Frequency of and risk factors associated with local recurrence after spinal stereotactic body radiation therapy without surgery.

PURPOSE: This study aimed to identify factors associated with local recurrence after spinal stereotactic body radiation therapy (SBRT), focusing on patient movement during treatment and tumor characteristics. METHODS: A total of 48 patients who underwent spinal SBRT alone without surgery from August 2017 to October 2022 were evaluated. Logistic regression analysis was conducted to identify factors associated with local recurrence, including patient movement and tumor characteristics such as soft tissue involvement and tumor volume. Patient movement during treatment was measured using cone beam computed tomography before and after irradiation. RESULTS: Among the included cases, 68.7% and 42.6% had soft tissue involvement and movement exceeding 1 mm, respectively. The median follow-up duration for local recurrence was 11.6 (range: 0.7-44.9) months, whereas the median duration to local recurrence was 6.3 months. Within 12 months, 29.3% of the patients experienced local recurrence, among whom 43.9% moved ≥ 1 mm during treatment, whereas 15.8% did not move. Univariable analysis found that both soft tissue involvement (OR = 10.3, 1.21-87.9; p = 0.033) and patient movement ≥ 1 mm (OR = 5.75, 1.45-22.8; p = 0.013) were associated with local recurrence. Multivariable analysis identified patient movement as an independent prognostic factor for local recurrence (OR = 5.15, 1.06-25.0; p = 0.042). CONCLUSION: Our results suggest that patient movement during spinal SBRT was associated with local recurrence, emphasizing the need for better immobilization techniques and shorter delivery times to improve tumor control.

Impact of concurrent antibody-drug conjugates and radiotherapy on symptomatic radiation necrosis in breast cancer patients with brain metastases: a multicenter retrospective study.

AIM: We aimed to investigate the impact of concurrent antibody-drug conjugates (ADC) and radiotherapy on symptomatic radiation necrosis (SRN) in breast cancer patients with brain metastases (BM). METHODS: This multicenter retrospective study uses four institutional data. Eligibility criteria were histologically proven breast cancer, diagnosed BM with gadolinium-enhanced MRI, a Karnofsky performance status of 60 or higher, and radiotherapy for all BM lesions between 2017 and 2022. Patients with leptomeningeal dissemination were excluded. Concurrent ADC was defined as using ADC within four weeks before or after radiotherapy. The cumulative incidence of SRN until December 2023 with death as a competing event was compared between the groups with and without concurrent ADC. Multivariable analysis was performed using the Fine-Gray model. RESULTS: Among the 168 patients enrolled, 48 (29%) received ADC, and 19 (11%) had concurrent ADC. Of all, 36% were HER2-positive, 62% had symptomatic BM, and 33% had previous BM radiation histories. In a median follow-up of 31 months, 18 SRNs (11%) were registered (11 in grade 2 and 7 in grade 3). The groups with and without concurrent ADC had 5 SRNs in 19 patients and 13 SRNs in 149, and the two-year cumulative incidence of SRN was 27% vs. 7% (P = 0.014). Concurrent ADC was associated with a higher risk of SRN on multivariable analysis (subdistribution hazard ratio, 3.0 [95% confidence interval: 1.1-8.3], P = 0.030). CONCLUSIONS: This study suggests that concurrent ADC and radiotherapy are associated with a higher risk of SRN in HER2-positive breast cancer patients.

Physiologically based pharmacokinetic modelling to predict potential drug-drug interactions of dersimelagon (MT-7117).

