Altered Expression of Astrocytic ATP Channels and Ectonucleotidases in the Cerebral Cortex and Hippocampus of Chronic Social Defeat Stress-Susceptible BALB/c Mice.

The increasing number of patients with depressive disorder is a serious socioeconomic problem worldwide. Although several therapeutic agents have been developed and used clinically, their effectiveness is insufficient and thus discovery of novel therapeutic targets is desired. Here, focusing on dysregulation of neuronal purinergic signaling in depressive-like behavior, we examined the expression profiles of ATP channels and ectonucleotidases in astrocytes of cerebral cortex and hippocampus of chronic social defeat stress (CSDS)-susceptible BALB/c mice. Mice were exposed to 10-d CSDS, and their astrocytes were obtained using a commercially available kit based on magnetic activated cell sorting technology. In astrocytes derived from cerebral cortex of CSDS-susceptible mice, the expression levels of mRNAs for connexin 43, P2X7 receptors and maxi anion channels were increased, those for connexin 43 and P2X7 receptors being inversely correlated with mouse sociability, and the expression of mRNAs for ecto-nucleoside triphosphate diphosphohydrase 2 and ecto-5'nucleotidase was decreased and increased, respectively. On the other hand, the alteration profiles of ATP channels and ectonucleotidases in hippocampal astrocytes of CSDS-susceptible mice were different from in the case of cortical astrocytes, and there was no significant correlation between expression levels of their mRNAs and mouse sociability. These findings imply that increased expression of ATP channels in cerebral cortex might be involved in the development of reduced sociability in CSDS-subjected BALB/c mice. Together with recent findings, it is suggested that ATP channels expressed by cortical astrocytes might be potential therapeutic targets for depressive disorder.

Establishment of an artificial urine model in vitro and rat or pig model in vivo to evaluate urinary crystal adherence.

The current study aimed to establish an experimental model in vitro and in vivo of urinary crystal deposition on the surface of ureteral stents, to evaluate the ability to prevent crystal adhesion. Non-treated ureteral stents were placed in artificial urine under various conditions in vitro. In vivo, ethylene glycol and hydroxyproline were administered orally to rats and pigs, and urinary crystals and urinary Ca were investigated by Inductively Coupled Plasma-Optical Emission Spectrometer. in vitro, during the 3- and 4-week immersion periods, more crystals adhered to the ureteral stent in artificial urine model 1 than the other artificial urine models (p < 0.01). Comparing the presence or absence of urea in the composition of the artificial urine, the artificial urine without urea showed less variability in pH change and more crystal adhesion (p < 0.05). Starting the experiment at pH 6.3 resulted in the highest amount of crystal adhesion to the ureteral stent (p < 0.05). In vivo, urinary crystals and urinary Ca increased in rat and pig experimental models. This experimental model in vitro and in vivo can be used to evaluate the ability to prevent crystal adhesion and deposition in the development of new ureteral stents to reduce ureteral stent-related side effects in patients.

Comparison of the efficacy of first­/second­generation EGFR­tyrosine kinase inhibitors and osimertinib for EGFR­mutant lung cancer with negative or low PD­L1 expression.

In epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) with negative or low programmed death ligand-1 (PD-L1) expression, the acquisition rate of the T790M mutation is higher after treatment with first-/second-generation EGFR-tyrosine kinase inhibitors (TKIs) and the progression-free survival (PFS) is longer in patients treated with osimertinib. The present study compared the clinical course after the initiation of each EGFR-TKI monotherapy in patients with EGFR-mutant NSCLC with negative or low PD-L1 expression. Data of patients with EGFR-mutant NSCLC with negative or low PD-L1 expression who were treated with EGFR-TKI monotherapy were retrieved and retrospectively analyzed. Between June 2013 and November 2023, 26 and 29 patients were treated with first-/second-generation EGFR-TKIs and osimertinib, respectively. The PFS time was longer in patients treated with osimertinib (median, 22.5 months) than in those treated with first-/second-generation EGFR-TKIs (median, 12.9 months). However, the EGFR-TKI treatment duration, defined as the PFS for osimertinib, or the sum of the PFS for first-/second-generation EGFR-TKIs and sequential osimertinib therapy after the acquisition of the T790M mutation, was similar between patients treated with first-/second-generation EGFR-TKIs (median, 23.0 months) and osimertinib (median, 22.5 months). The Cox proportional hazard model suggested that there was no significant difference in the EGFR-TKI treatment duration between patients treated with first-/second-generation EGFR-TKIs and patients treated with osimertinib (hazard ratio, 1.31, 95% CI, 0.55-3.13). In conclusion, first-/second-generation EGFR-TKIs and osimertinib were associated with a similar EGFR-TKI treatment duration in patients with EGFR-mutant NSCLC with negative or low PD-L1 expression. The findings suggested that both treatments are promising for this population.

