Masahide Saito

Evaluation of patient DVH‐based QA metrics for prostate VMAT: correlation between accuracy of estimated 3D patient dose and magnitude of MLC misalignment

The purpose of this study was to evaluate the accuracy of commercially available software, using patient DVH‐based QA metrics, by investigating the correlation between estimated 3D patient dose and magnitude of MLC misalignments. We tested 3DVH software with an ArcCHECK. Two different calculating modes of ArcCHECK Planned Dose Perturbation (ACPDP) were used: “Normal Sensitivity” and “High Sensitivity”. Ten prostate cancer patients treated with hypofractionated VMAT (67.6 Gy/26 Fr) in our hospital were studied. For the baseline plan, we induced MLC errors (−0.75,−0.5,−0.25,0.25,0.5, and 0.75 mm for each single bank). We calculated the dose differences between the ACPDP dose with error and TPS dose with error using gamma passing rates and using DVH‐based QA metrics. The correlations between dose estimation error and MLC position error varied with each structure and metric. A comparison using 1%/1 mm gamma index showed that the larger was the MLC error‐induced, the worse were the gamma passing rates. Slopes of linear fit to dose estimation error versus MLC position error for mean dose and D95 to the PTV were 1.76 and 1.40% mm−1, respectively, for “Normal Sensitivity”, and −0.53 and 0.88% mm−1, respectively, for “High Sensitivity”, showing better accuracy for “High Sensitivity” than “Normal Sensitivity”. On the other hand, the slopes for mean dose to the rectum and bladder, V35 to the rectum and bladder and V55 to the rectum and bladder, were −1.00,−0.55,−2.56,−1.25,−3.53, and 1.85% mm−1, respectively, for “Normal Sensitivity”, and −2.89,−2.39,−4.54,−3.12,−6.24, and −4.11% mm−1, respectively, for “High Sensitivity”, showing significant better accuracy for “Normal Sensitivity” than “High Sensitivity”. Our results showed that 3DVH had some residual error for both sensitivities. Furthermore, we found that “Normal Sensitivity” might have better accuracy for the DVH metric for the PTV and that “High Sensitivity” might have better accuracy for DVH metrics for the rectum and bladder. We must be willing to tolerate this residual error in clinical care. PACS number: 87.55Qr

Assessment of myocardial metabolic disorder associated with mediastinal radiotherapy for esophageal cancer -a pilot study.

BackgroundTo evaluate the dose-effect relations for myocardial metabolic disorders after mediastinal radiotherapy (RT) by performing iodine-123 β-methyl-iodophenyl pentadecanoic acid (I-123 BMIPP) scintigraphy.MethodsBetween 2011 and 2012, we performed I-123 BMIPP scintigraphy for patients with esophageal cancer before and six months after curative mediastinal RT. Single photon emission computed tomography (SPECT) images of pre-RT and post-RT were registered into RT dose distributions. The myocardium was contoured, and the regional RT dose was calculated. Normalization is required to compare pre- and post-RT SPECT images because the uptake pattern is changed due to the breathing level. Normalization was applied on the mean of SPECT counts in regions of the myocardium receiving less than 5 Gy. Relative values in each dose region (interval of 5 Gy) were calculated on the basis of this normalization for each patient. The reduction in the percent of relative values was calculated.ResultsFive patients were enrolled in this study. None of the patients had a past history of cardiac disease. The left ventricle was partially involved in RT fields in all patients. The patients received RT with median total doses of 60-66 Gy for the primary tumor and metastatic lymph nodes. Concomitant chemotherapy consisting of cisplatin or nedaplatin and 5-fluorouracil with RT was performed in 4 patients. All patients had reduced uptake corresponding to RT fields. Dose-effect relations for reduced uptake tended to be observed at 6 months after RT with mean decreases of 8.96% in regions at 10-15 Gy, 12.6% in regions at 20-25 Gy, 15.6% in regions at 30-35 Gy, 19.0% in regions at 40-45 Gy and 16.0% in regions at 50-55 Gy.ConclusionsDose-effect relations for myocardial metabolic disorders tended to be observed. We may need to make an effort to reduce high-dose mediastinal RT to the myocardium in RT planning.

