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 compared the effectiveness, safety, and tolerability of dose-dense paclitaxel and carboplatin plus bevacizumab (ddTC+Bev) with ddTC for advanced ovarian cancer. Methods: We retrospectively analyzed the clinical records of 134 patients who received ddTC+Bev or ddTC as first-line chemotherapy for stage III–IV ovarian cancer. Progressionfree survival as primary endpoint of this study was compared using the log-rank test. Cox proportional hazards model and propensity score matching (PSM) were used to analyze prognostic factors, and the frequency of adverse events was examined using the χ 2 test. Results: We categorized 134 patients in the ddTC+Bev (n=57) and ddTC (n=77) groups who started treatment at four related institutions from November 2013 to December 2017.No patients used poly (ADP-ribose) polymerase inhibitors as the first line maintenance therapy. The progression-free survival (PFS) of the ddTC+Bev group had a significantly better prognosis than that of the ddTC group (hazard ratio [HR]=0.50; 95% confidence interval [CI]=0.32–0.79; p<0.003). Multivariate analysis showed that ddTC+Bev regimen was a prognostic factor. However, intergroup comparison using PSM revealed that the PFS of the ddTC+Bev group had a nonsignificantly better prognosis than that of the ddTC group (HR=0.70; 95% CI=0.41–1.20; p=0.189). Few adverse events above G3 were noted for ddTC+Bev, which were sufficiently tolerable. Conclusion This study could not demonstrate that adding Bev to ddTC improves prognosis.Further studies with more cases are warranted.

Objective: This study compared the effectiveness, safety, and tolerability of dose-dense paclitaxel and carboplatin plus bevacizumab (ddTC+Bev) with ddTC for advanced ovarian cancer. Methods: We retrospectively analyzed the clinical records of 134 patients who received ddTC+Bev or ddTC as first-line chemotherapy for stage III–IV ovarian cancer. Progressionfree survival as primary endpoint of this study was compared using the log-rank test. Cox proportional hazards model and propensity score matching (PSM) were used to analyze prognostic factors, and the frequency of adverse events was examined using the χ 2 test. Results: We categorized 134 patients in the ddTC+Bev (n=57) and ddTC (n=77) groups who started treatment at four related institutions from November 2013 to December 2017.No patients used poly (ADP-ribose) polymerase inhibitors as the first line maintenance therapy. The progression-free survival (PFS) of the ddTC+Bev group had a significantly better prognosis than that of the ddTC group (hazard ratio [HR]=0.50; 95% confidence interval [CI]=0.32–0.79; p<0.003). Multivariate analysis showed that ddTC+Bev regimen was a prognostic factor. However, intergroup comparison using PSM revealed that the PFS of the ddTC+Bev group had a nonsignificantly better prognosis than that of the ddTC group (HR=0.70; 95% CI=0.41–1.20; p=0.189). Few adverse events above G3 were noted for ddTC+Bev, which were sufficiently tolerable. Conclusion This study could not demonstrate that adding Bev to ddTC improves prognosis.Further studies with more cases are warranted.

Objective: This study compared the effectiveness, safety, and tolerability of dose-dense paclitaxel and carboplatin plus bevacizumab (ddTC+Bev) with ddTC for advanced ovarian cancer. Methods: We retrospectively analyzed the clinical records of 134 patients who received ddTC+Bev or ddTC as first-line chemotherapy for stage III–IV ovarian cancer. Progressionfree survival as primary endpoint of this study was compared using the log-rank test. Cox proportional hazards model and propensity score matching (PSM) were used to analyze prognostic factors, and the frequency of adverse events was examined using the χ 2 test. Results: We categorized 134 patients in the ddTC+Bev (n=57) and ddTC (n=77) groups who started treatment at four related institutions from November 2013 to December 2017.No patients used poly (ADP-ribose) polymerase inhibitors as the first line maintenance therapy. The progression-free survival (PFS) of the ddTC+Bev group had a significantly better prognosis than that of the ddTC group (hazard ratio [HR]=0.50; 95% confidence interval [CI]=0.32–0.79; p<0.003). Multivariate analysis showed that ddTC+Bev regimen was a prognostic factor. However, intergroup comparison using PSM revealed that the PFS of the ddTC+Bev group had a nonsignificantly better prognosis than that of the ddTC group (HR=0.70; 95% CI=0.41–1.20; p=0.189). Few adverse events above G3 were noted for ddTC+Bev, which were sufficiently tolerable. Conclusion This study could not demonstrate that adding Bev to ddTC improves prognosis.Further studies with more cases are warranted.

