Publications by authors named "Jong Seok Lee"

548 Publications

Surgical management for adventitial cystic disease of common femoral vein.

Asian J Surg 2021 Sep 6. Epub 2021 Sep 6.

Division of Vascular and Transplant Surgery, Department of Surgery, College of Medicine, The Catholic University of Korea, Seoul, 06591, South Korea. Electronic address:

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http://dx.doi.org/10.1016/j.asjsur.2021.08.044DOI Listing
September 2021

Radiological criteria for selecting candidates for neoadjuvant chemotherapy for gastric cancer: an exploratory analysis from the PRODIGY study.

Gastric Cancer 2021 Sep 2. Epub 2021 Sep 2.

Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea.

Background: In this exploratory analysis from the PRODIGY study, we aimed to define the radiological criteria to identify patients with gastric cancer who may derive maximal clinical benefit from neoadjuvant chemotherapy.

Patients And Methods: There were 246 patients allocated to receive surgery followed by adjuvant S-1 (SC group) and 238 allocated to receive neoadjuvant chemotherapy (CSC group). As the PRODIGY's radiological method of lymph node (LN) evaluation considers short diameter and morphology (the size and morphology method), a method considering only short diameter was also employed. In the SC group, the correlation between radiologic and pathologic findings was analyzed. The hazard ratio (HR) for the progression-free survival (PFS) of the CSC group was analyzed in subgroups with different cT/N stages.

Results: cT4 disease showed a sensitivity of 85.6% for detecting pT4 and had a low proportion of pathologic stage (pStage) I disease (4.5%). Among the criteria determined by different cT/N stages by each method of LN positivity, those involving cT4Nany or cT4N + by both methods had a minimal proportion of pStage I disease (≤ 5%), while cT4Nany by both methods and cT4N + by the size and morphology method exhibited ≥ 75.9% sensitivity for detecting pStage III disease. The relative risk reduction in PFS of the CSC group was greatest in patients meeting the cT4Nany criterion defined by both methods (HR 0.67, 95% confidence interval 0.48-0.93).

Conclusions: The cT4Nany criterion, regardless of the radiological method used for LN evaluation, may help select patients with resectable gastric cancer for neoadjuvant chemotherapy.
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http://dx.doi.org/10.1007/s10120-021-01243-zDOI Listing
September 2021

Amivantamab in EGFR Exon 20 Insertion-Mutated Non-Small-Cell Lung Cancer Progressing on Platinum Chemotherapy: Initial Results From the CHRYSALIS Phase I Study.

J Clin Oncol 2021 Aug 2:JCO2100662. Epub 2021 Aug 2.

Janssen R&D, Spring House, PA.

Purpose: Non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor () exon 20 insertion (Exon20ins) mutations exhibits inherent resistance to approved tyrosine kinase inhibitors. Amivantamab, an EGFR-MET bispecific antibody with immune cell-directing activity, binds to each receptor's extracellular domain, bypassing resistance at the tyrosine kinase inhibitor binding site.

Methods: CHRYSALIS is a phase I, open-label, dose-escalation, and dose-expansion study, which included a population with Exon20ins NSCLC. The primary end points were dose-limiting toxicity and overall response rate. We report findings from the postplatinum Exon20ins NSCLC population treated at the recommended phase II dose of 1,050 mg amivantamab (1,400 mg, ≥ 80 kg) given once weekly for the first 4 weeks and then once every 2 weeks starting at week 5.

Results: In the efficacy population (n = 81), the median age was 62 years (range, 42-84 years); 40 patients (49%) were Asian, and the median number of previous lines of therapy was two (range, 1-7). The overall response rate was 40% (95% CI, 29 to 51), including three complete responses, with a median duration of response of 11.1 months (95% CI, 6.9 to not reached). The median progression-free survival was 8.3 months (95% CI, 6.5 to 10.9). In the safety population (n = 114), the most common adverse events were rash in 98 patients (86%), infusion-related reactions in 75 (66%), and paronychia in 51 (45%). The most common grade 3-4 adverse events were hypokalemia in six patients (5%) and rash, pulmonary embolism, diarrhea, and neutropenia in four (4%) each. Treatment-related dose reductions and discontinuations were reported in 13% and 4% of patients, respectively.

Conclusion: Amivantamab, via its novel mechanism of action, yielded robust and durable responses with tolerable safety in patients with Exon20ins mutations after progression on platinum-based chemotherapy.
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http://dx.doi.org/10.1200/JCO.21.00662DOI Listing
August 2021

Anti-inflammatory effect of Ailanthus altissima (Mill.) Swingle leaves in lipopolysaccharide-stimulated astrocytes.

J Ethnopharmacol 2021 Jul 13:114258. Epub 2021 Jul 13.

Chung-Ang University, 84 Heukseok-ro, Dongjak-gu, Seoul, 06974, Republic of Korea. Electronic address:

Ethnopharmacological Relevance: Activated astrocytes are involved in the progression of neurodegenerative diseases. Traditionally, Ailanthus altissima (Mill.) Swingle, widely distributed in East Asia, has been used as a medicine for the treatment of fever, gastric diseases, and inflammation. Although A. altissima has been reported to play an anti-inflammatory role in peripheral tissues or cells, its role in the central nervous system (CNS) remains unclear.

Aim Of The Study: In the present study, we investigated the anti-inflammatory effects and mechanism of action of A. altissima in primary astrocytes stimulated by lipopolysaccharide (LPS).

Materials And Methods: A nitrite assay was used to measure nitric oxide (NO) production, and the tetrazolium salt 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay was performed to determine cytotoxicity. The expression levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and mitogen-activated protein kinase (MAPK) were determined with western blotting. Reverse-transcription PCR was used to assess the expression of inflammatory cytokines. The levels of reactive oxygen species were measured using 2,7-dichlorodihydrofluorescein diacetate. Luciferase assay and immunocytochemistry were used for assessing nuclear factor-kappa B (NF-κB) transcription and p65 localization, respectively. Memory and social interaction were analyzed using the Y-maze and three-chamber tests, respectively.

Results: The ethanol extract of A. altissima leaves (AAE) inhibited iNOS and COX-2 expression in LPS-stimulated astrocytes. Moreover, AAE reduced the transcription of various proinflammatory mediators, hindered NF-κB activation, and suppressed extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) activation without p38 activation. Ultra-high performance liquid chromatography with mass spectrometry analysis revealed that AAE comprised ethyl gallate, quercetin, and kaempferol, along with luteolin, which has anti-inflammatory properties, and repressed LPS-induced nitrite levels and the nuclear translocation of p65. Finally, oral administration of AAE attenuated LPS-induced memory and social impairment in mice and repressed LPS-induced ERK and JNK activation in the cortices of mice.

Conclusion: AAE could have therapeutic uses in the treatment of neuroinflammatory diseases via suppression of astrocyte activation.
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http://dx.doi.org/10.1016/j.jep.2021.114258DOI Listing
July 2021

Flattening in the Anteroposterior Direction of the Terminal Ileum or Sigmoid Colon Lying Across the Psoas Muscle on Magnetic Resonance Enterography in Patients with Crohn's Disease.

