How much can screening reduce colorectal cancer mortality in Japan? Scenario-based estimation by microsimulation.

BACKGROUND: Screening is one of the effective interventions for the reduction of colorectal cancer mortality. Though the Japanese government recommends faecal occult blood test and colonoscopy as a follow-up examination following a diagnosis, both participation rates have not been so high and the national mortality rate has not shown a clear decreasing trend. METHODS: Microsimulation models simulate the life histories of a large population of individuals under various scenarios. In this study, we applied a microsimulation model to estimate the reduction of colorectal cancer mortality based on screening scenarios. RESULTS: The effect of reducing the age-standardized mortality rate for colorectal cancer was estimated at 9.4% for men and 6.0% for women under the scenario which calls for 50% participation in faecal occult blood test and 90% participation of follow-up examination. This scenario corresponds to the goal setting for screening in the third-term of the Basic Plan to Promote Cancer Control Programs in Japan. CONCLUSIONS: Our microsimulation model was found to be useful in estimating the mortality reduction effect of cancer control policy. Such modelling techniques can be utilized to develop effective and optimal cancer control programs.

A modified GAP model for East-Asian populations with idiopathic pulmonary fibrosis.

BACKGROUND: The easy-to-calculate gender, age, and lung physiology (GAP) model shows good predictive and discriminative performance in the prognosis of idiopathic pulmonary fibrosis (IPF). However, the GAP model was not effective in predicting the prognosis accurately in previous Japanese and Korean IPF cohort studies. Therefore, we developed a modified GAP model for the East-Asian populations by weighing the GAP variables. The validity of the modified GAP model was subsequently evaluated in East-Asian IPF patients. METHODS: The derivation cohort comprised 326 patients with IPF. Weights of the variables were adjusted on the basis of coefficients derived from Cox regression models. The total points were distributed to the three stages of the disease so that the number of patients included in each stage was appropriate. The validity of the modified model was analyzed in another Japanese cohort of 117 patients with IPF and a nationwide cohort of Korean patients with IPF. RESULTS: Predicted survival rates differed significantly in the derivation cohort using the modified GAP model for each stage of IPF (log-rank test: stage I vs. stage II, p < 0.001; stage II vs. stage III, p < 0.001). Model performance improved according to Harrell's C-index (at three years: 0.696 in the original GAP model to 0.738 in the modified model). The performance of the modified model was validated in the Japanese validation and Korean national cohorts. CONCLUSIONS: Our modification of the original GAP model showed improved performance in East-Asian IPF patient populations.

Lateral Position With Gantry Tilt Further Improves Computed Tomography Image Quality Reconstructed Using Single-Energy Metal Artifact Reduction Algorithm in the Oral Cavity.

OBJECTIVE: To assess the limitations of single-energy metal artifact reduction algorithm in the oral cavity and evaluate the availability of a solution by setting the patient in a lateral position (LP) with the use of a gantry tilt (GT). METHODS: We analyzed 88 patients with dental metals retrospectively in study 1, and 74 patients prospectively in study 2. Patients were classified: metal I with dental metals in 1 region, metal II in 2 regions, and metal III in 3 regions. Patients underwent neck computed tomography examinations in a supine position (SP) in study 1, and 2 positions, an LP with a GT and an SP, in study 2. All images were reconstructed with this algorithm. Image quality was scored using a 4-point scale: 1 = severe artifact, 2 = moderate artifact, 3 = slight artifact, 4 = no artifact. The scores were compared between metal I, metal II, and metal III using the Mann-Whitney U test in study 1, and between an LP with a GT and an SP using the Wilcoxon signed ranks test in study 2. RESULTS: The scores outside the dental arch were significantly higher in metal I than in metal II and metal III (3.0 ± 0.6 vs 2.3 ± 0.5 vs 2.2 ± 0.4; P < 0.0001 for metal I vs metal II and for metal I vs metal III) and significantly higher in an LP with a GT than an SP (3.2 ± 0.4 vs 2.3 ± 0.4; P < 0.0001). CONCLUSIONS: Single-energy metal artifact reduction algorithm could reduce metal artifacts adequately in patients with dental metals in 1 region, but not in 2 or more regions. However, even for the latter, combination of this algorithm and an LP with a GT could further improve the image quality.

Statistical inference for estimating the incidence of cancer at the prefectural level in Japan.

