Study of a plastic scintillating plate-based quality assurance system for pencil beam scanning proton beams.

INTRODUCTION: The purpose of this study was to evaluate a plastic scintillating plate-based beam monitoring system to perform quality assurance (QA) measurements in pencil beam scanning proton beam. METHODS: Single spots and scanned fields were measured with the high-resolution dosimetry system, consisting of a plastic scintillation plate coupled to a camera in a dark box at the isocenter. The measurements were taken at 110-190 MeV beam energies with 30° gantry angle intervals at each energy. Spot positions were determined using the plastic scintillating plate-based dosimetry system at the isocenter for 70-230 MeV beam energies with 30° gantry angle intervals. The effect of gantry angle on dose distribution was also assessed by determining the scanning pattern for daily QA and 25 fields treated with intensity-modulated proton therapy. RESULTS: Spot size, field flatness, and field symmetry of plastic scintillating plate-based dosimetry system were consistent with EBT3 at all investigated energies and angles. In all investigated energies and angles, the spot size measured was ±10% of the average size of each energy, the spot position measured was within ±2 mm, field flatness was within ±2%, and field symmetry was within ±1%. The mean gamma passing rates with the 3%/3 mm gamma criterion of the scanning pattern and 25 fields were 99.2% and 99.8%, respectively. CONCLUSIONS: This system can be effective for QA determinations of spot size, spot position, field flatness, and field symmetry over 360° of gantry rotation in a time- and cost-effective manner, with spatial resolution comparable to that of EBT3 film.

Reduced radiation exposure to circulating blood cells in proton therapy compared with X-ray therapy in locally advanced lung cancer: Computational simulation based on circulating blood cells.

Background: We estimated the dose of circulating blood cells (CBCs) in patients with locally advanced non-small cell lung cancer for predicting severe radiation-induced lymphopenia (SRIL) and compared pencil-beam scanning proton therapy (PBSPT) and intensity-modulated (photon) radiotherapy (IMRT). Materials and methods: After reviewing 325 patients who received definitive chemoradiotherapy with PBSPT (n = 37) or IMRT (n = 164). SRIL was diagnosed when two or more events of an absolute lymphocyte count < 200 µL occurred during the treatment course. Dose information for the heart and lungs was utilized for the time-dependent computational dose calculation of CBCs. Results: The dose distribution of CBCs was significantly lesser in the PBSPT group than that in the IMRT group. Overall, 75 (37.3%) patients experienced SRIL during the treatment course; 72 and 3 patients were treated with IMRT and PBSPT, respectively. SRIL was associated with poor progression-free and overall survival outcomes. Upon incorporating the dose information of CBCs for predicting SRIL, CBC D90% > 2.6 GyE was associated with the development of SRIL with the baseline lymphocyte count and target volume. Furthermore, PBSPT significantly reduced the dose of CBC D90% (odds ratio = 0.11; p = 0.004) compared with IMRT. Conclusion: The results of this study demonstrate the significance of the dose distribution of CBCs in predicting SRIL. Furthermore, reducing the dose of CBCs after PBSPT minimized the risk of SRIL. Lymphocyte-sparing radiotherapy in PBSPT could improve outcomes, particularly in the setting of maintenance immunotherapy.

Monitor unit prediction model for wobbling proton therapy with ridge filters.

PURPOSE: We introduced an output factor (cGy/MU) prediction model for wobbling proton beams over the full range of proton energy, scatterer thickness, and the width of spread-out Bragg peak (SOBP). MATERIALS AND METHODS: From December 2015 to August 2020, 1990 wobbling proton fields were used to treat patients, where 1714 fields had a diameter smaller than 11 cm and 276 had a diameter between 11 and 16 cm, which were designated as small and middle wobbling radius cases, respectively. The output factor is defined as the ratio of proton absorbed dose at mid-depth of SOBP to monitor unit (MU). It depends dominantly on proton energy, scatterer thickness, and the width of SOBP. We established the prediction model using the polynomial fitting function and determined its coefficients for the small and middle wobbling radius cases. We evaluated the accuracy of our prediction model by calculating the difference between predicted and measured output factors. RESULTS: For the small wobbling radius cases, the mean value of the output factor difference was 0.22% with a standard deviation of 1.3%. For the middle wobbling radius cases, the mean value was 0.20% and with a standard deviation of 0.79%. The large deviation was especially observed for wobbling proton beams having small field size and small width of SOBP. CONCLUSIONS: We made a prediction model of output factor for wobbling proton beams, thereby determining MU of each beam. This included the dependency of the output factor on the proton energy between 70 and 230 MeV, scatterer thickness, and the width of SOBP. For 93.6% of the small and 95.5% of the middle wobbling radius cases, the deviation between predicted and measured output factor was below 3%. The cases with deviations of predicted and measured output factor above 3% had small field size and small width of SOBP. The accuracy of our prediction model would be improved by adopting the field size effect and measuring more cases of small field size and small SOBP width in the future.

