Combination therapy with lenvatinib and radiation significantly inhibits thyroid cancer growth by uptake of tyrosine kinase inhibitor.

Although surgical treatment cures >90% of differentiated thyroid cancer (DTC) patients, the remaining patients, including advanced DTC cases, have poor clinical outcomes. These patients with inoperable disease have only two choices of radioactive iodine therapy and tyrosine kinase inhibitors such as lenvatinib, which have a high incidence of treatment-related adverse events and can only prolong progression free survival by approximately 5-15 months. In this study, we investigated the antitumor effects of combination therapy with lenvatinib and radiation (CTLR) for DTC. CTLR synergistically inhibited cell replication and colony formation in vitro and tumor growth in nude mice without apparent toxicities and suppressed the expression of proliferation marker (Ki-67). CTLR also induced apoptosis and G2/M phase cell cycle arrest. Moreover, quantitative analysis of the intracellular uptake of lenvatinib using liquid chromatography and mass spectrometry demonstrated that intracellular uptake of lenvatinib was significantly increased 48 h following irradiation. These data suggest that increased membrane permeability caused by irradiation increases the intracellular concentration of levatinib, contributing to the synergistic effect. This mechanism-based potential of combination therapy suggests a powerful new therapeutic strategy for advanced thyroid cancer with fewer side effects and might be a milestone for developing a regimen in clinical practice.

Efficacy of Combination Therapy with Lenvatinib and Radioactive Iodine in Thyroid Cancer Preclinical Model.

Patients with differentiated thyroid cancer (DTC) usually have good prognosis, while those with advanced disease have poor clinical outcomes. This study aimed to investigate the antitumor effects of combination therapy with lenvatinib and 131I (CTLI) using three different types of DTC cell lines with different profiling of sodium iodide symporter (NIS) status. The radioiodine accumulation study revealed a significantly increased radioiodine uptake in K1-NIS cells after lenvatinib treatment, while there was almost no uptake in K1 and FTC-133 cells. However, lenvatinib administration before radioiodine treatment decreased radioiodine uptake of K1-NIS xenograft tumor in the in vivo imaging study. CTLI synergistically inhibited colony formation and DTC cell migration, especially in K1-NIS cells. Finally, 131I treatment followed by lenvatinib administration significantly inhibited tumor growth of the NIS-expressing thyroid cancer xenograft model. These results provide important clinical implications for the combined therapy that lenvatinib should be administered after 131I treatment to maximize the treatment efficacy. Our synergistic treatment effects by CTLI suggested its effectiveness for RAI-avid thyroid cancer, which retains NIS function. This potential combination therapy suggests a powerful and tolerable new therapeutic strategy for advanced thyroid cancer.

Subcapsular hepatic hematoma: a case of chronic expanding hematoma of the liver.

BACKGROUND: A chronic expanding hematoma (CEH) enlarges as a result of slight bleeding over several months, and the tissue shows a mixture of blood breakdown products, granulation tissue with capillary ingrowth, and inflammatory tissue. This report presents a case of a subcapsular hepatic CEH that was treated with transarterial embolization (TAE) and hepatectomy. CASE PRESENTATION: A 56-year-old man presented with vomiting and right-sided abdominal pain. Plain abdominal computed tomography (CT) showed a high-density area of fluid collection beneath the capsule of the right hepatic lobe, which was diagnosed as a hematoma. From its anatomical position on the CT images, a subcapsular hepatic hematoma was diagnosed. Though conservative therapy was provided, CT-guided percutaneous drainage and TAE were performed due to worsening symptom. Because the patient's abdominal symptoms re-appeared, extended right segmentectomy including the hematoma was performed. In the resected specimen, the hematoma was located beneath the capsule of the right hepatic lobe, and it was displacing the hepatic parenchyma. Microscopic examination showed a thick fibrous capsule around the hematoma, peripheral lymphocyte and plasmacyte invasion, and aggregations of histiocytes containing phagocytosed hemosiderin. CONCLUSIONS: Anatomically, this was a case of a subcapsular hepatic hematoma, and pathologically it was shown to be a CEH. Complete surgical resection was effective treatment for this CEH.

