Purpose: This study aimed to investigate changes in target coverage using magnetic resonance–guided online adaptive radiotherapy (MRgoART) for kidney tumors and to evaluate the suitable timing of treatment. Materials and Methods: Among patients treated with 3-fraction MRgoART for kidney cancer, 18 tumors located within 1 cm of the gastrointestinal tract were selected. Stereotactic radiosurgery planning with a prescription dose of 26 Gy was performed using pretreatment simulation and three MRgoART timings with an adapt-to-shape method. The best MRgoART plan was defined as the plan achieving the highest percentage of planning target volume (PTV) coverage of 26 Gy. In clinical scenario simulation, MRgoART plans were evaluated in the order of actual treatment. Waiting for the next timing was done when the PTV coverage of 26 Gy did not achieve 95%–99% or did not increase by 5% or more compared to the pretreatment plan. Results: The median percentages of PTV receiving 26 Gy in pretreatment and the first, second, and third MRgoART were 82% (range, 19%), 63% (range, 7% to 99%), 88% (range, 31% to 99%), and 95% (range, 3% to 99%), respectively. Comparing pretreatment simulation plans with the best MRgoART plans showed a significant difference (p = 0.025). In the clinical scenario simulation, 16 of the 18 planning series, including nine plans with 95%–99% PTV coverage of 26 Gy and seven plans with increased PTV coverage by 5% or more, would be irradiated at a good timing. Conclusion MRgoART revealed dose coverage differences at each MRgoART timing. Waiting for optimal irradiation timing could be an option in case of suboptimal timing.

Purpose: This study aimed to investigate changes in target coverage using magnetic resonance–guided online adaptive radiotherapy (MRgoART) for kidney tumors and to evaluate the suitable timing of treatment. Materials and Methods: Among patients treated with 3-fraction MRgoART for kidney cancer, 18 tumors located within 1 cm of the gastrointestinal tract were selected. Stereotactic radiosurgery planning with a prescription dose of 26 Gy was performed using pretreatment simulation and three MRgoART timings with an adapt-to-shape method. The best MRgoART plan was defined as the plan achieving the highest percentage of planning target volume (PTV) coverage of 26 Gy. In clinical scenario simulation, MRgoART plans were evaluated in the order of actual treatment. Waiting for the next timing was done when the PTV coverage of 26 Gy did not achieve 95%–99% or did not increase by 5% or more compared to the pretreatment plan. Results: The median percentages of PTV receiving 26 Gy in pretreatment and the first, second, and third MRgoART were 82% (range, 19%), 63% (range, 7% to 99%), 88% (range, 31% to 99%), and 95% (range, 3% to 99%), respectively. Comparing pretreatment simulation plans with the best MRgoART plans showed a significant difference (p = 0.025). In the clinical scenario simulation, 16 of the 18 planning series, including nine plans with 95%–99% PTV coverage of 26 Gy and seven plans with increased PTV coverage by 5% or more, would be irradiated at a good timing. Conclusion MRgoART revealed dose coverage differences at each MRgoART timing. Waiting for optimal irradiation timing could be an option in case of suboptimal timing.

Purpose: This study aimed to investigate changes in target coverage using magnetic resonance–guided online adaptive radiotherapy (MRgoART) for kidney tumors and to evaluate the suitable timing of treatment. Materials and Methods: Among patients treated with 3-fraction MRgoART for kidney cancer, 18 tumors located within 1 cm of the gastrointestinal tract were selected. Stereotactic radiosurgery planning with a prescription dose of 26 Gy was performed using pretreatment simulation and three MRgoART timings with an adapt-to-shape method. The best MRgoART plan was defined as the plan achieving the highest percentage of planning target volume (PTV) coverage of 26 Gy. In clinical scenario simulation, MRgoART plans were evaluated in the order of actual treatment. Waiting for the next timing was done when the PTV coverage of 26 Gy did not achieve 95%–99% or did not increase by 5% or more compared to the pretreatment plan. Results: The median percentages of PTV receiving 26 Gy in pretreatment and the first, second, and third MRgoART were 82% (range, 19%), 63% (range, 7% to 99%), 88% (range, 31% to 99%), and 95% (range, 3% to 99%), respectively. Comparing pretreatment simulation plans with the best MRgoART plans showed a significant difference (p = 0.025). In the clinical scenario simulation, 16 of the 18 planning series, including nine plans with 95%–99% PTV coverage of 26 Gy and seven plans with increased PTV coverage by 5% or more, would be irradiated at a good timing. Conclusion MRgoART revealed dose coverage differences at each MRgoART timing. Waiting for optimal irradiation timing could be an option in case of suboptimal timing.

