Analysis of source dwell position during treatment in brachytherapy using CT scout images.

Purpose: Several cases of inaccurate irradiation in brachytherapy have been reported, occurring similarly to external radiation. Due to a large dose per fraction in brachytherapy, inaccurate irradiation can seriously harm a patient. Although various studies have been conducted, systems that detect inaccurate irradiation in brachytherapy are not as developed as those for external irradiation. This study aimed to construct a system that analyzes the source dwell position during irradiation using computed tomography (CT) scout images. The novelty of the study was that by using CT scout images, high versatility and analysis of absolute coordinates can be achieved. Material and methods: A treatment plan was designed with an iridium-192 (192Ir) source delivering radiation at two dwell positions in a tandem applicator. CT scout images were taken during irradiation, and acquired under different imaging conditions and applicator geometries. First, we confirmed whether a source was visible in CT scout images. Then, employing in-house MATLAB program, source dwell coordinates were analyzed using the images. An analysis was considered adequate when the resulting source dwell coordinates agreed with the treatment plan within ±1 mm, in accordance with AAPM TG56 guidelines for source dwell position accuracy. Results: The source dwelling was visible in CT scout image, which was enlarged or reduced depending on applicator geometries. The applicator was enlarged by 127% when 130 mm away from the center of CT gantry. The analysis results using our in-house program were considered adequate; although, analysis parameters required adjustments depending on imaging conditions. Conclusions: The proposed system can be easily implemented for image-guided brachytherapy and can analyze the absolute coordinates of source dwell position. Therefore, the system could be used for preventing inaccurate irradiation by verifying whether brachytherapy was performed properly.

Counting Distinguishable RNA Secondary Structures.

RNA secondary structures are essential abstractions for understanding spacial folding behaviors of those macromolecules. Many secondary structure algorithms involve a common dynamic programming setup to exploit the property that secondary structures can be decomposed into substructures. Dirks et al. noted that this setup cannot directly address an issue of distinguishability among secondary structures, which arises for classes of sequences that admit nontrivial symmetry. Circular sequences are among these. We examine the problem of counting distinguishable secondary structures. Drawing from elementary results in group theory, we identify useful subsets of secondary structures. We then extend an algorithm due to Hofacker et al. for computing the sizes of these subsets. This yields a cubic-time algorithm to count distinguishable structures compatible with a given circular sequence. Furthermore, this general approach may be used to solve similar problems for which the RNA structures of interest involve symmetries.

Multi-Institutional Study of End-to-End Dose Delivery Quality Assurance Testing for Image-Guided Brachytherapy Using a Gel Dosimeter.

PURPOSE: To quantify dose delivery errors for high-dose-rate image-guided brachytherapy (HDR-IGBT) using an independent end-to-end dose delivery quality assurance test at multiple institutions. The novelty of our study is that this is the first multi-institutional end-to-end dose delivery study in the world. MATERIALS AND METHODS: The postal audit used a polymer gel dosimeter in a cylindrical acrylic container for the afterloading system. Image acquisition using computed tomography, treatment planning, and irradiation were performed at each institution. Dose distribution comparison between the plan and gel measurement was performed. The percentage of pixels satisfying the absolute-dose gamma criterion was reviewed. RESULTS: Thirty-five institutions participated in this study. The dose uncertainty was 3.6% ± 2.3% (mean ± 1.96σ). The geometric uncertainty with a coverage factor of k = 2 was 3.5 mm. The tolerance level was set to the gamma passing rate of 95% with the agreement criterion of 5% (global)/3 mm, which was determined from the uncertainty estimation. The percentage of pixels satisfying the gamma criterion was 90.4% ± 32.2% (mean ± 1.96σ). Sixty-six percent (23/35) of the institutions passed the verification. Of the institutions that failed the verification, 75% (9/12) had incorrect inputs of the offset between the catheter tip and indexer length in treatment planning and 17% (2/12) had incorrect catheter reconstruction in treatment planning. CONCLUSIONS: The methodology should be useful for comprehensively checking the accuracy of HDR-IGBT dose delivery and credentialing clinical studies. The results of our study highlight the high risk of large source positional errors while delivering dose for HDR-IGBT in clinical practices.

