Assessment of using a gamma index analysis for patient-specific quality assurance in Japan.

PURPOSE: The Task Group 218 (TG-218) report was published by the American Association of Physicists in Medicine in 2018, recommending the appropriate use of gamma index analysis for patient-specific quality assurance (PSQA). The paper demonstrates that PSQA for radiotherapy in Japan appropriately applies the gamma index analysis considering TG-218. MATERIALS/METHODS: This survey estimated the acceptance state of radiotherapeutic institutes or facilities in Japan for the guideline using a web-based questionnaire. To investigate an appropriate PSQA of the facility-specific conditions, we researched an optimal tolerance or action level for various clinical situations, including different treatment machines, clinical policies, measurement devices, staff or their skills, and patient conditions. The responded data were analyzed using principal component analysis (PCA) and multidimensional scaling (MDS). The PCA focused on factor loading values of the first contribution over 0.5, whereas the MDS focused on mapped distances among data. RESULTS: Responses were obtained from 148 facilities that use intensity-modulated radiation therapy (IMRT), which accounted for 42.8% of the probable IMRT use in Japan. This survey revealed the appropriate application of the following universal criteria for gamma index analysis from the guideline recommendation despite the facility-specific variations (treatment machines/the number of IMRT cases/facility attributes/responded [representative] expertise or staff): (a) 95% pass rate, (b) 3% dose difference and 2-mm distance-to-agreement, and (c) 10% threshold dose. Conditions (a)-(c) were the principal components of the data by the PCA method and were mapped in a similar distance range, which was easily clustered from other gamma index analytic factors by the MDS method. Conditions (a)-(c) were the universally essential factors for the PSQA in Japan. CONCLUSION: We found that the majority of facilities using IMRT in each region of Japan complied with the guideline and conducted PSQA with deliberation under the individual facility-specific conditions.

Quantitative measurements of hip abduction strength in lumbar surgery patients.

BACKGROUND: We sought to evaluate the hip abduction strength in patients before and after lumbar surgery. MATERIALS AND METHODS: Eighty-four patients (51 males and 33 females) undergoing surgery for lumbar disc herniation or lumbar canal stenosis were selected. Mean age was 64.7 ± 13.8 years. Seven patients (8.3%) had surgery at multiple levels, including L2-L3 (group A), 27 (32.1%) patients had surgery at multiple levels including L3-L4 (group B), 32 (38.1%) patients had surgery at the L4-L5 level only (group C), and 18 (21.4%) patients had surgery at the L5-S1 level only (group D). Hip abduction strength was measured in the 84 patients preoperatively and in 49 patients postoperatively. RESULTS: In all patients, preoperative mean hip abduction strength on the symptomatic side and the asymptomatic side was 71.4 ± 34.5 N and 90.7 ± 36.5 N, respectively (p = 0.0008). In groups A and B, there were no significant differences between the mean hip abduction strength on the symptomatic and contralateral side. In group C, those on the symptomatic and contralateral side were 68.0 ± 33.5 N and 89.3 ± 34.8 N, respectively (p = 0.0181). In group D, those on the symptomatic and contralateral side were 74.3 ± 42.4 N and 101.7 ± 44.7 N, respectively (p = 0.0314). In the 49 patients of all groups that could be measured postoperatively, there were no significant differences between the mean hip abduction strength on both sides. CONCLUSIONS: It was confirmed that the gluteus medius, which was main hip abductor, was mainly innervated by L5 and its mean strength significantly improved postoperatively. The possibility of improvement of hip abduction strength, especially with unchanged tibialis anterior strength, could be very useful for operative decisions.

Association between Subclinical Hypothyroidism and Adverse Pregnancy Outcomes in Assisted Reproduction Technology Singleton Pregnancies: A Retrospective Study.

