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Gang Chen



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    EP1.03 - Biology (ID 193)

    • Event: WCLC 2019
    • Type: E-Poster Viewing in the Exhibit Hall
    • Track: Biology
    • Presentations: 13
    • Moderators:
    • Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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      EP1.03-01 - Molecular Spectrum of Patients with JAK1 Mutations in East Asian Non-Small Cell Lung Cancer (ID 188)

      08:00 - 18:00  |  Author(s): Gang Chen

      • Abstract

      Background

      JAK1 is a critical effector of pro-inflammatory cytokine signaling and plays important roles in immune function, while abnormal JAK1 activity has been linked to immunological and neoplastic diseases. The aim of this study is to investigate mutations and prognosis of non-small cell lung cancer (NSCLC) harboring JAK1 mutations.

      Method

      A total of 933 patients with non-small-cell lung cancer were recruited between July 2012 and December 2016. The status of JAK1 mutations and other genes were detected by next generation sequencing.

      Result

      JAK1 gene mutation rate was 1.50% (14/933) in non-small cell lung cancer, including D660G (2 patients), Q499E (1 patient), L954P (1 patient), C16* (1 patient), R239W (1 patient), S295* (1 patient), I359T (1 patient), E791K (1 patient), Q207L (1 patient), R69H (1 patient), H434Y (1 patient), K218N (1 patient) and E662Q (1 patient), and median overall survival (OS) for these patients was 13.0 months. Among them, all patients were JAK1 gene with co-occurring mutations. Briefly, patients with (n=3) or without (n=10) co-occurring EGFR mutations had a median OS of 14.5 months and 13.0 months respectively (P=0.70); patients with (n=13) or without (n=1) co-occurring TP53 mutations had a median OS of 15.0 months and 13.0 months respectively (P=0.64); patients with (n=5) or without (n=8) co-occurring KRAS mutations had a median OS of 11.0 months and 15.0 months respectively (P=0.79); patients with (n=3) or without (n=11) co-occurring NF1 mutations had a median OS of 11.0 months and 20.0 months respectively (P=0.11).

      Conclusion

      Althoght EGFR, TP53, KRAS, NF1 gene accompanied may have less correlation with JAK1 mutation in NSCLC patients, predict which patients may harbor JAK1 mutations, could have implications in triaging toward JAK1 variant identification for potential future targeted therapy. These data have implications for the identification of therapeutic target candidates.

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      EP1.03-03 - Association Between Molecular Spectrum of EZH2 Variants and Prognosis in Patients with Non-Small-Cell Lung Cancer in Chinese Patients (ID 93)

      08:00 - 18:00  |  Author(s): Gang Chen

      • Abstract

      Background

      Enhancer of zeste homolog 2 (EZH2) shows upregulated expression in tumors and is an important driver of tumor development and progression. However, the mechanism underlying the mediation of tumor aggressiveness in non-small-cell lung cancer (NSCLC) by EZH2 remains unclear. The aim of this study is to investigate mutations and prognosis of NSCLC harboring EZH2 mutations.

      Method

      A total of 1122 patients with non-small-cell lung cancer were recruited between July 2012 and December 2016. The status of EZH2 mutations and other genes were detected by next generation sequencing.

      Result

      EZH2 gene mutation rate was 0.62% (7/1122) in non-small cell lung cancer, including K515R (1 patient), I55M (1 patient), D142H (1 patient), K222N (1 patient), Q66R (1 patient), P486S (1 patient), and S652C (1 patient), and median overall survival (OS) for these patients was 20.0 months. Among them, all patients were EZH2 gene with co-occurring mutations. Briefly, patients with (n=2) or without (n=5) co-occurring EGFR mutations had a median OS of 16.0 months and 20.0 months respectively (P=0.88); patients with (n=6) or without (n=1) co-occurring TP53 mutations had a median OS of not up to now and 20.0 months respectively (P=0.79); patients with (n=2) or without (n=5) co-occurring BRAF mutations had a median OS of 14.0 months and 20.0 months respectively (P=0.45); patients with (n=2) or without (n=5) co-occurring SMARCA4 mutations had a median OS of 20.0 months and not up to now respectively (P=0.88).

      Conclusion

      EZH2 mutation may predict a worse prognosis of NSCLC. Methyltransferase inhibitor may be beneficial for NSCLC patients with specific EZH2 mutations. EGFR, TP53, BRAF, SMARCA4 gene accompanied may have less correlation with EZH2 mutation in NSCLC patients. The findings of this study could facilitate both clinical trial design and therapeutic strategies.

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      EP1.03-06 - POLD1 Mutations Define a Unique Molecular Class of Non-Small Cell Lung Cancer in Chinese Patients (ID 198)

      08:00 - 18:00  |  Author(s): Gang Chen

      • Abstract

      Background

      Somatic POLE mutations have been found in a subset of non-small cell lung cancer (NSCLC) while POLD1 mutations are reportedly rare in NSCLC. The aim of this study is to investigate mutations and prognosis of NSCLC harboring POLD1 mutations.

      Method

      A total of 833 patients with non-small-cell lung cancer were recruited between July 2012 and December 2016. The status of POLD1 mutations and other genes were detected by next generation sequencing.

