Assessment and validation of glottic motion using cone-beam CT and real-time cine MRI.

PURPOSE: This study aimed to assess the margin for the planning target volume (PTV) using the Van Herk formula. We then validated the proposed margin by real-time magnetic resonance imaging (MRI). METHODS: An analysis of cone-beam computed tomography (CBCT) data from early glottic cancer patients was performed to evaluate organ motion. Deformed clinical target volumes (CTV) after rigid registration were acquired using the Velocity program (Varian Medical Systems, Palo Alto, CA, USA). Systematic (Σ) and random errors (σ) were evaluated. The margin for the PTV was defined as 2.5 Σ + 0.7 σ according to the Van Herk formula. To validate this margin, we accrued healthy volunteers. Sagittal real-time cine MRI was conducted using the ViewRay system (ViewRay Inc., Oakwood Village, OH, USA). Within the obtained sagittal images, the vocal cord was delineated. The movement of the vocal cord was summed up and considered as the internal target volume (ITV). We then assessed the degree of overlap between the ITV and the PTV (vocal cord plus margins) by calculating the volume overlap ratio, represented as (ITV∩PTV)/ITV. RESULTS: CBCTs of 17 early glottic patients were analyzed. Σ and σ were 0.55 and 0.57 for left-right (LR), 0.70 and 0.60 for anterior-posterior (AP), and 1.84 and 1.04 for superior-inferior (SI), respectively. The calculated margin was 1.8 mm (LR), 2.2 mm (AP), and 5.3 mm (SI). Four healthy volunteers participated for validation. A margin of 3 mm (AP) and 5 mm (SI) was applied to the vocal cord as the PTV. The average volume overlap ratio between ITV and PTV was 0.92 (range 0.85-0.99) without swallowing and 0.77 (range 0.70-0.88) with swallowing. CONCLUSION: By evaluating organ motion by using CBCT, the margin was 1.8 (LR), 2.2 (AP), and 5.3 mm (SI). The margin acquired using CBCT fitted well in real-time cine MRI. Given that swallowing during radiotherapy can result in a substantial displacement, it is crucial to consider strategies aimed at minimizing swallowing and related motion.

Prognosis of Patients with Chronic Hepatitis C Genotype 1b Infection Treated Using Daclatasvir/Asunaprevir after Sustained Virologic Response: A 6-Year Multicenter Prospective Observational Study.

Aim and Objectives: Direct-acting antiviral (DAA) therapy can cure chronic hepatitis C (CHC), and daclatasvir (DCV)/asunaprevir (ASV) was the first interferon-free DAA therapy introduced in Korea. Patients who achieve sustained virologic response (SVR) after DAA treatment are expected to have good prognoses. Therefore, in this study, we aimed to investigate the prognosis of these patients. Materials and Methods: This multicenter prospective observational study included patients with CHC who achieved SVR after DCV/ASV treatment. The primary endpoint was hepatocellular carcinoma (HCC) occurrence, which was reviewed annually. Results: We included 302 patients (median follow-up duration: 38 [16.5-60.0] months; median age: 58 [49-67] years) in the study. Cirrhosis was observed in 103 patients (34.1%), and the median Child-Pugh score was 5.0. HCC occurred in 16 patients (5.3%) within six years post-SVR; these patients were older and had higher cirrhosis prevalence, alpha-fetoprotein levels, and fibrosis-4 index scores than did those without HCC development. Cox proportional hazards analysis revealed that age > 71 years (p = 0.005) and cirrhosis (p = 0.035) were significant risk factors for HCC occurrence. Conclusions: Although the prognoses of patients who achieved SVR with DCV/ASV therapy were generally good, the risk for HCC was present, especially in older patients and in those with cirrhosis. Hence, early treatment at younger ages and regular follow-up surveillance after achieving SVR are warranted.

Evaluation of initial patient setup methods for breast cancer between surface-guided radiation therapy and laser alignment based on skin marking in the Halcyon system.