Comparison of DVH‐based plan verification methods for VMAT: ArcCHECK‐3DVH system and dynalog‐based dose reconstruction

Abstract The purpose of this study was comparing dose‐volume histogram (DVH)‐based plan verification methods for volumetric modulated arc therapy (VMAT) pretreatment QA. We evaluated two 3D dose reconstruction systems: ArcCHECK‐3DVH system (Sun Nuclear corp.) and Varian dynalog‐based dose reconstruction (DBDR) system, developed in‐house. Fifteen prostate cancer patients (67.6 Gy/26 Fr), four head and neck cancer patient (66 Gy/33 Fr), and four esophagus cancer patients (60 Gy/30 Fr) treated with VMAT were studied. First, ArcCHECK measurement was performed on all plans; simultaneously, the Varian dynalog data sets that contained the actual delivered parameters (leaf positions, gantry angles, and cumulative MUs) were acquired from the Linac control system. Thereafter, the delivered 3D patient dose was reconstructed by 3DVH software (two different calculating modes were used: High Sensitivity (3DVH‐HS) and Normal Sensitivity (3DVH‐NS)) and in‐house DBDR system. We evaluated the differences between the TPS‐calculated dose and the reconstructed dose using 3D gamma passing rates and DVH dose index analysis. The average 3D gamma passing rates (3%/3 mm) between the TPS‐calculated dose and the reconstructed dose were 99.1 ± 0.6%, 99.7 ± 0.3%, and 100.0 ± 0.1% for 3DVH–HS, 3DVH–NS, and DBDR, respectively. For the prostate cases, the average differences between the TPS‐calculated dose and reconstructed dose in the PTV mean dose were 1.52 ± 0.50%, −0.14 ± 0.55%, and −0.03 ± 0.07% for 3DVH–HS, 3DVH–NS, and DBDR, respectively. For the head and neck and esophagus cases, the dose difference to the TPS‐calculated dose caused by an effect of heterogeneity was more apparent under the 3DVH dose reconstruction than the DBDR. Although with some residual dose reconstruction errors, these dose reconstruction methods can be clinically used as effective tools for DVH‐based QA for VMAT delivery.

Cytosolic Glutamine Synthetase Isozymes Play Redundant Roles in Ammonium Assimilation Under Low-Ammonium Conditions in Roots of Arabidopsis thaliana

Ammonium is a major nitrogen source for plants; it is assimilated into glutamine via a reaction catalyzed by glutamine synthetase (GLN). Arabidopsis expresses four cytosolic GLN genes, GLN1; 1, GLN1; 2, GLN1; 3 and GLN1; 4, in roots. However, the function and organization of these GLN1 isozymes in ammonium assimilation in roots remain unclear. In this study, we aimed to characterize the four GLN1 isozymes. The levels of growth of the wild type and gln1 single and multiple knockout lines were compared in a hydroponic culture at ammonium concentrations of 0.1 and 3 mM. Under the low-ammonium concentration, in single mutants for each GLN1 gene, there was little effect on growth, whereas the triple mutant for GLN1; 1, GLN1; 2 and GLN1; 3 grew slowly and accumulated ammonium. Under the high-ammonium concentration, the single mutant for GLN1; 2 showed 50% decreases in fresh weight and glutamine, whereas the other gln1 single mutants did not show notable changes in the phenotype. The double mutant for GLN1; 1 and GLN1; 2 showed less growth and a lower glutamine concentration than the single mutant for GLN1; 2. Promoter analysis indicated an overlapping expression of GLN1; 1 with GLN1; 2 in the surface layers of the roots. We thus concluded that: (i) at a low concentration, ammonium was assimilated by GLN1; 1, GLN1; 2 and GLN1; 3, and they were redundant; (ii) low-affinity GLN1; 2 could contribute to ammonium assimilation at concentrations ranging from 0.1 to 3 mM; and (iii) GLN1; 1 supported GLN1; 2 within the outer cell layers of the root.

Transcriptional repressor IAA17 is involved in nitrogen use by modulating cytosolic glutamine synthetase GLN1;2 in Arabidopsis roots

ABSTRACT Nitrogen is an essential element for plant growth. Development of the root system architecture is highly correlated with nitrogen availability from the environment. Recent studies show that auxin response modules are involved in nitrate-dependent lateral root growth. However, the role of auxin in nitrogen metabolism remains to be elucidated. Few researchers have addressed the effect of auxin signaling modules on the use of ammonium for nutrition. The purpose of this study was to describe and examine the relation between auxin signaling modules and ammonium for nutrition. The growth of T-DNA insertion lines for auxin signaling modules was compared with that of a wild type under different nitrogen regimes. Nitrogen use efficiency consists of two components: metabolism and uptake. The nitrogen usage index was calculated following elemental analysis to evaluate nitrogen metabolism. Isotope-labeled ammonium uptake was measured under nitrogen-deficient and -sufficient conditions. Transcriptional levels and accumulation of enzymes necessary for primary ammonium assimilation, glutamine synthetase and glutamate synthase were evaluated. One of the T-DNA insertion lines for the auxin signaling module, IAA17, showed severe growth reduction in hydroponic solution containing ammonium as a major nitrogen source. The accumulation of cytosolic glutamine synthetase was reduced in the roots of iaa17. The expression of cytosolic glutamine synthetase 1;2 in iaa17 did not respond to ammonium supply. Here we show that the auxin signaling module has an effect on ammonium use by regulating the transcriptional level of cytosolic glutamine synthetase 1;2 in the root, the gene essential for ammonium assimilation.

