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Jin-Haeng Chung
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EP1.12 - Small Cell Lung Cancer/NET (ID 202)
- Event: WCLC 2019
- Type: E-Poster Viewing in the Exhibit Hall
- Track: Small Cell Lung Cancer/NET
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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EP1.12-08 - Programmed Death-Ligand 1 and Human Leukocyte Antigen Class I Expression in Various Neuroendocrine Tumors of the Lung (Now Available) (ID 913)
08:00 - 18:00 | Author(s): Jin-Haeng Chung
- Abstract
Background
Pulmonary neuroendocrine tumors (PNETs) encompass a broad spectrum of tumors including typical carcinoid (TC) and atypical carcinoid (AC) tumors, small cell lung carcinoma (SCLC) and large cell neuroendocrine carcinoma (LCNEC) with important pathological, biological and clinical differences. Recently, FDA grants Atezolizumab regimen for use in combination with carboplatin and etoposide for the frontline treatment of patients with extensive stage SCLC. The aim of this study was to investigate Programmed death-ligand 1(PD-L1) and Human leukocyte antigen (HLA) class I expression patterns in PNETs.
Method
PD-L1 and HLA class I expression was evaluated by immunohistochemistry in a total of 37 resected lung neuroendocrine tumors using tissue microarray. Correlations between the expression of HLA class I/PD-L1 and clinicopathologic features and prognostic significance were analyzed.
Result
Of the 37 patients enrolled in this study, 32 patients (86.5%) were male and the median age was 66 years (range, 35–81 years), and 28 patients (75.6%) were current or ex-smokers. The pathologic stage (AJCC 8th) in the patients at presentation was IA(including IA1, IA2, IA3) in 11 patients (24.3%), IB in 4 patients (10.8%), IIA in 1 patients (2.7%), IIB in 4 patients (10.8%), IIIA in 10 patients (27.0%), IIIB in 4 patients (10.8%), and IVA in 1 patients (2.7%). Histologically, 6 patients (16.2%) were diagnosed TC, 5 patients (13.5%) with AC, 9 patients (24.3%) with SCLC, and 17 patients (45.9%) with LCNEC. Positive PD-L1 expression in tumor cells was 29.7% (11/37, 1% cut-off), and the numbers (proportions) of positive PD-L1 expression according to histologic subtypes were as follows; TC/AC/SCLC/LCNEC, 2(33.3%)/2(40.0%)/1(11.1%)/6(35.2%). HLA class I expression was reduced in 86.5% (32/37). The numbers (proportions) of reduced HLA class I expression according to histologic subtypes were as follows; TC/AC/SCLC/LCNEC, 5(83.3%)/5(100%)/8(88.9%)/14(82.4%). In survival analysis, (median overall survival (OS); 56 months) there was no significant difference in OS according to PD-L1 and HLA class I expression status. However, two cases with HLA(+)/PD-L1(+) showed more unfavorable survival curves and three cases with HLA(+)/PD-L1(-) showed a tendency of more favorable clinical course.
Conclusion
Lung NETs shows frequent HLA class I reduction and variable PD-L1 expression. Although this is a preliminary study including small number of NETs, the finding that NETs with HLA(+)/PD-L1(-) showed favorable clinical course suggests immune microenvironment might be one of the important biomarker for NETs of the lung.
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MA18 - Advances in Diagnosis of Common Types of NSCLC (ID 145)
- Event: WCLC 2019
- Type: Mini Oral Session
- Track: Pathology
- Presentations: 1
- Now Available
- Moderators:Yuko Minami, Mary Beth Beasley
- Coordinates: 9/10/2019, 11:30 - 13:00, Tokyo (1982)
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MA18.04 - Discussant - MA18.01, MA18.02, MA18.03 (Now Available) (ID 3791)
11:30 - 13:00 | Presenting Author(s): Jin-Haeng Chung
- Abstract
- Presentation
Abstract not provided
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P1.04 - Immuno-oncology (ID 164)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Immuno-oncology
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.04-72 - Tumor Mutational Burden as a Potential Predictive Biomarker of Response to PD-1/PD-L1 Blockade in Non-Small Cell Lung Cancer (ID 760)
09:45 - 18:00 | Author(s): Jin-Haeng Chung
- Abstract
Background
There is an unmet need for biomarkers that will identify patients more likely to respond to immune checkpoint inhibitors (ICIs) in non-small cell lung cancer (NSCLC). We aimed 1) to investigate the impact of tumor mutational burden (TMB) on outcomes of NSCLC patients treated with ICIs, 2) to determine the relationship between TMB, PD-L1 expression, and tumor-infiltrating lymphocytes (TILs), and 3) to present an algorithm that can best predict ICI therapy response through a combination of biomarkers.