Clinical results of transarterial embolization for post-partum hemorrhage in 62 patients.

AIM: The pathology of post-partum hemorrhage (PPH) differs depending on its cause, background and timing of bleeding, and the effectiveness of transarterial embolization (TAE) is thought to vary based on these characteristics. The aim of this study is to evaluate the treatment outcomes of TAE for PPH. METHODS: Technical success, initial clinical success (hemostasis without repeat TAE or surgical treatment after initial TAE) and final clinical success (hemostasis with or without repeat TAE, but without surgical treatment) were assessed in 62 Japanese patients. Factors affecting final clinical success were analyzed using univariate analysis. Values of P < 0.05 were considered statistically significant. Further, the clinical course and factors associated with rebleeding, return of menstruation and fertility, and complications of TAE were assessed. RESULTS: Final clinical success rate was significantly lower in cases with obstetrical disseminated intravascular coagulation (DIC) or the International Society on Thrombosis and Hemostasis (ISTH) DIC (P = 0.01, 0.03). Rebleeding (n = 9, 14.5%) was more common in patients with retained products of conception (RPOC) (P = 0.006). On long-term follow-up in 23 patients, return of menstruation was confirmed in 17 (73.9%) of these patients. Subsequent pregnancy was confirmed in seven patients (30.4%). TAE-related complications were seen in 6 patients (9.0%). There were no maternal deaths. CONCLUSIONS: Obstetrical and ISTH DIC reduced the success rate of TAE for PPH (P = 0.01, 0.03). Rebleeding, which is observed significantly more frequently in PPH caused by RPOC (P = 0.006), can be effectively treated by repeat TAE.

Phase I Study of Sorafenib in Combination with Intermittent Hepatic Arterial Infusion Chemotherapy for Unresectable Hepatocellular Carcinoma.

OBJECTIVES: We conducted a phase I study of sorafenib and intermittent hepatic arterial infusion chemotherapy using cisplatin for unresectable hepatocellular carcinoma. METHODS: Sorafenib was administered continuously, whereas cisplatin was administered once every 3 weeks. We estimated the safety and efficacy. RESULTS: Fifteen patients were enrolled into this study. The dose-limiting toxicities occurred at sorafenib 800 mg and cisplatin 20 mg/m2. The recommended dose was at sorafenib 400 mg and cisplatin 30 mg/m2. The disease control rate was 73.3%. CONCLUSIONS: This treatment is feasible for unresectable hepatocellular carcinoma. Further evaluation of the regimen in a randomized controlled trial is warranted.

Clinical outcomes of pancreatic ductal adenocarcinoma resection following neoadjuvant chemoradiation therapy vs. chemotherapy.

PURPOSE: We compared the clinical outcomes of pancreatic ductal adenocarcinoma (PDAC) resection after neoadjuvant chemoradiation therapy (NACRT) vs. chemotherapy (NAC). METHODS: The study population comprised 81 patients with UICC stage T3/4 PDAC, treated initially by NACRT with S-1 in 40 and by NAC with gemcitabine + S-1 in 41. This was followed by pancreatectomy with routine nerve plexus resection in 35 of the patients who had received NACRT and 32 of those who had received NAC. We compared the survival curves and clinical outcomes of these two groups. RESULTS: The rates of clinical response, surgical resectability, and margin-negative resection were similar. The NACRT group patients had significantly higher rates of Evans stage ≥IIB tumors (29 vs. 0 %, respectively, p = 0.010) and negative lymph nodes (49 vs. 16 %, respectively, p = 0.021) than the NAC group patients. There was no difference in disease-free survival between the groups, but the disease-specific survival of the NAC group patients was better than that of the NACRT group patients (p = 0.034). Patients undergoing pancreatectomy with nerve plexus resection following NACRT had significantly higher rates of intractable diarrhea and ascites but consequently received significantly less adjuvant chemotherapy and therapeutic chemotherapy for relapse. CONCLUSION: NACRT followed by pancreatectomy with nerve plexus resection is superior for achieving local control, but postoperative diarrhea and ascites may prohibit continuation of adjuvant chemotherapy or chemotherapy for relapse (UMIN4148).

