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Alectinib, an anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor (TKI), is the recommended first‐line treatment for ALK‐positive non‐small‐cell lung cancer (NSCLC) in Japan. Lorlatinib was approved as a subsequent therapeutic option after progression while receiving ALK TKI treatment. However, data on the use of lorlatinib in the second‐ or third‐line setting after alectinib failure are limited in Japanese patients. This retrospective real‐world observational study investigated the clinical effectiveness of lorlatinib in second‐ or later‐line settings after alectinib failure in Japanese patients. Clinical and demographic data collected in the Japan Medical Data Vision (MDV) database between December 2015 and March 2021 were used. Patients diagnosed with lung cancer who received lorlatinib following alectinib failure after the November 2018 marketing approval of lorlatinib in Japan were included. Of 1954 patients treated with alectinib, 221 were identified from the MDV database as receiving lorlatinib after November 2018. The median age of these patients was 62 years. Second‐line lorlatinib treatment was reported for 154 patients (70%); third‐ or later‐line lorlatinib treatment was reported for 67 patients (30%). The median duration of treatment (DOT) for all lorlatinib‐treated patients was 161 days (95% confidence interval [CI], 126–248), and 83 patients (37.6%) continued treatment after data cut‐off (March 31, 2021). Median DOTs of 147 days (95% CI, 113–242) and 244 days (95% CI, 109 to not reached) were reported with second‐line and third‐ or later‐line treatment, respectively. Consistent with clinical trial data, this real‐world observational study supports data suggesting the effectiveness of lorlatinib after alectinib failure in Japanese patients. [ABSTRACT FROM AUTHOR]

The long‐term behaviour of radiocaesium (137Cs) activity concentrations in forest ecosystems and their downstream impacts remain important issues in the deciduous broadleaf forests of Fukushima, Japan following the Fukushima Daiichi Nuclear Power Plant accident. To predict 137Cs cycling and discharge in the forest ecosystem, it is important to understand the spatial dynamics of the 137Cs inventory and transport along hillslopes. Therefore, we observed the spatial distribution of the 137Cs inventory and 137Cs transport via sediment and litter of a deciduous forest hillslope in Fukushima, Japan in 2016 and 2017 and examined how the spatial distribution of 137Cs inventory was formed using a mass balance model. In 2017, the 137Cs activity concentration was significantly greater in the downslope riparian area (455 kBq/m2) than in the upslope ridge area (179 kBq/m2). Annual 137Cs transport within litter and sediment contributed <0.5% to the current 137Cs inventory and cannot explain the current spatial variation of 137Cs inventory on the hillslope. The mass balance model results showed that if the initial 137Cs deposition was distributed uniformly in 2011, the spatial distribution of the hillslope 137Cs inventory was influenced mainly by the movement of leaf litter with a high 137Cs activity concentration. [ABSTRACT FROM AUTHOR]

Considering the increasing number of identified driver oncogene alterations, additional genetic tests are required to determine the treatment for advanced non‐small‐cell lung cancer (NSCLC). Next‐generation sequencing can detect multiple driver oncogenes simultaneously, enabling the analysis of limited amounts of biopsied tissue samples. In this retrospective, multicenter study (UMIN ID000039523), we evaluated real‐world clinical data using the Oncomine Dx Target Test Multi‐CDx System (Oncomine DxTT) as a companion diagnostic system. Patients with NSCLC who were tested for a panel of 46 genes using the Oncomine DxTT between June 2019 and January 2020 were eligible for enrollment. Patients from 19 institutions affiliated to the West Japan Oncology Group were recruited. The primary endpoint of the study was the success rate of genetic alteration testing in four driver genes (EGFR, ALK, ROS1, and BRAF) using the Oncomine DxTT. In total, 533 patients were enrolled in the study. The success rate of genetic alteration testing for all four genes was 80.1% (95% CI 76.5%‐83.4%). Surgical resection was associated with the highest success rate (88.0%), which was significantly higher than that for bronchoscopic biopsy (76.8%, P =.005). Multivariate analysis revealed a significant difference for surgical resection alone (P =.006, 95% CI 1.36‐6.18, odds ratio 2.90). Although the success rate of genetic alteration testing immediately after Oncomine DxTT induction was not sufficient in this study, optimizing specimen quantity and quality may improve the use of driver gene testing in clinical settings. [ABSTRACT FROM AUTHOR]

