We investigate the impact of the diabatic heating (Q1) over the Indian subcontinent and Tibetan Plateau (TP) sensible heat on the heat waves in South Korea in July and August over a recent 42‐year ...period. In particular, we emphasize the role of the convective activity across the region from northeastern Pakistan to northwestern India (PWI) induced by the heat from the TP, especially over the western and eastern TP. A composite analysis indicates that the composite differences between the heat‐wave summers (HWS) and non‐heat‐wave summers (NHWS) resemble the circum‐global teleconnection (CGT) pattern, which generates a high‐pressure anomaly over the Korean Peninsula, producing favourable conditions for heat waves in South Korea. The first coupled mode of the geopotential height at 250 hPa with the daily maximum temperature (TM) for July and August in South Korea is consistent with the composite pattern, suggesting that the diabatic heating over the Indian subcontinent induces a high‐pressure anomaly over the Korean Peninsula through a CGT‐like mechanism. The regression analysis of the wind vectors in the upper troposphere also indicates that the diabatic heating over the PWI region and associated TP sensible heating generates the strong convection over the PWI region, which corresponds to the anomalous anticyclonic circulation at 250 hPa over the western TP and the cyclonic circulation at 850 hPa over the PWI region. Moreover, the correlation patterns of the 250‐hPa geopotential height with the normalized rainfall amount index (IMRI) over the PWI region and the wave activity flux pattern confirm that the strong convective activity over the PWI region contributes to the anomalous high pressure and heat waves over the Korean Peninsula.
It is found that the PWI diabatic heating triggers anomalous South Asian High shifted to the western TP and then it stimulates stationary Rossby wave propagation and finally generates anomalous high pressures over the Korean Peninsula through stationary Rossby wave propagation, which contribute to the heat waves in South Korea.
Abstract
In this study, we aimed to investigate the feasibility of serum Krebs von den Lungen-6 (KL-6) as a potential biomarker for treatment-related ILD (TR-ILD) in lung cancer. We recruited ...patients with lung cancer in whom KL-6 was measured to differentiate between pneumonia and ILD (category 1), diagnose and assess the severity of suspicious ILD (category 2), or evaluate baseline levels before cancer treatment (category 3). Among 1,297 patients who underwent KL-6 testing, 422 had lung cancer, and TR-ILD was detected in 195 patients. In categories 1–2, median KL-6 level was higher in drug-induced ILD or acute exacerbation of underlying ILD than in no ILD or radiation-induced pneumonitis, and it was correlated with the severity of TR-ILD. High KL-6 level (cut-off: > 436U/mL) was an independent risk factor for severe TR-ILD, and low KL-6 level with high procalcitonin level (> 0.5 ng/mL) could exclude severe TR-ILD. Patients with severe TR-ILD had worse overall survival than those without, whereas high baseline KL-6 level was associated with worse survival, especially in patients without severe TR-ILD. Therefore, serum KL-6 may be a surrogate marker for predicting the occurrence and assessing the severity of TR-ILD at the time of suspected ILD and before lung cancer treatment.
Pulmonary arteriovenous malformation (PAVM) is a rare pulmonary disease. Although most patients with PAVMs are asymptomatic, cerebral complications associated with PAVMs are often fatal. This study ...aimed to evaluate the risk factors for cerebral complications in patients with PAVMs.
We retrospectively reviewed the medical charts of patients with PAVMs between 2003 and 2021 at two tertiary referral hospitals and one secondary hospital.
Fifty-five patients diagnosed with PAVMs were enrolled in this study. Most patients were female (89.1%), and the median age was 53 years. Thirty patients (54.5%) had incidentally detected PAVMs without symptoms. Twenty-four patients (43.7%) with PAVMs were treated with embolotherapy or surgery. Thirteen patients (23.6%) had cerebral complications. There was no significant difference in the development of cerebral complications according to treatment; however, older age (≥ 65 years) was associated with the development of new cerebral complications in untreated patients with PAVMs (odds ratio, 17.09; 95% confidence interval, 1.16-250.31; P = 0.038).
Older age (≥ 65 years) was a risk factor for the development of cerebral complications in patients with PAVMs; therefore, treatment should be considered in older patients with PAVMs.
Objectives
The optimal sequence for the administration of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) for treating non‐small cell lung cancer (NSCLC) is still unclear. ...This study aimed to evaluate the efficacy of sequential afatinib and osimertinib treatment in patients with NSCLC harboring EGFR mutations.
Materials and methods
Electronic records of patients with EGFR‐mutated NSCLC, who were administered afatinib and osimertinib (group A) or other chemotherapy (group B) between October 2014 and 2019, across 16 hospitals in South Korea were reviewed. The primary outcome, time on treatment (TOT), secondary outcome, and overall survival (OS) were estimated using the Kaplan–Meier method and log‐rank test. Multivariate analyses were performed using the Cox proportional hazards model.