AIMS: Dersimelagon is a novel, investigational, orally administered, selective agonist of the melanocortin-1 receptor that has demonstrated efficacy at increasing symptom-free light exposure and an acceptable safety profile in patients with protoporphyria. A phase 1 drug-drug interaction (DDI) study demonstrated that dersimelagon 300 mg has the potential for clinically relevant DDIs with drugs that are substrates for breast cancer resistance protein, such as atorvastatin and rosuvastatin. This study uses physiologically based pharmacokinetic (PBPK) modelling to further investigate the DDI effects at lower doses of dersimelagon with substrate drugs. METHODS: The data from in silico, in vitro and in vivo studies were used to construct a PBPK model for dersimelagon to assess the DDI potential between dersimelagon and substrate drugs for cytochrome P450 3A, P-glycoprotein, organic anion transporting polypeptide 1B1/1B3, organic anion transporter 3 and breast cancer resistance protein, including atorvastatin and rosuvastatin. RESULTS: The systemic exposure of atorvastatin based on the maximum plasma concentration and area under the plasma concentration-time curve was predicted to increase 1.21-fold and 1.25-fold, respectively, if coadministered with dersimelagon 100 mg, and 1.42-fold and 1.45-fold with dersimelagon 200 mg. The systemic exposure of rosuvastatin followed trends similar to atorvastatin (1.67-fold and 1.34-fold increase in maximum plasma concentration and area under the plasma concentration-time curve, respectively, with dersimelagon 100 mg, and 2.40-fold and 1.69-fold with dersimelagon 200 mg). CONCLUSION: Overall, PBPK modelling results indicate that the simulated changes in plasma exposure of atorvastatin and rosuvastatin following coadministration with dersimelagon 100 or 200 mg are not clinically significant, but caution and appropriate clinical monitoring should be recommended.

Development of an external system for monitoring the couch speed in radiotherapy using continuous bed movement.

PURPOSE: Total body irradiation before bone marrow transplantation for hematological malignancies using Radixact, a high-precision radiotherapy machine, can potentially reduce side effects and the risk of secondary malignancies. However, stable control of couch speed is critical, and direct assessment methods outlined in quality assurance guidelines are lacking. This study aims to develop a real-time couch speed verification system for the Radixact. METHODS: The developed system used a linear encoder to measure couch speed directly. Accuracy was verified via a linear stage, comparing measurements with a laser distance sensor. After placing a phantom simulating the human body on the Radixact couch, the couch speed was verified using predefined speed plans. RESULTS: Operating the linear stage at 0.1, 0.5, and 1.0 mm/s revealed that the maximum position error of the developed verification system compared to the laser distance sensor was nearly equivalent to the distance resolution of the system (0.05 mm/pulse), with negligible average speed error. When the Radixact couch operated at 0.1, 0.5, and 1.0 mm/s, the values obtained by the verification system agreed with the theoretical values within the sampling period (0.01 s) and distance resolution (0.05 mm). CONCLUSION: The verification system developed provides real-time monitoring of the speed of the Radixact table, ensuring treatment effectiveness and patient safety. It would guarantee the couch speed's soundness and contribute to the "visualization" of safety.

Recent trends of characteristics and treatments in adults with newly diagnosed brain metastases.

OBJECTIVE: We aimed to evaluate recent trends in characteristics and treatments among patients with brain metastases in clinical practice. METHODS: All newly diagnosed patients with brain metastases during 2016-2021 at a single cancer center were enrolled. We collected the detailed features of each patient and estimated the number of candidates considered to meet the following criteria used in common clinical trials: Karnofsky performance status ≥ 70 and mutated non-small cell lung cancer, breast cancer or melanoma. The brain metastases treatments were classified as follows: (i) stereotactic radiosurgery, (ii) stereotactic radiosurgery and systemic therapy, (iii) whole-brain radiotherapy, (iv) whole-brain radiotherapy and systemic therapy, (v) surgery, (vi) immune checkpoint inhibitor or targeted therapy, (vii) cytotoxic agents and (ix) palliative care. Overall survival and intracranial progression-free survival were estimated from brain metastases diagnosis to death or intracranial progression. RESULTS: A total of 800 brain metastases patients were analyzed; 597 (74.6%) underwent radiotherapy, and 422 (52.7%) underwent systemic therapy. In addition, 250 (31.3%) patients were considered candidates for common clinical trials. Compared to 2016, the later years tended to shift from whole-brain radiotherapy to stereotactic radiosurgery (whole-brain radiotherapy: 35.7-29.1% and stereotactic radiosurgery: 33.4-42.8%) and from cytotoxic agents to immune checkpoint inhibitor/targeted therapy (cytotoxic agents: 10.1-5.0 and immune checkpoint inhibitor/targeted therapy: 7.8-10.9%). There was also an increase in the proportion of systemic therapy combined with radiation therapy (from 26.4 to 36.5%). The median overall survival and progression-free survival were 12.7 and 5.3 months, respectively. CONCLUSIONS: This study revealed the diversity of brain metastases patient characteristics, recent changes in treatment selection and the percentage of candidates in clinical trials.

