Comprehensive analysis of aberrations in pan-cancer, with a focus on prognostic and therapeutic implications.

Background: is one of the most frequently mutated oncogenes in humans. aberrations play a significant role in various solid tumors, affecting patient prognosis and treatment outcomes.

Objectives: We identified features of genetic alterations in , including single amino acid substitutions and amplifications, based on the results of next-generation sequencing tests in 1667 advanced solid tumor patients.

Safety and efficacy of Artemisia argyi extract RW0117 for functional dyspepsia: A randomized, double-blind, placebo-controlled clinical study.

Ethnopharmacological Relevance: Artemisia argyi (A. argyi) is a herbaceous perennial plant that has long been employed in traditional medicine for the management of gastrointestinal conditions such as abdominal pain, gastric ulcer, diarrhea, and gastritis.

Aim Of The Study: To evaluate the efficacy and safety of RW0117, an ethanol extract of A.

Nivolumab plus cabozantinib in metastatic renal cell carcinoma: real-world evidence from the international ARON-1 study.

Introduction: Four approved immune-based combinations for untreated metastatic renal carcinoma have demonstrated survival benefits. The ARON-1 study (NCT05287464) analyzed real-world data of patients with metastatic renal cell carcinoma receiving first-line immuno-oncology combinations. This sub-analysis is focused on the nivolumab plus cabozantinib effectiveness.

Angiogenesis gene signatures in patient-derived tumor spheroids for genetic and tumor angiogenesis profiling.

: gastric cancers are highly vascular tumors, with elevated pro-angiogenic factors correlating with a poor prognosis. Despite advancements in precision medicine, there remains a critical need for platforms capable of identifying patient-specific therapeutic vulnerabilities. In this study, we present a 3D-printed patient-specific tumor angiogenesis chip that integrates genetic data to evaluate the molecular and functional characteristics of tumor angiogenesis in tumor spheroids derived from patients with gastric cancer.

Patient-reported Outcomes in KEYLYNK-010: Pembrolizumab Plus Olaparib Versus Abiraterone or Enzalutamide for Participants with Biomarker-unselected, Previously Treated Metastatic Castration-resistant Prostate Cancer.

Background And Objective: Pembrolizumab plus olaparib did not significantly improve radiographic progression-free survival or overall survival versus a next-generation hormonal agent (NHA) in participants with biomarker-unselected, pretreated metastatic castration-resistant prostate cancer (mCRPC) in the phase 3 KEYLYNK-010 trial. We present prespecified patient-reported outcomes (PROs) from KEYLYNK-010.

Methods: Participants were randomly assigned 2:1 to receive pembrolizumab plus olaparib or an NHA (abiraterone acetate or enzalutamide).

Prevalence and clinical implications of PIK3CA aberrations across cancer types: A real-world next-generation sequencing approach.

Background: Activation of the phosphatidylinositol 3-kinase (PI3K) pathway is a common oncogenic mechanism in various solid tumors and is often driven by aberrations in the PIK3CA gene. Recent advancements have shown effective treatment for patients with PIK3CA-mutated breast cancer; however, there is an unmet need for other malignancies. The aim of this study was to gain a better understanding of PIK3CA mutations and amplifications across cancer types.

Geographical Differences in the Management and Outcomes of Patients With Advanced Urothelial Carcinoma Treated With Pembrolizumab After Progression on Platinum-Based Chemotherapy: Results From ARON-2 Study.

Purpose: Our investigation assessed the impact of geographical disparities in the treatment of patients with advanced urothelial cancer (aUC) included in the international, real-world ARON-2 trial.

Patients And Methods: The study population comprised 1,137 patients with aUC treated with pembrolizumab for relapsed or progressive disease after platinum-based chemotherapy (PBC) at 63 institutions in 19 countries. Patients were divided into three geographical areas: Europe (area 1: 791 patients), the United States (area 2: 156 patients), and Asia (area 3: 190 patients).

Adjuvant Pembrolizumab Versus Placebo for Renal Cell Carcinoma in the East Asian Subgroup of the Phase 3 KEYNOTE-564 Study.

Purpose: Adjuvant pembrolizumab improved disease-free survival (DFS) and overall survival (OS) versus placebo in participants with renal cell carcinoma (RCC) at increased risk of recurrence after nephrectomy in the global phase 3 KEYNOTE-564 study. This post hoc subgroup analysis evaluated the efficacy and safety of adjuvant pembrolizumab in East Asian (Japan, South Korea, Taiwan) participants enrolled in KEYNOTE-564.

