Verifying the accuracy of self-reported smoking behavior in female volunteer soldiers.

Smoking rates in the military are evaluated through questionnaire surveying. Because the accurate identification of smokers facilitates the provision of smoking cessation services, this study conducted urine cotinine concentration testing to verify the accuracy of self-reported smoking behavior by female volunteer soldiers and analyzed the effects of second-hand smoking on urine cotinine concentrations. This study is a cross-sectional study conducted using purposive sampling on female volunteer soldiers receiving training at the Taichung Recruit Training Center in May 2014. This study simultaneously collected questionnaires and urine samples, and urine samples were analyzed with an enzyme-linked immunosorbent assay. The self-reported smoking rate of female volunteer soldiers was 19.3%, whereas the smoking rate as determined by urine cotinine concentration testing was 26.3%, indicating an overall underestimation of 7.0%. Chi-square (χ2) goodness of fit test results indicated that the distribution of self-reported smoking behaviors and that verified from urine cotinine concentration testing were significantly different. The sensitivity of self-reported smoking behavior was 66.7% with a specificity of 97.6%. There was no significant association between second-hand smoking and urine cotinine concentrations. Questionnaire survey self-reporting methods could underestimate the smoking behavior of female volunteer soldiers and routine testing with biochemical verification is necessary.

Neutron activation survey on patients following BNCT clinical trials at THOR.

In this work neutron activation surveys on 26 patients of recurrent head and neck cancer following boron neutron capture therapy (BNCT) were performed. By means of qualitative neutron activation analysis (NAA), radioactive nuclides activated from neutron capture reaction within patients were identified. The estimated activities of the corresponding radioactive nuclides were achieved based on several assumptions. Gamma-ray dose rate measurements utilizing a survey meter were taken at three chosen distances, namely, 0 cm, 30 cm and 100 cm away from the irradiated region of patients. The variations of gamma-ray dose rate against time were obtained. An approach to estimating the gamma-ray dose rate resulted from each individual radioactive nuclide is also presented.

The overview and prospects of BNCT facility at Tsing Hua Open-pool reactor.

The whole picture of the BNCT facility at Tsing Hua Open-pool Reactor will be presented which consists of the following aspects: the construction project, the beam quality, routine operations including the QA program for the beam delivery, determination of boron-10 concentration in blood, T/N ratio, and the clinical affairs including the patient recruit procedure and the patient irradiation procedure. The facility is positioned to serve for conducting clinical trials, emergent (compassionate) treatments, and R&D works.

Measurement of gamma-ray dose and neutron activation in BNCT beams using TLD-200.

In this work TLD-200 (CaF2:Dy) chips were used to measure the gamma-ray doses in a PMMA phantom exposed to the BNCT beam at Tsing Hua Open-pool Reactor (THOR). The self-irradiation component induced by the decay of Dy-165 was corrected. The neutron dose contamination was less than 0.3%. The Dy content in the TLD-200 chip was determined by using the modified absolute calibration method of NAA. The self-irradiation TL signal was also applied for the in situ calibration.

In-phantom neutron dose measurement using Gafchromic film dosimeter for QA of BNCT beams.

In order to improve the quality assurance (QA) procedure for beams of boron neutron capture therapy (BNCT), this study introduced using the Gafchromic film dosimeter for neutron dose measurement of BNCT beams. The crucial part of this study was investigating an approach to employ the Gafchromic film dosimeter placed inside a PMMA phantom irradiated by a BNCT beam. The spatial distribution of neutron dose of the film was determined using measurements and Monte Carlo calculations. By employing the present approach, the two-dimensional distributions of the neutron dose component of the film at specific depths in the phantom were successfully obtained. The determined neutron dose profiles were in good agreement with the calculated ones. This study also confirmed the finding that the film dosimeter is sensitive to thermal neutrons by comparing the depth-capture-reaction-rate and depth-dose distributions. Results of this work not only proved the feasibility of using the proposed method for the QA measurement of beam delivery but also revealed the advantages of easy-handling and remarkable spatial resolution of the film dosimeter when applied to BNCT fields. The present work can help to verify the dose uniformity and output stability of BNCT beams prior to clinical irradiation.

