Yujiro Nakajima

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.

Evaluation of deformable image registration between external beam radiotherapy and HDR brachytherapy for cervical cancer with a 3D‐printed deformable pelvis phantom

Purpose In this study, we developed a 3D‐printed deformable pelvis phantom for evaluating spatial DIR accuracy. We then evaluated the spatial DIR accuracies of various DIR settings for cervical cancer. Methods A deformable female pelvis phantom was created based on patient CT data using 3D printing. To create the deformable uterus phantom, we first 3D printed both a model of uterus and a model of the internal cavities of the vagina and uterus. We then made a mold using the 3D printed uterus phantom. Finally, urethane was poured into the mold with the model of the internal cavities in place, creating the deformable uterus phantom with a cavity into which an applicator could be inserted. To create the deformable bladder phantom, we first 3D printed models of the bladder and of the same bladder scaled down by 2 mm. We then made a mold using the larger bladder model. Finally, silicone was poured into the mold with the smaller bladder model in place to create the deformable bladder phantom with a wall thickness of 2 mm. To emulate the anatomical bladder, water was poured into the created bladder. We acquired phantom image without applicator for EBRT. Then, we inserted the applicator into the phantom to simulate BT. In this situation, we scanned the phantom again to obtain the phantom image for BT. We performed DIR using the two phantom images in two cases: Case A, with full bladder (170 ml) in both EBRT and BT images; and Case B with full bladder in the BT image and half‐full bladder (100 ml) in the EBRT image. DIR was evaluated using Dice similarity coefficients (DSCs) and 31 landmarks for the uterus and 25 landmarks for the bladder. A hybrid intensity and structure DIR algorithm implemented in RayStation with four DIR settings was evaluated. Results On visual inspection, reasonable agreement in shape of the uterus between the phantom and patient CT images was observed for both EBRT and BT, although some regional disagreements in shape of the bladder and rectum were apparent. The created phantom could reproduce the actual patients uterus deformation by the applicator. For both Case A and B, large variation was seen in landmark error among the four DIR parameters. In addition, although DSCs were comparable, moderate differences in landmark error existed between the two different DIR parameters selected from the four DIR parameters (i.e., DSC = 0.96, landmark error = 13.2 ± 5.7 mm vs. DSC = 0.97, landmark error = 9.7 ± 4.0 mm). This result suggests that landmark error evaluation might thus be more effective than DSC for evaluating DIR accuracy. Conclusions Our developed phantom enabled the evaluation of spatial DIR accuracy for the female pelvic region for the first time. Although the DSCs are high, the spatial errors can still be significant and our developed phantom facilitates their quantification. Our results showed that optimization is needed to identify suitable DIR settings. For determining suitable DIR settings, our method of evaluating spatial DIR accuracy using the 3D‐printed phantom may prove helpful.

Comparison of xerostomia incidence after three-dimensional conformal radiation therapy and contralateral superficial lobe parotid-sparing intensity-modulated radiotherapy for oropharyngeal and hypopharyngeal cancer

OBJECTIVE In the treatment of head-neck cancer, parotid-sparing intensity-modulated radiotherapy (IMRT) could reduce the incidence of xerostomia. When the parotid glands cannot be sufficiently spared because of the widespread tumor, contralateral superficial lobe parotid-sparing (CSLPS)-IMRT could be used to reduce marginal recurrence, however the success of this approach remains to be determined. The primary purpose of this study was to compare the incidence of xerostomia between three-dimensional conformal radiotherapy (3D-CRT) and CSLPS-IMRT for oropharyngeal and hypopharyngeal cancer. In a second aim, we also compared the clinical efficacy of 3D-CRT and CSLPS-IMRT. METHODS We retrospectively reviewed the medical records of locally advanced oropharyngeal and hypopharyngeal cancer patients who were treated with definitive concurrent chemoradiotherapy between June 2007 and April 2014. We estimated the average mean dose delivered to the parotid glands, the incidence of xerostomia≥Grade 2, patterns of failure, and survival outcomes. RESULTS Seventeen patients received 3D-CRT and 21 received CSLPS-IMRT. The average mean dose delivered to the superficial lobe of the contralateral parotid gland was 45.3Gy and 26.6Gy (p<0.001), and the incidence of xerostomia≥Grade 2 following treatment was 75% and 26% at 12 months (p=0.012) and 67% and 18% at 24 months (p=0.018) in the 3D-CRT and CSLPS-IMRT groups, respectively. Patterns of failure did not differ between the two groups. The 2-year progression-free survival was 59% and 62% (p=0.73), and the 2-year overall survival rate was 71% and 71% in the 3D-CRT and CSLPS-IMRT groups, respectively (p=0.76). CONCLUSION Incidence of xerostomia was significantly lower in patients receiving CSLPS-IMRT compared with 3D-CRT, while clinical efficacy did not differ between two treatment strategies.

