Purpose: Optimal treatment for stage IIIA/N2 non–small cell lung cancer (NSCLC) is controversial. We aimed to assess the efficacy and safety of adjuvant pembrolizumab for stage IIIA/N2 NSCLC completely resected after neoadjuvant concurrent chemoradiation therapy (CCRT). Materials and Methods: In this open-label, single-center, single-arm phase 2 trial, patients with stage IIIA/N2 NSCLC received adjuvant pembrolizumab for up to 2 years after complete resection following neoadjuvant CCRT. The primary endpoint was disease-free survival (DFS). Secondary endpoints included overall survival (OS) and safety. As an exploratory biomarker analysis, we evaluated the proliferative response of blood CD39+PD-1+CD8+ T cells using fold changes in the percentage of proliferating Ki-67+ cells from days 1 to 7 of cycle 1 (Ki-67D7/D1). Results: Between October 2017 and October 2018, 37 patients were enrolled. Twelve (32%) and three (8%) patients harbored EGFR and ALK alterations, respectively. Of 34 patients with programmed cell death ligand 1 assessment, 21 (62%), nine (26%), and four (12%) had a tumor proportion score of < 1%, 1%-50%, and ≥ 50%, respectively. The median follow-up was 71 months. The median DFS was 22.4 months in the overall population, with a 5-year DFS rate of 29%. The OS rate was 86% at 2 years and 76% at 5 years. Patients with tumor recurrence within 6 months had a significantly lower Ki-67D7/D1 among CD39+PD-1+CD8+ T cells than those without (p=0.036). No new safety signals were identified. Conclusion Adjuvant pembrolizumab may offer durable disease control in a subset of stage IIIA/N2 NSCLC patients after neoadjuvant CCRT and surgery.

Objective: : The association between boule (BOLL) and endothelin receptor type A (EDNRA) loci and intracranial aneurysm (IA) formation has been reported via genome-wide association studies. We sought to identify genome-wide interactions involving BOLL and EDNRA loci for IA in a Korean adult cohort. Methods: : Genome-wide pairwise interaction analyses of BOLL and EDNRA involving 250 patients with IA and 296 controls were performed using the additive effect model after adjusting for confounding factors. Results: : Among 512575 single-nucleotide polymorphisms (SNPs), 23 and 11 common SNPs suggested a genome-wide interaction threshold (p<1.25×10-8) involving rs700651 (BOLL) and rs6841581 (EDNRA). Rather than singe SNP effect of BOLL or EDNRA on IA development, they showed a synergistic effect on IA formation via multifactorial pair-wise interactions. The rs1105980 of PTCH1 gene showed the most significant interaction with rs700651 (natural log-transformed odds ratio [lnOR], 1.53; p=6.41×10-11). The rs74585958 of RYK gene interacted strongly with rs6841581 (lnOR, -19.91; p=1.64×10-9). Although, there was no direct interaction between BOLL and EDNRA variants, two EDNRA-interacting gene variants of TNIK (rs11925024 and rs1231) and FTO (rs9302654), and one BOLL-interacting METTL4 gene variant (rs549315) exhibited marginal interaction with BOLL gene. Conclusion : BOLL or EDNRA may have a synergistic effect on IA formation via multifactorial pair-wise interactions.

