Evaluation of the accuracy and clinical practicality of a calculation system for patient positional displacement in carbon ion radiotherapy at five sites.

PURPOSE: We developed a system for calculating patient positional displacement between digital radiography images (DRs) and digitally reconstructed radiography images (DRRs) to reduce patient radiation exposure, minimize individual differences between radiological technologists in patient positioning, and decrease positioning time. The accuracy of this system at five sites was evaluated with clinical data from cancer patients. The dependence of calculation accuracy on the size of the region of interest (ROI) and initial position was evaluated for clinical use. METHODS: For a preliminary verification, treatment planning and positioning data from eight setup patterns using a head and neck phantom were evaluated. Following this, data from 50 patients with prostate, lung, head and neck, liver, or pancreatic cancer (n = 10 each) were evaluated. Root mean square errors (RMSEs) between the results calculated by our system and the reference positions were assessed. The reference positions were manually determined by two radiological technologists to best-matching positions with orthogonal DRs and DRRs in six axial directions. The ROI size dependence was evaluated by comparing RMSEs for three different ROI sizes. Additionally, dependence on initial position parameters was evaluated by comparing RMSEs for four position patterns. RESULTS: For the phantom study, the average (± standard deviation) translation error was 0.17 ± 0.05, rotation error was 0.17 ± 0.07, and ΔD was 0.14 ± 0.05. Using the optimal ROI size for each patient site, all cases of prostate, lung, and head and neck cancer with initial position parameters of 10 mm or under were acceptable in our tolerance. However, only four liver cancer cases and three pancreatic cancer cases were acceptable, because of low-reproducibility regions in the ROIs. CONCLUSION: Our system has clinical practicality for prostate, lung, and head and neck cancer cases. Additionally, our findings suggest ROI size dependence in some cases.

The Impact of Gadolinium-based Contrast Agent for Carbon Ion Radiotherapy.

PURPOSE: The contrast agent used in the diagnostic department has high atomic numbers and might influence dose deposition in the particle therapy. In particular, the influence of gadolinium-based (Gd) contrast agent on range in carbon ion radiotherapy has not yet been evaluated. For this reason, we avoid carbon treatment and planning computed tomography (CT) acquisition on days when the contrast-enhanced magnetic resonance image (MRI) is performed. In this study, we evaluated the time required for this beam range effect to vanish by evaluating the temporal changes in the CT values after an enhanced MRI as well as the stopping power of Gd solution. MATERIALS AND METHODS: Two types of diluted solutions with Gd contrast agent were used for comparing their transferred stopping power (TSP) and measured stopping power (MSP). The TSP was calculated with a CT value to stopping power ratio table that was created previously. Additionally, to evaluate in vivo attenuation, we measured the CT values in the renal pelvis from the CT images with and without contrast agent for 73 patients. RESULTS: The maximum difference between the TSP and MSP was 85%. The difference between the TSP after 4 hours and the TSP with non-enhanced cases was less than 1%. Moreover, the difference between the MSP after 1 hour and the MSP with non-enhanced cases was less than 0.1%. CONCLUSION: It was found that the impact of Gd contrast agent can be neglected 1 hour after administration for carbon beam irradiation and 4 hours after for planning the CT image acquisition.

A Novel Evaluation Method for Displacement between Carbon Beam Axis and Positioning X-ray Axis Using an Imaging Plate.

PURPOSE: We developed an evaluation method for easily calculating displacement directly between the carbon beam axis and positioning X-ray axis. METHODS: A verification image was acquired by irradiating an imaging plate with a carbon beam and X-ray. The X-ray passed through a lead plate inserted in the range compensator holder. The displacement was calculated on the verification image from the center of a wire irradiated with carbon using a multi leaf collimator (MLC) and a wire irradiated with X-ray also using MLC. The accuracy of the method was evaluated by moving the carbon beam axis, the X-ray axis, and the setup angle. The weekly changes of vertical and lateral beams in all rooms were also evaluated. RESULTS: The displacements of the carbon beam axis and the setup angle did not influence the calculation results, whereas the displacement of the X-ray axis did (R=0.999). The displacements including weekly changes were all less than 1.00 mm. CONCLUSION: An evaluation method for calculating the displacement directly and simply between the carbon beam axis and positioning X-ray axis was developed and verified. The weekly changes of displacement between axes were evaluated to be acceptable at our facility.