Background: A randomized phase 3 study was performed to investigate the efficacy and safety of maintenance therapy with S-1 after induction therapy with carboplatin plus S-1 in patients with advanced squamous non-small cell lung cancer (NSCLC).Methods: Chemotherapy-naive patients with advanced or relapsed squamous NSCLC were treated with carboplatin (area under the curve of 5 on day 1 every 3 weeks) plus S-1 (40 mg/m2 twice per day on days 1-14 every 3 weeks) as induction therapy. Patients who did not progress after 4 cycles of induction therapy were randomized to receive either S-1 plus best supportive care (BSC) or BSC alone. The primary objective of the study was to confirm the superiority of S-1 plus BSC in comparison with BSC alone with respect to progression-free survival.Results: Of the 365 patients enrolled in the study, 347 participated in the induction phase, and 131 of these individuals were randomized to receive S-1 plus BSC (n = 67) or BSC alone (n = 64). The risk of disease progression was significantly lower for patients in the S-1 plus BSC arm than those in the BSC-alone arm (hazard ratio, 0.548; 95% confidence interval, 0.374-0.802; P = .0019). The most common toxicities during maintenance therapy with S-1 included anorexia, anemia, and fatigue, but most cases were not severe.Conclusions: Continued maintenance with S-1 plus BSC is an effective and well-tolerated treatment option for patients with advanced squamous NSCLC previously treated with carboplatin plus S-1. [ABSTRACT FROM AUTHOR]

Background: Interstitial lung disease (ILD) induced by anti‐programmed‐cell death‐1 (PD‐1) and anti‐PD‐ligand 1 (PD‐L1) is potentially life‐threatening and is a common reason of the discontinuation of therapy. In contrast, an enhancement in antitumor effects was reported in patients who developed immune‐related adverse events, including ILD. Although recent evidence suggests that radiologic patterns of ILD may reflect the severity of ILD and the antitumor immune responses to anti‐PD‐1/PD‐L1 therapies, the association between radiologic features and clinical outcomes remains unclear. Methods: Patients with advanced non‐small‐cell lung cancer who were treated with 1st to 3rd line anti‐PD‐1 therapy from January 2016 through October 2017 were identified at multiple institutions belonging to the Niigata Lung Cancer Treatment Group. ILD was diagnosed by the treating physicians, and chest computed tomography scans were independently reviewed to assess the radiologic features of ILD. Results: A total of 231 patients who received anti‐PD‐1 therapy were enrolled. Thirty‐one patients (14%) developed ILD. Sixteen patients were classified as having ground glass opacities (GGO), 16 were classified as having cryptogenic organizing pneumonia (COP), and one was classified as having pneumonitis not otherwise specified. Patients with GGO had significantly worse overall survival time compared to patients with COP (7.8 months (95% CI: 2.2‐NE) versus not reached (95% CI: 13.2‐NE); P = 0.0175). Multivariate analysis of all 231 patients also revealed that PS = 1 and ≥2 and GGO were significant predictors of a worse overall survival. Conclusions: This study demonstrated that patients who developed GGO exhibited worse outcomes among non‐small‐cell lung cancer patients receiving anti‐PD‐1 therapies. [ABSTRACT FROM AUTHOR]

Background: Although the clinical efficacy of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR‐TKIs) in EGFR‐mutant non‐small cell lung cancer (NSCLC) patients has been demonstrated, their efficacy in EGFR‐mutant NSCLCs with central nervous system (CNS) metastases and the role of radiotherapy remain unclear. This study aimed to determine if it is preferable to add upfront cranial radiotherapy to EGFR‐TKIs in patients with EGFR‐mutant NSCLC with newly diagnosed brain metastases. Methods: We retrospectively analyzed the data of EGFR‐mutant NSCLC patients with CNS metastases who received EGFR‐TKIs as a first‐line therapy. Results: A total of 104 patients were enrolled and 39 patients received upfront brain radiotherapy, while 65 patients received first and second generation EGFR‐TKIs first. The median time to treatment failure (TTF) was 7.8 months (95% confidence interval [CI]: 6.3–9.4). The median survival time (MST) was 24.0 months (95% CI: 20.1–30.1). The overall response rate of the CNS was 37%. The median CNS progression‐free survival (PFS) was 13.2 months (95% CI: 10.0–16.2). Brain radiotherapy prior to EGFR‐TKI prolonged TTF (11.2 vs. 6.8 months, P = 0.038) and tended to prolong CNS‐PFS (15.6 vs. 11.1 months, P = 0.096) but was not significantly associated with overall survival (MST 26.1 vs. 24.0 months, P = 0.525). Univariate and multivariate analyses indicated that poor performance status and the presence of extracranial metastases were poor prognostic factors related to overall survival. Conclusion: EGFR‐TKI showed a favorable effect for EGFR‐mutant NSCLC patients with CNS metastases. Prolonged TTF and CNS‐PFS were observed with upfront brain radiotherapy. [ABSTRACT FROM AUTHOR]