Information of prefectural cancer incidence in Japan is an important resource to plan an effective regional cancer control program. In order to obtain accurate prefectural cancer incidence, we have to adjust for both of completeness of regional cancer registries and regional dispersion, simultaneously, Then, we developed a hierarchal Bayes model with a completeness adjustment by using the relation between MI ratio (mortality divided by incidence) and proportion of death certificate notified among incidence. Prefectural cancer incidence is estimated with the 95% credible interval, which suggests that the national MI ratio should be 0.386 if the registry were complete. Because cancer behavior has a variation depending on prefecture, such accurate incidence must contribute to plan and assess regional cancer control program.

Simulation Models in Gastric Cancer Screening: A Systematic Review

Background: Together with such high-quality approaches as randomized controlled trials and large-scale cohort studies, simulation models are often employed to evaluate the effect of cancer screening methods and decide on their appropriateness. This study aimed to evaluate all effects of gastric cancer screening that have been assessed using simulation models, including cost-effectiveness, mortality reduction, and early-stage detection. Methods: We performed a systematic review using PubMed and Web of Science. We evaluated the effect of screening related to cost, such as incremental cost-effectiveness and incremental cost-effectiveness ratios; we also separately assessed effects other than cost, such as quality-adjusted life-years, number of deaths prevented, life-years saved, relative risk of mortality from gastric cancer, life expectancy, and incidence reduction. The methods targeted for evaluation were Helicobacter pylori testing or endoscopy. Results: We identified 19 studies dealing with simulation models in gastric cancer screenings: 14 examined H. pylori screening and 7 focused on endoscopy. Among those studies, two assessed both H. pylori and endoscopy screening. Most of the studies adopted a Markov model, and all the studies evaluated cost-effectiveness. Of the 14 H. pylori screening studies, 13 demonstrated cost-effectiveness and 11 also showed good results other than cost-effectiveness, such as extension of life-years and increase in early-stage detection. In three of the five endoscopy studies, the target population was patients; all five studies obtained good results for cost-effectiveness and four observed good results other than for cost-effectiveness. Conclusions: In this study, we showed that the H. pylori screening test was cost-effective in terms of simulation model investigations. However, the H. pylori screening test should not ordinarily be recommended since there is insufficient evidence that it reduces gastric cancer mortality. In Japan, simulation modeling should be employed to plan for cancer control, and the appropriate use of simulation models should be examined for future use.

An in vitro verification of strength estimation for moving an 125I source during implantation in brachytherapy.

This study aims to demonstrate the feasibility of a method for estimating the strength of a moving brachytherapy source during implantation in a patient. Experiments were performed under the same conditions as in the actual treatment, except for one point that the source was not implanted into a patient. The brachytherapy source selected for this study was 125I with an air kerma strength of 0.332 U (µGym2h-1), and the detector used was a plastic scintillator with dimensions of 10 cm × 5 cm × 5 cm. A calibration factor to convert the counting rate of the detector to the source strength was measured and then the accuracy of the proposed method was investigated for a manually driven source. The accuracy was found to be under 10% when the shielding effect of additional needles for implantation at other positions was corrected, and about 30% when the shielding was not corrected. Even without shielding correction, the proposed method can detect dead/dropped source, implantation of a source with the wrong strength, and a mistake in the number of the sources implanted. Furthermore, when the correction was applied, the achieved accuracy came close to within 7% required to find the Oncoseed 6711 (125I seed with unintended strength among the commercially supplied values of 0.392, 0.462 and 0.533 U).

Evaluation of the Japanese Metabolic Syndrome Risk Score (JAMRISC): a newly developed questionnaire used as a screening tool for diagnosing metabolic syndrome and insulin resistance in Japan.

OBJECTIVES: To prevent the onset of lifestyle-related diseases associated with metabolic syndrome (MetS) in Japan, research into the development of a useful screening method is strongly desired. We developed a new screening questionnaire (JAMRISC) utilizing a logistic regression model and evaluated its ability to predict the development of MetS, type 2 diabetes and other lifestyle-related diseases in Japanese populace. METHODS: JAMRISC questionnaire was sent to 1,850 individuals in Rumoi, a small city in Hokkaido. We received a total of 1,054 valid responses. To maximize the target individuals accurately diagnosed with MetS, logistic regression analysis was used to generate a unique metabolic syndrome score calculation formula as taking into consideration the clinical relevance of each question item as individual coefficients. RESULTS: The results of our comparative research utilizing both JAMRISC and Finnish Diabetes Risk Score (FINDRISC) questionnaires revealed the usefulness of JAMRISC for its ability to detect risks for MetS, pre-MetS, diabetes, and pre-diabetes. Study of disease risk detection via JAMRISC questionnaire targeting the 4283 residents of Rumoi indicated a high detection rate for pre-MetS (98.8 %), MetS (94.2 %), pre-diabetes (85.1 %) and type 2 diabetes (94.9 %). In addition, JAMRISC was useful not only as a MetS risk score test, but also as a screening tool for diagnosing insulin resistance. CONCLUSIONS: JAMRISC questionnaire is a useful instrument for the detection of early risk of not only MetS and type 2 diabetes but also insulin resistance.