Development of a broad band AC power amplifier for real time turbulence feedback control experiment in the Saskatchewan Torus-modified (STOR-M) tokamak.

A gated oscillating power amplifier has been developed for high frequency biasing and real time turbulent feedback experiments in the Saskatchewan Torus-modified tokamak. This oscillator is capable of providing a peak to peak oscillating output voltage of around ±60 V with a current around 30 A within the frequency band 1 kHz-50 kHz without any distortions. The overall output power is amplified by a two-stage metal oxide semiconductor field-effect transistor power op-amp as well as nine identical push-pull amplifiers in the final stages. The power amplifier input signal, collected from the plasma floating potential during the tokamak discharge, is optically isolated from the tokamak vessel ground. The filtered floating potential fluctuations with a band width of 5 kHz-40 kHz were amplified and fed to an electrode inserted into the plasma edge to study the response of the plasma turbulence. We observe that magnetic fluctuations are suppressed due to real time feedback of the floating potential.

Impact of visual feedback on dose-volume histograms for organs at risk in postoperative radiotherapy with deep inspiration breath-holding for patients treated with breast-conserving therapy: a planning study.

BACKGROUND: We evaluated the effectiveness of visual feedback (VF) on radiotherapy with deep inspiration breath-holding (DIBH), and reviewed the dose for organs at risk (OARs). METHODS: Respiratory motions during DIBH for 15 s were monitored during planning computed tomography (CT)-scanning and simulation for 40 patients after breast-conserving surgery from June 2007 to February 2008. For 22 of 40 patients, a goggle-type liquid crystal display monitor was used for VF. The opposing tangential field was planned. The prescribed dose was 50.0 Gy in 25 fractions. RESULTS: The mean differences of the chest wall respiratory movement in DIBH between planning CT-scanning and simulation were 4.7 ± 2.6 mm for the patients without VF and 1.0 ± 0.9 mm for those with VF (p < 0.01). The mean chest wall excursion as a whole in DIBH using VF (2.0 ± 1.0 mm) was smaller than in those without VF (4.1 ± 2.4 mm) (p < 0.01). According to reproducibility and stability parameters, 4 mm was added as a posterior margin to the clinical target volume for RT with VF, and 10 mm for those without VF. The mean heart doses were 1.3 ± 0.5 Gy with VF and 2.4 ± 1.1 Gy without VF (p < 0.01). Mean dose and max dose of right breast were significantly reduced in procedures with VF use vs. in those without VF (p < 0.01 and < 0.01, respectively). CONCLUSIONS: VF increases the accuracy of postoperative radiotherapy with DIBH, and also helps reduce the dose for OARs.

Incidence of organizing pneumonia after whole-breast radiotherapy for breast cancer, and risk factor analysis.

Radiation-induced organizing pneumonia (OP) reportedly occurs in ~2% of patients who receive whole-breast radiotherapy (WBRT). Though there are several reported risk factors, they remain unclear and controversial. We analyzed the incidence of and risk factors for OP after WBRT at our institution. We analyzed 665 breast cancer patients (with WBRT of 679 breasts) who underwent WBRT from October 2007 to September 2012 at our institution and were followed up for more than 1 year after completion of WBRT. Factors included in the analysis were age, the side affected, central lung distance (CLD), radiation dose, concurrent endocrine therapy, and chemotherapy. The median age was 56 years (range, 23-89 years). The sides affected were left, right and bilateral in 342, 309 and 14 patients, respectively. The median CLD was 1.1 cm (range, 0-3.0 cm). Concurrent endocrine therapy was performed in 236 patients, and chemotherapy was given in 215 patients; of these, 4 received concurrent chemotherapy. OP developed in nine patients (1.4%). The median time taken to develop OP after the completion of WBRT was 4 months (range, 2-12 months). All nine patients were treated with steroids, and symptoms promptly improved, except in two patients who relapsed. Statistical analysis revealed that only CLD (≥1.5 cm) was significantly associated with the development of OP (P = 0.004). In conclusion, the incidence of OP after WBRT was 1.4%, and CLD was a significant risk factor. In these patients, OP was controlled with steroid administration.

