Development and validation of an [18F]FDG-PET/CT radiomic model for predicting progression-free survival for patients with stage II - III thoracic esophageal squamous cell carcinoma who are treated with definitive chemoradiotherapy.

BACKGROUND: Radiomics is a method for extracting a large amount of information from images and used to predict treatment outcomes, side effects and diagnosis. In this study, we developed and validated a radiomic model of [18F]FDG-PET/CT for predicting progression-free survival (PFS) of definitive chemoradiotherapy (dCRT) for patients with esophageal cancer. MATERIAL AND METHODS: Patients with stage II - III esophageal cancer who underwent [18F]FDG-PET/CT within 45 days before dCRT between 2005 and 2017 were included. Patients were randomly assigned to a training set (85 patients) and a validation set (45 patients). Radiomic parameters inside the area of standard uptake value ≥ 3 were calculated. The open-source software 3D slicer and Pyradiomics were used for segmentation and calculating radiomic parameters, respectively. Eight hundred sixty radiomic parameters and general information were investigated.In the training set, a radiomic model for PFS was made from the LASSO Cox regression model and Rad-score was calculated. In the validation set, the model was applied to Kaplan-Meier curves. The median value of Rad-score in the training set was used as a cutoff value in the validation set. JMP was used for statistical analysis. RStudio was used for the LASSO Cox regression model. p < 0.05 was defined as significant. RESULTS: The median follow-up periods were 21.9 months for all patients and 63.4 months for survivors. The 5-year PFS rate was 24.0%. In the training set, the LASSO Cox regression model selects 6 parameters and made a model. The low Rad-score group had significantly better PFS than that the high Rad-score group (p = 0.019). In the validation set, the low Rad-score group had significantly better PFS than that the high Rad-score group (p = 0.040). CONCLUSIONS: The [18F]FDG-PET/CT radiomic model could predict PFS for patients with esophageal cancer who received dCRT.

Evaluation of the MVCT-based radiomic features as prognostic factor in patients with head and neck squamous cell carcinoma.

BACKGROUND: Megavoltage computed tomography (MVCT) images acquired during each radiotherapy session may be useful for delta radiomics. However, no studies have examined whether the MVCT-based radiomics has prognostic power. Therefore, the purpose of this study was to examine the prognostic power of the MVCT-based radiomics for head and neck squamous cell carcinoma (HNSCC) patients. METHODS: 100 HNSCC patients who received definitive radiotherapy were analyzed and divided into two groups: training (n = 70) and test (n = 30) sets. MVCT images obtained using TomoTherapy for the first fraction of radiotherapy and planning kilovoltage CT (kVCT) images obtained using Aquilion LB CT scanner were analyzed. Primary gross tumor volume (GTV) was propagated from kVCT to MVCT images using rigid registration, and 107 radiomic features were extracted from the GTV in MVCT and kVCT images. Least absolute shrinkage and selection operator (LASSO) Cox regression model was used to examine the association between overall survival (OS) and rad score calculated for each patient by weighting the feature value through the coefficient when features were selected. Then, the predictive values of MVCT-based and kVCT-based rad score and patient-, treatment-, and tumor-specific factors were evaluated. RESULTS: C-indices of the rad score for MVCT- and kVCT-based radiomics were 0.667 and 0.685, respectively. The C-indices of 6 clinical factors were 0.538-0.622. The 3-year OS was significantly different between high- and low-risk groups according to the MVCT-based rad score (50% vs. 83%; p < 0.01). CONCLUSIONS: Our results suggested that MVCT-based radiomics had stronger prognostic power than any single clinical factor and was a useful prognostic factor when predicting OS in HNSCC patients.

Impact of CT scan parameters on deformable image registration accuracy using deformable thorax phantom.