Quantification of the increase in thyroid cancer prevalence in Fukushima after the nuclear disaster in 2011--a potential overdiagnosis?

A thyroid ultrasound examination programme has been conducted in Fukushima Prefecture, Japan, after the nuclear disaster in 2011. Although remarkably high prevalence of thyroid cancer was observed, no relevant quantitative evaluation was conducted. We calculated the observed/expected (O/E) ratio of thyroid cancer prevalence for the residents aged ≤20 years. Observed prevalence was the number of thyroid cancer cases detected by the programme through the end of April 2015. Expected prevalence was calculated as cumulative incidence by a life-table method using the national estimates of thyroid cancer incidence rate in 2001-10 (prior to the disaster) and the population of Fukushima Prefecture. The underlying assumption was that there was neither nuclear accident nor screening intervention. The observed and estimated prevalence of thyroid cancer among residents aged ≤20 years was 160.1 and 5.2, respectively, giving an O/E ratio of 30.8 [95% confidence interval (CI): 26.2, 35.9]. When the recent increasing trend in thyroid cancer was considered, the overall O/E ratio was 22.2 (95% CI: 18.9, 25.9). The cumulative number of thyroid cancer deaths in Fukushima Prefecture, estimated with the same method (annual average in 2009-13), was 0.6 under age 40. Combined with the existing knowledge about radiation effect on thyroid cancer, our descriptive analysis suggests the possibility of overdiagnosis. Evaluation including individual-level analysis is required to further clarify the contribution of underlying factors.

The signal intensity ratio of the optic nerve to ipsilateral frontal white matter is of value in the diagnosis of acute optic neuritis.

OBJECTIVES: To evaluate the usefulness of the signal intensity ratio (SIR) of the optic nerve to the white matter (WM) on short tau inversion recovery (STIR) images to diagnose acute optic neuritis (AON). METHODS: The 405 consecutive patients with suspected orbital diseases underwent orbital magnetic resonance imaging (MRI) using a 3-T scanner between June 2008 and August 2011. Among them, 108 optic nerves (33 AON and 75 control) were retrospectively analysed. The averaged SIR (SIRave) and maximum SIR (SIRmax) were defined as the averaged signal intensity (SI) of the optic nerve divided by that of WM, and the maximum SI of the optic nerve divided by averaged SI of WM, respectively. These values were compared between AON and control using the Mann-Whitney U test. A P < 0.05 was considered statistically significant. RESULTS: SIRave and SIRmax were significantly (P < 0.001) higher in the AON compared to the control. At a cut-off SIRave value of 1.119, the sensitivity, specificity and accuracy were 0.939, 0.840, and 0.870; and at a cut-off SIRmax value of 1.281, these were 1.000, 0.720 and 0.806, respectively. CONCLUSION: The SIR of the optic nerve to WM on STIR images is of value in diagnosing AON. KEY POINTS: • We propose a method of diagnosing acute optic neuritis using 3-T MRI. • Our method is simple and objective and requires no novel imaging techniques. • Our method shows high diagnostic accuracy.

Detecting a Local Cohort Effect for Cancer Mortality Data Using a Varying Coefficient Model.

BACKGROUND: Cancer mortality is increasing with the aging of the population in Japan. Cancer information obtained through feasible methods is therefore becoming the basis for planning effective cancer control programs. There are three time-related factors affecting cancer mortality, of which the cohort effect is one. Past descriptive epidemiologic studies suggest that the cohort effect is not negligible in cancer mortality. METHODS: In this paper, we develop a statistical method for automatically detecting a cohort effect and assessing its statistical significance for cancer mortality data using a varying coefficient model. RESULTS: The proposed method was applied to liver and lung cancer mortality data on Japanese men for illustration. Our method detected significant positive or negative cohort effects. The relative risk was 1.54 for liver cancer mortality in the cohort born around 1934 and 0.83 for lung cancer in the cohort born around 1939. CONCLUSIONS: Cohort effects detected using the proposed method agree well with previous descriptive epidemiologic findings. In addition, the proposed method is expected to be sensitive enough to detect smaller, previously undetected birth cohort effects.

