Objective: DUO-E/GOG-3041/ENGOT-EN10 (NCT04269200) demonstrated statistically significant and clinically meaningful progression-free survival (PFS) improvement with durvalumab plus carboplatin/paclitaxel, followed by durvalumab with or without olaparib, vs. carboplatin/paclitaxel alone (intention-to-treat [ITT] population) in patients with newly diagnosed advanced or recurrent endometrial cancer. We evaluated efficacy and safety in the Japan subset of DUO-E. Methods: Patients with newly diagnosed International Federation of Gynecology and Obstetrics stage III/IV or recurrent endometrial cancer were randomized 1:1:1 to control arm (carboplatin/paclitaxel + durvalumab placebo [6 cycles] followed by durvalumab placebo + olaparib placebo), durvalumab arm (carboplatin/paclitaxel + durvalumab [1,120 mg every 3 weeks] [6 cycles] followed by durvalumab [1,500 mg every 4 weeks] + olaparib placebo), or durvalumab + olaparib arm (carboplatin/paclitaxel + durvalumab [6 cycles] followed by durvalumab + olaparib [300 mg twice a day]). Dual primary endpoints were investigatorassessed PFS for durvalumab and durvalumab + olaparib arms vs. control. This prespecified exploratory analysis evaluated PFS and safety in the Japan subset. Results: In the Japan subset (n=88) PFS favored durvalumab (hazard ratio=0.61, 95% confidence interval [CI]=0.32–1.12) and durvalumab + olaparib (0.44, 95% CI=0.22–0.85) vs. control; median PFS was 9.9 and 15.1 vs. 9.5 months, and the 18-month PFS rate was 37.0% and 42.1% vs. 22.2%, respectively. The safety profile in the Japan subset was generally consistent with the full safety analysis set and the established profiles of the individual agents. Conclusion Efficacy and safety in the Japan subset were generally consistent with outcomes in the DUO-E ITT population. This Japanese subset analysis of DUO-E supports carboplatin/ paclitaxel + durvalumab followed by durvalumab with or without olaparib as new treatment options in patients with advanced or recurrent endometrial cancer and is the first to report on these regimens in Japanese patients alone.

Objective: This study analyzed the efficacy of add-on atezolizumab to standard first-line bevacizumab-containing therapy in 56 Japanese patients with metastatic and recurrent cervical cancer treated across 8 sites under the Japanese Gynecologic Oncology Group between October 2018 and August 2021 in the BEATcc trial. Methods: Patients were randomized to standard arm (standard therapy: cisplatin 50 mg/m 2or carboplatin area under the curve of 5, paclitaxel 175 mg/m 2 , and bevacizumab 15 mg/kg) or experimental arm (standard therapy with atezolizumab 1,200 mg). Results: Of 56 patients, 30 were in experimental arm vs. 26, standard arm (age: 53.2±12.9 vs.54.7±12.2 years). Median progression-free survival was 15.8 months (95% confidence interval [CI]=10.4–26.1) in experimental arm vs. 11.1 months (8.4–16.5) in standard arm (hazard ratio [HR]=0.51; 95% CI=0.26–1.01). Median overall survival was 34.1 months (23.2–38.6) in the experimental arm vs. 31.6 months (16.4–36.5), standard arm (HR=0.53; 95% CI=0.23–1.21). Objective: response rate was 86.7% in experimental arm vs. 84.6%, standard arm. Complete response and partial response, respectively, were 23.3% and 63.3% in experimental arm and 26.9% and 57.7% in standard arm. Grade ≥3 adverse events occurred in 80.0%, experimental arm and 88.5%, standard arm. Gastrointestinal/genitourinary fistula incidence was lower in Japanese patients (1 patient receiving atezolizumab), likely due to stricter inclusion criteria. Conclusion Overall, add-on atezolizumab enhances the efficacy of bevacizumab and chemotherapy in Japanese patients as those in overall BEATcc population and could be considered a new first-line treatment option for metastatic, persistent, or recurrent cervical cancer in Japan.

Objective: Hospital treatment volume affects survival in patients with endometrial cancer;notably, initial treatment at high-volume centers improves survival outcomes. Our study assessed the effect of hospital treatment volume on cost-effectiveness and survival outcomes in patients with endometrial cancer in Japan. Methods: A decision-analytic model was evaluated using the following variables and their impact on cost-effectiveness: 1) hospital treatment volume (low-, intermediate-, and highvolume centers) and 2) postoperative recurrent risk factors based on pathological findings (high- and intermediate-risk or low-risk). Data were obtained from the Japan Society of Obstetrics and Gynecology database, systematic literature searches, and the Japanese Diagnosis Procedure Combination database. Quality-adjusted life years (QALY) was used as a measure of effectiveness. The model was built from a public healthcare perspective and the impact of uncertainty was assessed using sensitivity analyses. Results: A base-case analysis showed that the incremental cost-effectiveness ratio at high-volume centers was below a willingness-to-pay (WTP) threshold of ¥5,000,000with a maximum of ¥3,777,830/4.28 QALY for the high- and intermediate-risk group, and ¥2,316,695/4.57 QALY for the low-risk group. Treatment at the high-volume centers showed better efficiency and cost-effectiveness in both strategies compared to intermediate- or lowvolume centers. Sensitivity analyses showed that the model outcome was robust to changes in input values. With the WTP threshold, treatment at high-volume centers remained cost-effective in at least 73.6% and 78.2% of iterations for high- and intermediate-risk, and lowrisk groups, respectively. Conclusion Treatment at high-volume centers is the most cost-effective strategy for guiding treatment centralization in patients with endometrial cancer.