Clinical application of a gantry-attachable plastic scintillating plate dosimetry system in pencil beam scanning proton therapy beam monitoring.

PURPOSE: The entrance beam fluence of therapeutic proton scanning beams can be monitored using a gantry-attachable plastic scintillating plate (GAPSP). This study evaluated the clinical application of the GAPSP using a method that measures intensity modulated proton therapy (IMPT) beams for patient treatment. METHODS: IMPT beams for the treatment of nine patients, at sites that included the spine, head and neck, pelvis, and lung, were measured using the GAPSP, composed of an EJ-212 plastic scintillator and a CMOS camera. All energy layers distinguished by the GAPSP were accumulated to determine the dose distribution of the treatment field. The evaluated fields were compared with reference dose maps verified by quality assurance. RESULTS: Comparison of dose distributions of evaluation treatment fields with reference dose distributions showed that the 3%/1 mm average gamma passing rate was 96.4%, independent of the treatment site, energy range and field size. When dose distributions were evaluated using the same criteria for each energy layer, the average gamma passing rate was 91.7%. CONCLUSIONS: The GAPSP is a suitable, low-cost method for monitoring pencil beam scanning proton therapy, especially for non-spot scanning or additional collimation. The GAPSP can also estimate the treatment beam by the energy layer, a feature not common to other proton dosimetry tools.

Changes in High-Density Lipoprotein Cholesterol and Risks of Cardiovascular Events: A Post Hoc Analysis from the PICASSO Trial.

BACKGROUND AND PURPOSE: Whether pharmacologically altered high-density lipoprotein cholesterol (HDL-C) affects the risk of cardiovascular events is unknown. Recently, we have reported the Prevention of Cardiovascular Events in Asian Patients with Ischaemic Stroke at High Risk of Cerebral Haemorrhage (PICASSO) trial that demonstrated the non-inferiority of cilostazol to aspirin and superiority of probucol to non-probucol for cardiovascular prevention in ischemic stroke patients (clinicaltrials.gov: NCT01013532). We aimed to determine whether on-treatment HDL-C changes by cilostazol and probucol influence the treatment effect of each study medication during the PICASSO study. METHODS: Of the 1,534 randomized patients, 1,373 (89.5%) with baseline cholesterol parameters were analyzed. Efficacy endpoint was the composite of stroke, myocardial infarction, and cardiovascular death. Cox proportional hazards regression analysis examined an interaction between the treatment effect and changes in HDL-C levels from randomization to 1 month for each study arm. RESULTS: One-month post-randomization mean HDL-C level was significantly higher in the cilostazol group than in the aspirin group (1.08 mmol/L vs. 1.00 mmol/L, P<0.001). The mean HDL-C level was significantly lower in the probucol group than in the non-probucol group (0.86 mmol/L vs. 1.22 mmol/L, P<0.001). These trends persisted throughout the study. In both study arms, no significant interaction was observed between HDL-C changes and the assigned treatment regarding the risk of the efficacy endpoint. CONCLUSIONS: Despite significant HDL-C changes, the effects of cilostazol and probucol treatment on the risk of cardiovascular events were insignificant. Pharmacologically altered HDL-C levels may not be reliable prognostic markers for cardiovascular risk.

Quality assurance of isocentres for passive proton beam nozzles using motion capture cameras.