Purpose: The benefit of adjuvant chemotherapy following curative-intent surgery in pancreatic ductal adenocarcinoma (PDAC) patients who had received neoadjuvant FOLFIRINOX is unclear. This study aimed to assess the survival benefit of adjuvant chemotherapy in this patient population. Materials and Methods: This retrospective study included 218 patients with localized non-metastatic PDAC who received neoadjuvant FOLFIRINOX and underwent curative-intent surgery (R0 or R1) between January 2017 and December 2020. The association of adjuvant chemotherapy with disease-free survival (DFS) and overall survival (OS) was evaluated in overall patients and in the propensity score matched (PSM) cohort. Subgroup analysis was conducted according to the pathology-proven lymph node status. Results: Adjuvant chemotherapy was administered to 149 patients (68.3%). In the overall cohort, the adjuvant chemotherapy group had significantly improved DFS and OS compared to the observation group (DFS: median, 13.8 months [95% confidence interval (CI), 11.0 to 19.1] vs. 8.2 months [95% CI, 6.5 to 12.0]; p < 0.001; and OS: median, 38.0 months [95% CI, 32.2 to not assessable] vs. 25.7 months [95% CI, 18.3 to not assessable]; p=0.005). In the PSM cohort of 57 matched pairs of patients, DFS and OS were better in the adjuvant chemotherapy group than in the observation group (p < 0.001 and p=0.038, respectively). In the multivariate analysis, adjuvant chemotherapy was a significant favorable prognostic factor (vs. observation; DFS: hazard ratio [HR], 0.51 [95% CI, 0.36 to 0.71; p < 0.001]; OS: HR, 0.45 [95% CI, 0.29 to 0.71; p < 0.001]). Conclusion Among PDAC patients who underwent surgery following neoadjuvant FOLFIRINOX, adjuvant chemotherapy may be associated with improved survival. Randomized studies should be conducted to validate this finding.

Purpose: There are no reliable biomarkers to guide treatment for patients with borderline resectable pancreatic cancer (BRPC) in the neoadjuvant setting. We used plasma circulating tumor DNA (ctDNA) sequencing to search biomarkers for patients with BRPC receiving neoadjuvant mFOLFIRINOX in our phase 2 clinical trial (NCT02749136). Materials and Methods: Among the 44 patients enrolled in the trial, patients with plasma ctDNA sequencing at baseline or post-operation were included in this analysis. Plasma cell-free DNA isolation and sequencing were performed using the Guardant 360 assay. Detection of genomic alterations, including DNA damage repair (DDR) genes, were examined for correlations with survival. Results: Among the 44 patients, 28 patients had ctDNA sequencing data qualified for the analysis and were included in this study. Among the 25 patients with baseline plasma ctDNA data, 10 patients (40%) had alterations of DDR genes detected at baseline, inclu-ding ATM, BRCA1, BRCA2 and MLH1, and showed significantly better progression-free survival than those without such DDR gene alterations detected (median, 26.6 vs. 13.5 months; log-rank p=0.004). Patients with somatic KRAS mutations detected at baseline (n=6) had significantly worse overall survival (median, 8.5 months vs. not applicable; log-rank p=0.003) than those without. Among 13 patients with post-operative plasma ctDNA data, eight patients (61.5%) had detectable somatic alterations. Conclusion Detection of DDR gene mutations from plasma ctDNA at baseline was associated with better survival outcomes of pati-ents with borderline resectable pancreatic ductal adenocarcinoma treated with neoadjuvant mFOLFIRINOX and may be a prognostic biomarker.

Background: This study investigates the long-term efficacy and safety of evogliptin add-on therapy in patients with inadequately controlled type 2 diabetes mellitus (T2DM) previously received dapagliflozin and metformin (DAPA/MET) combination. Methods: In this multicenter randomized placebo-controlled phase 3 trial, patients with glycosylated hemoglobin (HbA1c) levels 7.0% to 10.5% (n=283) previously used DAPA 10 mg plus MET (≥1,000 mg) were randomly assigned to the evogliptin 5 mg once daily or placebo group (1:1). The primary endpoint was the difference in the HbA1c level from baseline at week 24, and exploratory endpoints included the efficacy and safety of evogliptin over 52 weeks (trial registration: ClinicalTrials.gov NCT04170998). Results: Evogliptin add-on to DAPA/MET therapy was superior in HbA1c reduction compared to placebo at weeks 24 and 52 (least square [LS] mean difference, –0.65% and –0.55%; 95% confidence interval [CI], –0.79 to –0.51 and –0.71 to –0.39; P<0.0001). The proportion of patients achieving HbA1c <7% was higher in the triple combination group at week 52 (32.14% vs. 8.51% in placebo; odds ratio, 5.62; P<0.0001). Evogliptin significantly reduced the fasting glucose levels and mean daily glucose levels with improvement in homeostatic model assessment of β-cell function (LS mean difference, 9.04; 95% CI, 1.86 to 16.21; P=0.0138). Adverse events were similar between the groups, and no serious adverse drug reactions were reported in the evogliptin group. Conclusion Long-term triple combination with evogliptin added to DAPA/MET showed superior HbA1c reduction and glycemic control compared to placebo at 52 weeks and was well tolerated.