The purpose of this study was to evaluate the deformable image registration (DIR) accuracy using various CT scan parameters with deformable thorax phantom. Our developed deformable thorax phantom (Dephan, Chiyoda Technol Corp, Tokyo, Japan) was used. The phantom consists of a base phantom, an inner phantom, and a motor-derived piston. The base phantom is an acrylic cylinder phantom with a diameter of 180 mm, which simulates the chest wall. The inner phantom consists of deformable, 20 mm thick disk-shaped sponges with 48 Lucite beads and 48 nylon cross-wires which simulate the vascular and bronchial bifurcations of the lung. Peak-exhale and peak-inhale images of the deformable phantom were acquired using a CT scanner (Aquilion LB, TOSHIBA). To evaluate the impact of CT scan parameters on DIR accuracy, we used the four tube voltages (80, 100, 120, and 135 kV) and six reconstruction algorithms (FC11, FC13, FC15, FC41, FC44, and FC52). Intensity-based DIR was performed between the two images using MIM Maestro (MIM software, Cleveland, USA). Fiducial markers (beads and cross-wires) based target registration error (TRE) was used for quantitative evaluation of DIR. In case with different tube voltages, the range of average TRE were 4.44-5.69 mm (reconstruction algorithm: FC13). In case with different reconstruction algorithms, the range of average TRE were 4.26-4.59 mm (tube voltage: 120 kV). The TRE were differed by up to 3.0 mm (3.96-6.96 mm) depending on the combination of tube voltage and reconstruction algorithm. Our result indicated that CT scan parameters had moderate impact of TRE, especially for reconstruction algorithms for the deformable thorax phantom.

Dosimetric impact of deformable image registration using radiophotoluminescent glass dosimeters with a physical geometric phantom.

PURPOSE: To study the dosimetry impact of deformable image registration (DIR) using radiophotoluminescent glass dosimeter (RPLD) and custom developed phantom with various inserts. METHODS: The phantom was developed to facilitate simultaneous evaluation of geometric and dosimetric accuracy of DIR. Four computed tomography (CT) images of the phantom were acquired with four different configurations. Four volumetric modulated arc therapy (VMAT) plans were computed for different phantom. Two different patterns were applied to combination of four phantom configurations. RPLD dose measurement was combined between corresponding two phantom configurations. DIR-based dose accumulation was calculated between corresponding two CT images with two commercial DIR software and various DIR parameter settings, and an open source software. Accumulated dose calculated using DIR was then compared with measured dose using RPLD. RESULTS: The mean ± standard deviation (SD) of dose difference was 2.71 ± 0.23% (range, 2.22%-3.01%) for tumor-proxy and 3.74 ± 0.79% (range, 1.56%-4.83%) for rectum-proxy. The mean ± SD of target registration error (TRE) was 1.66 ± 1.36 mm (range, 0.03-4.43 mm) for tumor-proxy and 6.87 ± 5.49 mm (range, 0.54-17.47 mm) for rectum-proxy. These results suggested that DIR accuracy had wide range among DIR parameter setting. CONCLUSIONS: The dose difference observed in our study was 3% for tumor-proxy and within 5% for rectum-proxy. The custom developed physical phantom with inserts showed potential for accurate evaluation of DIR-based dose accumulation. The prospect of simultaneous evaluation of geometric and dosimetric DIR accuracy in a single phantom may be useful for validation of DIR for clinical use.

Improvement of deep learning prediction model in patient-specific QA for VMAT with MLC leaf position map and patient's dose distribution.

PURPOSE: Deep learning-based virtual patient-specific quality assurance (QA) is a novel technique that enables patient QA without measurement. However, this method could be improved by further evaluating the optimal data to be used as input. Therefore, a deep learning-based model that uses multileaf collimator (MLC) information per control point and dose distribution in patient's CT as inputs was developed. METHODS: Overall, 96 volumetric-modulated arc therapy plans generated for prostate cancer treatment were used. We developed a model (Model 1) that can predict measurement-based gamma passing rate (GPR) for a treatment plan using data stored as a map reflecting the MLC leaf position at each control point (MLPM) and data of the dose distribution in patient's CT as inputs. The evaluation of the model was based on the mean absolute error (MAE) and Pearson's correlation coefficient (r) between the measured and predicted GPR. For comparison, we also analyzed models trained with the dose distribution in patient's CT alone (Model 2) and with dose distributions recalculated on a virtual phantom CT (Model 3). RESULTS: At the 2%/2 mm criterion, MAE[%] and r for Model 1, Model 2, and Model 3 were 2.32% ± 0.43% and 0.54 ± 0.03, 2.70% ± 0.26%, and 0.32 ± 0.08, and 2.96% ± 0.23% and 0.24 ± 0.22, respectively; at the 3%/3 mm criterion, these values were 1.25% ± 0.05% and 0.36 ± 0.18, 1.57% ± 0.35% and 0.19 ± 0.20, and 1.39% ± 0.32% and 0.17 ± 0.22, respectively. This result showed that Model 1 exhibited the lowest MAE and highest r at both criteria of 2%/2 mm and 3%3 mm. CONCLUSIONS: These findings showed that a model that combines the MLPM and dose distribution in patient's CT exhibited a better GPR prediction performance compared with the other two studied models.