Radiotherapy or systemic therapy versus combined therapy in patients with brain metastases: a propensity-score matched study.

AIM: This study aimed to evaluate the clinical benefits of systemic therapy (ST) combined with stereotactic radiosurgery (SRS) for brain metastases (BM). METHODS: The patient data were extracted from the institutional disease database from 2016 to 2021. Surgical and whole-brain radiotherapy cases and poor Karnofsky performance status (KPS < 70) were excluded. The eligible patients were divided into monotherapy (SRS alone or ST alone) and combined therapy (SRS and ST, combined within a month). Univariate and multivariate Cox proportional hazards analyses were used to examine factors associated with increased risk of death and intracranial progression. The propensity score for selecting treatment was calculated based on existing prognostic covariates. Two groups were matched 1:1 and compared for intracranial progression-free survival (PFS) and overall survival (OS). RESULTS: We identified 1605 patients and analyzed 928 (monotherapy: n = 494, combined therapy: n = 434). In a multivariable model, the combined therapy was independently associated with improved PFS and OS relative to the monotherapy. At the median follow-up of 383 days in the matched dataset, the combined therapy group showed significantly longer PFS (median, 7.4 vs. 5.0 months, P < 0.001) and OS (median, 23.1 vs. 17.2 months, P = 0.036) than the monotherapy group. The overall intracranial progression and mortality risk was reduced in the combined therapy group, with an estimated HR of 0.70 and 0.78. CONCLUSIONS: Combined therapy exhibited longer PFS and OS than monotherapy in BM patients. The results support the recent trend toward combining systemic and local therapies, encouraging future clinical trials.

Evaluation of radiophotoluminescent glass dosimeter response for therapeutic spot scanning proton beam: suggestion of linear energy transfer-based correction.

A radiophotoluminescent glass dosimeter (RGD) is used for a postal audit of a photon beam because of its various excellent characteristics. However, it has not been used for scanning proton beams because its response characteristics have not been verified. In this study, the response of RGD to scanning protons was investigated to develop a dosimetry protocol using the linear energy transfer (LET)-based correction factor. The responses of RGD to four maximum-range-energy-pattern proton beams were verified by comparing it with ionization chamber (IC) dosimetry. The LET at each measurement depth was calculated via Monte Carlo (MC) simulation. The LET correction factor ( k LET RGD ) was the ratio between the uncorrected RGD dose ( D raw RGD ) and the IC dose at each measurement depth. k LET RGD can be represented as a function of LET using the following equation: k LET RGD LET = - 0.035 LET + 1.090 . D raw RGD showed a linear under-response with increasing LET, and the maximum dose difference between the IC dose and D raw RGD was 15.2% at an LET of 6.07 keV/µm. The LET-based correction dose ( D LET RGD ) conformed within 3.6% of the IC dose. The mean dose difference (±SD) of D raw RGD and D LET RGD was -2.5 ± 6.9% and 0.0 ± 1.6%, respectively. To achieve accurate dose verification for scanning proton beams using RGD, we derived a linear regression equation based on LET. The results show that with appropriate LET correction, RGD can be used for dose verification of scanning proton beams.

Examination of the best head tilt angle to reduce the parotid gland dose maintaining a safe level of lens dose in whole-brain radiotherapy using the four-field box technique.

The parotid gland is recognized as a major-risk organ in whole-brain irradiation; however, the beam delivery from the left and right sides cannot reduce the parotid gland dose. The four-field box technique using a head-tilting device has been reported to reduce the parotid gland dose by excluding it from the radiation field. This study aimed to determine the appropriate head tilt angle to reduce the parotid gland dose in the four-field box technique. The bilateral, anterior, and posterior beams were set for each of ten patients. The orbitomeatal plane angle (OMPA) was introduced as an indicator that expresses the head tilt angle. Next, principal component analysis (PCA) was performed to understand the interrelationship between variables (dosimetric parameters of the lens and parotid gland and OMPA). In PCA, the angle between the OMPA vector and maximum lens dose or mean parotid gland dose vector was approximately opposite or close, indicating a negative or positive correlation [r = -0.627 (p < 0.05) or 0.475 (p < 0.05), respectively]. The OMPA that reduced the maximum lens dose to <10 Gy with a 95% confidence interval was approximately 14°. If the lens dose was not considered, the parotid gland dose could be reduced by decreasing the OMPA.