Evaluation of an aspiration-type semiautomatic cutting biopsy needle.

PURPOSE: The purpose of this study was to evaluate an aspiration-type semiautomatic cutting biopsy needle for biopsy of bovine tissue. MATERIAL AND METHODS: Aspiration-type semiautomatic cutting biopsy needles (18 gauge × 160 mm) with aspiration (Group A), aspiration-type semiautomatic biopsy needles without aspiration (Group Wo), or normal-type semiautomatic biopsy needles (18 gauge × 150 mm) (Group N) were used in 10 biopsies each of bovine liver or lung. The specimens were weighed with an electronic balance. RESULTS: Mean (standard deviation) weights for bovine liver specimens in Groups A, Wo, and N were 6.80 (0.615) mg, 5.62 (0.843) mg, and 4.19 (0.140) mg, respectively. Mean weights of bovine lung specimens from Groups A, Wo, and N were 2.98 (0.828) mg, 2.67 (0.832) mg, and 1.94 (0.864) mg, respectively. A significant difference was seen between the 3 groups for bovine liver. However, a significant difference was only seen between Groups A and N for bovine lung. CONCLUSION: Bovine liver and lung specimens obtained using the aspiration-type semiautomatic cutting biopsy needle were heavier than those obtained using the normal-type semiautomatic biopsy needle.

[Feasibility and Safety of Dexmedetomidine Sedation in Transarterial Embolization for Hepatocellular Carcinoma with Hepatitis C-Related Cirrhosis].

BACKGROUND: Dexmedetomidine (Precedex®)is an agonist of a2-adrenergic receptors in certain parts of the brain. It was approved for "procedural sedation in the non-intubation in under local anesthesia" in June 2013 in Japan. However, because of metabolism delay, dexmedetomidine has to be administered carefully to patients with liver dysfunction. PURPOSE: To evaluate the feasibility and safety of sedation using dexmedetomidine in percutaneous arterial chemoembolization for hepatocellular carcinoma with liver dysfunction. METHODS: Thirty consecutive cases of percutaneous arterial chemoembolization for hepatocellular carcinoma with hepatitis C-related cirrhosis(male, 23; female, 7; age, 74±5.9; weight, 62.7±12.3 kg; Child-Pugh A, 23; Child-Pugh B, 7)were analyzed retrospectively. Dexmedetomidine was administered at 3 mg/kg/h for 15 minutes as the initial loading dose and at 0.4 mg/kg/h as the maintenance dose. The sedation level was evaluated using the Ramsay sedation scale. RESULTS: In 30 of 30 cases, percutaneous arterial chemoembolization therapy could be performed with dexme- detomidine sedation. In 27 of 30 cases, the procedure was completed with the maintenance dose of 0.4 mg/kg/h. In 3 of 30 cases, the maintenance dose was increased to 0.6 mg/kg/h because of patient body motion. The mean administration time of dexmedetomidine was 82±30 minutes. The level of sedation measured with the Ramsay sedation scale at the end of the procedure was 3 points in 29 cases and 5 points in one case. Adverse events occurred in 3 of 30 cases. Intravenous drip leakage occurred in one case, vertigo occurred in one case, and vomiting occurred in one case. There were no adverse events requiring treatment. CONCLUSION: Sedation with dexmedetomidine in percutaneous arterial chemoembolization for hepatocellular carcinoma with liver dysfunction was feasible and safe.

Radiation dose of nurses during IR procedures: a controlled trial evaluating operator alerts before nursing tasks.