[Optimal parameter decision method in VMAT for lung tumors with respiratory motions].

When performing lung cancer treatments using volumetric modulated arc therapy (VMAT) technique, dose error related to respiratory motion of tumors and multi leaf collimator (MLC) movement may occur. The dose error causes daily dose variation in multiple fractionations irradiation. The purpose of this study is to verify the influence of the respiratory motion and the MLC movement on the daily dose variation, and to confirm the feasibility of deciding robust planning parameter against the dose variation. We prepared 5 VMAT plans for imitating lung tumor in thorax dynamic phantom. Dose calculations of these plans were done taking into account the respiratory motions. We examined the relation between dose variation and two parameters that were number of respiration in an arc and MLC gap width. We presented the relationship between the dose variation and each parameters using regression analysis, and we could derive the approximation formula for estimating the dose variation using these parameters. We could estimate dose variation in another VMAT plans using the approximation formula and another plans parameters. By confirming dose variation in planning procedure using this estimation method, we may decide planning parameter taking the dose variation into account. So, we could establish the estimation method to decide adequate planning parameters in VMAT.

Incidence of leukoencephalopathy after whole-brain radiation therapy for brain metastases.

PURPOSE: To evaluate the incidence of leukoencephalopathy after whole-brain radiation therapy (WBRT) in patients with brain metastases. METHODS AND MATERIALS: We retrospectively reviewed 111 patients who underwent WBRT for brain metastases from April 2001 through March 2008 and had evaluable computed tomography (CT) and/or magnetic resonance imaging (MRI) at least 1 month after completion of WBRT. We evaluated the leukoencephalopathy according to the Common Terminology Criteria for Adverse Events, version 3.0. The patients who had brain tumor recurrence after WBRT were censored at the last follow-up CT or MRI without recurrence. To evaluate the risk factors for leukoencephalopathy, bivariate analysis was performed using a logistic regression analysis adjusted for follow-up time. Factors included in the analysis were age, gender, dose fractionation, 5-fluorouracil, methotrexate, cisplatin, and other chemotherapeutic agents. RESULTS: The median age of the 111 patients was 60.0 years (range, 23-89 years). The median follow-up was 3.8 months (range, 1.0-38.1 months). Leukoencephalopathy developed in 23 of the 111 patients. Grades 1, 2, and 3 were observed in 8, 7, and 8 patients, respectively. The incidence was 34.4% (11 of 32), 42.9% (6 of 14), 66.7% (2 of 3), and 100% (2 of 2) of the patients who were followed up for ≥6, ≥12, ≥24, and ≥36 months, respectively. In the bivariate analysis, older age (≥65 years) was significantly correlated with higher risk of leukoencephalopathy (odds ratio 3.31; 95% confidence interval 1.15-9.50; P=.03). CONCLUSIONS: The incidence of leukoencephalopathy after WBRT was 34.4% with ≥6 months follow-up, and increased with longer follow-up. Older age was a significant risk factor. The schedule of WBRT for patients with brain metastases should be carefully determined, especially for favorable patients.

Management of the baseline shift using a new and simple method for respiratory-gated radiation therapy: detectability and effectiveness of a flexible monitoring system.