Background/Objectives: Women with subclinical hypothyroidism (SCH) were reported to be at an increased perinatal risk. We aimed to investigate the relationship between SCH and perinatal outcomes in singleton pregnancies resulting from assisted reproduction technology (ART). Methods: We retrospectively examined the perinatal outcomes of ART singleton pregnancies in women who underwent thyroid function screening before conception and delivered at our hospital from January 2020 to July 2023. We defined SCH as thyroid-stimulating hormone (TSH) levels > 2.5 mU/L and normal free T4 levels. The patients were categorized into three groups: normal thyroid function (group A), SCH without levothyroxine therapy (group B), and SCH with levothyroxine therapy (group C). The risks of preterm birth, preeclampsia, fetal growth restriction, manual placental removal, and blood loss at delivery were compared among the three groups. Results: Out of the 650 ART singleton deliveries, 581 were assigned to group A, 34 to group B, and 35 to group C. The preterm birth rate at <34 weeks was significantly higher in group B and significantly lower in group C than in group A. The rate of preterm delivery at <34 weeks increased in correlation with TSH levels. Levothyroxine therapy was the significant preventive factor for preterm birth at <34 weeks. Conclusions: The preterm birth rate before 34 weeks was significantly higher in the SCH group. Levothyroxine therapy is a significant protective factor against preterm birth before 34 weeks. Universal screening for thyroid function and appropriate hormone therapy in pregnant women may help reduce perinatal risks, including preterm birth.

Correcting for the effect of ambient pressure fluctuations on measured output from a linear accelerator with a sealed monitor chamber.

Objective.Ambient pressure fluctuations deform the walls of a sealed monitor chamber in a linear accelerator (LINAC) and affect the output. This study retrospectively quantified the output variations accompanying ambient pressure fluctuations in a LINAC equipped with a sealed monitor chamber and introduced a novel approach of calculating the adjusted output free from the effect of ambient pressure fluctuations.Approach.The output data for the 6 MV and 10 MV X-rays measured between March 2014 and September 2015 were analysed. This period was further divided into four sub-periods according to the output calibrations. Output behaviours were modelled using multiple regression analysis with ambient pressure and the time elapsed since the last calibration as explanatory variables. The output variations accompanying ambient pressure fluctuations were calculated using regression parameters and were subtracted from the measured outputs to obtain the adjusted outputs.Main results.The partial regression coefficients for ambient pressure varied from -2.3 × 10-4to -1.8 × 10-4cGy/MU/hPa for 6 MV and from -1.9 × 10-4to -1.2 × 10-4cGy/MU/hPa for 10 MV X-rays. These partial regression coefficient values were comparable among the four sub-periods and the two x-ray energies, respectively. These findings suggest that the degree of the output variations accompanying ambient pressure fluctuations is independent of x-ray energies and is determined by the internal structure of the chamber and the pressure differential between the inside and outside of the chamber. The adjusted outputs showed a better fit with the time trend line than the measured outputs.Significance.This study demonstrates a novel procedure for obtaining the adjusted outputs and allows precise observation of the output behaviours of a LINAC equipped with a sealed monitor chamber. Combined observation of the measured and adjusted output facilitates the detection of output anomalies, thus contributing to quality control (QC) of LINACs.

Ultrasound-Guided Peripheral Nerve Blocks Performed by Orthopedic Surgeons: A Retrospective, Multicenter Study in Akita Prefecture, Japan.