      Result

      POLD1 gene mutation rate was 1.20% (10/833) in non-small cell lung cancer, including L357Rfs*36 (1 patient), R225H (1 patient), D76H (1 patient), I659M (1 patient), T582R (1 patient), A930T (1 patient), A749S (1 patient), G178V (1 patient), V455L (1 patient) and D102N (1 patient), and median overall survival (OS) for these patients was 13.0 months. Among them, all patients were POLD1 gene with co-occurring mutations. Briefly, patients with (n=4) or without (n=6) co-occurring EGFR mutations had a median OS of not up to now and 11.0 months respectively (P=0.11); patients with (n=8) or without (n=2) co-occurring TP53 mutations had a median OS of 13.0 months and 12.6 months respectively (P=0.80); patients with (n=2) or without (n=8) co-occurring NRAS mutations had a median OS of 15.0 months and 13.0 months respectively (P=0.61); patients with (n=3) or without (n=7) co-occurring PTPRD mutations had a median OS of not up to now and 13.0 months respectively (P=0.79).

      Conclusion

      POLD1 mutations represents an uncommon phenotype in NSCLC and may thus reprensent a candidate biomarker for response to immunotherapy in patients with NSCLC.

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      EP1.03-07 - Prevalence and Clinicopathological Characteristics of EIF1AX Mutations in Chinese Patients with Non-Small Cell Lung Cancer (ID 127)

      08:00 - 18:00  |  Author(s): Gang Chen

      • Abstract

      Background

      The EIF1AX gene was recently described as a new thyroid cancer-related gene. Its mutations were mainly reported in poorly differentiated (PDTC) and anaplastic thyroid cancers (ATC), but also in well-differentiated thyroid cancer (WDTC) and in benign thyroid lesions, although less frequently. The prevalence of these mutations in non-small-cell lung cancer (NSCLC) is unknown. The aim of this study is to investigate mutations and prognosis of NSCLC harboring EIF1AX mutations.

      Method

      A total of 923 patients with non-small-cell lung cancer were recruited between July 2012 and December 2016. The status of EIF1AX mutations and other genes were detected by next generation sequencing.

      Result

      EIF1AX gene mutation rate was 1.30% (12/923) in non-small cell lung cancer, including D125N (1 patient), G6D (1 patient), R14G (1 patient), G15D (1 patient), W70C (1 patient), K3N (1 patient), G9D (1 patient), R13P (1 patient), R14S (1 patient), R57G (1 patient), G135E (1 patient), and P2L (1 patient), and median overall survival (OS) for these patients was 20.0 months. Among them, all patients were EIF1AX gene with co-occurring mutations. Among them, 11 patients with co-occurring mutations had a median OS of 20.0 months, and OS of one patient without complex mutations was 19.8 months. No statistically significant difference was found between the two groups (P=0.84). Briefly, patients with (n=2) or without (n=10) co-occurring TP53 mutations had a median OS of 14.0 months and 20.0 months respectively (P=0.87); patients with (n=2) or without (n=10) co-occurring STK11 mutations had a median OS of 4.0 months and 20.0 months respectively (P=0.02); patients with (n=3) or without (n=9) co-occurring NRAS mutations had a median OS of 4.0 months and 20.0 months respectively (P=0.17); patients with (n=3) or without (n=9) co-occurring KRAS mutations had a median OS of not up to now and 20.0 months respectively (P=0.88).

      Conclusion

      There is no significant difference of molecular features in EIF1AX gene mutations in NSCLC. Patients with complex mutations benefited more from therapy than those with single mutations. Next generation sequencing provides a simplified strategy and reasonably high detection rate for EIF1AX mutation, which suggested application of the strategies into clinical molecular diagnostics.

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      EP1.03-09 - Epidemiological Study of TSC1 Mutations Among Non-Small Cell Lung Cancer Patients in China (ID 115)

      08:00 - 18:00  |  Author(s): Gang Chen

      • Abstract

      Background

      The tuberous sclerosis complex 1 (TSC1) is an endogenous regulator of the mechanistic target of rapamycin (mTOR). While mTOR has been shown to play an important role in neoplasm. The aim of this study is to investigate mutations and prognosis of NSCLC harboring TSC1 mutations.

      Method

      A total of 1106 patients with non-small-cell lung cancer were recruited between July 2012 and December 2016. The status of TSC1 mutations and other genes were detected by next generation sequencing.

      Result

      TSC1 gene mutation rate was 1.90% (21/1106) in non-small cell lung cancer, including Q654E (2 patients), R429K (2 patients), A1072D (1 patient), R850S (1 patient), E625K (1 patient), R715Q (1 patient), A84T (1 patient), S1038G (1 patient), M1090I (1 patient), D903H (1 patient), I143N (1 patient), Q3H (1 patient), L134F (1 patient), T1065M (1 patient), V407M (1 patient), S673F (1 patient), D675Y (1 patient), Q149H (1 patient) and T1144P plus L916M (1 patient), and median overall survival (OS) for these patients was 14.0 months. Among them, all patients were TSC1 gene with co-occurring mutations. Briefly, patients with (n=12) or without (n=9) co-occurring TP53 mutations had a median OS of 14.0 months and 15.0 months respectively (P=0.58); patients with (n=9) or without (n=12) co-occurring KRAS mutations had a median OS of not up to now and 14.0 months respectively (P=0.56); patients with (n=2) or without (n=19) co-occurring BRAF mutations had a median OS of 18.5 months and 12.0 months respectively (P=0.71); patients with (n=4) or without (n=17) co-occurring CDKN2A mutations had a median OS of 8.0 months and 18.0 months respectively (P=0.47).

      Conclusion

      Accompanied gene has not well been connected with TSC1 gene mutations. Our finding expands the mutant spectrum of TSC1 gene and adds new understanding of the phenotype.

