Analysis of Poor Prognostic Factors and Treatment Strategies in Platinum-Based Systemic Therapy After EGFR-TKI Failure in Patients With Advanced Nonsmall Cell Lung Cancer Harboring EGFR Mutations.

Background: The aim of this study was to identify poor prognostic factors and explore optimal second-line treatment strategies for patients with epidermal growth factor receptor (EGFR)-mutant nonsmall cell lung cancer (NSCLC) who developed resistance to EGFR tyrosine kinase inhibitors (TKIs).

Patients And Methods: We retrospectively evaluated patients with advanced or recurrent EGFR-mutant NSCLC who received platinum-based systemic therapy after EGFR-TKI failure from January 2017 to July 2022 at 20 institutions. Logistic regression analysis was used to identify factors associated with 1-year mortality after the start of systemic therapy.

Real-world treatment outcomes before and after chemoimmunotherapy approval in EGFR-mutant NSCLC after EGFR-TKI failure: a Japanese cohort study.

Background: In Japan, chemoimmunotherapy was approved as treatment for advanced or recurrent non-small-cell lung cancer (NSCLC), including for patients with epidermal growth factor receptor (EGFR) mutations, in December 2018. However, the impact of its approval on real-world clinical outcomes among patients with EGFR-mutant NSCLC remains unclear. The aim of our study was to assess that impact.

Utility of serum CYFRA 21-1 as a prognostic biomarker in ALK-positive non-small cell lung cancer treated with ALK-TKIs: a retrospective cohort study.

Background: Anaplastic lymphoma kinase (ALK) fusion gene-positive non-small cell lung cancer (NSCLC) represents 3-7% of all cases and causes oncogene addiction. Although ALK tyrosine kinase inhibitors (ALK-TKIs) are effective for treating ALK-positive NSCLC, some patients still show suboptimal responses and poor outcomes. Clinically simple and detectable biomarkers for this group are limited.

Impact of mutant protein expression on clinical outcomes in patients with EGFR L858R-mutated non-small cell lung cancer.

Background: Currently, patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) are typically treated with osimertinib monotherapy. However, in some patients, the therapeutic efficacy of osimertinib is suboptimal, leading to heterogeneity in treatment response, which presents a clinical challenge. It remains unclear how the expression level of EGFR-mutant protein affects osimertinib treatment and clinical outcomes.

Chemoimmunotherapy Outcomes and Prognostic Factors in Patients with Advanced, Low PD-L1-Expressing Non-Small Cell Lung Cancer.

Unlabelled: Chemoimmunotherapy is recommended for patients with non-small cell lung cancer (NSCLC) with low PD-L1 expression, but the effect of additional immunotherapy is heterogeneous in this population. To identify patients who do not benefit from the addition of immune checkpoint inhibitors (ICI) to chemotherapy, we conducted a retrospective study at 19 institutions in Japan. We analyzed 851 patients with advanced NSCLC with a PD-L1 tumor proportion score of 1% to 49% who received chemoimmunotherapy (n = 504) or chemotherapy (n = 347) between March 2017 and June 2022.

Outcomes of chemotherapy with or without immunotherapy in older patients with non-small cell lung cancer and low PD-L1 expression.

Background: Immune checkpoint inhibitors (ICIs) in combination with chemotherapy have demonstrated efficacy in the treatment of non-small cell lung cancer (NSCLC) with a programmed death ligand 1 (PD-L1) tumor proportion score (TPS) of 1-49%. However, older patients remain underrepresented in clinical trials, and optimal treatment strategies for this population remain unclear. This study sought to evaluate the efficacy and safety of first-line treatment with either platinum-based chemotherapy alone (Chemo) or in combination with ICIs (ICI/Chemo) in older patients with NSCLC who have low PD-L1 expression.

Combination therapy of avutometinib and MRTX1133 synergistically suppresses cell growth by inducing apoptosis in KRASG12D-mutated pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy with a poor prognosis, and over 90% of PDAC cases involve activating mutations in the oncogene KRAS. Therapeutic strategies that inhibit the mitogen-activated protein kinase pathway, a critical effector pathway in KRAS-mutated cancers, have garnered significant attention. Among several molecular-targeted drugs, avutometinib (CKI27(2)/CH5126766/RO5126766/VS-6766), a novel dual RAF/MEK clamp, shows promise for patients with KRAS-mutated cancers.

