effect of radiation-induced genomic instability is to increase the rate of transition of non-initiated cells to initiated cells with a proliferative advantage. The magnitude of such an acceleration cannot be inferred from epidemiological data alone, but must be complemented by radiobiological measurements.

Monte Carlo dosimetry of the eye plaque design used at the St. Erik Eye Hospital for (125)I brachytherapy.

PURPOSE: At St. Erik Eye Hospital in Stockholm, Sweden, ocular tumors of apical height above 6 mm are treated with brachytherapy, using iodine-125 seeds attached to a gold alloy plaque while the treatment planning is performed assuming homogeneous water surroundings. The aim of this work was to investigate the dose-modifying effects of the plaque and the seed fixating silicone rubber glue. METHODS AND MATERIALS: The impact of the gold plaque and silicone rubber glue was studied with the Monte Carlo N-particle transport code, version 5. RESULTS: For the 2 cm most proximal to the plaque surface along the plaque's central axis, the eyeball received 104.6-93.0% of the dose in all-water conditions. CONCLUSIONS: The 0.3 mm thick layer of silicone rubber glue, used for seed fixation, attenuates photons little enough to allow characteristic X-rays from the gold alloy plaque to reach the eyeball. Close to the plaque, the dose rates were higher with the plaque and glue present, than in homogeneous water conditions. This is in contrast to what has been reported for more commonly used eye plaques, demonstrating the importance of investigating the dosimetry of individual treatment systems.

No clinically relevant effect on cognitive outcomes after low-dose radiation to the infant brain: a population-based cohort study in Sweden.

UNLABELLED: While the detrimental effects of cranial radiotherapy on the developing brain are well known, the effects on cognitive performance of low doses of ionizing radiation is less studied. We performed a population-based cohort study to determine whether low doses of ionizing radiation to the brain in infancy affects cognitive function later in life. Further we hypothesized that the dose to the hippocampus predicts cognitive late side effects better than the anterior or the posterior brain doses. MATERIAL AND METHODS: During 1950-1960 3860 boys were treated with radiation in Sweden for cutaneous hemangiomas before the age of 18 months. Of these, 3030 were analyzed for military test scores at the age of 18 years and 2559 for the highest obtained educational level. RESULTS: Logical, spatial and technical test scores were not affected by increasing irradiation doses. The verbal test scores displayed a significant trend for decreasing scores with increasing doses to the hippocampus (p = 0.005). However, the absolute mean difference between the zero dose and the highest dose category (median 680 mGy) was very small, only 0.64 stanine points, and the significance was dependent on the highest dose category, containing few subjects. The educational level was not affected by brain irradiation. Overall, the hippocampal dose was a better predictor of late cognitive side effects than the doses to the anterior or the posterior brain. In conclusion, there was no decrease in logical, spatial and technical verbal or global test scores after ionizing radiation doses up to 250 mGy, but a subtle decrease in verbal test scores if the highest dose category was included (median 680 mGy). However, the clinical relevance of this decline in the highest dose group is questionable, since we could not find any effect on the highest obtained educational level.

A pooled analysis of thyroid cancer incidence following radiotherapy for childhood cancer.

Childhood cancer five-year survival now exceeds 70-80%. Childhood exposure to radiation is a known thyroid carcinogen; however, data are limited for the evaluation of radiation dose-response at high doses, modifiers of the dose-response relationship and joint effects of radiotherapy and chemotherapy. To address these issues, we pooled two cohort and two nested case-control studies of childhood cancer survivors including 16,757 patients, with 187 developing primary thyroid cancer. Relative risks (RR) with 95% confidence intervals (CI) for thyroid cancer by treatment with alkylating agents, anthracyclines or bleomycin were 3.25 (0.9-14.9), 4.5 (1.4-17.8) and 3.2 (0.8-10.4), respectively, in patients without radiotherapy, and declined with greater radiation dose (RR trends, P = 0.02, 0.12 and 0.01, respectively). Radiation dose-related RRs increased approximately linearly for <10 Gy, leveled off at 10-15-fold for 10-30 Gy and then declined, but remained elevated for doses >50 Gy. The fitted RR at 10 Gy was 13.7 (95% CI: 8.0-24.0). Dose-related excess RRs increased with decreasing age at exposure (P < 0.01), but did not vary with attained age or time-since-exposure, remaining elevated 25+ years after exposure. Gender and number of treatments did not modify radiation effects. Thyroid cancer risks remained elevated many decades following radiotherapy, highlighting the need for continued follow up of childhood cancer survivors.

Breast cancer risk after radiation treatment at infancy: potential consequences of radiation-induced genomic instability.

Swedish hemangioma patients were treated in infancy mainly by external application of radium-226 starting from 1920. This work analysed the radiation risk among 17,158 women with a total of 678 breast cancer incidence cases with models of carcinogenesis and empirical excess relative risk models. Models incorporating effects of genomic instability were developed and applied to the hemangioma cohort. The description of the radiation risk was significantly improved with a model of genomic instability at an early stage of carcinogenesis.

