Publications by authors named "Young Chul Kim"

391 Publications

Efficacy and dose of afatinib in patients with non-small cell lung cancer after failure of prior gefitinib or erlotinib treatment.

Thorac Cancer 2021 Apr 3. Epub 2021 Apr 3.

Lung and Esophageal Cancer Clinic, Department of Internal Medicine, Chonnam National University Medical School, Chonnam National University Hwasun Hospital, Hwasun, South Korea.

Background: We report a subgroup analysis of afatinib with respect to its efficacy, safety, and the long-term survival of patients in a Named Patient Use program at a single institution.

Methods: We analyzed 60 patients with stage IV non-small cell lung cancer (NSCLC) who had been treated with ≥1 line of platinum-based chemotherapy and had activating epidermal growth factor receptor (EGFR) mutations or disease control for ≥6 months with prior EGFR inhibitors. Afatinib was started on a daily dose of 50 mg, which was decreased according to the adverse events and tolerability.

Results: A total of 13 patients achieved partial remission, whereas 33, 12, and two showed stable disease, had progression, and were not evaluable, respectively, resulting in an objective response rate and disease control rate of 21.7% and 76.7%, respectively. The median progression-free survival (PFS) was 5.4 (95% confidence interval [CI]: 4.0-7.7) months and median overall survival (OS) was 10.1 (8.5-13.6) months. Toxicities leading to drug discontinuation were experienced by four patients (6.7%). Grade 3 diarrhea occurred in 10 patients (16.7%), and afatinib dose reductions were required in 35 patients. The PFS and OS were significantly longer for patients whose dose was reduced to 40 or 30 mg than for those without dose reduction (7.0 vs 3.1 months and 13.5 vs 8.1 months, respectively, p < 0.05).

Conclusions: The efficacy of afatinib was similar to that identified in the global data without unexpected adverse events. Survival analyses support the currently approved dose of afatinib as first-line treatment for NSCLC.
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http://dx.doi.org/10.1111/1759-7714.13957DOI Listing
April 2021

Experience from Asian centers in a named-patient-use program for afatinib in patients with advanced non-small-cell lung cancer who had progressed following prior therapies, including patients with uncommon EGFR mutations.

Int J Clin Oncol 2021 May 30;26(5):841-850. Epub 2021 Mar 30.

Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.

Background: This study evaluated outcomes among patients with advanced/metastatic non-small-cell lung cancer (NSCLC) treated at Asian centers participating in the global named-patient-use (NPU) program for afatinib.

Methods: Patients had progressed after initial benefit with erlotinib or gefitinib, and/or had an EGFR or HER2 mutation, had no other treatment options, and were ineligible for afatinib trials. The recommended starting dose of afatinib was 50 mg/day. Dose modifications were allowed, and afatinib was continued as long as deemed beneficial. Response and survival information was provided voluntarily. Safety reporting was mandatory.

Results: 2242 patients (26% aged ≥ 70 years, 96% with adenocarcinoma) received afatinib at centers in 10 Asian countries. Most were heavily pre-treated, including prior treatment with erlotinib or gefitinib. Of 1281 patients tested, 1240 had EGFR mutations (common: 1034/1101; uncommon: 117/1101). There were no new safety signals, the most common adverse events being rash and diarrhea. Objective response rate (ORR) was 24% overall (n = 431 with data available), 27% for patients with common EGFR mutations (n = 230) and 28% for those with uncommon mutations (n = 32); median time to treatment failure (TTF) in these groups was 7.6 months (n = 1550), 6.4 months (n = 692) and 8.4 months (n = 83), respectively. In patients with EGFR exon 20 insertions (n = 23) and HER2 mutations (n = 12), median TTF exceeded 12 months.

Conclusions: Patient outcomes in this study were similar to those reported in the analysis of the global NPU. Afatinib achieved clinical benefits in patients with refractory NSCLC. ORR and TTF were similar between patients with tumors harboring uncommon and common EGFR mutations.
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http://dx.doi.org/10.1007/s10147-021-01869-0DOI Listing
May 2021

Efficacy of an inpatient smoking cessation program at a single regional cancer center: A prospective observational study.

Medicine (Baltimore) 2021 Feb;100(6):e24745

Jeonnam Tobacco Control Center, Chonnam National University Hwasun Hospital, Jeonnam.

Abstract: Smoking is the leading cause of preventable death and a risk factor for cancer, but smoking cessation is difficult even in patients who need hospitalization. This study aimed to investigate the usefulness of an inpatient smoking cessation consultation program and to analyze the clinical factors associated with abstinence. In this observational study, patients received regular counseling for 6 months, and abstinence was objectively assessed via urine and exhaled carbon monoxide testing. Cessation rates were assessed at 4 weeks and 6 months, and clinical characteristics associated with cessation success were investigated. Of the 571 patients referred to participate in the program, 170 (29.8%) were enrolled, and only 2 (1.2%) used smoking cessation drugs in addition to counseling. The smoking cessation rate was 77.6% after 4 weeks and 59.1% after 6 months. The cessation rates were significantly higher in patients with cancer than in those without cancer at both timepoints (63.8% vs 21.9%, P < .001, 53.6% vs 12.5%, P < .001), and they were also higher in the first admission group than in the re-admission group (87.4% vs 74.7%, P = .033, 88.5% vs 76.1%, P = .037). In patients with lung cancer, progression-free survival and overall survival tended to be better in those enrolled in the program (P = .158, P = .183). In conclusion, the inpatient smoking cessation program was associated with a high abstinence rate. Most patients maintained cessation without medication, suggesting that initial admission, along with a cancer diagnosis, can provide enough motivation to abstain from smoking. In addition, the smoking cessation effort showed potential to improve survival during lung cancer treatment.
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http://dx.doi.org/10.1097/MD.0000000000024745DOI Listing
February 2021

Clinical characteristics and prognosis of patients with Pneumocystis jirovecii pneumonia without a compromised illness.

PLoS One 2021 4;16(2):e0246296. Epub 2021 Feb 4.

Department of Internal Medicine, Chonnam National University Hospital, Gwangju, Republic of Korea.

Objective: 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.

Methods: 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).

Results: 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).

Conclusions: 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.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0246296PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7861382PMC
February 2021

Hypersensitivity reactions to multiple anti-tuberculosis drugs.

PLoS One 2021 4;16(2):e0246291. Epub 2021 Feb 4.

Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Chonnam National University Hospital, Gwangju, South Korea.

Objective: This study aimed to evaluate hypersensitivity reactions to anti-tuberculosis (TB) drugs.

Methods: We retrospectively compared the clinical manifestations and treatment outcomes of single and multiple drug hypersensitivity reactions (DHRs).