PURPOSE: The objective of this work is to determine mechanical, radiation, and imaging isocentres in three-dimensional (3D) coordinates and verifying coincidence of isocentres of passively scattered proton beam using a visual tracking system (VTS) and an in-house developed phantom named the Eagle. METHODS: The Eagle phantom consists of two modules: The first, named Eagle-head, is used for determining 3D mechanical isocentre of gantry rotation. The second, named Eagle-body, is used for determining 3D radiation and imaging isocentres. The Eagle-body has four slots wherein radiochromic films were inserted for measuring the 3D radiation isocentre and a metal bead was embedded in the centre of one cube to determine the imaging isocentre; this was determined by analysing cone-beam computed tomography images of the cube. Infrared reflective markers that can be tracked by VTS were attached to the Eagle at predetermined locations. The tracked data were converted into 3D treatment room coordinates. The developed method was compared with other methods to assess accuracy. RESULTS: The isocentres were determined in mm with respect to the laser isocentre. The mechanical, radiation, and imaging isocentres were (-0.289, 0.189, 0.096), (-0.436, -0.217, 0.009), and (0.134, 0.142, 0.103), respectively. When compared with other methods, the difference in coordinates was (-0.033, -0.107, 0.014) and (0.003, 0.067, 0.039) for radiation and imaging isocentres, respectively. CONCLUSION: The developed system was found to be useful in providing fast and accurate measurements of the three isocentres in the 3D treatment room coordinate system.

Feasibility study of a plastic scintillating plate-based treatment beam fluence monitoring system for use in pencil beam scanning proton therapy.

PURPOSE: The purpose of this study was to describe a plastic scintillating plate-based gantry-attachable dosimetry system for pencil beam scanning proton therapy to monitor entrance proton beam fluence, and to evaluate the dosimetric characteristics of this system and its feasibility for clinical use. METHODS: The dosimetry system, consisting of a plastic scintillating plate and a CMOS camera, was attached to a dedicated scanning nozzle and scintillation during proton beam irradiation was recorded. Dose distribution was calculated from the accumulated recorded frames. The dosimetric characteristics (energy dependency, dose linearity, dose rate dependency, and reproducibility) of the gantry-attachable dosimetry system for use with therapeutic proton beams were measured, and the feasibility of this system during clinical use was evaluated by determining selected quality assurance items at our institution. RESULTS: The scintillating plate shortened the range of the proton beam by the water-equivalent thickness of the plate and broadened the spatial profile of the single proton spot by 11% at 70 MeV. The developed system functioned independently of the beam energy (<1.3%) and showed dose linearity, and also functioned independently of the dose rate. The feasibility of the system for clinical use was evaluated by comparing the measured quality assurance dose distribution to that of the treatment planning system. The gamma passing rate with a criterion of 3%/3 mm was 97.58%. CONCLUSIONS: This study evaluated the dosimetric characteristics of a plastic scintillating plate-based dosimetry system for use with scanning proton beams. The ability to account for the interference of the dosimetry system on the therapeutic beam enabled offline monitoring of the entrance beam fluence of the pencil beam scanning proton therapy independent of the treatment system with high resolution and in a cost-effective manner.

High-precision quality assurance of robotic couches with six degrees of freedom.

A robotic couch capable of six degrees of freedom (6-DoF) of motion was introduced for state-of-the-art radiation therapy. Patient treatment requires precise quality assurance (QA) of 6-DoF. Unfortunately, conventional methods do not provide the requisite accuracy and precision. Therefore, we developed a high-precision automated QA system using a visual tracking system (VTS). The VTS comprises four motion-sensing cameras, a cube with infrared reflective markers. To acquire data in treatment room coordinates, a transformation matrix from VTS coordinates to treatment room coordinates was determined. The mean error and standard deviation of linear and rotational motions, as well as couch sagging were analyzed from continuously acquired images in the moving couch. The accuracy of VTS was 0.024 mm deviation for the sinusoidal motion, and the accuracy of the transformation matrix was 0.02 mm. In a cross-comparison, the difference between Laser Tracker (FARO) measurements was 0.14 ±â€¯0.12 mm for translation and 0.032 ±â€¯0.026° on average for yaw rotation. The new system provides QA of yaw, pitch and roll motion as well as sagging of the couch and sub-millimeter/degree accuracy together with precision.

Prevention of cardiovascular events in Asian patients with ischaemic stroke at high risk of cerebral haemorrhage (PICASSO): a multicentre, randomised controlled trial.