TU-G-BRD-09: Evaluation of Patient DVH-Based QA Metrics for Prostate VMAT: Correlation Between Accuracy of Estimated 3D Patient Dose and MLC Position Error

Purpose: The purpose of this study was to evaluate the accuracy of patient DVH-based QA metrics and test the hypothesis: measurement-guided 3D dose reconstruction (MGDR) captures the induced dose error. Methods: We used 3DVH software with an ArcCHECK to estimate 3D patient dose by MGDR. Two different calculating modes of MGDR were used: “Normal Sensitivity” and “High Sensitivity”. Ten prostate cancer patients treated with hypo-fractionated VMAT (67.6 Gy/26 Fr) were studied. For the baseline plan, we induced MLC errors (−0.75, −0.5, −0.25, 0.25, 0.5 and 0.75 mm for each single bank), generated by in-house software. We compared the 3D patient dose estimated by 3DVH and that calculated by the treatment planning system. We evaluated the correlation between dose estimation error and MLC position error. Results: Slopes of linear fit to dose estimation error versus MLC position error for mean dose and D95 to the PTV were 1.76 and 1.40% mm-1, respectively, for “Normal Sensitivity” and −0.53 and −0.88% mm-1, respectively, for “High Sensitivity”, showing better accuracy for “High Sensitivity” than “Normal Sensitivity”. On the other hand, the slopes for mean dose to the rectum and bladder and V55 to the rectum and bladder were −1.00, −0.55, −3.53 and −1.85% mm-1, respectively, for “Normal Sensitivity” and −2.89, −2.39, −6.24 and −4.11% mm-1, respectively, for “High Sensitivity”, showing significant better accuracy for “Normal Sensitivity” than “High Sensitivity”. Conclusion: Our results showed that 3DVH had some residual error for both sensitivities, indicating the MGDR could capture a part of the induced error but not all of the induced error.Furthermore, we found that “Normal Sensitivity” might have better accuracy for the DVH metric for PTV and that “High Sensitivity” might have better accuracy for DVH metrics for the rectum and bladder. We must be willing to tolerate this residual error in clinical care.

Left Ventricular T1 Mapping during Chemotherapy–Radiation Therapy: Serial Assessment of Participants with Esophageal Cancer

Purpose To assess changes in left ventricular function and tissue composition by using MRI after chemotherapy-radiation therapy in participants with esophageal cancer. Materials and Methods Between January 2013 and April 2015, this prospective study enrolled 24 participants (42% women; mean age, 63 years; range, 49-73 years) scheduled for chemotherapy-radiation therapy. 3.0-T MRI examinations were performed before, at 0.5 year, and at 1.5 years after chemotherapy-radiation therapy. Myocardial native T1, postcontrast T1, and extracellular volume were measured in basal septum (as irradiated areas) and apical lateral wall (as nonirradiated areas). Left ventricular function, prevalence of late gadolinium enhancement, and T1 and extracellular volume values were compared over the follow-up period by using Friedman or Cochran Q tests, followed by Dunn test. Results In 14 participants who were followed up for 1.5 years, native T1 and extracellular volume in the septum were elevated at 0.5 year compared with baseline (1183 msec ± 46 [standard deviation] vs 1257 msec ± 35; 26% ± 3 vs 32% ± 3; adjusted P < .01 for both), but not in the lateral wall. Left ventricular stroke volume index and late gadolinium enhancement changed at 1.5 years compared with baseline (41 mL/m2 ± 11 vs 36 mL/m2 ± 9; P = .046; 7% [one of 14] vs 78% [11 of 14]; P < .01). Other measures of left ventricular function did not change during the follow-up period (P > .10 for all). Conclusion Native T1 and extracellular volume could detect early changes in myocardium at 0.5 year after chemotherapy-radiation therapy, whereas left ventricular stroke volume index and late gadolinium enhancement showed abnormality at 1.5 years.

