Retrospective analysis of treatment-positioning accuracy and dose error in boron neutron capture therapy using a sitting-position treatment system for head and neck cancer.

The neutron beam in boron neutron capture therapy (BNCT) exhibits poor directionality and significantly decreasing neutron flux with increasing distance. Therefore, the treatment site must be close to the irradiation aperture. Some patients with head and neck cancer may benefit from a sitting-position setup. The study aim was to evaluate the treatment-positioning accuracy and dose error in sitting patients receiving BNCT. Thirty-two patients with head and neck cancer who underwent sitting-position BNCT at Southern Tohoku BNCT Research Center were included in the study. Horizontal (ΔX) and vertical (ΔY) errors were defined as the displacement between the treatment planning system (TPS) digital reconstructed radiograph and the pre-treatment X-ray image. Using in-house software, image matching was performed. The beam-axial directional (ΔZ) error was compared with the parameters entered into the TPS and the actual pre-treatment measured values. The translational-position error was reflected in the TPS's patient coordinate system with respect to the reference plan. Re-dose calculations were performed to evaluate the effect of positional error on tumor and normal-tissue doses. The [ΔX, ΔY, ΔZ] DRR-CR mean ± 1SD were - 0.40 ± 2.0, 0.30 ± 2.3, and - 1.4 ± 1.5 mm, respectively. The Dmean and D98% tumor-dose errors were 1.22 % ± 1.44 % and 0.99 % ± 1.63 %, respectively. The D2% pharyngeal and oral mucosal-dose errors were 0.98 % ± 1.91 % and 1.21 % ± 1.78 %, respectively. The tumor- and normal-tissue dose errors were typically < 5 %. High-precision treatment was feasible in sitting-positioned BNCT.

Long-term beam output stability of an accelerator-based boron neutron capture therapy system.

BACKGROUND: Accelerator-based boron neutron capture therapy (AB-BNCT) systems are becoming commercially available and are expected to be widely used in hospitals. To ensure the safety of BNCT, establishing a quality assurance (QA) program and properly managing the stability of the system are necessary. In particular, a high level of beam output stability is required to avoid accidents because beam output is a major factor in patient dose. However, no studies have analyzed the long-term beam output stability of AB-BNCT systems. PURPOSE: This study aimed to retrospectively analyze the long-term stability of the beam output by statistical process control (SPC) based on the QA results over 3 years. METHODS: The data analyzed are the results of daily QA (DQA) and weekly QA (WQA) in an AB-BNCT system and were taken between June 2020 and September 2023. The evaluation of the stability of the beam output was based on the reaction rate between gold and neutrons calculated using the activation foil method using a gold foil. In DQA, which can be performed in a short time, the gold foil was applied directly to the beam irradiation aperture in air. In WQA, measurements were performed at the phantom surface, 2-cm depth, and 6-cm depth using a dedicated water phantom. The acquired data were retrospectively analyzed by individuals and a moving range chart (I-MR chart), exponentially weighted moving average control chart (EWMA chart), and several process capability indexes (PCIs). RESULTS: Over 99% of the DQA I-MR chart results were within control limits, whereas the WQA I-MR chart results showed that 1.8%, 4.1%, and 2.0% of the measurements exceeded the control limits at the surface, 2-cm depth, and 6-cm depth, respectively. The variation in the reaction rate of the gold foil before and after the replacement of the target was <0.5%. The EWMA chart results revealed no significant beam output drift for either DQA or WQA. Most measured data were normal based on the results of the Anderson-Darling test and met the requirements for PCI evaluation; most PCI values were >1.0; however, the Cpmk of DQA and the 2- and 6-cm depth WQAs between August 2021 and November 2022 in treatment course 2 were 0.83, 0.77, and 0.87, respectively, which were <1.0. CONCLUSIONS: The long-term stability of beam output was confirmed using SPC in an AB-BNCT system. The results of the control chart revealed no significant variation or drift in the beam output, and the quantitative evaluation using PCI revealed high stability. A routine QA program will enable us to provide safe BNCT.

Evaluation of calculation accuracy and computation time in a commercial treatment planning system for accelerator-based boron neutron capture therapy.

