TENERGY: multicenter phase II study of Atezolizumab monotherapy following definitive Chemoradiotherapy with 5-FU plus Cisplatin in patients with unresectable locally advanced esophageal squamous cell carcinoma.

BACKGROUND: The standard treatment for patients with unresectable locally advanced esophageal squamous cell carcinoma (ESCC) is definitive chemoradiotherapy (CRT) using 5-FU plus cisplatin. However, complete response (CR) rates are low at 11-25%, resulting in 9-10 months of median overall survival (OS). An improved therapeutic efficacy by combining immunotherapy with radiation has been reported in patients with locally advanced non-small cell lung cancer. The results using ESCC cell lines suggest sequential treatment with anti-PD-L1 agents soon after completion of CRT is the most effective combination. METHODS: TENERGY trial is a multicenter, phase II, proof-of-concept study to assess the efficacy and safety of atezolizumab following definitive CRT in patients with locally advanced ESCC. The main inclusion criteria are unresectable locally advanced ESCC without distant metastasis, completion of 60 Gy of radiation plus two concomitant cycles of chemotherapy (cisplatin 70 mg/m2 on day 1 and 5-FU 700 mg/m2 on days 1-4, every 28 days), and adequate organ function. Within 6 weeks after CRT, participants will start taking 1200 mg of atezolizumab every three weeks and continue until 12 months or disease progression. The primary endpoint is the confirmed CR rate by the investigator's assessment. Secondary endpoints include overall response rate, progression-free survival (PFS), OS, adverse events, and confirmed CR rate by central assessment. We will enroll 50 patients (40 with primary locally advanced ESCC and 10 with postoperative locoregionally recurrent ESCC). We will obtain biopsies from the primary site and will collect blood at 3 time points (before CRT, after CRT, and four weeks after the start of atezolizumab) for an exploratory biomarker study. We will analyze the phenotype of immune-competent cells, neoantigens, tumor mutational burden, PD-L1 status, and Human Leukocyte Antigen haplotyping. DISCUSSION: The synergistic efficacies of the sequential combination of CRT and atezolizumab should improve the CR rate, resulting in survival improvement for patients with unresectable locally advanced ESCC. Because CRT is a standard treatment option for patients with early stage to locally advanced ESCC, the sequential combination of CRT and atezolizumab has the potential to change the standard ESCC treatments. TRIAL REGISTRATION: UMIN000034373, 10/04/2018 and EPOC1802.

Usefulness of hybrid deformable image registration algorithms in prostate radiation therapy.

To evaluate the accuracy of commercially available hybrid deformable image registration (DIR) algorithms when using planning CT (pCT) and daily cone-beam computed tomography (CBCT) in radiation therapy for prostate cancer. The hybrid DIR algorithms in RayStation and MIM Maestro were evaluated. Contours of the prostate, bladder, rectum, and seminal vesicles (SVs) were used as region-of-interest (ROIs) to guide image deformation in the hybrid DIR and to compare the DIR accuracy. To evaluate robustness of the hybrid DIR for prostate cancer patients with organs with volume that vary on a daily basis, such as the bladder and rectum, the DIR algorithms were performed on ten pairs of CT volumes from ten patients who underwent prostate intensity-modulated radiation therapy or volumetric modulated arc therapy. In a visual evaluation, MIM caused unrealistic image deformation in soft tissues, organs, and pelvic bones. The mean dice similarity coefficient (DSC) ranged from 0.46 to 0.90 for the prostate, bladder, rectum, and SVs; the SVs had the lowest DSC. Target registration error (TRE) at the centroid of the ROIs was about 2 mm for the prostate and bladder, and about 6 mm for the rectum and SVs. RayStation did not cause unrealistic image deformation, and could maintain the shape of pelvic bones in most cases. The mean DSC and TRE at the centroid of the ROIs were about 0.9 and within 5 mm generally. In both software programs, the use of ROIs to guide image deformation had the possibility to reduce any unrealistic image deformation and might be effective to keep the DIR physically reasonable. The pCT/CBCT DIR for the prostate cancer did not reduce the DIR accuracy because of the use of ROIs to guide the image deformation.

Dosimetric comparison between proton beam therapy and photon radiation therapy for locally advanced non-small cell lung cancer.