PURPOSE: In respiratory-gated radiation therapy, a baseline shift decreases the accuracy of target coverage and organs at risk (OAR) sparing. The effectiveness of audio-feedback and audio-visual feedback in correcting the baseline shift in the breathing pattern of the patient has been demonstrated previously. However, the baseline shift derived from the intrafraction motion of the patient's body cannot be corrected by these methods. In the present study, the authors designed and developed a simple and flexible system. METHODS: The system consisted of a web camera and a computer running our in-house software. The in-house software was adapted to template matching and also to no preimage processing. The system was capable of monitoring the baseline shift in the intrafraction motion of the patient's body. Another marker box was used to monitor the baseline shift due to the flexible setups required of a marker box for gated signals. The system accuracy was evaluated by employing a respiratory motion phantom and was found to be within AAPM Task Group 142 tolerance (positional accuracy <2 mm and temporal accuracy <100 ms) for respiratory-gated radiation therapy. Additionally, the effectiveness of this flexible and independent system in gated treatment was investigated in healthy volunteers, in terms of the results from the differences in the baseline shift detectable between the marker positions, which the authors evaluated statistically. RESULTS: The movement of the marker on the sternum [1.599 +/- 0.622 mm (1 SD)] was substantially decreased as compared with the abdomen [6.547 +/- 0.962 mm (1 SD)]. Additionally, in all of the volunteers, the baseline shifts for the sternum [-0.136 +/- 0.868 (2 SD)] were in better agreement with the nominal baseline shifts than was the case for the abdomen [-0.722 +/- 1.56 mm (2 SD)]. The baseline shifts could be accurately measured and detected using the monitoring system, which could acquire the movement of the marker on the sternum. The baseline shift-monitoring system with the displacement-based methods for highly accurate respiratory-gated treatments should be used to make most of the displacement-based gating methods. CONCLUSIONS: The advent of intensity modulated radiation therapy and volumetric modulated radiation therapy facilitates margin reduction for the planning target volumes and the OARs, but highly accurate irradiation is needed to achieve target coverage and OAR sparing with a small margin. The baseline shifts can affect treatment not only with the respiratory gating system but also without the system. Our system can manage the baseline shift and also enables treatment irradiation to be undertaken with high accuracy.

Causes of photopenic defects in the lower sternum on bone scintigraphy and correlation with multidetector CT.

PURPOSE: To determine the cause of this photopenia in the lower sternum on bone scintigraphy and its correlation with sternal foramen on multidetector computed tomography (MDCT). METHODS: Between January and December 2008, we studied 1053 patients who underwent bone scintigraphy and CT scanning that included the chest. Bone scintigraphy showed photopenic areas in the lower sternum in 58 of these 1053 patients. The study population consisted of 19 men and 37 women, aged from 15 to 87 years (mean: 60.4 years). RESULTS: Of the 58 patients with photopenic areas in the lower sternum, 25 (43%) showed a sternal foramen by MDCT, whereas 33 patients (57%) showed no sternal foramen. However, of the total study population of 1053 patients, MDCT showed sternal foramen in 33 patients (3.1%). In 7 of the 33 patients with sternal foramen by MDCT, bone scintigraphy showed no photopenic areas. On the basis of CT morphometry of the sternum, the possible causes of photopenia in the lower sternum in patients without sternal foramen are as follows: thin middle portion of sternum bone marrow, a focal defect or notch in the posterior sternal cortex, high accumulation of peripheral lesions, and bone metastasis. CONCLUSION: This study revealed that not all patients showing photopenic areas in the lower sternum have sternal foramen and not all patients with sternal foramen show photopenic areas by bone scintigraphy. It is important to exclude metastasis when photopenic areas are detected, and inform the clinician to avoid the serious complication of cardiac tamponade.

Increased anticoagulant activity of warfarin used in combination with doxifluridine.

PURPOSE: The purpose of this article is to report the first case of markedly increased anticoagulant activity of warfarin when used in combination with doxifluridine, given as a replacement for capecitabine. METHODS: International normalized ratio (INR) of a 73-year-old female patient receiving warfarin was increased after starting chemotherapy using oral fluoropyrimidines (capecitabine or doxifluridine). Since the concomitant use of warfarin and the oral fluoropyrimidines was unavoidable in this case, the warfarin dosage was adjusted to keep INR within goal range (1.7-2.7). To evaluate the effects of the oral fluoropyrimidines on the anticoagulant activity of warfarin, the INR/Dose (warfarin dose in mg/day) was used. RESULTS: To keep INR within goal range, the maintenance dosage of warfarin was reduced during the treatment with doxifluridine as well as capecitabine. It was finally reduced from 5 mg daily in the absence of oral fluoropyrimidines to 1.5 mg daily during the concomitant use of doxifluridine (600 mg daily). In contrast, the higher INR/Dose (1.03-1.66) was continued during the concomitant use of warfarin and doxifluridine compared with the INR/Dose before the start of chemotherapy (about 0.5). These results clearly indicate that the anticoagulant activity of warfarin was markedly increased by the concomitant use of doxifluridine as well as capecitabine. CONCLUSIONS: It is important that physicians closely monitor anticoagulant activity in patients concomitantly receiving doxifluridine and warfarin, and appropriately adjust the dose of warfarin.