Purpose: The current standard chemotherapy for advanced biliary tract cancer (BTC) has limited benefit,and novel therapies need to be investigated. Materials and Methods: In this prospective cohort study, programmed death ligand-1 (PD-L1)–positive BTC patientswho progressed on first-line gemcitabine plus cisplatin were enrolled. Pembrolizumab 200mg was administered intravenously every 3 weeks. Results: Between May 2018 and February 2019, 40 patients were enrolled. Pembrolizumab wasgiven as second-line (47.5%) or  third-line therapy (52.5%). The objective response ratewas 10% and 12.5% by Response Evaluation Criteria in Solid Tumor (RECIST) v1.1 andimmune-modified RECIST (imRECIST) and median duration of response was 6.3 months.Among patients with progressive disease as best response, one patient (1/20, 5.0%)achieved complete response subsequently. The median progression-free survival (PFS) andoverall survival (OS) were 1.5 months (95% confidence interval [CI], 0.0 to 3.0) and 4.3months (95% CI, 3.5 to 5.1), respectively, and objective response per imRECIST was significantlyassociated with PFS (p < 0.001) and OS (p=0.001). Tumor proportion score  50%was significantly associated with higher response rates including the response after pseudoprogression(vs. < 50%; 37.5% vs. 6.5%; p=0.049). Conclusion Pembrolizumab showed modest anti-tumor activity in heavily pretreated PD-L1–positiveBTC patients. In patients who showed objective response, durable response could beachieved.

OBJECTIVES: The purpose of this study was to investigate the distinctive features of bodily panic symptoms and the predisposing conditions in Korean patients with panic disorder. METHODS: This was a retrospective chart review study and the data were collected from twelve university-affiliated hospitals in Korea. The patients selected met the diagnostic criteria for panic disorder, were older than 20 years of age, and had initially visited a psychiatry department. The assessments included the chief complaints related to bodily panic symptoms, recent stressors, recent history of alcohol and sleep problems, and time to visit an outpatient clinic. RESULTS: A total of 814 participants were included in the study. The most commonly experienced symptoms were cardiovascular and respiratory symptoms, which were observed in 63.9% and 55.4% of participants, respectively. Just before the onset of a panic attack, 25.6% of participants experienced sleep-related problems. Episodic binge drinking was also frequently observed (13.2%) and was more prevalent in men than in women (22.6% vs. 4.9%, p<0.001). About 75% of participants experienced stressful life events just before panic onset. Work-related issues were more prevalent in men than in women (22.0% vs. 13.4%, p=0.001). Family-related issues (4.8% vs. 14.1%, p<0.001) and conflict with a spouse or partner (4.0% vs.11.7%, p<0.001) were more prominent in women than in men. CONCLUSION Our results suggest that cardiovascular symptoms are the most common bodily panic symptoms in Korean patients. Our results suggest that a substantial portion of the Korean patients experienced stressful life events, sleep problems, and/or episodic binge drinking just before the onset of panic disorder.