Evaluation of rectum and bladder dose accumulation from external beam radiotherapy and brachytherapy for cervical cancer using two different deformable image registration techniques

ABSTRACT We evaluated dose–volume histogram (DVH) parameters based on deformable image registration (DIR) between brachytherapy (BT) and external beam radiotherapy (EBRT) that included a center-shielded (CS) plan. Eleven cervical cancer patients were treated with BT, and their pelvic and CS EBRT were studied. Planning CT images for EBRT and BT (except for the first BT, used as the reference image) were deformed with DIR to reference image. We used two DIR parameter settings: intensity-based and hybrid. Mean Dice similarity coefficients (DSCs) comparing EBRT with the reference for the uterus, rectum and bladder were 0.81, 0.77 and 0.83, respectively, for hybrid DIR and 0.47, 0.37 and 0.42, respectively, for intensity-based DIR (P < 0.05). D1 cm3 for hybrid DIR, intensity-based DIR and DVH addition were 75.1, 81.2 and 78.2 Gy, respectively, for the rectum, whereas they were 93.5, 92.3 and 94.3 Gy, respectively, for the bladder. D2 cm3 for hybrid DIR, intensity-based DIR and DVH addition were 70.1, 74.0 and 71.4 Gy, respectively, for the rectum, whereas they were 85.4, 82.8 and 85.4 Gy, respectively, for the bladder. Overall, hybrid DIR obtained higher DSCs than intensity-based DIR, and there were moderate differences in DVH parameters between the two DIR methods, although the results varied among patients. DIR is only experimental, and extra care should be taken when comparing DIR-based dose values with dose–effect curves established using DVH addition. Also, a true evaluation of DIR-based dose accumulation would require ground truth data (e.g. measurement with physical phantom).

Comparison of visual biofeedback system with a guiding waveform and abdomen-chest motion self-control system for respiratory motion management

Irregular breathing can influence the outcome of 4D computed tomography imaging and cause artifacts. Visual biofeedback systems associated with a patient-specific guiding waveform are known to reduce respiratory irregularities. In Japan, abdomen and chest motion self-control devices (Abches) (representing simpler visual coaching techniques without a guiding waveform) are used instead; however, no studies have compared these two systems to date. Here, we evaluate the effectiveness of respiratory coaching in reducing respiratory irregularities by comparing two respiratory management systems. We collected data from 11 healthy volunteers. Bar and wave models were used as visual biofeedback systems. Abches consisted of a respiratory indicator indicating the end of each expiration and inspiration motion. Respiratory variations were quantified as root mean squared error (RMSE) of displacement and period of breathing cycles. All coaching techniques improved respiratory variation, compared with free-breathing. Displacement RMSEs were 1.43 ± 0.84, 1.22 ± 1.13, 1.21 ± 0.86 and 0.98 ± 0.47 mm for free-breathing, Abches, bar model and wave model, respectively. Period RMSEs were 0.48 ± 0.42, 0.33 ± 0.31, 0.23 ± 0.18 and 0.17 ± 0.05 s for free-breathing, Abches, bar model and wave model, respectively. The average reduction in displacement and period RMSE compared with the wave model were 27% and 47%, respectively. For variation in both displacement and period, wave model was superior to the other techniques. Our results showed that visual biofeedback combined with a wave model could potentially provide clinical benefits in respiratory management, although all techniques were able to reduce respiratory irregularities.

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.

