An increased relative eosinophil count as a predictive dynamic biomarker in non-small cell lung cancer patients treated with immune checkpoint inhibitors.

BACKGROUND: An increased relative eosinophil count (REC) has potential as a predictive biomarker for a beneficial clinical response and outcome to cancer immunotherapies. Therefore, the present study investigated the impact of an increased posttreatment REC on the prognosis of non-small cell lung cancer (NSCLC) patients treated with immune checkpoint inhibitors (ICIs). METHODS: We retrospectively reviewed all 151 patients diagnosed with NSCLC and treated with ICI monotherapy and blood test data between March 2016 and August 2021 at National Hospital Organization Kochi Hospital and Tokushima University. RESULTS: A total of 151 patients with a mean age of 69 years were included. REC after 4 weeks of initial ICI monotherapy was higher than pretreatment REC in 87 patients but not in 64. REC after 4 weeks of the ICI treatment with and without an increased REC were 4.4 and 1.8%, respectively (p < 0.001). Disease control rates (DCR) were significantly higher in patients with than in those without an increased REC (84% vs. 47%, p < 0.001). The median overall survival (OS) of lung cancer patients with or without an increased REC were 674 and 234 days, respectively. A Kaplan-Meier univariate analysis revealed a significant difference in OS between the two groups (p < 0.001). A Cox proportional regression analysis identified an increased REC as an independent predictor of OS (p = 0.003). CONCLUSION: ICI-treated NSCLC patients with an increased REC after 4 weeks of treatment had a better DCR and prognosis than the other patients examined.

Pretreatment eosinophil counts as a predictive biomarker in non-small cell lung cancer patients treated with immune checkpoint inhibitors.

BACKGROUND: The peripheral blood eosinophil count prior to treatment has potential as a predictive biomarker for a beneficial clinical response to cancer immunotherapies. Therefore, the present study investigated the impact of the eosinophil count on overall survival (OS) in non-small cell lung cancer (NSCLC) patients treated with immune checkpoint inhibitors (ICI). METHODS: We retrospectively reviewed all patients diagnosed with NSCLC and treated with ICI monotherapy between March 2016 and August 2021 at National Hospital Organization Kochi Hospital and Tokushima University. RESULTS: A total of 166 patients were included. Fifty-five patients had an eosinophil count of less than 100 cells/µL (Eo < 100). Nighty-eight patients had an eosinophil count of 100 cells/µL or more, but less than 500 cells/µL (100 ≤ Eo < 500). Thirteen patients had an eosinophil count of 500 cells/µL or more (Eo ≥500). The median OS of all lung cancer patients was 476 days. The median OS of lung cancer patients with Eo <100, 100 ≤ Eo <500, and Eo ≥500 was 339, 667, and 143 days, respectively. A Kaplan-Meier univariate analysis showed a significant difference in OS between these three groups (p < 0.001). A Cox proportional regression analysis identified 100 ≤ Eo <500 (p = 0.04), ECOG PS score ≥ 2 (p = 0.02), tumor size ≥5 cm (p = 0.02), and PD-L1 ≥ 1% (p = 0.01) as independent predictors of OS. CONCLUSION: OS was significantly longer in ICI-treated NSCLC patients with a pretreatment eosinophil count of 100 ≤ Eo <500 than in the other patients and, thus, has potential as a new predictive biomarker.

Early mortality factors in immune checkpoint inhibitor monotherapy for advanced or metastatic non-small cell lung cancer.