Objective: Hospital treatment volume affects survival in patients with endometrial cancer;notably, initial treatment at high-volume centers improves survival outcomes. Our study assessed the effect of hospital treatment volume on cost-effectiveness and survival outcomes in patients with endometrial cancer in Japan. Methods: A decision-analytic model was evaluated using the following variables and their impact on cost-effectiveness: 1) hospital treatment volume (low-, intermediate-, and highvolume centers) and 2) postoperative recurrent risk factors based on pathological findings (high- and intermediate-risk or low-risk). Data were obtained from the Japan Society of Obstetrics and Gynecology database, systematic literature searches, and the Japanese Diagnosis Procedure Combination database. Quality-adjusted life years (QALY) was used as a measure of effectiveness. The model was built from a public healthcare perspective and the impact of uncertainty was assessed using sensitivity analyses. Results: A base-case analysis showed that the incremental cost-effectiveness ratio at high-volume centers was below a willingness-to-pay (WTP) threshold of ¥5,000,000with a maximum of ¥3,777,830/4.28 QALY for the high- and intermediate-risk group, and ¥2,316,695/4.57 QALY for the low-risk group. Treatment at the high-volume centers showed better efficiency and cost-effectiveness in both strategies compared to intermediate- or lowvolume centers. Sensitivity analyses showed that the model outcome was robust to changes in input values. With the WTP threshold, treatment at high-volume centers remained cost-effective in at least 73.6% and 78.2% of iterations for high- and intermediate-risk, and lowrisk groups, respectively. Conclusion Treatment at high-volume centers is the most cost-effective strategy for guiding treatment centralization in patients with endometrial cancer.

Objective: Hospital treatment volume affects survival in patients with endometrial cancer;notably, initial treatment at high-volume centers improves survival outcomes. Our study assessed the effect of hospital treatment volume on cost-effectiveness and survival outcomes in patients with endometrial cancer in Japan. Methods: A decision-analytic model was evaluated using the following variables and their impact on cost-effectiveness: 1) hospital treatment volume (low-, intermediate-, and highvolume centers) and 2) postoperative recurrent risk factors based on pathological findings (high- and intermediate-risk or low-risk). Data were obtained from the Japan Society of Obstetrics and Gynecology database, systematic literature searches, and the Japanese Diagnosis Procedure Combination database. Quality-adjusted life years (QALY) was used as a measure of effectiveness. The model was built from a public healthcare perspective and the impact of uncertainty was assessed using sensitivity analyses. Results: A base-case analysis showed that the incremental cost-effectiveness ratio at high-volume centers was below a willingness-to-pay (WTP) threshold of ¥5,000,000with a maximum of ¥3,777,830/4.28 QALY for the high- and intermediate-risk group, and ¥2,316,695/4.57 QALY for the low-risk group. Treatment at the high-volume centers showed better efficiency and cost-effectiveness in both strategies compared to intermediate- or lowvolume centers. Sensitivity analyses showed that the model outcome was robust to changes in input values. With the WTP threshold, treatment at high-volume centers remained cost-effective in at least 73.6% and 78.2% of iterations for high- and intermediate-risk, and lowrisk groups, respectively. Conclusion Treatment at high-volume centers is the most cost-effective strategy for guiding treatment centralization in patients with endometrial cancer.

Objective: The purposes of this trial were to demonstrate the feasibility and effectiveness of the hybrid of intracavitary and interstitial brachytherapy (HBT) for locally advanced cervical cancer patients in the phase I/II prospective clinical trial. Methods: Patients with FIGO stage IB2-IVA uterine cervical cancer pretreatment width of which was ≥5 cm measured by magnetic resonance imaging were eligible for this clinical trial. The protocol therapy included 30–30.6 Gy in 15–17 fractions of whole pelvic radiotherapy concurrent with weekly CDDP, followed by 24 Gy in 4 fractions of HBT and pelvic radiotherapy with a central shield up to 50–50.4 Gy in 25–28 fractions. The primary endpoint of phase II part was 2-year pelvic progression-free survival (PPFS) rate higher than historical control of 64%. Results: Between October 2015 and October 2019, 73 patients were enrolled in the initial registration and 52 patients proceeded to the secondary registration. With the median follow-up period of 37.3 months (range, 13.9–52.9 months), the 2- PPFS was 80.7% (90% confidence interval [CI]=69.7%–88%). Because the lower range of 90% CI of 2-year PPFS was 69.7%, which was higher than the historical control ICBT data of 64%, therefore, the primary endpoint of this study was met. Conclusion The effectiveness of HBT were demonstrated by a prospective clinical study. Because the dose goal determined in the protocol was lower than 85 Gy, there is room in improvement for local control. A higher dose might have been needed for tumors with poor responses.