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      EP1.03-13 - Molecular Characteristics of East Asian Patients with VHL-Mutated Non-Small-Cell Lung Cancer: A Retrospective Study (ID 113)

      08:00 - 18:00  |  Author(s): Gang Chen

      • Abstract

      Background

      The von Hippel-Lindau (VHL) gene is inactivated frequently in sporadic clear-cell renal cell carcinomas (ccRCCs) by genetic alteration. However, the pathological or prognostic significance of VHL gene alteration has not been well defined in the other cancers, especially non-small cell lung cancer (NSCLC). The aim of this study is to investigate mutations and prognosis of NSCLC harboring VHL mutations.

      Method

      A total of 972 patients with non-small-cell lung cancer were recruited between July 2012 and December 2016. The status of VHL mutations and other genes were detected by next generation sequencing.

      Result

      VHL gene mutation rate was 0.72% (7/972) in non-small cell lung cancer, including W117fs*15 (1 patient), G44A (1 patient), G44V (1 patient), P81S (1 patient), R120T (1 patient), E51K (1 patient) and T100A (1 patient), and median overall survival (OS) for these patients was 22.0 months. Among them, all patients were VHL gene with co-occurring mutations. Briefly, patients with (n=2) or without (n=5) co-occurring EGFR mutations had a median OS of 22.0months and 12.0 months respectively (P=0.16); patients with (n=3) or without (n=4) co-occurring TP53 mutations had a median OS of not up to now and 12.0 months respectively (P=0.23); patients with (n=3) or without (n=4) co-occurring KRAS mutations had a median OS of 3.0 months and 22.0 months respectively (P=0.07); patients with (n=2) or without (n=5) co-occurring SETD2 mutations had a median OS of 3.0 months and 22.0 months respectively (P=0.01).

      Conclusion

      The present study expanded the database on VHL gene mutations in NSCLC and enriched the spectrum of known somatic mutations of the VHL gene. Chemotherapy may be considered as a possible treatment for carriers of the mutation. SETD2 mutated accompanied mutations might play a poor prognosis in VHL gene mutation NSCLC.

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      EP1.03-14 - Clinicopathologic Characteristics and Outcomes of Chinese Patients with Non-Small-Cell Lung Cancer and INPP4B Mutations (ID 109)

      08:00 - 18:00  |  Author(s): Gang Chen

      • Abstract

      Background

      Inositol polyphosphate 4-phosphatase B (INPP4B) has been identified as a tumour suppressor in different human cancers. However, the role of INPP4B in the angiogenesis of human non-small cell lung cancer (NSCLC) remains unclear. The aim of this study is to investigate mutations and prognosis of NSCLC harboring INPP4B mutations.

      Method

      A total of 750 patients with non-small-cell lung cancer were recruited between July 2012 and December 2016. The status of INPP4B mutations and other genes were detected by next generation sequencing.

      Result

      INPP4B gene mutation rate was 2.80% (21/750) in non-small cell lung cancer, including p.R623K (2 patients), p.N378S (1 patient), p.G187W (1 patient), p.V117I (1 patient), c.1721-1G>T (1 patient), p.R818* (1 patient), p.T829R (1 patient), p.Q753H (1 patient), p.L542M (1 patient), p.I68M (1 patient), p.Q814E (1 patient), p.K448N (1 patient), p.C617F (1 patient), p.Q600H (1 patient), p.G479* (1 patient), p.L155Q (1 patient), p.P572A (1 patient), p.L16V (1 patient), p.F652Y (1 patient), and p.T671S plus p.N228K (1 patient), and median overall survival (OS) for these patients was 15.0 months. Among them, all patients were INPP4B gene with co-occurring mutations. Briefly, patients with (n=2) or without (n=19) co-occurring EGFR mutations had a median OS of 20.0 months and 5.5 months respectively (P=0.01); patients with (n=17) or without (n=4) co-occurring TP53 mutations had a median OS of 15.0 months and 14.4 months respectively (P=0.68); patients with (n=7) or without (n=14) co-occurring PTPRD mutations had a median OS of not up to now and 15.0 months respectively (P=0.48); patients with (n=8) or without (n=13) co-occurring KRAS mutations had a median OS of 17.0 months and 15.0 months respectively (P=0.68).

      Conclusion

      INPP4B mutations were observed in 2.80 % of cases of NSCLC. INPP4B-mutated NSCLC can exhibit other driver gene alterations. No clinical characteristics were significantly associated with INPP4B mutation.

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      EP1.03-17 - Outcomes of Molecular Characteristics in Chinese BAP1-Mutant Non-Small Cell Lung Cancer Patients (ID 140)

      08:00 - 18:00  |  Author(s): Gang Chen

      • Abstract

      Background

      BRCA1-Associated-Protein 1 (BAP1) is a dynamic tumor suppressor which, when mutated, has been associated with an increased risk of uveal melanoma, cutaneous melanoma, mesothelioma, and several other cancers. There is some clinical evidence for the use of BAP1 mutations as prognostic and predictive biomarker. The aim of this study is to investigate mutations and prognosis of non-small-cell lung cancer (NSCLC) harboring BAP1 mutations.

      Method

      A total of 851 patients with non-small-cell lung cancer were recruited between July 2012 and December 2016. The status of BAP1 mutations and other genes were detected by next generation sequencing.