BACKGROUND: The optimal treatment for patients with ischaemic stroke with a high risk of cerebral haemorrhage is unclear. We assessed the efficacy and safety of cilostazol versus aspirin, with and without probucol, in these patients. METHODS: In this randomised, controlled, 2 × 2 factorial trial, we enrolled patients with ischaemic stroke with a history of or imaging findings of intracerebral haemorrhage or two or more microbleeds from 67 centres in three Asian countries. Patients were randomly assigned (1:1:1:1) to receive oral cilostazol (100 mg twice a day), aspirin (100 mg once a day), cilostazol plus probucol (250 mg twice a day), or aspirin plus probucol with centralised blocks stratified by centre. Cilostazol versus aspirin was investigated double-blinded; probucol treatment was open-label, but the outcome assessor was masked to assignment. The co-primary outcomes were incidence of the composite of stroke, myocardial infarction, or vascular death (efficacy) and incidence of haemorrhagic stroke (safety), which were assessed in intention-to-treat and modified intention-to-treat populations. Efficacy was analysed with a non-inferiority test and a superiority test if non-inferiority was satisfied. Safety was assessed with a superiority test only. This trial is registered with ClinicalTrials.gov, NCT01013532. FINDINGS: Between Aug 1, 2009, and Aug 31, 2015, we randomly assigned 1534 patients to one of the four study groups, of whom 1512 were assessed for the co-primary endpoints. During a median follow-up of 1·9 years (IQR 1·0-3·0), the incidence of composite vascular events was 4·27 per 100 person-years in patients who received cilostazol and 5·33 per 100 person-years in patients who received aspirin (HR 0·80, 95% CI 0·57-1·11; non-inferiority p=0·0077; superiority p=0·18). Incidence of cerebral haemorrhage was 0·61 per 100 person-years in patients who received cilostazol and 1·20 per 100 person-years in those who received aspirin (HR 0·51, 97·5% CI 0·20-1·27; superiority p=0·18). The incidence of vascular events was 3·91 per 100 person-years in the probucol group compared with 5·75 per 100 person-years in the non-probucol group (HR 0·69, 95% CI 0·50-0·97; superiority p=0·0316). The incidence of cerebral haemorrhage was 0·72 per 100 person-years in the probucol group and 1·11 per 100 person-years in the non-probucol group (HR 0·65, 97·5% CI 0·27-1·57; p=0·55). Adverse events were similar across the four study groups; the most common events were dizziness, headache, diarrhoea, and constipation. INTERPRETATION: In patients with ischaemic stroke at high risk of cerebral haemorrhage, cilostazol was non-inferior to aspirin for the prevention of cardiovascular events, but did not reduce the risk of haemorrhagic stroke. Addition of probucol to aspirin or cilostazol could be beneficial for reducing the incidence of cardiovascular events. FUNDING: Korea Otsuka Pharmaceutical.

Interobserver variation in target volume for salvage radiotherapy in recurrent prostate cancer patients after radical prostatectomy using CT versus combined CT and MRI: a multicenter study (KROG 13-11).

PURPOSE: To investigate interobserver variation in target volume delineations for prostate cancer salvage radiotherapy using planning computed tomography (CT) versus combined planning CT and magnetic resonance imaging (MRI). MATERIALS AND METHODS: Ten radiation oncologists independently delineated a target volume on the planning CT scans of five cases with different pathological status after radical prostatectomy. Two weeks later, this was repeated with the addition of planning MRI. The volumes obtained with CT only and combined CT and MRI were compared, and the effect of the addition of planning MRI on interobserver variability was assessed. RESULTS: There were large differences in clinical target volume (CTV) delineated by each observer, regardless of the addition of planning MRI (9.44-139.27 cm3 in CT only and 7.77-122.83 cm3 in CT plus MRI) and no significant differences in the mean and standard deviation of CTV. However, there were decreases in mean volume and standard deviation as a result of using the planning MRI. CONCLUSION: This study showed substantial interobserver variation in target volume delineation for salvage radiotherapy. The combination of planning MRI with CT tended to decrease the target volume and the variation.

Final diagnosis of patients with clinically suspected vestibular neuritis showing normal caloric response.