PURPOSE: To compare radiation exposure of nurses when performing nursing tasks associated with interventional procedures depending on whether or not the nurses called out to the operator before approaching the patient. MATERIALS AND METHODS: In a prospective study, 93 interventional radiology procedures were randomly divided into a call group and a no-call group; there were 50 procedures in the call group and 43 procedures in the no-call group. Two monitoring badges were used to calculate effective dose of nurses. In the call group, the nurse first told the operator she was going to approach the patient each time she was about to do so. In the no-call group, the nurse did not say anything to the operator when she was about to approach the patient. RESULTS: In all the nursing tasks, the equivalent dose at the umbilical level inside the lead apron was below the detectable limit. The equivalent dose at the sternal level outside the lead apron was 0.16 µSv ± 0.41 per procedure in the call group and 0.51 µSv ± 1.17 per procedure in the no-call group. The effective dose was 0.018 µSv ± 0.04 per procedure in the call group and 0.056 µSv ± 0.129 per procedure in the no-call group. The call group had a significantly lower radiation dose (P = .034). CONCLUSIONS: Radiation doses of nurses were lower in the group in which the nurse called to the operator before she approached the patient.

Portopulmonary venous anastomosis in balloon-occluded retrograde transvenous obliteration for the treatment of gastric varices.

BACKGROUND AND AIM: Several reports have described portopulmonary venous anastomosis (PPVA). However, in balloon-occluded retrograde transvenous obliteration (BRTO), attention has not been paid to paradoxical embolism. The objective of this study was to investigate the existence of a right-left shunt due to PPVA when the drainage vein is occluded by a balloon during BRTO. METHODS: The subjects were 19 patients who underwent BRTO. Whether PPVA was present was confirmed on balloon-occluded retrograde transvenous venography (BRTV). After BRTV, a retrograde bolus injection of 20 mL of carbon dioxide (CO2 ) via the balloon catheter was performed under balloon occlusion, and the flow of bubbles into both ventricles was observed with four-chamber view echocardiography. During the same balloon occlusion, bolus injection of CO2 into the inferior vena cava was performed, followed by echocardiography. RESULTS: PPVA was confirmed on BRTV in four patients (21.1%). On echocardiography with retrograde CO2 injection, bubbles were confirmed in the left ventricle in six patients (31.6%). On echocardiography with CO2 injection into the inferior vena cava, bubbles were not confirmed in the left ventricle in any cases. CONCLUSIONS: When the draining vein was occluded with a balloon and blood flow in a gastrorenal or gastrocaval shunt was stopped during BRTO, PPVA was confirmed in 21.1% of cases on retrograde angiography, and a right-left shunt was confirmed in 31.6% of cases on echocardiography.

Detection of Portal Vein Stenosis by Technetium-99m-Diethylenetriaminepentaacetic Acid-Galactosyl Human Serum Albumin Liver Scintigraphy after Living-Donor Liver Transplantation.

BACKGROUND/AIM: To investigate portal vein stenosis after living-donor liver transplantation by liver scintigraphy. METHODOLOGY: A 63-year-old woman with hepatic cirrhosis due to autoimmune hepatitis underwent living-donor liver transplantation using a graft donated by her daughter. Technetium-99m-diethylenetriaminepentaacetic acid-galactosyl human serum albumin (Tc-99m-GSA) scintigraphy was used to determine the maximum rate of Tc-99m-GSA removal (GSA-Rmax) by hepatocytes, as a parameter of hepatic functional reserve. RESULTS: Conventional liver function parameters on laboratory tests and graft volume on computed tomography (CT) were almost unchanged at postoperative month (POM) 12. GSA-Rmax was 0.11 mg/min before surgery and increased 5-fold to approximately 0.5 mg/min at POM 1 and 3, followed by a decrease to 0.25 mg/min at POM 6 and 12. Enhanced CT did not detect blood flow in the intra- or extrahepatic portions of the portal vein at POM 12. The portal vein stenosis was dilated with a balloon catheter, followed by deployment of a self-expanding stent across the stenotic segment via the transileocolic vein. GSA-Rmax recovered to 0.5 mg/min at POM 15, and subsequently remained high. CONCLUSIONS: Decreased GSA-Rmax at POM 6 indicated that the portal vein stenosis was affecting graft function. Tc-99m-GSA liver scintigraphy may be a useful noninvasive method for evaluation of graft functional reserve.