      Result

      BAP1 gene mutation rate was 1.88% (16/851) in non-small cell lung cancer, including H94Y (1 patient), T177P (1 patient), E198Gfs*45 (1 patient), R238K (1 patient), D34Y (1 patient), Y173C (1 patient), E450K (1 patient), G41C (1 patient), S325F (1 patient), P293L (1 patient), Q28* (1 patient), E498K (1 patient), E631Q (1 patient), H144D (1 patient), Q280* (1 patient), (1 patient) and R518L (1 patient), and median overall survival (OS) for these patients was 24.0 months. Among them, all patients were BAP1 gene with co-occurring mutations. Briefly, patients with (n=4) or without (n=12) co-occurring EGFR mutations had a median OS of 14.5 months and not up to now respectively (P=0.35); patients with (n=9) or without (n=7) co-occurring TP53 mutations had a median OS of not up to now and 24.0 months respectively (P=0.79); patients with (n=3) or without (n=13) co-occurring CDKN2A mutations had a median OS of 24.0 months and not up to now respectively (P=0.57); patients with (n=4) or without (n=12) co-occurring KEAP1 mutations had a median OS of 5.0 months and 24.0 months respectively (P=0.07).

      Conclusion

      BAP1 genetic alter occurs in a subset of NSCLC, and improved understanding of the implications of BAP1 aberrations is critical for the identification of therapeutic target candidates.

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      EP1.03-18 - Analysis of IDH1 Mutation Spectrum from Non-Small-Cell Lung Cancer in East Asian Patients (ID 95)

      08:00 - 18:00  |  Author(s): Gang Chen

      • Abstract

      Background

      Isocitrate dehydrogenase 1 (IDH1) is a metabolic enzyme that converts isocitrate to alpha-ketoglutarate. IDH1 mutations are associated with the accumulation of the oncometabolite D-2-hydroxyglutarate, which acts as an epigenetic modifier, and the development of multiple malignancies. Previous studies uncovered mutations in IDH1 in several malignancies, with the most frequent mutation being IDH1 R132H. It has been demonstrated that IDH1 expression is induced in non-small-cell lung cancer (NSCLC). The aim of this study is to investigate mutations and prognosis of NSCLC harboring IDH1 mutations.

      Method

      A total of 893 patients with non-small-cell lung cancer were recruited between July 2012 and December 2016. The status of IDH1 mutations and other genes were detected by next generation sequencing.

      Result

      IDH1 gene mutation rate was 1.23% (11/893) in non-small cell lung cancer, including Q138S (1 patient), D79V (1 patient), T373N (1 patient), C114* (1 patient), W336L (1 patient), I99M (1 patient), G104R (1 patient), R132C (1 patient), A193S (1 patient), Y34C (1 patient) and H67R (1 patient), and median overall survival (OS) for these patients was 11.0 months. Among them, all patients were IDH1 gene with co-occurring mutations. Briefly, patients with (n=9) or without (n=2) co-occurring TP53 mutations had a median OS of not up to now months and 8.5 months respectively (P=0.32); patients with (n=2) or without (n=9) co-occurring KMT2D mutations had a median OS of 11.5 months and 11.0 months respectively (P=0.80); patients with (n=5) or without (n=6) co-occurring KRAS mutations had a median OS of not up to now months and 8.0 months respectively (P=0.22); patients with (n=2) or without (n=9) co-occurring CREBBP mutations had a median OS of 15.5 months and 8.0 months respectively (P=0.67).

      Conclusion

      Our results demonstrated that decreased IDH1 gene mutation correlated with poor overall survival in NSCLC patients. IDH1 gene mutation may define a subset of patients with lung cancer appropriate for investigational therapeutic strategies.

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      EP1.03-19 - The Frequency and Prognosis of MDM2 Mutations in East Asian Non-Small-Cell Lung Cancer Patients (ID 107)

      08:00 - 18:00  |  Author(s): Gang Chen

      • Abstract

      Background

      In neoplasm, the mouse double minute 2 (MDM2) is an oncoprotein that contributes to the promotion of cell growth, survival, invasion, and therapeutic resistance. The aim of this study is to investigate mutations and prognosis of non-small cell lung cancer (NSCLC) harboring MDM2 mutations.

      Method

      A total of 1152 patients with non-small-cell lung cancer were recruited between July 2012 and December 2016. The status of MDM2 mutations and other genes were detected by next generation sequencing.

      Result

      MDM2 gene mutation rate was 0.52% (6/1152) in non-small cell lung cancer, including D179N (1 patient), S84L (1 patient), T195M (1 patient), V234L (1 patient), A471S (1 patient) and E184Q (1 patient), and median overall survival (OS) for these patients was 24.0 months. Among them, all patients were MDM2 gene with co-occurring mutations. Briefly, patients with (n=2) or without (n=4) co-occurring EGFR mutations had a median OS of 18.5 months and 24.0 months respectively (P=0.89); patients with (n=4) or without (n=2) co-occurring TP53 mutations had a median OS of 24.0 months and 7.0 months respectively (P=0.05); patients with (n=2) or without (n=4) co-occurring BRCA1 mutations had a median OS of 24.0 months and 13.0 months respectively (P=0.20); patients with (n=2) or without (n=4) co-occurring KEAP1 mutations had a median OS of 15.5 months and 24.0 months respectively (P=0.59).

      Conclusion

      MDM2 mutations represent a distinct subset of NSCLC. Next generation sequencing showed that MDM2 mutations commonly co-existed with other driver genes. Our results show that MDM2 mutations delineate an aggressive subtype of lung cancer for which a targeted treatment through MDM2 inhibition might offer new opportunities.