Results: Twenty-eight patients were diagnosed with anti-TB DHRs using oral drug provocation tests. Of these 28 patients, 17 patients (60.7%) had DHRs to a single drug and 11 (39.3%) had multiple DHRs. The median age of patients was 57.5 years (interquartile range [IQR], 39.2-73.2). Of the total patients, 18 patients (64.3%) were men. The median number of anti-TB drugs causing multiple DHRs was 2.0 (IQR 2.0-3.0). Rifampin was the most common drug that caused DHRs in both the single and multiple DHR groups (n = 8 [47.1%] and n = 9 [52.9%], respectively). The treatment success rate was lower in the multiple DHR group than in the single DHR group; however, the difference was not statistically significant (81.8% vs. 94.1%; P = 0.543).

Conclusions: Multiple anti-TB DHRs were common in all patients who experienced DHRs, and rifampin was the most common causative drug. The treatment outcomes appeared to be poorer in patients with multiple DHRs than in those with single DHRs.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0246291PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7861523PMC
February 2021

Clinical impact of rebiopsy among patients with epidermal growth factor receptor-mutant lung adenocarcinoma in a real-world clinical setting.

Thorac Cancer 2021 03 2;12(6):890-898. Epub 2021 Feb 2.

Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.

Background: In this study, we investigated the risk factors of acquired T790M mutation among patients with lung adenocarcinoma with epidermal growth factor receptor (EGFR) tyrosine mutation who were treated with EGFR-tyrosine kinase inhibitors (TKIs). The aim was to identify the clinical impact of rebiopsy.

Methods: This multicenter, retrospective cohort study was conducted in South Korea from January 2007 to June 2017. Patients with adenocarcinoma with EGFR mutation who underwent rebiopsy and were treated with EGFR-TKIs were included.

Results: Of a total of 352 patients, T790M mutation was identified in 156 (41.9%) at the time of rebiopsy. The median duration from initial biopsy to rebiopsy was 17 months. Univariate logistic regression analysis revealed associations of exon 19 deletion (odds ratio [OR], 1.643; p = 0.026), absence of L858R (OR, 0.627; p = 0.042), and previous EGFR-TKI treatment duration (OR, 1.039; p < 0.001) with T790M mutation. Previous EGFR-TKI treatment duration (OR, 3.580; p < 0.001) was independently associated with T790M mutation. A multivariate Cox proportional hazard model revealed that brain metastasis at initial diagnosis (hazard ratio, 1.390; p = 0.050) tended to be associated with T790M mutation. Among the patients with T790M mutation at rebiopsy, the osimertinib user group (n = 90) had a better one-year survival (68.7 vs. 58.3%, p = 0.048) than the osimertinib nonuser group (n = 66).

Conclusions: Rebiopsy might affect the clinical course of patients with EGFR-mutant adenocarcinoma who receive EGFR-TKIs.
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http://dx.doi.org/10.1111/1759-7714.13857DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7952806PMC
March 2021

Phase II open-label multicenter study to assess the antitumor activity of afatinib in lung cancer patients with activating epidermal growth factor receptor mutation from circulating tumor DNA: Liquid-Lung-A.

Thorac Cancer 2021 02 3;12(4):444-452. Epub 2020 Dec 3.

Department of Internal Medicine, Chonnam National University Medical School and CNU Hwasun Hospital, Hwasun, Jeonnam, Korea.

Background: Mutation analysis of circulating tumor DNA (ctDNA) is used for diagnosing lung cancer. This trial aimed to assess the efficacy of afatinib in treatment-naïve patients with lung cancer harboring epidermal growth factor receptor mutations (EGFRm, exon 19 deletions or exon 21 point mutations) detected based on ctDNA.

Methods: The primary objective was the objective response rate (ORR) in the response evaluable (RE) population. EGFRm analysis of ctDNA was performed using PANA Mutype. Of the 331 patients screened, ctDNA was positive in 21% (68/331) in the detection of activating EGFRm. Among 81 subjects with tumor EGFRm, 48 showed matched EGFRm in their ctDNA (59% sensitivity).

Results: Therapy with afatinib 40 mg was initiated in 21 (female, 17; adenocarcinoma, 20) patients (intention-to-treat, ITT); dose modifications were made in 15 (71%). The ORR was 74% in the RE population (14/19); 11 patients showed EGFRm only in ctDNA (Group A), whereas 10 exhibited the same EGFRm in their ctDNA and tumor DNA (Group B). There was no significant difference in ORR between Groups A and B (80% and 67% RE, respectively). Median progression-free survival (PFS) was 12.0 months, and no significant difference was observed according to the final afatinib dose, type of EGFRm, and Group A versus B. After progression, T790M mutation was found in 40% (6/15) of patients, and osimertinib was used as a second-line treatment.

Conclusions: Afatinib showed similar ORR and PFS in patients with lung cancer harboring EGFRm in their ctDNA regardless of tumor EGFRm results.

Key Points: SIGNIFICANT FINDINGS OF THE STUDY: Afatinib showed favorable ORR and PFS regardless of the tumor EGFR mutation status results, similar to the findings of previous trials assessing afatinib as first-line treatment of EGFR-mutated non-small cell lung cancer based on tumor genotyping.

What This Study Adds: Our findings emphasize that the survival benefit of afatinib treatment can be achieved not only by appropriate dose reduction with frequent and detailed monitoring of toxicities, but also by using noninvasive (ctDNA) assays in a real-world setting.
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http://dx.doi.org/10.1111/1759-7714.13763DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7882376PMC
February 2021

Glutathione Peroxidase 3 as a Biomarker of Recurrence after Lung Cancer Surgery.

J Clin Med 2020 Nov 24;9(12). Epub 2020 Nov 24.

Lung and Esophageal Cancer Clinic, Chonnam National University Hwasun Hospital, 322 Seoyang-ro, Hwasun-eup, Hwasun-gun, Jeollanam-do 58128, Korea.

We aimed to examine the usefulness of serum glutathione peroxidase 3 (GPx3) as a biomarker of lung cancer recurrence after complete resection. We prospectively collected serial serum samples at the baseline, as well as 3, 6 and 12 months after surgery from complete resection cases in 2013. GPx3 levels were measured by enzyme-linked immunosorbent assay. Statistical tests including t-tests and Cox proportional hazard regression analyses were performed. Totally, 135 patients were enrolled, and 39 (28.9%) showed relapse during the median follow-up period (63.60 months; range, 0.167-81.867). The mean GPx3 change was significantly higher in the recurrence group at 6 months (0.32 ± 0.38 vs. 0.15 ± 0.29, = 0.016) and 12 months (0.40 ± 0.37 vs. 0.13 ± 0.28, = 0.001). The high GPx3 change group showed significantly higher 60-months recurrence rates than the low group (48.1% vs. 25.2% at 3 months, = 0.005; 54.5% vs. 28.9% at 6 months, = 0.018; 38.3% vs. 18.3% at 12 months, = 0.035). High GPx3 change at 3 months were independent risk factors of recurrence (hazard ratio (HR) 3.318, 95% confidence interval (CI), 1.582-6.960, = 0.002) and survival (HR 3.150, 95% CI, 1.301-7.628, = 0.011). Therefore, serum GPx3 changes after surgery may be useful predictive biomarkers for recurrence in lung cancer. Larger-scale validation studies are warranted to confirm these findings.
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http://dx.doi.org/10.3390/jcm9123801DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7760369PMC
November 2020

Development of a high-dose vaccine formulation for prevention of megalocytivirus infection in rock bream (Oplegnathus fasciatus).