Method
We performed targeted deep sequencing on 22 primary and 8 paired metastatic NSCLC from 15 patients treated with ICIs (two primary samples from 7 patients).
Result
The median TMB across all samples was 9.46 mutations/Mb (IQR 1.762–22.03). Applying the cutoff of TMB to 8 mutations/Mb, which best predicts ICI response using receiver operating characteristic curves, 46.7% and 53.3% were high and low TMB group, respectively. There was no correlation between TMB, PD-L1 expression, and TILs. The response rate (RR) to ICIs for patients with high versus low TMB was 3/7 (42.8%) versus 1/8 (12.5%; p>0.05) (Figure 1). The median TMB for responders (n=4) versus nonresponders (n=11) treated with ICIs was 11.2 versus 8.8 mutations/mb. When patients were classified into four groups according to TMB (Figure 2), PD-L1 positivity, and TIL, 50% (2/4) of the patients with TMBhiPD-L1posTILhi showed clinical benefit to ICI. One of the two patients who did not respond to ICI despite TMBhiPD-L1posTILhi group was sarcomatoid carcinoma and one was KRAS-mutant adenocarcinoma. In patients with TMBhiPD-L1negTILlow and TMBlowPD-L1posTILhi, the RR was 40% (2/5). All of TMBlowPD-L1negTILlow group were non-responder (0/6).
Conclusion
TMB can be a potential predictive biomarker of response to ICI treatment in NSCLC patients. An algorithmic approach, which takes into account the integration of TMB, PD-L1 expression, and TIL, may be more effective in screening ICI response groups.
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P1.09 - Pathology (ID 173)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Pathology
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.09-28 - A Significant Discordance Between PANAMutyper™ and Targeted Deep Sequencing for Detecting EGFR Mutation in NSCLC (ID 1083)
09:45 - 18:00 | Author(s): Jin-Haeng Chung
- Abstract
Background
Activating mutations in the tyrosine kinase domain of EGFR are predictive biomarkers for response to EGFR-tyrosine kinase inhibitor (TKI) therapy in non-small cell lung cancer (NSCLC). This study aimed to screen EGFR mutations by PNA clamping-assisted fluorescence melting curve analysis (PANAMutyper™) and targeted deep sequencing, and to evaluate the feasibility of targeted deep sequencing for detection of the mutations.
Method
We examined EGFR mutations in exons 18, 19, 20, and 21 using PANAmutyper™ for consecutive 2170 NSCLC tissues from November 2016 to March 2019. Of these, targeted deep sequencing was performed in 74 patients.
Result
EGFR mutations were identified in 46.4% (1007/2170); 479 (47.6%) had mutations at exon 19, 442(43.9%) at exon 21, 156(15.5%) at exon 20 (including 97 cases with T790M), and 46(4.6%) at exon 18. EGFR mutations were significantly more common in women (63.9%) than men (31.4%) (p <0.001), in adenocarcinoma (54.7%) compared to non-adenocarcinoma (15.3%) (p <0.001). 11.3% (11/97) of T790M mutations was identified in TKI-naïve patients. Interestingly, 27.3% (3/11) of the primary T790M existed alone without L858R or exon 19 deletions. We observed a significant discordance (24.3%: 18/74) of the EGFR mutation between PANAMutyper™ and targeted deep sequencing. Moreover, targeted deep sequencing revealed eight nonsynonymous single‐nucleotide variations, ten insertion‐deletion variations and one amplification in EGFR, which were not detectable by the PANAMutyper™. In 2 out of 18 discordant cases, EGFR mutations were detected only in PANAMutyper™.
Conclusion
EGFR mutations were found frequently in non-adenocarcinomatous NSCLCs, emphasizing that testing for EGFR mutations is essential for all NSCLC patients. As T790M was found in TKI-naive patients, we cannot exclude the possibility of this mutation being a rare mutation existing from the beginning. Taken together, our study demonstrates that primary T790M alone exists and there is a significant discordance between PANAMutyper™ and targeted deep sequencing. The significance of these discrepancies should be carefully interpreted for the patient's treatment and clinical outcome.