PURPOSE: Pancreatic cancer associated double primary tumors are rare and their clinicopathologic characteristics are not well elucidated. MATERIALS AND METHODS: Clinicopathologic factors of 1,352 primary pancreatic cancers with or without associated double primary tumors were evaluated. RESULTS: Of resected primary pancreatic cancers, 113 (8.4%) had associated double primary tumors, including 26 stomach, 25 colorectal, 18 lung, and 13 thyroid cancers. The median interval between the diagnoses of pancreatic cancer and associated double primary tumors was 0.5 months. Overall survival (OS) of pancreatic cancer patients with associated double primary tumors was longer than those with pancreatic cancer only (median, 23.1 months vs. 17.0 months; p=0.002). Patients whose pancreatic cancers were resected before the diagnosis of metachronous tumors had a better OS than patients whose pancreatic cancer resected after the diagnosis of metachronous tumors (48.9 months and 13.5 months, p=0.001) or those whose pancreatic cancers were resected synchronously with non-pancreas tumors (19.1 months, p=0.043). The OS of pancreatic cancer patients with stomach (33.9 months, p=0.032) and thyroid (117.8 months, p=0.049) cancers was significantly better than those with pancreas cancer only (17.0 months). CONCLUSION: About 8% of resected pancreatic cancers had associated double primary tumors, and those from the colorectum, stomach, lung, and thyroid were common. Patients whose pancreatic cancer was resected before the diagnosis of metachronous tumors had better OS than those resected after the diagnosis of metachronous tumors or those resected synchronously.
Diagnosis ; Humans ; Lung ; Neoplasms, Multiple Primary ; Neoplasms, Second Primary ; Pancreas ; Pancreatic Neoplasms* ; Prognosis* ; Stomach ; Thyroid Gland ; Thyroid Neoplasms

Pulmonary artery sarcoma (PAS) is a rare, poorly differentiated malignancy arising from the intimal layer of the pulmonary artery. Contrast-enhanced chest computed tomography (CT) is a good diagnostic modality that shows a low-attenuation filling defect of the pulmonary artery in PAS patients. An 18-year-old man was referred to our hospital for the evaluation and management of cavitary pulmonary lesions that did not respond to treatment. A contrast-enhanced CT of the chest was performed, which showed a filling defect within the right interlobar pulmonary artery. The patient underwent a curative right pneumonectomy after confirmation of PAS. Although lung parenchymal lesions of PAS are generally nonspecific, it can be presented as cavities indicate pulmonary infarcts. Clinicians must consider the possibility of PAS as well as pulmonary thromboembolism in patients with pulmonary infarcts. So, we report the case with PAS that was diagnosed during the evaluation of cavitary pulmonary lesions and reviewed the literatures.
Adolescent ; Humans ; Lung ; Pneumonectomy ; Pulmonary Artery* ; Pulmonary Embolism ; Pulmonary Infarction ; Sarcoma* ; Thorax ; Tomography, X-Ray Computed

BACKGROUNDNo clinical study has systematically analyzed and compared circumferential neointimal and plaque distribution of stent neointimal proliferation and in native atherosclerotic plaques. This study aimed to investigate and compare the pattern of instent neointimal formation and native atherosclerosis in the coronary bifurcation lesions by volumetric analysis using systematic intravascular ultrasound (IVUS).

METHODSWe examined bifurcation lesions in native coronary artery (plaque group, n = 102) and stented bifurcations at 9-month follow-up (neointima group, n = 51) using volumetric IVUS analysis of both the main vessel (MV) and side branch (SB). Three 5-mm segments were analyzed; the proximal MV (MVp), distal MV (MVd) and SB ostium (SBo). For each segment, volumetric analysis was performed in each of four quadrants (divided according to the branch takeoff and the geometric center of the lumen); carinal, epicardial, abcarinal, and myocardial. The eccentricity index was defined as the ratio of the abcarinal plaque (or neointimal) volume to the carinal plaque (or neointimal) volume.

RESULTSThe plaque distribution differed significantly between the four quadrants, with the largest in the abcarinal quadrant, followed by the myocardial, epicardial, and carinal quadrants. The distribution of neointima was similar in the MV, but the four quadrants in the SB did not differ significantly. The eccentricity indices of both the MVd (P < 0.001) and SBo (P = 0.001) were significantly higher for the plaque group than the neointima group.

CONCLUSIONSThe distribution of neointimal proliferation seems to have a similar pattern to that of atherosclerotic plaque in native coronary arteries, particularly in the main vessel, but the trend is less prominent.

Aged ; Coronary Artery Disease ; diagnostic imaging ; Female ; Humans ; Male ; Middle Aged ; Neointima ; diagnostic imaging ; Plaque, Atherosclerotic ; diagnostic imaging ; Ultrasonography