Cardiac-sparing radiotherapy for the left breast cancer with deep breath-holding.

PURPOSE: The aim of this study was to evaluate the effect of decreasing the irradiated cardiac volume in breast-conserving therapy (BCT) using breath-adapted radiation therapy (BART). MATERIALS AND METHODS: The radiation therapy (RT)-computed tomography (CT) of 21 patients with left breast cancer during free breathing (FB), end-inspiration gating (IG) with audio-prompting, and deep inspiration breath-hold (DIBH) were subjected to BART planning analysis. Respiratory movement was monitored during CT scanning with the respiratory-gating system. The opposing tangential fields were planned for each respiratory-gated CT. The dose-volume histograms (DVHs) of the heart, lung, and breast of each respiratory phase were compared. RESULTS: The median respiratory movement of the right chest wall was 5.6 mm with FB CT, 10.9 mm with audioprompting CT, and 21.3 mm from end-inspiration to DIBH. The median left ventricular volume receiving >50% of the prescribed dose was 2.9% for FB, 0.2% for IG, and 0% for DIBH. DIBH led to significant cardiac spattering effect compared with FB or IG (P < 0.01). The median lung volume receiving 20 Gy or more was 5.0% for FB, 4.7% for IG, and 4.3% for DIBH. There were no significant differences between each respiratory phase. CONCLUSION: We concluded that radiotherapy on the DIBH facilitates a reduction of the irradiated heart volume compared to FB and IG.

Possible application of flow cytometry for evaluation of the structure and functional status of WASP in peripheral blood mononuclear cells.

The Wiskott-Aldrich syndrome protein (WASP), which is defective in Wiskott-Aldrich syndrome (WAS) patients, is an intracellular protein expressed in non-erythroid hematopoietic cells. Previously, we have established methods to detect intracellular WASP expression in peripheral blood mononuclear cells (PBMNCs) using flow cytometric analysis (FCM-WASP) and have revealed that WAS patients showed absent or very low level intracellular WASP expression in lymphocytes and monocytes, while a significant amount of WASP was detected in those of normal individuals. We applied these methods for diagnostic screening of WAS patients and WAS carriers, as well as to the evaluation of mixed chimera in WAS patients who had previously undergone hematopoietic stem cell transplantation. During these procedures, we have noticed that lymphocytes from normal control individuals showed dual positive peaks, while their monocytes invariably showed a single sharp WASP-positive peak. To investigate the basis of the dual positive peaks (WASP(low-bright) and WASP(high-bright)), we characterized the constituent linage lymphocytes of these two WASP-positive populations. As a result, we found each WASP(low/high) population comprised different linage PBMNCs. Furthermore, we propose that the difference between the two WASP-positive peaks did not result from any difference in WASP expression in the cells, but rather from a difference in the structural and functional status of the WASP protein in the cells. It has been shown that WASP may exist in two forms; an activated or inactivated form. Thus, the structural and functional WASP status or configuration could be evaluated by flow cytometric analysis.

[Examination of formula for enhanced dynamic wedge factors in symmetric and asymmetric fields].

We proposed a formula for the enhanced dynamic wedge (EDW) factor in the half-field (HF) that combined the formula proposed by Liu et al. in 1998 and their formula in 2003. When the EDW was used for irradiation to the tangent line of the HF breast, the values calculated by our formula and the measured values were consistent within 0.5%. We showed that our proposed formula was useful, easy to use, and more accurate than the conventional formula. The purpose of this study was to examine the available range of the wedge factor of symmetrical and asymmetric EDW calculated by our formula. As a result of the examination, the values calculated by our formula and the measured values were consistent within 2% except for highly asymmetric EDW. We created a spreadsheet to calculate the wedge factor easily and accurately. We will examine the reason why the calculated and measured values were greater than 2%, and improve our formula so that it can be used in a wider range.

