Kunihiko Tateoka

Dosimetric verification in participating institutions in a stereotactic body radiotherapy trial for stage I non-small cell lung cancer: Japan clinical oncology group trial (JCOG0403)

A multicentre phase II trial of stereotactic body radiotherapy for T1N0M0 non-small cell lung cancer was initiated in Japan as the Japan Clinical Oncology Group trial (JCOG0403). Before starting the trial, a decision was made to evaluate the treatment machine and treatment planning in participating institutions to minimize the variations of the prescription dose between the institutions. We visited the 16 participating institutions and examined the absolute dose at the centre of a simulated spherical tumour of 3.0 cm diameter in the lung using the radiation treatment planning systems in each institution. A lung phantom for stereotactic body radiotherapy (SBRT) was developed and used for the treatment planning and film dosimetry. In the JCOG radiotherapy study group, the no model-based calculation algorithm or the model-based calculation algorithm with a dose kernel unscaled for heterogeneities were selected for use in the initial SBRT trials started in 2004, and the model-based calculation algorithm with a dose kernel scaled for heterogeneities was selected for the coming trial. The findings of this study suggest that the clinical results of lung SBRT trials should be carefully evaluated in comparison with the actual dose given to patients.

Results and DVH analysis of late rectal bleeding in patients treated with 3D-CRT or IMRT for localized prostate cancer

In patients undergoing radiotherapy for localized prostate cancer, dose–volume histograms and clinical variables were examined to search for correlations between radiation treatment planning parameters and late rectal bleeding. We analyzed 129 patients with localized prostate cancer who were managed from 2002 to 2010 at our institution. They were treated with 3D conformal radiation therapy (3D-CRT, 70 Gy/35 fractions, 55 patients) or intensity-modulated radiation therapy (IMRT, 76 Gy/38 fractions, 74 patients). All radiation treatment plans were retrospectively reconstructed, dose–volume histograms of the rectum were generated, and the doses delivered to the rectum were calculated. Time to rectal bleeding ranged from 9–53 months, with a median of 18.7 months. Of the 129 patients, 33 patients had Grade 1 bleeding and were treated with steroid suppositories, while 25 patients with Grade 2 bleeding received argon plasma laser coagulation therapy (APC). Three patients with Grade 3 bleeding required both APC and blood transfusion. The 5-year incidence rate of Grade 2 or 3 rectal bleeding was 21.8% for the 3D-CRT group and 21.6% for the IMRT group. Univariate analysis showed significant differences in the average values from V65 to V10 between Grades 0–1 and Grades 2–3. Multivariate analysis demonstrated that patients with V65 ≥ 17% had a significantly increased risk (P = 0.032) of Grade 2 or 3 rectal bleeding. Of the 28 patients of Grade 2 or 3 rectal bleeding, 17 patients (60.7%) were cured by a single session of APC, while the other 11 patients required two sessions. Thus, none of the patients had any further rectal bleeding after the second APC session.

Relation between Ku80 and microRNA-99a expression and late rectal bleeding after radiotherapy for prostate cancer

BACKGROUND AND PURPOSE Late rectal bleeding is one of the severe adverse events after radiotherapy for prostate cancer. New biomarkers are needed to allow a personalized treatment. MATERIALS AND METHODS Four patients each with grade 0-1 or grade 2-3 rectal bleeding were randomly selected for miRNA array to examine miRNA expression in peripheral blood lymphocytes (PBLs). Based on results of miRNA array, 1 of 348 miRNAs was selected for microRNA assays. Then, expression of DNA-dependent protein kinase mRNA and miR-99a was analyzed in the PBLs of 97 patients. PBLs were exposed to 4Gy of X-ray ex-vivo. RESULTS In the discovery cohort, grade 2-3 rectal bleeding was significantly higher in the Ku80 <1.09 expression group compared with ⩾1.09 group (P=0.011). In radiation-induced expression of miR-99a, grade 2-3 rectal bleeding was significantly higher in the miR-99a IR(+)/IR(-) >0.93 group compared with ⩽0.93 group (P=0.013). Most patients with grade 2-3 rectal bleeding were in the group with low Ku80 and high miR-99a expression. In the validation cohort, similar results were obtained. CONCLUSION A combination of low Ku80 expression and highly-induced miR-99a expression could be a promising marker for predicting rectal bleeding after radiotherapy.

Assessment of Similarity Measures for Accurate Deformable Image Registration

Purpose: Deformable image registration is widely used in radiation therapy applications. There are several different algorithms for deformable image registration. The purpose of this study was to evaluate the optimal similarity measures needed to obtain accurate deformable image registration by using a phantom. Methods: To evaluate the optimal similarity measures for the deformable image registration, we compared several similarity measures, including the normalized correlation coefficient, the mutual information, the dice similarity coefficient, and the Tanimoto coefficient. In this study, the mutual information was normalized to have a value of 1 when there is complete correspondence between the images in order to compare it with other similarity measures. First, a reference image was acquired with the phantom located in the center of the field of view of a computed tomography. The phantom consisted of two sections a Teflon sphere and four samples of various electron density values. Then, to acquire the moving images, the phantom was scanned for various displacement values as it was moved to the left (range: 1.00-30.0 mm). Second, images for various Teflon sphere diameters (range: 0–25.4 mm) were acquired with the CT scanner. The image similarity for each condition was compared with the reference image by using several similarity measures. Results: In the moved phantom study, although the normalized correlation coefficient, dice similarity coefficient, and Tanimoto coefficient showed the same tendency of sensitivity for measuring image similarity, the mutual information showed significant sensitivity for both of the two distinct sections of the phantom. In the study in which the phantom sphere diameter was varied, the mutual information also showed the best performance among the tested similarity measures. Conclusions: Mutual information appears to have an advantage over other similarity measures for accurate deformable image registration.