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      EP1.03-24 - Clinicopathologic Characteristics and Survival Outcome in Chinese Patients with Non-Small Cell Lung Cancer and HGF Mutations (ID 137)

      08:00 - 18:00  |  Author(s): Gang Chen

      • Abstract

      Background

      Hepatocyte growth factor (HGF) is the ligand for the tyrosine kinase receptor MET (Mesenchymal Epithelial Transition Factor also known as Hepatocyte Growth Factor Receptor, HGFR). HGF and its receptor, MET, play critical roles in cell proliferation, angiogenesis and invasion in a wide variety of cancers, especially non-small cell lung caner (NSCLC). The aim of this study is to investigate mutations and prognosis of NSCLC harboring HGF mutations.

      Method

      A total of 526 patients with non-small-cell lung cancer were recruited between July 2012 and December 2016. The status of HGF mutations and other genes were detected by next generation sequencing.

      Result

      HGF gene mutation rate was 4.56% (24/526) in non-small cell lung cancer, including E437K (1 patient) , L677I (1 patient), S386L (1 patient), R242Q (1 patient), H717N (1 patient), G520R (1 patient), R234H (1 patient), A713G (1 patient), P703S (1 patient), D264N (1 patient), N127K (1 patient), G506E (1 patient), C84* (1 patient), R647Q (1 patient), G133V (1 patient), D257N (1 patient), S386L (1 patient), S166R (1 patient), P27H (1 patient), C612* (1 patient), W528L (1 patient), G133V (1 patient), G694Wfs*31 (1 patient), and T143S plus G146A (1 patient), and median overall survival (OS) for these patients was 20.0 months. Among them, all patients were HGF gene with co-occurring mutations. Briefly, patients with (n=4) or without (n=20) co-occurring EGFR mutations had a median OS of not up to now and 20.0 months respectively (P=0.18); patients with (n=19) or without (n=5) co-occurring TP53 mutations had a median OS of 20.0 months and 21.0 months respectively (P=0.96); patients with (n=4) or without (n=21) co-occurring BRAF mutations had a median OS of not up to now and 20.0 months respectively (P=0.46); patients with (n=5) or without (n=19) co-occurring ERBB4 mutations had a median OS of 20.0 months and 19.6 months respectively (P=0.83).

      Conclusion

      EGFR, TP53, BRAF and ERBB4 gene accompanied may have less correlation with HGF mutation in NSCLC patients. Results of ongoing studies will provide a platform for further research to offer individualized therapy with the purpose of improving outcomes.

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      EP1.03-28 - Frequency and Molecular Characteristics of BRCA1 Mutations in Non-Small Cell Lung Cancer from East Asian Patients (ID 145)

      08:00 - 18:00  |  Author(s): Gang Chen

      • Abstract

      Background

      Previously identified as a breast and ovarian cancer susceptibility gene, BRCA1 has gained major scientific interest as a potential prognostic and/or predictive marker for various tumors, including non-small-cell lung cancer (NSCLC), the leading cause of cancer related mortality worldwide. The aim of this study is to investigate mutations and prognosis of NSCLC harboring BRCA1 mutations.

      Method

      A total of 730 patients with non-small-cell lung cancer were recruited between July 2012 and December 2016. The status of BRCA1 mutations and other genes were detected by next generation sequencing.

      Result

      BRCA1 gene mutation rate was 2.60% (19/730) in non-small cell lung cancer, including Y856H (3 patients), M1689T (2 patients), N909I (2 patients), G275D (2 patients), N473S (2 patients), S1217C (1 patient), M1628T (1 patient), E649* (1 patient), R1443* (1 patient), V191I (1 patient), I783V (1 patient), M669T (1 patient), and R71K (1 patient), and median overall survival (OS) for these patients was 14.0 months. Among them, all patients were BRCA1 gene with co-occurring mutations. Briefly, patients with (n=3) or without (n=16) co-occurring EGFR mutations had a median OS of 20.0 months and 13.0 months respectively (P=0.56); patients with (n=4) or without (n=15) co-occurring TP53 mutations had a median OS of 20.0 months and 19.5 months respectively (P=0.82); patients with (n=4) or without (n=15) co-occurring PIK3CA mutations had a median OS of not up to now and 13.5 months respectively (P=0.36); patients with (n=5) or without (n=14) co-occurring CDKN2A mutations had a median OS of not up to now months and 13.5 months respectively (P=0.28).

      Conclusion

      Our data reveal BRCA1 mutations represent a distinct subset of NSCLC. NGS might be useful for evaluation of BRCA1 unclassified variants. Our results show that BRCA1 mutations delineate an aggressive subtype of lung cancer for which a targeted treatment through PARP inhibition might offer new opportunities.

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      EP1.03-35 - Prevalence, Clinicopathologic Characteristics, and Molecular Associations of IGF1R Mutations in East Asian Patients with NSCLC (ID 155)

      08:00 - 18:00  |  Author(s): Gang Chen

      • Abstract

      Background

      IGF1R is a ubiquitous receptor tyrosine kinase that plays critical roles in cell proliferation, growth and survival. Clinical studies have demonstrated upregulation of IGF1R mediated signaling in a number of malignancies including colon, breast, and lung cancers. The aim of this study is to investigate mutations and prognosis of non-small cell lung cancer (NSCLC) harboring IGF1R mutations.

      Method

      A total of 812 patients with non-small-cell lung cancer were recruited between July 2012 and December 2016. The status of IGF1R mutations and other genes were detected by next generation sequencing.