Development of an automatic evaluation method for patient positioning error.

Highly accurate radiotherapy needs highly accurate patient positioning. At our facility, patient positioning is manually performed by radiology technicians. After the positioning, positioning error is measured by manually comparing some positions on a digital radiography image (DR) to the corresponding positions on a digitally reconstructed radiography image (DRR). This method is prone to error and can be time-consuming because of its manual nature. Therefore, we propose an automated measuring method for positioning error to improve patient throughput and achieve higher reliability. The error between a position on the DR and a position on the DRR was calculated to determine the best matched position using the block-matching method. The zero-mean normalized cross correlation was used as our evaluation function, and the Gaussian weight function was used to increase importance as the pixel position approached the isocenter. The accuracy of the calculation method was evaluated using pelvic phantom images, and the method's effectiveness was evaluated on images of prostate cancer patients before the positioning, comparing them with the results of radiology technicians' measurements. The root mean square error (RMSE) of the calculation method for the pelvic phantom was 0.23 ± 0.05 mm. The coefficients between the calculation method and the measurement results of the technicians were 0.989 for the phantom images and 0.980 for the patient images. The RMSE of the total evaluation results of positioning for prostate cancer patients using the calculation method was 0.32 ± 0.18 mm. Using the proposed method, we successfully measured residual positioning errors. The accuracy and effectiveness of the method was evaluated for pelvic phantom images and images of prostate cancer patients. In the future, positioning for cancer patients at other sites will be evaluated using the calculation method. Consequently, we expect an improvement in treatment throughput for these other sites.

Robustness of patient positioning for interfractional error in carbon ion radiotherapy for stage I lung cancer: Bone matching versus tumor matching.

BACKGROUND AND PURPOSE: Patient positioning was compared by tumor matching (TM) and conventional bony structure matching (BM) in carbon ion radiotherapy for stage I non-small cell lung cancer to evaluate the robustness of TM and BM in determining interfractional error. MATERIAL AND METHODS: Sixty irradiation fields were analyzed. Computed tomography (CT) images acquired before treatment initiation for confirmation (Conf-CT) were obtained under the same settings as the treatment planning CT images and used to evaluate both positioning methods. The dose distributions were recalculated for Conf-CT using both BM and TM, and the dose-volume histogram parameters [V95% of clinical target volume, V5Gy(RBE) of normal lung, and acceptance ratio (ratio of cases with V95% > 95%)] were evaluated. The required margin, which in 90% of cases achieved the acceptable condition, was also examined. RESULTS: Using BM and TM, the median V95% was 98.93% and 100% (p < 0.001) and the mean V5Gy(RBE) was 135.9 and 125.8 (p = 0.694), respectively. The estimated required margins were 7.9 and 3.3 mm and increased by 53.9% and 2.5% of V5Gy(RBE), respectively, compared with planning. CONCLUSIONS: TM ensured a better dose distribution than did BM. To enable TM, volumetric imaging is crucial and should replace 2D radiographs for carbon therapy of stage I lung cancer.

Potential Pitfalls of a Fiducial Marker-matching Technique in Carbon-ion Radiotherapy for Lung Cancer.