BACKGROUND: This study was conducted to evaluate the efficiency and accuracy of the daily patient setup for breast cancer patients by applying surface-guided radiation therapy (SGRT) using the Halcyon system instead of conventional laser alignment based on the skin marking method. METHODS AND MATERIALS: We retrospectively investigated 228 treatment fractions using two different initial patient setup methods. The accuracy of the residual rotational error of the SGRT system was evaluated by using an in-house breast phantom. The residual translational error was analyzed using the couch position difference in the vertical, longitudinal, and lateral directions between the reference computed tomography and daily kilo-voltage cone beam computed tomography acquired from the record and verification system. The residual rotational error (pitch, yaw, and roll) was also calculated using an auto rigid registration between the two images based on Velocity. The total setup time, which combined the initial setup time and imaging time, was analyzed to evaluate the efficiency of the daily patient setup for SGRT. RESULTS: The average residual rotational errors using the in-house fabricated breast phantom for pitch, roll, and yaw were 0.14°, 0.13°, and 0.29°, respectively. The average differences in the couch positions for laser alignment based on the skin marking method were 2.7 ± 1.6 mm, 2.0 ± 1.2 mm, and 2.1 ± 1.0 mm for the vertical, longitudinal, and lateral directions, respectively. For SGRT, the average differences in the couch positions were 1.9 ± 1.2 mm, 2.9 ± 2.1 mm, and 1.9 ± 0.7 mm for the vertical, longitudinal, and lateral directions, respectively. The rotational errors for pitch, yaw, and roll without the surface-guided radiation therapy approach were 0.32 ± 0.30°, 0.51 ± 0.24°, and 0.29 ± 0.22°, respectively. For SGRT, the rotational errors were 0.30 ± 0.22°, 0.51 ± 0.26°, and 0.19 ± 0.13°, respectively. The average total setup times considering both the initial setup time and imaging time were 314 s and 331 s, respectively, with and without SGRT. CONCLUSION: We demonstrated that using SGRT improves the accuracy and efficiency of initial patient setups in breast cancer patients using the Halcyon system, which has limitations in correcting the rotational offset.

Image-Guided Versus Conventional Brachytherapy for Locally Advanced Cervical Cancer: Experience of Single Institution with the Same Practitioner and Time Period.

PURPOSE: This study aimed to compare treatment outcomes and toxicity profile between imaged-guided brachytherapy (IGBT) versus conventional brachytherapy (CBT) performed by the same practitioner during the same time period. MATERIALS AND METHODS: Medical records of 104 eligible patients who underwent brachytherapy for locally advanced cervical cancer were retrospectively reviewed. Fifty patients (48.1%) underwent IGBT, and 54 (51.9%) patients underwent CBT. All patients underwent concurrent chemoradiation with cisplatin. High-dose-rate intracavitary brachytherapy with dose prescription of 25-30 Gy in 4-6 fractions was performed for all patients. Late lower gastrointestinal (GI) and urinary toxicities occurred more than 3 months after the end of brachytherapy were included for comparative and dosimetric analyses. RESULTS: The median follow-up period was 18.33 months (range, 3.25 to 38.43 months). There were no differences in oncologic outcomes between the two groups. The IGBT group had lower rate of actuarial grade ≥ 3 toxicity than the CBT group (2-year, 4.5% vs. 25.7%; p=0.030). Cumulative equieffective D2cc of sigmoid colon was significantly correlated with grade ≥ 2 lower GI toxicity (p=0.033), while equieffective D2cc of rectum (p=0.055) and bladder (p=0.069) showed marginal significance with corresponding grade ≥ 2 toxicities in the IGBT group. Half of grade ≥ 3 lower GI toxicities impacted GI tract above the rectum. Optimal thresholds of cumulative D2cc of sigmoid colon and rectum were 69.7 Gy and 70.8 Gy, respectively, for grade ≥ 2 lower GI toxicity. CONCLUSION: IGBT showed superior toxicity profile to CBT. Evaluating the dose to the GI tract above rectum by IGBT might prevent some toxicities.

Near-maximum rib dose is the most relevant risk factor for ipsilateral spontaneous rib fracture: a dosimetric analysis of breast cancer patients after radiotherapy.

PURPOSE: Spontaneous rib fracture (SRF) is a common late complication in treated breast cancer patients. This study evaluated the incidence and risk factors of ipsilateral SRF after radiotherapy (RT) in breast cancer patients. In addition, we identified dosimetric parameters that were significantly associated with ipsilateral SRF. METHODS: We retrospectively reviewed 2204 patients with breast cancer who underwent RT between 2014 and 2016, and were followed up with bone scans. We evaluated clinical risk factors for ipsilateral SRF. Dose-volume histogram analysis was also performed for patients (n = 538) whose dosimetric data were available. All ipsilateral ribs were manually delineated, and dosimetric parameters of the ribs were converted into the equivalent dose in 2 Gy fractions (EQD2). RESULTS: Most of the patients with SRF (87.3%) were asymptomatic, and the remaining symptomatic patients complained of mild tenderness or chest wall discomfort; these symptoms all resolved within 6 months without any treatment. Ipsilateral SRF occurred in 14.5% of patients 3 years after RT. The median time to develop ipsilateral SRF was 15 months. In dosimetric analysis, near-maximum rib dose (D2cc) best predicted ipsilateral SRF. The cut-off value of D2cc was EQD2 52 Gy, as determined by receiver operating characteristic analysis. In multivariate analysis including dosimetric variables, D2cc EQD2 ≥ 52 Gy was the only significant risk factor for ipsilateral SRF. CONCLUSION: Our data demonstrated that near-maximum rib dose was the best dosimetric parameter to predict ipsilateral SRF in RT-treated breast cancer patients. In addition, our results suggest that patients who received RT with exceeding rib dose cut-off value and had ipsilateral SRF on bone scan be recommended routine follow-up without additional imaging tests.