A phase II study of adaptive two-step intensity-modulated radiation therapy (IMRT) with chemotherapy for loco-regionally advanced nasopharyngeal cancer (JCOG1015).

BACKGROUND: A phase II study of adaptive two-step intensity-modulated radiotherapy (IMRT) with chemotherapy for nasopharyngeal cancer (NPC) (JCOG1015) was conducted to evaluate the efficacy and safety. METHODS: Patients aged 20-75 years with stages II-IVB NPC were enrolled. As adaptive two-step IMRT, computed tomography planning was performed twice before IMRT for the initial plan of 46 Gy/23 fractions and during treatment for the boost plan of 24 Gy/12 fractions with a total dose of 70 Gy. Chemotherapy (cisplatin 80 mg/m2/3-weeks × 3 courses) was administered concurrently with IMRT, followed by adjuvant chemotherapy (cisplatin at 70 mg/m2 with 5-FU 700 at mg/m2 for 5 days/4 weeks × 3 courses). RESULTS: Between 2011 and 2014, 75 patients were enrolled from 12 institutions. The 3-year overall survival (OS) for the 75 patients was 88%, and the upper and lower limits of the 95% CI of 78%-94% were higher than the expected 3-year OS of 75% for the target population adjusted by the actual proportion of stage II:III:IV = 21%:44%:35%. The 3-year progression-free survival (PFS) and loco-regional PFS were 71% [59-80%] and 77% [66-85%], respectively. Although no grade 4-5 late toxicities were observed, 15 patients (20%) developed grade 3 late toxicities. Grade 2 xerostomia was noted in 26%, 12%, and 9% at 1, 2, and 3 years after starting IMRT, respectively. CONCLUSIONS: Adaptive two-step IMRT for NPC demonstrated an excellent 3-year OS with acceptable toxicities. This method may be one treatment option for locally advanced NPC.

Prediction of Human Distribution Volumes of Compounds in Various Elimination Phases Using Physiologically Based Pharmacokinetic Modeling and Experimental Pharmacokinetics in Animals.

Predicting the pharmacokinetics of compounds in humans is an important part of the drug development process. In this study, the plasma concentration profiles of 10 marketed compounds exhibiting two-phase elimination after intravenous administration in humans were evaluated in terms of distribution volumes just after intravenous administration (V 1), at steady state (V ss), and in the elimination phase (Vß ) using physiologically based pharmacokinetic (PBPK) modeling implemented in a commercially available simulator (Simcyp). When developing human PBPK models, the insight gained from prior animal PBPK models based on nonclinical data informed the optimization of the lipophilicity input of the compounds and the selection of the appropriate mechanistic tissue partition methods. The accuracy of V 1, V ss, and Vß values predicted that using human PBPK models developed in accordance with prior animal PBPK models was superior to using those predicted using conventional approaches, such as allometric scaling, especially for V 1 and Vß By conventional approaches, the V 1 and Vß values of 4-5 of 10 compounds were predicted within a 3-fold error of observed values, whereas V ss values for their majority were predicted as such. PBPK models predicted V 1, V ss, and Vß values for almost all compounds within 3-fold errors, resulting in better predictions of plasma concentration profiles than allometric scaling. The distribution volumes predicted using human PBPK models based on prior animal PBPK modeling were more accurate than those predicted without reference to animal models. This study demonstrated that human PBPK models developed with consideration of animal PBPK models could accurately predict distribution volumes in various elimination phases.

Development of twist-correction system for radiotherapy of head and neck cancer patients.