Evaluation of Unity 1.5 T MR-linac plan quality in patients with prostate cancer.

The Unity magnetic resonance (MR) linear accelerator (MRL) with MR-guided adaptive radiotherapy (MRgART) is capable of online MRgART where images are acquired on the treatment day and the radiation treatment plan is immediately replanned and performed. We evaluated the MRgART plan quality and plan reproducibility of the Unity MRL in patients with prostate cancer. There were five low- or moderate-risk and five high-risk patients who received 36.25 Gy or 40 Gy, respectively in five fractions. All patients underwent simulation magnetic resonance imaging (MRI) and five online adaptive MRI. We created plans for 5, 7, 9, 16, and 20 beams and for 60, 100, and 150 segments. We evaluated the target and organ doses for different number of beams and segments, respectively. Variation in dose constraint between the simulation plan and online adaptive plan was measured for each patient to assess plan reproducibility. The plan quality improved with the increasing number of beams. However, the proportion of significantly improved dose constraints decreased as the number of beams increased. For some dose parameters, there were statistically significant differences between 60 and 100 segments, and 100 and 150 segments. The plan of five beams exhibited limited reproducibility. The number of segments had minimal impact on plan reproducibility, but 60 segments sometimes failed to meet dose constraints for online adaptive plan. The optimization and delivery time increased with the number of beams and segments. We do not recommend using five or fewer beams for a reproducible and high-quality plan in the Unity MRL. In addition, many number of segments and beams may help meet dose constraints during online adaptive plan. Treatment with the Unity MRL should be performed with the appropriate number of beams and segments to achieve a good balance among plan quality, delivery time, and optimization time.

Durvalumab after chemoradiotherapy for locally advanced non-small cell lung cancer prolonged distant metastasis-free survival, progression-free survival and overall survival in clinical practice.

BACKGROUND: In clinical practice, the effect of durvalumab and radiation pneumonitis (RP) on survival after intensity-modulated radiotherapy (IMRT) is not fully understood. The purpose of this retrospective study was to investigate factors related to distant metastasis-free survival (DMFS), progression-free survival (PFS) and overall survival (OS) after IMRT for locally advanced non-small cell lung cancer (LA-NSCLC). METHODS: All patients who were treated with conventional fractionated IMRT for LA-NSCLC between April 2016 and March 2021 were eligible. Time-to-event data were assessed by using the Kaplan-Meier estimator, and the Cox proportional hazards model was used for prognostic factor analyses. Factors that emerged after the start of IMRT, such as durvalumab administration or the development of RP, were analysed as time-dependent covariates. RESULTS: A total of 68 consecutive patients treated with conventional fractionated IMRT for LA-NSCLC were analysed. Sixty-six patients completed radiotherapy, 50 patients received concurrent chemotherapy, and 36 patients received adjuvant durvalumab. During the median follow-up period of 14.3 months, 23 patients died, and tumour progression occurred in 37 patients, including 28 patients with distant metastases. The 1-year DMFS rate, PFS rate and OS rate were 59.9%, 48.7% and 84.2%, respectively. Grade 2 RP occurred in 16 patients, grade 3 in 6 patients and grade 5 in 1 patient. The 1-year cumulative incidences of grade 2 or higher RP and grade 3 or higher RP were 33.8% and 10.3%, respectively. The results of multivariate analyses showed that durvalumab had a significantly lower hazard ratio (HR) for DMFS, PFS and OS (HR 0.31, p < 0.01; HR 0.33, p < 0.01 and HR 0.32, p = 0.02), respectively. Grade 2 or higher RP showed significance for DMFS and a nonsignificant trend for OS (HR 2.28, p = 0.04 and HR 2.12, p = 0.13), respectively, whereas a higher percentage of lung volume receiving 20 Gy or higher was significant for PFS (HR 2.25, p = 0.01). CONCLUSIONS: In clinical practice, durvalumab administration following IMRT with concomitant chemotherapy showed a significant survival benefit. Reducing the risk of grade 2 or higher RP would also be beneficial.