Clinical trials for treating recurrent head and neck cancer with boron neutron capture therapy using the Tsing-Hua Open Pool Reactor.

Head and neck (HN) cancer is an endemic disease in Taiwan, China. Locally recurrent HN cancer after full-dose irradiation poses a therapeutic challenge, and boron neutron capture therapy (BNCT) may be a solution that could provide durable local control with tolerable toxicity. The Tsing-Hua Open Pool Reactor (THOR) at National Tsing-Hua University in Hsin-Chu, provides a high-quality epithermal neutron source for basic and clinical BNCT research. Our first clinical trial, entitled "A phase I/II trial of boron neutron capture therapy for recurrent head and neck cancer at THOR", was carried out between 2010 and 2013. A total of 17 patients with 23 recurrent HN tumors who had received high-dose photon irradiation were enrolled in the study. The fructose complex of L-boronophenylalanine was used as a boron carrier, and a two-fraction BNCT treatment regimen at 28-day intervals was used for each patient. Toxicity was acceptable, and although the response rate was high (12/17), re-recurrence within or near the radiation site was common. To obtain better local control, another clinical trial entitled "A phase I/II trial of boron neutron capture therapy combined with image-guided intensity-modulated radiotherapy (IG-IMRT) for locally recurrent HN cancer" was initiated in 2014. The first administration of BNCT was performed according to our previous protocol, and IG-IMRT was initiated 28 days after BNCT. As of May 2017, seven patients have been treated with this combination. The treatment-related toxicity was similar to that previously observed with two BNCT applications. Three patients had a complete response, but locoregional recurrence was the major cause of failure despite initially good responses. Future clinical trials combining BNCT with other local or systemic treatments will be carried out for recurrent HN cancer patients at THOR.

QA measurement of gamma-ray dose and neutron activation using TLD-400 for BNCT beam.

TLD-400 (CaF2:Mn) chips were applied for the gamma-ray dose measurement in a PMMA phantom exposed to a BNCT beam because of their very low neutron sensitivity. Since TLD-400 chips possess an adequate amount of Mn activator they have been employed in this work simultaneously for neuron activation measurement. The self-irradiation TL signals owing to the decay of the neutron induced 56Mn activity have been applied for a calibration of the TLD-400 chip in situ, where the activities were measured by an HPGe detector system and the energy deposition per disintegration of 56Mn was calculated by applying a Monte Carlo code. It was accidentally found that the irradiated TLD-400 chips were capable of emitting prominent scintillation lights owing to the induced 56Mn activity, which can easily be recorded by the TLD reader without heating and after a calibration can be used to determine the 56Mn activity.

Validation of Self-reported Smoking with Urinary Cotinine Levels and Influence of Second-hand Smoke among Conscripts.

Accurate identification of smoking behaviour is crucial to monitor the smoking rate. This study used urinary cotinine (UC) as a biomarker to verify the effectiveness of self-reported smoking behaviour among conscripts during recruit training. The influence of second-hand smoke (SHS) on the UC concentration was also analysed. A cross-sectional study was conducted from July 2014 to December 2014. The participants comprised a total of 621 military service and basic military training conscripts. A self-administered questionnaire survey and a urine test were performed to verify the participants' smoking behaviour. The UC concentration of 100 ng/mL was adopted as the baseline to identify smokers. A high level of consistency was observed between the conscripts' self-reported results and the results validated by the UC concentrations (the overall kappa coefficient was 0.918). Moreover, the overall sensitivity and specificity were 92.9% and 98.1%, respectively. The sensitivity for the military service conscripts was significantly lower than that for the basic military training conscripts (86.1% vs. 97.5%, P-value = 0.002). For the self-reported nonsmokers among the military service conscripts, SHS exposure was related to their UC concentrations. The method of self-reporting through a questionnaire survey can serve as a tool to assess conscripts' smoking behaviour.

Dose Conversion Coefficients Based on Taiwanese Reference Phantoms and Monte Carlo Simulations for Use in External Radiation Protection.