BACKGROUND/AIM: To analyze the accuracy of patient positioning and dose distribution quality using a fiducial marker-matching technique in carbon-ion radiotherapy (C-ion RT) for stage I lung cancer. PATIENTS AND METHODS: Thirteen patients with 26 fiducial markers and 104 radiation fields were examined. Change in the fiducial marker position coordinates from the gross tumor volume center (Δm), and change in the water-equivalent path length of the chest wall (ΔWEL) were measured in each radiation field. Criterion for an acceptable change in dose distribution was defined as the percentage of D95 (%D95) at gross tumor volume greater than 90% of the prescribed dose. RESULTS: Thirteen radiation fields (12.5%) were classified as unacceptable. Δm and ΔWEL had significant negative correlations with %D95 and thus were significant factors related to unacceptable irradiation fields. CONCLUSION: Patient positioning using a fiducial marker-matching technique resulted in 12.5% of radiation fields demonstrating unacceptable degradation due to Δm and ΔWEL.

Study of interleukin-6 in the spread of colorectal cancer: the diagnostic significance of IL-6.

We investigated the diagnostic significance of IL-6 for lymph node metastasis and/or hepatic metastasis from colorectal cancer in 65 patients and evaluated the contributions of 8 factors (IL-6, HGF, IL-1beta, TNF-alpha, TGF-beta1, ELAM-1, ICAM-1, VCAM-1) toward Dukes.s classification of 53 patients. We also examined IL-6 expression in tumor tissue. From the receiver operating characteristic (ROC) curve analysis, an optimal cutoff value of 5.8 pg/ml was determined to classify lymph node and/or hepatic metastasis, and that of 6.3 pg/ml was determined to classify hepatic metastasis. These values indicated sensitivities of 55.0% and 71.4%, and specifi cities of 100% and 88.6%, respectively. IL-6, HGF, and ELAM-1 were very useful for distinguishing among Dukes.s A/B group, C group, and D group. In all cases with high IL-6 values (more than 25.0 pg/ml), immunohistochemical staining was positive for IL-6 in the cytoplasm of cancer cells. IL-6 is strongly suspected to be involved in lymph node and/or hepatic metastasis by promoting it through HGF, and serum IL-6 value (pg/ml) would be useful diagnostically to estimate whether or not there is a high risk of lymph node and/or hepatic metastasis.

The Ionomic Study of Vegetable Crops.

Soil contains various essential and nonessential elements, all of which can be absorbed by plants. Plant ionomics is the study of the accumulation of these elements (the ionome) in plants. The ionomic profile of a plant is affected by various factors, including species, variety, organ, and environment. In this study, we cultivated various vegetable crop species and cultivars under the same field conditions and analyzed the level of accumulation of each element in the edible and nonedible parts using ionomic techniques. The concentration of each element in the edible parts differed between species, which could be partly explained by differences in the types of edible organs (root, leaf, seed, and fruit). For example, the calcium concentration was lower in seeds and fruit than in other organs because of the higher dependency of calcium accumulation on xylem transfer. The concentration of several essential microelements and nonessential elements in the edible parts also varied greatly between cultivars of the same species, knowledge of which will help in the breeding of vegetables that are biofortified or contain lower concentrations of toxic elements. Comparison of the ionomes of the fruit and leaves of tomato (Solanum lycopersicum) and eggplant (S. melongena) indicated that cadmium and boron had higher levels of accumulation in eggplant fruit, likely because of their effective transport in the phloem. We also found that homologous elements that have been reported to share the same uptake/transport system often showed significant correlation only in a few families and that the slopes of these relationships differed between families. Therefore, these differences in the characteristics of mineral accumulation are likely to affect the ionomic profiles of different families.

Application of ionomics to plant and soil in fields under long-term fertilizer trials.