This study aims to evaluate the feasibility of using a commercially available boron neutron capture therapy (BNCT) dose calculation program (NeuCure® Dose Engine) in terms of calculation accuracy and computation time. Treatment planning was simulated under the following calculation parameters: 1.5-5.0 mm grid sizes and 1-10% statistical uncertainties. The calculated monitor units (MUs) and computation times were evaluated. The MUs calculated on grid sizes larger than 2 mm were overestimated by 2% compared with the result of 1.5 mm grid. We established the two-step method for the routine administration of BNCT: multiple calculations involved in beam optimization should be done at a 5 mm grid and a 10% statistical uncertainty (the shortest computation time: 10.3 ± 2.1 min) in the first-step, and final dose calculations should be performed at a 2 mm grid and a 10% statistical uncertainty (satisfied clinical accuracy: 6.9 ± 0.3 h) in the second-step.

Preliminary Investigation of the Efficacy and Indications of Proton Beam Therapy for Stage IV Pancreatic Adenocarcinoma.

BACKGROUND: The present study aimed to evaluate proton beam therapy (PBT) for stage IV pancreatic adenocarcinoma and its metastases and define the criteria for eligibility. Materials and methods: We retrospectively evaluated the patients who had a histopathological diagnosis of pancreatic adenocarcinoma, had progressed to stage IV, and underwent PBT for both the primary and some metastatic lesions between 2017 and 2022. PBT was performed using the passive scattering technique. RESULTS: Sixteen patients (median age, 72 years; range, 55-85 years) were enrolled. All patients had stage IV pancreatic cancer at the initiation of PBT. The median duration from the date of stage IV diagnosis to the initiation of PBT was 5.8 (range, 0.4-13.5) months. Three patients had been diagnosed as having recurrent stage IV cancer at other institutions before their referral to our hospital because they had local recurrence and distant metastases after the resection of the primary tumor. Chemotherapy was as follows: pre-PBT, 0, 1, 2, and 3 lines in 4, 7, 4, and 1 patients, respectively; concurrent with PBT, 0 and 1 line in 11 and 5 patients, respectively; post-PBT, 0 and 1 line in 5 and 5 patients, respectively; and unknown, 6 patients. The median survival times (MSTs) from the date of stage IV diagnosis for the with or without non-irradiated active metastatic tumor were 11.4 and 20.1 months, respectively. Univariate analysis revealed that the performance status (PS) levels (p < 0.01), the carbohydrate antigen (CA) 19-9 tumor marker levels (p < 0.01), active tumors not treated with irradiation (p = 0.02), and with or without post-PBT chemotherapy (p < 0.01) were statistically significant factors. Multivariate analysis revealed that the CA 19-9 tumor marker levels (p= 0.04), the number of metastatic lesions (p = 0.049), and with or without non-irradiated active metastatic tumors (p = 0.02) were significant factors. CONCLUSION: PBT is indicated when the number of metastases is limited to ≤ 4 lesions and all tumors can be irradiated within the smallest possible number of irradiation fields that can be performed within the patient's tolerable time, which is a subjective duration that depends on the patient's reaction during each session. It may be a viable treatment option for patients with oligometastatic pancreatic cancer.

Evaluation of Diaphragm Position Variations During Proton Therapy for Pediatric Patients With Neuroblastoma.

Background To evaluate the respiratory-induced intrafractional diaphragm motion and interfractional diaphragm displacement in pediatric patients with neuroblastoma (NBL). Materials and methods Ten pediatric patients with a mean age of 4.5 years (range: 1.8-8.7 years) with abdominal NBL treated with proton therapy (PT) have been evaluated. Intrafractional motion and interfractional displacement have been analyzed by using cine radiography and orthogonal X-ray images, respectively. In each case, the cranio-caudal positions of the diaphragm have been measured as an index. This study has investigated the possible correlations between intrafractional diaphragm motion and height. Additionally, interfractional displacement and its time trend during the treatment course have been analyzed. Results The average right and left diaphragm intrafractional motions of 8.3 mm (range: 4.4-11.5 mm) and 6.4 mm (range: 2.2-11.8 mm) were observed, respectively; however, no significant correlation has been observed with height. An interfractional displacement of 5 mm or more has been observed in 20 out of 152 fractions (13%). The average absolute value of the interfractional displacement was 2.5 mm (range: 0-8.6 mm). Interfractional displacement did not show a peculiar tendency throughout the treatment period. Conclusions It was suggested that respiratory-induced diaphragm position variation in children varies greatly among individuals, and accurately estimating it based on height is difficult. Thus, these individual evaluations are considered indispensable.