The shortage of doctors is a societal problem, especially in rural areas such as Akita Prefecture, Japan. Therefore, it is not unusual in Akita for orthopedic surgeons to perform upper and lower limb surgeries under ultrasound-guided peripheral nerve blocks managed by the operators themselves. Multicenter studies of ultrasound-guided peripheral nerve blocks performed by orthopedic surgeons have not been reported. The purpose of this study was to clarify the safety and reliability of ultrasound-guided peripheral nerve blocks performed by orthopedic surgeons in Akita. A total of 1,674 upper extremity surgery cases operated under ultrasound-guided peripheral nerve blocks at 8 hospitals in Akita prefecture from April 2016 to April 2018 were investigated retrospectively. These blocks were performed by a total of 37 orthopedic surgeons, including senior surgeons and residents. In 321 of the 1,674 cases (19%), local anesthetics were added to the surgical field. Two cases with special factors were converted to general anesthesia. There were 2 cases of complications associated with the nerve block, but they were all transient and recovered promptly. The block site and the hospital where the block was performed showed a significant relationship with the addition of local anesthetics to the surgical site (P < 0.001). Surgery time, age at surgery, and surgical site showed no significant relationships with the addition of local anesthetics. The volume of the anesthetic used for the nerve block showed a significant inverse relationship with the addition of local anesthetics (P=0.040). Many orthopedic surgeons in Akita prefecture began to perform ultrasound-guided peripheral nerve blocks, which had a reliable anesthesia effect with no noticeable complications, whether performed by residents or senior orthopedic surgeons, and this is a useful anesthetic technique for orthopedic surgeons.

New algorithm to simulate organ movement and deformation for four-dimensional dose calculation based on a three-dimensional CT and fluoroscopy of the thorax.

PURPOSE: The aim of this study was to develop a 4D-modeling algorithm, designated "3D+," to simulate organ movement and deformation for 4D dose calculation without the need for 4D-CT or deformable image registration and to assess the validity of this algorithm. METHODS: This 3D+ algorithm virtually creates 4D-CT images by deforming static 3D-CT data according to a typical motion model and motion data at multiple observation points collected via fluoroscopy. A typical motion model intended for patients with lung tumors immobilized with a vacuum pillow inside a stereotactic body frame was constructed. The geometric accuracy of virtual 4D-CT images created using this 3D+ algorithm was evaluated in eight patients by comparing the simulated results with actual 4D-CT images in terms of visual assessment, landmark analysis, and comparison of the radial distance from the tumor centroid to the body or lung surface. RESULTS: The average accuracy for all patients, as determined via landmark analysis, was 2.8 +/- 1.8 mm, very similar to results obtained through 4D-CT and deformable image registrations. Error in the radial distance from the tumor centroid to the body or lung surface was generally within 1.0 or 2.0 mm, respectively, in virtual versus actual 4D-CT images. Therefore, it is assumed that these geometric errors would have only negligible effects on dose calculation. CONCLUSIONS: 4D modeling of the thorax utilizing the 3D+ algorithm shows acceptable accuracy and is more suited for routine clinical use in terms of processing time than conventional 4D-CT and deformable image registration. The 3D+ algorithm may be useful for simulating dose distribution for advanced beam delivery techniques, such as real-time tumor tracking irradiation and adaptive radiation therapy.

Impact of motion velocity on four-dimensional target volumes: a phantom study.

This study aims to assess the impact of motion velocity that may cause motion artifacts on target volumes (TVs) using a one-dimensional moving phantom. A 20 mm diameter spherical object embedded in a QUASAR phantom sinusoidally moved with approximately 5.0 or 10.0 mm amplitude (A) along the longitudinal axis of the computed tomography (CT) couch. The motion period was manually set in the range of 2.0-10.0 s at approximately 2.0 s interval. Four-dimensional (4D) CT images were acquired by a four-slice CT scanner (LightSpeed RT; General Electric Medical Systems, Waukesha, WI) with a slice thickness of 1.25 mm in axial cine mode. The minimum gantry rotation of 1.0 s was employed to achieve the maximum in-slice temporal resolution. Projection data over a full gantry rotation (1.0 s) were used for image reconstruction. Reflective marker position was recorded by the real-time positioning management system (Varian Medical Systems, Palo Alto, CA). ADVANTAGE 4D software exported ten respiratory phase volumes and the maximum intensity volume generated from all reconstructed data (MIV). The threshold to obtain static object volume (V0, 4.19 ml) was used to automatically segment TVs on CT images, and then the union of TVs on 4D CT images (TV(4D)) was constructed. TVs on MIV (TV(MIV)) were also segmented by the threshold that can determine the area occupied within the central slice of TV(MIV). The maximum motion velocity for each phase bin was calculated using the actual averaged motion period displayed on ADVANTAGE 4D software (T), the range of phases used to construct the target phase bin (phase range), and a mathematical model of sinusoidal function. Each volume size and the motion range of TV in the cranial-caudal (CC) direction were measured. Subsequently, cross-correlation coefficients between TV size and motion velocity as well as phase range were calculated. Both misalignment and motion-blurring artifacts were caused by high motion velocity, Less than 6% phase range was needed to construct the 4D CT data set, except for T of 2.0 s. While the positional differences between the TV and ideal centroid in the CC direction were within the voxel size for T > or = 6.0 s, the differences were up to 2.43 and 4.15 mm for (A,T) = (5.0 mm, 2.0 s) and (10.0 mm, 2.0 s), respectively. The maximum volumetric deviations between TV sizes and V0 were 43.68% and 91.41% for A of 5.0 and 10.0 mm, respectively. TV(MIV) sizes were slightly larger than TV(4D) sizes. Volumetric deviation between TV size and V0 had a stronger correlation with motion velocity rather than phase range. This phantom study demonstrated that motion artifacts were substantially reduced when the phantom moved longitudinally at low motion velocity during 4D CT image acquisition; therefore, geometrical uncertainties due to motion artifacts should be recognized when determining TVs, especially with a fast period.