A comparison of the dose distributions between the brachytherapy 125I source models, STM1251 and Oncoseed 6711, in a geometry lacking radiation equilibrium scatter conditions.

The purpose of this study was to estimate the uncertainty in the dose distribution for the (125)I source STM1251, as measured with a radiophotoluminescent glass rod dosimeter and calculated using the Monte Carlo code EGS5 in geometry that included the source structure reported by Kirov et al. This was performed at a range of positions in and on a water phantom 18 cm in diameter and 16 cm in length. Some dosimetry positions were so close to the surface that the backscatter margin was insufficient for photons. Consequently, the combined standard uncertainty (CSU) at the coverage factor k of 1 was 11.0-11.2% for the measurement and 1.8-3.6% for the calculation. The calculation successfully reproduced the measured dose distribution within 13%, with CSU at k ≤ 1.6 (P > 0.3). Dose distributions were then compared with those for the (125)I source Oncoseed 6711. Our results supported the American Association of Physicists in Medicine Task Group No. 43 Updated Protocol (TG43U1) formalism, in which STM1251 dose distributions were more penetrating than those of Oncoseed 6711. This trend was also observed in the region near the phantom surface lacking the equilibrium radiation scatter conditions. In this region, the difference between the TG43U1 formalism and the measurement and calculation performed in the present study was not significant (P > 0.3) for either of the source models. Selection of the source model based on the treatment plans according to the TG43U1 formalism will be practical.

Serological surveillance development for tropical infectious diseases using simultaneous microsphere-based multiplex assays and finite mixture models.

BACKGROUND: A strategy to combat infectious diseases, including neglected tropical diseases (NTDs), will depend on the development of reliable epidemiological surveillance methods. To establish a simple and practical seroprevalence detection system, we developed a microsphere-based multiplex immunoassay system and evaluated utility using samples obtained in Kenya. METHODS: We developed a microsphere-based immuno-assay system to simultaneously measure the individual levels of plasma antibody (IgG) against 8 antigens derived from 6 pathogens: Entamoeba histolytica (C-IgL), Leishmania donovani (KRP42), Toxoplasma gondii (SAG1), Wuchereria bancrofti (SXP1), HIV (gag, gp120 and gp41), and Vibrio cholerae (cholera toxin). The assay system was validated using appropriate control samples. The assay system was applied for 3411 blood samples collected from the general population randomly selected from two health and demographic surveillance system (HDSS) cohorts in the coastal and western regions of Kenya. The immunoassay values distribution for each antigen was mathematically defined by a finite mixture model, and cut-off values were optimized. FINDINGS: Sensitivities and specificities for each antigen ranged between 71 and 100%. Seroprevalences for each pathogen from the Kwale and Mbita HDSS sites (respectively) were as follows: HIV, 3.0% and 20.1%; L. donovani, 12.6% and 17.3%; E. histolytica, 12.8% and 16.6%; and T. gondii, 30.9% and 28.2%. Seroprevalences of W. bancrofti and V. cholerae showed relatively high figures, especially among children. The results might be affected by immunological cross reactions between W. bancrofti-SXP1 and other parasitic infections; and cholera toxin and the enterotoxigenic E. coli (ETEC), respectively. INTERPRETATION: A microsphere-based multi-serological assay system can provide an opportunity to comprehensively grasp epidemiological features for NTDs. By adding pathogens and antigens of interest, optimized made-to-order high-quality programs can be established to utilize limited resources to effectively control NTDs in Africa.

Strength estimation of a moving 125Iodine source during implantation in brachytherapy: application to linked sources.