Outcome of Intermittent Thoracentesis versus Pigtail Catheter Drainage for Hepatic Hydrothorax.

Background/Aims: The management of hepatic hydrothorax (HH) remains a challenging clinical scenario with suboptimal options. We investigated the effect and safety of pigtail catheter drainage compared to intermittent thoracentesis. Methods: This multicenter, retrospective study included 164 cirrhotic patients with recurrent pleural effusion from March 2012 to June 2017. Patients with neoplasms, cardiopulmonary disease, and infectious conditions were excluded. We compared the clinical outcomes of pigtail catheter drainage versus thoracentesis for variables including complications related to procedures, overall survival, and re-admission rates. Results: A total of 164 patients were divided into pigtail catheter (n = 115) and thoracentesis (n = 49) groups. During the follow-up period of 6.93 months after discharge, 98 patients died (pigtail; n = 47 vs. thoracentesis; n = 51). The overall survival (p = 0.61) and 30-day mortality (p = 0.77) rates were similar between the pigtail catheter and thoracentesis groups. Only MELD scores were associated with overall survival (adjusted HR, 1.08; p < 0.01) in patients with HH. Spontaneous pleurodesis occurred in 59 patients (51.3%) in the pigtail catheter group. Re-admission rates did not differ between the pigtail catheter and thoracentesis groups (13.2% vs 19.6% p = 0.7). A total of five complications occurred, including four total cases of bleeding (one patient in the pigtail catheter group and three in the thoracentesis group) and one case of empyema in the pigtail catheter group. Conclusions: Pigtail catheter drainage is not inferior to that of intermittent thoracentesis for the management of HH, proving it may be an effective and safe clinical option.

Evaluation of the dosimetric and radiobiological parameters in four radiotherapy regimens for synchronous bilateral breast cancer.

This study is to investigate the optimal treatment option for synchronous bilateral breast cancer (SBBC) by comparing dosimetric and radiobiological parameters of intensity-modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT) plans using single and dual isocenters. Twenty patients with SBBC without lymph node involvement were selected retrospectively. Four treatment plans were generated for each patient using the Eclipse treatment planning system (Varian Medical System, Palo Alto, CA, USA) following two delivery techniques with two isocenter conditions-IMRT using a single isocenter (IMRT_Iso1), VMAT using a single isocenter (VMAT_Iso1), IMRT using dual isocenters (IMRT_Iso2), and VMAT using dual isocenters (VMAT_Iso2). A dose of 42.56 Gy in 16 fractions was prescribed for the planning target volume (PTV). All plans were calculated using the Acuros XB algorithm and a photon optimizer for a 6-MV beam of a Vital Beam linear accelerator. PTV-related dosimetric parameters were analyzed. Further, the homogeneity index, conformity index, and conformation number were computed to evaluate plan quality. Dosimetric parameters were also measured for the organs at risk (OARs). In addition, the equivalent uniform dose corresponding to an equivalent dose related to a reference of 2 Gy per fraction, the tumor control probability, and the normal tissue complication probability were calculated based on the dose-volume histogram to investigate the radiobiological impact on PTV and OARs. IMRT_Iso1 exhibited similar target coverage and a certain degree of dosimetric improvement in OAR sparing compared to the other techniques. It also exhibited some radiobiological improvement, albeit insignificant. Although IMRT_Iso1 significantly increased monitor unit compared to VMAT_Iso1, which is the best option in terms of delivery efficiency, there was only a 22% increase in delivery time. Therefore, in conclusion, IMRT_Iso1, the complete treatment of which can be completed using a single setup, is the most effective method for treating SBBC.

Platelet-to-White Blood Cell Ratio Is Associated with Adverse Outcomes in Cirrhotic Patients with Acute Deterioration.

