The study of greening shotcrete considered the landscape

This study concerns the protection method and the natural maintenance of aging shotcrete. In Japan, in the high economic growth period in 1960’s, a great number of slopes were formed to construct many roads and most slope protection methods were to cover shotcrete on the slope. In recent years, with concerns about the environmental and landscape, the construction of shotcrete is decreasing. However, even now about 7,000,000㎡of shotcrete is laid every year, and it is predicted that the total amount of shotcrete is enormous. Now, about 60 years passes after a great number of shotcrete was laid, and shotcrete have been aging. Therefore, we suggested the method which construct for directly aging shotcrete in the protection method and the greening protection method is considering cost and risk with new construction. We adopt the protection method by rock bolt and rope net. In this study, at first, we establish the vegetation base suitable for growth of plants which can be use together with the protection method. And then, we install many kind of the vegetation base that gave the vegetation on a model shotcrete. Finally, we compared the rates of water retention and vegetation growth

Development of monitoring tool by pharmacists

Purpose: Drug side effects often lead to serious outcomes. Administration of second-generation antipsychotics has resulted in diabetic ketoacidosis and diabetic coma leading to death. Therefore, pharmacists are required to collect information on clinical test values, determine the appropriate test timing, and coordinate with doctors for further clinical laboratory orders, all of which are labor- and time-intensive tasks. In this study, we developed a side effect-monitoring tool and aimed to clarify the influence and efficiency of monitoring side effects by using the tool in patients taking atypical antipsychotics in whom it is necessary to check clinical test values such as blood sugar levels. Methods: We extracted clinical test values for patients treated with second-generation antipsychotics from electronic medical records. The test values are automatically displayed in the side effect grade classification specified by CTCAE ver. 4.0. A database was constructed using scripts to provide alerts for the timing of clinical testing. The pharmacist used this tool to confirm clinical test values for patients taking medication and requested the physician to inspect orders based on the appropriate test timings. Results: The management tool reduced the pharmacists’ effort in collecting information on patients’ prescription status and test values. It enabled patients to undergo tests at the appropriate time according to the progression of glucose metabolism and allowed for easy monitoring of side effects. Conclusion: The results suggested that regardless of pharmacists’ experience or skill, the introduction of this tool enables centralization of side-effect monitoring and can contribute to proper drug use

Early Circulating Tumor DNA Dynamics and Efficacy of Lorlatinib in Patients With Treatment-Naive, Advanced, ALK-Positive NSCLC

Introduction: Circulating tumor DNA (ctDNA) has been used as a biomarker for prognostication and response to treatment. Here, we evaluate ctDNA as a potential biomarker for response to lorlatinib, a third-generation ALK tyrosine kinase inhibitor in patients with treatment-naive, advanced, ALK-positive NSCLC in the ongoing phase 3 CROWN study (NCT03052608). Methods: Molecular responses were calculated using mean variant allele frequency (VAF), longitudinal mean change in VAF (dVAF), and ratio to baseline. Efficacy assessments (progression-free survival [PFS] and objective response rate) were paired with individual patient ctDNA and analyzed for association. Results: Compared with baseline, mean VAF at week 4 was decreased in both treatment arms. Considering all detected somatic variants, a reduction in dVAF (≤0) was associated with a longer PFS in the lorlatinib arm. The hazard ratio (HR) for a dVAF less than or equal to 0 versus more than 0 was 0.50 (95% confidence interval [CI]: 0.23–1.12) in the lorlatinib arm. A similar association was not observed for crizotinib (HR = 1.00, 95% CI: 0.49–2.03). Comparing molecular responders with nonresponders, patients treated with lorlatinib who had a molecular response had longer PFS (HR = 0.37, 95% CI: 0.16–0.85); patients treated with crizotinib who had a molecular response had similar PFS as those without a molecular response (HR = 1.48, 95% CI: 0.67–3.30). Conclusions: In patients with treatment-naive, advanced, ALK-positive NSCLC, early ctDNA dynamics predicted better outcome with lorlatinib but not with crizotinib. These results suggest that ctDNA may be used to monitor and potentially predict efficacy of lorlatinib treatment.</p

Early Circulating Tumor DNA Dynamics and Efficacy of Lorlatinib in Patients With Treatment-Naive, Advanced, ALK-Positive NSCLC