Evaluation of a creatinine clearance correction equation based on body fat mass in older Japanese patients with diabetes.

Background: The estimation of creatinine clearance (CCr) in older adult patients with diabetes is subject to deviations from the results of actual measurements because of changes in body composition. In the present study, we aimed to create a correction for the equation used for the estimation of CCr in older adult Asian patients with diabetes using body composition parameters. Methods: We enrolled 50 older Japanese patients with diabetes in whom the measured values of CCr were compared with values estimated using the Cockcroft-Gault equation. The relationships between the error in the estimated CCr and body composition parameters were investigated, and the Cockcroft-Gault equation was corrected using the appropriate parameters. To evaluate the generalizability of the corrected equation, the utility of the Cockcroft-Gault equation, which was corrected on the basis of body composition measured using a household body composition meter, was also investigated. Results: Body fat mass (BFM) was closely correlated with the error in the estimated CCr. The BFM-corrected Cockcroft-Gault equation was more accurate than the original equation. Similarly, the error became smaller using BFM measured with a household body composition meter. Conclusion: The BFM-corrected Cockcroft-Gault equation may provide an accurate method of estimating CCr that can be used in general practice.

Analysis of respiratory-induced motion trajectories of individual liver segments in patients with hepatocellular carcinoma.

PURPOSE: To analyze the respiratory-induced motion trajectories of each liver segment for hepatocellular carcinoma (HCC) to derive a more accurate internal margin and optimize treatment protocol selection. MATERIALS AND METHODS: Ten-phase-gated four-dimensional computed tomography (4DCT) scans of 14 patients with HCC were analyzed. For each patient, eight representative regions of interest (ROI) were delineated on each liver segment in all 10 phases. The coordinates of the center of gravity of each ROI were obtained for each phase, and then the respiratory motion in the left-right (LR), anteroposterior (AP), and craniocaudal (CC) directions was analyzed. Two sets of motion in each direction were also compared in terms of only two extreme phases and all 10 phases. RESULTS: Motion of less than 5 mm was detected in 12 (86%) and 10 patients (71%) in the LR and AP directions, respectively, while none in the CC direction. Motion was largest in the CC direction with a maximal value of 19.5 mm, with significant differences between liver segment 7 (S7) and other segments: S1 (p < 0.036), S2 (p < 0.041), S3 (p < 0.016), S4 (p < 0.041), and S5 (p < 0.027). Of the 112 segments, hysteresis >1 mm was observed in 4 (4%), 2 (2%), and 15 (13%) in the LR, AP, and CC directions, respectively, with a maximal value of 5.0 mm in the CC direction. CONCLUSION: A significant amount of respiratory motion was detected in the CC direction, especially in S7, and S8. Despite the small effect of hysteresis, it can be observed specifically in the right lobe. Therefore, caution is required when using 4DCT to determine IM using only end-inspiration and end-expiration. Understanding the respiratory motion in individual liver segments can be helpful when selecting an appropriate treatment protocol.

Optimal Bladder Volume for Hypofractionated Proton Therapy in Each Localized Prostate Cancer Risk Group.

Background This study aimed to determine the optimal bladder volume (BV) for hypofractionated proton therapy in prostate cancer (PC). Materials and methods Two hundred patients with PC were enrolled in this study and classified into low-, intermediate-, and high-risk groups. Treatment planning was performed by assuming a hypofractionated schedule of 63 Gy (relative biological effectiveness) in 21 fractions. The dose indices of the bladder (V60 and V50) were calculated and classified into four groups according to the BV. A cutoff value with a 95% confidence interval was calculated on the basis of the mean and standard deviation of the dose indices. These values were compared with the dose constraints (V60 < 15 % and V50 < 30 %). Results The dose indices were higher in the high-risk group than in the other risk groups. The cutoff value exceeded dose constraints in the low- and intermediate-risk groups with a BV of â‰¦ 149 cc. Additionally, the cutoff value exceeded the dose constraint in the high-risk group with a BV of ≦ 199 cc. In all the cases, the group with a BV of â‰§ 200 cc was below the dose constraint. Conclusions In this study, the relationship between the dose and volume of the bladder in hypofractionated PT for PC was evaluated using a 95% CI to determine the optimal BV. The BV should be changed for each risk group, and a larger BV is required for a high-risk group than for other risk groups.