Background: The platelet-to-white blood cell ratio (PWR) is a hematologic marker of the systemic inflammatory response. Recently, the PWR was revealed to have a role as an independent prognostic factor for mortality in patients with hepatitis B virus (HBV)-related acute-on-chronic failure (ACLF) and HBV-related liver cirrhosis (LC) with acute decompensation (AD). However, the prognostic role of the PWR still needs to be investigated in LC patients with AD. In this study, we analyzed whether the PWR could stratify the risk of adverse outcomes (death or liver transplantation (LT)) in these patients. Methods: A prospective cohort of 1670 patients with AD of liver cirrhosis ((age: 55.2 ± 7.8, male = 1226 (73.4%)) was enrolled and evaluated for 28-day and overall adverse outcomes. Results: During a median follow-up of 8.0 months (range, 1.9−15.5 months), 424 (25.4%) patients had adverse outcomes (death = 377, LT = 47). The most common etiology of LC was alcohol use (69.7%). The adverse outcome rate was higher for patients with a PWR ≤ 12.1 than for those with a PWR > 12.1. A lower PWR level was a prognostic factor for 28-day adverse outcomes (PWR: hazard ratio 1.707, p = 0.034) when adjusted for the etiology of cirrhosis, infection, ACLF, and the MELD score. In the subgroup analysis, the PWR level stratified the risk of 28-day adverse outcomes regardless of the presence of ACLF or the main form of AD but not for those with bacterial infection. Conclusions: A lower PWR level was associated with 28-day adverse outcomes, indicating that the PWR level can be a useful and simple tool for stratifying the risk of 28-day adverse outcomes in LC patients with AD.

Dosimetric evaluation of magnetic resonance imaging-guided adaptive radiation therapy in pancreatic cancer by extent of re-contouring of organs-at-risk.

PURPOSE: The safety of online contouring and planning for adaptive radiotherapy is unknown. This study aimed to evaluate the dosimetric difference of the organ-at-risk (OAR) according to the extent of contouring in stereotactic magnetic resonance image-guided adaptive RT (SMART) for pancreatic cancer. MATERIALS AND METHODS: We reviewed the treatment plan data used for SMART in patients with pancreatic cancer. For the online contouring and planning, OARs within 2 cm from the planning target volume (PTV) in the craniocaudal direction were re-controlled daily at the attending physician's discretion. The entire OARs were re-contoured retrospectively for data analysis. We termed the two contouring methods the Rough OAR and the Full OAR, respectively. The proportion of dose constraint violation and other dosimetric parameters was analyzed. RESULTS: Nineteen patients with 94 fractions of SMART were included in the analysis. The dose constraint was violated in 10.6% and 43.6% of the fractions in Rough OAR and Full OAR methods, respectively (p = 0.075). Patients with a large tumor, a short distance from gross tumor volume (GTV) to OAR, and a tumor in the body or tail were associated with more occult dose constraint violations-large tumor (p = 0.027), short distance from GTV to OAR (p = 0.061), tumor in body or tail (p = 0.054). No dose constraint violation occurred outside 2 cm from the PTV. CONCLUSION: More occult dose constraint violations can be found by the Full OAR method in patients with pancreatic cancer with some clinical factors in the online re-planning for SMART. Re-contouring all the OARs would be helpful to detect occult dose constraint violations in SMART planning. Since the dosimetric profile of SMART cannot be represented by a single fraction, patient selection for the Full OAR method should be weighted between the clinical usefulness and the time and workforce required.

Circulating miRNA is a useful diagnostic biomarker for nonalcoholic steatohepatitis in nonalcoholic fatty liver disease.

Nonalcoholic steatohepatitis (NASH) is considered as a progressive form of nonalcoholic fatty liver disease (NAFLD). To distinguish NASH from nonalcoholic fatty liver (NAFL), we evaluated the diagnostic value of circulating miRNAs. Small RNA sequencing was performed on 12 NAFL patients and 12 NASH patients, and the miRNA expression was compared. After selecting miRNAs for the diagnosis of NASH, we analyzed the diagnostic accuracy of each miRNA and the combination of miRNAs. External validation was performed using quantitative reverse transcription PCR. Among the 2,588 miRNAs, 26 miRNAs significantly increased in the NASH group than in the NAFL group. Among the 26 elevated miRNAs in the NASH group, 8 miRNAs were selected, and in silico analysis was performed. Only four miRNAs (miR-21-5p, miR-151a-3p, miR-192-5p, and miR-4449) showed significant area under the receiver operating characteristic curve (AUC) values for NASH diagnosis. The combination of the four miRNAs showed satisfactory diagnostic accuracy for NASH (AUC 0.875; 95% CI 0.676-0.973). External validation revealed similar diagnostic accuracy for NASH (AUC 0.874; 95% CI 0.724-0.960). NASH represents significantly distinct miRNA expression profile compared with NAFL. The combination of serum circulating miRNAs can be used as a novel biomarker for the NASH diagnosis in NAFLD.

Evaluation of a new foetal shielding device for pregnant brain tumour patients.