Reference phantoms are widely applied to evaluate the radiation dose for external exposure. However, the frequently used reference phantoms are based on Caucasians. Dose estimation for Asians using a Caucasian phantom can result in significant errors. This study recruited 40 volunteers whose body sizes are close to the average Taiwanese population. Magnetic resonance imaging was performed to obtain the organ volume for construction of the Taiwanese reference man (TRM) and Taiwanese reference woman (TRW). The dose conversion coefficients (DCC) resulting from photo beams in anterior-posterior, posterior-anterior, right-lateral, left-lateral, and isotropic irradiation geometries were estimated. In the anterior-posterior geometry, the mean DCC differences among organs between the TRM and ORNL phantom at 0.1, 1, and 10 MeV were 7.3%, 5.8%, and 5.2%, respectively. For the TRW, the mean differences from the ORNL phantom at the three energies were 10.6%, 7.4%, and 8.3%. The DCCs of the Taiwanese reference phantoms and the ORNL phantom presented similar trends in other geometries. The torso size of the phantom and the mass and geometric location of the organ have a significant influence on the DCC. The Taiwanese reference phantoms can be used to establish dose guidelines and regulations for radiation protection from external exposure.

Construction of Taiwanese Adult Reference Phantoms for Internal Dose Evaluation.

In the internal dose evaluation, the specific absorbed fraction (SAF) and S-value are calculated from the reference phantom based on Caucasian data. The differences in height and weight between Caucasian and Asian may lead to inaccurate dose estimation. In this study, we developed the Taiwanese reference phantoms. 40 volunteers were recruited. Magnetic resonance images (MRI) were obtained, and the contours of 15 organs were drawn. The Taiwanese reference man (TRM) and Taiwanese reference woman (TRW) were constructed. For the SAF calculation, the differences in the self-absorption SAF (self-SAF) between the TRM, TRW, and Oak Ridge National Laboratory (ORNL) adult phantom were less than 10% when the difference in organ mass was less than 20%. The average SAF from liver to pancreas of TRM was 38% larger than that of the ORNL adult phantom, and the result of TRW was 2.02 times higher than that of the ORNL adult phantom. For the S-value calculation, the ratios of TRW and ORNL adult phantom ranged from 0.91 to 1.57, and the ratios of TRM and ORNL adult phantom ranged from 1.04 to 2.29. The SAF and S-value results were dominantly affected by the height, weight, organ mass, and geometric relationship between organs. By using the TRM and TRW, the accuracy of internal dose evaluation can be increased for radiation protection and nuclear medicine.

Fractionated Boron Neutron Capture Therapy in Locally Recurrent Head and Neck Cancer: A Prospective Phase I/II Trial.

PURPOSE: To investigate the efficacy and safety of fractionated boron neutron capture therapy (BNCT) for recurrent head and neck (H&N) cancer after photon radiation therapy. METHODS AND MATERIALS: In this prospective phase 1/2 trial, 2-fraction BNCT with intravenous L-boronophenylalanine (L-BPA, 400 mg/kg) was administered at a 28-day interval. Before each fraction, fluorine-18-labeled-BPA-positron emission tomography was conducted to determine the tumor/normal tissue ratio of an individual tumor. The prescription dose (D80) of 20 Gy-Eq per fraction was selected to cover 80% of the gross tumor volume by using a dose volume histogram, while minimizing the volume of oral mucosa receiving >10 Gy-Eq. Tumor responses and adverse effects were assessed using the Response Evaluation Criteria in Solid Tumors v1.1 and the Common Terminology Criteria for Adverse Events v3.0, respectively. RESULTS: Seventeen patients with a previous cumulative radiation dose of 63-165 Gy were enrolled. All but 2 participants received 2 fractions of BNCT. The median tumor/normal tissue ratio was 3.4 for the first fraction and 2.5 for the second, whereas the median D80 for the first and second fraction was 19.8 and 14.6 Gy-Eq, respectively. After a median follow-up period of 19.7 months (range, 5.2-52 mo), 6 participants exhibited a complete response and 6 exhibited a partial response. Regarding acute toxicity, 5 participants showed grade 3 mucositis and 1 participant showed grade 4 laryngeal edema and carotid hemorrhage. Regarding late toxicity, 2 participants exhibited grade 3 cranial neuropathy. Four of six participants (67%) receiving total D80 > 40 Gy-Eq had a complete response. Two-year overall survival was 47%. Two-year locoregional control was 28%. CONCLUSIONS: Our results suggested that 2-fraction BNCT with adaptive dose prescription was effective and safe in locally recurrent H&N cancer. Modifications to our protocol may yield more satisfactory results in the future.