Background/Aims: Covered self-expandable metallic stents (cSEMS) have become popular for endoscopic ultrasound-guided hepaticogastrostomy with transmural stenting (EUS-HGS). We compared the time to recurrent biliary obstruction (TRBO), complications, and reintervention rates between EUS-HGS using plastic stent (PS) and cSEMS in patients with unresectable malignancies at multicenter institutions in Japan. Methods: Patients with unresectable malignant biliary obstruction who underwent EUS-HGS between April 2015 and July 2020 at any of the six participating facilities were enrolled. Primary endpoint: TRBO; secondary endpoints: rate of complications other than recurrent biliary obstruction and technical success rate of reintervention were evaluated. Results: PS and cSEMS were used for EUS-HGS in 109 and 43 patients, respectively. The TRBO was significantly longer in the cSEMS group than in the PS group (646 vs. 202 days). Multivariate analysis identified two independent factors associated with a favorable TRBO: combined EUS-guided antegrade stenting with EUS-HGS and the use of cSEMS. No significant difference was observed in the rate of complications other than recurrent biliary obstruction between the two groups. The technical success rate of reintervention was 85.7% for PS and 100% for cSEMS (p=0.309). Conclusions cSEMS might be a better option for EUS-HGS in patients with unresectable malignancies, given the longer TRBO.

Objective: Direct oral anticoagulants (DOACs) are increasingly being used for the treatment of cancer-associated venous thromboembolism (CAT). However, there is limited evidence of the efficacy of DOACs for the treatment of gynecological CAT. Thus, this study aimed to investigate the efficacy and safety of edoxaban for the treatment of gynecological CAT using Japanese real-world data. Methods: We reviewed the medical records of patients with 371 gynecological cancer who received edoxaban or vitamin K antagonist (VKA) between January 2011 and December 2018. Results: Altogether, 211 and 160 patients were treated with edoxaban and VKA, respectively. Fourteen patients (6.8%) in the edoxaban group and 22 (13.8%) in the VKA group showed recurrence of venous thromboembolism (VTE). Cumulative VTE recurrence was not significantly different between the 2 groups (p=0.340). Adverse events occurred in 15 (7.1%) and 11 (6.9%) patients in the edoxaban and VKA groups, respectively (p=0.697). Subgroup analysis of the edoxaban and VKA groups according to different tumor types, including ovarian, endometrial, and cervical cancer, showed equivalent outcomes in terms of VTE recurrence and adverse events. Patients without pulmonary embolism (PE) were mostly omitted from initial unfractionated heparin (UFH) therapy prior to administration of edoxaban. However, this did not increase the recurrence of VTE. Conclusion This study confirmed that edoxaban is effective and safe for the treatment of gynecological CAT. This finding was consistent for different types of gynecological cancer. Additionally, initial UFH therapy prior to the administration of edoxaban may be unnecessary for patients without PE.

Subdural hematoma or effusion is a common complication in ventriculoperitoneal shunts. However, the incidence of subdural hematoma in shunted patients requiring a surgical procedure has been decreasing recently, since it can be treated with a newly developed pressure-programmable valve system. We treated two shunted patients with subdural hematomas caused by simple falls during gait training. The management was complicated, involving multiple surgical procedures. Case 1 : A 65-year-old woman, who had undergone ventriculoperitoneal shunting for normal pressure hydrocephalus after removal of a meningioma, suffered mild head trauma due to a fall during gait training and developed consciousness disturbance after 2 hours. Computed tomography revealed an acute subdural hematoma with marked midline shift. Emergency craniotomy and hematoma evacuation were performed. Case 2 : A 61-year-old man, who had previously undergone ventriculoperitoneal shunting for normal pressure hydrocephalus after subarachnoid hemorrhage, fell to the floor during gait training. Computed tomography demonstrated a thin subdural hematoma, thus the pressure-programmable valve was adjusted to a higher pressure. However, the hematoma continued to enlarge and his level of consciousness deteriorated. Consequently, shunt ligation and irrigation of the chronic subdural hematoma were performed 6 days after the head trauma. Brain atrophy and a lowering of the intracranial pressure, which are both shunt-related complications, may have contributed to these patient's subdural hematomas forming after such relatively minor head traumas. In conclusion, rehabilitation physicians treating shunted patients must be aware of the possibility of a catastrophic intracranial hemorrhage following minor head trauma and of the various treatment-related difficulties arising in such a scenario including exacerbation of hydrocephalus, meningitis, and rebleeding.