OBJECTIVE: To assess the feasibility of proton beam therapy for the patients with locally advanced non-small lung cancer. METHODS: The dosimetry was analyzed retrospectively to calculate the doses to organs at risk, such as the lung, heart, esophagus and spinal cord. A dosimetric comparison between proton beam therapy and dummy photon radiotherapy (three-dimensional conformal radiotherapy) plans was performed. Dummy intensity-modulated radiotherapy plans were also generated for the patients for whom curative three-dimensional conformal radiotherapy plans could not be generated. RESULTS: Overall, 33 patients with stage III non-small cell lung cancer were treated with proton beam therapy between December 2011 and August 2014. The median age of the eligible patients was 67 years (range: 44-87 years). All the patients were treated with chemotherapy consisting of cisplatin/vinorelbine or carboplatin. The median prescribed dose was 60 GyE (range: 60-66 GyE). The mean normal lung V20 GyE was 23.6% (range: 14.9-32%), and the mean normal lung dose was 11.9 GyE (range: 6.0-19 GyE). The mean esophageal V50 GyE was 25.5% (range: 0.01-63.6%), the mean heart V40 GyE was 13.4% (range: 1.4-29.3%) and the mean maximum spinal cord dose was 40.7 GyE (range: 22.9-48 GyE). Based on dummy three-dimensional conformal radiotherapy planning, 12 patients were regarded as not being suitable for radical thoracic three-dimensional conformal radiotherapy. All the dose parameters of proton beam therapy, except for the esophageal dose, were lower than those for the dummy three-dimensional conformal radiotherapy plans. In comparison to the intensity-modulated radiotherapy plan, proton beam therapy also achieved dose reduction in the normal lung. None of the patients experienced grade 4 or worse non-hematological toxicities. CONCLUSIONS: Proton beam therapy for patients with stage III non-small cell lung cancer was feasible and was superior to three-dimensional conformal radiotherapy for several dosimetric parameters.

[A practical procedure to improve the accuracy of radiochromic film dosimetry: a integration with a correction method of uniformity correction and a red/blue correction method].

It has been reported that the light scattering could worsen the accuracy of dose distribution measurement using a radiochromic film. The purpose of this study was to investigate the accuracy of two different films, EDR2 and EBT2, as film dosimetry tools. The effectiveness of a correction method for the non-uniformity caused from EBT2 film and the light scattering was also evaluated. In addition the efficacy of this correction method integrated with the red/blue correction method was assessed. EDR2 and EBT2 films were read using a flatbed charge-coupled device scanner (EPSON 10000G). Dose differences on the axis perpendicular to the scanner lamp movement axis were within 1% with EDR2, but exceeded 3% (Maximum: +8%) with EBT2. The non-uniformity correction method, after a single film exposure, was applied to the readout of the films. A corrected dose distribution data was subsequently created. The correction method showed more than 10%-better pass ratios in dose difference evaluation than when the correction method was not applied. The red/blue correction method resulted in 5%-improvement compared with the standard procedure that employed red color only. The correction method with EBT2 proved to be able to rapidly correct non-uniformity, and has potential for routine clinical IMRT dose verification if the accuracy of EBT2 is required to be similar to that of EDR2. The use of red/blue correction method may improve the accuracy, but we recommend we should use the red/blue correction method carefully and understand the characteristics of EBT2 for red color only and the red/blue correction method.

Identification of reproducible radiomic features from on-board volumetric images: A multi-institutional phantom study.