Demonstration of the importance of a dedicated neutron beam monitoring system for BNCT facility.

The neutron beam monitoring system is indispensable to BNCT facility in order to achieve an accurate patient dose delivery. The neutron beam monitoring of a reactor-based BNCT (RB-BNCT) facility can be implemented through the instrumentation and control system of a reactor provided that the reactor power level remains constant during reactor operation. However, since the neutron flux in reactor core is highly correlative to complicated reactor kinetics resulting from such as fuel depletion, poison production, and control blade movement, some extent of variation may occur in the spatial distribution of neutron flux in reactor core. Therefore, a dedicated neutron beam monitoring system is needed to be installed in the vicinity of the beam path close to the beam exit of the RB-BNCT facility, where it can measure the BNCT beam intensity as closely as possible and be free from the influence of the objects present around the beam exit. In this study, in order to demonstrate the importance of a dedicated BNCT neutron beam monitoring system, the signals originating from the two in-core neutron detectors installed at THOR were extracted and compared with the three dedicated neutron beam monitors of the THOR BNCT facility. The correlation of the readings between the in-core neutron detectors and the BNCT neutron beam monitors was established to evaluate the improvable quality of the beam intensity measurement inferred by the in-core neutron detectors. In 29 sampled intervals within 16 days of measurement, the fluctuations in the mean value of the normalized ratios between readings of the three BNCT neutron beam monitors lay within 0.2%. However, the normalized ratios of readings of the two in-core neutron detectors to one of the BNCT neutron beam monitors show great fluctuations of 5.9% and 17.5%, respectively.

Are high energy proton beams ideal for AB-BNCT? A brief discussion from the viewpoint of fast neutron contamination control.

High energy proton beam (>8MeV) is favorable for producing neutrons with high yield. However, the produced neutrons are of high energies. These high energy neutrons can cause severe fast neutron contamination and degrade the BNCT treatment quality if they are not appropriately moderated. Hence, this study aims to briefly discuss the issue, from the viewpoint of fast neutron contamination control, whether high energy proton beam is ideal for AB-BNCT or not. In this study, D2O, PbF4, CaF2, and Fluental(™) were used standalone as moderator materials to slow down 1-, 6-, and 10-MeV parallelly incident neutrons. From the calculated results, we concluded that neutrons produced by high energy proton beam could not be easily moderated by a single moderator to an acceptable contamination level and still with reasonable epithermal neutron beam intensity. Hence, much more complicated and sophisticated designs of beam shaping assembly have to be developed when using high energy proton beams.

Dose estimation of animal experiments at the THOR BNCT beam by NCTPlan and Xplan.

Dose estimation of animal experiments affects many subsequent derived quantities, such as RBE and CBE values. It is important to ensure the trustiness of calculated dose of the irradiated animals. However, the dose estimation was normally calculated using simplified geometries and tissue compositions, which led to rough results. This paper introduces the use of treatment planning systems NCTplan and Xplan for the dose estimation. A mouse was taken as an example and it was brought to hospital for micro-PET/CT scan. It was found that the critical organ doses of an irradiated mouse calculated by simplified model were unreliable in comparison to Xplan voxel model. The difference could reach the extent of several tenths percent. It is recommended that a treatment planning system should be introduced to future animal experiments to upgrade the data quality.

Cosmic-ray neutron simulations and measurements in Taiwan.