Technical Note: Evaluation of the latency and the beam characteristics of a respiratory gating system using an Elekta linear accelerator and a respiratory indicator device, Abches

PURPOSE To evaluate the basic performance of a respiratory gating system using an Elekta linac and an Abches respiratory-monitoring device. METHODS The gating system was comprised of an Elekta Synergy linac equipped with a ResponseTM gating interface module and an Abches respiratory-monitoring device. The latencies from a reference respiratory signal to the resulting Abches gating output signal and the resulting monitor-ion-chamber output signal were measured. Then, the flatness and symmetry of the gated beams were measured using a two-dimensional ionization chamber array for fixed and arc beams, respectively. Furthermore, the beam quality, TPR20,10 , and the output of the fixed gated beams were also measured using a Farmer chamber. Each of the beam characteristics was compared with each of those for nongated irradiation. RESULTS The full latencies at beam-on and beam-off for 6-MV gated beams were 336.4 ± 23.4 ms and 87.6 ± 7.1 ms, respectively. The differences in flatness between the gated and nongated beams were within 0.91% and 0.87% for the gun-target and left-right directions, respectively. In the same manner, the beam symmetries were within 0.68% and 0.82%, respectively. The percentage differences in beam quality and beam output were below 1% for a beam-on time range of 1.1-7 s. CONCLUSION The latency of the Elekta gating system combined with Abches was found to be acceptable using our measurement method. Furthermore, we demonstrated that the beam characteristics of the gating system using our respiratory indicator were comparable with the nongated beams for a single-arc gated beam delivery.

Comparison of MLC error sensitivity of various commercial devices for VMAT pre‐treatment quality assurance

Abstract The purpose of this study was to compare the MLC error sensitivity of various measurement devices for VMAT pre‐treatment quality assurance (QA). This study used four QA devices (Scandidos Delta4, PTW 2D‐array, iRT systems IQM, and PTW Farmer chamber). Nine retrospective VMAT plans were used and nine MLC error plans were generated for all nine original VMAT plans. The IQM and Farmer chamber were evaluated using the cumulative signal difference between the baseline and error‐induced measurements. In addition, to investigate the sensitivity of the Delta4 device and the 2D‐array, global gamma analysis (1%/1, 2%/2, and 3%/3 mm), dose difference (1%, 2%, and 3%) were used between the baseline and error‐induced measurements. Some deviations of the MLC error sensitivity for the evaluation metrics and MLC error ranges were observed. For the two ionization devices, the sensitivity of the IQM was significantly better than that of the Farmer chamber (P < 0.01) while both devices had good linearly correlation between the cumulative signal difference and the magnitude of MLC errors. The pass rates decreased as the magnitude of the MLC error increased for both Delta4 and 2D‐array. However, the small MLC error for small aperture sizes, such as for lung SBRT, could not be detected using the loosest gamma criteria (3%/3 mm). Our results indicate that DD could be more useful than gamma analysis for daily MLC QA, and that a large‐area ionization chamber has a greater advantage for detecting systematic MLC error because of the large sensitive volume, while the other devices could not detect this error for some cases with a small range of MLC error.

TU-AB-202-01: Multi-Institutional Validation Study of Commercially Available Deformable Image Registration Software for Thoracic Images

PURPOSE The purpose of this study was to assess the accuracy of commercially available deformable image registration (DIR) software for thoracic images on multi-institution. Furthermore, we determined the variation in the DIR accuracy among institutions due to different DIR algorithms and DIR procedures. METHODS Thoracic four-dimensional (4D) CT images of ten patients with esophagus or lung cancer were used. Datasets for these patients were provided by DIR-lab (dir-lab.com) and included a coordinate list of anatomical landmarks (300 bronchial bifurcations) that had been manually identified. DIR was performed between peak-inhale and peak-exhale images. DIR registration error was determined by calculating the difference at each landmark point between displacement calculated by DIR software and that calculated by the landmark. RESULTS Eleven institutions participated in this study: Four institutions used RayStation (RaySearch Laboratories, Stockholm, Sweden), five institutions used MIM software (MIM Software Inc, Cleveland, OH) and three institutions used Velocity (Varian Medical Systems, Palo Alto, CA). The range of average absolute registration errors over all cases were 0.48-1.51 mm (right-left), 0.53-2.86 mm (anterior-posterior), 0.85-4.46 mm (superiorinferior) and 1.26-6.20 mm (three-dimensional [3D]). For each DIR software, the average 3D registration error (range) was 3.28mm (1.26-3.91 mm) for RayStation; MIM was 3.29mm (2.17-3.61 mm); Velocity was 5.01mm (4.02-6.20 mm). These results showed that there was moderate variation among institutions, even though the DIR software was same. CONCLUSION We evaluated the commercially available DIR software using thoracic 4D CT images on multi-center. Our results demonstrated that DIR accuracy differed among institutions because it was dependent on both DIR software and DIR procedure. Our results could be helpful for establishment of prospective clinical trials and widespread use of DIR software. In addition, in clinical care, we should try to find the optimal DIR procedure, when DIR was performed using thoracic 4D-CT data to calculate the accumulated dose.