BACKGROUND: Radiomics analysis using on-board volumetric images has attracted research attention as a method for predicting prognosis during treatment; however, the lack of standardization is still one of the main concerns. PURPOSE: This study investigated the factors that influence the reproducibility of radiomic features extracted from on-board volumetric images using an anthropomorphic radiomics phantom. Furthermore, a phantom experiment was conducted with different treatment machines from multiple institutions as external validation to identify reproducible radiomic features. METHODS: The phantom was designed to be 35 × 20 × 20 cm with eight types of heterogeneous spheres (⌀ = 1, 2, and 3 cm). On-board volumetric images were acquired using 15 treatment machines from eight institutions. Of these, kilovoltage cone-beam computed tomography (kV-CBCT) image data acquired from four treatment machines at one institution were used as an internal evaluation dataset to explore the reproducibility of radiomic features. The remaining image data, including kV-CBCT, megavoltage-CBCT (MV-CBCT), and megavoltage computed tomography (MV-CT) provided by seven different institutions (11 treatment machines), were used as an external validation dataset. A total of 1,302 radiomic features, including 18 first-order, 75 texture, 465 (i.e., 93 × 5) Laplacian of Gaussian (LoG) filter-based, and 744 (i.e., 93 × 8) wavelet filter-based features, were extracted within the spheres. The intraclass correlation coefficient (ICC) was calculated to explore feature repeatability and reproducibility using an internal evaluation dataset. Subsequently, the coefficient of variation (COV) was calculated to validate the feature variability of external institutions. An absolute ICC exceeding 0.85 or COV under 5% was considered indicative of a highly reproducible feature. RESULTS: For internal evaluation, ICC analysis showed that the median percentage of radiomic features with high repeatability was 95.2%. The ICC analysis indicated that the median percentages of highly reproducible features for inter-tube current, reconstruction algorithm, and treatment machine were decreased by 20.8%, 29.2%, and 33.3%, respectively. For external validation, the COV analysis showed that the median percentage of reproducible features was 31.5%. A total of 16 features, including nine LoG filter-based and seven wavelet filter-based features, were indicated as highly reproducible features. The gray-level run-length matrix (GLRLM) was classified as containing the most frequent features (N = 8), followed by the gray-level dependence matrix (N = 7) and gray-level co-occurrence matrix (N = 1) features. CONCLUSIONS: We developed the standard phantom for radiomics analysis of kV-CBCT, MV-CBCT, and MV-CT images. With this phantom, we revealed that the differences in the treatment machine and image reconstruction algorithm reduce the reproducibility of radiomic features from on-board volumetric images. Specifically, the most reproducible features for external validation were LoG or wavelet filter-based GLRLM features. However, the acceptability of the identified features should be examined in advance at each institution before applying the findings to prognosis prediction.

Technical note: determination of the optimized image processing and template matching techniques for a patient intrafraction motion monitoring system.

PURPOSE: In this work, the authors determine the optimal template matching method and selection of pixel data for use in a system for monitoring patient intrafraction motion. METHODS: The motion monitoring system is based on optical tracking of a marker block placed on the patient. The temporal resolution of the system was evaluated with a respiratory motion phantom. The phantom moved the marker with a peak-to-peak amplitude of 0.6-4.0 cm and a period of 1, 3, and 6 s. Three template matching methods were applied: Sum of squared difference (SSD), sum of absolute difference (SAD), and normalized cross-correlation (NCC) using each of four pixel color data schemes (RGB and gray level modified by one of three image processing steps). An in-house algorithm called auto region-of-interest (AutoROI) automatically reset the marker detection region-of-interest to improve the calculation speed. RESULTS: RGB and gray level temporal resolutions were 54.22 ± 10.81 (1 SD) s and 12.70 ± 3.87 (1 SD) s, respectively. The temporal resolution when using SSD and SAD was higher than when using NCC. Positional accuracy was within 1 mm. Both values were within the tolerance specified by AAPM Task Group 142. To avoid misidentification of the marker, a threshold-based self-validation within the marker recognition system was implemented and was found to improve the tracking of motion with a high amplitude and short period. CONCLUSIONS: An intrafraction motion monitoring system using SSD or SAD and applied to gray pixel data can achieve high temporal resolution and positional accuracy.

Detection of anatomical changes using two-dimensional x-ray images for head and neck adaptive radiotherapy.

PURPOSE: To develop a system for detecting anatomical changes using two-dimensional (2D) x-ray images. METHODS: Ten patients with head and neck cancer were retrospectively analyzed using 2D x-ray and cone-beam computed tomography (CBCT) images. The 2D x-ray images were acquired daily, whereas the CBCT images were acquired weekly during the treatment period. The developed system imported the 2D x-ray images obtained on the initial treatment day and on another day, and thereafter converted them into the water equivalent thickness (WET) using the conversion table. The difference between the WET images for the first and other treatment days (ΔWET) was calculated as the quantitative value for anatomical changes and visualized to recognize the anatomical change location. We compared ΔWET and the difference in the lateral neck distance (ΔLND) on the corresponding CBCT images. ΔLND was used as the ground truth for anatomical changes. ΔWET and ΔLND were measured at the first cervical vertebra (C1) and the tumor center (TC). C1 and TC were selected to observe the volume changes in the parotid gland and tumor, respectively. Sensitivity and specificity were calculated to evaluate the performance of the 2D-WET system. The cut-off values of WET and LND were set to 2-10 mm. Furthermore, intensity-modulated proton therapy (IMPT) plans for six patients with rescan CT images were generated. The IMPT plans on the rescan CT images were compared to the original plans on simulation CT using the dosimetric parameters for the target and the organs at risk. RESULTS: The mean differences between ΔWET and ΔLND for C1 and TC were -0.62 ± 1.66 mm and -0.93 ± 1.28 mm (mean ± 1 SD), respectively. ΔWET in the proposed system was in good agreement with ΔLND using the CBCT images. In the sensitivity and specificity results for C1 and TC with cut-off values from 2 to 10 mm, the sensitivity was >85% for all cut-off values, while the specificity was >90% at 5-10 mm and <90% at less than 5 mm. The average ΔWET at the time of replanning was 12.8 mm which resulted in maximum dose increase in the spinal cord D1cc by 8.4 Gy, the parotid gland D50 by 26.6 Gy, and the oral cavity D50 by 23.2 Gy. CONCLUSIONS: We developed a new system for detecting anatomical changes using 2D x-ray images. The developed system with ΔWET showed an agreement with ΔLND at C1 and TC with an average difference of less than 1 mm. ΔWET detected anatomical changes with high sensitivity and specificity with a cut-off value of 5-10 mm. This system can monitor daily anatomical changes without causing high exposure to patients and requiring any inefficient work, and it can be applied to daily online adaptive proton beam therapy and triggered adaptive radiotherapy.