Patterns of failure after salvage chemoradiotherapy for postoperative loco-regional recurrent esophageal cancer: 20-year experience in a single institution in Japan.

PURPOSE: The purpose of the present study was to evaluate patterns of recurrence after salvage chemoradiotherapy (SCRT) for postoperative loco-regional recurrent esophageal cancer. METHODS: We reviewed records for 114 patients with postoperative loco-regional recurrent esophageal cancer treated by platinum-based chemoradiotherapy between 2000 and 2020, and we evaluated the patterns of failure in patients who had recurrence again or who had been observed for 2 years or more after SCRT at the last observation date. RESULTS: One hundred and three patients were enrolled in this study. The median observation period for survivors was 60 months. Fifty-three patients died of esophageal cancer and nine patients died of other diseases. The 5-year overall survival rate, cause-specific survival rate and disease-control rate were 43.7%, 45.3% and 37.0%, respectively. Sixty-five patients had failure after SCRT. In those patients, 26 patients had only distant organ or non-regional lymph node metastases, 26 patients had only loco-regional failure, and 13 patients had both. Of those 65 patients, 64 patients showed failure within 42 months after SCRT. Of 39 patients with loco-regional failure, failure in the irradiated field was observed in 28 patients. Of those 28 patients, 27 patients showed failure within 24 months and the other patient showed failure at 26.5 months. CONCLUSIONS: The patterns of failure after SCRT for patients with postoperative loco-regional recurrent esophageal cancer were shown. The patterns of failure suggest that follow-up for at least 4 years after SCRT should be performed for those patients.

IMRT improves local control in patients with nasopharyngeal carcinoma compared with conventional radiotherapy: propensity score-matched analysis.

BACKGROUND: It is still controversial whether intensity-modulated radiotherapy has an obvious advantage over conventional radiotherapy. The purposes of this study were to evaluate prognostic factors in pre-treatment characteristics for nasopharyngeal carcinoma and to compare treatment outcomes in patients who received intensity-modulated radiotherapy and patients who received two-dimensional radiotherapy or three-dimensional radiotherapy. METHODS: We reviewed patients with nasopharyngeal carcinoma who received chemoradiotherapy in our hospital during the period from 2000 to 2017, and we excluded patients who had a history of surgery for nasopharyngeal carcinoma and those who had distant metastases before treatment. A total of 72 patients who were treated by radiotherapy with concurrent chemotherapy were enrolled. All of the patients were irradiated with a total dose of 58-70 Gy. Overall survival, locoregional control and progression-free survival rates were compared in the groups treated by intensity-modulated radiotherapy and two-dimensional/three-dimensional radiotherapy. Propensity score matching was performed to homogenize the two groups. RESULTS: The median follow-up period was 62.5 months. After propensity score matching, in patients treated with intensity-modulated radiotherapy, the 5-year rate of overall survival, locoregional control and progression-free survival were 73.5, 95.2 and 72.7%, respectively. In patients treated with two-dimensional/three-dimensional radiotherapy, the 5-year rate of overall survival, locoregional control and progression-free survival were 69.1, 67.7 and 51.8%, respectively. There was a significant difference between the groups only in locoregional control. Late toxicities of grade 2 or higher were occurred in 38.5 and 24.2% of the patients treated by two-dimensional/three-dimensional radiotherapy and intensity-modulated radiotherapy, respectively. CONCLUSIONS: Our results suggested that intensity-modulated radiotherapy is more effective than two-dimensional/three-dimensional radiotherapy in patients with nasopharyngeal carcinoma, especially in locoregional control.

Development of a physical geometric phantom for deformable image registration credentialing of radiotherapy centers for a clinical trial.