Korean J Radiol 2021 Jul 14. Epub 2021 Jul 14.

Inflammatory Bowel Disease Center, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.

Objective: Flattening in the anteroposterior direction (AP flattening) of the terminal ileum (TI) or sigmoid colon (SC) lying across the psoas muscle, on magnetic resonance enterography (MRE), might mimic bowel inflammation in the coronal view. This study investigated the prevalence of AP flattening and the factors associated with its development.

Materials And Methods: A total of 364 surgery-naïve patients with Crohn's disease (CD) who had undergone MRE were retrospectively reviewed. AP flattening was defined as a luminal collapse in the anteroposterior direction, with a bowel width in the axial plane < 1/4 of the normal diameter without reduction of bowel width in coronal images. The prevalence of AP flattening of the TI and SC on MRE in patients with bowel segments lying across the psoas muscle was determined. We further compared the rate of AP flattening between MRE and computed tomography enterography (CTE) in a subcohort of patients with prior CTE. The factors associated with AP flattening were analyzed using multivariable logistic regression in a subcohort of patients with endoscopic findings of TI.

Results: Three hundred and twenty-two and 363 patients, respectively, had TI and SC lying across the psoas muscle. The prevalence of AP flattening on MRE was 7.5% (24/322) in TI and 5.2% (19/363) in SC. The prevalences were significantly higher on MRE than on CTE in both the TI (7.3% [12/164] vs. 0.6% [1/164]; = 0.003) and SC (5.8% [11/190] vs. 1.6% [3/190]; = 0.039). AP flattening of the TI was independently and strongly associated with the absence of CD inflammation on endoscopy, with an adjusted odds ratio of 0.066 ( = 0.003) for the presence versus the absence (reference) of inflammation.

Conclusion: AP flattening of the TI or SC lying across the psoas muscle was uncommon and predominantly observed on MRE of the bowel without CD inflammation.
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http://dx.doi.org/10.3348/kjr.2020.1420DOI Listing
July 2021

A Prognostic Model to Facilitate Palliative Care Referral in Oncology Outpatients.

Cancer Res Treat 2021 Jul 13. Epub 2021 Jul 13.

Division of Hematology and Medical Oncology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea.

Purpose: We aimed to develop a prognostic model to assist palliative care referral at least 3 months before death in advanced cancer patients treated at an outpatient medical oncology clinic.

Materials And Methods: In this prospective cohort study, a total of 200 patients were enrolled at a tertiary cancer center in South Korea. The major eligibility criterion was an expected survival of less than a year as estimated by their oncologists. We analyzed the influences of known prognostic factors along with chemotherapy status, mid-arm circumference, and triceps skinfold thickness on survival time.

Results: The mean age of the patients was 64.5 years, 36% were female, and the median survival time was 7.6 months. In the multivariate analysis, we found 6 significant factors related to poor survival: a poor Eastern Cooperative Oncology Group (ECOG) performance status (≥2), not undergoing chemotherapy, anorexia, a low lymphocyte level (<12%), a high lactate dehydrogenase (LDH) level (≥300 IU/L), and a low mid-arm circumference (<23 cm). We developed a prognostic model (score, 0-8.0) to predict 3-month survival based on the multivariate analysis. Patients who scored ≥4.0 points had a short survival of less than 3 months (p<0.001). The discriminating ability of the prognostic model using the area under the receiver operating characteristic curve (AUC) was 0.88.

Conclusion: The prognostic model using ECOG performance status, chemotherapy status, anorexia, lymphocytes, LDH, and mid-arm circumference can predict 3-month survival in medical oncology outpatients. It can alert oncologists to refer patients to palliative care specialists before it is too late.
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http://dx.doi.org/10.4143/crt.2021.483DOI Listing
July 2021

Clinicopathologic Characteristics and Clinical Outcome of Localized Liposarcoma: A Single Center Experience Over 25 Years and Evaluation of PD-L1 Expression.

Cancer Res Treat 2021 Jul 6. Epub 2021 Jul 6.

Department of Oncology, Asan Medical Center University of Ulsan College of Medicine, Seoul, Korea.

Purpose: For liposarcoma (LPS), clinical course and proper treatment strategies have not been well-established. Recently, immune-checkpoint inhibitors have shown potential efficacy in LPS. We aimed to describe the clinical course of LPS and evaluate the clinical impact of PD-L1.

Materials And Methods: We reviewed all consecutive patients (n=332) who underwent curative-intent surgery for localized LPS at Asan Medical Center between 1989 and 2017. PD-L1 testing was performed in well-differentiated and dedifferentiated LPS.

Results: The median age was 56 years with males comprising 60.8%. Abdomen-pelvis (47.6%) and well-differentiated (37.7%) were the most frequent primary site and histologic subtype, respectively. During a median follow-up of 81.2 months, recurrence was observed in 135 (40.7%), and 86.7% (117/135) were loco-regional. Well-differentiated subtype (HR=0.38), abdomen-pelvis origin (HR=2.43), tumor size larger than 5cm (HR=1.83), positive resection margin (HR=2.58), and postoperative radiotherapy (HR=0.36) were significantly related with recurrence-free survival as well as visceral involvement (HR=1.84) and multifocality (HR=3.79) in abdomen-pelvis LPS. PD-L1 was positive in 31.5% (23/73) and 51.3% (39/76) of well-differentiated and dedifferentiated LPS, respectively, but had no impact on survival outcomes.

Conclusion: Clinical course of LPS was heterogeneous according to histology and anatomic location. Clear resection margin was important to lower recurrence and postoperative radiotherapy might have additional benefit. A decent portion of well-differentiated and dedifferentiated LPS were positive for PD-L1, but its prognostic role was unclear. Further research is needed to determine clinical implications of PD-L1, especially for advanced-stage LPS with unmet needs for effective systemic treatment.
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http://dx.doi.org/10.4143/crt.2021.496DOI Listing
July 2021

Comparison of the Predictive Power of a Combination versus Individual Biomarker Testing in Non-Small Cell Lung Cancer Patients treated with immune checkpoint inhibitors.

Cancer Res Treat 2021 Jul 7. Epub 2021 Jul 7.

Department of Pathology; Seoul National University Bundang Hospital, Seongnam, Korea.

Purpose: Since tumor mutational burden (TMB) and gene expression profiling (GEP) have complementary effects, they may have improved predictive power when used in combination. Here, we investigated the ability of TMB and GEP to predict the immunotherapy response in patients with non-small cell lung cancer (NSCLC) and assessed if this combination can improve predictive power compared to that when used individually.

Materials And Methods: This retrospective cohort study included 30 patients with NSCLC who received immune checkpoint inhibitors (ICI) therapy at the Seoul National University Bundang Hospital. PD-L1 protein expression was assessed using immunohistochemistry, and TMB was measured by targeted deep sequencing. Gene expression was determined using NanoString® nCounter analysis for the PanCancer IO360 panel, and enrichment analysis were performed.