BACKGROUND: The present study aimed to propose a new foetal shielding device for pregnant cancer patients to reduce the foetal dose associated with treatment techniques using multiple gantry angles, such as intensity-modulated radiation therapy (IMRT) or volumetric modulated arc therapy (VMAT). METHODS: Three shielding structures were designed to minimise the scattered and leaked radiation from various gantry angles and radiation scattering within the patient. The base-plate part that can be placed on the treatment couch was designed to reduce the scattered and leaked radiation generated at gantry angles located near 180°. A body shielding part that can cover the lower chest and abdomen was designed, and a neck-shielding structure was added to reduce the internal and external radiation scattering from the treatment area. Evaluation plans were generated to assess the foetal dose reduction by the foetal shielding device in terms of the shielding material thickness, distance from the field edge, and shielding component using the flattened 6 MV photon beam (6MV) and flattening filter-free 6 MV photon beam (6MV-FFF). In addition, the effectiveness of the foetal shielding device was evaluated in a pregnant brain tumour patient. RESULTS: The shielding material consisting of three parts was placed on frames composed of four arch shapes with a vertical curved structure, connection bar at the top position, and base plate. Each shielding part resulted in reductions in the radiation dose according to the treatment technique, as the thickness of the shielding material increased and the foetal dose decreased. In addition, a foetal dose reduction of approximately 50% was confirmed at 50 cm from the field edge by using the designed shielding device in most delivery techniques. In patients, the newly designed shielding structures can effectively eliminate up to about 49% of the foetal dose generated from various gantry angles used in VMAT or IMRT. CONCLUSIONS: We designed a foetal shielding device consisting of three parts to effectively reduce the dose delivered to the foetus, and evaluated the device with various treatment techniques for a pregnant patient with brain tumour. The foetal shielding device shielded the scattered/leaked radiation from the treatment machine, and also effectively reduced internal scattering from the treatment area in the patient.

Development of Dosimetric Verification System for Patient-Specific Quality Assurance of High-Dose-Rate Brachytherapy.

Purpose: The aim of this study was to develop a dosimetric verification system (DVS) using a solid phantom for patient-specific quality assurance (QA) of high-dose-rate brachytherapy (HDR-BT). Methods: The proposed DVS consists of three parts: dose measurement, dose calculation, and analysis. All the dose measurements were performed using EBT3 film and a solid phantom. The solid phantom made of acrylonitrile butadiene styrene (ABS, density = 1.04 g/cm3) was used to measure the dose distribution. To improve the accuracy of dose calculation by using the solid phantom, a conversion factor [CF(r)] according to the radial distance between the water and the solid phantom material was determined by Monte Carlo simulations. In addition, an independent dose calculation program (IDCP) was developed by applying the obtained CF(r). To validate the DVS, dosimetric verification was performed using gamma analysis with 3% dose difference and 3 mm distance-to-agreement criterion for three simulated cases: single dwell position, elliptical dose distribution, and concave elliptical dose distribution. In addition, the possibility of applying the DVS in the high-dose range (up to 15 Gy) was evaluated. Results: The CF(r) between the ABS and water phantom was 0.88 at 0.5 cm. The factor gradually increased with increasing radial distance and converged to 1.08 at 6.0 cm. The point doses 1 cm below the source were 400 cGy in the treatment planning system (TPS), 373.73 cGy in IDCP, and 370.48 cGy in film measurement. The gamma passing rates of dose distributions obtained from TPS and IDCP compared with the dose distribution measured by the film for the simulated cases were 99.41 and 100% for the single dwell position, 96.80 and 100% for the elliptical dose distribution, 88.91 and 99.70% for the concave elliptical dose distribution, respectively. For the high-dose range, the gamma passing rates in the dose distributions between the DVS and measurements were above 98% and higher than those between TPS and measurements. Conclusion: The proposed DVS is applicable for dosimetric verification of HDR-BT, as confirmed through simulated cases for various doses.

Four-dimensional inverse-geometry computed tomography: a preliminary study.