PURPOSE: This study aimed to develop a physical geometric phantom for the deformable image registration (DIR) credentialing of radiotherapy centers for a clinical trial and tested the feasibility of the proposed phantom at multiple domestic and international institutions. METHODS AND MATERIALS: The phantom reproduced tumor shrinkage, rectum shape change, and body shrinkage using several physical phantoms with custom inserts. We tested the feasibility of the proposed phantom using 5 DIR patterns at 17 domestic and 2 international institutions (21 datasets). Eight institutions used the MIM software (MIM Software Inc, Cleveland, OH); seven used Velocity (Varian Medical Systems, Palo Alto, CA), and six used RayStation (RaySearch Laboratories, Stockholm, Sweden). The DIR accuracy was evaluated using the Dice similarity coefficient (DSC) and Hausdorff distance (HD). RESULTS: The mean and one standard deviation (SD) values (range) of DSC were 0.909 ± 0.088 (0.434-0.984) and 0.909 ± 0.048 (0.726-0.972) for tumor and rectum proxies, respectively. The mean and one SD values (range) of the HD value were 5.02 ± 3.32 (1.53-20.35) and 5.79 ± 3.47 (1.22-21.48) (mm) for the tumor and rectum proxies, respectively. In three patterns evaluating the DIR accuracy within the entire phantom, 61.9% of the data had more than a DSC of 0.8 in both tumor and rectum proxies. In two patterns evaluating the DIR accuracy by focusing on tumor and rectum proxies, all data had more than a DSC of 0.8 in both tumor and rectum proxies. CONCLUSIONS: The wide range of DIR performance highlights the importance of optimizing the DIR process. Thus, the proposed method has considerable potential as an evaluation tool for DIR credentialing and quality assurance.

FDG-PET might not contribute to improving survival in patients with locally advanced inoperable esophageal cancer.

BACKGROUND: In Japan, positron emission tomography using 18F-fluorodeoxyglucose (FDG-PET) has been covered by the national health insurance for esophageal cancer since 2006. FDG-PET is commonly performed in advanced esophageal cancer. The aim of this study was to determine the effect of FDG-PET on survival in patients with locally advanced inoperable esophageal cancer. METHODS: We retrospectively reviewed all patients with cT4 and without M1 esophageal cancer on CT in our institution between 2000 and 2014, and data for 78 patients who meet the eligibility criteria described below were used for analysis in this study. The eligibility criteria included (1) cT4 esophageal cancer without distant metastases or M1 lymph node metastasis (UICC 2002), (2) histologically proven squamous cell carcinoma, (3) 20-79 years of age, (4) having undergone at least 1 cycle of concomitant chemotherapy, (5) having been irradiated with 50 Gy or more, and (6) no other active malignant tumor during treatment. RESULTS: Two patients were excluded because abdominal lymph node metastases or neck lymph node metastases were detected by FDG-PET. In 78 eligible patients, FDG-PET was not performed before treatment in 41 of the 78 patients and was performed in the other patients. The median observation period was 68 months. The 3-year and 5-year overall survival rates in 78 patients were 36.9% and 30.8%, respectively. There was no significant difference in overall survival or progression-free survival between patients in whom FDG-PET was performed and those in whom FDG-PET was not performed (12.0 months vs. 11.0 months, p = 0.920 and 6.0 months vs. 6.0 months, p = 0.844, respectively). CONCLUSIONS: Compared with only CT, additional information from FDG-PET is not associated with improving survival in patients with locally advanced esophageal cancer. Our results suggest that FDG-PET might not have much meaning for survival in locally advanced esophageal cancer.

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. © RSNA, 2018 Online supplemental material is available for this article.

[Field Shape Optimization Technique Based on Dose Volume Histogram Using Daily Cone-beam Computed Tomography in Three-dimensional Conformal Radiation Therapy for Localized Prostate Cancer: Develop and Evaluation].

This study aimed to develop and evaluate field shape optimization technique based on dose calculation using daily cone-beam computed tomography (CBCT) to compensate for interfractional anatomic changes in three-dimensional conformal radiation therapy (3D-CRT) for prostate cancer. For each of 10 patients, 9-10 CBCT images were obtained throughout the treatment course. The prostate, seminal vesicles, and rectum were manually contoured in all CBCT images. Subsequently, plan adaptation was performed with a program developed in-house. This program calculates dose distributions on CBCT images and optimizes field shape to minimize rectal dose while keeping the target at the optimal dose coverage (the planning target volume D95% receives 95% of the prescription dose). To evaluate the adaptive planning approach, we re-calculated dose distributions on CBCT images based on the conventional and adaptive plans. For the entire cohort, plan adaptation improved rectal V50 Gy, V60 Gy, V65 Gy, and V70 Gy by -7.71±8.43%, -8.30±8.90%, -7.91±8.51% and -7.03±7.70% on average (±SD), respectively. Our results demonstrate that adaptive planning approach is superior to the conventional planning approach for optimizing dose distribution, and this adaptive approach can optimize field shape in 3 min. The proposed approach can be an effective solution for the problem of interfractional anatomic changes in 3D-CRT for prostate cancer.