Breast cancer risk among Swedish hemangioma patients and possible consequences of radiation-induced genomic instability.

Breast cancer incidence among 17,158 female Swedish hemangioma patients was analyzed with empirical excess relative risk models and with a biologically-based model of carcinogenesis. The patients were treated in infancy mainly by external application of radium-226. The mean and median absorbed doses to the breast were 0.29 and 0.04Gy, and a total of 678 breast cancer cases have been observed. Both models agree very well in the risk estimates with an excess relative risk and excess absolute risk at the age of 50 years, about the mean age of breast cancer incidence, of 0.25Gy(-1)(95% CI 0.14; 0.37) and 30.7 (10(5) BYR Gy)(-1) (95% CI 16.9; 42.8), respectively. Models incorporating effects of radiation-induced genomic instability were developed and applied to the hemangioma cohort. The biologically-based description of the radiation risk was significantly improved with a model of genomic instability at an early stage of carcinogenesis.

Experience from long-term monitoring of RAKR ratios in (192)Ir brachytherapy.

BACKGROUND: Ratios of values of brachytherapy source strengths, as measured by hospitals and vendors, comprise constant differences as, e.g., systematic errors in ion chamber calibration factors and measurement setup. Such ratios therefore have the potential to reveal the systematic changes in routines or calibration services at either the hospital or the vendor laboratory, which could otherwise be hidden by the uncertainty in the source strength values. METHODS: The RAKR of each new source in 13 afterloading units at five hospitals were measured by well-type ion chambers and compared to values for the same source stated on vendor certificates. RESULTS: Differences from unity in the ratios of RAKR values determined by hospitals and vendors are most often small and stable around their mean values to within +/- 1.5%. Larger deviations are rare but occur. A decreasing ratio, seen at two hospitals for the same source, was useful in detecting an erroneous pressure gauge at the vendor's site. CONCLUSIONS: Establishing a mean ratio of RAKR values, as measured at the hospital and supplied on the vendor certificate, and monitoring this as a function of time are an easy way for the early detection of problems with equipment or routines at either the hospital or the vendor site.

Is the use of a surrogate urethra an option in prostate high-dose-rate brachytherapy?

PURPOSE: To investigate the accuracy and the dosimetric consequences of substituting a surrogate urethra assumed to be at the geometric center of the prostate, in place of the true urethra when using high-dose-rate (HDR) brachytherapy for the treatment of prostate cancer. METHODS AND MATERIALS: One hundred prostate cancer patients treated with HDR brachytherapy constituted the study group. A pre-plan was made with the urethra visualized. The true urethra was defined, and a surrogate urethra was placed at the geometric center of the prostate. The distance between the two urethras was measured. The deviation was evaluated at the base, middle, and apex. To evaluate the dosimetric consequences for the true urethra when using a surrogate urethra, two different dose plans were made: one based on the true urethra and one based on the surrogate urethra. The dose-volume histograms for the true urethra were analyzed. RESULTS: The deviation between the true urethra and the surrogate urethra was greatest at the base of the prostate. A statistically significant difference was seen between the dosimetric parameters for the true and the surrogate urethra when the dose plan was made using the surrogate urethra. In this situation the dose to the true urethra was increased above our defined maximum tolerance limit. CONCLUSIONS: When using dose plans made according to a surrogate urethra the dose to the true urethra might be too high to be acceptable. If the true urethra is not visualized, severe damage could easily develop in a significant number of patients.

Clinical outcome in patients with prostate cancer treated with external beam radiotherapy and high dose-rate iridium 192 brachytherapy boost: a 6-year follow-up.

To report the long-term results for treatment of localized carcinoma of the prostate using high dose rate (HDR) brachytherapy, conformal external beam radiotherapy (3D EBRT) and neo-adjuvant hormonal therapy (TAB). From 1998 through 1999, 154 patients with localized prostate cancer were entered in the trial. Biologically no evidence of disease (bNED) was defined at PSA levels < 2 microg/l. In order to compare the results of this treatment with other treatment modalities, the patient's pre-treatment data were used to calculate the estimated 5-year PSA relapse free survival using Kattan's nomograms for radical prostatectomy (RP) and 3D EBRT. After 6 years of follow-up, 129 patients remain alive. The actual 5-year relapse-free survival is 84%. None of the patients demonstrated clinical signs of local recurrence. The median PSA at follow-up among the relapse-free patients was 0.05 microg/l. Among the 80 patients who presented with clinical stage T3 tumours, 55 (68%) were relapse-free. The expected 5-year relapse-free survival using nomograms for RP and 3D EBRT was 54% and 70%, respectively. Late rectal toxicity RTOG grade 3 occurred in 1% of the patients. Late urinary tract toxicity RTOG grade 3 developed in 4% of the patients. Combined treatment, utilizing HDR, 3D EBRT and TAB, produces good clinical results. Rectal toxicity is acceptable. Urinary tract toxicity, most likely can be explained by the fact that during the first years of this treatment, no effort was made to localize the urethra, which was assumed to be in the middle of the prostate.