Materials And Methods: Eligible participants were randomly assigned 1:1 to receive adjuvant pembrolizumab 200 mg or placebo intravenously every 3 weeks for ≤17 cycles.

Erdafitinib versus Chemotherapy in Fibroblast Growth Factor Receptor-Altered Advanced or Metastatic Urothelial Cancer After Progression on Anti-programmed Death-(Ligand) 1 Therapy: An Exploratory Analysis of the Asian Subpopulation in the THOR Phase 3 Study.

Introduction: The randomized phase 3 THOR study showed significantly longer survival with erdafitinib (pan-fibroblast growth factor receptor [FGFR] inhibitor) over chemotherapy in adults with FGFR-altered locally advanced or metastatic urothelial cancer (la/mUC) who had progressed during or after anti-programmed death-(ligand) 1 (anti-PD-[L]1) therapy (Cohort 1). This exploratory post-hoc analysis was conducted to evaluate the efficacy and safety of erdafitinib in the Asian subpopulation within THOR Cohort 1.

Patients And Methods: Eligible patients were randomized in a 1:1 ratio to receive erdafitinib (8 mg once daily with pharmacodynamically guided up-titration to 9 mg) or chemotherapy (vinflunine or docetaxel once every 3 weeks).

Avelumab First-line Maintenance for Advanced Urothelial Carcinoma: Long-term Outcomes from the JAVELIN Bladder 100 Trial in Patients with Nonvisceral or Lymph Node-only Disease.

In the JAVELIN Bladder 100 randomized phase 3 trial (N = 700), avelumab first-line maintenance plus best supportive care (BSC) significantly prolonged overall survival (OS; primary endpoint) and progression-free survival (PFS) versus BSC alone in patients with advanced urothelial carcinoma (aUC) without progression after first-line platinum-based chemotherapy (PBC). Here, we report exploratory analyses of subgroups with nonvisceral metastases at the start of PBC (including bone metastases) or lymph node-only disease at randomization. The median OS with avelumab versus control in patients with nonvisceral metastases (n = 318) was 31.

Pembrolizumab plus Lenvatinib in patients with metastatic Renal Cell Carcinoma: real-world evidences from the international ARON- 1 study.

Background: Pembrolizumab plus lenvatinib is a treatment option for metastatic Renal Cell Carcinoma (mRCC). In the ARON-1 study we investigated we the real-world experiences gained from the use of this combination for mRCC.

Methods: We retrospectively investigated real-world clinical outcomes of mRCC patients receiving pembrolizumab plus lenvatinib within the ARON-1 study.

Avelumab First-line Maintenance for Advanced Urothelial Carcinoma: Long-term Analyses of Patient-reported Outcomes and Quality-adjusted Time Without Symptoms or Toxicity from the JAVELIN Bladder 100 Trial.

Background And Objective: In JAVELIN Bladder 100, avelumab first-line maintenance plus best supportive care (BSC) significantly prolonged overall survival versus BSC alone, with no detrimental impact on quality of life (QOL), in patients with advanced urothelial carcinoma without progression following first-line platinum-based chemotherapy. We report long-term analyses of patient-reported outcomes (PROs) in patients treated with avelumab (any duration or ≥12 mo) and a post hoc analysis comparing quality-adjusted time without symptoms or toxicity (Q-TWiST) between arms.

Methods: PROs were assessed using National Comprehensive Cancer Network/Functional Assessment of Cancer Therapy Bladder Symptom Index-18 (FBlSI-18) and EuroQol 5-level EQ-5D (EQ-5D-5L).

Primary Repair of Chronic Quadriceps Tendon Rupture With Dermal Allograft Augmentation: Surgical Technique and Case Review.

Background: Repair of chronic quadriceps tendon ruptures has high rates of rerupture and extensor lag. Dermal allograft augmentation of tendon repairs has shown to increase repair strength and healing rates.

Indications: We supplement primary quadriceps repair with dermal allograft augmentation in cases where tissue degeneration has occurred secondary to a subacute or chronic nature to help facilitate incorporation of the tendon tissue to bone.

Paradoxical Effect of Myosteatosis on the Immune Checkpoint Inhibitor Response in Metastatic Renal Cell Carcinoma.