Vaccine 2020 12 11;38(51):8107-8115. Epub 2020 Nov 11.

Department of Aquatic Life Medicine, Pukyong National University, Busan 48513, Republic of Korea.

A formalin-inactivated red sea bream iridovirus (RSIV) vaccine was prepared using the culture supernatant of a persistently infected Pagrus major fin cell line (PI-PMF) with IVS-1 strain (RSIV subtype II Meglaocytivirus). Rock bream (Oplegnathus fasciatus) were injected with a high-dose, ultracentrifuged megalocytivirus vaccine (Ultra HSCMV, 7.0 × 10 copies/mL), a high-dose supernatant of cultured megalocytivirus vaccine (HSCMV, 1.0 × 10 copies/mL), a supernatant of cultured megalocytivirus vaccine (SCMV, 1.0 × 10 copies/mL), and a low-dose of cultured megalocytivirus vaccine (LSCMV, 1.0 × 10 copies/mL). The vaccine efficacies for the various vaccine formulations were determined done following injection challenge with IVS-1 (1.0 × 10 copies/0.1 mL/fish), and the four different vaccines exhibited cumulative mortalities of 10.0 ± 0.0%, 48.3 ± 7.6%, 75.0 ± 5.0%, and 100.0 ± 0.0%, respectively. Additionally, the dose-dependent vaccine efficacy was also confirmed using two different cohabitation methods that included challenges G (general) and I (individual). When squalene + aluminum hydroxide (SqAl) was used as an adjuvant for the HSCMV or SCMV vaccine, cumulative mortalities of 30.0 ± 5.0% and 48.3 ± 7.6%, respectively, were obtained; moreover, these two adjuvants exhibited the highest efficacy in this study. The observed difference in survival post-challenge for the different vaccine concentrations was not reflected in the differences in neutralizing antibody titers. It was found that the water temperature during immune induction plays a less important a role than the water temperature during the challenge test, in which lowering the water temperature from 25 °C to 21 °C during a challenge improved the level of protection from cumulative mortalities from 35% to 10%. This study demonstrated that protection against mortality using inactivated vaccines against RSIVD in rock bream, which are known to be the most susceptible species to RSIV infection, is dependent upon antigen dose and temperature during the challenge.
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http://dx.doi.org/10.1016/j.vaccine.2020.11.001DOI Listing
December 2020

Characteristics of female lung cancer in Korea: analysis of Korean National Lung Cancer Registry.

J Thorac Dis 2020 Sep;12(9):4612-4622

Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.

Backgrounds: The present study evaluated Korean women with lung cancer and compared the clinical characteristics of ever-smoker and never-smoker groups using the National Lung Cancer Registry.

Methods: In affiliation with the Korean Central Cancer Registry, the Korean Association for Lung Cancer constructed a registry into which 10% of the lung cancer cases in Korea were registered. Female lung cancer patients with valid smoking history were evaluated.

Results: Among 735 female lung cancer patients, 643 (87.5%) were never-smokers and 92 (12.5%) were smokers. The median survival was significantly longer in the never-smoker group (28 14 months; P<0.001). Among 683 patients with non-small cell lung cancer (NSCLC), the never-smoker group showed significantly longer median survival (29 14 months; P=0.002) and a higher proportion of stage I cancer (40.3% 25.7%; P<0.001). Survival analysis of the NSCLC patients showed that smoking status, receiving only supportive care, EGFR mutation status, lung cancer stage, and forced vital capacity (FVC) (%) were significantly associated with mortality in the multivariate analysis (P=0.025, HR 2.39, 95% CI: 1.12-5.11; P=0.017, HR 3.14, 95% CI: 1.22-8.06; P=0.033, HR 0.63, 95% CI: 0.41-0.96; P<0.001, HR 11.88, 95% CI: 5.79-24.38; P=0.002, HR 0.98, 95% CI: 0.96-0.99, respectively).

Conclusions: In Korean women with NSCLC, smoking status, not receiving active anticancer treatment, EGFR mutation status, lung cancer stage, and pulmonary function were significantly associated with mortality.
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http://dx.doi.org/10.21037/jtd-20-1671DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7578488PMC
September 2020

Potentially fatal complications of systemic air embolism after computed tomography-guided transthoracic needle biopsy in lung cancer harboring epithelial growth factor receptor mutation: A case report.

Thorac Cancer 2020 11 2;11(11):3401-3406. Epub 2020 Oct 2.

Department of Internal Medicine, Chonnam National University Hwasun Hospital, Jeonnam, Republic of Korea.

Air embolism is a rare, fatal complication of computed tomography (CT)-guided transthoracic needle biopsy (TTNB) of the lung. Here, we report a patient who developed an air embolism after CT-guided TTNB, which led to ST-elevation myocardial infarction and acute cerebral ischemia. The patient recovered completely without critical sequelae and was diagnosed with adenocarcinoma harboring activating epidermal growth factor receptor (EGFR) mutation. The patient responded to subsequent treatment with gefitinib. KEY POINTS: SIGNFICANT FINDINGS OF THE STUDY: Air embolism is a rare, fatal complication of CT-guided transthoracic lung biopsy. Only a few cases have been previously reported where myocardial and cerebral infarction occurred after TTNB, demonstrated not only on CT scan, but also electrocardiogram and electroencephalogram. WHAT THIS STUDY ADDS: Detection of driver gene mutation is crucial for planning lung cancer treatment. Despite the need for tissue biopsy, air embolism propagation to vital organs could result in severe end-organ damage and multidisciplinary approaches are needed to improve initial outcomes.
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http://dx.doi.org/10.1111/1759-7714.13686DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7606022PMC
November 2020

Influence of gene expression on survival of clear cell renal cell carcinoma.

Cancer Med 2020 11 28;9(22):8662-8675. Epub 2020 Sep 28.

Department of Cancer Epidemiology, Moffitt Cancer Center and Research Institute, Tampa, FL, USA.