Impact of immune-related adverse events on clinical outcomes in patients with advanced non-small cell lung cancer with low PD-L1 expression, focusing on pneumonitis: a multicenter retrospective study in Japan.

Background: Severe immune-related adverse events (irAEs) are often associated with combined immunotherapy and chemotherapy in patients with non-small cell lung cancer (NSCLC). However, their effect on clinical outcomes has yet to be fully elucidated. In this study, we investigated the impact of irAEs, particularly pneumonitis, on clinical outcomes in patients receiving combined immunotherapy and chemotherapy for NSCLC.

Impact of EGFR Mutation Subtypes on Response to Chemoimmunotherapy and Chemotherapy in Non-Small-Cell Lung Cancer After EGFR-TKI Failure.

Background: The efficacy of immune checkpoint inhibitor (ICI) monotherapy on non-small-cell lung cancer (NSCLC) varies by epidermal growth factor receptor (EGFR) mutation subtypes. However, the impact of these subtypes on the clinical outcomes of chemoimmunotherapy (Chemo+ICI) or platinum-based chemotherapy (Chemo) in real-world practice remains unclear.

Objective: This study evaluated the impact of EGFR mutation subtypes on NSCLC treatment outcomes of Chemo and Chemo+ICI.

Exploration of clinical Biomarkers for guiding treatment selection between chemotherapy and combination therapy with Atezolizumab, Bevacizumab, Carboplatin, and Paclitaxel in EGFR-Mutant NSCLC patients after EGFR-TKI Therapy: The SPIRAL-STEP study.

Objectives: In patients with non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations, a chemoimmunotherapy regimen of atezolizumab, bevacizumab, carboplatin, and paclitaxel (ABCP) has shown promising outcomes following treatment with EGFR-tyrosine kinase inhibitors (EGFR-TKIs). However, evidence on whether ABCP provides a survival advantage over platinum-based chemotherapy in real-world clinical settings remains limited. This study aimed to investigate the efficacy and safety of ABCP versus platinum-based chemotherapy in patients with EGFR-mutant NSCLC who underwent EGFR-TKI treatment.

FAN score predicts prognosis after platinum-based first-line chemotherapy in patients with metastatic urothelial carcinoma.

We have reported that the FAN score, which consists of the fibrosis-4 (Fib-4) index, albumin-bilirubin (ALBI) score, and neutrophil-lymphocyte ratio (NLR), is a prognostic marker for patients receiving pembrolizumab for mUC. However, it remains unclear whether the FAN score is a prognostic factor for platinum-based first-line chemotherapy. We included 126 patients with mUC who received platinum-based first-line chemotherapy.

Efficacy of Second-line Nivolumab Tyrosine Kinase Inhibitors for Renal Cell Carcinoma With Bone Metastases.

Background/aim: Combination therapy with immune checkpoint inhibitors has become the standard first-line treatment for metastatic renal cell carcinoma (mRCC), leading to changes in second-line treatment options, such as nivolumab or tyrosine kinase inhibitors (TKIs). However, very few studies have compared the efficacy of these drugs in patients with mRCC, particularly those with bone metastases (BM), which are associated with a poor prognosis. This study compared the efficacy of nivolumab and TKIs as second-line treatments for mRCC patients with BM and examined the microenvironments of primary tumors and BM lesions.

Comparative analysis of first-line treatment in NSCLC including unresectable stage III (IIIB/IIIC) and stage IV with low PD-L1 expression: Clinical trial eligible versus ineligible patients.

Background: Clinical trial eligible patients with advanced non-small cell lung cancer (aNSCLC) and low programmed cell death ligand 1 (PD-L1) expression achieve greater benefit from immune checkpoint inhibitor (ICI) combination chemotherapy (ICI-Chemo) compared with Chemo alone. We examined whether patients ineligible for clinical trials may benefit from ICI-Chemo.

Methods: This multicenter retrospective cohort study enrolled patients with aNSCLC, including unresectable Stage III (IIIB/IIIC) and IV disease with a PD-L1 tumor proportion score of 1-49% treated with ICI-Chemo or Chemo as first-line therapy from 2018 to 2023 in Japan.