This study sought to demonstrate the feasibility of estimating the source strength during implantation in brachytherapy. The requirement for measuring the strengths of the linked sources was investigated. The utilized sources were (125)I with air kerma strengths of 8.38-8.63 U (µGy m(2) h(-1)). Measurements were performed with a plastic scintillator (80 mm × 50 mm × 20 mm in thickness). For a source-to-source distance of 10.5 mm and at source speeds of up to 200 mm s(-1), a counting time of 10 ms and a detector-to-needle distance of 5 mm were found to be the appropriate measurement conditions. The combined standard uncertainty (CSU) with the coverage factor of 1 (k = 1) was ∼15% when using a grid to decrease the interference by the neighboring sources. Without the grid, the CSU (k = 1) was ∼5%, and an 8% overestimation due to the neighboring sources was found to potentially cause additional uncertainty. In order to improve the accuracy in estimating source strength, it is recommended that the measurment conditions should be optimized by considering the tradeoff between the overestimation due to the neighboring sources and the intensity of the measured value, which influences the random error.

A dosimetry method for low dose rate brachytherapy by EGS5 combined with regression to reflect source strength shortage.

The post-implantation dosimetry for brachytherapy using Monte Carlo calculation by EGS5 code combined with the source strength regression was investigated with respect to its validity. In this method, the source strength for the EGS5 calculation was adjusted with the regression, so that the calculation would reproduce the dose monitored with the glass rod dosimeters (GRDs) on a water phantom. The experiments were performed, simulating the case where one of two (125)I sources of Oncoseed 6711 was lacking strength by 4-48%. As a result, the calculation without regression was in agreement with the GRD measurement within 26-62%. In this case, the shortage in strength of a source was neglected. By the regression, in order to reflect the strength shortage, the agreement was improved up to 17-24%. This agreement was also comparable with accuracy of the dose calculation for single source geometry reported previously. These results suggest the validity of the dosimetry method proposed in this study.

Short-term projection of cancer incidence in Japan using an age-period interaction model with spline smoothing.

OBJECTIVE: In Japan, population-based cancer incidence data are reported several years behind the latest year of cancer mortality data. To bridge this gap, we aimed to determine a short-term projection method for cancer incidence. METHODS: Data between 1985 and 2007 were obtained from the population-based cancer registries in four prefectures (Miyagi, Yamagata, Fukui and Nagasaki). Three projection models were examined: generalized linear model with age and period (A + P linear); generalized linear model with age, period and their interactions (A*P linear); and generalized additive model with age, period and their interactions smoothed by spline (A*P spline). We performed a 5-year projection for the years 2000 and 2005, based on the data of 1985-95 and 1985-2000, respectively. Seven cancer sites (stomach, liver, colorectal, lung, female breast, cervix uteri and prostate) and all cancers combined were analyzed. The accuracy of projection was evaluated by whether each observed number fell within the 95% confidence interval of the projected number. RESULTS: The A*P spline model accurately projected 8 of 13 cancer site-sex combinations, whereas the number of site-sex combinations of accurate projection was 2 and 6 for A + P linear and A*P linear models, respectively. For liver and colorectal cancers, the A*P spline model alone performed accurate projections; the relative differences between projected and observed numbers of cancer incidence ranged between -0.4 and +10.9% for the A*P spline, and between +7.4 and +37.6% for the other two models. All three models failed to project sudden increases in prostate cancer between 2000 and 2005. CONCLUSIONS: The A*P spline model is a candidate method for the projection of cancer incidence in Japan. However, we need a continuous validation for prostate cancer.

Measurement of the strength of iodine-125 seed moving at unknown speed during implantation in brachytherapy.

The aim of this study is to demonstrate the feasibility of estimating the strength of the moving radiation source during patient implantation. The requirement for the counting time was investigated by comparing the results of the measurements for the static source with those for the source moving at 2, 5, 10 and 20 cm s(-1). The utilized source was (125)I with an air-kerma strength of 0.432 U (µGym(2)h(-1)). The detector utilized was a plastic scintillation detector (8 cm × 5 cm × 2 cm in thickness) set at 8 cm away from the needle to guide the source. Experiments were conducted in order to determine the most desirable counting time. Analysis using the maximum of the measured values while the source passed through the needle indicated that the results for the moving source increased more than those for the static source as the counting time decreased. The combined standard uncertainty, with the coverage factor of 1, was within 4% at the counting time of 100 ms. This investigation supported the feasibility of the method proposed for estimating the source strength during the implantation procedure, regardless of the source speed. The method proposed is a potential option for reducing the risk of accidental replacements of sources with those of incorrect strengths.

Temperature dependent N-glycosylation of plasma membrane heat shock protein Hsp30p in Saccharomyces cerevisiae.