Approximately 10%-20% of patients with clinically localized clear cell renal cell carcinoma (ccRCC) at time of surgery will subsequently experience metastatic progression. Although considerable progression was seen in the systemic treatment of metastatic ccRCC in last 20 years, once ccRCC spreads beyond the confines of the kidney, 5-year survival is less than 10%. Therefore, significant clinical advances are urgently needed to improve overall survival and patient care to manage the growing number of patients with localized ccRCC. We comprehensively evaluated expression of 388 candidate genes related with survival of ccRCC by using TCGA RNAseq (n = 515), Total Cancer Care (TCC) expression array data (n = 298), and a well characterized Moffitt RCC cohort (n = 248). We initially evaluated all 388 genes for association with overall survival using TCGA and TCC data. Eighty-one genes were selected for further analysis and tested on Moffitt RCC cohort using NanoString expression analysis. Expression of nine genes (AURKA, AURKB, BIRC5, CCNE1, MK167, MMP9, PLOD2, SAA1, and TOP2A) was validated as being associated with poor survival. Survival prognostic models showed that expression of the nine genes and clinical factors predicted the survival in ccRCC patients with AUC value: 0.776, 0.821 and 0.873 for TCGA, TCC and Moffitt data set, respectively. Some of these genes have not been previously implicated in ccRCC survival and thus potentially offer insight into novel therapeutic targets. Future studies are warranted to validate these identified genes, determine their biological mechanisms and evaluate their therapeutic potential in preclinical studies.
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http://dx.doi.org/10.1002/cam4.3475DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7666730PMC
November 2020

A Phase II Trial of Osimertinib as the First-Line Treatment of Non-Small Cell Lung Cancer Harboring Activating EGFR Mutations in Circulating Tumor DNA: LiquidLung-O-Cohort 1.

Cancer Res Treat 2021 Jan 21;53(1):93-103. Epub 2020 Sep 21.

Department of Internal Medicine, Chonnam National University Hwasun Hospital, Hwasun, Korea.

Purpose: Osimertinib is a potent, irreversible third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor for both EGFR-activating and T790M resistant mutation. The treatment efficacy of osimertinib was assessed in previously untreated patients with metastatic non-small cell lung carcinoma (NSCLC) harboring activating EGFR mutations in circulating tumor DNA (ctDNA) as well as tumor DNA.

Materials And Methods: Patients with activating EGFR mutations in their tumor DNA underwent screening with ctDNA analysis using Mutyper and Cobas v2 assays. Enrolled subjects received osimertinib 80 mg, once daily. Primary endpoint was objective response rate (ORR) and secondary endpoints were ctDNA test sensitivity, progression-free survival (PFS), duration of response (DoR), and safety.

Results: Among 39 screened patients, 29 were ctDNA positive for activating EGFR mutations and 19 were enrolled (ex19del, n=11; L858R/L861Q, n=7; G719A, n=1). Median age was 70 and most patients had brain metastases (15/19, 79%). ctDNA test sensitivity for activating EGFR mutations was 74% using both methods and 62% (Mutyper) or 64% (Cobas v2) for individual methods. ORR was 68% (13/19), median PFS was 11.1 months (95% confidence interval [CI], 0.0 to 26.7), and median DoR was 17.6 months (95% CI, 3.5 to 31.7). ORR and median PFS were significantly superior with ex19del (91%; 21.9 months; 95% CI, 5.5 to 38.3) than with L858R/L861Q (43%; 5.1 months; 95% CI, 2.3 to 7.9). One patient discontinued the drug because of drug-related interstitial pneumonitis.

Conclusion: Osimertinib had favorable efficacy in the first-line treatment of metastatic NSCLC harboring activating EGFR mutations in ctDNA as well as tumor DNA.
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http://dx.doi.org/10.4143/crt.2020.459DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7812005PMC
January 2021

Vitiligo-like depigmentation after pembrolizumab treatment in patients with non-small cell lung cancer: a case report.

Transl Lung Cancer Res 2020 Aug;9(4):1585-1590

Lung and Esophageal Cancer Clinic, Chonnam National University Hwasun Hospital, Jeonnam, Korea.

Immune checkpoint inhibitors (ICIs) targeting programmed death-1 (PD-1) pathway have significantly improved outcomes for patients with a variety of malignancies, including non-small cell lung cancer (NSCLC). In contrast, the incidence of immune-related cutaneous adverse events such as vitiligo have been on the rise because of the increasing use of ICIs. Vitiligo-like depigmentation has been reported in only 2.0% to 8.3% of patients with melanoma and is considered a favorable prognostic factor. However, it has been rarely reported in patients with non-melanoma malignancies. We describe a case of vitiligo-like skin depigmentation after pembrolizumab use in a patient with stage IV NSCLC. Multiple ill-defined painless and non-pruritic depigmented patches appeared on the patient's hands, scrotum, and lower lip after five months of pembrolizumab. We continued treatment with pembrolizumab 2 mg/kg for 14 months with close monitoring of vitiligo lesions until the progression of brain metastasis, but the vitiligo-like depigmentation did not improve by the combined excimer laser and topical corticosteroid therapy. Clinicians should be aware that immune-related cutaneous adverse events such as vitiligo-like depigmentation are not limited to cases of melanoma but arise as a direct result of anti-PD-1 therapy.
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http://dx.doi.org/10.21037/tlcr-20-386DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7481606PMC
August 2020

Development and characterization of megalocytivirus persistently-infected cell cultures for high yield of virus.

Tissue Cell 2020 Oct 21;66:101387. Epub 2020 May 21.

Department of Aquatic Life Medicine, Pukyong National University, Busan, 48513, South Korea.

Megalocytivirus infection is a major threat in rock bream aquaculture in Korea. To produce a highly concentrated megalocytivirus, primary cells, established cell line and persistently infected cell line were used in this study. Megalocytivirus was inoculated in primary fin cell cultures of red sea bream (Pagrus major), rock bream (Oplegnathus fasciatus), olive flounder (Paralichthys olivaceus) and black sea bream (Acanthopagrus schlegelii) and produced at similar concentrations of 10 viral particles/mL in all cultures while produced 10 viral particles/mL in grunt fin (GF) cell line. Since only red sea bream fin culture was amenable to subculturing for more than 100 times, it was established into Pagrus major fin (PMF) cell line. A persistently infected PMF cell line (PI-PMF) was obtained by continuous subculturing every 7 days as a batch culture system (PI-PMF-B) after infecting with megalocytivirus. Virus in supernatant of PI-PMF-B was maintained at high concentrations throughout over 50 consecutive subcultures in a relatively narrow range from 10 to 10 viral particles/mL with high level of CPE. For a more efficient and convenient production, a semi-batch culture system (PI-PMF-S) was developed in which culture media were exchanged at intervals of 3 days without subculturing for more than 50 media exchanges. Despite low virus productivity in a single cell (specific virus productivity, SVP), total cell number was increased in PI-PMF-S, allowing us to efficiently obtain a much higher concentration of virus (10 to 10 viral particles/mL) than in PMF-B. This is the first study to report detailed new methods for continuous and efficient production of high concentrations of megalocytivivrus with characterization of viral propagation in persistently infected cells.
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http://dx.doi.org/10.1016/j.tice.2020.101387DOI Listing
October 2020

A role for tubular Na/H exchanger NHE3 in the natriuretic effect of the SGLT2 inhibitor empagliflozin.

Am J Physiol Renal Physiol 2020 10 7;319(4):F712-F728. Epub 2020 Sep 7.

Department of Medicine, University of California-San Diego and Veterans Affairs San Diego Healthcare System, San Diego, California.