Objectives: Chronic kidney disease (CKD) complicated by secondary hyperparathyroidism (SHPT) is associated with an increased risk of fragility fractures. Etelcalcetide (EC) is a treatment for SHPT that reduces serum parathyroid hormone (PTH) levels. However, the effects of combined treatment with osteoporosis drugs such as teriparatide (TPTD) remain unclear. This study investigates the combined effects of EC and TPTD on bone in CKD model rats. Methods: The CKD model was established in 8-week-old male Wistar rats by feeding them a 0.75% adenine diet for 4 weeks. At 20 weeks of age, the rats were divided into 4 groups (n = 9–10 in each group): CKD group (vehicle administration), TPTD group (30 μg/kg, 3 times/week), EC group (0.6 mg/kg, daily), and Comb group (TPTD and EC combined). EC was injected for 12 weeks starting at 20 weeks of age, and TPTD was injected for 8 weeks starting at 24 weeks of age. After treatment, the followings were evaluated: bone mineral density, bone strength, biochemical tests, bone and fat histomorphometry, and micro-computed tomography. Results: In CKD model rats, the combination of EC and TPTD was more effective in increasing cortical bone thickness and bone strength and inhibiting porosity. In addition, the combined treatment decreased bone marrow adiposity and fibrosis, and it increased bone mass and improved bone microstructure in trabecular bone. Conclusions With the observed benefits such as improved bone mass, bone strength, structural properties, and bone marrow adiposity, combination therapy may be a potential way to improve bone fragility in CKD.

This technical note demonstrates kinematically aligned Oxford unicompartmental knee arthroplasty using the Microplasty instrumentation system with custom-made devices. The medial joint line is evaluated preoperatively; if it is aligned and parallel with the lateral joint line, they are considered to comprise the coronal knee joint line (CJL). In this case, the coronal inclination of a spoon gauge inserted into the medial joint space indicates the CJL. Otherwise, an accessory spoon is inserted and connected to the medial spoon to refer to the posterior condylar line, which is considered the CJL. The tibial cutting block is then connected without changing the inclination of the spoon and the coronal tilt of the tibial extramedullary rod is adjusted, which is implemented with a custom-made ankle yoke. The remainder of the steps is then identical to the conventional Microplasty procedure. This technique can imitate the cutting line to the CJL, which might be considered ideal from mechanical and kinematic perspectives.

As a screening tool for detecting latent pre-locomotive syndrome (latent pre-LS) in women over the age of 40, measuring handgrip strength with a cut-off value of 26 kg was proposed in a previous report. However, this screening method missed 22% of latent pre-LS. It would be beneficial to screen almost persons with latent pre-LS in community pharmacies. In this study, it was investigated whether screening using the combination of measuring handgrip strength and the questionnaire, “Loco-check,” which was proposed by the Japanese Orthopaedic Association, improved the detection of latent pre-LS in the same group mentioned above. Combining only one of the “Loco-check” questions, “I cannot put on a pair of socks while standing on one leg,” with the measurement of handgrip strength with the cut-off value of 26 kg, the detection of latent pre-LS was increased to 90.2%. The odds ratio was 9.72 in logistic regression analysis. Using the combination of the measurement of handgrip strength and the response to one question is both rapid and convenient. Therefore, in this study, this screening combination is proposed to be a useful tool in community pharmacies for detecting early latent pre-LS.

Background: To evaluate the clinical outcomes and second-look arthroscopic findings after intra-articular adipose-derived regenerative cell (ADRC) injection as treatment for knee osteoarthritis (OA). Methods: ADRCs were administered to 11 patients (19 knees; mean age, 61.7 years) with knee OA. Subcutaneous adipose tissue was harvested by liposuction from both thighs, and arthroscopic lavage was performed, followed by ADRC injection (mean dose, 1.40 × 10 7 cells) into the synovial fluid. Outcome measures included the Knee Injury and Osteoarthritis Outcome Score, Lysholm score, and visual analog scale score. Arthroscopic examinations were performed to assess the International Cartilage Repair Society cartilage injury grade preoperatively and overall repair postoperatively. Noninvasive assessments were performed at baseline and at 1-, 3-, and 6-month follow-ups; arthroscopic assessments were performed at baseline and at 6 months. Results: All outcome measures significantly improved after treatment. This improvement was evident 1 month after treatment and was sustained until the 6-month follow-up. Data from second-look arthroscopy showed better repair in low-grade cartilage lesions than in lesions with a greater degree of damage. No patients demonstrated worsening of Kellgren-Lawrence grade, and none underwent total knee arthroplasty during this period. Conclusions Clinical outcomes were improved in patients with knee OA after ADRC administration. Cartilage regeneration was more effective in smaller damaged lesions than in bigger lesions.