Evaluation of functionally weighted dose-volume parameters for thoracic stereotactic ablative radiotherapy (SABR) using CT ventilation

For the purpose of reducing radiation pneumontisis (RP), four-dimensional CT (4DCT)-based ventilation can be used to reduce functionally weighted lung dose. This study aimed to evaluate the functionally weighted dose-volume parameters and to investigate an optimal weighting method to realize effective planning optimization in thoracic stereotactic ablative radiotherapy (SABR). Forty patients treated with SABR were analyzed. Ventilation images were obtained from 4DCT using deformable registration and Hounsfield unit-based calculation. Functionally-weighted mean lung dose (fMLD) and functional lung fraction receiving at least x Gy (fVx) were calculated by two weighting methods: thresholding and linear weighting. Various ventilation thresholds (5th-95th, every 5th percentile) were tested. The predictive accuracy for CTCAE grade ≧ 2 pneumonitis was evaluated by area under the curve (AUC) of receiver operating characteristic analysis. AUC values varied from 0.459 to 0.570 in accordance with threshold and dose-volume metrics. A combination of 25th percentile threshold and fV30 showed the best result (AUC: 0.570). AUC values with fMLD, fV10, fV20, and fV40 were 0.541, 0.487, 0.548 and 0.563 using a 25th percentile threshold. Although conventional MLD, V10, V20, V30 and V40 showed lower AUC values (0.516, 0.477, 0.534, 0.552 and 0.527), the differences were not statistically significant. fV30 with 25th percentile threshold was the best predictor of RP. Our results suggested that the appropriate weighting should be used for better treatment outcomes in thoracic SABR.

Impact of a commercially available model-based dose calculation algorithm on treatment planning of high-dose-rate brachytherapy in patients with cervical cancer

Abstract We evaluated the impact of model-based dose calculation algorithms (MBDCAs) on high-dose-rate brachytherapy (HDR-BT) treatment planning for patients with cervical cancer. Seven patients with cervical cancer treated using HDR-BT were studied. Tandem and ovoid applicators were used in four patients, a vaginal cylinder in one, and interstitial needles in the remaining two patients. MBDCAs were applied to the Advanced Collapsed cone Engine (ACE; Elekta, Stockholm, Sweden). All plans, which were originally calculated using TG-43, were re-calculated using both ACE and Monte Carlo (MC) simulations. Air was used as the rectal material. The mean difference in the rectum D2cm3 between ACErec-air and MCrec-air was 8.60 ± 4.64%, whereas that in the bladder D2cm3 was −2.80 ± 1.21%. Conversely, in the small group analysis (n = 4) using water instead of air as the rectal material, the mean difference in the rectum D2cm3 between TG-43 and ACErec-air was 11.87 ± 2.65%, whereas that between TG-43 and ACErec-water was 0.81 ± 2.04%, indicating that the use of water as the rectal material reduced the difference in D2cm3 between TG-43 and ACE. Our results suggested that the differences in the dose–volume histogram (DVH) parameters of TG-43 and ACE were large for the rectum when considerable air (gas) volume was present in it, and that this difference was reduced when the air (gas) volume was reduced. Also, ACE exhibited better dose calculation accuracy than that of TG-43 in this situation. Thus, ACE may be able to calculate the dose more accurately than TG-43 for HDR-BT in treating cervical cancers, particularly for patients with considerable air (gas) volume in the rectum.

Dosimetric evaluation of MLC-based dynamic tumor tracking radiotherapy using digital phantom: Desired setup margin for tracking radiotherapy

The purpose of this study is to evaluate the dosimetric impact of the margin on the multileaf collimator-based dynamic tumor tracking plan. Furthermore, an equivalent setup margin (EM) of the tracking plan was determined according to the gated plan. A 4-dimensional extended cardiac-torso was used to create 9 digital phantom datasets of different tumor diameters (TDs) of 1, 3, and 5 cm and motion ranges (MRs) of 1, 2, and 3 cm. For each dataset, respiratory gating (30% to 70% phase) and tumor tracking treatment plans were prepared using 8-field 3-dimensional conformal radiation therapy by 4-dimensional dose calculation. The total lung V20 was calculated to evaluate the dosimetric impact for each case and to estimate the EM with the same impact on lung V20 obtained with the gating plan with a setup margin of 5 mm. The EMs for {TD = 1 cm, MR = 1 cm}, {TD = 1 cm, MR = 2 cm}, and {TD = 1 cm, MR = 3 cm} were estimated as 5.00, 4.16, and 4.24 mm, respectively. The EMs for {TD = 5 cm, MR = 1 cm}, {TD = 5 cm, MR = 2 cm}, and {TD = 5 cm, MR = 3 cm} were estimated as 4.24 mm, 6.35 mm, and 7.49 mm, respectively. This result showed that with a larger MR, the EM was found to be increased. In addition, with a larger TD, the EM became smaller. Our result showing the EMs provided the desired accuracy for multileaf collimator-based dynamic tumor tracking radiotherapy.

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.