Inhibitors of proximal tubular Na-glucose cotransporter 2 (SGLT2) are natriuretic, and they lower blood pressure. There are reports that the activities of SGLT2 and Na-H exchanger 3 (NHE3) are coordinated. If so, then part of the natriuretic response to an SGLT2 inhibitor is mediated by suppressing NHE3. To examine this further, we compared the effects of an SGLT2 inhibitor, empagliflozin, on urine composition and systolic blood pressure (SBP) in nondiabetic mice with tubule-specific NHE3 knockdown (NHE3-ko) and wild-type (WT) littermates. A single dose of empagliflozin, titrated to cause minimal glucosuria, increased urinary excretion of Na and bicarbonate and raised urine pH in WT mice but not in NHE3-ko mice. Chronic empagliflozin treatment tended to lower SBP despite higher renal renin mRNA expression and lowered the ratio of SBP to renin mRNA, indicating volume loss. This effect of empagliflozin depended on tubular NHE3. In diabetic Akita mice, chronic empagliflozin enhanced phosphorylation of NHE3 (S552/S605), changes previously linked to lesser NHE3-mediated reabsorption. Chronic empagliflozin also increased expression of genes involved with renal gluconeogenesis, bicarbonate regeneration, and ammonium formation. While this could reflect compensatory responses to acidification of proximal tubular cells resulting from reduced NHE3 activity, these effects were at least in part independent of tubular NHE3 and potentially indicated metabolic adaptations to urinary glucose loss. Moreover, empagliflozin increased luminal α-ketoglutarate, which may serve to stimulate compensatory distal NaCl reabsorption, while cogenerated and excreted ammonium balances urine losses of this "potential bicarbonate." The data implicate NHE3 as a determinant of the natriuretic effect of empagliflozin.
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http://dx.doi.org/10.1152/ajprenal.00264.2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7642886PMC
October 2020

Enhancement parameters of contrast-enhanced computed tomography for pancreatic ductal adenocarcinoma: Correlation with pathologic grading.

World J Gastroenterol 2020 Jul;26(28):4151-4158

Department of Radiology, Hallym University Sacred Heart Hospital, Gyeonggi-do 14068, South Korea.

Background: Pancreatic ductal adenocarcinoma (PDA) is a malignancy with a high mortality rate and short survival time. The conventional computed tomography (CT) has been worldwide used as a modality for diagnosis of PDA, as CT enhancement pattern has been thought to be related to tumor angiogenesis and pathologic grade of PDA.

Aim: To evaluate the relationship between the pathologic grade of pancreatic ductal adenocarcinoma and the enhancement parameters of contrast-enhanced CT.

Methods: In this retrospective study, 42 patients (Age, mean ± SD: 62.43 ± 11.42 years) with PDA who underwent surgery after preoperative CT were selected. Two radiologists evaluated the CT images and calculated the value of attenuation at the aorta in the arterial phase and the pancreatic phase (VA and VA) and of the tumor (VT and VT) by finding out four regions of interest. Ratio between the tumor and the aorta enhancement on the arterial phase and the pancreatic phase (TAR and TAR) was figured out through dividing VT by VA and VT by VA. Tumor-to-aortic enhancement fraction (TAF) was expressed as the ratio of the difference between attenuation of the tumor on arterial and parenchymal images to that between attenuation of the aorta on arterial and pancreatic images. The Kruskal-Wallis analysis of variance and Mann-Whitney test for statistical analysis were used.

Results: Forty-two PDAs (23 men and 19 women) were divided into three groups: Well-differentiated ( 13), moderately differentiated ( 21), and poorly differentiated ( 8). TAF differed significantly between the three groups ( = 0.034) but TAR ( = 0.164) and TAR ( = 0.339) did not. The median value of TAF for poorly differentiated PDAs (0.1011; 95%CI: 0.01100-0.1796) was significantly higher than that for well-differentiated PDAs (0.1941; 95%CI: 0.1463-0.3194).

Conclusion: Calculation of TAF might be useful in predicting the pathologic grade of PDA.
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http://dx.doi.org/10.3748/wjg.v26.i28.4151DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7403799PMC
July 2020

Artificial intelligence and lung cancer treatment decision: agreement with recommendation of multidisciplinary tumor board.

Transl Lung Cancer Res 2020 Jun;9(3):507-514

Lung and Esophageal Cancer Clinic, Chonnam National University, Hwasun Hospital, Hwasun, Republic of Korea.

Background: IBM Watson for Oncology (WFO) is a cognitive computing system helping physicians quickly identify key information in a patient's medical record, surface relevant evidence, and explore treatment options. This study assessed the possibility of using WFO for clinical treatment in lung cancer patients.

Methods: We evaluated the level of agreement between WFO and multidisciplinary team (MDT) for lung cancer. From January to December 2018, newly diagnosed lung cancer cases in Chonnam National University Hwasun Hospital were retrospectively examined using WFO version 18.4 according to four treatment categories (surgery, radiotherapy, chemoradiotherapy, and palliative care). Treatment recommendations were considered concordant if the MDT recommendations were designated 'recommended' by WFO. Concordance between MDT and WFO was analyzed by Cohen's kappa value.

Results: In total, 405 (male 340, female 65) cases with different histology (adenocarcinoma 157, squamous cell carcinoma 132, small cell carcinoma 94, others 22 cases) were enrolled. Concordance between MDT and WFO occurred in 92.4% (k=0.881, P<0.001) of all cases, and concordance differed according to clinical stages. The strength of agreement was very good in stage IV non-small cell lung carcinoma (NSCLC) (100%, k=1.000) and extensive disease small cell lung carcinoma (SCLC) (100%, k=1.000). In stage I NSCLC, the agreement strength was good (92.4%, k=0.855). The concordance was moderate in stage III NSCLC (80.8%, k=0.622) and relatively low in stage II NSCLC (83.3%, k=0.556) and limited disease SCLC (84.6%, k=0.435). There were discordant cases in surgery (7/57, 12.3%), radiotherapy (2/12, 16.7%), and chemoradiotherapy (15/129, 11.6%), but no discordance in metastatic disease patients.

Conclusions: Treatment recommendations made by WFO and MDT were highly concordant for lung cancer cases especially in metastatic stage. However, WFO was just an assisting tool in stage I-III NSCLC and limited disease SCLC; so, patient-doctor relationship and shared decision making may be more important in this stage.
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http://dx.doi.org/10.21037/tlcr.2020.04.11DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7354125PMC
June 2020

Baseline Serum Interleukin-6 Levels Predict the Response of Patients with Advanced Non-small Cell Lung Cancer to PD-1/PD-L1 Inhibitors.

Immune Netw 2020 Jun 20;20(3):e27. Epub 2020 May 20.

Department of Internal Medicine, College of Medicine, Chungnam National University, Daejeon, Korea.

