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Hyojin Kim
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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): Hyojin Kim
- 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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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 | Presenting Author(s): Hyojin Kim
- 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): Hyojin Kim
- 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.