Elective nodal irradiation is not necessary in chemoradiotherapy for postoperative loco-regional recurrent esophageal cancer.

PURPOSE: The purposes of the present study were to evaluate prognostic factors for patients with postoperative loco-regional recurrent esophageal cancer treated with chemoradiotherapy by multivariate analysis and to determine which irradiation is better, involved field irradiation or elective nodal irradiation, by matched-pair analysis. METHODS: We reviewed records for 80 patients with postoperative loco-regional recurrent esophageal cancer treated by chemoradiotherapy between 2000 and 2014. The median follow-up period was 62.0 months. Thirty-one cases were treated with elective nodal irradiation and were randomly matched by risk factors to 49 cases treated with involved field irradiation (1:1). RESULTS: Fifty-one patients had disease recurrence again, and irradiated-field failure was observed in 26 patients. The 5-year overall survival rate was 30.5% with a median survival period of 26.5 months. Grade 3 or higher late toxicity was observed in only one patient. In multivariate analysis, short disease-free interval and anastomotic recurrence were statistically significant unfavorable prognostic factors for overall survival (hazard ratios: 2.1 and 2.5, respectively). Matched-pair analysis including disease-free interval, pattern of recurrence and number of recurrent regions revealed that overall survival rate and irradiated-field control rate in patients treated with involved field irradiation were significantly better than those in patients treated with elective nodal irradiation (P = 0.016 and P = 0.014, respectively). CONCLUSIONS: Short disease-free interval and anastomotic recurrence are unfavorable factors and elective nodal irradiation is not necessary in chemoradiotherapy for patients with postoperative loco-regional recurrent esophageal cancer.

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

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.

Evaluation of the Positional Accuracy and Dosimetric Properties of a Three-dimensional Printed Device for Head and Neck Immobilization.

Our aim was to investigate the feasibility of a three-dimensional (3D) -printed head-and-neck (HN) immobilization device by comparing its positional accuracy and dosimetric properties with those of a conventional immobilization device (CID). We prepared a 3D-printed immobilization device (3DID) consisting of a mask and headrest with acrylonitrile-butadiene-styrene resin developed from the computed tomography data obtained by imaging a HN phantom. For comparison, a CID comprising a thermoplastic mask and headrest was prepared using the same HN phantom. We measured the setup error using the ExacTrac X-ray image system. Furthermore, using the ionization chamber and the water-equivalent phantom, we measured the changes in the dose due to the difference in the immobilization device material from the photon of 4 MV and 6 MV. The positional accuracy of the two devices were almost similar in each direction except in the vertical, lateral, and pitch directions (t-test, p<0.0001), and the maximum difference was 1 mm, and 1°. The standard deviations were not statistically different in each direction except in the longitudinal (F-test, p=0.034) and roll directions (F-test, p<0.0001). When the thickness was the same, the dose difference was almost similar at a 50 mm depth. At a 1 mm depth, the 3DID-plate had a 2.9-4.2% lower dose than the CID-plate. This study suggested that the positional accuracy and dosimetric properties of 3DID were almost similar to those of CID.

Chemoradiotherapy for T4 and/or M1 lymph node esophageal cancer: experience since 2000 at a high-volume center in Japan.

PURPOSE: To review data for patients with stage T4 and/or M1 lymph node (lym) esophageal cancer who have been treated with definitive chemoradiotherapy since 2000 at a high-volume center in Japan. PATIENTS AND METHODS: We retrospectively reviewed all patients with T4 and/or M1 lym esophageal cancer who were treated by definitive chemoradiotherapy between 2000 and 2010. The eligibility criteria included (1) histopathologically proven esophageal cancer, (2) T4 and/or M1 lym (UICC 2002), (3) 20-79 years of age, (4) having undergone at least 1 cycle of concomitant chemotherapy, (5) having been irradiated with ≥ 50 Gy, and (6) having no other active malignant tumor during treatment. Toxicity was graded according to the Common Terminology Criteria for Adverse Events (CTCAE v3.0). RESULTS: Data from 128 patients (70 with clinical stage III, 58 with clinical stage IV) were used for analysis in this study. The median observation period for survivors was 46.3 months. The 2- and 4-year overall survival rates were 32.8 and 24.4 %, respectively. The overall survival of patients without M1 lym was significantly better than that of patients with Ml lym (4-year, 32.6 vs 11.7 %, log-rank test; p = 0.04). Overall survival in more recent patients (2006-2010) did not show improvement when compared with past patients (2000-2005). Eight patients had late toxicities of grade ≥3. CONCLUSIONS: T4 patients without M1 lym showed a relatively good 4-year survival rate of approximately 33 %; however, the results did not show significant improvement after 2000.