To propose a concept for correcting the twist between the head and neck and the body frequently occurring in radiotherapy patients and to develop a prototype device for achieving this. Furthermore, the operational accuracy of this device under no load was evaluated. We devised a concept for correcting the twist of patients by adjustment of the three rotation (pitch, roll, and yaw) angles in two independent plates connected by a joint (fulcrum). The two plates (head and neck plate and body plate) rotate around the fulcrum by adjusting screws under each of them. A prototype device was created to materialize this concept. First, after all adjusting screws were set to the zero position, the rotation angle of each plate was measured by a digital goniometer. Repeatability was evaluated by performing 20 repeated measurements. Next, to confirm the rotational accuracy of each plate of the prototype device, the calculated rotation angles for 20 combinations of patterns of traveled distances of the adjusting screws were compared with those measured by the digital goniometer and cone-beam computed tomography (CT). The repeatability (standard deviation: SD) of the pitch, roll, and yaw angles of the head and neck plate was 0.04°, 0.05°, and 0.03°, and the repeatability (SD) of the body plate was 0.05°, 0.04°, and 0.04°, respectively. The mean differences ± SD between the calculated and measured pitch, roll, and yaw angles for the head and neck plate with the digital goniometer were 0.00 ± 0.06°, -0.01 ± 0.06°, and -0.04 ± 0.04°, respectively. The differences for the body plate were -0.03 ± 0.04°, 0.03 ± 0.05°, and 0.02 ± 0.05°, respectively. Results of the cone-beam CT were similar to those of the digital goniometer. The prototype device exhibited good performance regarding the rotational accuracy and repeatability under no load. The clinical implementation of this concept is expected to reduce the residual error of the patient position due to the twist.

Impact of treatment planning using a structure block function on the target and organ doses related to patient movement in cervical esophageal cancer: A phantom study.

Helical tomotherapy (HT) can restrict beamlets passing through the virtual contour on computed tomography (CT) image in dose optimization, reducing the dose to organs at risk (OARs). Beamlet restriction limits the incident beamlet angles; thus, the proper planning target volume (PTV) margin may differ from that of the standard treatment plan without beamlet restriction, depending on the patient's movement during dose delivery. Dose distribution changes resulting from patient movement have not been described for treatment plans with beamlet restriction. This study quantified changes in dose distribution to the target and OARs when beamlet restriction is applied to cervical esophageal cancer treatment plan using HT by systematically shifting a phantom. Treatment plans for cervical esophageal cancers with and without beamlet restriction modes [directional block (DB) and nonblock (NB), respectively] were designed for CT images of the RANDO phantom. The PTV margin for the DB mode was set to be the same as that for the NB mode (5 mm). The CT image was intentionally shifted by ±1, ±2, and ±3 voxels in the left-right, anterior-posterior, and superior-inferior directions, and the dose distribution was recalculated for each position using the fluence for the NB or DB mode. When the phantom shift was within the same PTV margin as the NB mode, changes in doses to the targets, lungs, heart, and spinal cord in the DB mode were small as those in the NB mode. In conclusion, the virtual contour shape used in this study would provide safe delivery even with patient movement within the same PTV margin as for the NB mode.

[Development of an In-house Couch Model to Improve Dose Attenuation Correction Accuracy for a Couch with Different Thickness in the Superior-inferior Direction].

As the couch used in external radiation therapy attenuate radiation by interaction, it is necessary to correct attenuation of radiation by inserting a couch model in the treatment planning systems. For a couch whose thickness is different in the superior-inferior direction, it is possible to perform dose calculations with an error within ±1% by using separate different couch models provided by vendors. However, it is difficult to correct attenuation correction accurately with a single couch model. In this study, we created an in-house couch model which can set couch shape and physical density in detail by acquiring CT images of actual couch. When we performed dose calculation by optimizing the physical densities of in-house and vendor couch, it was found that the difference between the measured and the calculated values can be significantly reduced by using in-house couch model. Additionally, by using in-house couch model, it is found that the dose attenuation can be corrected within ±1% for a couch whose thickness is different in the superior-inferior direction.

Analysis of modulation factor to shorten the delivery time in helical tomotherapy.