Chyluria after ligation of the thoracic duct: a rare complication after thoracoscopic-assisted esophagectomy for esophageal cancer.

Chyluria is leakage of lymphatic fluid into the urine, following trauma to or obstruction of the lymphatic system. We herein report a rare case of chyluria after esophagectomy for esophageal cancer. A 69-year-old male complaining of epigastric pain and reflux symptoms was diagnosed with advanced esophageal cancer and regional lymph node metastases. After receiving neoadjuvant chemotherapy to control the regional lymph node metastases, the patient underwent transthoracic excision of the esophagus assisted by thoracoscopy, with excision of the azygos vein and thoracic duct, esophagostomy and tube gastrostomy. On postoperative day 22, the urine appeared ivory white in color, and urine tests showed a high triglyceride level, thus confirming the diagnosis of chyluria. The chyluria decreased temporarily after switching the patient from enteral nutrition (EN) to parental nutrition, but it emerged again after the resumption of EN. Lymphangiography at that stage showed the flow of lipiodol into the pelvis of the left kidney. Resolution of the chyluria was noted after lymphangiography. He underwent esophageal reconstruction with a gastric tube through an anterior mediastinal route, and was discharged 36 days after the second operation. He was thereafter followed up at the outpatient clinic with radiotherapy.

Direct puncture embolization using N-butyl cyanoacrylate for a hepatic artery pseudoaneurysm.

Massive hemobilia caused by hepatic artery pseudoaneurysm is an uncommon but potentially fatal complication that can occur after biliary intervention. Previous intervention or surgery, atherosclerotic disease, inflammation and even anatomic variants may make the pseudoaneurysm inaccessible to transcatheter approach, therefore it is not always feasible. The present report describes a case of successful embolization of a hepatic artery pseudoaneurysm with N-butyl cyanoacrylate via direct puncture as an alternative approach. The case presentation is followed by the technical points and the properties of N-butyl cyanoacrylate that are particularly advantageous for use in direct puncture procedures.

Comparison of Tc-99m GSA scintigraphy and CT volumetry for evaluation in portal vein embolization.

PURPOSE: To determine the correlation of the rate of change of each future remnant liver (FRL) before and after portal vein embolization (PVE), by CT volumetry and Tc-99m galactosyl human serum albumin scintigraphy (GSA scintigraphy). MATERIAL AND METHODS: From December 2007 to July 2012, ten patients underwent PVE before hepatic resection. CT volumetry and GSA scintigraphy were performed before and after PVE. The FRL was divided at Cantlie's line for CT volumetry, and volume change rates before and after PVE were calculated. The maximum removal rate (Rmax) was calculated using a radiopharmacokinetic model in GSA scintigraphy. The FRL Rmax change rates before and after PVE were calculated. The correlation between the volume change rates and the Rmax change rates was analyzed. RESULTS: The FRL volume change rate was 1.28 ± 0.26 (mean ± SD); the FRL hypertrophied in all patients significantly (p = 0.005). The FRL Rmax change rate was 1.66 ± 0.75; excluding one patient, there was significant FRL Rmax increase (p = 0.022). Although both increased significantly, no correlation between the volume change rate and the Rmax change rate was observed. CONCLUSION: No correlation was observed between the FRL volume rate and the Rmax rate.

Intra-arterial infusion of thrombin: animal experiments.

PURPOSE: Thrombin inhibits cadherin on vascular endothelial cells, rapidly and reversibly increasing endothelial permeability. The purpose of this study was to evaluate the feasibility of trans-arterial infusion with thrombin. MATERIAL AND METHODS: Ten rabbits with right thigh tumor were randomly divided into two groups: A thrombin group and a control group. In the thrombin group, a suspension of thrombin (300 IU), cisplatin (3 mg), lipiodol (0.3 ml) and iopamidol (0.3 ml) was infused into the right femoral artery. In the control group, a suspension of cisplatin, lipiodol and iopamidol was infused. Platinum concentrations in plasma were measured five and ten minutes after administration. Platinum concentrations were also measured in tumor specimens excised 30 minutes after infusion. RESULTS: At both five and ten minutes after infusion, platinum concentrations in plasma were significantly lower for the thrombin group than for the control group. Platinum concentration in tumor tissue was significantly higher for the thrombin group than for the control group. CONCLUSION: The present results suggest that transarterial infusion with thrombin may offer a number of pharmacological advantages.