The HSP30 gene of the budding yeast Saccharomyces cerevisiae encodes a seven-transmembrane heat shock protein expressed in response to various types of stress including heat shock. Although Hsp30p contains a potential N-glycosylation consensus sequence (Asn(2)-Asp(3)-Thr(4)), whether it is actually N-glycosylated has not been verified. Here we demonstrate that N-glycosylation is induced at Asn(2) of Hsp30p by severe heat shock, ethanol stress, and acetic acid stress. Mild heat shock and glucose depletion induced the expression but not N-glycosylation of Hsp30p, indicating the N-glycosylation to be dependent on temperature and environmental conditions. N-glycosylation did not affect on the intracellular localization of Hsp30p but its physiological role under severe heat shock conditions. Since limited information is available on stress-responsive or condition-induced N-glycosylation, our findings provide new insight into the regulation of cellular stress response in yeast.

MEM spectral analysis for predicting influenza epidemics in Japan.

OBJECTIVES: The prediction of influenza epidemics has long been the focus of attention in epidemiology and mathematical biology. In this study, we tested whether time series analysis was useful for predicting the incidence of influenza in Japan. METHODS: The method of time series analysis we used consists of spectral analysis based on the maximum entropy method (MEM) in the frequency domain and the nonlinear least squares method in the time domain. Using this time series analysis, we analyzed the incidence data of influenza in Japan from January 1948 to December 1998; these data are unique in that they covered the periods of pandemics in Japan in 1957, 1968, and 1977. RESULTS: On the basis of the MEM spectral analysis, we identified the periodic modes explaining the underlying variations of the incidence data. The optimum least squares fitting (LSF) curve calculated with the periodic modes reproduced the underlying variation of the incidence data. An extension of the LSF curve could be used to predict the incidence of influenza quantitatively. CONCLUSIONS: Our study suggested that MEM spectral analysis would allow us to model temporal variations of influenza epidemics with multiple periodic modes much more effectively than by using the method of conventional time series analysis, which has been used previously to investigate the behavior of temporal variations in influenza data.

Cancer incidence and incidence rates in Japan in 2006: based on data from 15 population-based cancer registries in the monitoring of cancer incidence in Japan (MCIJ) project.

The Japan Cancer Surveillance Research Group estimated the cancer incidence in 2006 as part of the Monitoring of Cancer Incidence in Japan (MCIJ) project, on the basis of data collected from 15 of 32 population-based cancer registries. The total number of incidences in Japan for 2006 was estimated as 664 398 (C00-C96). The leading cancer site was stomach for men and breast for women. Age-standardized incidence rates remained at almost the same level as for the previous 3 years.

A dosimetry study of the Oncoseed 6711 using glass rod dosimeters and EGS5 Monte Carlo code in a geometry lacking radiation equilibrium scatter conditions.

PURPOSE: The aim of this study was to develop a dose calculation method which is applicable to the interseed attenuation and the geometry lacking the equilibrium radiation scatter conditions in brachytherapy. METHODS: The dose obtained from measurement with a radiophotoluminescent glass rod dosimeter (GRD) was compared to the dose calculated with the Monte Carlo (MC) code "EGS5," using the 125I source structure detailed in by Kennedy et al. The GRDs were irradiated with 125I Oncoseed 6711 in a human head phantom. The phantom was a cylinder made of 2 mm thick PMMA with a diameter of 18 cm and length of 16 cm. Some of the GRD positions were so close to the phantom surface that the backscatter margin was less than 5 cm, insufficient for photons. RESULTS: The EGS5 simulations were found to reproduce the relative dose distributions as measured with the GRDs to within 25% uncertainty in the geometry lacking the equilibrium radiation scatter conditions. The absolute value of the GRD measurement agreed with the American Association of Physicist in Medicine Task Group No 43 Updated Protocol (AAPM-TG43U1) formalism to within 3% of the reference point (r = 1 cm, theta = 90 degrees), where the TG43U1 is especially reliable because of the abundant data accumulation in composing the formalism. The factor to normalize the measured or calculated dose to the TG43U1 estimate at the reference point was evaluated to be 0.97 for the GRD measurement and 1.8 for the MC calculation, which uses the integration of the apparent activity with the time as the amount of disintegration during the irradiation. Also, F(r,theta) and g(r) estimated by this calculation method were consistent with those proposed in the TG43U1. CONCLUSIONS: The results of this investigation support the validity of both the MC calculation method and GRD measurement in this study as well as the TG-43U1 formalism. Also, this calculation is applicable to interseed attenuation and the geometry lacking the equilibrium radiation scatter.