Although various studies on predictive markers in the use of PD-1/PD-L1 inhibitors are in progress, only PD-L1 expression levels in tumor tissues are currently used. In the present study, we investigated whether baseline serum levels of IL-6 can predict the treatment response of patients with advanced non-small cell lung cancer (NSCLC) treated with PD-1/PD-L1 inhibitors. In our cohort of 125 NSCLC patients, the objective response rate (ORR) and disease control rate (DCR) were significantly higher in those with low IL-6 (<13.1 pg/ml) than those with high IL-6 (ORR 33.9% vs. 11.1%, p=0.003; DCR 80.6% vs. 34.9%, p<0.001). The median progression-free survival was 6.3 months (95% confidence interval [CI], 3.9-8.7) in the low IL-6 group, significantly longer than in the high IL-6 group (1.9 months, 95% CI, 1.6-2.2, p<0.001). The median overall survival in the low IL-6 group was significantly longer than in the high IL-6 group (not reached vs. 7.4 months, 95% CI, 4.8-10.0). Thus, baseline serum IL-6 levels could be a potential biomarker for predicting the efficacy and survival benefit of PD-1/PD-L1 inhibitors in NSCLC.
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http://dx.doi.org/10.4110/in.2020.20.e27DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7327149PMC
June 2020

Western Diet Promotes Renal Injury, Inflammation, and Fibrosis in a Murine Model of Alström Syndrome.

Nephron 2020 6;144(8):400-412. Epub 2020 Jul 6.

Division of Nephrology & Hypertension, Department of Medicine, University of California San Diego & VA San Diego Healthcare System, San Diego, California, USA,

Introduction: Alström syndrome is a rare recessive genetic disease caused by mutations in ALMS1, which encodes a protein that is related to cilia function and intracellular endosome trafficking. The syndrome has been linked to impaired glucose metabolism and CKD. Polymorphisms in Alms1 have likewise been linked to CKD, but little is known about the modification of the phenotype by environmental factors.

Methods: To gain further insights, the fat aussie (foz) mouse strain, a genetic murine model of Alström syndrome, was exposed to a normal chow (NC) or to a Western diet (WD, 20% fat, 34% sucrose by weight, and 0.2% cholesterol) and renal outcomes were measured.

Results: Body weight and albuminuria were higher in foz than in wild-type (WT) mice on both diets but WD significantly increased the difference. Measurement of plasma creatinine and cystatin C indicated that glomerular filtration rate was preserved in foz versus WT independent of diet. Renal markers of injury, inflammation, and fibrosis were similar in both genotypes on NC but significantly greater in foz than in WT mice on WD. A glucose tolerance test performed in foz and WT mice on WD revealed similar basal blood glucose levels and subsequent blood glucose profiles.

Conclusions: WD sensitizes a murine model of Alström syndrome to kidney injury, inflammation, and fibrosis, an effect that may not be solely due to effects on glucose metabolism. Polymorphisms in Alms1 may induce CKD in part by modulating the deleterious effects of high dietary fat and sucrose on kidney outcome.
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http://dx.doi.org/10.1159/000508636DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8011852PMC
July 2020

Real-World Experience of Nivolumab in Non-small Cell Lung Cancer in Korea.

Cancer Res Treat 2020 Oct 15;52(4):1112-1119. Epub 2020 May 15.

Division of Hematology-Oncology, Department of Internal Medicine, Chungbuk National University Hospital, Chungbuk National University College of Medicine, Cheongju, Korea.

Purpose: The introduction of immune checkpoint inhibitors represents a major advance in the treatment of lung cancer, allowing sustained recovery in a significant proportion of patients. Nivolumab is a monoclonal anti-programmed death cell protein 1 antibody licensed for the treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC) after prior chemotherapy. In this study, we describe the demographic and clinical outcomes of patients with advanced NSCLC treated with nivolumab in the Korean expanded access program.

Materials And Methods: Previously treated patients with advanced nonsquamous and squamous NSCLC patients received nivolumab at 3 mg/kg every 2 weeks up to 36 months. Efficacy data including investigator-assessed tumor response, progression data, survival, and safety data were collected.

Results: Two hundred ninety-nine patients were treated across 36 Korean centers. The objective response rate and disease control rate were 18% and 49%, respectively; the median progression-free survival was 2.1 months (95% confidence interval [CI], 1.87 to 3.45), and the overall survival (OS) was 13.2 months (95% CI, 10.6 to 18.9). Patients with smoking history and patients who experienced immune-related adverse events showed a prolonged OS. Cox regression analysis identified smoking history, presence of immune-related adverse events as positive factors associated with OS, while liver metastasis was a negative factor associated with OS. The safety profile was generally comparable to previously reported data.

Conclusion: This real-world analysis supports the use of nivolumab for pretreated NSCLC patients, including those with an older age.
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http://dx.doi.org/10.4143/crt.2020.245DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7577826PMC
October 2020

Physiological function and molecular composition of ATP-sensitive K channels in human gastric smooth muscle.

J Smooth Muscle Res 2020 ;56(0):29-45

Department of Surgery, College of Medicine, Chungbuk National University, Chungdae-ro 1, Seowon-gu, Cheongju, Chungbuk 28644, Korea.

Gastric motility is controlled by slow waves. In general, the activation of the ATP-sensitive K (K) channels in the smooth muscle opposes the membrane excitability and produces relaxation. Since metabolic inhibition and/or diabetes mellitus are accompanied by dysfunctions of gastric smooth muscle, we examined the possible roles of K channels in human gastric motility. We used human gastric corpus and antrum smooth muscle preparations and recorded the mechanical activities with a conventional contractile measuring system. We also identified the subunits of the K channels using Western blot. Pinacidil (10 μM), a K channel opener, suppressed contractions to 30% (basal tone to -0.2 g) of the control. The inhibitory effect of pinacidil on contraction was reversed to 59% of the control by glibenclamide (20 μM), a K channel blocker. The relaxation by pinacidil was not affected by a pretreatment with L-arginine methyl ester, tetraethylammonium, or 4-aminopyridine. Pinacidil also inhibited the acetylcholine (ACh)-induced tonic and phasic contractions in a glibenclamide-sensitive manner (42% and 6% of the control, respectively). Other K channel openers such as diazoxide, cromakalim and nicorandil also inhibited the spontaneous and ACh-induced contractions. Calcitonin gene-related peptide (CGRP), a gastric neuropeptide, induced muscle relaxation by the activation of K channels in human gastric smooth muscle. Finally, we have found with Western blot studies, that human gastric smooth muscle expressed K channels which were composed of Kir 6.2 and SUR2B subunits.
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http://dx.doi.org/10.1540/jsmr.56.29DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7324727PMC
September 2020

A pictorial review on clinicopathologic and radiologic features of duodenal gastrointestinal stromal tumors.

Diagn Interv Radiol 2020 Jul;26(4):277-283

Department of Pathology, Hallym University Sacred Heart Hospital, Gyeonggi-do, Republic of Korea.