A Serine Protease Inhibitor, Camostat Mesilate, Suppresses Urinary Plasmin Activity and Alleviates Hypertension and Podocyte Injury in Dahl Salt-Sensitive Rats.

In proteinuric renal diseases, the serine protease (SP) plasmin activates the epithelial sodium channel (ENaC) by cleaving its γ subunit. We previously demonstrated that a high-salt (HS) diet provoked hypertension and proteinuria in Dahl salt-sensitive (DS) rats, accompanied by γENaC activation, which were attenuated by camostat mesilate (CM), an SP inhibitor. However, the effects of CM on plasmin activity in DS rats remain unclear. In this study, we investigated the effects of CM on plasmin activity, ENaC activation, and podocyte injury in DS rats. The DS rats were divided into the control diet, HS diet (8.0% NaCl), and HS+CM diet (0.1% CM) groups. After weekly blood pressure measurement and 24-h urine collection, the rats were sacrificed at 5 weeks. The HS group exhibited hypertension, massive proteinuria, increased urinary plasmin, and γENaC activation; CM treatment suppressed these changes. CM prevented plasmin(ogen) attachment to podocytes and mitigated podocyte injury by reducing the number of apoptotic glomerular cells, inhibiting protease-activated receptor-1 activation, and suppressing inflammatory and fibrotic cytokine expression. Our findings highlight the detrimental role of urinary plasmin in the pathogenesis of salt-sensitive hypertension and glomerular injury. Targeting plasmin with SP inhibitors, such as CM, may be a promising therapeutic approach for these conditions.

Optimal Bladder Condition in Volumetric Modulated Arc Therapy for Prostate Cancer: The Role of Superior-Inferior Lengths of the Bladder and Dose Constraints.

Background Optimal bladder conditions based on dose constraints in prostate cancer radiation therapy (RT) are important. In this study, the superior-inferior (SI) lengths of the bladder were assessed to define the ideal bladder state for RT. Materials and methods In this study, 50 prostate cancer cases treated with three-dimensional conformal radiation therapy between January and December 2021 were retrospectively analyzed. Using their CT data, a volumetric modulated arc therapy (VMAT) plan was simulated. Bladder dose constraints and dimensions, including SI, right-left (RL), and anterior-posterior (AP) lengths, were assessed. In total, 28 cases met the dose constraints and 22 cases did not meet the dose constraints.  Results Median bladder volumes (BVs) for compliant and non-compliant cases were 163.6 ml and 88.5 ml, respectively (p<0.0001). For compliant plans, median bladder dimensions were RL: 78 mm, AP: 89 mm, and SI: 51 mm. Non-compliant plans showed RL: 72 mm, AP: 84 mm, and SI: 42 mm, with significant differences (SI: p=0.0004, RL: p=0.0065, AP: p=0.037). Established thresholds were SI: 46 mm, RL: 92 mm, AP: 75 mm, and BV: 142.8 ml. SI showed the strongest correlation with BV (coefficient: 0.78). Conclusions This study analyzed the SI lengths of the bladder concerning dose constraints in VMAT for prostate cancer. It was concluded that smooth treatment planning could be achieved with proper consideration of the bladder's SI distance. Further case collection and prospective studies are warranted.

Suppression of Indoxyl Sulfate Accumulation Reduces Renal Fibrosis in Sulfotransferase 1a1-Deficient Mice.

Renal fibrosis is the final manifestation of chronic kidney disease (CKD); its prevention is vital for controlling CKD progression. Indoxyl sulfate (IS), a typical sulfate-conjugated uremic solute, is produced in the liver via the enzyme sulfotransferase (SULT) 1A1 and accumulates significantly during CKD. We investigated the toxicopathological role of IS in renal fibrosis using Sult1a1-KO mice and the underlying mechanisms. The unilateral ureteral obstruction (UUO) model was created; kidney IS concentrations, inflammation, and renal fibrosis were assessed on day 14. After UUO treatment, inflammation and renal fibrosis were exacerbated in WT mice, with an accumulation of IS in the kidney. However, they were significantly suppressed in Sult1a1-KO mice. CD206+ expression was upregulated, and ß-catenin expression was downregulated in Sult1a1-KO mice. To confirm the impact of erythropoietin (EPO) on renal fibrosis, we evaluated the time-dependent expression of EPO. In Sult1a1-KO mice, EPO mRNA expression was improved considerably; UUO-induced renal fibrosis was further attenuated by recombinant human erythropoietin (rhEPO). Thus, UUO-induced renal fibrosis was alleviated in Sult1a1-KO mice with a decreased accumulation of IS. Our findings confirmed the pathological role of IS in renal fibrosis and identified SULT1A1 as a new therapeutic target enzyme for preventing and attenuating renal fibrosis.