Vestibular neuritis is one of the most common peripheral causes of acute vestibular syndrome, of which the diagnosis is generally based on a comprehensive interpretation of clinical and laboratory findings following reasonable exclusion of other disorders. This study aimed to investigate the final diagnosis of patients admitted to hospital under the clinical impression of vestibular neuritis who showed no unilateral caloric paresis. Forty-five patients who visited the emergency department with isolated acute spontaneous vertigo were included. Among them, six patients (13%) developed definitive spontaneous vertigo lasting longer than 20min again after discharge from hospital, accompanied by hearing loss, which was audiometrically documented, leading to a final diagnosis of definite Ménière's disease. Nine patients (20%) revisited our clinic with recurrent episodic vertigo without any documented hearing loss or auditory symptoms such as hearing loss, tinnitus or ear fullness, which led to a final diagnosis of possible Ménière's disease. In four patients (9%), initial spontaneous vertigo and nystagmus changed to positional vertigo and nystagmus on the second hospital day. In 26 patients (58%), neither another episode of vertigo nor auditory symptoms developed during follow-up period (7-92months), a condition to which the authors gave an arbitrary diagnosis of "mild unilateral vestibular deficit". In conclusion, patients admitted to hospital under clinical impression of vestibular neuritis may have various final diagnoses, and "mild unilateral vestibular deficit" was the most common final diagnosis among patients who did not meet the diagnostic criteria of vestibular neuritis.

The Effect of Sleep Disordered Breathing on Olfactory Functions: Analysis by Apnea-Hypopnea Index.

OBJECTIVES: One hypothesis of obstructive sleep apnea syndrome (OSAS) is that long-standing snoring vibrations and hypoxia of the nerves cause a local neuropathy in the upper airway during sleep. The aim of this study was to investigate olfactory function in subjects comprising snorers and untreated subjects with OSAS, and to correlate data with polysomnographic parameters. METHODS: Sixty-nine patients were evaluated for snoring from January 2010 to December 2013. The mild group (apneahypopnea index [AHI]<15) consisted of 19 subjects, and the moderate-severe group (AHI≥15) consisted of 50 subjects. Exclusion criteria were conductive olfactory dysfunction, previous tonsil or soft palatal surgery, central sleep apnea, and medications that are known to affect peripheral nerves. Nocturnal polysomnography and olfactory function test such as Korean version of Sniffin's stick test I, II (KVSS I, II) were performed. RESULTS: There was a significant difference in body mass index, average oxygen saturation (SaO2), lowest SaO2, average snoring duration, and KVSS I, II between the two groups. AHI was related to odor threshold score, and average SaO2 was related to odor discrimination score. But, odor identification score showed no relation with AHI and average SaO2 except for age. Average SaO2 and AHI were closely related to the function of smell. CONCLUSION: Hypoxia and low nasal airflow caused by OSAS may have an effect on the olfactory function. On comparison between the two groups, patients with a high AHI, especially those with OSAS, had an olfactory dysfunction. Also, low average oxygen is the main risk factor in determining the olfactory function. In people with OSAS, the possibility of olfactory dysfunction should be considered and an olfactory function test should be performed.

Change of nystagmus direction during a head-roll test in lateral semicircular canal cupulolithiasis.

OBJECTIVE: To demonstrate positional nystagmus during a head-roll test in two patients with lateral semicircular canal (LSCC) cupulolithiasis who presented with spontaneous detachment of otoliths from the LSCC cupula, and to confirm that otoliths may adhere to both the utricle and canal sides of the cupula. PATIENTS AND METHODS: Using video nystagmography, positional nystagmus was evaluated in two patients with LSCC cupulolithiasis who showed the change of nystagmus direction during a head-roll test. RESULTS: Both patients presented with persistent left-beating and right-beating nystagmus when the head was bent forward and backward, respectively. This suggests the presence of either cupulolithiasis on the right side or light cupula on the left side of the LSCC. In Case 1, transformation from cupulolithiasis to canalolithiasis occurred, implicating the detachment of otoliths from the canal side of the right LSCC cupula. In Case 2, vigorous right-beating nystagmus was followed by persistent left-beating nystagmus when the head was rolled to the left. Following this, direction-fixed left-beating nystagmus was observed at all positions, which may indicate that otoliths attached on utricle side of the right LSCC cupula were detached and fell into the utricle under the influence of gravity. A conversion of nystagmus direction may be explained by an expression of short-term adaptation of vestibular tone. CONCLUSIONS: Otoliths can be attached to either side of the cupula in LSCC cupulolithiasis. Because it is difficult to determine the attached side at the time of diagnostic maneuver, the therapeutic approach should include maneuvers designed to detach otolith particles from both the utricle and canal side.

Secondary cancer-incidence risk estimates for external radiotherapy and high-dose-rate brachytherapy in cervical cancer: phantom study.