Results: Eleven (36.7%) patients showed a durable clinical benefit (DCB), whereas nineteen (63.3%) showed no durable benefit (NDB). TMB and enrichment scores (ES) showed significant differences between the DCB and NDB groups (p=0.044, 0.017, respectively); however, no significant correlations were observed among TMB, ES, and PD-L1. ES was the best single biomarker for predicting DCB (Area under the curve [AUC]=0.794), followed by TMB (AUC=0.679) and PD-L1 (AUC=0.622). TMB and ES showed the highest AUC (0.8373) among other combinations (AUC, TMB and PD-L1=0.7775; AUC, PD-L1 and ES=0.7632) and was similar to that of all biomarkers used together (0.8325).

Conclusion: The combination of TMB and ES may be an effective predictive tool to identify patients with NSCLC patients who would possibly benefit from ICI therapies.
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http://dx.doi.org/10.4143/crt.2021.583DOI Listing
July 2021

Relationships between metabolic syndrome and aspects of abdominal aortic aneurysm.

Asian J Surg 2021 Jun 17. Epub 2021 Jun 17.

Division of Vascular and Transplant Surgery, Department of Surgery, Incheon St. Mary's Hospital, The Catholic University of Korea, Incheon, 21431, South Korea; Division of Vascular and Transplant Surgery, Department of Surgery, College of Medicine, The Catholic University of Korea, Seoul, 06591, South Korea. Electronic address:

Background: Metabolic syndrome (MetS) is a cluster of metabolic abnormalities strongly associated with risks of cardiovascular diseases. However, a relationship between MetS and aneurysmal disease as compared with occlusive disease has not been confirmed. Therefore, correlations of MetS and abdominal aortic aneurysm (AAA) were evaluated.

Methods: Between March 2011 and February 2020, 354 patients diagnosed with AAA were enrolled and divided into the MetS (n = 164) and the no-MetS (n = 190) groups. Individual components of MetS, characteristics of AAA, rupture rate, and survival rate were evaluated for both groups. Additionally, correlations between MetS and AAA were evaluated with focusing on effects of diabetes mellitus (DM).

Results: The size of AAA was significantly larger in the MetS group compared with the no-MetS group (P < 0.05). The rupture rate was significantly higher in the MetS group compared with the no-MetS group (P < 0.05) and the survival rate was significantly higher in the no-MetS group (P < 0.05). In terms of DM, the size of AAA was significantly larger in the no-DM group compared with the DM group (P < 0.05). MetS was significantly more prevalent in the DM group compared with the no-DM group (P < 0.05). Finally, the rupture and survival rates were not statistically different between the DM and the no-DM groups (P > 0.05).

Conclusions: Although larger prospective studies are necessary, we suggest that MetS proportionally aggravates the status of AAA and survival rate. Therefore, surveillance for MetS and individual components may help to restrict the expansion of AAA.
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http://dx.doi.org/10.1016/j.asjsur.2021.05.046DOI Listing
June 2021

PRODIGY: A Phase III Study of Neoadjuvant Docetaxel, Oxaliplatin, and S-1 Plus Surgery and Adjuvant S-1 Versus Surgery and Adjuvant S-1 for Resectable Advanced Gastric Cancer.

J Clin Oncol 2021 Sep 16;39(26):2903-2913. Epub 2021 Jun 16.

Department of Pathology, Yonsei University College of Medicine, Seoul, Republic of Korea.

Purpose: Adjuvant chemotherapy after D2 gastrectomy is standard for resectable locally advanced gastric cancer (LAGC) in Asia. Based on positive findings for perioperative chemotherapy in European phase III studies, the phase III PRODIGY study (ClinicalTrials.gov identifier: NCT01515748) investigated whether neoadjuvant docetaxel, oxaliplatin, and S-1 (DOS) followed by surgery and adjuvant S-1 could improve outcomes versus standard treatment in Korean patients with resectable LAGC.

Patients And Methods: Patients 20-75 years of age, with Eastern Cooperative Oncology Group performance status 0-1, and with histologically confirmed primary gastric or gastroesophageal junction adenocarcinoma (clinical TNM staging: T2-3N+ or T4Nany) were randomly assigned to D2 surgery followed by adjuvant S-1 (40-60 mg orally twice a day, days 1-28 every 6 weeks for eight cycles; SC group) or neoadjuvant DOS (docetaxel 50 mg/m, oxaliplatin 100 mg/m intravenously day 1, S-1 40 mg/m orally twice a day, days 1-14 every 3 weeks for three cycles) before D2 surgery, followed by adjuvant S-1 (CSC group). The primary objective was progression-free survival (PFS) with CSC versus SC. Two sensitivity analyses were performed: intent-to-treat and landmark PFS analysis.

Results: Between January 18, 2012, and January 2, 2017, 266 patients were randomly assigned to CSC and 264 to SC at 18 Korean study sites; 238 and 246 patients, respectively, were treated (full analysis set). Follow-up was ongoing in 176 patients at data cutoff (January 21, 2019; median follow-up 38.6 months [interquartile range, 23.5-62.1]). CSC improved PFS versus SC (adjusted hazard ratio, 0.70; 95% CI, 0.52 to 0.95; stratified log-rank = .023). Sensitivity analyses confirmed these findings. Treatments were well tolerated. Two grade 5 adverse events (febrile neutropenia and dyspnea) occurred during neoadjuvant treatment.

Conclusion: PRODIGY showed that neoadjuvant DOS chemotherapy, as part of perioperative chemotherapy, is effective and tolerable in Korean patients with LAGC.
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http://dx.doi.org/10.1200/JCO.20.02914DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8425847PMC
September 2021

Possible Persistence of Multiferroic Order down to Bilayer Limit of van der Waals Material NiI.

Nano Lett 2021 Jun 7;21(12):5126-5132. Epub 2021 Jun 7.

Department of Physics and Photon Science, Gwangju Institute of Science and Technology (GIST), Gwangju 61005, Republic of Korea.

Realizing a state of matter in two dimensions has repeatedly proven a novel route of discovering new physical phenomena. Van der Waals (vdW) materials have been at the center of these now extensive research activities. They offer a natural way of producing a monolayer of matter simply by mechanical exfoliation. This work demonstrates that the possible multiferroic state with coexisting antiferromagnetic and ferroelectric orders persists down to the bilayer flake of NiI. By exploiting the optical second-harmonic generation technique, both magnitude and direction of the ferroelectric order, arising from the cycloidal spin order, are successfully traced. The possible multiferroic state's transition temperature decreases from 58 K for the bulk to about 20 K for the bilayer. Our observation will spur extensive efforts to demonstrate multifunctionality in vdW materials, which have been tried mostly by using heterostructures of singly ferroic ones until now.
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http://dx.doi.org/10.1021/acs.nanolett.1c01095DOI Listing
June 2021

Anterior neck soft tissue measurements on computed tomography to predict difficult laryngoscopy: a retrospective study.

Sci Rep 2021 Apr 19;11(1):8438. Epub 2021 Apr 19.

Department of Anesthesiology and Pain Medicine, Anesthesia and Pain Research Institute, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea.