Purpose: This study aimed to investigate changes in target coverage using magnetic resonance–guided online adaptive radiotherapy (MRgoART) for kidney tumors and to evaluate the suitable timing of treatment. Materials and Methods: Among patients treated with 3-fraction MRgoART for kidney cancer, 18 tumors located within 1 cm of the gastrointestinal tract were selected. Stereotactic radiosurgery planning with a prescription dose of 26 Gy was performed using pretreatment simulation and three MRgoART timings with an adapt-to-shape method. The best MRgoART plan was defined as the plan achieving the highest percentage of planning target volume (PTV) coverage of 26 Gy. In clinical scenario simulation, MRgoART plans were evaluated in the order of actual treatment. Waiting for the next timing was done when the PTV coverage of 26 Gy did not achieve 95%–99% or did not increase by 5% or more compared to the pretreatment plan. Results: The median percentages of PTV receiving 26 Gy in pretreatment and the first, second, and third MRgoART were 82% (range, 19%), 63% (range, 7% to 99%), 88% (range, 31% to 99%), and 95% (range, 3% to 99%), respectively. Comparing pretreatment simulation plans with the best MRgoART plans showed a significant difference (p = 0.025). In the clinical scenario simulation, 16 of the 18 planning series, including nine plans with 95%–99% PTV coverage of 26 Gy and seven plans with increased PTV coverage by 5% or more, would be irradiated at a good timing. Conclusion MRgoART revealed dose coverage differences at each MRgoART timing. Waiting for optimal irradiation timing could be an option in case of suboptimal timing.

Purpose: This study aimed to investigate changes in target coverage using magnetic resonance–guided online adaptive radiotherapy (MRgoART) for kidney tumors and to evaluate the suitable timing of treatment. Materials and Methods: Among patients treated with 3-fraction MRgoART for kidney cancer, 18 tumors located within 1 cm of the gastrointestinal tract were selected. Stereotactic radiosurgery planning with a prescription dose of 26 Gy was performed using pretreatment simulation and three MRgoART timings with an adapt-to-shape method. The best MRgoART plan was defined as the plan achieving the highest percentage of planning target volume (PTV) coverage of 26 Gy. In clinical scenario simulation, MRgoART plans were evaluated in the order of actual treatment. Waiting for the next timing was done when the PTV coverage of 26 Gy did not achieve 95%–99% or did not increase by 5% or more compared to the pretreatment plan. Results: The median percentages of PTV receiving 26 Gy in pretreatment and the first, second, and third MRgoART were 82% (range, 19%), 63% (range, 7% to 99%), 88% (range, 31% to 99%), and 95% (range, 3% to 99%), respectively. Comparing pretreatment simulation plans with the best MRgoART plans showed a significant difference (p = 0.025). In the clinical scenario simulation, 16 of the 18 planning series, including nine plans with 95%–99% PTV coverage of 26 Gy and seven plans with increased PTV coverage by 5% or more, would be irradiated at a good timing. Conclusion MRgoART revealed dose coverage differences at each MRgoART timing. Waiting for optimal irradiation timing could be an option in case of suboptimal timing.