Artificial intelligence-based image-domain material decomposition in single-energy computed tomography for head and neck cancer.

PURPOSE: While dual-energy computed tomography (DECT) images provide clinically useful information than single-energy CT (SECT), SECT remains the most widely used CT system globally, and only a few institutions can use DECT. This study aimed to establish an artificial intelligence (AI)-based image-domain material decomposition technique using multiple keV-output learning of virtual monochromatic images (VMIs) to create DECT-equivalent images from SECT images. METHODS: This study involved 82 patients with head and neck cancer. Of these, the AI model was built with data from the 67 patients with only DECT scans, while 15 patients with both SECT and DECT scans were used for SECT testing. Our AI model generated VMI50keV and VMI100keV from VMI70keV equivalent to 120-kVp SECT images. We introduced a loss function for material density images (MDIs) in addition to the loss for VMIs. For comparison, we trained the same model with the loss for VMIs only. DECT-equivalent images were generated from SECT images and compared with the true DECT images. RESULTS: The prediction time was 5.4 s per patient. The proposed method with the MDI loss function quantitatively provided more accurate DECT-equivalent images than the model trained with the loss for VMIs only. Using real 120-kVp SECT images, the trained model produced precise DECT images of excellent quality. CONCLUSION: In this study, we developed an AI-based material decomposition approach for head and neck cancer patients by introducing the loss function for MDIs via multiple keV-output learning. Our results suggest the feasibility of AI-based image-domain material decomposition in a conventional SECT system without a DECT scanner.

Synthetic Low-Energy Monochromatic Image Generation in Single-Energy Computed Tomography System Using a Transformer-Based Deep Learning Model.

While dual-energy computed tomography (DECT) technology introduces energy-specific information in clinical practice, single-energy CT (SECT) is predominantly used, limiting the number of people who can benefit from DECT. This study proposed a novel method to generate synthetic low-energy virtual monochromatic images at 50 keV (sVMI50keV) from SECT images using a transformer-based deep learning model, SwinUNETR. Data were obtained from 85 patients who underwent head and neck radiotherapy. Among these, the model was built using data from 70 patients for whom only DECT images were available. The remaining 15 patients, for whom both DECT and SECT images were available, were used to predict from the actual SECT images. We used the SwinUNETR model to generate sVMI50keV. The image quality was evaluated, and the results were compared with those of the convolutional neural network-based model, Unet. The mean absolute errors from the true VMI50keV were 36.5 ± 4.9 and 33.0 ± 4.4 Hounsfield units for Unet and SwinUNETR, respectively. SwinUNETR yielded smaller errors in tissue attenuation values compared with those of Unet. The contrast changes in sVMI50keV generated by SwinUNETR from SECT were closer to those of DECT-derived VMI50keV than the contrast changes in Unet-generated sVMI50keV. This study demonstrated the potential of transformer-based models for generating synthetic low-energy VMIs from SECT images, thereby improving the image quality of head and neck cancer imaging. It provides a practical and feasible solution to obtain low-energy VMIs from SECT data that can benefit a large number of facilities and patients without access to DECT technology.

Solitary Fibrous Tumor With an Acute Subdural Hematoma: A Case Report and Review of the Literature.

Solitary fibrous tumor (SFT) is a rare interstitial tumor that originates from various soft tissues, and SFTs occurring within the cranium are extremely rare. While intracranial SFTs with cerebral hemorrhage or subarachnoid hemorrhage have been reported, there have been no reports of intracranial SFTs causing subdural hematoma. In this case, we report on an intracranial SFT accompanied by a subdural hematoma. A 29-year-old female was emergently transported due to the sudden onset of persistent headache and vomiting that began the night before. CT and MRI imaging revealed a hemorrhagic tumor under the tentorium and an acute subdural hematoma extending along the tentorium. The excised tumor was diagnosed as an SFT through histopathological examination. After undergoing radiation therapy, no recurrence has been observed. This is the first case report of an SFT accompanied by a subdural hematoma, and it is vital to recognize that SFTs can be associated with subdural hematomas for proper diagnosis and treatment planning.