Predicting difficult laryngoscopy is an essential component of the airway management. We aimed to evaluate the use of anterior neck soft tissue measurements on computed tomography for predicting difficult laryngoscopy and to present a clear measurement protocol. In this retrospective study, 281 adult patients whose tracheas were intubated using a direct laryngoscope for thyroidectomy were enrolled. On computed tomography, the distances from the midpoint of the thyrohyoid membrane to the closest concave point of the vallecular (membrane-to-vallecula distance; dMV), and to the most distant point of the epiglottis (membrane-to-epiglottis distance; dME) were measured, respectively. The extended distances straight to the skin anterior from the dMV and dME were called the skin-to-vallecula distance (dSV) and skin-to-epiglottis distance (dSE), respectively. Difficult laryngoscopy was defined by a Cormack-Lehane grade of > 2. Difficult laryngoscopy occurred in 40 (14%) cases. Among four indices, the dMV showed the highest prediction ability for difficult laryngoscopy with an area under the receiver operating characteristic curve of 0.884 (95% confidence interval 0.841-0.919, P < 0.001). The optimal dMV cut-off value for predicting difficult laryngoscopy was 2.33 cm (sensitivity 75.0%; specificity 93.8%). The current study provides novel evidence that increased dMV is a potential predictive indicator of difficult laryngoscopy.
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http://dx.doi.org/10.1038/s41598-021-88076-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8055648PMC
April 2021

Avelumab Versus Docetaxel in Patients With Platinum-Treated Advanced NSCLC: 2-Year Follow-Up From the JAVELIN Lung 200 Phase 3 Trial.

J Thorac Oncol 2021 08 9;16(8):1369-1378. Epub 2021 Apr 9.

CRCM, INSERM, CNRS, Aix Marseille University, Marseille, France(∗); Gustave Roussy Cancer Campus, Villejuif, France. Electronic address:

Introduction: In the JAVELIN Lung 200 trial, avelumab (anti-programmed death-ligand 1 [PD-L1] antibody) did not significantly prolong overall survival (OS) versus docetaxel in patients with platinum-treated PD-L1+ NSCLC. We report greater than 2-year follow-up data.

Methods: Patients with stage IIIB or IV or recurrent NSCLC with disease progression after platinum-doublet chemotherapy were randomized 1:1 to avelumab 10 mg/kg every 2 weeks or docetaxel 75 mg/m every 3 weeks. The primary end point was OS in patients with PD-L1+ tumors (greater than or equal to 1% tumor cell expression; IHC 73-10 pharmDx assay).

Results: Of 792 patients, 529 had PD-L1+ tumors (264 versus 265 in the avelumab versus docetaxel arms, respectively). As of March 4, 2019, median duration of follow-up for OS in the PD-L1+ population was 35.4 months in the avelumab arm and 34.7 months in the docetaxel arm; study treatment was ongoing in 25 (9.5%) versus 0 patients, respectively. In the PD-L1+ population, 2-year OS rates (95% confidence interval [CI]) with avelumab versus docetaxel were 29.9% (24.5%-35.5%) versus 20.5% (15.6%-25.8%); in greater than or equal to 50% PD-L1+ subgroups, 2-year OS rates were 36.4% (29.1%-43.7%) versus 17.7% (11.8%-24.7%) and in the greater than or equal to 80% subgroup were 40.2% (31.3%-49.0%) versus 20.3% (12.9%-28.8%), respectively. Median duration of response (investigator assessed) was 19.1 months (95% CI: 10.8-34.8) versus 5.7 months (95% CI: 4.1-8.3). Safety profiles for both arms were consistent with the primary analysis.

Conclusions: Although the JAVELIN Lung 200 primary analysis (reported previously) revealed that avelumab did not significantly prolong OS versus docetaxel in patients with platinum-treated PD-L1+ NSCLC, posthoc analyses at 2 years of follow-up revealed that 2-year OS rates were doubled with avelumab in subgroups with higher PD-L1 expression (greater than or equal to 50% and greater than or equal to 80%).
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http://dx.doi.org/10.1016/j.jtho.2021.03.009DOI Listing
August 2021

Avelumab Versus Docetaxel in Patients With Platinum-Treated Advanced NSCLC: 2-Year Follow-Up From the JAVELIN Lung 200 Phase 3 Trial.

J Thorac Oncol 2021 08 9;16(8):1369-1378. Epub 2021 Apr 9.

CRCM, INSERM, CNRS, Aix Marseille University, Marseille, France(∗); Gustave Roussy Cancer Campus, Villejuif, France. Electronic address:

Introduction: In the JAVELIN Lung 200 trial, avelumab (anti-programmed death-ligand 1 [PD-L1] antibody) did not significantly prolong overall survival (OS) versus docetaxel in patients with platinum-treated PD-L1+ NSCLC. We report greater than 2-year follow-up data.

Methods: Patients with stage IIIB or IV or recurrent NSCLC with disease progression after platinum-doublet chemotherapy were randomized 1:1 to avelumab 10 mg/kg every 2 weeks or docetaxel 75 mg/m every 3 weeks. The primary end point was OS in patients with PD-L1+ tumors (greater than or equal to 1% tumor cell expression; IHC 73-10 pharmDx assay).

Results: Of 792 patients, 529 had PD-L1+ tumors (264 versus 265 in the avelumab versus docetaxel arms, respectively). As of March 4, 2019, median duration of follow-up for OS in the PD-L1+ population was 35.4 months in the avelumab arm and 34.7 months in the docetaxel arm; study treatment was ongoing in 25 (9.5%) versus 0 patients, respectively. In the PD-L1+ population, 2-year OS rates (95% confidence interval [CI]) with avelumab versus docetaxel were 29.9% (24.5%-35.5%) versus 20.5% (15.6%-25.8%); in greater than or equal to 50% PD-L1+ subgroups, 2-year OS rates were 36.4% (29.1%-43.7%) versus 17.7% (11.8%-24.7%) and in the greater than or equal to 80% subgroup were 40.2% (31.3%-49.0%) versus 20.3% (12.9%-28.8%), respectively. Median duration of response (investigator assessed) was 19.1 months (95% CI: 10.8-34.8) versus 5.7 months (95% CI: 4.1-8.3). Safety profiles for both arms were consistent with the primary analysis.

Conclusions: Although the JAVELIN Lung 200 primary analysis (reported previously) revealed that avelumab did not significantly prolong OS versus docetaxel in patients with platinum-treated PD-L1+ NSCLC, posthoc analyses at 2 years of follow-up revealed that 2-year OS rates were doubled with avelumab in subgroups with higher PD-L1 expression (greater than or equal to 50% and greater than or equal to 80%).
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http://dx.doi.org/10.1016/j.jtho.2021.03.009DOI Listing
August 2021

A phase II study of brentuximab vedotin in patients with relapsed or refractory Epstein-Barr virus-positive and CD30-positive lymphomas.

Haematologica 2021 Aug 1;106(8):2277-2280. Epub 2021 Aug 1.

Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea; Seoul National University Cancer Research Institute, Seoul.