Dosimetric effect of six degrees of freedom couch top with rotational setup error corrections in proton therapy.

PURPOSE: To investigate the dosimetric effect of six degrees of freedom (6DoF) couch top with rotational corrections in proton therapy (PT). METHODS: The water equivalent thickness (WET) was measured using a proton beam with a 6DoF couch top and patient immobilization base plate (PIBP) placed in front of a motorized water phantom. The accuracy verification was performed with the beam axis set perpendicular to the 6DoF couch top and tilted in 10° steps from 10° to 30°. Up to 3° rotational correction may be added during the actual treatment to correct the rotational setup error on our system. The measured and calculated values using the treatment planning system were compared. Additionally, the effect of the 3° difference was evaluated using actual measurements concerning each angle on the proton beam range. RESULTS: The WET of the 6DoF couch top and PIBP were 8.5 ± 0.1 mm and 6.8 ± 0.1 mm, respectively. The calculation and the actual measurement at each angle agreed within 0.2 mm at the maximum. A maximum difference of approximately 0.6 mm was confirmed when tilted at 3° following 30° with the 6DoF couch top plus PIBP. CONCLUSIONS: The dosimetric effect of the 6DoF couch top with rotational corrections in PT differs depending on the incidence angle on the couch top, and it increased with the increased oblique angle of incidence. However, the effect on the range was as small as 0.6 mm at the maximum. The amount of rotational correction, the angle of incidence of the beam, and the effect of rotational corrections on the proton beam range may differ depending on the structure of the couch top. Therefore, sufficient prior confirmation, and subsequent periodical quality assurance management are important.

Identification of Induced Radionuclides Produced from Dental Metals in Proton Beam Therapy for Head and Neck Cancer.

Purpose: To identify the induced radionuclides produced from dental metals in proton beam therapy and investigate the accuracy of the Monte Carlo (MC) simulation by comparing the measured radioactivity. Methods and Materials: Two dental metals of pure titanium and gold-silver-palladium alloy, commonly used in Japan, were used in this study. The dental metal placed at the center of Spread-out Bragg Peak was irradiated by 150-MeV passive scattering proton beam. The gamma rays emitted from the activated dental metals were measured using a high purity germanium (HPGe) detector. The induced radionuclides were identified from the measured gamma-ray energies. Furthermore, the Particle and Heavy Ion Transport code System v.3.24 and DCHAIN were used for the MC simulation. The measured radionuclides and their radioactivity were compared with the simulation results. Results: In the MC simulation for the activated titanium, vanadium-47, with a half-life of 32.6 minutes had the strongest radioactivity among the induced radionuclides. The energy peaks of gamma rays emitted from titanium-51, scandium-43, scandium-44, and annihilation gamma rays were observed for the activated titanium in the HPGe detector. In the MC simulation for the activated gold-silver-palladium alloy, silver-108, with a half-life of 2.4 minutes had the strongest radioactivity. The energy peaks of gamma rays emitted from silver-104, silver-104 m, silver-108, and annihilation gamma rays were observed for the activated gold-silver-palladium alloy in the HPGe detector. Furthermore, the induced radionuclides and their radioactivity in the MC simulation were consistent with the measurement results for both dental metals, except for a few radionuclides. Conclusions: We identify the induced radionuclides produced from 2 dental metals and compared their radioactivity between the measurements and the MC simulation. Although the identification of the induced radionuclides using the MC simulation remains uncertain, the MC simulation can be clinically effective for pre-estimating the induced radionuclides in proton beam therapy.

Safety of hydrogel spacers for rectal wall protection in patients with prostate cancer: A retrospective analysis of 200 consecutive cases.