Regimen Selection for Chemoimmunotherapy in Nonsquamous Non-Small Cell Lung Cancer with Low PD-L1 Expression: A Multicenter Retrospective Cohort Study.

Background: Although chemoimmunotherapy is recommended for advanced nonsquamous non-small cell lung cancer (NSCLC) with low programmed cell death ligand 1 (PD-L1) expression, no head-to-head comparisons of immune checkpoint inhibitors (ICIs) have been performed. Therefore, we compared the effect and safety of regimens in these patients to guide evidence-based treatment.

Methods: This retrospective study included patients with advanced nonsquamous NSCLC with a PD-L1 tumor proportion score of 1% to 49% administered ICI combination platinum-based chemotherapy between May 2018 and May 2023 at 19 institutions in Japan.

Bacterial information in serum extracellular vesicles reflects the inflammation of adherent perinephric fat.

Adipose tissue and bacterial flora are involved in metabolism in the human body. However, the relationship between the two remains unclear. Recently, the presence of circulating bacterial DNAs has been reported.

PSA Kinetics Affect Prognosis in Patients With Castration-resistant Prostate Cancer Treated With Enzalutamide.

Background/aim: There is little evidence regarding the predictive value of prostate-specific antigen (PSA) kinetics in patients with castration-resistant prostate cancer treated with an androgen receptor signaling inhibitor. This study investigated the correlation between PSA kinetics and prognosis in patients with castration-resistant prostate cancer treated with enzalutamide.

Patients And Methods: We analyzed data from 103 patients who received enzalutamide as primary treatment for castration-resistant prostate cancer at our hospital, focusing on the associations between overall survival and PSA kinetics variables, such as maximal PSA response, PSA nadir, and time to PSA nadir.

The Significance of Longitudinal Psoas Muscle Loss in Predicting the Maintenance Efficacy of Durvalumab Treatment Following Concurrent Chemoradiotherapy in Patients with Non-Small Cell Lung Cancer: A Retrospective Study.

Sarcopenia assessed at a single time point is associated with the efficacy of immunotherapy, and we hypothesized that longitudinal changes in muscle mass may also be important. This retrospective study included patients with non-small cell lung cancer (NSCLC) who received durvalumab treatment after concurrent chemoradiotherapy (CCRT) between January 2017 and April 2023. Muscle loss and sarcopenia were assessed based on the lumbar skeletal muscle area.

Cumulative incidence and risk factors for medication-related osteonecrosis of the jaw during long-term prostate cancer management.

Bone-modifying agents (BMA) are extensively used in treating patients with prostate cancer with bone metastases. However, this increases the risk of medication-related osteonecrosis of the jaw (MRONJ). The safety of long-term BMA administration in clinical practice remains unclear.

Epithelial-mesenchymal transition status is a remarkable biomarker for the combination treatment with avutometinib and defactinib in KRAS-mutated non-small cell lung cancer.

Background: Recent therapeutic strategies for KRAS-mutated cancers that inhibit the MAPK pathway have attracted considerable attention. The RAF/MEK clamp avutometinib (VS-6766/CH5126766/RO5126766/CKI27) is promising for patients with KRAS-mutated cancers. Although avutometinib monotherapy has shown clinical activity in patients with KRAS-mutated cancers, effective combination strategies will be important to develop.

The prognostic impact of peripheral blood eosinophil counts in metastatic renal cell carcinoma patients treated with nivolumab.

Although immune checkpoint inhibitors (ICIs) have gained approval for metastatic renal cell carcinoma (mRCC), the response rate is still limited. Therefore, it is urgent to explore novel markers of responses to ICIs that can help assess clinical benefits. Recently, it has been noted that peripheral blood eosinophil counts are an independent factor correlated with clinical outcome of ICIs in some types of cancer.

Japanese sake making using wild yeasts isolated from natural environments.

Saccharomyces cerevisiae is one of the most important microorganisms for the food industry, including Japanese sake, beer, wine, bread, and other products. For sake making, Kyokai sake yeast strains are considered one of the best sake yeast strains because these strains possess fermentation properties that are suitable for the quality of sake required. In recent years, the momentum for the development of unique sake, which is distinct from conventional sake, has grown, and there is now a demand to develop unique sake yeasts that have different sake making properties than Kyokai sake yeast strains.