This study introduces and evaluates respiratory-correlated four-dimensional (4D) inverse geometry computed tomography (IGCT). The projection data of the IGCT were acquired in a single gantry rotation over 120 s. Three virtual phantoms-static Defrise, 4D Shepp-Logan, and 4D extended cardiac-torso (XCAT)-were used to obtain projection data for the IGCT and cone-beam computed tomography (CBCT). The projection acquisition parameters were determined to eliminate vacancies in the Radon space for an accurate rebinning process. Phase-based sorting was conducted within 10 phase bins, and the sorted projection data were binned into a cone beam geometry. Finally, Feldkamp-Davis-Kress reconstruction was conducted independently at each phase. The reconstructed images were compared using the structural similarity index measure (SSIM) and root mean square error (RMSE). The vertical profile of the Defrise reconstruction image was uniform, and the cone beam artefact was reduced in the IGCT image. Under an ideal projection acquisition condition, the mean coronal plane SSIMs of the Shepp-Logan and 4D XCAT phantoms were 0.899 and 0.706, respectively, which were higher than those of the CBCT (0.784 and 0.623, respectively). Similarly, the mean RMSEs of the coronal plane IGCT (0.036 and 0.158) exhibited an improvement over those of the CBCT (0.165 and 0.261, respectively). The mean standard deviations of the SSIM and RMSE were lower for IGCT than for CBCT. In particular, the SSIM and RMSE of the sagittal and coronal planes of the Shepp-Logan IGCT images were stable in all phase bins; however, those of the CBCT changed depending on the phase bins. Poor image quality was observed for IGCT under inappropriate conditions. This was caused by a vacancy in the Radon space, owing to an inappropriate scan setting. Overall, the proposed 4D IGCT exhibited better image quality than conventional CBCT.

Spermidine promotes melanin production through an MITF signalling pathway.

Melanin plays an important role in determining skin colour. Apoptosis of melanocytes and defect in melanin production cause vitiligo. Various studies have been conducted to treat the disease, but its treatment is still difficult. Therefore, this study aimed to investigate the effect of spermidine, which is known as an inhibitor of ageing-related oxidized proteins, on melanogenesis. Even though spermidine above 50 µM had no effect on antioxidant activity and DOPA oxidation, it displayed tyrosinase activity. However, spermidine at 2000 µM was cytotoxic in B16F1 cells using MTT assay. Spermidine above 125 µM decreased the amount of intracellular hydrogen peroxide in a concentration-dependent manner in DCFH-DA analysis. It was also found that spermidine above 2000 µM increased melanin synthesis in living cells. However, spermidine above 1000 µM increased melanin synthesis in a concentration-dependent manner in H2 O2 -treated B16F1 cells. Furthermore, spermidine enhanced the expression of tyrosine hydroxylase via MITF transcription factor involved in melanogenesis in H2 O2 -treated B16F1 cells. Therefore, these results suggest that spermidine could be applied as a potential stimulator of melanin synthesis for the prevention of hair greying.

Dose Super-Resolution in Prostate Volumetric Modulated Arc Therapy Using Cascaded Deep Learning Networks.

PURPOSE: This study proposes a cascaded network model for generating high-resolution doses (i.e., a 1 mm grid) from low-resolution doses (i.e., ≥3 mm grids) with reduced computation time. METHODS: Using the anisotropic analytical algorithm with three grid sizes (1, 3, and 5 mm) and the Acuros XB algorithm with two grid sizes (1 and 3 mm), dose distributions were calculated for volumetric modulated arc therapy plans for 73 prostate cancer patients. Our cascaded network model consisted of a hierarchically densely connected U-net (HD U-net) and a residual dense network (RDN), which were trained separately following a two-dimensional slice-by-slice procedure. The first network (HD U-net) predicted the downsampled high-resolution dose (generated through bicubic downsampling of the baseline high-resolution dose) using the low-resolution dose; subsequently, the second network (RDN) predicted the high-resolution dose from the output of the first network. Further, the predicted high-resolution dose was converted to its absolute value. We quantified the network performance using the spatial/dosimetric parameters (dice similarity coefficient, mean dose, maximum dose, minimum dose, homogeneity index, conformity index, and V95%, V70%, V50%, and V30%) for the low-resolution and predicted high-resolution doses relative to the baseline high-resolution dose. Gamma analysis (between the baseline dose and the low-resolution dose/predicted high-resolution dose) was performed with a 2%/2 mm criterion and 10% threshold. RESULTS: The average computation time to predict a high-resolution axial dose plane was <0.02 s. The dice similarity coefficient values for the predicted doses were closer to 1 when compared to those for the low-resolution doses. Most of the dosimetric parameters for the predicted doses agreed more closely with those for the baseline than for the low-resolution doses. In most of the parameters, no significant differences (p-value of >0.05) between the baseline and predicted doses were observed. The gamma passing rates for the predicted high-resolution does were higher than those for the low-resolution doses. CONCLUSION: The proposed model accurately predicted high-resolution doses for the same dose calculation algorithm. Our model uses only dose data as the input without additional data, which provides advantages of convenience to user over other dose super-resolution methods.

Development of a deformable lung phantom with 3D-printed flexible airways.