      Result

      IGF1R gene mutation rate was 1.60% (13/812) in non-small cell lung cancer, including N977I (2 patients), S751T (1 patient), E1043D (1 patient), G171W (1 patient), E563K (1 patient), R275C (1 patient), F921[2>1] (1 patient), E712K (1 patient), R222W (1 patient), D1024A (1 patient), A760T (1 patient), and K533N (1 patient), and median overall survival (OS) for these patients was 9.0 months. Among them, all patients were IGF1R gene with co-occurring mutations. Briefly, patients with (n=3) or without (n=10) co-occurring EGFR mutations had a median OS of 6.0 months and 11.0 months respectively (P=0.10); patients with (n=12) or without (n=1) co-occurring TP53 mutations had a median OS of 18.0 months and 8.0 months respectively (P=0.68); patients with (n=4) or without (n=9) co-occurring KRAS mutations had a median OS of 14.5 months and 7.0 months respectively (P=0.76); patients with (n=5) or without (n=8) co-occurring NF1 mutations had a median OS of not up to now and 6.5 months respectively (P=0.24).

      Conclusion

      EGFR, TP53, KRAS, NF1 gene accompanied may have less correlation with IGF1R mutation in NSCLC patients. We report different mutations than those previously reported, which emphasizes the importance of personalized medicine that could be empowered by the use of bioinformatics tools in the diagnostic process and therapeutic approaches.

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    EP1.14 - Targeted Therapy (ID 204)

    • Event: WCLC 2019
    • Type: E-Poster Viewing in the Exhibit Hall
    • Track: Targeted Therapy
    • Presentations: 2
    • Moderators:
    • Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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      EP1.14-46 - The KIF5B-RET Fusion as a Novel Mechanism of Acquired EGFR Tyrosine Kinase Inhibitor Resistance in Lung Adenocarcinoma (ID 103)

      08:00 - 18:00  |  Author(s): Gang Chen

      • Abstract

      Background

      Lung cancer is a common malignancy and a leading cause of cancer deaths worldwide. Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. And most NSCLC patients with epidermal growth factor receptor (EGFR) mutations respond well to the treatment with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). Unfortunately, almost all patients with effective EGFR-TKIs therapy eventually develop drug resistance in about 1 year. The most common mechanism of acquired resistance to first-generation EGFR-TKI treatment is the development of the T790M mutation in exon 20 of the EGFR, which occurs in almost one half of cases of acquired resistance.

      Method

      In this case report, we present a 72-year-old male non-smoker patient with an EGFR exon 19 deletion diagnosed with lung adenocarcinoma (LADC), who initially responded to first-generation EGFR-TKI treatment, but developed acquired resistance, and was shown to have gene detected by the next generation sequencing.

      Result

      Repeated liquid biopsy showed the KIF5B-RET fusion gene by next generation sequencing. Therefore, cabozantinib was added to the treatment, and stable disease (SD) was achieved. Unfortunately, the patient did not acquire long-term benefits and the progression-free survival (PFS) was only 2 months

      Conclusion

      Our results suggested that the KIF5B-RET fusion gene is a possible novel cause of acquired resistance to first-generation EGFR-TKIs.

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      EP1.14-47 - Lung Adenocarcinoma with Concurrent KRAS Mutation and ALK Rearrangement Responding to Crizotinib (ID 108)

      08:00 - 18:00  |  Author(s): Gang Chen

      • Abstract

      Background

      Chromosomal translocation resulting in the fusion between the echinoderm microtubule-associated protein-like 4 (EML4) gene and the anaplastic lymphoma kinase (ALK) gene has been considered as a novel oncogenic fusion in a subset of non-small cell lung cancer (NSCLC), mostly in non-smokers with adenocarcinoma. EML4-ALK translocations are commonly reported to be mutually exclusive with EGFR or KRAS mutations.

      Method

      We reported a rare case of 47-year-old female was diagnosed with lung adenocarcinoma and treated with three cycles of chemotherapy. A biopsy acquired after disease progression revealed concurrent KRAS mutation and ALK translocation by a NGS assay.

      Result

      Based on molecular findings, treatment was initiated with crizotinib in September, 2016. After 2 months of therapy, the patient achieved a partial response. Afterwards, the patient was further administrated with crizotinib for 9 months with a stable disease before tumor progression.

      Conclusion

      A further understanding of the molecular biology with multiple oncogenic drivers will promote the optimal treatment for NSCLC.

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    P1.03 - Biology (ID 161)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Biology
    • Presentations: 2
    • Moderators:
    • Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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      P1.03-35 - Analysis of TET2 Gene Aberrations in East Asian Non-Small-Cell Lung Cancer Patients and Evaluation of Their Prognosis (ID 97)

      09:45 - 18:00  |  Author(s): Gang Chen

      • Abstract

      Background

      Ten-eleven translocation 2 (TET2) enzymes are frequently deregulated in cancer, but the genetic spectrum of TET2 mutation non-small cell lung cancer patients (NSCLC) patients is unclear. The aim of this study is to investigate mutations and prognosis of NSCLC harboring TET2 mutations.

      Method

      A total of 895 patients with non-small-cell lung cancer were recruited between July 2012 and December 2016. The status of TET2 mutations and other genes were detected by next generation sequencing.