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http://dx.doi.org/10.3324/haematol.2021.278301DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8327727PMC
August 2021

Programmed death-ligand 1 expression level as a predictor of EGFR tyrosine kinase inhibitor efficacy in lung adenocarcinoma.

Transl Lung Cancer Res 2021 Feb;10(2):699-711

Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea.

Background: The main objective of this study was to investigate the impact of programmed death-ligand 1 (PD-L1) expression on the efficacy of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) in patients with advanced non-small cell lung cancer (NSCLC).

Methods: This study analyzed 108 patients with NSCLC who had received EGFR-TKI as first-line systemic treatment at Seoul National University Bundang Hospital and Seoul National University Hospital between December 2012 and October 2018. The National Cancer Center Research Institute (NCCRI) and The Cancer Genome Atlas (TCGA) datasets were analyzed to investigate the mechanisms underlying EGFR-TKI-resistance in tumors with high PD-L1 expression.

Results: Among the 108 patients, 55, 37, and 16 had negative (PD-L1 Tumor proportion score <1%), weak (1-49%), and strong (≥50%) PD-L1 expression, respectively. Patients with strong PD-L1 expression had significantly shorter median progression-free survival (PFS; 7.07 months) than patients with weak (14.73 months, P<0.001) or negative (12.70 months, P=0.001) PD-L1 expression. After adjustment for covariates by Cox regression, PD-L1 expression remained a significant indicator of adverse prognosis. In EGFR-TKI-refractory patients, the frequency of T790M mutation and the PFS following treatment with third-generation EGFR-TKI and PD-1 antibody were similar in the three groups. TCGA and NCCRI database analysis showed that high PD-L1 expression in EGFR-mutated NSCLCs correlated with IL-6/JAK/STAT3 signaling and high mutation frequency.

Conclusions: Strong PD-L1 expression in tumors might be a surrogate indicator of poor response to first-line EGFR-TKIs in NSCLC patients with sensitizing EGFR mutations, and may reflect a resistance mechanism involving JAK-STAT signaling.
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http://dx.doi.org/10.21037/tlcr-20-893DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947423PMC
February 2021

Nivolumab and Ipilimumab as Maintenance Therapy in Extensive-Disease Small-Cell Lung Cancer: CheckMate 451.

J Clin Oncol 2021 Apr 8;39(12):1349-1359. Epub 2021 Mar 8.

Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, South Korea.

Purpose: In extensive-disease small-cell lung cancer (ED-SCLC), response rates to first-line platinum-based chemotherapy are robust, but responses lack durability. CheckMate 451, a double-blind phase III trial, evaluated nivolumab plus ipilimumab and nivolumab monotherapy as maintenance therapy following first-line chemotherapy for ED-SCLC.

Methods: Patients with ED-SCLC, Eastern Cooperative Oncology Group performance status 0-1, and no progression after ≤ 4 cycles of first-line chemotherapy were randomly assigned (1:1:1) to nivolumab 1 mg/kg plus ipilimumab 3 mg/kg once every 3 weeks for 12 weeks followed by nivolumab 240 mg once every 2 weeks, nivolumab 240 mg once every 2 weeks, or placebo for ≤ 2 years or until progression or unacceptable toxicity. Primary end point was overall survival (OS) with nivolumab plus ipilimumab versus placebo. Secondary end points were hierarchically tested.

Results: Overall, 834 patients were randomly assigned. The minimum follow-up was 8.9 months. OS was not significantly prolonged with nivolumab plus ipilimumab versus placebo (hazard ratio [HR], 0.92; 95% CI, 0.75 to 1.12; = .37; median, 9.2 9.6 months). The HR for OS with nivolumab versus placebo was 0.84 (95% CI, 0.69 to 1.02); the median OS for nivolumab was 10.4 months. Progression-free survival HRs versus placebo were 0.72 for nivolumab plus ipilimumab (95% CI, 0.60 to 0.87) and 0.67 for nivolumab (95% CI, 0.56 to 0.81). A trend toward OS benefit with nivolumab plus ipilimumab was observed in patients with tumor mutational burden ≥ 13 mutations per megabase. Rates of grade 3-4 treatment-related adverse events were nivolumab plus ipilimumab (52.2%), nivolumab (11.5%), and placebo (8.4%).

Conclusion: Maintenance therapy with nivolumab plus ipilimumab did not prolong OS for patients with ED-SCLC who did not progress on first-line chemotherapy. There were no new safety signals.
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http://dx.doi.org/10.1200/JCO.20.02212DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8078251PMC
April 2021

A single-arm feasibility study of gradual dose de-escalation of antiemetic dexamethasone for older patients receiving chemotherapy.

J Geriatr Oncol 2021 07 26;12(6):922-929. Epub 2021 Feb 26.

Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea.

Objectives: To investigate whether discontinuation of prophylactic dexamethasone by gradual dose de-escalation is practicable in older patients with cancer undergoing moderately emetogenic chemotherapy.

Materials And Methods: This single-arm, feasibility study prospectively enrolled 40 patients (≥70 years old) with colorectal cancer, who were scheduled to undergo adjuvant FOLFOX chemotherapy, and ten patients ≤60 years old to serve as a control group for pharmacokinetic study. All patients received an antiemetic regimen consisting of intravenous dexamethasone 8 mg and palonosetron at day 1 of the first cycle and underwent phone interviews using symptom questionnaires at day 7 of each cycle. Dexamethasone was tapered off through gradual de-escalation by 2 mg per cycle, when complete response (CR; no emesis and no rescue therapy) was achieved. Primary endpoint was the proportion of patients who discontinued dexamethasone completely.

Results: The median age of the patient was 74 years, and 50% were male. Of the 40 patients, 36 completed twelve cycles of chemotherapy, and 73% (N = 29) were able to discontinue dexamethasone completely. The mean (±SD) dose of dexamethasone per cycle was 3.0 mg (±2.4 mg), which was reduced to 37.5% of the initial dose level. The severity of patient-reported nausea did not significantly change over chemotherapy cycle. Geriatric assessment revealed no decline in any domain and fasting blood glucose and hemoglobin A1c levels were not elevated after twelve cycles of chemotherapy, compared to the baseline.

Conclusion: Gradual dose de-escalation and discontinuation of prophylactic dexamethasone is feasible without compromising its antiemetic effect in older patients undergoing chemotherapy.
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http://dx.doi.org/10.1016/j.jgo.2021.02.018DOI Listing
July 2021

Local Critic Training for Model-Parallel Learning of Deep Neural Networks.

IEEE Trans Neural Netw Learn Syst 2021 Feb 19;PP. Epub 2021 Feb 19.