Technical note: improved positioning protocol for patient setup accuracy in conventional radiotherapy for lung cancer.

This study aimed to investigate an improved setup protocol for maintaining patient setup accuracy, with minimal or no use of image-guided radiation therapy in conventional radiotherapy for lung cancer. A coordinate value for the treatment couch in the anterior-posterior (AP) direction was obtained from the first fraction using bony anatomy image guidance. The coordinate value was invariably used for patient positioning in the second and subsequent treatment fractions. The errors of 2410 setup image sets (anterior and lateral) from 105 patients with lung cancer were analyzed. The systematic and random patient positioning errors in the AP direction were 0.6 ± 1.0 mm. Such errors accounted for 97% of all fractions within ± 2 mm. The protocol resulted in minimal patient setup errors in the AP direction using only one image for guidance; therefore, it may be applied to conventional radiotherapy for lung cancer in case of insufficient image guidance.

Development of a three-dimensionally movable phantom system for dosimetric verifications.

The authors developed a three-dimensionally movable phantom system (3D movable phantom system) which can reproduce three-dimensional movements to experimentally verify the impact of radiotherapy treatment-related movements on dose distribution. The phantom system consists of three integrated components: a three-dimensional driving mechanism (3D driving mechanism), computer control system, and phantoms for film dosimetry. The 3D driving mechanism is a quintessential part of this system. It is composed of three linear-motion tables (single-axis robots) which are joined orthogonally to each other. This mechanism has a motion range of 100 mm, with a maximum velocity of 200 mm/s in each dimension, and 3D motion ability of arbitrary patterns. These attributes are sufficient to reproduce almost all organ movements. The positional accuracy of this 3D movable phantom system in a state of geostationary is less than 0.1 mm. The maximum error in terms of the absolute position on movement was 0.56 mm. The positional reappearance error on movement was up to 0.23 mm. The observed fluctuation of time was 0.012 s in the cycle of 4.5 s of oscillation. These results suggested that the 3D movable phantom system exhibited a sufficient level of accuracy in terms of geometry and timing to reproduce interfractional organ movement or setup errors in order to assess the influence of these errors on high-precision radiotherapy such as stereotactic irradiation and intensity-modulated radiotherapy. In addition, the authors 3D movable phantom system will also be useful in evaluating the adequacy and efficacy of new treatment techniques such as gating or tracking radiotherapy.

Geometrical differences in target volumes between slow CT and 4D CT imaging in stereotactic body radiotherapy for lung tumors in the upper and middle lobe.