A low modulation factor (MF) maintaining a good dose distribution contributes to the shortening of the delivery time and efficiency of the treatment plan in helical tomotherapy. The purpose of this study was to reduce the delivery time using initial values and the upper limit values of MF. First, patients with head and neck cancer (293 cases) or prostate cancer (181 cases) treated between June 2011 and July 2015 were included in the analysis of MF values. The initial MF value (MFinitial ) was defined as the average MFactual value, and the upper limit of the MF value (MFUL ) was defined according the following equation: MFUL = 2 × standard deviation of MFactual value + the average MFactual Next, a treatment plan was designed for patients with head and neck cancer (62 cases) and prostate cancer (13 cases) treated between December 2015 and June 2016. The average MFactual value for the nasopharynx, oropharynx, hypopharynx, and prostate cases decreased from 2.1 to 1.9 (p = 0.0006), 1.9 to 1.6 (p < 0.0001), 2.0 to 1.7 (p < 0.0001), and 1.8 to 1.6 (p = 0.0004) by adapting the MFinitial and the MFUL values, respectively. The average delivery time for the nasopharynx, oropharynx, hypopharynx, and prostate cases also decreased from 19.9 s cm-1 to 16.7 s cm-1 (p < 0.0001), 15.0 s cm-1 to 13.9 s cm-1 (p = 0.025), 15.1 s cm-1 to 13.8 s cm-1 (p = 0.015), and 23.6 s cm-1 to 16.9 s cm-1 (p = 0.008) respectively. The delivery time was shortened by the adaptation of MFinitial and MFUL values with a reduction in the average MFactual for head and neck cancer and prostate cancer cases.

Establishment of the Commissioning Procedure for Modifying the Beam Model of Helical Tomotherapy.

Although much evidence about the helical tomotherapy system are available, there is not a document about the procedure of quality assurance (QA) for changing the beam model. This study establishes the commissioning procedure for modifying the beam model of helical tomotherapy. Firstly, some intensity-modulated radiotherapy (IMRT) plans were created, and compared them with the calculated dose and the measured dose. Secondly, the absorbed doses to water in the machine-specific reference field and the plan-class specific reference field with a protocol in Japan; Standard Dosimetry of Absorbed Dose to Water in External Beam Radiotherapy (Standard Dosimetry 12) were measured. Thirdly, we reconfirmed patient-specific quality assurance. The recommended commissioning procedure after the change of the beam model was shown through three verification processes. This report would be helpful for not only changing the beam model of helical tomotherapy but also introducing Standard Dosimetry 12 to a clinic.

International prostate symptom score (IPSS) change and changing factor in intensity-modulated radiotherapy combined with androgen deprivation therapy for prostate cancer.

The purposes of this study on prostate cancer are to demonstrate the time course of International Prostate Symptom Score (IPSS) after intensity-modulated radiation therapy (IMRT) combined with androgen deprivation therapy (ADT) and to examine the factor associated with the IPSS change. This study included 216 patients treated with IMRT between 2006 and 2010. Patients were evaluated in three groups according to baseline IPSS as defined by the American Urological Association classification, where IPSSs of 0 to 7, 8 to 19, and 20 to 35 represent mild (n = 124), moderate (n = 70), and severe (n = 22) symptom groups, respectively. The average IPSSs ± standard deviation at baseline vs. those at 24 months after IMRT were 3.5 ± 2.1 vs. 5.1 ± 3.6 in the mild group (P < 0.001), 12.6 ± 3.4 vs. 10.0 ± 6.0 in the moderate group (P = 0.0015), and 23.8 ± 2.9 vs. 14.4 ± 9.1 in the severe group (P < 0.001). Among factors of patient and treatment characteristics, age, IPSS classification, pretreatment GU medications, and positive biopsy rates were associated with the IPSS difference between baseline and 24 months (P = 0.023, < 0.001, 0.044, and 0.028, respectively). In conclusion, patients with moderate to severe urinary symptoms can exhibit improvement in urinary function after IMRT, whereas patients with mild symptoms may have slightly worsened functions. Age, baseline IPSS, GU medications, and tumor burden in the prostate can have an effect on the IPSS changes.

A cross-national investigation of CT, MRI, PET, mammography, and radiation therapy resources and utilization.