In this article, we propose a novel model-parallel learning method, called local critic training, which trains neural networks using additional modules called local critic networks. The main network is divided into several layer groups, and each layer group is updated through error gradients estimated by the corresponding local critic network. We show that the proposed approach successfully decouples the update process of the layer groups for both convolutional neural networks (CNNs) and recurrent neural networks (RNNs). In addition, we demonstrate that the proposed method is guaranteed to converge to a critical point. We also show that trained networks by the proposed method can be used for structural optimization. Experimental results show that our method achieves satisfactory performance, reduces training time greatly, and decreases memory consumption per machine. Code is available at https://github.com/hjdw2/Local-critic-training.
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http://dx.doi.org/10.1109/TNNLS.2021.3057380DOI Listing
February 2021

Real-world outcomes of anti-PD1 antibodies in platinum-refractory, PD-L1-positive recurrent and/or metastatic non-small cell lung cancer, and its potential practical predictors: first report from Korean Cancer Study Group LU19-05.

J Cancer Res Clin Oncol 2021 Aug 1;147(8):2459-2469. Epub 2021 Feb 1.

Department of Medical Oncology, Seoul St. Mary's Hospital, The Catholic University, 222 Banpo-daero, Seocho-gu, Seoul, 06591, Republic of Korea.

Purpose: Although immune-checkpoint inhibitors have become a new therapeutic option for recurrent/metastatic non-small cell lung cancers (R/M-NSCLC), its clinical benefit in the real-world is still unclear.

Methods: We investigated 1181 Korean patients with programmed death-1 ligand 1 (PD-L1)-positive [tumor proportion score (TPS) ≥ 10% by the SP263 assay or ≥ 50% by the 22C3 assay] R/M-NSCLC treated with pembrolizumab or nivolumab after failure of platinum-based chemotherapy.

Results: The median age was 67 years, 13% of patients had ECOG-PS ≥ 2, and 27% were never-smokers. Adenocarcinoma was predominant (61%) and 18.1% harbored an EGFR activating mutation or ALK rearrangement. Pembrolizumab and nivolumab were administered to 51.3% and 48.7, respectively, and 42% received them beyond the third-line chemotherapy. Objective response rate (ORR) was 28.6%. Pembrolizumab group showed numerically higher ORR (30.7%) than the nivolumab group (26.4%), but it was comparable with that of the nivolumab group having PD-L1 TPS ≥ 50% (32.4%). Median progression-free survival (PFS) and overall survival (OS) were 2.9 (95% CI 0-27.9) and 10.7 months (95% CI 0-28.2), respectively. In multivariable analysis, concordance of TPS ≥ 50% in both PD-L1 assays and the development of immune-related adverse events (irAEs) were two significant predictors of better ORR, PFS, and OS. EGFR mutation could also predict significantly worse OS outcomes.

Conclusion: The real-world benefit of later-line anti-PD1 antibodies was comparable to clinical trials in patients with R/M-NSCLC, although patients generally were more heavily pretreated and had poorer ECOG-PS. Concordantly high PD-L1 TPS ≥ 50% and development of irAE could independently predict better treatment outcomes, while EGFR mutation negatively affected OS.
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http://dx.doi.org/10.1007/s00432-021-03527-4DOI Listing
August 2021

Parl. Extracts Reduce Acute Inflammation by Targeting Oxidative Stress.

Evid Based Complement Alternat Med 2021 13;2021:7924645. Epub 2021 Jan 13.

College of Pharmacy, Chung-Ang University, Seoul 06974, Republic of Korea.

Parl. (PTP) has traditionally been used for edible and medicinal purposes to treat several disorders, including diabetes and neuralgia. Therefore, this study sought to evaluate the inhibitory effects of PTP leaf ethanol extracts on acute inflammation. Moreover, the reactive oxygen species (ROS) scavenging activity, superoxide dismutase (SOD) activity, lipopolysaccharide (LPS)-induced nitric oxide (NO) generation, and HO-induced lipid peroxidation capacity of PTP were assessed in RAW 264.7 macrophages. Our results suggest that PTP prevents cell damage caused by oxidative free radicals and downregulates the expression of LPS-induced inflammation-associated factors including inducible nitric oxidase synthetase (iNOS), cyclooxygenase-2 (COX-2), and prostaglandin E (PGE). PTP inhibited NO production by 53.5% ( < 0.05) and iNOS expression by 71.5% ( < 0.01) at 100 g/mL. PTP at 100 g/mL also inhibited ROS generation by 58.2% ( < 0.01) and SOD activity by 29.3%, as well as COX-2 expression by 83.3% ( < 0.01) and PGE2 expression by 98.6% ( < 0.01). The anti-inflammatory effects of PTP were confirmed using an arachidonic acid (AA)-induced ear edema mouse model. Ear thickness and myeloperoxidase (MPO) activity were evaluated as indicators of inflammation. PTP inhibited edema formation by 64.5% ( < 0.05) at 1.0 mg/ear. A total of 16 metabolites were identified in PTP extracts and categorized into subgroups, including two phenolic acids (mainly quinic acid), seven flavonoids, five lignans, one sesquiterpenoid, and one long-chain fatty acid. Therefore, our results suggest that PTP possesses anti-inflammatory properties.
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http://dx.doi.org/10.1155/2021/7924645DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7817271PMC
January 2021

Clinical pattern of failure after a durable response to immune check inhibitors in non-small cell lung cancer patients.

Sci Rep 2021 01 28;11(1):2514. Epub 2021 Jan 28.

Department of Internal Medicine, Bundang Hospital, Seoul National University College of Medicine, 82, Gumi-ro 173 beon-gil, Bundang-Gu, Seongnam, Gyeonggi-do, 13620, Republic of Korea.

Although immune checkpoint inhibitors (ICIs) can induce durable responses in non-small-cell lung cancer (NSCLC) patients, a significant proportion of responders still experience progressive disease after a period of response. Limited data are available on the clinical patterns of acquired resistance (AR) to ICIs. Clinical and radiologic data from 125 NSCLC patients treated with anti-PD-1 or PD-L1 antibodies between 2011 and 2018 at two tertiary academic institutions were retrospectively reviewed. Overall, 63 (50.4%) patients experienced AR after ICI treatment in a median of 10.7 months. Among the 13 patients with a partial response with ICI, 12 (32.4%) had only lymph node progression. Most patients (n = 52, 82.5%) had one or two sites with progression (oligo-progression). The median overall survival (OS) after progression was significantly longer in the extrathoracic group than in the thoracic and liver progression groups (30.2 months [95% confidence interval (CI), 13.4 to not reached (NR)], 11.7 months [95% CI, 9.5-21.1], and 5.4 months [95% CI, 2.6-NR], respectively, P < 0.001). Patients with oligo-progression had significantly longer OS after AR than did the multi-progression patients (18.9 months [95% CI, 10.6-NR] vs. 8.8 months [95% CI, 5.7-NR], P = 0.04). No significant difference in progression-free survival was observed between the subsequent chemotherapy and the ICI after AR groups (P = 0.723). Patients with AR after ICI treatment had a unique progression pattern with oligo-progression and high rates of progression only in the lymph nodes. Local treatment and/or continuation of ICIs beyond AR might be an effective option.
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http://dx.doi.org/10.1038/s41598-021-81666-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7844257PMC
January 2021

Association of pericardial adipose tissue with left ventricular structure and function: a region-specific effect?

Cardiovasc Diabetol 2021 01 25;20(1):26. Epub 2021 Jan 25.