Results
Of the 737 patients who received frontline afatinib treatment, 324 with complete records were selected (group A: 126, group B: 198). All patients in group A were T790M positive after afatinib, while patients in group B were all negative or unknown. The median TOT was 35.4 months (95% confidence interval CI: 27.7−45.6) in group A and 20.8 months (95% CI: 19.4−24.0) in group B. The median TOT with afatinib was 13.0 months (95% CI: 12.0−13.9) overall and 15.7 months (95% CI: 13.9−17.3) in group A. The 2‐ and 3‐year survival rates were 86.0 and 69.3% in group A and 75.9 and 55.3% in group B, respectively.
Conclusion
Sequential afatinib and osimertinib treatment resulted in better survival rates than treatment with afatinib followed by other chemotherapies.
Our study evaluated the real‐world efficacy of sequential treatment of afatinib and osimertinib, and compared it with other chemotherapies as a second‐line treatment. Promising real‐world data on first‐line afatinib and second‐line osimertinib may maximize sustained clinical benefit with avoiding chemotherapy and may warrant consideration, though tailored personalized approaches are necessary.
Pneumocystis jirovecii pneumonia (PCP) is a fatal respiratory infection, mostly associated with immunocompromised conditions. Several reports have described PCP development in patients who were not ...immunocompromised, but the clinical course and prognosis of PCP are not well understood. We compared the clinical characteristics and prognoses between patients with and without immunocompromised conditions who developed PCP.
We retrospectively analyzed patients who had been treated for PCP from three hospitals. We defined immunocompromised (IC) status as following: human immunodeficiency virus (HIV) infection; hematological malignancy; solid organ tumor under chemotherapy; rheumatic disease; medication with immunosuppressive agents. Patients without immunocompromised status were defined as being non-immunocompromised (non-IC).
The IC and non-IC groups comprised 173 and 14 patients. The median ages were 62.0 and 74.0 years in the IC and the non-IC group, respectively. The median interval between admission and anti-PCP treatment was significantly longer for patients in the non-IC group than that for patients in the IC group (7 vs. 2 days). The in-hospital mortality rates were significantly higher for patients in the non-IC group than that for patients in the IC group (71.4% vs. 43.9%; P = 0.047). A longer interval between admission and anti-PCP therapy was associated with increased 90-day mortality rate in patients with PCP (hazard ratio, 1.082; 95% confidence interval, 1.015-1.153; P = 0.016).
Patients with PCP with no predisposing illnesses were older and had higher mortality rates than IC patients with PCP. Delayed anti-PCP treatment was associated with increased 90-day mortality.
This study aimed to evaluate treatment outcomes and safety of afatinib in patients with squamous cell carcinoma of the lung (LSCC) who progressed after chemotherapy and immunotherapy. We recruited ...patients both retrospectively and prospectively and collected the outcomes and safety data. Additionally, we performed next-generation sequencing using tumor tissue and/or plasma to explore potential molecular biomarkers. Altogether, 42 patients were included in the final analysis. The median number of prior treatments was three (range 1-8), and the median TTF was 2.1 months. Objective response rate and disease control rate were 16.2% and 59.5%, respectively, and median duration of response was 4.0 months among response evaluable patients (
= 37). Treatment-related adverse events (TRAEs, including diarrhea, stomatitis, and paronychia) occurred in 22 (52.3%) patients; however, most were grade 2 or lower, and only 5 cases were grade 3. TRAEs led to dose modification in 17 (40.5%) and discontinuation in 4 (9.5%) patients. The TTF in patients with
mutations was significantly longer than that in patients without (6.8 vs. 2.1 months,
= 0.045). Our results highlight that afatinib is a reasonable treatment option in terms of effectiveness and safety, and
mutation can be used as a predictive biomarker in clinical settings.
Afatinib is an ErbB family blocker approved for the treatment of epidermal growth factor receptor mutation‐positive nonsmall‐cell lung cancer. A pivotal trial demonstrated significant clinical ...benefits with manageable toxicity of afatinib as a second‐line treatment option in squamous cell carcinoma of the lung (SCC) which led to approval in >60 countries. However, these results were derived from a controlled study conducted in selected patients and are not necessarily representative of the real‐world use of this drug. In addition, data on afatinib use after immunotherapy in this clinical setting are lacking. The aim of this study is to evaluate the treatment outcomes and safety of afatinib as a second‐ or later‐line treatment for SCC and to identify potential predictive biomarkers. As a real‐world observational study, 130 eligible patients with advanced SCC, who progressed after platinum‐based chemo‐ and immunotherapy, will be enrolled. Treatment outcomes and safety data will be collected for both the retrospective and prospective cohorts, and molecular profiling using tissue and plasma will be performed for the prospective cohort. The primary endpoint is time to treatment failure, and the secondary endpoints are objective response rate, progression‐free survival, overall survival, and safety. Comparison of clinical outcomes with respect to the different programmed death‐ligand 1 expression and molecular characteristics will also be carried out. This study will provide additional evidence on the usefulness of afatinib as a subsequent treatment, as well as feasible molecular biomarkers to predict its efficacy in this clinical setting.