PURPOSE: Immune checkpoint inhibitors (ICI) are a promising treatment, but may cause hyperprogressive disease and early death. The present study investigated early mortality factors in ICI monotherapy for lung cancer. PATIENTS AND METHODS: We retrospectively reviewed all patients diagnosed with advanced or metastatic non-small cell lung cancer (NSCLC) and treated with ICI monotherapy (nivolumab, pembrolizumab, and atezolizumab) between March 2016 and August 2021 at National Hospital Organization Kochi Hospital and Tokushima University. Early death was defined as patients who died within 60 days of ICI treatment. RESULTS: A total of 166 patients were included. The majority of patients (87%) had an Eastern cooperative oncology group (ECOG) Performance status (PS) of 0/1. There were 21 early deaths. Significant differences were observed in ECOG PS, the histological type, liver metastasis, tumor size, the white blood cell count, neutrophils (%), lymphocytes (%), the neutrophil-to-lymphocyte ratio in serum (sNLR), C-reactive protein (CRP), and albumin between the groups with or without early death. Univariate logistic regression analyses identified ECOG PS score ≥ 2, liver metastasis, tumor size ≥ 5 cm, neutrophils ≥ 69%, lymphocytes < 22%, sNLR ≥ 4, CRP ≥ 1 mg/dl, and albumin < 3.58 g/dl as significant risk factors for early death. A multivariate logistic regression analysis revealed that liver metastasis (Odds ratio [OR], 10.3; p = 0.008), ECOG PS score ≥ 2 (OR, 8.0; p = 0.007), and a smoking history (OR, 0.1; p = 0.03) were significant risk factors for early death. CONCLUSION: Liver metastases, ECOG PS score ≥ 2, and a non-smoking history are early mortality factors in ICI monotherapy for advanced or metastatic NSCLC.

Efficacy of osimertinib in epidermal growth factor receptor-mutated non-small-cell lung cancer patients with pleural effusion.

BACKGROUND: Osimertinib is a standard first-line treatment for advanced non-small-cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations. Although malignant pleural effusion (PE) is a common clinical problem in NSCLC, information about the efficacy of osimertinib in patients with PE is limited, especially regarding its efficacy in EGFR T790M-negative patients with PE remains unclear. METHODS: We retrospectively reviewed the medical records of patients with NSCLC harboring EGFR mutations who were treated with osimertinib in our institution between May 2016 and December 2020. RESULTS: A total of 63 patients with EGFR mutated NSCLC were treated with osimertinib; 33 (12 with PE) had no EGFR T790M mutation, while 30 (12 with PE) had EGFR T790M mutation. In EGFR T790M-negative NSCLC, the progression-free survival (PFS) of the patients with PE was comparable to that of the patients without PE (median PFS 19.8 vs. 19.8 months, p = 0.693). In EGFR T790M- positive NSCLC, the PFS and overall survival (OS) of the patients with PE were significantly shorter than those of the patients without PE (median PFS 16.8 vs. 8.3 months, p = 0.003; median OS 44.9 vs. 14.2 months, p = 0.007). In the multivariate analysis, the presence of PE was independently associated with shorter PFS and OS in EGFR T790M-positive NSCLC patients, but not EGFR T790M-negative patients. CONCLUSIONS: These data suggest the efficacy of osimertinib may differ between EGFR T790M-positive and -negative NSCLC patients with PE.

A case of pulmonary pleomorphic carcinoma with preexisting interstitial pneumonia successfully treated with pembrolizumab.

Pulmonary pleomorphic carcinoma is often refractory to chemotherapy and follows an aggressive clinical course. Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of advanced lung cancer, and a few cases with pleomorphic carcinoma have been reported to show tumor shrinkage after therapy with ICIs. When treating patients with ICIs, patient selection is essential, and monitoring and management of immune-related adverse events, including pneumonitis, are needed. We herein report a case of pulmonary pleomorphic carcinoma with preexisting interstitial pneumonia treated with pembrolizumab, antiprogrammed cell death 1 antibody. Our report highlights important considerations necessary when treating advanced pleomorphic carcinoma patients complicated with interstitial pneumonia. We also review the literature regarding the use of ICIs in such patients.

[Endoventricular Stepwise Plication for Left Ventricular Aneurysm].