Division of Cardiology, Korea University Ansan Hospital, 123, Jeokgeum-ro, Danwon-gu, Gyeonggi-do, 15355, Ansan, South Korea.

Background: The independent role of pericardial adipose tissue (PAT) as an ectopic fat associated with cardiovascular disease (CVD) remains controversial. This study aimed to determine whether PAT is associated with left ventricular (LV) structure and function independent of other markers of general obesity.

Methods: We studied 2471 participants (50.9 % women) without known CVD from the Korean Genome Epidemiology Study, who underwent 2D-echocardiography with tissue Doppler imaging (TDI) and computed tomography measurement for PAT.

Results: Study participants with more PAT were more likely to be men and had higher cardiometabolic indices, including blood pressure, glucose, and cholesterol levels (all P < 0.001). Greater pericardial fat levels across quartiles of PAT were associated with increased LV mass index and left atrial volume index (all P < 0.001) and decreased systolic (P = 0.015) and early diastolic (P < 0.001) TDI velocities, except for LV ejection fraction. These associations remained after a multivariable-adjusted model for traditional CV risk factors and persisted even after additional adjustment for general adiposity measures, such as waist circumference and body mass index. PAT was also the only obesity index independently associated with systolic TDI velocity (P < 0.001).

Conclusions: PAT was associated with subclinical LV structural and functional deterioration, and these associations were independent of and stronger than with general and abdominal obesity measures.
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http://dx.doi.org/10.1186/s12933-021-01219-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7836147PMC
January 2021

First-Line Nivolumab Plus Ipilimumab Versus Chemotherapy in Advanced NSCLC With 1% or Greater Tumor PD-L1 Expression: Patient-Reported Outcomes From CheckMate 227 Part 1.

J Thorac Oncol 2021 04 21;16(4):665-676. Epub 2021 Jan 21.

Princess Alexandra Hospital, Woolloongabba, Australia.

Introduction: In CheckMate 227 (NCT02477826), patients with treatment-naive stage IV or recurrent NSCLC and 1% or greater tumor programmed death ligand 1 expression had significantly improved overall survival with nivolumab plus ipilimumab versus chemotherapy. We present the patient-reported outcomes (PROs).

Methods: Patients (N = 1189) were randomized to nivolumab plus ipilimumab, nivolumab, or chemotherapy. PROs were exploratory. Changes in Lung Cancer Symptom Scale (LCSS) average symptom burden index, LCSS 3-item global index, EQ-5D visual analog scale (VAS), and EQ-5D utility index were analyzed descriptively. Mixed-effect model repeated measures and time-to-first deterioration and improvement analyses were conducted.

Results: PRO completion rates were generally greater than 80%. On-treatment improvements from baseline in LCSS measures of symptom burden and global health status with nivolumab plus ipilimumab generally met or exceeded the minimal important difference (smallest clinically meaningful change) from weeks 24 and 30, respectively; improvements with chemotherapy generally remained below the minimal important difference. Mean on-treatment EQ-5D VAS scores for both treatments approached the U.K. population norm at week 24, remaining so throughout the treatment period. Mixed-effect model repeated measures analyses revealed numerically greater improvements from baseline with nivolumab plus ipilimumab versus chemotherapy across LCSS average symptom burden index and 3-item global index, and EQ-5D VAS and utility index. Nivolumab plus ipilimumab had delayed time-to-first deterioration (hazard ratio [95% confidence interval] 0.74 [0.56 to 0.98]) and a trend for more rapid time-to-first improvement (1.24 [0.98 to 1.59]) versus chemotherapy.

Conclusions: Nivolumab plus ipilimumab revealed delayed deterioration and numerical improvement in symptoms and health-related quality of life versus chemotherapy in patients with advanced NSCLC and 1% or greater programmed death ligand 1 expression.
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http://dx.doi.org/10.1016/j.jtho.2020.12.019DOI Listing
April 2021

Tumor LAG-3 and NY-ESO-1 expression predict durable clinical benefits of immune checkpoint inhibitors in advanced non-small cell lung cancer.

Thorac Cancer 2021 03 17;12(5):619-630. Epub 2021 Jan 17.

Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, South Korea.

Background: Immune checkpoint inhibitors (ICIs) are an established treatment for non-small cell lung cancer (NSCLC) that have demonstrated durable clinical benefits (DCBs). Previous studies have suggested NY-ESO-1 and LAG-3 to be surrogate markers of ICI responses in NSCLC; therefore, we explored the predictive value of their expression in NSCLC.

Methods: We retrospectively reviewed the records of 38 patients with advanced NSCLC treated with anti-PD-1 monoclonal antibodies from 2013 to 2016 at Seoul National University Hospital and Seoul National University Bundang Hospital after failed platinum-based chemotherapy. Tumor tissues from each patient were subjected to immunohistochemical analysis to determine NY-ESO-1, LAG-3, and PD-L1 expression, whose ability to predict progression-free survival (PFS) and overall survival (OS) was then analyzed alongside their positive (PPV) and negative (NPV) predictive values.

Results: NY-ESO-1 or LAG-3 expression was detected in all tumor samples from patients with high PD-L1 expression and was significantly associated with favorable outcomes, unlike PD-L1 expression. Patients with both NY-ESO-1- and LAG-3-expressing tumors had a high DCB rate and those with triple-positive PD-L1, LAG-3, and NY-ESO expression had a superior median OS and PFS than those with triple-negative expression. Furthermore, LAG-3 and NY-ESO-1 co-expression was an independent predictor of both PFS and OS, while LAG-3 displayed a good NPV.

Conclusions: Patients with NSCLC who co-express NY-ESO-1 or LAG-3 with PD-L1 exhibit greater DCBs and improved long-term survival following anti-PD-1 therapy. Moreover, NY-ESO-1 and LAG-3 could be novel predictive biomarkers of survival and should be considered in the future use of ICIs.
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http://dx.doi.org/10.1111/1759-7714.13834DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7919166PMC
March 2021

Outcome and status of postcardiac arrest care in Korea: results from the Korean Hypothermia Network prospective registry.

Clin Exp Emerg Med 2020 Dec 31;7(4):250-258. Epub 2020 Dec 31.

Department of Emergency Medicine, Wonju Severance Christian Hospital, Yonsei University College of Medicine, Wonju, Korea.

Objective: High-quality intensive care, including targeted temperature management (TTM) for patients with postcardiac arrest syndrome, is a key element for improving outcomes after out-of-hospital cardiac arrest (OHCA). We aimed to assess the status of postcardiac arrest syndrome care, including TTM and 6-month survival with neurologically favorable outcomes, after adult OHCA patients were treated with TTM, using data from the Korean Hypothermia Network prospective registry.

Methods: We used the Korean Hypothermia Network prospective registry, a web-based multicenter registry that includes data from 22 participating hospitals throughout the Republic of Korea. Adult comatose OHCA survivors treated with TTM between October 2015 and December 2018 were included. The primary outcome was neurological outcome at 6 months.