PURPOSE: This study aimed to analyze the domestic and international landscape of imaging diagnostics and treatments, focusing on Japan, to provide current insights for policymaking, clinical practice enhancement, and international collaboration. METHODS: Data from 1996 to 2021 were collected from Japan's Ministry of Health, Labor and Welfare database for medical device counts of CT, MRI, PET, mammography, and radiotherapy. The National Database of Health Insurance Claims and Specific Health Checkups of Japan was utilized for examination numbers. An international comparison was made with data from 41 countries using the Organization for Economic Cooperation and Development (OECD) database. RESULTS: The data included a total of 108,596 CT devices, 47,233 MRI devices, 2998 PET devices, 20,641 MMG devices, and 8023 RT devices during the survey period. Upon international comparison, Japan ranked first in CT and MRI devices per million people and second in examination numbers per 1000 people. The number of PET devices per million people exceeded OECD averages; however, the number of examinations per 1000 people was below the OECD average in 2020 (Japan: 4.0, OECD: 4.9). Although Japan exceeded OECD averages in mammography device counts (Japan: 33.8, OECD: 24.5 in 2020), radiotherapy device counts were similar to OECD averages (Japan: 8.3, OECD: 7.9 in 2020). CONCLUSION: We have analyzed the utilization of equipment in the context of diagnostic imaging and radiotherapy in Japan. Since the initial survey year, all devices have shown an upward trend. However, it is essential not only to increase the number of devices and examinations but also to address the chronic shortage of radiologists and allied health professionals. Based on the insights gained from this study, understanding the actual status of diagnostic imaging and radiation therapy equipment is critical for grasping the domestic situation and may contribute to improving the quality of healthcare in Japan.

Evaluation of Age-Related Changes in Teneligliptin Pharmacokinetics in Japanese and European Descent Subjects Using a Physiologically Based Pharmacokinetic Model.

INTRODUCTION: Drugs often show differing pharmacokinetic (PK) profiles, such as higher plasma concentrations, in older people than in younger people owing to age-related decreases in physiological functions. However, it is difficult to evaluate the PK in older populations. Therefore, we simulated the plasma age-related changes in the PK of teneligliptin, a dipeptidyl peptidase-4 inhibitor, using physiologically based PK (PBPK) models. METHODS: The previously developed PBPK model was revalidated by comparison between simulated data and clinical study data that included older subjects (up to 75 years old). We then simulated the plasma concentration-time profiles for teneligliptin at a dose of 20 mg (single and multiple doses) in virtual Japanese (20-70 years old) and European descent (20-98 years old) subjects. PK parameters were calculated by race and age group. RESULTS: We confirmed the validity of the previous PBPK model by comparison between simulated data and clinical study data. In the evaluation of age-related changes in PK after single and multiple doses using the PBPK model, the area under the plasma concentration-time curve (AUC) of teneligliptin tended to increase slightly with age in both populations up to 70 years old. However, no clear age-related change in the maximum plasma concentration (Cmax) of teneligliptin was observed. In the European descent subjects aged ≥ 70 years, the AUC tended to increase but the ratio of the change in Cmax was smaller than that in AUC. In both populations, there were positive correlations between AUC and age, but not between Cmax and age. CONCLUSION: The simulation using a PBPK model showed a tendency for the AUC of teneligliptin to increase with age, whereas Cmax was less affected by age than AUC.

Risk Stratification by Combination of Heart and Lung Dose in Locally Advanced Non-Small-Cell Lung Cancer after Radiotherapy.

Background/Objectives: Despite advancements in treatment for patients with unresectable locally advanced non-small cell lung cancer (LA-NSCLC), overall survival (OS) remains poor. The specific effects of varying heart and lung doses on OS in LA-NSCLC patients have not been thoroughly investigated, especially their combined impact on survival. This study aimed to examine the impact on OS of both individual and combined heart and lung doses in patients with LA-NSCLC treated with radiotherapy over a three-year follow-up period. Methods: A total of 120 patients who received definitive radiotherapy for LA-NSCLC (stage III, 92.5%) from January 2015 to January 2020 were retrospectively reviewed. The endpoint in this study was OS. Each patient was followed for a fixed period of three years. Results: Univariate Cox regression analysis showed that OS was significantly related to mean heart dose (MHD, hazard ratio [HR], 3.4 [1.8-6.3]; p < 0.001), pericardium V40 (HR, 3.2 [1.7-6.0]; p < 0.001), and total lung V20 (HR, 2.6 [1.4-5.0]; p = 0.003), and these were independent predictors for worse OS in multivariate analysis. Kaplan-Meier curve analysis with log-rank tests revealed that survival was significantly worse in patients with higher MHD (p < 0.001), pericardium V40 (p < 0.001), and total lung V20 (p = 0.002). Combining MHD and total lung V20, and pericardium V40 and total lung V20 provided enhanced risk stratification for OS (p < 0.001 for both combinations). Conclusions: The combination of heart and lung doses provided enhanced and more detailed risk stratification in prediction of OS for a fixed period of three years in LA-NSCLC patients treated with radiotherapy.