Since stereotactic body radiotherapy (SBRT) was started for patients with lung tumor in 1998 in our institution, x-ray fluoroscopic examination and slow computed tomography (CT) scan with a rotation time of 4 s have been routinely applied to determine target volumes. When lung tumor motion observed with x-ray fluoroscopy is larger than 8 mm, diaphragm control (DC) is used to reduce tumor motion during respiration. After the installation of a four-dimensional (4D) CT scanner in 2006, 4D CT images have been supplementarily acquired to determine target volumes. It was found that target volumes based on slow CT images were substantially different from those on 4D CT images, even for patients with lung tumor motion no larger than 8 mm. Although slow CT scan might be expected to fare well for lung tumors with motion range of 8 mm or less, the potential limitations of slow CT scan are unknown. The purpose of this study was to evaluate the geometrical differences in target volumes between slow CT and 4D CT imaging for lung tumors with motion range no larger than 8 mm in the upper and middle lobe. Of the patients who underwent SBR between October 2006 and April 2008, 32 patients who had lung tumor with motion range no larger than 8 mm and did not need to use DC were enrolled in this study. Slow CT and 4D CT images were acquired under free breathing for each patient. Target volumes were manually delineated on slow CT images (TV(slow CT)). Gross tumor volumes were also delineated on each of the 4D CT volumes and their union (TV(4D CT)) was constructed. Volumetric and statistical analyses were performed for each patient. The mean +/- standard deviation (S.D.) of TV(slow CT)/TV(4D CT) was 0.75 +/- 0.17 (range, 0.38-1.10). The difference between sizes of TV(slow CT) and TV(4D CT) was not statistically significant (P = 0.096). A mean of 8% volume of TV(slow CT) was not encompassed in TV(4D CT) (mean +/- S.D. = 0.92 +/- 0.07). The patients were separated into two groups to test whether the quality of target delineation on slow CT scans depends on respiratory periods below or above the CT rotation time of 4 s. No significant difference was observed between these groups (P = 0.229). Even lung tumors with motion range no larger than 8 mm might not be accurately depicted on slow CT images. When only a single slow CT scan was used for lung tumors with motion range of 8 mm or less, 95% confidence values for additional margins for TV(slow CT) to encompass TV(4D CT) were 4.0, 5.4, 4.9, 5.1, 1.8, and 1.7 mm for lateral, medial, ventral, dorsal, cranial, and caudal directions, respectively.

Interinstitutional variations in planning for stereotactic body radiation therapy for lung cancer.

PURPOSE: The aim of this study was to assess interinstitutional variations in planning for stereotactic body radiation therapy (SBRT) for lung cancer before the start of the Japan Clinical Oncology Group (JCOG) 0403 trial. METHODS AND MATERIALS: Eleven institutions created virtual plans for four cases of solitary lung cancer. The created plans should satisfy the target definitions and the dose constraints for the JCOG 0403 protocol. RESULTS: FOCUS/XiO (CMS) was used in six institutions, Eclipse (Varian) in 3, Cadplan (Varian) in one, and Pinnacle3 (Philips/ADAC) in one. Dose calculation algorithms of Clarkson with effective path length correction and superposition were used in FOCUS/XiO; pencil beam convolution with Batho power law correction was used in Eclipse and Cadplan; and collapsed cone convolution superposition was used in Pinnacle3. For the target volumes, the overall coefficient of variation was 16.6%, and the interinstitutional variations were not significant. For maximal dose, minimal dose, D95, and the homogeneity index of the planning target volume, the interinstitutional variations were significant. The dose calculation algorithm was a significant factor in these variations. No violation of the dose constraints for the protocol was observed. CONCLUSION: There can be notable interinstitutional variations in planning for SBRT, including both interobserver variations in the estimate of target volumes as well as dose calculation effects related to the use of different dose calculation algorithms.

Hypofractionated high-dose irradiation for the treatment of malignant astrocytomas using simultaneous integrated boost technique by IMRT.