Results: Of the 1,354 registered OHCA survivors treated with TTM, 550 (40.6%) survived 6 months, and 413 (30.5%) had good neurological outcomes. We identified 839 (62.0%) patients with preClinsumed cardiac etiology. A total of 937 (69.2%) collapses were witnessed, shockable rhythms were demonstrated in 482 (35.6%) patients, and 421 (31.1%) patients arrived at the emergency department with prehospital return of spontaneous circulation. The most common target temperature was 33°C, and the most common target duration was 24 hours.

Conclusion: The survival and good neurologic outcome rates of this prospective registry show great improvements compared with those of an earlier registry. While the optimal target temperature and duration are still unknown, the most common target temperature was 33°C, and the most common target duration was 24 hours.
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http://dx.doi.org/10.15441/ceem.20.035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7808836PMC
December 2020

Updated Overall Survival and PD-L1 Subgroup Analysis of Patients With Extensive-Stage Small-Cell Lung Cancer Treated With Atezolizumab, Carboplatin, and Etoposide (IMpower133).

J Clin Oncol 2021 02 13;39(6):619-630. Epub 2021 Jan 13.

Vanderbilt University Medical Center, Nashville, TN.

Purpose: IMpower133 (ClinicalTrials.gov identifier: NCT02763579), a randomized, double-blind, phase I/III study, demonstrated that adding atezolizumab (anti-programmed death-ligand 1 [PD-L1]) to carboplatin plus etoposide (CP/ET) for first-line (1L) treatment of extensive-stage small-cell lung cancer (ES-SCLC) resulted in significant improvement in overall survival (OS) and progression-free survival (PFS) versus placebo plus CP/ET. Updated OS, disease progression patterns, safety, and exploratory biomarkers (PD-L1, blood-based tumor mutational burden [bTMB]) are reported.

Patients And Methods: Patients with untreated ES-SCLC were randomly assigned 1:1 to receive four 21-day cycles of CP (area under the curve 5 mg per mL/min intravenously [IV], day 1) plus ET (100 mg/m IV, days 1-3) with atezolizumab (1,200 mg IV, day 1) or placebo, and then maintenance atezolizumab or placebo until unacceptable toxicity, disease progression, or loss of clinical benefit. Tumor specimens were collected; PD-L1 testing was not required for enrollment. The two primary end points, investigator-assessed PFS and OS, were statistically significant at the interim analysis. Updated OS and PFS and exploratory biomarker analyses were conducted.

Results: Patients received atezolizumab plus CP/ET (n = 201) or placebo plus CP/ET (n = 202). At the updated analysis, median follow-up for OS was 22.9 months; 302 deaths had occurred. Median OS was 12.3 and 10.3 months with atezolizumab plus CP/ET and placebo plus CP/ET, respectively (hazard ratio, 0.76; 95% CI, 0.60 to 0.95; descriptive = .0154). At 18 months, 34.0% and 21.0% of patients were alive in atezolizumab plus CP/ET and placebo plus CP/ET arms, respectively. Patients derived benefit from the addition of atezolizumab, regardless of PD-L1 immunohistochemistry or bTMB status.

Conclusion: Adding atezolizumab to CP/ET as 1L treatment for ES-SCLC continued to demonstrate improved OS and a tolerable safety profile at the updated analysis, confirming the regimen as a new standard of care. Exploratory analyses demonstrated treatment benefit independent of biomarker status.
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http://dx.doi.org/10.1200/JCO.20.01055DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8078320PMC
February 2021

Olmutinib in T790M-positive non-small cell lung cancer after failure of first-line epidermal growth factor receptor-tyrosine kinase inhibitor therapy: A global, phase 2 study.

Cancer 2021 May 12;127(9):1407-1416. Epub 2021 Jan 12.

Hanmi Pharmaceutical Company, Ltd, Seoul, Republic of Korea.

Background: In this open-label, international phase 2 study, the authors assessed the efficacy and safety of olmutinib in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) who had a confirmed T790M mutation and disease progression on previous epidermal growth factor receptor-tyrosine kinase inhibitor therapy.

Methods: Patients aged ≥20 years received once-daily oral olmutinib 800 mg continuously in 21-day cycles. The primary endpoint was the objective response rate (patients who had a confirmed best overall response of a complete or partial response), assessed by central review. Secondary endpoints included the disease control rate, the duration of objective response, progression-free survival, and overall survival. Adverse events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (version 4.03).

Results: Overall, 162 patients (median age, 63 years; women, >60%) were enrolled from 68 sites in 9 countries. At the time of database cutoff, 23.5% of enrolled patients remained on treatment. The median treatment duration was 6.5 months (range, 0.03-21.68 months). Overall, 46.3% of patients (95% CI, 38.4%-54.3%) had a confirmed objective response (all partial responses). The best overall response (the objective response rate regardless of confirmation) was 51.9% (84 patients; 95% CI, 43.9%-59.8%). The confirmed disease control rate for all patients was 86.4% (95% CI, 80.2%-91.3%). The median duration of objective response was 12.7 months (95% CI, 8.3-15.4 months). Estimated median progression-free survival was 9.4 months (95% CI, 6.9-12.3 months), and estimated median overall survival was 19.7 months (95% CI, 15.1 months to not reached). All patients experienced treatment-emergent adverse events, and 71.6% of patients had grade ≥3 treatment-emergent adverse events.

Conclusions: Olmutinib has meaningful clinical activity and a manageable safety profile in patients with T790M-positive non-small cell lung cancer who received previous epidermal growth factor receptor-tyrosine kinase inhibitor therapy.
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http://dx.doi.org/10.1002/cncr.33385DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8247868PMC
May 2021

A Fluorescent Probe for Selective Facile Detection of HS in Serum Based on an Albumin-Binding Fluorophore and Effective Masking Reagent.

ACS Omega 2020 Dec 9;5(50):32507-32514. Epub 2020 Dec 9.

Department of Chemistry, Gwangju Institute of Science and Technology (GIST), 123 Cheomdangwagi-ro, Buk-gu, Gwangju 61005, Korea.

A fluorescent probe (4-(2-(4-(diethylamino)phenyl)-4-methyl-5-oxo-4,5-dihydrothieno[3,2-]pyridin-7-yl)phenyl 2,4-dinitrobenzenesulfonate, ) for facile detection of HS in serum was developed based on the combination of an environment-sensitive fluorophore (2-(4-(diethylamino)phenyl)-7-(4-hydroxyphenyl)-4-methylthieno[3,2-]pyridin-5(4)-one, ) with albumin and the 2,4-dinitrobenzene sulfonyl (DNBS) group as a recognition unit for HS. showed remarkable fluorescence enhancement due to HS-triggered thiolysis followed by the formation of a fluorescent fluorophore ()-albumin complex. The HS detection limit of was estimated to be 3.2 μM, and achieves a high selectivity to HS over biothiols by employing 2-formyl benzene boronic acid (2-FBBA) as an effective masking reagent. Furthermore, under optimized sensing conditions, could be applied to accurately determine spiked HS in human serum without the need for any further procedure for the removal of serum proteins.
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http://dx.doi.org/10.1021/acsomega.0c04659DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7758950PMC
December 2020
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