Pure Red Cell Aplasia and Chromosomal Abnormality in a Patient With Lung Adenocarcinoma Receiving Immune Checkpoint Inhibitors: A Case Report.

BACKGROUND/AIM: Immune checkpoint inhibitors can induce immune-related adverse events in various organs, thus careful observation is required. CASE REPORT: A 69-year-old man was diagnosed with advanced lung adenocarcinoma and treated with combined therapy of carboplatin plus pemetrexed plus pembrolizumab. After two cycles of treatment, anemia was noted. Myelosuppression due to cytotoxic anticancer agents was suspected and the cytotoxic agents were discontinued, followed by three courses of pembrolizumab monotherapy. However, the anemia persisted, requiring red blood cell transfusions. A bone marrow biopsy revealed erythroblast hypoplasia and chromosomal abnormalities, resulting in a diagnosis of pure red cell aplasia. These adverse events were considered immune-related because of the treatment history with an immune checkpoint inhibitor, and 60 mg/day (1 mg/kg/day) of prednisolone was initiated. Anemia improved, and it did not recur during the tapering of prednisolone. CONCLUSION: Immune-related pure red cell aplasia should be considered for patients presenting anemia during treatment with immune checkpoint inhibitors.

Influence of etching mode on bonding performance of self-adhesive flowable resin composites to bovine teeth.

This study aimed to evaluate the bonding performance of self-adhesive flowable resin composites (SARs) to bovine teeth. Three SARs, one experimental, and two commercially available products, were used. The study parameters were shear bond strength (SBS), microleakage, and scanning electron microscopy (SEM) evaluation of bonding interfaces. The SBS of the materials was 14.1-15.1 MPa to enamel, 22.2-23.2 MPa to etched enamel, and 7.4-10.7 MPa to dentin. Specimens with pre-etching showed lower microleakage scores than those without pre-etching. SEM images of the interfaces of the materials showed excellent adaptation regardless of the substrate or etching mode. The study results indicate that enamel pre-etching can improve the bonding performance of SARs.

Immune Checkpoint Inhibitor Therapy for Patients With Non-small Cell Lung Cancer Ineligible for Platinum Doublet Chemotherapy.

BACKGROUND/AIM: Combined therapy with immune checkpoint inhibitors plus platinum doublet chemotherapy has a survival advantage over platinum doublet chemotherapy in patients with non-small cell lung cancer. However, a variety of factors make it difficult to administer treatment with platinum doublet chemotherapy in many patients in clinical practice and there are few reports on the efficacy and safety of first-line treatments with immune checkpoint inhibitors for patients who are ineligible for platinum doublet chemotherapy. This observational study aimed to evaluate the efficacy and safety of first-line immune checkpoint inhibitor therapy for this population. PATIENTS AND METHODS: We retrospectively assessed the survival and adverse events from the initiation of first-line immune checkpoint inhibitor therapy, including pembrolizumab or nivolumab plus ipilimumab in patients with non-small cell lung cancer who were ineligible for platinum doublet chemotherapy. RESULTS: Data from 48 patients were analyzed. Seventeen patients showed a performance status (PS) of ≥2 while 16 and 15 patients were considered ineligible for platinum doublet chemotherapy because of age and comorbidities, respectively. The median (95% confidential interval, CI) progression-free survival (PFS) and overall survival (OS) of the 48 patients were 7.1 (1.7-13.7) and 31.7 (8.8-not estimated) months, respectively. The two-year PFS and OS rates (95% CI) were 30.8% (18.2%-47.2%) and 50.7% (33.7%-67.7%), respectively. In patients with a PS of ≥2, the median (95% CI) PFS and OS were 1.6 (1.2-not estimated) and 5.5 (2.3-not estimated) months, respectively. The two-year PFS and OS rates (95% CI) were 34.3% (15.8%-59.2%) and 45.3% (22.2%-70.7%), respectively. CONCLUSION: Patients with non-small cell lung cancer and a PS of 0-1 who were ineligible for platinum doublet chemotherapy had favorable outcome after the initiation of ICI therapy, and even in patients with a PS of ≥2, they achieved high two-year PFS and OS rates.