This study was designed to estimate radiation-induced secondary cancer risks from high-dose-rate (HDR) brachytherapy and external radiotherapy for patients with cervical cancer based on measurements of doses absorbed by various organs. Organ doses from HDR brachytherapy and external radiotherapy were measured using glass rod dosimeters. Doses to out-of-field organs were measured at various loca-tions inside an anthropomorphic phantom. Brachytherapy-associated organ doses were measured using a specialized phantom that enabled applicator insertion, with the pelvis portion of the existing anthropomorphic phantom replaced by this new phantom. Measured organ doses were used to calculate secondary cancer risk based on Biological Effects of Ionizing Radiation (BEIR) VII models. In both treatment modalities, organ doses per prescribed dose (PD) mostly depended on the distance between organs. The locations showing the highest and lowest doses were the right kidney (external radiotherapy: 215.2 mGy; brachytherapy: 655.17 mGy) and the brain (external radiotherapy: 15.82 mGy; brachytherapy: 2.49 mGy), respectively. Organ doses to nearby regions were higher for brachytherapy than for external beam therapy, whereas organ doses to distant regions were higher for external beam therapy. Organ doses to distant treatment regions in external radiotherapy were due primarily to out-of-field radiation resulting from scattering and leakage in the gantry head. For brachytherapy, the highest estimated lifetime attributable risk per 100,000 population was to the stomach (88.6), whereas the lowest risks were to the brain (0.4) and eye (0.4); for external radiotherapy, the highest and lowest risks were to the thyroid (305.1) and brain (2.4). These results may help provide a database on the impact of radiotherapy-induced secondary cancer incidence dur-ing cervical cancer treatment, as well as suggest further research on strategies to counteract the risks of radiotherapy-associated secondary malignancies.

Conversion between geotropic and apogeotropic persistent direction-changing positional nystagmus.

CONCLUSION: Clinical features in the course of conversion differed between patients with SSNHL and cupulopathy, which indicates that the pathophysiology of persistent geotropic or apogeotropic DCPN and the mechanism of the change in nystagmus direction may differ between the two groups. OBJECTIVE: The aim of this study is to investigate clinical characteristics of 10 patients with persistent DCPN who exhibited a conversion of nystagmus direction between geotropic and apogeotropic, and discuss possible mechanisms. METHODS: Using video-oculography, serial examinations of nystagmus in a head-roll test were performed. RESULTS: Of these 10 patients, five had sudden sensorineural hearing loss (SSNHL) and the remaining five had cupulopathy. In SSNHL, direction of nystagmus changed from geotropic to apogeotropic in three patients and from apogeotropic to geotropic in two patients. In cupulopathy, persistent apogeotropic DCPN always preceded persistent geotropic DCPN. The change in nystagmus direction occurred earlier in patients with cupulopathy (1 or 2 days after vertigo onset) than in patients with SSNHL (4-23 days after vertigo onset). While the null plane was consistently identified on one side, regardless of the nystagmus direction in cupulopathy, it was not always identified on the side of hearing loss in SSNHL.

Temporomandibular Joint Herniation Into the External Auditory Canal: Two Cases Involving a Persistent Foramen Tympanicum.

A congenital bony defect of the external auditory canal (EAC) may cause temporomandibular joint (TMJ) herniation into the EAC. This rare condition is known as persistent foramen tympanicum. We report 2 cases of symptomatic TMJ herniation through a patent foramen tympanicum. The patients complained of mastication-induced tinnitus. Otoscopic examination revealed that a whitish protruding mass at the anterior wall of the EAC bulged when the patients closed their mouths. After conservative managements such as avoidance of chewing foods on the affected side for 2 months, mastication-induced tinnitus disappeared and the size of protruding mass was decreased in one of the patients. Surgical repair of the bony defect has been the treatment of choice. In cases when symptoms are trivial and patients do not want surgical treatment, however, conservative management would be a sound alternative.

Preclinical investigation for developing injectable fiducial markers using a mixture of BaSO4 and biodegradable polymer for proton therapy.