Ionomics is the study of elemental accumulation in living organisms using high-throughput elemental profiling. In the present study, we examined the ionomic responses to nutrient deficiency in maize grown in the field in long-term fertilizer trials. Furthermore, the available elements in the field soils were analyzed to investigate their changes under long-term fertilizer treatment and the ionomic relationships between plant and soil. Maize was cultivated in a field with the following five long-term fertilizer treatments: complete fertilization, fertilization without nitrogen, without phosphorus, without potassium, and no fertilization. Concentrations of 22 elements in leaves at an early flowering stage and in soils after harvest were determined. The fertilizer treatments changed the availabilities of many elements in soils. For example, available cesium was decreased by 39 % and increased by 126 % by fertilizations without nitrogen and potassium, respectively. Effects of treatments on the ionome in leaves were evaluated using the translocation ratio (the concentration in leaves relative to the available concentration in soils) for each element. Nitrogen deficiency specifically increased the uptake ability of molybdenum, which might induce the enhancement of nitrogen assimilation and/or endophytic nitrogen fixation in plant. Potassium deficiency drastically enhanced the uptake ability of various cationic elements. These elements might act as alternatives to K in osmoregulation and counterion of organic/inorganic anions. Two major groups of elements were detected by multivariate analyses of plant ionome. Elements in the same group may be linked more or less in uptake and/or translocation systems. No significant correlation between plant and soil was found in concentrations of many elements, even though various soil extraction methods were applied, implying that the interactions between the target and other elements in soil must be considered when analyzing mineral dynamics between plant and soil.

Technical approach to individualized respiratory-gated carbon-ion therapy for mobile organs.

We propose a strategy of individualized image acquisitions and treatment planning for respiratory-gated carbon-ion therapy. We implemented it in clinical treatments for diseases of mobile organs such as lung cancers at the Gunma University Heavy Ion Medical Center in June 2010. Gated computed tomography (CT) scans were used for treatment planning, and four-dimensional (4D) CT scans were used to evaluate motion errors within the gating window to help define the internal margins (IMs) and planning target volume for each patient. The smearing technique or internal gross tumor volume (IGTV = GTV + IM), where the stopping power ratio was replaced with the tumor value, was used for range compensation of moving targets. Dose distributions were obtained using the gated CT images for the treatment plans. The influence of respiratory motion on the dose distribution was verified with the planned beam settings using 4D CT images at some phases within the gating window before the adoption of the plan. A total of 14 lung cancer patients were treated in the first year. The planned margins with the proposed method were verified with clinical X-ray set-up images by deriving setup and internal motion errors. The planned margins were considered to be reasonable compared with the errors, except for large errors observed in some cases.

Clinical significance of interleukin-6 (IL-6) in the spread of gastric cancer: role of IL-6 as a prognostic factor.

BACKGROUND: It is becoming clear that various cytokines are associated with the spread of cancer cells. The purpose of this study was to compare interleukin (IL)-6 levels in patients with gastric cancer to elucidate the role of IL-6 in predicting the spread of tumors. METHODS: In 60 patients, we assessed the correlation of serum IL-6 (pg/ml) with stage, histological findings, hepatic metastasis, and related factors (hepatocyte growth factor [HGF], IL-1beta, tumor necrosis factor [TNF]-alpha, and transforming growth factor [TGF]-beta1). We also investigated the diagnostic significance of the IL-6 level for advanced gastric cancer and lymph node metastasis, as well as the association between IL-6 elevation and outcome. Finally, we examined the expression of IL-6 in tumor tissue. RESULTS: Significant relationships were seen between serum IL-6 and stage, depth of tumor invasion (pT), lymphatic invasion (ly), venons invasion (v)*, lymph node metastasis (pN), hepatic metastasis (cH), and HGF (P < 0.01; *P < 0.05). With regard to the diagnostic significance of the IL-6 level for advanced gastric cancer and lymph node metastasis, when the cutoff value of IL-6 was set at 1.97 pg/ml, the sensitivity was 81.8% and 87.5%; specificity was 66.7% and 58.3%; and accuracy was 77.1% and 72.9%, respectively. The 1- and 3-year cumulative survival rates for patients with an IL-6 value of more than 1.97 pg/ml (69.0% and 43.4%, respectively) were significantly lower than those for patients with an IL-6 value of 1.97 pg/ml or less (94.4% and 87.2%, respectively; P < 0.05). Immunohistochemical staining was positive for IL-6 in the cytoplasm of cancer cells. CONCLUSION: We suspect that IL-6 is involved in cancer invasion and lymph node and/or hepatic metastasis. Our results indicate that IL-6 could be used as a prognostic factor for survival.