Scanning electron microscopy observation of dentin bond interfaces in different types of resin luting cements.

This study aimed to observe and compare the resin luting cement (RLC)/dentin interfaces of different types of RLC systems with scanning electron microscopy (SEM). This study evaluated six self-adhesive resin luting cement systems (SARLCs), four systems combining a SARLC with a tooth primer (SARLCPs), and six conventional resin luting cement systems (CVRLCs). Cured resin composite rods were bonded to bovine dentin using RLCs in different etching modes. The morphological features at the interfaces were observed using SEM. Although all RLCs in etch-&-rinse (ER) mode showed a clear hybrid layer, most SARLCs had a thinner and more porous hybrid layer than the SARLCPs and CVRLCs. All SARLCPs with primer and CVRLCs showed a thin high-density layer below the primer layer in both etching modes. CVRLCs and SARLCPs with primer treatment systems may be more versatile and reliable when compared to simplified RLC systems.

Influence of different curing modes on the bonding effectiveness of self-adhesive resin luting cements in combination with universal adhesives.

OBJECTIVES: This study aimed to investigate the immediate dentin bond performance and bond durability of self-adhesive resin luting cements (RLCs) in combination with universal adhesives in different curing modes. METHODS: Two self-adhesive RLCs were used with universal adhesives as primers. They were also used alone as self-adhesive RLCs. Two multiple-step RLC systems were used as comparison materials. To measure the shear bond strength (SBS) in different curing modes, 12 specimens were prepared for each group. Stainless-steel rods were bonded to bovine dentin, and the bonded specimens were assigned to the baseline group (stored for 24 h) and artificially aged group (thermal cycling [TC], 10,000 cycles). After each storage period, the SBS of the bonded specimens was measured. The Knoop hardness number (KHN) of the cured RLCs was measured with or without primer application in different curing modes at 24 h and after 10,000 TC. The representative RLC/dentin interfaces were observed using scanning electron microscopy (SEM). RESULTS: Dentin SBS was significantly influenced by the RLC system but not by the curing mode. Self-adhesive RLCs alone showed significantly lower SBS values than self-adhesive RLCs with primer regardless of the curing mode or storage period. The storage period, curing mode, and RLC system significantly influenced the KHN. SIGNIFICANCE: The use of universal adhesives as a primer may help enhance the immediate dentin bond performance and bond durability of self-adhesive RLCs.

Treatment of saliva contamination of resin core foundation before adhesive luting.

This study aimed to evaluate the influence of surface pretreatment on the shear bond strength of resin luting cement to saliva-contaminated resin core foundation. The surface free energy (γS) of the adherent surfaces was examined. The two-way analysis of variance revealed that the surface pretreatment and storage conditions had a significant effect on the strength of the bond to resin core foundation. The γS values of the saliva-contaminated group were significantly lower than those of the other groups, and they tended to improve after surface pretreatment. The tendency of improvement in γS values differed depending on the type of pretreatment agents. Surface treatment with solutions containing functional monomers is effective in removing saliva contaminants from the resin core foundation surfaces and in creating an effective bonding surface for the resin luting cement.

Peripheral CD4 memory T cells predict the efficacy of immune checkpoint inhibitor therapy in patients with non-small cell lung cancer.

Immune checkpoint inhibitors have significantly improved the prognosis in patients with non-small cell lung cancer, compared with cytotoxic agents. However, the prediction of treatment response is often difficult, even after assessing the tumor programmed death-ligand 1 expression. We conducted this observational study to analyze the association between the differentiation of peripheral CD4 + T cells and the efficacy of immune checkpoint inhibitor therapy. We enrolled patients who were diagnosed with non-small cell lung cancer and received immune checkpoint inhibitor therapy between 2020 and 2022. Blood samples were collected at the start of immune checkpoint inhibitor therapy, and the expressions of PD-1, CCR7, and CD45RA in peripheral CD4 + T cells were analyzed by flow cytometry. The association between the findings of flow cytometry and survival after the initiation of the immune checkpoint inhibitor therapy was evaluated. Forty patients with non-small cell lung cancer were enrolled. The Cox proportional hazards model showed that an increased proportion of CD45RA-CD4 + T cells was associated with a reduced risk of progression after adjustment for performance status, tumor programmed death-ligand 1 expression level, mutation status of the epidermal growth factor receptor gene, and combined therapy with cytotoxic agents. The present study showed that the proportion of peripheral CD45RA- CD4 + T cells was associated with progression-free survival after the initiation of immune checkpoint inhibitor therapy, independent of several clinical factors.