Single-Fraction Palliative High-Dose-Rate Brachytherapy for Symptom Management in a 97-Year-Old Patient With Dementia.

Background: Delivering cancer treatment to elderly patients with dementia is often challenging. We describe performing palliative surface mold brachytherapy (SMBT) in an elderly patient with advanced dementia for pain control using music therapy to assist with agitation. Case Description: The patient was a 97-year-old Japanese woman with advanced dementia. Exudate was observed from her tumor, and she complained of Grade 2 severity pain using Support team assessment schedule (STAS), especially when undergoing would dressings. Given her advanced dementia, she was not considered a candidate for radical surgery or external beam radiotherapy. We instead treated her with high-dose-rate (HDR) SMBT. Due to her advanced dementia associated with agitation, she could not maintain her position. She was able to remain calm while listening to traditional Japanese enka music, which enables our team to complete her radiation without using anesthetics or sedating analgesics. Her localized pain severity decreased ≤21 days and the exudate fluid disappeared ≤63 days after HDR-SMBT. Her tumor was locally controlled until her death from intercurrent disease 1 year after HDR-SMBT. Discussion: Single fraction palliative HDR-SMBT was useful for successful treatment of skin cancer in an elderly patient. Traditional Japanese music helped reduce her agitation to complete HDR-SMBT. For elderly patients with agitation associated with dementia, we should consider using music and music therapy to facilitate radiation therapy.

Effective optimization strategy for large optimization volume object, remaining volume at risk (RVR):α-value selection and usage from generalized equivalent uniform dose (gEUD) curve deviation perspective.

Objective.A large optimization volume for intensity-modulated radiation therapy (IMRT), such as the remaining volume at risk (RVR), is traditionally unsuitable for dose-volume constraint control and requires planner-specific empirical considerations owing to the patient-specific shape. To enable less empirical optimization, the generalized equivalent uniform dose (gEUD) optimization is effective; however, the utilization of parametera-values remains elusive. Our study clarifies thea-value characteristics for optimization and to enable effectivea-value use.Approach.The gEUD can be obtained as a function of itsa-value, which is the weighted generalized mean; its curve has a continuous, differentiable, and sigmoid shape, deforming in its optimization state with retained curve characteristics. Using differential geometry, the gEUD curve changes in optimization is considered a geodesic deviation intervened by the forces between deforming and retaining the curve. The curvature and gradient of the curve are radically related to optimization. The vertex point (a=ak) was set and thea-value roles were classified into the following three parts of the curve with respect to thea-value: (i) high gradient and middle curvature, (ii) middle gradient and high curvature, and (iii) low gradient and low curvature. Then, a strategy for multiplea-values was then identified using RVR optimization.Main results.Eleven head and neck patients who underwent static seven-field IMRT were used to verify thea-value characteristics and curvature effect for optimization. The lowera-value (i) (a= 1-3) optimization was effective for the whole dose-volume range; in contrast, the effect of highera-value (iii) (a= 12-20) optimization addressed strongly the high-dose range of the dose volume. The middlea-value (ii) (arounda=ak) showed intermediate but effective high-to-low dose reduction. Thesea-value characteristics were observed as superimpositions in the optimization. Thus, multiple gEUD-based optimization was significantly superior to the exponential constraints normally applied to the RVR that surrounds the PTV, normal tissue objective (NTO), resulting in up to 25.9% and 8.1% improvement in dose-volume indices D2% and V10Gy, respectively.Significance.This study revealed an appropriatea-value for gEUD optimization, leading to favorable dose-volume optimization for the RVR region using fixed multiplea-value conditions, despite the very large and patient-specific shape of the region.