PURPOSE: We evaluated the clinical significance of hypofractionated high-dose irradiation using simultaneous integrated boost technique with intensity-modulated radiation therapy (IMRT) for the treatment of malignant astrocytomas (MAs). METHODS AND MATERIALS: Twenty-five patients with MAs were treated by IMRT. Three layered planning target volumes (PTVs) were contoured. PTV-1 was the area of enhanced lesion with 5-mm margin; PTV-2 was the area with 15-mm margin surrounding the PTV-1; PTV-3 was the area of perifocal edema. Irradiation was performed in 8 fractions, and only the dose for PTV-1 was escalated from 48 Gy to 68 Gy while maintaining the dose for PTV-2 (40 Gy) and PTV-3 (32 Gy). The clinical outcome of IMRT was compared with 60 MA patients treated by conventional external beam irradiation (EBI). RESULTS: The progression-free survival of patients in the IMRT group was significantly longer than that in the EBI group (p < 0.0001). No distant failure was observed in both groups. In the IMRT group, dissemination was the most frequent cause of death (70%). The overall survival of patients in the IMRT group was better than that in the EBI group (p = 0.043). CONCLUSIONS: Our regimen of IMRT contributed to the control of both the regional and infiltrating tumors, resulting in better survival of patients.

Development of a four-dimensional image-guided radiotherapy system with a gimbaled X-ray head.

PURPOSE: To develop and evaluate a new four-dimensional image-guided radiotherapy system, which enables precise setup, real-time tumor tracking, and pursuit irradiation. METHODS AND MATERIALS: The system has an innovative gimbaled X-ray head that enables small-angle (+/-2.4 degrees ) rotations (pan and tilt) along the two orthogonal gimbals. This design provides for both accurate beam positioning at the isocenter by actively compensating for mechanical distortion and quick pursuit of the target. The X-ray head is composed of an ultralight C-band linear accelerator and a multileaf collimator. The gimbaled X-ray head is mounted on a rigid O-ring structure with an on-board imaging subsystem composed of two sets of kilovoltage X-ray tubes and flat panel detectors, which provides a pair of radiographs, cone beam computed tomography images useful for image guided setup, and real-time fluoroscopic monitoring for pursuit irradiation. RESULTS: The root mean square accuracy of the static beam positioning was 0.1 mm for 360 degrees of O-ring rotation. The dynamic beam response and positioning accuracy was +/-0.6 mm for a 0.75 Hz, 40-mm stroke and +/-0.4 mm for a 2.0 Hz, 8-mm stroke. The quality of the images was encouraging for using the tomography-based setup. Fluoroscopic images were sufficient for monitoring and tracking lung tumors. CONCLUSIONS: Key functions and capabilities of our new system are very promising for precise image-guided setup and for tracking and pursuit irradiation of a moving target.

[Stereotactic body radiotherapy (SBRT)].

The techniques of three-dimensional conformal radiotherapy (3 D-CRT) and patient immobilization have recently been developed, enabling us to focus high doses on the target with relatively less irradiation of normal tissues. In radiotherapy for solitary lung tumors, the local control may be safely improved by delivering a higher dose at only the target volume using these techniques. Recently, several clinical studies on stereotactic body radiotherapy (SRT) using the 3 D-CRT technique for solitary lung tumors have been reported. The single dose used is 10-15 Gy, and the total sessions are three to five. The local control rate is more than 90% and complication rates are very low. Therefore, this treatment is a promising new non-invasive treatment for early stage lung cancer. A multi-institutional clinical study, JCOG 0403, in now underway.

An on-site audit system for dosimetry credentialing of intensity-modulated radiotherapy in Japanese Clinical Oncology Group (JCOG) clinical trials.