Introduction: Circulating tumor DNA (ctDNA) has been used as a biomarker for prognostication and response to treatment. Here, we evaluate ctDNA as a potential biomarker for response to lorlatinib, a third-generation ALK tyrosine kinase inhibitor in patients with treatment-naive, advanced, ALK-positive NSCLC in the ongoing phase 3 CROWN study (NCT03052608). Methods: Molecular responses were calculated using mean variant allele frequency (VAF), longitudinal mean change in VAF (dVAF), and ratio to baseline. Efficacy assessments (progression-free survival [PFS] and objective response rate) were paired with individual patient ctDNA and analyzed for association. Results: Compared with baseline, mean VAF at week 4 was decreased in both treatment arms. Considering all detected somatic variants, a reduction in dVAF (≤0) was associated with a longer PFS in the lorlatinib arm. The hazard ratio (HR) for a dVAF less than or equal to 0 versus more than 0 was 0.50 (95% confidence interval [CI]: 0.23–1.12) in the lorlatinib arm. A similar association was not observed for crizotinib (HR = 1.00, 95% CI: 0.49–2.03). Comparing molecular responders with nonresponders, patients treated with lorlatinib who had a molecular response had longer PFS (HR = 0.37, 95% CI: 0.16–0.85); patients treated with crizotinib who had a molecular response had similar PFS as those without a molecular response (HR = 1.48, 95% CI: 0.67–3.30). Conclusions: In patients with treatment-naive, advanced, ALK-positive NSCLC, early ctDNA dynamics predicted better outcome with lorlatinib but not with crizotinib. These results suggest that ctDNA may be used to monitor and potentially predict efficacy of lorlatinib treatment.</p

Japanese Lung Cancer Society Guidelines for Stage IV NSCLC With EGFR Mutations

Patients with NSCLC in East Asia, including Japan, frequently contain EGFR mutations. In 2018, we published the latest full clinical practice guidelines on the basis of those provided by the Japanese Lung Cancer Society Guidelines Committee. The purpose of this study was to update those recommendations, especially for the treatment of metastatic or recurrent EGFR-mutated NSCLC. We conducted a literature search of systematic reviews of randomized controlled and nonrandomized trials published between 2018 and 2019 that multiple physicians had reviewed independently. On the basis of those studies and the advice from the Japanese Society of Lung Cancer Expert Panel, we developed updated guidelines according to the Grading of Recommendations, Assessment, Development, and Evaluation system. We also evaluated the benefits of overall and progression-free survival, end points, toxicities, and patients’ reported outcomes. For patients with NSCLC harboring EGFR-activating mutations, the use of EGFR tyrosine kinase inhibitors (EGFR TKIs), especially osimertinib, had the best recommendation as to first-line treatment. We also recommended the combination of EGFR TKI with other agents (platinum-based chemotherapy or antiangiogenic agents); however, it can lead to toxicity. In the presence of EGFR uncommon mutations, except for an exon 20 insertion, we also recommended the EGFR TKI treatment. However, we could not provide recommendations for the treatment of EGFR mutations with immune checkpoint inhibitors, including monotherapy, and its combination with cytotoxic chemotherapy, because of the limited evidence present in the literature. The 2020 Japanese Lung Cancer Society Guidelines can help community-based physicians to determine the most appropriate treatments and adequately provide medical care to their patients

Predicting osimertinib‐treatment outcomes through EGFR mutant‐fraction monitoring in the circulating tumor DNA of EGFR T790M‐positive patients with non‐small cell lung cancer (WJOG8815L)

The WJOG8815L phase II clinical study involves patients with non‐small cell lung cancer (NSCLC) that harbored the EGFR T790M mutation, which confers resistance to EGFR tyrosine kinase inhibitors (TKIs). The purpose of this study was to assess the predictive value of monitoring EGFR genomic alterations in circulating tumor DNA (ctDNA) from patients with NSCLC that undergo treatment with the third‐generation EGFR‐TKI osimertinib. Plasma samples of 52 patients harboring the EGFR T790M mutation were obtained pretreatment (Pre), on day 1 of treatment cycle 4 (C4) or cycle 9 (C9), and at diagnosis of disease progression or treatment discontinuation (PD/stop). CtDNA was screened for EGFR‐TKI‐sensitizing mutations, the EGFR T790M mutation, and other genomic alterations using the cobas EGFR Mutation Test v2 (cobas), droplet digital PCR (ddPCR), and targeted deep sequencing. Analysis of the sensitizing—and T790M—EGFR mutant fractions (MFs) was used to determine tumor mutational burden. Both MFs were found to decrease during treatment, whereas rebound of the sensitizing EGFR MF was observed at PD/stop, suggesting that osimertinib targeted both T790M mutation‐positive tumors and tumors with sensitizing EGFR mutations. Significant differences in the response rates and progression‐free survival were observed between the sensitizing EGFR MF‐high and sensitizing EGFR MF‐low groups (cutoff: median) at C4. In conclusion, ctDNA monitoring for sensitizing EGFR mutations at C4 is suitable for predicting the treatment outcomes in NSCLC patients receiving osimertinib (Clinical Trial Registration No.: UMIN000022076)