Dosimetry of anal radiation in high-dose-rate brachytherapy for prostate cancer.

PURPOSE: The objective of this study is to determine the radiation dose to the anus during brachytherapy using high-dose-rate Ir-192 sources. METHODS AND MATERIALS: Thermoluminescence dosimeters were used for measuring the dose to the distal part of the anus in 10 patients, and in a prostate phantom to measure the radiation dose during the transport of the radiation source. RESULTS: The measured dose to the anus in vivo was on average 0.85 Gy (range, 0.48-1.37 Gy) per treatment. The transport dose using 15 and 19 needles in the prostate phantom was 0.07 and 0.08 Gy, respectively. CONCLUSIONS: The dose delivered to the anus using high-dose-rate brachytherapy with Ir-192 sources is quite low. There is a contribution to the anal radiation dose during the transport of the Ir-192 source into the needles. However, in clinical practice when using 15-20 needles, the dose from transporting the Ir-192 source can be ignored.

Reduced-intensity conditioning regimen using low-dose total body irradiation before allogeneic transplant for hematologic malignancies: Experience from the European Group for Blood and Marrow Transplantation.

PURPOSE: The high rate of toxicity is the limitation of myeloblastive regimens before allogeneic transplantation. A reduced intensity regimen can allow engraftment of stem cells and subsequent transfer of immune cells for the induction of a graft-vs.-tumor reaction. METHODS AND MATERIALS: The data from 130 patients (80 males and 50 females) treated between 1998 and 2003 for various hematologic malignancies were analyzed. The median patient age was 50 years (range, 3-72 years). Allogeneic transplantation using peripheral blood or bone marrow, or both, was performed in 104 (82%), 22 (17%), and 4 (3%) patients, respectively, from HLA identical sibling donors (n = 93, 72%), matched unrelated donors (n = 23, 18%), mismatched related donors (4%), or mismatched unrelated donors (6%). Total body irradiation (TBI) at a dose of 2 Gy delivered in one fraction was given to 101 patients (78%), and a total dose of 4-6 Gy was given in 29 (22%) patients. The median dose rate was 14.3 cGy/min (range, 6-16.4). RESULTS: After a median follow-up period of 20 months (range, 1-62 months), engraftment was obtained in 122 patients (94%). Acute graft-vs.-host disease of Grade 2 or worse was observed in 37% of patients. Multivariate analysis showed three favorable independent factors for event-free survival: HLA identical sibling donor (p < 0.0001; relative risk [RR], 0.15), complete remission (p < 0.0001; RR, 3.08), and female donor to male patient (p = 0.006; RR 2.43). For relapse, the two favorable prognostic factors were complete remission (p < 0.0001, RR 0.11) and HLA identical sibling donor (p = 0.0007; RR 3.59). CONCLUSIONS: In this multicenter study, we confirmed high rates of engraftment and chimerism after the reduced intensity regimen. Our results are comparable to those previously reported. Radiation parameters seem to have no impact on outcome. However, the lack of a statistically significant difference in terms of dose rate may have been due, in part, to the small population size in the subgroup analysis.

Prostate displacement kit: reducing the radiation dose to the rectum.

During high dose-rate brachytherapy boost in 20 patients the use of a prostate-water-rectal-displacement-kit contributed to an increase in the distance between the prostate and the rectum, however, the prostate was not totally immobilized by the needles, implying the necessity for an very careful on-line dose-planning dosimetry.

Prostate volume determination: differential volume measurements comparing CT and TRUS.

PURPOSE: To compare the differences in prostate volume assessed by computerized tomography (CT), step-section transrectal ultrasound (TRUS-step), and TRUS with ellipsoid-formula volume calculation (TRUS-ellipsoid). METHODS AND MATERIALS: Thirty-one patients with localized prostate cancer treated with combined external conformal radiotherapy and high dose rate brachytherapy, who had prostate volumes evaluated using CT, TRUS-step and TRUS-ellipsoid according to our clinical routine for dose planning. The measurements were collected retrospectively based on actual dose-plans. RESULTS: The prostate volume was on average 34 cc (range 18-60 cc) according to CT, 28 cc (range 12-57 cc) and 24 cc (range 13-44 cc) according to TRUS-step and TRUS-ellipsoid, respectively. The differences between the lengths measured were most pronounced with a mean length of 4.5 cm (range 3.0-6.0 cm) defined by CT as compared to 3.6 cm (range 3.0-5.0 cm) and 3.6 cm (range 2.8-5.0 cm) when defined by TRUS-step and TRUS-ellipsoid, respectively. CONCLUSION: CT defined volumes are 30% larger than volumes defined with TRUS-step. This is probably due to uncertainty in defining the apex of the prostate and thereby the length of the prostate using CT. When defining target in radiotherapy, it is important to be aware of the differences in volumes depending on the technique used.