PURPOSE: This study was undertaken to analyze the results of intensity-modulated radiotherapy (IMRT) dosimetry credentialing using a phantom in the Japanese Clinical Oncology Group clinical trials. METHODS: All measurements were performed on-site. The IMRT phantom consisted of a phantom shell and a module. Two types of structures, including a C-shaped planning target volume (PTV) around a column-shaped organ at risk (OAR), were included in the module. Each participating institution was asked to image, plan, and treat the phantom. A prescription dose of 2Gy should cover 95% of the PTV. The plan should limit the maximum doses to the PTV and OAR to less than 110% and 60%, respectively. The pass criteria were ±3% in terms of chamber dosimetry and a difference in profile position ⩽2mm in the high-dose gradient area of film dosimetry. The positional difference was defined as the largest distance between the measured and calculated positions at doses of 60% or 80%. These tolerances were based on the Japanese Society for Radiation Oncology IMRT guidelines. RESULTS: Credentialing was performed on a total of 44 treatment machines in 32 institutions from 2009 to 2015. All differences between measured and planned doses at the measurement points of the PTV were within 3%. The means±standard deviations of the positional differences were 1.0±0.4mm and 0.9±0.3mm without and with the phantom shell, respectively. CONCLUSIONS: The dose differences and positional differences met the desired criteria in all institutions.

Factors related to curved femur in elderly Japanese women.

BACKGROUND: Multiple factors are involved in the development of atypical femoral fractures, and excessive curvature of the femur is thought to be one of them. However, the pathogenesis of femoral curvature is unknown. We evaluated the influence of factors related to bone metabolism and posture on the development of femoral curvature. METHODS: A total of 139 women participated in the present study. Curvatures were measured using antero-posterior and lateral radiography of the femur. We evaluated some bone and vitamin D metabolism markers in serum, the bone mineral density (BMD), lumbar spine alignment, and pelvic tilt. RESULTS: We divided the women into two groups, curved and non-curved groups, based on the average plus standard deviation as the cut-off between the groups. When univariate logistic regression analysis was performed to detect factors affecting femoral curvature, the following were identified as indices significantly affecting the curvature: age of the patients, serum concentrations of calcium, intact parathyroid hormone, pentosidine, homocysteine and 25-hydroxyvitamin D (25(OH)D), and BMD of the proximal femur (P < 0.05) both in the lateral and anterior curvatures. When we used multivariate analyses to assess these factors, only 25(OH)D and age (lateral and anterior standardized odds ratio: 0.776 and 0.385, and 2.312 and 4.472, respectively) affected the femoral curvature (P < 0.05). CONCLUSION: Femoral curvature is strongly influenced by age and serum vitamin D.

LW6, a hypoxia-inducible factor 1 inhibitor, selectively induces apoptosis in hypoxic cells through depolarization of mitochondria in A549 human lung cancer cells.

Hypoxia­inducible factor 1 (HIF­1) activates the transcription of genes that act upon the adaptation of cancer cells to hypoxia. LW6, an HIF­1 inhibitor, was hypothesized to improve resistance to cancer therapy in hypoxic tumors by inhibiting the accumulation of HIF­1α. A clear anti­tumor effect under low oxygen conditions would indicate that LW6 may be an improved treatment strategy for cancer in hypoxia. In the present study, the HIF­1 inhibition potential of LW6 on the growth and apoptosis of A549 lung cancer cells in association with oxygen availability was evaluated. LW6 was observed to inhibit the expression of HIF­1α induced by hypoxia in A549 cells at 20 mM, independently of the von Hippel­Lindau protein. In addition, at this concentration, LW6 induced hypoxia­selective apoptosis together with a reduction in the mitochondrial membrane potential. The intracellular reactive oxygen species levels increased in LW6­treated hypoxic A549 cells and LW6 induced a hypoxia­selective increase of mitochondrial O2•­. In conclusion, LW6 inhibited the growth of hypoxic A549 cells by affecting the mitochondria. The inhibition of the mitochondrial respiratory chain is suggested as a potentially effective strategy to target apoptosis in cancer cells.

[3D-CRT and intensity modulated radiation therapy (IMRT)].