Practical dosimetry procedure of air kerma for kilovoltage X-ray imaging in radiation oncology using a 0.6-cc cylindrical ionization chamber with a cobalt absorbed dose-to-water calibration coefficient.

In this study, we implemented a practical dosimetry procedure of air kerma for kilovoltage X-ray beams using a 0.6-cc cylindrical ionization chamber, and validated the procedure with the accuracy of the measurements using the 0.6-cc chamber compared to the measurements using a 6-cc chamber and a semiconductor device. In addition, the kerma area products (KAPs) were compared with the dose reference levels of radiology. A modified air kerma formalism using a 0.6-cc cylindrical ionization chamber air kerma formalism with a cobalt absorbed dose-to-water calibration coefficient was implemented. Validation of the formalism showed good agreement between the 0.6-cc chamber and the 6-cc chamber (< 5%), and between the 0.6-cc chamber and the semiconductor device (< 2%) in the 60-120 kV range. The KAPs for four RO machines had difference factors of 0.04-15.4 and 0.01-4.1 from their median and maximum dose reference levels in radiology, respectively.

Verification of dose distribution in high dose-rate brachytherapy for cervical cancer using a normoxic N-vinylpyrrolidone polymer gel dosimeter.

The polymer gel dosimeter has been proposed for use as a 3D dosimeter for complex dose distribution measurement of high dose-rate (HDR) brachytherapy. However, various shapes of catheter/applicator for sealed radioactive source transport used in clinical cases must be placed in the gel sample. The absorbed dose readout for the magnetic resonance (MR)-based polymer gel dosimeters requires calibration data for the dose-transverse relaxation rate (R2) response. In this study, we evaluated in detail the dose uncertainty and dose resolution of three calibration methods, the multi-sample and distance methods using the Ir-192 source and the linear accelerator (linac) method using 6MV X-rays. The use of Ir-192 sources increases dose uncertainty with steep dose gradients. We clarified that the uniformly irradiated gel sample improved the signal-to-noise ratio (SNR) due to the large slice thickness of MR images and could acquire an accurate calibration curve using the linac method. The curved tandem and ovoid applicator used for intracavitary irradiation of HDR brachytherapy for cervical cancer were reproduced with a glass tube to verify the dose distribution. The results of comparison with the treatment planning system (TPS) calculation by gamma analysis on the 3%/2 mm criterion were in good agreement with a gamma pass rate of 90%. In addition, the prescription dose could be evaluated accurately. We conclude that it is easy to place catheter/applicator in the polymer gel dosimeters, making them a useful tool for verifying the 3D dose distribution of HDR brachytherapy with accurate calibration methods.

Multi-Institutional Study of End-to-End Dose Delivery Quality Assurance Testing for Image-Guided Brachytherapy Using a Gel Dosimeter.