Influence of surface roughness of universal shade resin composites on color adjustment potential.

This study aimed to determine the influence of surface roughness of the color adjustment potential restoration of universal resin composites. A structural colored resin composite (Omnichroma, OC) and a pigment-employed universal shade resin composite (Beautifil Unishade, BU) were used. Each resin composite was placed in a cavity to determine its ability to match the color of artificial teeth. The surface of the resin composites was polished with #800- or #2000-grit SiC paper before performing color measurements. One-way analysis of variance and Tukey post hoc tests were performed (α=0.05). The color difference (ΔE*ab) ranged from 2.5-3.9 for OC and 1.8-8.7 for BU. OC has a more stable color adjustment than BU. The color adjustment potential of universal resin composites was affected by the surface roughness of the restorations.

Prenylated-coumarins from Gmelina arborea and evaluation for neurotrophic activity.

A MeOH extract of the stem of Gmelina arborea Roxb. ex Sm. (Lamiaceae) exhibited neurite outgrowth-promoting activity in NGF-mediated PC12 cells. Bioassay-guided fractionation resulted in the isolation of eight previously undescribed prenylated coumarin compounds along with nine known compounds. Structural elucidation of these compounds was accomplished by analysis of extensive spectroscopic data, comparison with the literature, and chemical reactions. It was the first time to find prenylated coumarin compounds from G. arborea. Among the isolated compounds, N-methylflindersine and artanin showed neurite outgrowth-promoting activity in NGF-mediated PC12 cells.

Association Between the Severity of Immune-related Adverse Events and the Prognosis in Patients With Non-small Cell Lung Cancer Receiving Treatment With Immune Checkpoint Inhibitors.

BACKGROUND/AIM: Among patients with non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICI), survival is reported to be longer in those experiencing immune-related adverse events (irAEs). We evaluated the progression-free survival (PFS) in the absence of further treatment after ICI therapy was discontinued because of the emergence of irAEs in patients with NSCLC. PATIENTS AND METHODS: Data from patients with NSCLC in whom ICI therapy was discontinued because of the development of irAEs were retrospectively analyzed. The primary endpoint was the PFS from the last day of administration of ICIs, in the absence of any further treatment. RESULTS: A total of 162 patients with NSCLC received treatment with ICIs between January 2016 and December 2021. Among them, ICI therapy was discontinued in 33 patients because of the appearance of irAEs. The median (95% confidence interval) PFS in the absence of any treatment after the last administration of ICIs was 7.2 (4.2-12.3) months. According to the Common Terminology Criteria for Adverse Events, the Cox proportional hazards model was used to identify the severity of irAEs, which were determined to be significantly associated with the PFS in the absence of any further treatment after the last administration of ICI therapy. CONCLUSION: Although the present study showed that the PFS in patients with NSCLC was relatively long in the absence of any further treatment after the last administration of ICIs, the PFS was associated with the severity of the irAEs, and some patients showed early disease progression or death.

Associations of immune checkpoint inhibitor therapy efficacy with clinical parameters and tumor­infiltrating CD68­positive cell counts in patients with EGFR­mutant non­small cell lung cancer.

Immune checkpoint inhibitor (ICI) therapy has been less effective in patients with non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations than in patients with EGFR wild-type NSCLC. This retrospective study was conducted to investigate the associations of clinical parameters with the efficacy of ICI therapy in patients with EGFR-mutant NSCLC. Clinical information was retrieved from the medical charts, and immunohistochemical analysis was performed in some cases to determine the tumor-infiltrating CD68-positive cell count. Data from 46 patients were included in the analysis. The median (95% confidence interval) progression-free survival and overall survival from the initiation of ICI therapy was 1.4 months (1.0-1.7 months) and 6.4 months (3.9-19.0 months), respectively. Analysis using a Cox proportional hazards model revealed that tumor programmed death-ligand 1 expression was associated with the overall survival of patients with EGFR-mutant NSCLC after ICI treatment. The tumor-infiltrating CD68-positive cell count was evaluated in 11 patients. Comparison using the log-rank test revealed that the progression-free survival time after ICI treatment was longer in the patients with lower tumor-infiltrating CD68-positive cell counts than those with higher tumor-infiltrating CD68-positive cell counts. The present analysis demonstrated that PD-L1 expression and the tumor-infiltrating CD68-positive cell count may be associated with the efficacy of ICI therapy in patients with NSCLC harboring EGFR mutations.