Three-dimensional conformal radiation therapy (3D-CRT) conforms a high dose region closer to the target volume than does 2D radiation therapy. IMRT is the advanced form of 3D-CRT. With IMRT technique, using multiple intensity modulated beams, one can deliver a high dose of radiation to the target and a low dose to the surrounding normal structures. IMRT planning provides improved tumor target coverage when compared to 3D-CRT treatment planning. There is significant sparing of critical structures and other normal tissues. IMRT also produces dose distributions capable of delivering different dose prescriptions to multiple targets, providing a new opportunity for differential dose painting to increase the dose selectively to specific image-defined regions. Preliminary findings indicate that IMRT is a new clinically feasible tool in radiation oncology. The initial results of clinical studies demonstrate reduced xerostomia in head and neck cancer and also effectively reduced acute and late occurring toxicities, improving the QOL of patients treated for prostate cancer. According to these studies, IMRT will allow dose escalation, leading to better tumor control without normal tissue damage. On the other hand, there are some problems for IMRT in Japan: There are few medical physicists, which results in radiation technologists playing most clinical technological roles, including some dosimetrical and physical activities. Social recognition and economical and legal support for medical physicists should be established in providing better patient care services.

[Dosimetric verification in intensity modulated radiation therapy].

As part of dosimetric verification for IMRT intensity modulated radiation therapy, we examined the selection of a dosimeter in accordance with the purpose of physical measurement and the process of data analysis. Because of the high dose conformation in the target volume and minimum dose in the organs at risk (OAR) in IMRT, dosimetric verification is essential. Because the performance of dosimetric verification in a patient is not allowed, a physical phantom and dosimeter must be used. Dose verification using a physical phantom, from which the beam data optimized for a patient slated for IMRT are transferred, may cause latent error as a result of change in the depth of each beam toward an isocenter. This effect may change the dose distribution and prescription dose. The basic methods of dosimetric verification with physical measurement are point dosimetry, when the reference dose is given at a point by planning software, and volumetric dosimetry, when planning software gives the dose as a volumetric configuration. While the most accurate dosimetry is done using a calibrated ionization chamber, IMRT requires volumetric dosimetry using some kind of portal film or a polymer gel dosimeter, because of the need for dosimetric verification for an irregular dose distribution in IMRT. The importance of indirect dosimetry using these methods is to provide calibration as a dosimeter, absolute dose, and preservation of calibration. In our study, the verification of dose distribution for IMRT using portal film and a RANDO phantom could be performed with an error of less than 2% in all cases. The measurement error for the central dose using a JARP-type ionization chamber and MixDP was less than 3% in all cases except for the case with the maximum error. At the moment, IMRT requires a great deal of effort in the processes of planning, dosimetric verification, and isocenter checking in every fraction to maintain high accuracy. Although the need for a large amount of effort in the service of maintaining accuracy may be reasonable, it could be enough to inhibit the spread of IMRT. It is hoped that an easy method of dosimetric verification that still maintains a high level of accuracy will develop as a result of this great effort.

A kernel-based method for markerless tumor tracking in kV fluoroscopic images.

Markerless tracking of respiration-induced tumor motion in kilo-voltage (kV) fluoroscopic image sequence is still a challenging task in real time image-guided radiation therapy (IGRT). Most of existing markerless tracking methods are based on a template matching technique or its extensions that are frequently sensitive to non-rigid tumor deformation and involve expensive computation. This paper presents a kernel-based method that is capable of tracking tumor motion in kV fluoroscopic image sequence with robust performance and low computational cost. The proposed tracking system consists of the following three steps. To enhance the contrast of kV fluoroscopic image, we firstly utilize a histogram equalization to transform the intensities of original images to a wider dynamical intensity range. A tumor target in the first frame is then represented by using a histogram-based feature vector. Subsequently, the target tracking is then formulated by maximizing a Bhattacharyya coefficient that measures the similarity between the tumor target and its candidates in the subsequent frames. The numerical solution for maximizing the Bhattacharyya coefficient is performed by a mean-shift algorithm. The proposed method was evaluated by using four clinical kV fluoroscopic image sequences. For comparison, we also implement four conventional template matching-based methods and compare their performance with our proposed method in terms of the tracking accuracy and computational cost. Experimental results demonstrated that the proposed method is superior to conventional template matching-based methods.