PURPOSE: To quantify dose delivery errors for high-dose-rate image-guided brachytherapy (HDR-IGBT) using an independent end-to-end dose delivery quality assurance test at multiple institutions. The novelty of our study is that this is the first multi-institutional end-to-end dose delivery study in the world. MATERIALS AND METHODS: The postal audit used a polymer gel dosimeter in a cylindrical acrylic container for the afterloading system. Image acquisition using computed tomography, treatment planning, and irradiation were performed at each institution. Dose distribution comparison between the plan and gel measurement was performed. The percentage of pixels satisfying the absolute-dose gamma criterion was reviewed. RESULTS: Thirty-five institutions participated in this study. The dose uncertainty was 3.6% ± 2.3% (mean ± 1.96σ). The geometric uncertainty with a coverage factor of k = 2 was 3.5 mm. The tolerance level was set to the gamma passing rate of 95% with the agreement criterion of 5% (global)/3 mm, which was determined from the uncertainty estimation. The percentage of pixels satisfying the gamma criterion was 90.4% ± 32.2% (mean ± 1.96σ). Sixty-six percent (23/35) of the institutions passed the verification. Of the institutions that failed the verification, 75% (9/12) had incorrect inputs of the offset between the catheter tip and indexer length in treatment planning and 17% (2/12) had incorrect catheter reconstruction in treatment planning. CONCLUSIONS: The methodology should be useful for comprehensively checking the accuracy of HDR-IGBT dose delivery and credentialing clinical studies. The results of our study highlight the high risk of large source positional errors while delivering dose for HDR-IGBT in clinical practices.

Management of the baseline shift using a new and simple method for respiratory-gated radiation therapy: detectability and effectiveness of a flexible monitoring system.

PURPOSE: In respiratory-gated radiation therapy, a baseline shift decreases the accuracy of target coverage and organs at risk (OAR) sparing. The effectiveness of audio-feedback and audio-visual feedback in correcting the baseline shift in the breathing pattern of the patient has been demonstrated previously. However, the baseline shift derived from the intrafraction motion of the patient's body cannot be corrected by these methods. In the present study, the authors designed and developed a simple and flexible system. METHODS: The system consisted of a web camera and a computer running our in-house software. The in-house software was adapted to template matching and also to no preimage processing. The system was capable of monitoring the baseline shift in the intrafraction motion of the patient's body. Another marker box was used to monitor the baseline shift due to the flexible setups required of a marker box for gated signals. The system accuracy was evaluated by employing a respiratory motion phantom and was found to be within AAPM Task Group 142 tolerance (positional accuracy <2 mm and temporal accuracy <100 ms) for respiratory-gated radiation therapy. Additionally, the effectiveness of this flexible and independent system in gated treatment was investigated in healthy volunteers, in terms of the results from the differences in the baseline shift detectable between the marker positions, which the authors evaluated statistically. RESULTS: The movement of the marker on the sternum [1.599 +/- 0.622 mm (1 SD)] was substantially decreased as compared with the abdomen [6.547 +/- 0.962 mm (1 SD)]. Additionally, in all of the volunteers, the baseline shifts for the sternum [-0.136 +/- 0.868 (2 SD)] were in better agreement with the nominal baseline shifts than was the case for the abdomen [-0.722 +/- 1.56 mm (2 SD)]. The baseline shifts could be accurately measured and detected using the monitoring system, which could acquire the movement of the marker on the sternum. The baseline shift-monitoring system with the displacement-based methods for highly accurate respiratory-gated treatments should be used to make most of the displacement-based gating methods. CONCLUSIONS: The advent of intensity modulated radiation therapy and volumetric modulated radiation therapy facilitates margin reduction for the planning target volumes and the OARs, but highly accurate irradiation is needed to achieve target coverage and OAR sparing with a small margin. The baseline shifts can affect treatment not only with the respiratory gating system but also without the system. Our system can manage the baseline shift and also enables treatment irradiation to be undertaken with high accuracy.

[A Preliminary Study of Optimal Imaging Acquisition Parameters for Fiducial Markers in Liver Stereotactic Body Radiotherapy].

In liver stereotactic body radiotherapy (SBRT) using fiducial markers, the accuracy of automatic image recognition of fiducial markers is important, and the imaging dose cannot be neglected in image-guided radiotherapy. Optimal imaging parameters of fiducial markers were investigated for automatic image recognition and imaging dose. We investigated automatic recognition with fiducial markers of different shapes and sizes. In addition, the optimum imaging conditions were examined based on the automatic recognition when the presence or absence of a filter, focal spot size, and phantom thickness were altered using the fiducial markers with a high automatic recognition. The results for different shapes and sizes of fiducial markers showed that larger markers were recognized more automatically, whereas shorter markers were recognized in the correct position. By using the filter, we were able to reduce the imaging dose by one third or one half compared to the case without the filter. The results for the focal spot size showed that using a larger size resulted in higher automatic recognition accuracy than using a smaller size. For the relationship between the automatically recognized imaging conditions and the air kerma when the phantom thickness was altered, it was necessary to keep the tube current-time product constant and increase the tube voltage in order to avoid poor recognition accuracy. The parameters we proposed are effective in shortening the treatment time and reducing the imaging dose because they allow us to acquire images with low doses and high accuracy of automatic recognition.