Duodenal gastrointestinal stromal tumors (GISTs) are rare, and studies on their management are not sufficient. Owing to the complex anatomy of the duodenum and pancreatic head, GISTs can be misdiagnosed as pancreatic head tumors. Surgical resection is the first treatment for localized duodenal GISTs; thus, noninvasive imaging is important for the diagnosis and treatment of GISTs. Computed tomography, magnetic resonance imaging and endoscopic ultrasonography findings can be helpful for the diagnosis of duodenal GISTs and can help differentiate GISTs from other adjacent tumors.
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http://dx.doi.org/10.5152/dir.2019.19432DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7360074PMC
July 2020

Tepotinib in Non-Small-Cell Lung Cancer with Exon 14 Skipping Mutations.

N Engl J Med 2020 09 29;383(10):931-943. Epub 2020 May 29.

From Memorial Sloan Kettering Cancer Center, New York (P.K.P.); the Oncology Department, Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology (E.F.), and Dr. Rosell Oncology Institute, Dexeus University Hospital, Quirónsalud Group (S.V.), Barcelona; Centre Hospitaliere Universitaire (CHU) Bordeaux, Service des Maladies Respiratoires, Bordeaux (R.V.), Université de Lille, CHU Lille, Thoracic Oncology Department, Centre National de la Recherche Scientifique, INSERM, Institut Pasteur de Lille, UMR9020-UMR-S 1277-Canther, Lille (A.B.C.), CHU de Toulouse, Institut Universitaire du Cancer de Toulouse, Université Paul Sabatier, Toulouse (J.M.), and Institut de Cancérologie de l'Ouest Rene Gauducheau Centre, Saint-Herblain (H. Senellart) - all in France; Saitama Cancer Center, Saitama (H. Sakai), and the Department of Thoracic Oncology, Kanagawa Cancer Center, Yokohama (T.K.) - both in Japan; the Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan (M.C.G.), and the Department of Surgery, Oncology and Gastroenterology, University of Padua and Oncologia Medica 2, Istituto Oncologico Veneto, IRCCS, Padua (P.C.) - both in Italy; Antwerp University Hospital, Edegem, Belgium (J.V.M., J.R.); Asklepios Lung Clinic, Munich-Gauting (N.R.), Pius Hospital Oldenburg, University Medicine Oldenburg, Oldenburg (F.G.), Translational Medicine, Department of Bioinformatics (D.J.), Translational Innovation Platform, Oncology (C.S.), the Department of Biostatistics (R.B.), Translational Medicine, Department of Clinical Biomarkers and Companion Diagnostics (J. Straub), and Global Clinical Development (A.J., J. Scheele), Merck, Darmstadt - all in Germany; the Department of Lung Cancer and Thoracic Oncology, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland (D.K.); Yonsei Cancer Center, Yonsei University College of Medicine, Seoul (B.C.C.), the Center for Lung Cancer, National Cancer Center, Goyang (J.-Y.H.), and Chonnam National University Medical School and Hwasun Hospital, Hwasun (Y.-C.K.) - all in South Korea; Lurie Cancer Center, Northwestern University Feinberg School of Medicine, Chicago (J.D.P.); the Department of Medicine, Vanderbilt Ingram Cancer Center, Nashville (L.H.); the Faculty of Medicine, School of Medicine, National Yang-Ming University (G.-C.C.), the Division of Chest Medicine, Department of Internal Medicine, Tri-service General Hospital, National Defense Medical Center (C.-L.T.), National Taiwan University Hospital (J.C.-H.Y.), and the Department of Chest Medicine, Taipei Veterans General Hospital, and School of Medicine, National Yang-Ming University (Y.-M.C.), Taipei, and the Division of Chest Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung (G.-C.C.) - both in Taiwan; the Department of Thoracic Oncology, Netherlands Cancer Institute, Amsterdam (E.F.S.), and the Department of Pulmonology, University of Groningen and University Medical Center Groningen, Groningen (A.J.W.) - both in the Netherlands; and M.D. Anderson Cancer Center, University of Texas, Houston (J.V.H., X.L.).

Background: A splice-site mutation that results in a loss of transcription of exon 14 in the oncogenic driver occurs in 3 to 4% of patients with non-small-cell lung cancer (NSCLC). We evaluated the efficacy and safety of tepotinib, a highly selective MET inhibitor, in this patient population.

Methods: In this open-label, phase 2 study, we administered tepotinib (at a dose of 500 mg) once daily in patients with advanced or metastatic NSCLC with a confirmed exon 14 skipping mutation. The primary end point was the objective response by independent review among patients who had undergone at least 9 months of follow-up. The response was also analyzed according to whether the presence of a exon 14 skipping mutation was detected on liquid biopsy or tissue biopsy.

Results: As of January 1, 2020, a total of 152 patients had received tepotinib, and 99 patients had been followed for at least 9 months. The response rate by independent review was 46% (95% confidence interval [CI], 36 to 57), with a median duration of response of 11.1 months (95% CI, 7.2 to could not be estimated) in the combined-biopsy group. The response rate was 48% (95% CI, 36 to 61) among 66 patients in the liquid-biopsy group and 50% (95% CI, 37 to 63) among 60 patients in the tissue-biopsy group; 27 patients had positive results according to both methods. The investigator-assessed response rate was 56% (95% CI, 45 to 66) and was similar regardless of the previous therapy received for advanced or metastatic disease. Adverse events of grade 3 or higher that were considered by investigators to be related to tepotinib therapy were reported in 28% of the patients, including peripheral edema in 7%. Adverse events led to permanent discontinuation of tepotinib in 11% of the patients. A molecular response, as measured in circulating free DNA, was observed in 67% of the patients with matched liquid-biopsy samples at baseline and during treatment.

Conclusions: Among patients with advanced NSCLC with a confirmed exon 14 skipping mutation, the use of tepotinib was associated with a partial response in approximately half the patients. Peripheral edema was the main toxic effect of grade 3 or higher. (Funded by Merck [Darmstadt, Germany]; VISION ClinicalTrials.gov number, NCT02864992.).
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http://dx.doi.org/10.1056/NEJMoa2004407DOI Listing
September 2020

Artificial Neural Network for Combined Steam-Carbon Dioxide Reforming of Methane.

J Nanosci Nanotechnol 2020 Sep;20(9):5730-5733

School of Chemical Engineering and the Research Institute for Catalysis, Chonnam National University, 77 Yongbong-ro, Buk-gu, Gwangju 61186, Republic of Korea.

The CH₄ conversion, CO₂ conversion, and H₂/CO ratio were set as dependent variables, as the feed rate, flow rate and reaction temperature as independent variables in the complex reaction of methane. We used the Artificial Neural Network (ANN) technique to build a model of the process. The ANN technique was able to predict the reforming process with higher accuracy due to the training capability. The reaction temperature has the greatest effect on the CO₂-CH₄ reforming reaction. This is because the catalytic reaction temperature has a direct influence on the thermodynamic value and the reaction rate and the equilibrium state.
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http://dx.doi.org/10.1166/jnn.2020.17634DOI Listing
September 2020

Modeling of Complex Reforming Reaction of Methane by Response Surface Methodology.