      Result

      TET2 gene mutation rate was 1.90% (17/895) in non-small cell lung cancer, including G126W (1 patient), E1477* (1 patient), I1871Nfs*4 (1 patient), T665K (1 patient), Y60F (1 patient), D932H (1 patient), M533I (1 patient), R1262W (1 patient), N71Kfs*5 (1 patient), Q769* (1 patient), W1198C (1 patient), Y1645Ifs*16 (1 patient), Q1532* (1 patient), R369W (1 patient), D648Y (1 patient), G1370V (1 patient) and T344K (1 patient), and median overall survival (OS) for these patients was 19.0 months. Among them, all patients were TET2 gene with co-occurring mutations. Briefly, patients with (n=15) or without (n=2) co-occurring TP53 mutations had a median OS of 19.0 months and 4.0 months respectively (P<0.01); patients with (n=3) or without (n=10) co-occurring CTNNB1 mutations had a median OS of 13.0 months and 19.0 months respectively (P=0.90); patients with (n=3) or without (n=10) co-occurring NF1 mutations had a median OS of not up to now months and 13.0 months respectively (P=0.87), patients with (n=3) or without (n=10) co-occurring KDM5C mutations had a median OS of not up to now months and 13.0 months respectively (P=0.75).

      Conclusion

      TET2 oncogenic activation through mutation defines a novel and distinct subset of NSCLC. CTNNB1, NF1 and KDM5C gene accompanied may have less correlation with KIT mutation in NSCLC patients. TP53 accompanied mutations might play a good prognosis in TET2 gene mutation non-small cell lung cancer.

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      P1.03-47 - KEAP1 Mutations in East Asian Patients with NSCLC: An Investigation of Prevalence, Clinicopathologic Characteristics and Prognosis (ID 104)

      09:45 - 18:00  |  Author(s): Gang Chen

      • Abstract

      Background

      The KEAP1/NRF2 pathway is a master regulator of the cellular redox state through the induction of several antioxidant defence genes implicated in chemotherapeutic drugs resistance of tumor cells. Because of the rarity of those mutations, associated clinical features and prognostic significance have not been thoroughly described so far. The aim of this study is to investigate mutations and prognosis of NSCLC harboring KEAP1 mutations.

      Method

      A total of 317 patients with non-small-cell lung cancer were recruited between July 2012 and December 2016. The status of KEAP1 mutations and other genes were detected by next generation sequencing.

      Result

      KEAP1 gene mutation rate was 10.09% (32/317) in non-small cell lung cancer, including D618Tfs*54 (2 patients), W252L (1 patient), G158C (1 patient), D618Tfs*54 (1 patient), L237Q (1 patient), R415C (1 patient), K97N (1 patient), C368F (1 patient), A95T (1 patient), C273F (1 patient), S243F (1 patient), E149K (1 patient), H96L (1 patient), L70Q (1 patient), G558W (1 patient), E493K (1 patient), A40P (1 patient), E343V (1 patient), E219* (1 patient), G158C (1 patient), D235Tfs*3 (1 patient), I125T (1 patient), R320L (1 patient), R470H (1 patient), E244* (1 patient), G158V (1 patient), C368F (1 patient), I185F (1 patient), N157_M161del (1 patient), R336* (1 patient) and E219Q plus D526N (1 patient), and median overall survival (OS) for these patients was 13.5 months. Among them, all patients were KEAP1 gene with co-occurring mutations. Briefly, patients with (n=20) or without (n=12) co-occurring TP53 mutations had a median OS of 14.5 months and 13.5 months respectively (P=0.71); patients with (n=15) or without (n=17) co-occurring KRAS mutations had a median OS of 15.0 months and 12.0 months respectively (P=0.79); patients with (n=16) or without (n=16) co-occurring STK11 mutations had a median OS of 13.5 months and 18.0 months respectively (P=0.60); patients with (n=4) or without (n=28) co-occurring PIK3CA mutations had a median OS of not up to now and 12.0 months respectively (P=0.16).

      Conclusion

      KEAP1 gene mutation coexists with other gene mutation in NSCLC. TP53, KRAS, STK11 and PIK3CA gene accompanied may have less correlation with KEAP1 mutation in NSCLC patients. Analysis of KEAP1 mutations shows promise as a way to refine individual patients with NSCLC, and provides more insight into effective treatment strategies for patients with KEAP1 mutations.

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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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      P1.09-05 - ALK Testing in Chinese Advanced NSCLC Patients: A National-Wide Multicenter Prospective Real-World Data Study (The RATICAL Study) (ID 1800)

      09:45 - 18:00  |  Author(s): Gang Chen

      • Abstract

      Background

      ALK-tyrosine kinase inhibitors increase ORR and PFS times in ALK-fusion positive NSCLC patients. It is therefore crucial to assess the efficacy of different methods for detecting ALK rearrangement. At present, there are most testing methods approved by cFDA to detect ALK rearrangement in China. However, many issues regarding to the procedure and quality control (QC) data of ALK testing in the routine clinical practice is still to be studied. This study is to evaluate the ALK testing platforms, testing procedures, result interpretation quality control and clinicopathological characteristics of ALK positive patients in the real world for Chinese lung cancer patients, and achieve expert consensus on the clinical practice of ALK testing.

      Method

      Top 31 hospitals with lung cancer patients in China will participate in the study. All advanced NSCLC subjects who received ALK gene test and all ALK positive NSCLC patients who received surgical treatment from Oct. 2018 to Dec. 2019 will be enrolled. The testing platforms include IHC-VentanaFISHRT-PCR and NGS. It is expected to enroll a total of 30,000 cases, and the clinicopathological information of the patients will be collected. Ring study and interpretation training will be conducted before the study initiated. When 2,000 and 10,000 cases are enrolled, the interim summary and quality control will be conducted respectively. The results were the interim summary and quality control results of 2,000 cases.