Comparison of a Hybrid IMRT/VMAT technique with non-coplanar VMAT and non-coplanar IMRT for unresectable olfactory neuroblastoma using the RayStation treatment planning system-EUD, NTCP and planning study.

The purpose of this study was to compare hybrid intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (Hybrid IMRT/VMAT), with non-coplanar (nc) IMRT and nc-VMAT treatment plans for unresectable olfactory neuroblastoma (ONB). Hybrid IMRT/VMAT, nc-IMRT and nc-VMAT plans were optimized for 12 patients with modified Kadish C stage ONB. Dose prescription was 65 Gy in 26 fractions. Dose-volume histogram parameters, conformation number (CN), homogeneity index (HI), integral dose and monitor units (MUs) delivered per fraction were assessed. Equivalent uniform dose (EUD) and normal tissue complication probability (NTCP) based on the EUD model (NTCPLogit) and the Lyman-Kutcher-Burman model (NTCPLKB) were also evaluated. We found that the Hybrid IMRT/VMAT plan significantly improved the CN for clinical target volume (CTV) and planning treatment volume (PTV) compared with the nc-VMAT plan. In general, sparing of organs at risk (OARs) is similar with the three techniques, although the Hybrid IMRT/VMAT plan resulted in a significantly reduced Dmax to contralateral (C/L) optic nerve compared with the nc-IMRT plan. The Hybrid IMRT/VMAT plan significantly reduce EUD to the ipsilateral (I/L) and C/L optic nerve in comparison with the nc-IMRT plan and nc-VMAT plan, but the difference in NTCP between the three technique was <1%. We concluded that the Hybrid IMRT/VMAT technique can offer improvement in terms of target conformity and EUD for optic nerves, while achieving equal or better OAR sparing compared with nc-IMRT and nc-VMAT, and can be a viable radiation technique for treating unresectable ONB. However, the clinical benefit of these small differences in dosimetric data, EUD and NTCP of optic nerves may be minimal.

End-to-end delivery quality assurance of computed tomography-based high-dose-rate brachytherapy using a gel dosimeter.

PURPOSE: The purpose of this study was to develop a novel quality assurance (QA) program to check the entire treatment chain of image-guided brachytherapy with dose distribution evaluation in a single setup and irradiation using a gel dosimeter. METHODS AND MATERIALS: A polymer gel was used, and the readout was performed by magnetic resonance scanning. A CT-based treatment plan was generated using the Oncentra planning system (Elekta, Sweden), and irradiation was performed three times using an afterloading device with an Ir-192 source. The dose-response curve of the gel was created using 6-MV X-ray, which is independent of the source beams. Planar gamma images on a coronal plane along the source transport axis were calculated using the measured dose as a reference, and the calculated doses were used in several error simulations (no error; 2.0 or 2.5 mm systematic and random source dwell mispositioning; and dose error of 2%, 5%, 10%, and 20%). RESULTS: The dose-R2 (spin-spin relaxation rate) conversion table revealed that the uncertainty and dose resolution of 6-MV X-ray were better than those of Ir-192 and also constant between the three measurements. With the 3%/1 mm criteria, there were statistically significant differences between each pair of settings except dose error of 2% and 5%. CONCLUSION: This work depicts a simple and efficient end-to-end test that can provide a clinically useful tool for QA of image-guided brachytherapy. In this QA program, air kerma strength and dwell position setting could also be verified. This test can also distinguish between different types of error.

Radiobiological model-based approach to determine the potential of dose-escalated robust intensity-modulated proton radiotherapy in reducing gastrointestinal toxicity in the treatment of locally advanced unresectable pancreatic cancer of the head.