J Nanosci Nanotechnol 2020 Sep;20(9):5725-5729

School of Chemical Engineering and the Research Institute for Catalysis, Chonnam National University, 77 Yongbong-ro, Buk-gu, Gwangju 61186, Republic of Korea.

The objective of this study was to investigate the effect of feed composition, space velocity, and reaction temperature on methane/carbon dioxide conversion and H₂/CO ratio. Independent variables were feed ratio, flow rate, and reaction temperature while CH₄ conversion, CO₂ conversion, and H₂/CO ratio were set as dependent variables in the complex reaction of methane. As a result of mixed reforming reaction of methane through RSM modeling method, the reaction temperature was found to have the greatest influence. This is because the reaction temperature has the greatest influence on the reaction rate and equilibrium state as a factor directly affecting the thermodynamic value of the catalyst.
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http://dx.doi.org/10.1166/jnn.2020.17633DOI Listing
September 2020

Combined Steam-Carbon Dioxide Reforming of Methane: Modeling Using Response Surface Methodology (RSM).

J Nanosci Nanotechnol 2020 Sep;20(9):5720-5724

School of Chemical Engineering and the Research Institute for Catalysis, Chonnam National University, 77 Yongbong-ro, Buk-gu, Gwangju 61186, Republic of Korea.

In this paper, combined steam-carbon dioxide reforming of methane (CSDRM) on a nickel-based catalyst is investigated by using response surface methodology (RSM). Models were developed based on central composite design (CCD), conducted on methane, carbon dioxide conversion, and H₂/CO ratio with feed ratio, flow rate, and temperature. In Analysis of variance analysis (ANOVA), good agreement was shown between predicted data from RSM model and experimental data as well. This indicated, high adjusted ( square, coefficient of determination), -value over 0.75, and -value less than 0.05. CH₄ and CO₂ conversion were considerably improved at higher reaction temperature, because of the endothermic nature of the CSDRM. Also, H₂/CO ratio was affected by feed ratio. The minutiae of development of the model, testing, etc. is presented in this study.
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http://dx.doi.org/10.1166/jnn.2020.17628DOI Listing
September 2020

Application of Artificial Neural Network Over Nickel-Based Catalyst for Combined Steam-Carbon Dioxide of Methane Reforming (CSDRM).

J Nanosci Nanotechnol 2020 Sep;20(9):5716-5719

School of Chemical Engineering and the Research Institute for Catalysis, Chonnam National University, 77 Yongbong-ro, Buk-gu, Gwangju 61186, Republic of Korea.

The application of artificial neural network (ANN) for modeling, combined steam-carbon dioxide reforming of methane over nickel-based catalysts, was investigated. The artificial neural network model consisted of a 3-layer feed forward network, with hyperbolic tangent function. The number of hidden neurons is optimized by minimization of mean square error and maximization of ( square, coefficient of determination) and set of 8 neurons. With feed ratio, flow rate, and temperature as independent variables, methane, carbon dioxide conversion, and H₂/CO ratio, were measured using artificial neural network. Coefficient of determination () values of 0.9997, 0.9962, and 0.9985 obtained, and MAE (Mean Absolute Error), MSE (Mean Squared Error), RMSE (Root Mean Squared Error), and MAPE (Mean Absolute Percentage Error) showed low value. This study indicates ANN can successfully model a highly nonlinear process and function.
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http://dx.doi.org/10.1166/jnn.2020.17627DOI Listing
September 2020

Delayed diagnosis of lung cancer due to misdiagnosis as worsening of sarcoidosis: a case report.

BMC Pulm Med 2020 Mar 21;20(1):71. Epub 2020 Mar 21.

Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Republic of Korea.

Background: The concurrence of sarcoidosis and primary lung cancer is very rare. We report a very rare case with a delayed diagnosis of primary lung cancer due to its misdiagnosis as worsening of pulmonary sarcoidosis.

Case Presentation: A 68-year-old man presented to the outpatient department for evaluation of a mass in the right hilar area with lymphadenopathies in subcarinal and both interlobar areas on chest computed tomography (CT). Sufficient core samples were obtained from subcarinal and bilateral interlobar lymph nodes using endobronchial ultrasonography (EBUS) guided transbronchial needle aspiration (TBNA). EBUS could not reach the right hilar lymph node due to its high angle. The pathologic findings were consistent with sarcoidosis. After 5 months, chest CT revealed aggravation of the right upper paratracheal lymphadenopathy. Assuming worsening of sarcoidosis, he was prescribed an oral corticosteroid for 5 months. However, follow-up chest CT showed a newly developed right lower paratracheal lymphadenopathy and worsening right hilar lymphadenopathy. Bronchoscopy and EBUS were performed once again. Transbronchial lung biopsy from the right upper lobe and EBUS-TBNA from the right lower paratracheal lymph node revealed adenocarcinoma from the lung.

Conclusions: Although coexistence of sarcoidosis and lung cancer is very rare, the clinician should consider the possibility of accompanying lung cancer in sarcoidosis patients who are not responding to initial corticosteroid therapy.
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http://dx.doi.org/10.1186/s12890-020-1105-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7085152PMC
March 2020

Usefulness of computed tomography in predicting ethmoidal arterial bleeding in refractory epistaxis.

Eur Arch Otorhinolaryngol 2020 Jul 13;277(7):1969-1975. Epub 2020 Mar 13.

Department of Otorhinolaryngology, Gyeongsang National University College of Medicine and Gyeongsang National University Hospital, Jinju, Republic of Korea.

Purpose: Epistaxis that is refractory to conservative management can be treated with endoscopic sphenopalatine artery ligation (ESPAL). Although rare, ethmoidal artery (EA) bleeding can be a cause of rebleeding after successful ESPAL. EA bleeding is diagnosed by angiography and can also be identified during surgical exploration. However, since the angiographic embolization of the EA is contraindicated, surgical hemostasis is mandatory. This study investigated whether paranasal sinus (PNS) CT could provide information for predicting EA bleeding without angiography in patients with refractory epistaxis requiring ESPAL.

Methods: Forty-seven patients, who were surgically treated [with ESPAL or EA ligation (EAL)] for refractory epistaxis from March 2010 to June 2019, were retrospectively analyzed. A positive PNS CT finding for EA bleeding was defined as the presence of soft tissue densities having continuity with the EA pathway, accompanied by a partially deficient surrounding bony canal. These findings as well as soft tissue densities in each paranasal sinus were compared between the ESPAL and EAL groups.

Results: All patients in the EAL group had positive CT findings of EA bleeding, compared to only 12.2% in the ESPAL group (P < 0.001). The rate of soft tissue densities within the frontal and sphenoid sinuses were noted in 26.8% and 17.1% of patients in the ESPAL group, compared to 83.3% and 83.3% of patients in the EAL group (P = 0.013 and P = 0.003, respectively).

Conclusion: PNS CT might be useful for predicting EA bleeding in patients with refractory epistaxis requiring surgical hemostasis.
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http://dx.doi.org/10.1007/s00405-020-05914-yDOI Listing
July 2020