Objective: In Japan, perioperative prophylaxis of pulmonary embolism (PE) in gynecologic cancer patients with preoperative asymptomatic venous thromboembolism (VTE) has not been well established yet. The GOTIC-VTE trial was a prospective, multi-center, single-arm clinical trial to investigate the prevention of postoperative symptomatic PE onset by seamless anticoagulant therapy from the preoperative period to 4 weeks after surgery instead of using intermittent pneumatic compression. Methods: Anticoagulant therapy was started immediately after asymptomatic VTE diagnosis and stopped preoperatively according to the rules of each institution. Unfractionated heparin administration was resumed within 12 hours postoperatively, and this was followed by the switch to low-molecular-weight heparin and subsequently, edoxaban; this cycle was continued for 28 days. Primary outcome was the occurrence of symptomatic PE in 28 days postoperatively. Secondary outcomes were the incidence of VTE-related events in 28 days and 6 months postoperatively and protocol-related adverse events. Results: Between February 2018 and September 2020, 99 patients were enrolled; of these, 82patients were assessed as the full analysis set, including 58 for ovarian cancer, fallopian tube, or peritoneal cancer; 21 for endometrial cancer; and 3 for cervical cancer. No symptomatic PE was observed within 28 days postoperatively; two patients had bleeding events (major bleeding and clinically relevant nonmajor bleeding) and three had grade 3 adverse events (increased alanine transaminase, aspartate aminotransferase, or gamma-glutamyl transferase). Conclusion The multifaceted perioperative management for gynecologic malignancies with asymptomatic VTE effectively prevented postoperative symptomatic PE.Trial Registration: JRCT Identifier: jRCTs031180124

Objective: In the global phase 3 Study 309/KEYNOTE-775 (NCT03517449) at the first interim analysis, lenvatinib+pembrolizumab significantly improved progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) versus treatment of physician’s choice chemotherapy (TPC) in patients with previously treated advanced/recurrent endometrial cancer (EC). This exploratory analysis evaluated outcomes in patients enrolled in East Asia at the time of prespecified final analysis. Methods: Women ≥18 years with histologically confirmed advanced, recurrent, or metastatic EC with progressive disease after 1 platinum-based chemotherapy (2 if 1 given in neoadjuvant/ adjuvant setting) were enrolled. Patients were randomized 1:1 to lenvatinib 20 mg orally once daily plus pembrolizumab 200 mg intravenously every 3 weeks (≤35 cycles) or TPC (doxorubicin or paclitaxel). Primary endpoints were PFS per RECIST v1.1 by blinded independent central review and OS. No alpha was assigned for this subgroup analysis. Results: Among 155 East Asian patients (lenvatinib+pembrolizumab, n=77; TPC, n=78), median follow-up time (data cutoff: March 1, 2022) was 34.3 (range, 25.1–43.0) months.Hazard ratios (HRs) with 95% confidence intervals (CIs) for PFS (lenvatinib+pembrolizumab vs. TPC) were 0.74 (0.49–1.10) and 0.64 (0.44–0.94) in the mismatch repair proficient (pMMR) and all-comer populations, respectively. HRs (95% CI) for OS were 0.68 (0.45–1.02) and 0.61 (0.41–0.90), respectively. ORRs were 36% with lenvatinib+pembrolizumab and 22% with TPC (pMMR) and 39% and 21%, respectively (all-comers). Treatment-related adverse events occurred in 97% and 96% (grade 3–5, 74% and 72%), respectively. Conclusion Lenvatinib+pembrolizumab provided clinically meaningful benefit with manageable safety compared with TPC, supporting its use in East Asian patients with previously treated advanced/recurrent EC.

Objective: In Japan, perioperative prophylaxis of pulmonary embolism (PE) in gynecologic cancer patients with preoperative asymptomatic venous thromboembolism (VTE) has not been well established yet. The GOTIC-VTE trial was a prospective, multi-center, single-arm clinical trial to investigate the prevention of postoperative symptomatic PE onset by seamless anticoagulant therapy from the preoperative period to 4 weeks after surgery instead of using intermittent pneumatic compression. Methods: Anticoagulant therapy was started immediately after asymptomatic VTE diagnosis and stopped preoperatively according to the rules of each institution. Unfractionated heparin administration was resumed within 12 hours postoperatively, and this was followed by the switch to low-molecular-weight heparin and subsequently, edoxaban; this cycle was continued for 28 days. Primary outcome was the occurrence of symptomatic PE in 28 days postoperatively. Secondary outcomes were the incidence of VTE-related events in 28 days and 6 months postoperatively and protocol-related adverse events. Results: Between February 2018 and September 2020, 99 patients were enrolled; of these, 82patients were assessed as the full analysis set, including 58 for ovarian cancer, fallopian tube, or peritoneal cancer; 21 for endometrial cancer; and 3 for cervical cancer. No symptomatic PE was observed within 28 days postoperatively; two patients had bleeding events (major bleeding and clinically relevant nonmajor bleeding) and three had grade 3 adverse events (increased alanine transaminase, aspartate aminotransferase, or gamma-glutamyl transferase). Conclusion The multifaceted perioperative management for gynecologic malignancies with asymptomatic VTE effectively prevented postoperative symptomatic PE.Trial Registration: JRCT Identifier: jRCTs031180124