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 125I with an air-kerma strength of 0.432 U (μGym2h–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.

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 125I 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.

Uncertainty in patient set-up margin analysis in radiation therapy

We investigated the uncertainty in patient set-up margin analysis with a small dataset consisting of a limited number of clinical cases over a short time period, and propose a method for determining the optimum set-up margin. Patient set-up errors from 555 registration images of 15 patients with prostate cancer were tested for normality using a quantile-quantile (Q-Q) plot and a Kolmogorov–Smirnov test with the hypothesis that the data were not normally distributed. The ranges of set-up errors include the set-up errors within the 95% interval of the entire patient data histogram, and their equivalent normal distributions were compared. The patient set-up error was not normally distributed. When the patient set-up error distribution was assumed to have a normal distribution, an underestimate of the actual set-up error occurred in some patients but an overestimate occurred in others. When using a limited dataset for patient set-up errors, which consists of only a small number of the cases over a short period of time in a clinical practice, the 2.5% and 97.5% intervals of the actual patient data histogram from the percentile method should be used for estimating the set-up margin. Since set-up error data is usually not normally distributed, these intervals should provide a more accurate estimate of set-up margin. In this way, the uncertainty in patient set-up margin analysis in radiation therapy can be reduced.

Analysis of the optimum internal margin for respiratory-gated radiotherapy using end-exhalation phase assessments using a motion phantom

We aimed to optimize internal margin (IM) determination for respiratory‐gated radiotherapy using end‐expiratory phase assessments using a motion phantom. Four‐dimensional computed tomography (4D CT) data were acquired using a GE LightSpeed RT CT scanner, a respiratory‐gating system, and a motion phantom designed to move sinusoidally. To analyze the accuracy of 4D CT temporal resolution, a 25.4 mm diameter sphere was inserted into the motion phantom, and we measured the differences in sphere diameters between static and end‐exhalation phase images. In addition, the IM obtained from the maximum intensity projection within the gating window (MIPGW) image was compared to theoretical value. Cranial–caudal motion displacement ranged from 5.0 to 30.0 mm, and the respiratory period ranged from 2.0 to 6.0 sec. Differences in sphere diameters between static and end‐exhalation phase images ranged from 0.37 to 4.6 mm, with 5.0 ‐mm and 30 mm target displacements, respectively. Differences between the IM obtained from the MIPGW and the theoretical values ranged from 1.12 to 6.23 mm with 5.0 mm and 30 mm target displacements, respectively. These differences increased in proportion to the target velocity due to a motion artifact generated during tube rotation. In this study, the IMs obtained using the MIPGW image were overestimated in all cases. We therefore propose that the internal target volume (ITV) for respiratory‐gated radiotherapy should be determined by adding the calculated value to the end‐exhalation phase image. We also demonstrate a methodology for subtracting motion artifacts from the ITV using a motion phantom. PACS numbers: 87.53.Kn, 87.55.Gh, 87.56.jk

Analysis of Prostate Deformation during a Course of Radiation Therapy for Prostate Cancer.

Purpose Accurate analysis of the correlation between deformation of the prostate and displacement of its center of gravity (CoG) is important for efficient radiation therapy for prostate cancer. In this study, we addressed this problem by introducing a new analysis approach. Method A planning computed tomography (CT) scan and 7 repeat cone-beam CT scans during the course of treatment were obtained for 19 prostate cancer patients who underwent three-dimensional conformal radiation therapy. A single observer contoured the prostate gland only. To evaluate the local deformation of the prostate, it was divided into 12 manually defined segments. Prostate deformation was calculated using in-house developed software. The correlation between the displacement of the CoG and the local deformation of the prostate was evaluated using multiple regression analysis. Results The mean value and standard deviation (SD) of the prostate deformation were 0.6 mm and 1.7 mm, respectively. For the majority of the patients, the local SD of the deformation was slightly lager in the superior and inferior segments. Multiple regression analysis revealed that the anterior-posterior displacement of the CoG of the prostate had a highly significant correlation with the deformations in the middle-anterior (p < 0.01) and middle-posterior (p < 0.01) segments of the prostate surface (R2 = 0.84). However, there was no significant correlation between the displacement of the CoG and the deformation of the prostate surface in other segments. Conclusion Anterior-posterior displacement of the CoG of the prostate is highly correlated with deformation in its middle-anterior and posterior segments. In the radiation therapy for prostate cancer, it is necessary to optimize the internal margin for every position of the prostate measured using image-guided radiation therapy.

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

Abstract The purpose of this study was to estimate the uncertainty in the dose distribution for the 125I 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 125I 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.