BACKGROUND: The purpose of this study was to determine the potential of escalated dose radiation (EDR) robust intensity-modulated proton radiotherapy (ro-IMPT) in reducing GI toxicity risk in locally advanced unresectable pancreatic cancer (LAUPC) of the head in term of normal tissue complication probability (NTCP) predictive model. METHODS: For 9 patients, intensity-modulated radiotherapy (IMRT) was compared with ro-IMPT. For all plans, the prescription dose was 59.4GyE (Gray equivalent) in 33 fractions with an equivalent organ at risk (OAR) constraints. Physical dose distribution was evaluated. GI toxicity risk for different endpoints was estimated using published NTCP Lyman Kutcher Burman (LKB) models for stomach, duodenum, small bowel, and combine stomach and duodenum (Stoduo). A Wilcoxon signed-rank test was used for dosimetry parameters and NTCP values comparison. RESULT: The dosimetric results have shown that, with similar target coverage, ro-IMPT achieves a significant dose-volume reduction in the stomach, small bowel, and stoduo in low to high dose range in comparison to IMRT. NTCP evaluation for the endpoint gastric bleeding of stomach (10.55% vs. 13.97%, P = 0.007), duodenum (1.87% vs. 5.02%, P = 0.004), and stoduo (5.67% vs. 7.81%, P = 0.008) suggest reduced toxicity by ro-IMPT compared to IMRT. ∆NTCP IMRT - ro-IMPT (using parameter from Pan et al. for gastric bleed) of ≥5 to < 10% was seen in 3 patients (33%) for stomach and 2 patients (22%) for stoduo. An overall GI toxicity relative risk (NTCPro-IMPT/NTCPIMRT) reduction was noted (0.16-0.81) for all GI-OARs except for duodenum (> 1) with endpoint grade ≥ 3 GI toxicity (using parameters from Holyoake et al.). CONCLUSION: With similar target coverage and better conformity, ro-IMPT has the potential to substantially reduce the risk of GI toxicity compared to IMRT in EDR of LAUPC of the head. This result needs to be further evaluated in future clinical studies.

[Summary of the Report of Task Group 100 of the AAPM: Application of Risk Analysis Methods to Radiation Therapy Quality Management].

In 2016, the American Association of Physicists in Medicine (AAPM) has published a report of task group (TG) 100 with a completely new concept, entitled "application of risk analysis methods to radiation therapy quality management." TG-100 proposed implementation of risk analysis in radiotherapy to prevent harmful radiotherapy accidents. In addition, it enables us to conduct efficient and effective quality management in not only advanced radiotherapy such as intensity-modulated radiotherapy and image-guided radiotherapy but also new technology in radiotherapy. It should be noted that treatment process in modern radiotherapy is absolutely more complex and it needs skillful staff and adequate resources. TG-100 methodology could identify weakness in radiotherapy procedure through assessment of failure modes that could occur in overall treatment processes. All staff in radiotherapy have to explore quality management in radiotherapy safety.

A feasibility study of independent verification of dose calculation for Vero4DRT using a Clarkson-based algorithm.

Dose verification for a gimbal-mounted image-guided radiotherapy system, Vero4DRT (Mitsubishi Heavy Industries Ltd., Tokyo, Japan) is usually carried out by pretreatment measurement. Independent verification calculations using Monte Carlo methods for Vero4DRT have been published. As the Clarkson method is faster and easier to use than measurement and Monte Carlo methods, we evaluated the accuracy of an independent calculation verification program and its feasibility as a secondary check for Vero4DRT. Computed tomography (CT)-based dose calculation was performed using a modified Clarkson-based algorithm. In this study, 120 patients' treatment plans were collected in our institute. The treatments were performed using conventional irradiation for lung and prostate, 3-dimensional (3D) conformal stereotactic body radiotherapy (SBRT) for the lung, and intensity-modulated radiation therapy (IMRT) for the prostate. Differences between the treatment planning system (TPS) and the Clarkson-based independent dose verification software were computed, and confidence limits (CLs, mean ± 2 standard deviation %) for Vero4DRT were compared with the CLs for the C-arms linear accelerators in the previous study. The results of the CLs, the conventional irradiation, SBRT, and IMRT showed 2.2 ± 3.5% (CL of the C-arms linear accelerators: 2.4 ± 5.3%), 1.1 ± 1.7% (-0.3 ± 2.0%), 4.8 ± 3.7% (5.4 ± 5.3%), and -0.5 ± 2.5% (-0.1 ± 3.6%) differences, respectively. The dose disagreement between the TPS and CT-based independent dose verification software was less than the 5% action level of American Association of Physicists in Medicine (AAPM) Task Group 114 (TG114). The CLs for the gimbal-mounted Vero4DRT were similar to the deviations for C-arms linear accelerators.

Liver phantom design and dosimetric verification in participating institutions for a proton beam therapy in patients with resectable hepatocellular carcinoma: Japan Clinical Oncology Group trial (JCOG1315C).