This study used simulations of galactic cosmic ray in the atmosphere to investigate the neutron background environment in Taiwan, emphasising its altitude dependence and spectrum variation near interfaces. The calculated results were analysed and compared with two measurements. The first measurement was a mobile neutron survey from sea level up to 3275 m in altitude conducted using a car-mounted high-sensitivity neutron detector. The second was a previous measured result focusing on the changes in neutron spectra near air/ground and air/water interfaces. The attenuation length of cosmic-ray neutrons in the lower atmosphere was estimated to be 163 g cm(-2) in Taiwan. Cosmic-ray neutron spectra vary with altitude and especially near interfaces. The determined spectra near the air/ground and air/water interfaces agree well with measurements for neutrons below 10 MeV. However, the high-energy portion of spectra was observed to be much higher than our previous estimation. Because high-energy neutrons contribute substantially to a dose evaluation, revising the annual sea-level effective dose from cosmic-ray neutrons at ground level in Taiwan to 35 µSv, which corresponds to a neutron flux of 5.30 × 10(-3) n cm(-2) s(-1), was suggested.

Dosimetric performance evaluation regarding proton beam incident angles of a lithium-based AB-BNCT design.

The (7)Li(p,xn)(7)Be nuclear reaction, based on the low-energy protons, could produce soft neutrons for accelerator-based boron neutron capture therapy (AB-BNCT). Based on the fact that the induced neutron field is relatively divergent, the relationship between the incident angle of proton beam and the neutron beam quality was evaluated in this study. To provide an intense epithermal neutron beam, a beam-shaping assembly (BSA) was designed. And a modified Snyder head phantom was used in the calculations for evaluating the dosimetric performance. From the calculated results, the intensity of epithermal neutrons increased with the increase in proton incident angle. Hence, either the irradiation time or the required proton current can be reduced. When the incident angle of 2.5-MeV proton beam is 120°, the required proton current is ∼13.3 mA for an irradiation time of half an hour.

Effective dose evaluation for BNCT brain tumor treatment based on voxel phantoms.

For BNCT treatments, in addition to tumor target doses, non-negligible doses will result in all the remaining organs of the body. This work aims to evaluate the effective dose as well as the average absorbed doses of each of organs of patients with brain tumor treated in the BNCT epithermal neutron beam at THOR. The effective doses were evaluated according to the definitions of ICRP Publications 60 and 103 for the reference male and female computational phantoms developed in ICRP Publication 110 by using the MCNP5 Monte Carlo code with the THOR-Y09 beam source. The effective dose acquired in this work was compared with the results of our previous work calculated for an adult hermaphrodite mathematical phantom. It was found that the effective dose for the female voxel phantom is larger than that for the male voxel phantom by a factor of 1.2-1.5 and the effective dose for the voxel phantom is larger than that for the mathematical phantom by a factor of 1.3-1.6. For a typical brain tumor BNCT, the effective dose was calculated to be 1.51Sv and the average absorbed dose for eye lenses was 1.07Gy.

Computational study of room scattering influence in the THOR BNCT treatment room.

BNCT dosimetry has often employed heavy Monte Carlo calculations for the beam characterization and the dose determination. However, these calculations commonly ignored the scattering influence between the radiations and the room structure materials in order to facilitate the calculation speed. The aim of this article attempts to explore how the room scattering affects the physical quantities such as the capture reaction rate and the gamma-ray dose rate under in-phantom and free-air conditions in the THOR BNCT treatment room. The geometry and structure materials of the treatment room were simulated in detail. The capture reaction rates per atom, as well as the gamma-ray dose rate were calculated in various sizes of phantoms and in the free-air condition. Results of this study showed that the room scattering has significant influence on the physical quantities, whether in small phantoms or in the free-air condition. This paper may be of importance in explaining the discrepancies between measurements and calculations in the BNCT dosimetry using small phantoms, in addition to provide a useful consideration with a better understanding of how the room scattering influence acts in a BNCT facility.

Fractionated BNCT for locally recurrent head and neck cancer: experience from a phase I/II clinical trial at Tsing Hua Open-Pool Reactor.

To introduce our experience of treating locally and regionally recurrent head and neck cancer patients with BNCT at Tsing Hua Open-Pool Reactor in Taiwan, 12 patients (M/F=10/2, median age 55.5 Y/O) were enrolled and 11 received two fractions of treatment. Fractionated BNCT at 30-day interval with adaptive planning according to changed T/N ratios was feasible, effective and safe for selected recurrent head and neck cancer in this trial.