Efficacy and safety of trifluridine/tipiracil in older and younger patients with metastatic gastric or gastroesophageal junction cancer: subgroup analysis of a randomized phase 3 study (TAGS)

Age groups; Gastrointestinal neoplasms; TrifluridineGrupos de edad; Neoplasias gastrointestinales; TrifluridinaGrups d'edat; Neoplàsies gastrointestinals; TrifluridinaBackground Trifluridine and tipiracil (FTD/TPI) demonstrated survival benefit vs placebo and manageable safety in previously treated patients with metastatic gastric/gastroesophageal junction cancer (mGC/GEJC) in the randomized, placebo-controlled, phase 3 TAGS study. This subgroup analysis of TAGS examined efficacy/safety outcomes by age. Methods In TAGS, patients with mGC/GEJC and ≥ 2 prior therapies were randomized (2:1) to receive FTD/TPI 35 mg/m2 or placebo, plus best supportive care. A preplanned subgroup analysis was performed to evaluate efficacy and safety outcomes in patients aged < 65, ≥ 65, and ≥ 75 years. Results Among 507 randomized patients (n = 337 FTD/TPI; n = 170 placebo), 55%, 45%, and 14% were aged < 65, ≥ 65, and ≥ 75 years, respectively. Overall survival hazard ratios for FTD/TPI vs placebo were 0.67 (95% CI 0.51–0.89), 0.73 (95% CI 0.52–1.02), and 0.67 (95% CI 0.33–1.37) in patients aged < 65, ≥ 65, and ≥ 75 years, respectively. Regardless of age, patients receiving FTD/TPI experienced improved progression-free survival and stayed longer on treatment than those receiving placebo. Among FTD/TPI-treated patients, frequencies of any-cause grade ≥ 3 adverse events (AEs) were similar across age subgroups (80% each), although grade ≥ 3 neutropenia was more frequent in older patients [40% (≥ 65 and ≥ 75 years); 29% (< 65 years)]; AE-related discontinuation rates did not increase with age [14% (< 65 years), 12% (≥ 65 years), and 12% (≥ 75 years)]. Conclusions The results of this subgroup analysis show the efficacy and tolerability of FTD/TPI treatment regardless of age in patients with mGC/GEJC who had received 2 or more prior treatments.This study was sponsored by Taiho Oncology, Inc., and Taiho Pharmaceuticals Co., Ltd. Professional medical writing and editorial assistance were provided by Vasupradha Vethantham, PhD, and Jennifer L. Robertson, PhD, at Ashfield MedComms, an Ashfield Health company, funded by Taiho Oncology, Inc

ラットカンミクロゾームカラノジアシルグリセロールアシルトランスフェーゼ - ブンリトアシルキョウヨタイトクイセイ

京都大学0048新制・課程博士医学博士甲第1955号医博第488号新制||医||231(附属図書館)5212UT51-52-N20京都大学大学院医学研究科生理系専攻(主査)教授 佐野 晴洋, 教授 早石 修, 教授 沼 正作学位規則第5条第1項該当Kyoto UniversityDA

Digitally Guided Direct Composite Injection Technique with a Bi-layer Clear Mini-Index for the Management of Extensive Occlusal Caries in a Pediatric Patient : A Case Report

Purpose: This case report presents a direct composite inverse injection technique using a bi-layer clear mini-index fabricated with a digital workflow to restore extensive posterior occlusal cavities in a 13-year-old patient. Materials and Methods: After a root canal treatment in the right mandibular first molar and step-wise excavation of deep caries in the left mandibular first molar, the extensive occlusal restorations were digitally designed using CAD software, upon which digital wax-ups were 3D-printed. Bi-layer clear mini-indices consisting of a hard outer plastic layer and an elastic inner silicone layer were prepared from the 3D-printed cast. The bonding surfaces were deproteinized using a 6% sodium hypochlorite solution, and an antioxidant (Clearfil DC Activator; Kuraray Noritake) was utilized to improve the dentin bonding durability of a 2-step self-etch adhesive (Clearfil SE Bond 2; Kuraray Noritake). Subsequently, a highly filled universal-shade flowable resin composite (RC) was incrementally placed into the cavities. To create the final occlusal morphology, the same RC was inversely injected through the opening of the bi-layer indices. Results: The workflow was feasible, and the occlusal cavities were efficiently restored using the injection technique. Occlusal carving and adjustments of the morphology were not necessary, leading to less chair time. At the 1-year follow-up, the clinical outcome was excellent. Conclusion: The injection technique with a bi-layer clear mini-index accurately translated the digital wax-ups into large, final restorations. Precise morphology and shortened chair time enhanced patient satisfaction, but at the expense of multiple visits

Digitally Guided Direct Composite Injection Technique with a Bi-layer Clear Mini-Index for the Management of Extensive Occlusal Caries in a Pediatric Patient : A Case Report

Purpose: This case report presents a direct composite inverse injection technique using a bi-layer clear mini-index fabricated with a digital workflow to restore extensive posterior occlusal cavities in a 13-year-old patient. Materials and Methods: After a root canal treatment in the right mandibular first molar and step-wise excavation of deep caries in the left mandibular first molar, the extensive occlusal restorations were digitally designed using CAD software, upon which digital wax-ups were 3D-printed. Bi-layer clear mini-indices consisting of a hard outer plastic layer and an elastic inner silicone layer were prepared from the 3D-printed cast. The bonding surfaces were deproteinized using a 6% sodium hypochlorite solution, and an antioxidant (Clearfil DC Activator; Kuraray Noritake) was utilized to improve the dentin bonding durability of a 2-step self-etch adhesive (Clearfil SE Bond 2; Kuraray Noritake). Subsequently, a highly filled universal-shade flowable resin composite (RC) was incrementally placed into the cavities. To create the final occlusal morphology, the same RC was inversely injected through the opening of the bi-layer indices. Results: The workflow was feasible, and the occlusal cavities were efficiently restored using the injection technique. Occlusal carving and adjustments of the morphology were not necessary, leading to less chair time. At the 1-year follow-up, the clinical outcome was excellent. Conclusion: The injection technique with a bi-layer clear mini-index accurately translated the digital wax-ups into large, final restorations. Precise morphology and shortened chair time enhanced patient satisfaction, but at the expense of multiple visits