BACKGROUND AND PURPOSE: In Japan, the first domestic clinical trial of proton beam therapy for the liver was initiated as the Japan Clinical Oncology Group trial (JCOG1315C: Non-randomized controlled study comparing proton beam therapy and hepatectomy for resectable hepatocellular carcinoma). Purposes of this study were to develop a new dosimetric verification system and to carry out a credentialing for the JCOG1315C clinical trial. MATERIALS AND METHODS: Accuracy and differences in doses in proton treatment planning among participating institutions were surveyed and investigated. We designed and developed a suitable water tank-type liver phantom for a dosimetric verification of proton beam therapy for liver. In a visiting survey of five institutions participating in the clinical trial, we performed the dosimetric verification using the liver phantom and an air-filled ionization chamber. RESULTS: The shape of the dose distributions calculated in proton treatment planning was characteristic and dependent on the manufacturers of the proton beam therapy system, the proton treatment planning system and the setup at the participating institutions. Widths of the lateral penumbra were 5.8-12.7 mm among participating institutions. The accuracy between the calculated and the measured doses in the proton irradiation was within 3% at five measurement points including both points on the isocenter and off the isocenter. CONCLUSIONS: These findings confirmed the accuracy of the delivery doses in the institutions participating in the clinical trial, and the clinical trial with integration of all institutions (five institutions) could be initiated.

Impact of shoulder deformation on volumetric modulated arc therapy doses for head and neck cancer.

PURPOSE: When using volumetric modulated arc therapy (VMAT) for head and neck cancer, setup errors regarding the shoulders can create loss of target coverage or increased organ-at-risk doses. This study created variations of realistic shoulder deformations to understand the associated VMAT dosimetric effects and investigated water-equivalent thickness (WET) differences using in-house software. METHODS: Ten patients with head and neck cancer with lower neck involvement were retrospectively and randomly enrolled. Their retrospective analysis comprised treatment planning using RayStation 5.0 (RaySearch Laboratories, Stockholm, Sweden), shoulder deformation of 5-15 mm in three-dimensional axes using the ImSimQA package (Oncology Systems Limited, Shrewsbury, Shropshire, UK), and evaluation of the clinical impact of the dose distribution after recalculating the dose distribution using computed tomography images of deformed shoulders and deforming the dose distribution. Additionally, our in-house software program was used to measure WET differences for shoulder deformation. RESULTS: WET differences were greater in the superoinferior (SI) direction than in the other directions (the WET difference was >20 mm for 15-mm SI deformation). D99%, D98%, and D95% for all clinical target volumes were within 3%. Local dose differences of more than ±10% were found for normal tissues at the level of the shoulder for 15-mm movement in the SI direction. CONCLUSIONS: Shoulder deformation of >6 mm could cause large dose variations delivered to the targeted tissue at the level of the shoulder. Thus, to ensure delivery of appropriate treatment coverage to the targeted tissue, shoulder deformation should be taken into consideration during the planning stage.

Range optimization for target and organs at risk in dynamic adaptive passive scattering proton beam therapy - A proof of concept.

PURPOSE: The purpose of this study was to design and develop a new range optimization for target and organs at risk (OARs) in dynamic adaptive proton beam therapy (PBT). METHODS: The new range optimization for target and OARs (RO-TO) was optimized to maintain target dose coverage but not to increase the dose exposure of OARs, while the other procedure, range optimization for target (RO-T), only focused on target dose coverage. A retrospective analysis of a patient who received PBT for abdominal lymph node metastases was performed to show the effectiveness of our new approach. The original plan (OP), which had a total dose of 60 Gy (relative biological effectiveness; RBE), was generated using six treatment fields. Bone-based registration (BR) and tumor-based registration (TR) were performed on each pretreatment daily CT image dataset acquired once every four fractions, to align the isocenter. RESULTS: Both range adaptive approaches achieved better coverage (D95%) and homogeneity (D5%-D95%) than BR and TR only. However, RO-T showed the greatest increases in D2cc and Dmean values of the small intestine and stomach and exceeded the limitations of dose exposure for those OARs. RO-TO showed comparable or superior dose sparing compared with the OP for all OARs. CONCLUSIONS: Our results suggest that BR and TR alone may reduce target dose coverage, and that RO-T may increase the dose exposure to the OARs. RO-TO may achieve the planned dose delivery to the target and OARs more efficiently than the OP. The technique requires testing on a large clinical dataset.