PURPOSE: The aim of this study is to investigate the use of mixture of BaSO4 and biodegradable polymer as an injectable nonmetallic fiducial marker to reduce artifacts in x-ray images, decrease the absorbed dose distortion in proton therapy, and replace permanent metal markers. METHODS: Two samples were made with 90 wt. % polymer phosphate buffer saline (PBS) and 10 wt. % BaSO4 (B1) or 20 wt. % BaSO4 (B2). Two animal models (mice and rats) were used. To test the injectability and in vivo gelation, a volume of 200 µl at a pH 5.8 were injected into the Sprague-Dawley rats. After sacrificing the rats over time, the authors checked the gel morphology. Detectability of the markers in the x-ray images was tested for two sizes (diameters of 1 and 2 mm) for B1 and B2. Four samples were injected into BALB/C mice. The polymer mixed with BaSO4 transform from SOL at 20 °C with a pH of 6.0 to GEL in the living body at 37 °C with a pH of 7.4, so the size of the fiducial marker could be controlled by adjusting the injected volume. The detectability of the BaSO4 marker was measured in x-ray images of cone beam CT (CBCT), on-board imager [anterior-posterior (AP), lateral], and fluoroscopy (AP, lateral) using a Novalis-TX (Varian Medical Systems, Palo Alto, CA) repeatedly over 4 months. The volume, HU, and artifacts for the markers were measured in the CBCT images. Artifacts were compared to those of gold marker by analyzing the HU distribution. The dose distortion in proton therapy was computed by using a Monte Carlo (MC) code. A cylindrical shaped marker (diameter: 1 or 2 mm, length: 3 mm) made of gold, stainless-steel [304], titanium, and 20 wt. % BaSO4 was positioned at the center of the spread-out Bragg peak (SOBP) in parallel or perpendicular to the beam entrance. The dose distortion was measured on the depth dose profile across the markers. RESULTS: Transformation to GEL and the biodegradation were verified. All BaSO4 markers could be detected in the CBCT. In the OBI and fluoroscopy images, all markers visible in the AP, but only B2(2 mm) could be identified in the lateral images. Changes of BaSO4 position were not detected in vivo (mice). The volume of the markers decreased by up to 65% and the HU increased by 22%, on average. The mean HU values around the B1, B2, and gold markers were 121.30 [standard deviation (SD): 54.86], 126.31 (SD: 62.13), and 1070.7 (SD: 235.16), respectively. The MC-simulated dose distortion for the BaSO4 markers was less than that of the commercially used markers. The dose reduction due to the gold marker was largest (15.05%) followed by stainless steel (7.92%) and titanium (6.92%). Dose reduction by B2 (2 mm) was 4.75% and 0.53% in parallel and perpendicular orientations, respectively. CONCLUSIONS: BaSO4 mixed with PBS is a good contrast agent in biodegradable polymer marker because of minimal artifacts in x-ray images and minimal dose reduction in proton therapy. The flexibility of the size is considered to be an advantage of this material over solid type fiducials.

Development of a 3D optical scanning-based automatic quality assurance system for proton range compensators.

PURPOSE: A new automatic quality assurance (AutoRCQA) system using a three-dimensional scanner (3DS) with system automation was developed to improve the accuracy and efficiency of the quality assurance (QA) procedure for proton range compensators (RCs). The system performance was evaluated for clinical implementation. METHODS: The AutoRCQA system consists of a three-dimensional measurement system (3DMS) based on 3DS and in-house developed verification software (3DVS). To verify the geometrical accuracy, the planned RC data (PRC), calculated with the treatment planning system (TPS), were reconstructed and coregistered with the measured RC data (MRC) based on the beam isocenter. The PRC and MRC inner surfaces were compared with composite analysis (CA) using 3DVS, using the CA pass rate for quantitative analysis. To evaluate the detection accuracy of the system, the authors designed a fake PRC by artificially adding small cubic islands with side lengths of 1.5, 2.5, and 3.5 mm on the inner surface of the PRC and performed CA with the depth difference and distance-to-agreement tolerances of [1 mm, 1 mm], [2 mm, 2 mm], and [3 mm, 3 mm]. In addition, the authors performed clinical tests using seven RCs [computerized milling machine (CMM)-RCs] manufactured by CMM, which were designed for treating various disease sites. The systematic offsets of the seven CMM-RCs were evaluated through the automatic registration function of AutoRCQA. For comparison with conventional technique, the authors measured the thickness at three points in each of the seven CMM-RCs using a manual depth measurement device and calculated thickness difference based on the TPS data (TPS-manual measurement). These results were compared with data obtained from 3DVS. The geometrical accuracy of each CMM-RC inner surface was investigated using the TPS data by performing CA with the same criteria. The authors also measured the net processing time, including the scan and analysis time. RESULTS: The AutoRCQA system accurately detected all fake objects in accordance with the given criteria. The median systematic offset of the seven CMM-RCs was 0.08 mm (interquartile range: -0.25 to 0.37 mm) and -0.08 mm (-0.58 to 0.01 mm) in the X- and Y-directions, respectively, while the median distance difference was 0.37 mm (0.23-0.94 mm). The median thickness difference of the TPS-manual measurement at points 1, 2, and 3 was -0.4 mm (-0.4 to -0.2 mm), -0.2 mm (-0.3 to 0.0 mm), and -0.3 mm (-0.6 to -0.1 mm), respectively, while the median difference of 3DMS was 0.0 mm (-0.1 to 0.2 mm), 0.0 mm (-0.1 to 0.3 mm), and 0.1 mm (-0.1 to 0.2 mm), respectively. Thus, 3DMS showed slightly better values compared to the manual measurements for points 1 and 3 in statistical analysis (p < 0.05). The average pass rate of the seven CMM-RCs was 97.97% ± 1.68% for 1-mm CA conditions, increasing to 99.98% ± 0.03% and 100% ± 0.00% for 2- and 3-mm CA conditions, respectively. The average net analysis time was 18.01 ± 1.65 min. CONCLUSIONS: The authors have developed an automated 3DS-based proton RC QA system and verified its performance. The AutoRCQA system may improve the accuracy and efficiency of QA for RCs.