Objective: In the global phase 3 Study 309/KEYNOTE-775 (NCT03517449) at the first interim analysis, lenvatinib+pembrolizumab significantly improved progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) versus treatment of physician’s choice chemotherapy (TPC) in patients with previously treated advanced/recurrent endometrial cancer (EC). This exploratory analysis evaluated outcomes in patients enrolled in East Asia at the time of prespecified final analysis. Methods: Women ≥18 years with histologically confirmed advanced, recurrent, or metastatic EC with progressive disease after 1 platinum-based chemotherapy (2 if 1 given in neoadjuvant/ adjuvant setting) were enrolled. Patients were randomized 1:1 to lenvatinib 20 mg orally once daily plus pembrolizumab 200 mg intravenously every 3 weeks (≤35 cycles) or TPC (doxorubicin or paclitaxel). Primary endpoints were PFS per RECIST v1.1 by blinded independent central review and OS. No alpha was assigned for this subgroup analysis. Results: Among 155 East Asian patients (lenvatinib+pembrolizumab, n=77; TPC, n=78), median follow-up time (data cutoff: March 1, 2022) was 34.3 (range, 25.1–43.0) months.Hazard ratios (HRs) with 95% confidence intervals (CIs) for PFS (lenvatinib+pembrolizumab vs. TPC) were 0.74 (0.49–1.10) and 0.64 (0.44–0.94) in the mismatch repair proficient (pMMR) and all-comer populations, respectively. HRs (95% CI) for OS were 0.68 (0.45–1.02) and 0.61 (0.41–0.90), respectively. ORRs were 36% with lenvatinib+pembrolizumab and 22% with TPC (pMMR) and 39% and 21%, respectively (all-comers). Treatment-related adverse events occurred in 97% and 96% (grade 3–5, 74% and 72%), respectively. Conclusion Lenvatinib+pembrolizumab provided clinically meaningful benefit with manageable safety compared with TPC, supporting its use in East Asian patients with previously treated advanced/recurrent EC.

Objective: In Japan, perioperative prophylaxis of pulmonary embolism (PE) in gynecologic cancer patients with preoperative asymptomatic venous thromboembolism (VTE) has not been well established yet. The GOTIC-VTE trial was a prospective, multi-center, single-arm clinical trial to investigate the prevention of postoperative symptomatic PE onset by seamless anticoagulant therapy from the preoperative period to 4 weeks after surgery instead of using intermittent pneumatic compression. Methods: Anticoagulant therapy was started immediately after asymptomatic VTE diagnosis and stopped preoperatively according to the rules of each institution. Unfractionated heparin administration was resumed within 12 hours postoperatively, and this was followed by the switch to low-molecular-weight heparin and subsequently, edoxaban; this cycle was continued for 28 days. Primary outcome was the occurrence of symptomatic PE in 28 days postoperatively. Secondary outcomes were the incidence of VTE-related events in 28 days and 6 months postoperatively and protocol-related adverse events. Results: Between February 2018 and September 2020, 99 patients were enrolled; of these, 82patients were assessed as the full analysis set, including 58 for ovarian cancer, fallopian tube, or peritoneal cancer; 21 for endometrial cancer; and 3 for cervical cancer. No symptomatic PE was observed within 28 days postoperatively; two patients had bleeding events (major bleeding and clinically relevant nonmajor bleeding) and three had grade 3 adverse events (increased alanine transaminase, aspartate aminotransferase, or gamma-glutamyl transferase). Conclusion The multifaceted perioperative management for gynecologic malignancies with asymptomatic VTE effectively prevented postoperative symptomatic PE.Trial Registration: JRCT Identifier: jRCTs031180124