A 69-year-old man was treated with oral anticoagulation for the left ventricular (LV) aneurysm. Echocardiography revealed dyskinetic apex with a mobile thrombus. The estimated LV end-diastolic and end-systolic volume index (LVEDVI, LVESVI) was 76 and 44 ml/m2, respectively. After the LV was opened at the apex parallel to the left anterior descending artery, removal of LV thrombus was performed. LV volume was 70 ml, and diameter of LV aneurysm was 3 cm. After setting a neo-apex, the boundary between the normal and aneurysmal scar tissue were doubly encircled by a pledgeted 2-0 polypropylene suture, and preserved the same diameter as the "aneurysmal neck" (3 cm) in order to secure the minimal residual LV volume. Similarly, second and third circular stitches were placed toward the neo-apex to make the ventricle into an elliptical shape. A postoperative echocardiography showed a well-reconstructed physiologic shape, LV volume( LVEDVI 62 ml/m2, LVESVI 27 ml/m2), and improved LV function.

Bioelectrical impedance analysis for perioperative water management in adult cardiovascular valve disease surgery.

PURPOSE: Bioelectrical impedance analysis (BIA) has been used recently to measure the body water of patients with acute heart failure. We used BIA in this study to better understand, and possibly identify a predictive marker for, perioperative water behavior in cardiac surgery patients. METHODS: We measured body water and studied its behavior in 44 patients undergoing surgery for cardiac valvular disease at our hospital. Measurements included the levels of extracellular water (ECW), intracellular water (ICW), and total body water, the edema index (EI), and the ratio of ECW to total body water. The first measured EI was defined as the "preoperative EI" and the maximum as the "peak EI". RESULTS: A negative correlation was found between the preoperative EI and the preoperative estimated glomerular filtration rate (eGFR) (R = 0.644, p < 0.001). Positive correlations were found between the peak EI and the ICU stay (R = 0.625, p < 0.001), the peak EI and the ventilation time (R = 0.366, p < 0.01), and the preoperative EI and the ICU stay (R = 0.464, p = 0.026). CONCLUSION: The EI is possibly a predictive marker for perioperative water management in cardiac surgery.

Salvage therapy with azacitidine for pediatric acute myeloid leukemia with t(16;21)(p11;q22)/FUS-ERG and early relapse after allogeneic blood stem cell transplantation: A case report.

Acute myeloid leukemia (AML) with FUS-ERG has a poor prognosis regardless of allo-hematopoietic stem cell transplantation (HSCT). Maintenance therapy such as azacitidine after allo-HSCT for AML with FUS-ERG may be clinically meaningful.

Administration of high dose eicosapentaenoic acid enhances anti-inflammatory properties of high-density lipoprotein in Japanese patients with dyslipidemia.

OBJECTIVE: It has been reported that high-density lipoprotein (HDL) loses anti-inflammatory function and promotes atherosclerosis under pathological conditions. However, no pharmacological therapy to improve HDL function is currently available. We aimed to evaluate the effect of oral administration of eicosapentaenoic acid (EPA) on HDL function. METHODS: Japanese patients with dyslipidemia were treated with EPA (1800 mg/day, 4 weeks), and anti-inflammatory functions of HDL were assessed utilizing in vitro cell-based assays. RESULTS: The EPA treatment did not change serum cholesterol and triglyceride levels, but it significantly increased EPA concentrations in the serum and HDL fraction. The EPA/arachidonic acid ratio in the HDL was in proportion to that in the serum, suggesting that the orally administered EPA was efficiently incorporated into the HDL particles. The HDL after EPA treatment showed significantly increased activity of anti-oxidative enzyme, paraoxonase-1. In addition, the EPA-rich HDL significantly improved endothelial cell migration, and markedly inhibited cytokine-induced expression of vascular cell adhesion molecule-1, in human umbilical vein endothelial cells, compared to HDL before the EPA treatment. Moreover, the EPA-rich HDL augmented cholesterol efflux capacity from macrophages. CONCLUSION: Oral administration of EPA regenerated anti-oxidative and anti-inflammatory functions of HDL, and promoted cholesterol efflux from macrophages. Therefore, EPA may transform "dysfunctional HDL" to "functional", in patients with coronary risk factors.