PURPOSE: Deformable lung phantoms have been proposed to investigate four-dimensional (4D) imaging and radiotherapy delivery techniques. However, most phantoms mimic only the lung and tumor without pulmonary airways. The purpose of this study was to develop a reproducible, deformable lung phantom with three-dimensional (3D)-printed airways. METHODS: The phantom consists of: (a) 3D-printed flexible airways, (b) flexible polyurethane foam infused with iodinated contrast agents, and (c) a motion platform. The airways were simulated using publicly available breath-hold computed tomography (CT) image datasets of a human lung through airway segmentation, computer-aided design modeling, and 3D printing with a rubber-like material. The lung was simulated by pouring liquid expanding foam into a mold with the 3D-printed airways attached. Iodinated contrast agents were infused into the lung phantom to emulate the density of the human lung. The lung/airways phantom was integrated into our previously developed motion platform, which allows for compression and decompression of the phantom in the superior-inferior direction. We quantified the reproducibility of the density (lung), motion/deformation (lung and airways), and position (airways) using breath-hold CT scans (with the phantom compressed and decompressed) repeated every two weeks over a 2-month period as well as 4D CT scans (with the phantom continuously compressed and decompressed) repeated twice over four weeks. The density reproducibility was quantified with a difference image (created by subtracting the rigidly registered baseline and the repeated images) in each of the compressed and decompressed states. Reproducibility of the motion/deformation was evaluated by comparing the baseline displacement vector fields (DVFs) derived from deformable image registration (DIR) between the compressed and decompressed phantom CT images with those of repeated scans and calculating the difference in the displacement vectors. Reproducibility of the airway position was quantified based on DIR between the baseline and repeated images. RESULTS: For the breath-hold CT scans, the mean difference in lung density between baseline and week 8 was -1.3 (standard deviation 33.5) Hounsfield unit (HU) in the compressed state and 0.4 (36.8) HU in the decompressed state, while large local differences were observed around the high-contrast structures (caused by small misalignments). By visual inspection, the DVFs (between the compressed and decompressed states) at baseline and last time point (week 8 for the breath-hold CT scans) demonstrated a similar pattern. The mean lengths of displacement vector differences between baseline and week 8 were 0.5 (0.4) mm for the lung and 0.3 (0.2) mm for the airways. The mean airway displacements between baseline and week 8 were 0.6 (0.5) mm in the compressed state and 0.6 (0.4) mm in the decompressed state. We also observed similar results for the 4D CT scans (week 0 vs week 4) as well as for the breath-hold CT scans at other time points (week 0 vs weeks 2, 4, and 6). CONCLUSIONS: We have developed a deformable lung phantom with 3D-printed airways based on a human lung CT image. Our findings indicate reproducible density, motion/deformation, and position. This phantom is based on widely available materials and technology, which represents advantages over other deformable phantoms.

Development and dosimetric assessment of a patient-specific elastic skin applicator for high-dose-rate brachytherapy.

PURPOSE: The purpose of this study was to develop a patient-specific elastic skin applicator and to evaluate its dosimetric characteristics for high-dose-rate (HDR) brachytherapy. METHODS AND MATERIALS: We simulated the treatment of a nonmelanoma skin cancer on the nose. An elastic skin applicator was manufactured by pouring the Dragon Skin (Smooth-On Inc., Easton, PA) with a shore hardness of 10A into an applicator mold. The rigid skin applicator was printed using high-impact polystyrene with a shore hardness of 73D. HDR plans were generated using a Freiburg Flap (FF) applicator and patient-specific rigid and elastic applicators. For dosimetric assessment, dose-volumetric parameters for target volume and normal organs were evaluated. Global gamma evaluations were performed, comparing film measurements and treatment planning system calculations with various gamma criteria. The 10% low-dose threshold was applied. RESULTS: The V120% values of the target volume were 56.9%, 70.3%, and 70.2% for HDR plans using FF, rigid, and elastic applicators, respectively. The maximum doses of the right eyeball were 21.7 Gy, 20.5 Gy, and 20.5 Gy for the HDR plans using FF, rigid, and elastic applicators, respectively. The average gamma passing rates were 82.5% ± 1.5%, 91.6% ± 0.8%, and 94.8% ± 0.2% for FF, rigid, and elastic applicators, respectively, with 3%/3 mm criterion. CONCLUSIONS: Patient-specific elastic skin applicator showed better adhesion to irregular or curved body surfaces, resulting in better agreement between planned and delivered dose distributions. The applicator suggested in this study can be effectively implemented clinically.

A respiratory-guided 4D digital tomosynthesis.