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P2.03 - Biology (ID 162)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Biology
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.03-30 - Genetic Characteristics of Lung Cancer in Patients with Idiopathic Pulmonary Fibrosis (ID 369)
10:15 - 18:15 | Author(s): Jin-Haeng Chung
- Abstract
Background
Idiopathic pulmonary fibrosis (IPF) is well known to be associated with lung cancer. However, the genetic alteration contributing to lung cancer development from IPF has not been elucidated. The objective of this study is to investigate the genetic characteristics of IPF-related lung cancer by using next-generation sequencing.
Method
Patients with IPF who diagnosed lung cancer and underwent pulmonary resection surgery at Seoul National University Bundang Hospital were included. We extracted DNA from three parts of pathologic specimen of the same patient; normal, IPF, and lung cancer tissue. Using the DNA extracted from each tissue, whole exome sequencing was performed.
Result
Twenty consecutive IPF patients with lung cancer were included. Median age at diagnosis was 72 years, all patients were male and 19 patients (95%) were former or current smokers. Fourteen patients (70%) had squamous cell carcinoma, five patients (25%) had adenocarcinoma, and one (5%) had large cell carcinoma. TP53 (10/20, 50%) was the most frequently identified genetic mutation in lung cancer tissue, followed by LILRB4 (9/20, 45%). These genetic mutations were not observed in IPF tissue of the same patient. The genetic mutations of FAM231B (5/20, 25%), PSPN (4/20, 20%), GNAQ (4/20, 20%) were also observed in lung cancer tissue, but not in IPF tissue. Genetic mutations of PRH2 and THAP12 were identified both IPF and lung cancer tissue. The frequency of mutations was observed to increase in the order of normal, IPF, and lung cancer tissue (PRH2, 12% vs 35% vs 40%; THAP12, 6% vs 20% vs 25%).
Conclusion
Various genetic mutations are associated with the development of lung cancer from IPF. Certain sequential patterns of genetic mutations may be present in IPF-associated lung cancer. Our findings provide insight into the genomic landscape about IPF-related lung cancer.
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P2.09 - Pathology (ID 174)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Pathology
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.09-24 - IASLC Global Survey for Pathologists on PD-L1 Testing for Non-Small Cell Lung Cancer (ID 906)
10:15 - 18:15 | Author(s): Jin-Haeng Chung
- Abstract
Background
PD-L1 immunohistochemistry (IHC) is now performed for advanced non-small cell lung cancer (NSCLC) patients to examine their eligibility for pembrolizumab treatment, as well as in Europe for durvalumab therapy after chemoradiation for stage III NSCLC patients. Four PD-L1 clinical trial validated assays (commercial assays) have been FDA/EMA approved or are in vitro diagnostic tests in multiple countries, but high running costs have limited their use; thus, many laboratories utilize laboratory-developed tests (LDTs). Overall, the PD-L1 testing seems to be diversely implemented across different countries as well as across different laboratories.
Method
The Immune biomarker working group of the IASLC international pathology panel conducted an international online survey for pathologists on PD-L1 IHC testing for NSCLC patients from 2/1/2019 to 5/31/2019. The goal of the survey was to assess the current prevalence and practice of the PD-L1 testing and to identify issues to improve the practice globally. The survey included more than 20 questions on pre-analytical, analytical and post-analytical aspects of the PDL1 IHC testing, including the availability/type of PD-L1 IHC assay(s) as well as the attendance at a training course(s) and participation in a quality assurance program(s).
Result
344 pathologists from 310 institutions in 64 countries participated in the survey. Of those, 38% were from Europe (France 13%), 23% from North America (US 17%) and 17% from Asia. 53% practice thoracic pathology and 36%, cytopathology. 11 pathologists from 10 countries do not perform PD-L1 IHC and 7.6% send out to outside facility. Cell blocks are used by 75% of the participants and cytology smear by 9.9% along with biopsies and surgical specimens. Pre-analytical conditions are not recorded in 45% of the institutions. Clone 22C3 is the most frequently used (61.5%) (59% with the commercial assay; 41% with LDT) followed by clone SP263 (45%) (71% with the commercial assay; 29% with LDT). Overall, one or several LDTs are used by 57% of the participants. A half of the participants reported turnaround time as 2 days or less, while 13% reported it as 5 days or more. Importantly, 20% of the participants reported no quality assessment, 15%, no formal training session for PD-L1interpretation and 14%, no standardized reporting system.
Conclusion
There is marked heterogeneity in PD-L1 testing practice across individual laboratories. In addition, the significant minority reported a lack of quality assurance, formal training and/or standardized reporting system that need to be established to improve the PD-L1 testing practice globally.