Vibration- and hyperventilation-induced nystagmus in patients with Ramsay Hunt syndrome with vertigo.

OBJECTIVES: The aims of this study were to compare vibration-induced nystagmus (VIN) and hyperventilation-induced nystagmus (HVIN) findings in patients with Ramsay Hunt syndrome with vertigo (RHS-V), sudden sensorineural hearing loss with vertigo (SSNHL-V), and vestibular neuritis (VN) during the acute stage and to address the possible lesion sites of vestibular deficit in RHS-V. STUDY DESIGN: Case series with chart review. SETTING: Tertiary referral center. METHODS: We conducted a retrospective case series study in 27 patients with SSNHL-V, 104 patients with VN, and 17 patients with RHS-V and evaluated the findings of VIN and HVIN tests. RESULTS: An abnormal VIN was observed in 91% of the patients with VN, 89% of those with SSNHL-V, and 94% of those with RHS-V, and the prevalence of abnormal VIN was not significantly different (P = .436). An abnormal HVIN was observed in 51% of the patients with VN, 22% of those with SSNHL-V, and 59% of those with RHS-V. While the prevalence of an abnormal HVIN was significantly different between SSNHL-V and VN groups (P = .007) and between SSNHL-V and RHS-V groups (P = .014), that between VN and RHS-V groups did not show a significant difference (P = .547). CONCLUSION: Since the results of HVIN in RHS-V patients were more similar to those in VN patients than those in SSNHL-V patients, a lesioned site may be more likely within the vestibular nerve than the inner ear as a cause for vestibular deficit in patients with RHS-V who show caloric canal paresis of 25% or greater.

The first private-hospital based proton therapy center in Korea; status of the Proton Therapy Center at Samsung Medical Center.

PURPOSE: The purpose of this report is to describe the proton therapy system at Samsung Medical Center (SMC-PTS) including the proton beam generator, irradiation system, patient positioning system, patient position verification system, respiratory gating system, and operating and safety control system, and review the current status of the SMC-PTS. MATERIALS AND METHODS: The SMC-PTS has a cyclotron (230 MeV) and two treatment rooms: one treatment room is equipped with a multi-purpose nozzle and the other treatment room is equipped with a dedicated pencil beam scanning nozzle. The proton beam generator including the cyclotron and the energy selection system can lower the energy of protons down to 70 MeV from the maximum 230 MeV. RESULTS: The multi-purpose nozzle can deliver both wobbling proton beam and active scanning proton beam, and a multi-leaf collimator has been installed in the downstream of the nozzle. The dedicated scanning nozzle can deliver active scanning proton beam with a helium gas filled pipe minimizing unnecessary interactions with the air in the beam path. The equipment was provided by Sumitomo Heavy Industries Ltd., RayStation from RaySearch Laboratories AB is the selected treatment planning system, and data management will be handled by the MOSAIQ system from Elekta AB. CONCLUSION: The SMC-PTS located in Seoul, Korea, is scheduled to begin treating cancer patients in 2015.