Efficacy of immune checkpoint inhibitor therapy in patients with pulmonary sarcomatoid carcinoma in clinical practice.

OBJECTIVE: Studies have suggested the potential efficacy of immune checkpoint inhibitors (ICIs) for pulmonary sarcomatoid carcinoma. This multicenter observational study was conducted to evaluate the efficacy of systemic ICI therapy and chemoradiation followed by durvalumab therapy for pulmonary sarcomatoid carcinoma. METHODS: We analyzed the data of patients with pulmonary sarcomatoid carcinoma who received systemic ICI therapy or chemoradiation followed by durvalumab therapy between 2016 and 2022. RESULTS: In this study, data of a total of 22 patients who received systemic ICI therapy and four patients who received chemoradiation followed by durvalumab therapy were analyzed. In the patients who received systemic ICI therapy, the median progression-free survival after initiation of therapy was 9.6 months, and the overall survival did not reach the median. The 1-year progression-free survival rate and overall survival rate were estimated to be 45.5% and 50.1%, respectively. Although the log-rank test revealed no significant association between the tumor expression level of programmed death ligand-1 (tumor proportion score evaluated using 22C3 antibody: ≥50% vs. <50%) and the survival duration, the majority of patients showing long-term survival showed a tumor proportion score of ≥50%. Of four patients treated with chemoradiation followed by durvalumab therapy, two patients showed an overall survival of ≥30 months, whereas the remaining two patients died within 12 months. CONCLUSION: The progression-free survival of patients who received systemic ICI therapy was 9.6 months, suggesting that ICI therapy might be effective in patients with pulmonary sarcomatoid carcinoma.

Association of Tumor PD-L1 Expression With Time on Treatment Using EGFR-TKIs in Patients With EGFR-Mutant Non-small Cell Lung Cancer.

BACKGROUND/AIM: The association between tumor PD-L1 expression and the rate of acquisition of the T790M mutation during treatment with first-/second-generation epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) is a matter of study. This retrospective study was conducted to evaluate the association of tumor PD-L1 expression with the time on treatment under EGFR-TKIs in patients with EGFR-mutant non-small cell lung cancer (NSCLC), treated with first-/second-generation EGFR-TKIs. PATIENTS AND METHODS: We conducted a retrospective review of the medical charts of patients with EGFR-mutant NSCLC treated with first- /second-generation EGFR-TKIs. Time on treatment with EGFR-TKIs was defined as the sum of progression-free survival period (PFS) from the start of treatment with first- /second-generation EGFR-TKIs and the PFS from the start of osimertinib treatment after acquisition of the T790M mutation. Tumor PD-L1 expression was evaluated using the 22C3 antibody. RESULTS: Data of a total of 49 patients were analyzed, including 20 patients with negative tumor PD-L1 expression (tumor proportion score <1%) and 29 patients with positive tumor PD-L1 expression (tumor proportion score ≥1%). In the negative tumor PD-L1 expression group, the T790M mutation was detected in 12 (75%) of the 16 patients. In the positive tumor PD-L1 expression group, the T790M mutation was detected 6 (31.6%) out of the 19 patients in whom it was tested. The median (95% confidence interval) time on treatment with EGFR-TKIs was 21.7 (12.9-24.8) months and 12.3 (5.6-22.2) months in the negative and positive tumor PD-L1 expression groups, respectively. Analysis using a Cox proportional hazards model identified performance status and presence/absence of tumor PD-L1 expression as significantly associated with the time on treatment with EGFR-TKIs. CONCLUSION: EGFR-mutant NSCLC patients with negative tumor PD-L1 expression showed a higher rate of acquisition of the T790M mutation and implementation rate of osimertinib therapy, leading to a longer time on treatment with EGFR-TKI.

Case Series of Pleomorphic Carcinoma of the Lung Treated With Immune Checkpoint Inhibitors.