Background: Combinations of exercise and nutritional interventions might improve the functional prognosis for cachectic cancer patients. However, high attrition and poor compliance with interventions limit their efficacy. We aimed to test the feasibility of the early induction of new multimodal interventions specific for elderly patients with advanced cancer Nutrition and Exercise Treatment for Advanced Cancer (NEXTAC) programme. Methods: This was a multicentre prospective single‐arm study. We recruited 30 of 46 screened patients aged ≥70 years scheduled to receive first‐line chemotherapy for newly diagnosed, advanced pancreatic, or non‐small‐cell lung cancer. Physical activity was measured using pedometers/accelerometer (Lifecorder®, Suzuken Co., Ltd., Japan). An 8 week educational intervention comprised three exercise and three nutritional sessions. The exercise interventions combined home‐based low‐intensity resistance training and counselling to promote physical activity. Nutritional interventions included standard nutritional counselling and instruction on how to manage symptoms that interfere with patient's appetite and oral intake. Supplements rich in branched‐chain amino acids (Inner Power®, Otsuka Pharmaceutical Co., Ltd., Japan) were provided. The primary endpoint of the study was feasibility, which was defined as the proportion of patients attending ≥4 of six sessions. Secondary endpoints included compliance and safety. Results: The median patient age was 75 years (range, 70–84). Twelve patients (40%) were cachectic at baseline. Twenty‐nine patients attended ≥4 of the six planned sessions (96.7%, 95% confidence interval, 83.3 to 99.4). One patient dropped out due to deteriorating health status. The median proportion of days of compliance with supplement consumption and exercise performance were 99% and 91%, respectively. Adverse events possibly related to the NEXTAC programme were observed in five patients and included muscle pain (Grade 1 in two patients), arthralgia (Grade 1 in one patient), dyspnoea on exertion (Grade 1 in one patient), and plantar aponeurositis (Grade 1 in one patient). Conclusions: The early induction of multimodal interventions showed excellent compliance and safety in elderly patients with newly diagnosed pancreatic and non‐small‐cell lung cancer receiving concurrent chemotherapy. We are now conducting a randomized phase II study to measure the impact of these interventions on functional prognosis. [ABSTRACT FROM AUTHOR]

Soil is the largest carbon reservoir in terrestrial ecosystems; it stores twice as much carbon as the atmosphere. It is well documented that global warming can lead to accelerated microbial decomposition of soil organic carbon (SOC) and enhance the release of CO2 from the soil to the atmosphere; however, the magnitude and timing of this effect remain highly uncertain due to a lack of quantitative data concerning the heterogeneity of SOC biodegradability. Therefore, we sought to identify SOC pools with respect to their specific mean residence times (MRTs), to use those SOC pools to partition soil respiration sources, and to estimate the potential response of the pools to warming. We collected surface soil and litter samples from a cool-temperate deciduous forest in Japan, chemically separated the samples into SOC fractions, estimated their MRTs based on radiocarbon (14C) isotope measurements, and used the data to construct a model representing the soil as a complex of six SOC pools with different MRT ranges. We estimate that a minor, fast-cycling SOC pool with an MRT of less than 10 years (corresponding to the O horizon and recognizable plant leaf fragments in the A1 horizon) is responsible for 73% of annual heterotrophic respiration and 44% of total soil respiration. However, the predicted response of these pools to warming demonstrates that the rate of SOC loss from the fast-cycling SOC pool diminishes quickly (within several decades) because of limited substrate availability. In contrast, warming will continue to accelerate SOC loss from slow-cycling pools with MRTs of 20–200 years over the next century. Although using a 14C-based approach has drawbacks, these estimates provide quantitative insights into the potential importance of slow-cycling SOC dynamics for the prediction of positive feedback to climate change. [ABSTRACT FROM AUTHOR]

The purpose of the present paper was to examine the differences in the levels of hematological or biochemical parameters among elderly hospital patients, nursing home residents, and mass health check-up recipients. One hundred and 44 geriatric inpatients (aged ≥ 65 years), 237 outpatients, 146 nursing home residents, 120 aged examinees from mass health check-ups, and 512 younger health check-up examinees (controls) were included in the present study. They were divided into five male and five female subgroups, respectively. The levels of hemoglobin (Hb), white blood cells (WBC), serum albumin (Alb), Ca, albumin-corrected Ca, Na, creatinine (Cr), and total cholesterol (TC) were determined and compared. There were significantly lower levels of Hb, Alb, Ca, Na, and TC in inpatients than in other groups in both sexes. In contrast, higher levels of WBC and Cr were found in inpatients. Among women there was no difference in the level of any parameter between nursing home residents, health check-up examinees, and controls. The data indicate that the levels of these parameters are affected to a greater extent in inpatients, and that female nursing home residents and health check-up examinees show values similar to those of controls. [ABSTRACT FROM AUTHOR]