OBJECTIVE: To evaluate the safety and complications of hydrogel spacer implantation. METHODS: This single-center historical cohort study retrospectively analyzed cases of hydrogel spacer implantation between October 2018 and March 2022. The survey items were the rates of possible hydrogel injection implementation, the success rate of hydrogel implantation including asymmetry, higher position, rectal wall infiltration, subcapsular injection, and other adverse events, and width created by the spacer. To investigate the learning curve, 1, 2, and 3 points were assigned to adverse event grades G1, G2, and G3, respectively. Spacer effectiveness obstruction, such as asymmetry was assigned 3 points. A Mann-Whitney U test was performed to assess statistically significant differences. RESULTS: The study included a total of 200 patients with a median (range) age of 70 (44-85) years. In 10 (5%) patients, hydrogel injection implementation was not possible. Of 190 patients who underwent hydrogel spacer placement, 168 (88%) received a satisfactory placement. The median (range) width of hydrogel spacers was 13.1 (4.4-18.7) mm. Spacer asymmetry, higher position, rectal wall infiltration, and prostate subcapsular infiltration occurred in 7 (3.7%), 5 (2.6%), 12 (6.3%), and 1 (0.5%) patients, respectively. G1 and G3 adverse events occurred in 13 (7%) and 4 (2%) patients, respectively. Practitioner #1 who performed the highest number of procedures had significantly (p = 0.04) lower total scores in group B. CONCLUSION: Spacer implantation yielded favorable outcomes with a high percentage of appropriate spacer implantation, and few major complications.

The serine protease plasmin plays detrimental roles in epithelial sodium channel activation and podocyte injury in Dahl salt-sensitive rats.

Salt-sensitive hypertension is associated with poor clinical outcomes. The epithelial sodium channel (ENaC) in the kidney plays pivotal roles in sodium reabsorption and blood pressure regulation, in which its γ subunit is activated by extracellular serine proteases. In proteinuric nephropathies, plasmin filtered through injured glomeruli reportedly activates γENaC in the distal nephron and causes podocyte injury. We previously reported that Dahl salt-sensitive (DS) rats fed a high-salt (HS) diet developed hypertension and proteinuria along with γENaC activation and that a synthetic serine protease inhibitor, camostat mesilate, mitigated these changes. However, the role of plasmin in DS rats remained unclear. In this study, we evaluated the relationship between plasmin and hypertension as well as podocyte injury and the effects of plasmin inhibitors in DS rats. Five-week-old DS rats were divided into normal-salt diet, HS diet, and HS+plasmin inhibitor (either tranexamic acid [TA] or synthetic plasmin inhibitor YO-2) groups. After blood pressure measurement and 24 h urine collection over 5 weeks, rats were sacrificed for biochemical analyses. The HS group displayed severe hypertension and proteinuria together with activation of plasmin in urine and γENaC in the kidney, which was significantly attenuated by YO-2 but not TA. YO-2 inhibited the attachment of plasmin(ogen) to podocytes and alleviated podocyte injury by inhibiting apoptosis and inflammatory/profibrotic cytokines. YO-2 also suppressed upregulation of protease-activated receptor-1 and phosphorylated ERK1/2. These results indicate an important role of plasmin in the development of salt-sensitive hypertension and related podocyte injury, suggesting plasmin inhibition as a potential therapeutic strategy.

Camostat mesilate, a serine protease inhibitor, exerts aquaretic effects and decreases urinary exosomal AQP2 levels.

Serine proteases (SPs) play physiological roles in the kidney. We previously reported that a synthetic SP inhibitor, camostat mesilate (CM), suppressed sodium reabsorption in the renal tubule and showed natriuretic effects in aldosterone-infused rats. Here, we aimed to explore novel physiological roles of SPs in the renal tubule and understand the mechanism of actions of SP inhibitors, by administering CM to healthy rats. Sprague-Dawley rats were classified into control and CM (subcutaneous sustained-release pellet) groups and sacrificed on day 7. CM significantly increased urine volumes by approximately two-fold in a urinary sodium- and osmolyte excretion-independent manner, indicating the occurrence of free water excretion. Serum vasopressin, potassium, and calcium levels and the osmolality in the renal medulla, which all affect free water reabsorption in the renal tubule, remained unchanged after CM administration. CM decreased urinary exosomal AQP2 excretion, suggesting suppression of AQP2 activity in the collecting duct. These changes were reversed by desmopressin infusion. Water diuresis caused by CM was independent of its action on prostasin or TMPRSS4. Our results revealed the association of SP inhibition with free water handling and demonstrated that CM administration exerted diuretic effects with AQP2 downregulation, suggesting SP inhibitors as a new class of aquaretic drugs.