[Polarity effects of commercial plane-parallel ionization chamber in therapeutic electron dosimetry-Results with C-134A ionization chamber.].

Plane-parallel ionization chambers that exhibit polar effects with low energy electron beams are recommended for therapeutic electron dosimetry. In this study, the polarity effects of a C-134A ionization chamber, a major commercially available plane-parallel ionization chamber in Japan, were characterized as a function of mean energy at various depths. Polarity effects were measured at representative depths along depth dose curves of nominal 4, 6, 9, 12 and 15 MeV electron beams, and were compared with previously reported results. Polarity errors for the ionization chamber studied were shown to monotonically increase with decreasing mean energy at a given depth and were maximal at about 1-2 MeV. It was also shown that polarity errors depended on the energy of the incident electron beam. The polarity error of the C-134A ionization chamber was larger than that of other previously investigated plane-parallel ionization chambers. Because the magnitude of polarity effects should be determined throughout the depth dose curve in therapeutic electron dosimetry, it is always necessary to measure ionization readings taken at both polarities.

[Absorbed dose measurement of photon beam with Farmer-type ionization chambers in Japanese dosimetry protocols].

The Japan Society of Medical Physics (JSMP) has published a new dosimetry protocol "JSMP-01" (standard dosimetry of absorbed dose in external beam radiotherapy) which conforms to the recommendations of the International Atomic Energy Agency (IAEA TRS-398) and the American Association of Physicists in Medicine (AAPM TG-51) protocols for the calibration of radiotherapy beams. Since the new protocol offers the physical data for the Famer-type ionization chambers of the various wall materials, the user can measure the absorbed dose at reference point (D(r)) using most of the commercially available Famer-type ionization chambers. In this paper, the six Famer-type ionization chambers of the various wall materials are examined for photon beam by two ways. To verify the JSMP-01 protocol as the first way, D(r) was cross-measured based on the JSMP-01 protocol using a Farmer-type ionization chamber of the acrylic wall material which is called "JARP-chamber" and the Farmer-type ionization chambers of the various wall materials, and compared. To compare the basic data in previous and new protocols as the second way, D(r) was measured based on the previous protocol (JSMP-86) and the JSMP-01 protocol using the Farmer-type ionization chambers of the various wall materials. Dose calculation was made using common exposure calibration factor for (60)Co gamma-rays (Nc) for each of the Farmer-type ionization chambers. Measurement was made with each ionization chamber for 6 and 10 MV photon beams in two facilities. D(r) were found to agree to that of JARP-chamber within about +/- 1% despite significant differences of ratio of calibration factor (k(D,X)) and beam quality conversion factor (k(Q)) for photon beams. The ratios JSMP-01/JSMP-86 of the reference dose were found to lie on between 0.999 and 1.004 for 6 MV and on between 0.999 and 1.005 for 10 MV depending upon the Farmer-type ionization chambers used. The largest discrepancies between the previous and new protocols arise from the use of different data of k(D,x) x k(Q) and C(lambda) for the absorbed dose conversion factors of each ionization chamber.

Confirming or excluding the diagnosis of Wiskott-Aldrich syndrome in children with thrombocytopenia of an unknown etiology.

Early diagnosis is an important factor in a better prognosis in patients with Wiskott-Aldrich syndrome (WAS), but it is not always easy to distinguish between WAS and immune thrombocytopenic purpura on clinical grounds. To confirm or to exclude a WAS diagnosis promptly for children with thrombocytopenia, the authors performed flow cytometric screening of Wiskott-Aldrich syndrome protein (WASP) for 10 children with thrombocytopenia of an unknown etiology. Five children were diagnosed with WAS, and the remaining 5 were diagnosed as having non-WAS causes of thrombocytopenia. There were no ambiguous results, and these were confirmed by genetic analysis. The authors conclude that screening by flow cytometry for WASP is recommended for boys with persistent thrombocytopenia of an unknown etiology.