The aim of this research was to introduce and evaluate a respiratory-guided slow gantry rotation 4D digital tomosynthesis (DTS). For each of ten volunteers, two breathing patterns were obtained for 3 min, one under free breathing conditions and the other with visual respiratory-guidance using an in-house developed respiratory monitoring system based on pressure sensing. Visual guidance was performed using a 4 s cycle sine wave with an amplitude corresponding to the average of end-inhalation peaks and end-exhalation valleys from the free-breathing pattern. The scan range was 40 degrees for each simulation, and the frame rate and gantry rotation speed were determined so that one projection per phase should be included. Both acquisition time and the number of total projections to be acquired (NPA) were calculated. Applying the obtained respiration pattern and the corresponding sequence, virtual projections were acquired under a typical geometry of Varian on-board imager for two virtual phantoms, modified Shepp-Logan (mSL) and extended cardiac-torso (XCAT). For the XCAT, two different orientations were considered, anterior-posterior (i.e. coronal) and left-right (i.e. sagittal). Projections were sorted to ten phases and image reconstruction was made using a modified filtered back-projection. Reconstructed images were compared with the planned breathing data (i.e. ideal situation) by structural similarity index (SSIM) and normalized root-mean-square error (NRMSE). For each case, simulation with guidance (SwG) showed motion-related artefact reduction compared to that under free-breathing (SuFB). SwG required less NPA but provided slightly higher SSIM and lower NRMSE values in all phantom images than SuFB did. In addition, the distribution of projections per phase was more regular in SwG. Through the proposed respiratory-guided 4D DTS, it is possible to reduce imaging dose while improving image quality. (Institutional Review Board approval: MC17DESI0086).

Dosimetric and radiobiological comparison in different dose calculation grid sizes between Acuros XB and anisotropic analytical algorithm for prostate VMAT.

To investigate feasible treatment planning parameters, we aimed to evaluate the dosimetric and radiobiological impact of the dose calculation algorithm and grid size in the volumetric modulated arc therapy (VMAT) plan for prostate cancer. Twenty patients were selected, and the treatment plans were initially generated with anisotropic analytical algorithm (AAA) and recalculated with Acuros XB (AXB) algorithm. Various dose grids were used for AXB (1, 2, and 3 mm) and AAA (1, 3, and 5 mm) plan. Dosimetric parameters such as homogeneity index (HI) and conformity index (CI), and radiobiological parameters such as tumor control probability (TCP) and normal tissue complication probability (NTCP) were calculated. Significant differences were observed in the planning target volume (PTV) coverage between both algorithms, and the V95%, HI, and CI of AAA were significantly affected by grid (p < 0.01). On 1 mm grid, the mean rectal dose difference between both algorithms was 2.87% of the prescription dose (p < 0.01), which was the highest among the critical organs. The TCP and NTCP of the AAA were higher than those of AXB (p < 0.01). Compared to AXB with 1 mm grid, the 2 mm grid showed comparable dose calculation accuracy with short calculation time. This study found that the PTV and rectum show significant differences according to dose calculation algorithm and grid. Considering the dose calculation performance for heterogeneous area, we recommend AXB with 2 mm grid for improving treatment efficiency of prostate VMAT.

To propose adding index of achievement (IOA) to IMRT QA process.

BACKGROUND: In intensity modulated radiation therapy (IMRT) quality assurance (QA), evaluation of QA result using a pass/non-pass strategy under an acceptance criterion often suffers from lack of information on how good the plan is in absolute manner. In this study, we suggested adding an index system, previously developed for dose painting technique, to current IMRT QA process for better understanding of QA result. METHODS: The index system consists of three indices, index of achievement (IOA), index of hotness (IOH) and index of coldness (IOC). As indicated by its name, IOA does measure the level of agreement. IOH and IOC, on the other hand, measure the magnitude of overdose and underdose, respectively. A systematic analysis was performed with three 1-dimensional hypothetical dose distributions to investigate the characteristics of the index system. The feasibility of the system was also assessed with clinical volumetric modulated arc therapy (VMAT) QA cases from 8 head & neck and 5 prostate patients. In both simulation studies, certain amount of errors was intentionally induced to each dose distribution. Furthermore, we applied the proposed system to compare calculated with actual measured data for a total of 60 patients (30 head & neck and 30 prostate cases). QA analysis was made using both the index system and gamma method, and results were compared. RESULTS: While the gamma evaluation showed limited sensitivity in evaluating QA result depending on the level of tolerance criteria used, the proposed indices tended to better distinguish plans in terms of the amount of errors. Hotness and coldness of prescribed dose in the plan could be evaluated quantitatively by the indices. CONCLUSIONS: The proposed index system provides information with which IMRT QA result would be better evaluated, especially when gamma pass rates are identical or similar among multiple plans. In addition, the independency of the index system on acceptance criteria would help making clear communications among readers of published articles and researchers in multi-institutional studies.