Dosemetric Parameters Predictive of Rib Fractures after Proton Beam Therapy for Early-Stage Lung Cancer.

Proton beam therapy (PBT) is the preferred modality for early-stage lung cancer. Compared with X-ray therapy, PBT offers good dose concentration as revealed by the characteristics of the Bragg peak. Rib fractures (RFs) after PBT lead to decreased quality of life for patients. However, the incidence of and the risk factors for RFs after PBT have not yet been clarified. We therefore explored the relationship between irradiated rib volume and RFs after PBT for early-stage lung cancer. The purpose of this study was to investigate the incidence and the risk factors for RFs following PBT for early-stage lung cancer. We investigated 52 early-stage lung cancer patients and analyzed a total of 215 irradiated ribs after PBT. Grade 2 RFs occurred in 12 patients (20 ribs); these RFs were symptomatic without displacement. No patient experienced more severe RFs. The median time to grade 2 RFs development was 17 months (range: 9-29 months). The three-year incidence of grade 2 RFs was 30.2%. According to the analysis comparing radiation dose and rib volume using receiver operating characteristic curves, we demonstrated that the volume of ribs receiving more than 120 Gy3 (relative biological effectiveness (RBE)) was more than 3.7 cm(3) at an area under the curve of 0.81, which increased the incidence of RFs after PBT (P < 0.001). In this study, RFs were frequently observed following PBT for early-stage lung cancer. We demonstrated that the volume of ribs receiving more than 120 Gy3 (RBE) was the most significant parameter for predicting RFs.

Long-term results of chemoradiotherapy for stage II-III thoracic esophageal cancer in a single institution after 2000 -with a focus on comparison of three protocols.

BACKGROUND: To evaluate the long-term results of chemoradiotherapy (CRT) for stage II-III thoracic esophageal cancer mainly by comparing results of three protocols retrospectively. METHODS: Between 2000 and 2012, 298 patients with stage II-III thoracic esophageal cancer underwent CRT. Patients in Group A received two cycles of cisplatin (CDDP) at 70 mg/m(2) (day 1 and 29) and 5-fluorouracil (5-FU) at 700 mg/m(2)/24 h (day 1-4 and 29-32) with radiotherapy (RT) of 60 Gy without a break. Patients in Group B received two cycles of CDDP at 40 mg/m(2) (day 1, 8, 36 and 43) and 5-FU at 400 mg/m(2)/24 h (day 1-5, 8-12, 36-40 and 43-47) with RT of 60 Gy with a 2-week break. Patients in Group C received two cycles of nedaplatin at 70 mg/m(2) (day 1 and 29) and 5-FU at 500 mg/m(2)/24 h (day 1-4 and 29-32) with RT of 60-70 Gy without a break. Differences in prognostic factors between the groups were analyzed by univariate and multivariate analyses. RESULTS: The 5-year overall survival rates for patients in Group A, Group B and Group C were 52.4, 45.2 and 37.2%, respectively. The 5-year overall survival rates for patients in Stage II, Stage III (non-T4) and Stage III (T4) were 64.0, 40.1 and 22.5%, respectively. The 5-year overall survival rates for patients who received 1 cycle and 2 cycles of concomitant chemotherapy were 27.9 and 46.0%, respectively. In univariate analysis, stage, performance status and number of concomitant chemotherapy cycles were significant prognostic factors (p < 0.001, p = 0.008 and p < 0.001, respectively). In multivariate analysis, stage, protocol and number of concomitant chemotherapy cycles were significant factors (p < 0.001, p = 0.043 and p < 0.001, respectively). CONCLUSIONS: The protocol used in Group A may be an effective protocol of CRT for esophageal cancer. It may be important to complete the scheduled concomitant chemotherapy with the appropriate intensity of CRT.

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.