AIM: We report, herein, three cases of pleomorphic carcinoma of the lung treated with immune checkpoint inhibitors. Case 1: A 73-year-old man was diagnosed as having pleomorphic carcinoma of the lung and treated with pembrolizumab alone. However, he showed no response and died 4 months after the initiation of the treatment. Case 2: A 66-year-old man was diagnosed as having pleomorphic carcinoma of the lung. He was started on a combination regimen of pembrolizumab plus carboplatin plus nab-paclitaxel, and a remarkable response was observed. Case 3: A 49-year-old man was diagnosed as having pleomorphic carcinoma of the lung. He was started on pembrolizumab monotherapy as second-line treatment. Eleven months after the treatment initiation, computed tomography revealed the decrease of tumor diameter. CONCLUSION: Immune checkpoint inhibitor therapy is expected to improve the prognosis of patients with pleomorphic carcinoma of the lung.

Immune Checkpoint Inhibitor for Non-small Cell Lung Cancer With Negative or Low Tumor PD-L1 Expression.

Background/Aim: We conducted a retrospective analysis of the survival durations of 25 patients diagnosed as having non-squamous cell non-small cell lung cancer with negative or low tumor programmed death-ligand 1 (PD-L1) expression treated with immune checkpoint inhibitor (ICI) monotherapy. Patients and Methods: The progression-free (PFS) and overall (OS) survival were calculated from the initiation of ICI monotherapy. The association between the patient characteristics and the PFS was analyzed using Cox proportional hazards model. Results: The median PFS was 2.6 months, and the 12-month PFS rate was 9.3%. The median OS was 5.5 months, and the 12-month OS rate was 39.8%. A Cox proportional hazards model identified the neutrophil/lymphocyte ratio and presence of liver metastasis as being significantly associated with PFS. Conclusion: Our findings suggest that a subset of patients with non-squamous cell non-small cell lung cancer who show negative or low tumor PD-L1 expression could benefit from ICI monotherapy.

Association of Tumor PD-L1 Expression with the T790M Mutation and Progression-Free Survival in Patients with EGFR-Mutant Non-Small Cell Lung Cancer Receiving EGFR-TKI Therapy.

BACKGROUND: Among patients with non-small cell lung cancer (NSCLC), we compared the progression-free survival (PFS) and proportion of acquisition of T790M mutation of the epidermal growth receptor gene (EGFR) after first-line treatment with epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) in patient groups with and without tumor expression of programmed death ligand-1 (PD-L1). METHODS: Data of patients with EGFR-mutant NSCLC were retrospectively analyzed. Tumor PD-L1 expression was evaluated by immunohistochemistry using the 22C3 antibody. T790M gene mutation was evaluated by Cobas EGFR assay using tissues or humoral specimens. RESULTS: Data of 47 patients with EGFR-mutant NSCLC were analyzed. The median (95% confidence interval) PFS in the PD-L1-negative and -positive patient groups were 12.9 (9.7-15.4) months and 9.0 (5.1-12.3) months, respectively (p = 0.029). T790M gene mutation was analyzed in 27 patients. The proportion of acquisition of T790M mutation of EGFR after first-line treatment with an EGFR-TKI was higher in the PD-L1-negative patient group than in the PD-L1-positive patient group (8/11 patients (72.7%) vs. 4/16 patients (25.0%); p = 0.022). CONCLUSIONS: Patients with negative tumor PD-L1 expression showed longer PFS and a higher proportion of acquisition of T790M mutation of EGFR after first-line treatment with an EGFR-TKI.

Relationship between Patient Characteristics and the Timing of Provision of Explanation about DNAR to Patients with Advanced Lung Cancer.

Objective The aim of the present study was to analyze the relationship between the patient characteristics and the timing of provision of an explanation about "Do Not Attempt Resuscitation (DNAR)" by attending physicians to advanced lung cancer patients. Methods We conducted a retrospective analysis of patients with advanced or postoperative recurrent lung cancer in whom systemic therapy was initiated between 2015 and 2016. Results The data of a total of 74 patients with lung cancer, including 59 patients with non-small cell lung cancer and 15 with small cell lung cancer were analyzed. The median overall survival of the patients was 10.0 months. Records of the explanation about DNAR by the physicians were available for 57 of the 74 (77.0%) patients. For 48 (64.9%) patients, the explanation was provided after the discontinuation of anticancer treatment, and for 9 (12.2%) patients, it was provided during the course of anticancer treatment. The provision of an explanation about DNAR during the course of treatment was associated with a poor performance status at the start of treatment (p=0.028), the tumor histology (p=0.037), the presence of driver gene mutation in the tumor (p=0.029), and shorter survival after the discontinuation of anticancer treatment (p<0.001). Conclusion The results suggested that the timing of provision of an explanation about DNAR was associated with patient characteristics and the predicted prognosis.