Background: Treatment for metastatic renal cell carcinoma (mRCC) has shifted from tyrosine kinase inhibitor (TKI) therapy to immune checkpoint inhibitor (ICI)-based therapy, improving outcomes but with variable individual responses. This study investigated the prognostic implications of pretreatment low skeletal muscle mass (LSMM) and myosteatosis in patients with mRCC undergoing first-line ICI-based therapies, comparing outcomes between PD-1 inhibitor + CTLA-4 inhibitor and PD-1 inhibitor + TKI, incorporating single-cell RNA sequencing.

Methods: A retrospective analysis was performed on 90 patients with mRCC treated with ICI-based therapies between November 2019 and March 2023.

Epidermal Growth Factor Receptor Aberrations Identified by Next-generation Sequencing in Patients with Metastatic Cancers.

Purpose: The epidermal growth factor receptor (EGFR) is a therapeutic target with confirmed clinical efficacy for several cancer types. We aimed to identify EGFR aberrations and their associations with other genomic alterations in patients with metastatic diseases of various cancers.

Materials And Methods: We used real-world data from the next-generation sequencing (NGS) of 3,286 patients with metastatic cancer at the Samsung Medical Center.

Real-Life Impact of Enfortumab Vedotin or Chemotherapy in the Sequential Treatment of Advanced Urothelial Carcinoma: The ARON-2 Retrospective Experience.

Background: Recently, a plethora of novel systemic agents have been incorporated into the therapeutic armamentarium of advanced urothelial carcinoma (aUC). The antibody-drug conjugate (ADC), enfortumab vedotin (EV), has demonstrated relevant clinical benefit in patients with aUC refractory to platinum and immune-checkpoint inhibitor (ICI) therapy. Our study provides a retrospective, international, real-world analysis comparing the effectiveness of EV to chemotherapy in this setting.

Concomitant medications in patients with metastatic urothelial carcinoma receiving enfortumab vedotin: real-world data from the ARON-2 study.

Patients with metastatic urothelial carcinoma (mUC) are typically elderly and often have other comorbidities that require the use of concomitant medications. In our study we evaluated the association of concomitant use of antibiotics (ATBs), proton pump inhibitors (PPIs), corticosteroids, statins, metformin and insulin with patient outcomes and we validated the prognostic role of a concomitant drug score in mUC patients treated with enfortumab vedotin (EV) monotherapy. Data from 436 patients enrolled in the ARON-2 retrospective study were analyzed according to the concomitant medications used at baseline.

Dose-response Association Between Alcohol Consumption and Kidney Cancer Risk Differs According to Glycemic Status: A Nationwide Cohort Study of 9.4 Million Individuals.

Purpose: Previous studies suggested an association between alcohol consumption and reduced kidney cancer risk. Given a potential interaction between alcohol's insulin-sensitizing effect and hyperglycemia-related insulin resistance, we aimed to assess whether the dose-response association between alcohol intake and kidney cancer risk varies based on glycemic status.

Materials And Methods: This nationwide cohort study analyzed data from 9,492,331 adults who underwent a national health screening program in 2009 and were followed until 2018.

Clinical outcomes by baseline metastases in patients with renal cell carcinoma treated with lenvatinib plus pembrolizumab versus sunitinib: Post hoc analysis of the CLEAR trial.

Lenvatinib plus pembrolizumab significantly improved efficacy versus sunitinib in treatment of advanced renal cell carcinoma (aRCC) in the phase 3 CLEAR study. We report results of an exploratory post hoc analysis of tumor response data based on baseline metastatic characteristics of patients who received lenvatinib plus pembrolizumab versus sunitinib, at the final overall survival analysis time point of CLEAR (cutoff: July 31, 2022). Treatment-naïve adults with aRCC were randomized to: lenvatinib (20 mg PO QD in 21-day cycles) plus pembrolizumab (n = 355; 200 mg IV Q3W); lenvatinib plus everolimus (not reported here); or sunitinib (n = 357; 50 mg PO QD; 4 weeks on/2 weeks off).

Efficacy and safety of pembrolizumab in patients with advanced urothelial carcinoma deemed potentially ineligible for platinum-containing chemotherapy: Post hoc analysis of KEYNOTE-052 and LEAP-011.

Background: First-line pembrolizumab monotherapy is a standard of care for platinum-ineligible patients with advanced urothelial carcinoma (UC). No global standardized definition of platinum ineligibility exists. This study aimed to evaluate the efficacy and safety of pembrolizumab monotherapy in patients with UC who met various criteria for platinum ineligibility.