This study will evaluate the treatment outcomes and safety of afatinib as a second‐ or later‐line treatment for SCC and identify potential predictive biomarkers. As a real‐world observational study, 130 eligible patients with advanced SCC, who progressed after platinum‐based chemo‐ and immunotherapy, will be enrolled. Treatment outcomes and safety data will be collected for both the retrospective and prospective cohorts, and molecular profiling using tissue and plasma will be performed for the prospective cohort.
Higher concentrations of particulate matter (PM) have been shown to cause deterioration of the symptoms of respiratory and cardiovascular disease in several regional studies. Here, we aimed to ...investigate the healthcare utilization of lung cancer patients associated with short-term exposure to PM at the national level in Korea.
We extracted the data of 210 558 subjects over a period of 3 years (2015-2017), who were diagnosed with lung cancer before 2015 and benefited from the National Health Insurance Sharing Service. We performed the interpolation method using the geographic information system to calculate the estimated mean PM
and PM
concentrations by regions and classified three groups as high (upper 10%), intermediate (10%-90%), and low (bottom 10%) based on the mean PM mass concentrations of the month.
The monthly average number of outpatient visits was significantly increased in high PM
urban areas (46.296 vs. 50.646, p = 0.015). In high PM
nationwide regions, the monthly average number of emergency admission was significantly increased (0.528 vs. 0.785, p = 0.001). The outpatient visits tended to change with PM
concentration and correlated with PM
/PM
concentrations in urban and nationwide areas. In high PM
urban regions, there was a significant increase in bronchodilator prescriptions (3.102 vs. 3.758, p = 0.008). Concerning high PM
nationwide regions, there were significantly increased prescriptions of antibiotics, steroids, bronchodilators, antihistamines, and mucolytics.
This study suggests that exposure to PM
is significantly associated with hospital utilization and drug prescription in lung cancer patients.
Background
About 3%–5% of non‐small cell lung cancer (NSCLC) presents positive anaplastic lymphoma kinase (ALK). Recently, several target agents have been approved as a treatment for ALK‐positive ...NSCLC. This study aimed to analyze the real‐world efficacy and outcome when administered crizotinib, the first approved target agent for ALK‐positive NSCLC, according to first‐ or late‐line treatment.
Methods
A total of 290 patients with ALK‐positive advanced NSCLC who were treated with crizotinib in 15 institutions in South Korea from January 2009 to December 2018 were enrolled.
Results
The median age of patients was 57.0 years, and 50.3% were male. The median follow‐up duration was 29.3 months. Among them, 113 patients received crizotinib as first‐line therapy. The objective response rate (ORR) was 60.1% (57.0% for first‐line recipients, 61.8% for second−/later‐line). Median (95% CI) progression‐free survival (PFS) was 13.7 (11.6–17.0) months. For first‐line recipients, overall survival (OS) was 26.3 (17.6–35.0) months. No significant difference in ORR, PFS and OS, according to the setting of crizotinib initiation, was observed. In a multivariate Cox regression analysis, old age, male gender, initially metastatic, and number of metastatic organs were associated with poor PFS and OS. The most common adverse events were nausea and vomiting, and severe adverse event leading to dose adjustment was hepatotoxicity.
Conclusions
ORR, PFS, OS, and adverse event profiles were comparable to previous clinical trials. Our findings could aid in the efficient management of ALK‐positive lung cancer patients.
This study aimed to add real-world evidence to the literature regarding the effectiveness and safety of durvalumab consolidation (DC) after concurrent chemoradiotherapy (CCRT) in the treatment of ...unresectable stage III non-small cell lung cancer (NSCLC). Using a hospital-based NSCLC patient registry and propensity score matching in a 2:1 ratio, we conducted a retrospective cohort study of patients with unresectable stage III NSCLC who completed CCRT with and without DC. The co-primary endpoints were 2-year progression-free survival and overall survival. For the safety evaluation, we evaluated the risk of any adverse events requiring systemic antibiotics or steroids. Of 386 eligible patients, 222 patients-including 74 in the DC group-were included in the analysis after propensity score matching. Compared with CCRT alone, CCRT with DC was associated with increased progression-free survival (median: 13.3 vs. 7.6 months, hazard ratioHR: 0.63, 95% confidence intervalCI: 0.42-0.96) and overall survival (HR: 0.47, 95% CI: 0.27-0.82) without an increased risk of adverse events requiring systemic antibiotics or steroids. While there were differences in patient characteristics between the present real-world study and the pivotal randomized controlled trial, we demonstrated significant survival benefits and tolerable safety with DC after the completion of CCRT.