Dosimetric effects of the ipsilateral shoulder position variations in the sitting-positioned boron neutron capture therapy for lower neck tumor.

We aimed to evaluate dosimetric effects of ipsilateral shoulder position variations (ISPVs) in sitting-positioned boron neutron capture therapy (BNCT) for lower neck tumor. The ISPVs were simulated using deformed shoulder images that can simulate arbitrary shape. The dose-volume parameters for the tumor in the rotated shoulder plans considerably varied compared with that for the mucosa. Even in a small number of cases, these differences were clearly observed among patients. The ISPVs in lower neck BNCT have great dosimetric effects.

Dosimetric effect of set-up error in accelerator-based boron neutron capture therapy for head and neck cancer.

The dosimetric effect of set-up error in boron neutron capture therapy (BNCT) for head and neck cancer remains unclear. In this study, we analyzed the tendency of dose error by treatment location when simulating the set-up error of patients. We also determined the tolerance level of the set-up error in BNCT for head and neck cancer. As a method, the distal direction was shifted with an interval of 2.5 mm, from 0.0 mm to +20.0 mm and compared with the dose at the reference position. Similarly, the horizontal direction and vertical direction were shifted, with an interval of 5.0 mm, from -20.0 mm to +20.0 mm. In addition, cases with 3.0 mm and 5.0 mm simultaneous shifts in all directions were analyzed as the worst-case scenario. The dose metrics of the minimum dose of the tumor and the maximum dose of the mucosa were evaluated. From unidirectional set-up error analysis, in most cases, the set-up errors with dose errors within ±5% were Δdistal < +2.5 mm, Δhorizontal < ±5.0 mm and Δvertical < ±5.0 mm. In the simulation of 3.0 mm shifts in all directions, the errors in the minimum tumor dose and maximum mucosal dose were -3.6% ±1.4% (range, -5.4% to -0.6%) and 2% ±1.4% (range, 0.4% to 4.5%), respectively. From these results, if the set-up error was within ±3.0 mm in each direction, the dose errors of the tumor and mucosa could be suppressed within approximately ±5%, which is suggested as a tolerance level.

Dose-volume comparison of intensity modulated proton therapy and volumetric modulated arc therapy for cervical esophageal cancer.

Proton therapy for cervical esophageal cancer has many issues to be considered, such as the physiological curvature of the spine and the large range change from the neck to the trunk. We clarified the dosimetric characteristics of intensity modulated proton therapy (IMPT) for cervical esophageal cancer by comparing with volumetric modulated arc therapy (VMAT). Ten patients with cervical esophageal cancer were retrospectively planned for VMAT, 2-field IMPT (2F-IMPT), and 3-field IMPT (3F-IMPT). All plans were optimized to reach clinically acceptable levels. For planning target volume (PTV) coverage, 95% of the PTV should be covered by 95% of the prescription dose, unless the spinal cord limit is violated. The organs at risk included the lung, spinal cord, larynx, skin, and whole body. The prescription dose was 60 Gy relative biological effectiveness (RBE) in 30 fractions to the PTV. We compared the results according to dose-volume metrics. Significant dose reductions were achieved at lung doses, especially at low dose volumes of 20 Gy RBE or less in IMPT plans compared with VMAT plans (p < 0.05). Although the spinal cord PRV was below the tolerance level, the results were also significantly higher in VMAT plans than in IMPT plans (p < 0.001). Spinal cord PRV Dmean was significantly higher in 3F-IMPT than in 2F-IMPT (p < 0.001). In addition, it was confirmed that the integral whole body dose can be dramatically reduced in IMPT plans compared with VMAT plans. Both of 2F-IMPT and 3F-IMPT could effectively reduce spinal cord dose, as well as low integral whole body dose to a certain extent, while maintaining similar target coverage compared to VMAT. IMPT could be a promising treatment technique for patients with cervical esophageal cancer.