      Result

      The 2263 enrollees (mean age, 63 years) included 1365 males (60.32%) and 907 females (39.68%). 205 (of 2263, 9.06%) cases were ALK positive. The ALK positive rate of females (11.10%) was significantly higher than that of males (7.74%). The ALK positive rate of non-smoking patients (11.54%) was significantly higher than that of smoking patients (5.70%). In addition to ALK, the positive rate of EGFR, KRAS, ROS1, HER2, MET, RET and BRAF gene alterations was 46.05%, 9.52%, 3.13%, 3.09%, 2.98%, 2.12% and 0.94%, respectively. Total rate of all driver gene mutation was 60.37% in males, while it was 91.71% in female. Total rate of all driver gene mutation was 59.77% in smoking patients and 90.44% in non-smoking patients. Concurrent mutation of ALK with EGFR, KRAS or ROS1 was 0.33%, 0.45% and 0.22%, respectively. The fusion of EML4-ALK accounted for 75%. The inconsistency rate of IHC-Ventana with FISH, RT-PCR, NGS was 95.07%, 91.30% and 95.45%, respectively. For ALK IHC quality control, 109 slides were used for ring study, and 31 pathologists participated in the interpretion. Among 60 negative cases, 25 cases (41.7%) were diagnosed as positive (false positive) by at least one pathologist. Among 49 positive cases, 12 cases (24.5%) were diagnosed as negative (false negative) by at least one pathologist; 34 cases (31.2%) were diagnosed as inconclusive by at least one pathologist. There were 3.5% and 1.1% of cases found to be misinterpreted during the internal QC and regional QC, respectively.

      Conclusion

      NSCLC patients harboring ALK gene translocation have unique clinicopathological characteristics. Some problems will still be encountered in the real world clinical practice of ALK testing, which need to be guided by establishment of expert consensus.

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    P1.11 - Screening and Early Detection (ID 177)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Screening and Early Detection
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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      P1.11-09 - Risk of Second Primary Malignancy After Non-Small-Cell Lung Cancer: A Competing Risk Nomogram Based on the SEER Database (ID 975)

      09:45 - 18:00  |  Author(s): Gang Chen

      • Abstract
      • Slides

      Background

      With the improvement of survival for non-small-cell lung cancer (NSCLC), research focused on second primary malignancy (SPM) in NSCLC survivors is becoming urgent. This study aimed to estimate the incidence and risk of SPM in NSCLC patients.

      Method

      We retrospectively analysed 78,175 NSCLC patients diagnosed between 2004 and 2010 in SEER database, with 3,161 (4.04%) SPM cases observed. We firstly evaluated the crude and cumulative incidence of SPM. SPM incidence in NSCLC survivors compared to that in the age-specific reference population was calculated as standardized incidence ratio (SIR). A competing risk nomogram was also built, to predict the risk of SPM.

      Result

      The crude and 10-year cumulative incidences of SPM were 4.04% and 5.05% (95% CI 4.87%-5.25%), respectively, while the SIR was 1.62 (95% CI 1.56-1.68). Initial primary cancer (IPC) diagnosed when aged 60-74 years old, male, black people, being married, IPC in the upper lobe and indicators of better prognosis of IPC were risk factors of SPM after the initial primary NSCLC. A competing risk nomogram was built for the prediction of SPM after the initial primary NSCLC. (Fig. 1) The nomogram was well calibrated and had good discriminative ability, with c-index of 0.80. It showed a significantly wide interval of SPM cumulative incidence between the first and tenth-decile according to the risk model (1.04% vs. 16.70%, p<0.05). The decision curve analysis indicated that the clinical net benefit of the risk model was larger than that in other scenarios (all-screening or no-screening) in a range of threshold probabilities (1% to 20%).

      figure 1.png

      Conclusion

      Our study firstly performed a systematic estimation of the incidence of SPM in NSCLC, which implied the necessity of a risk predicting model. We developed the first competing risk nomogram to predict the risk of SPM, which performed well in the evaluation and might be helpful for individualized SPM screening.

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    P2.04 - Immuno-oncology (ID 167)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Immuno-oncology
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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      P2.04-13 - Interleukin-18 and Lung Cancer: A Mendelian Randomization Study (ID 336)

      10:15 - 18:15  |  Author(s): Gang Chen

      • Abstract
      • Slides

      Background

      Previous studies have shown that Interleukin-18 (IL-18) suppresses the growth of lung cancer. IL-18 might restore natural killer cell-mediated immunosurveillance against MHC class I-deficient tumors and enhance the therapeutic effects of cancer immunotherapy. However, whether there is a causal influence of higher IL-18 protecting against lung cancer remains unknown. We aim to explore whether genetically predicted circulating level of IL-18 is associated with lung cancer through 2-sample Mendelian randomization (MR) analysis.

      Method

      We obtained the summary data for significant single-nucleotide polymorphisms (SNPs, P<5×10–8 ) associated with serum IL-18 from a genome-wide association study of 8293 healthy adults. Their associations with lung cancer and its histological subtypes were evaluated in the International Lung Cancer Consortium (ILCCO, 11348 lung cancer cases, and 15861 controls) applying Inverse variance–weighted (IVW) meta-analysis, Weighted-median analysis, Mendelian randomization–Egger regression, Simple mode method, and Weighted mode method. We also performed several sensitivity analyses to evaluate the potential violation of MR assumptions.

      Result

      Genetically predicted IL-18 level is associated with lower risk of lung cancer (Odds ratio [OR] per 1 standard deviation (SD) increase: 0.824, 95% confidence interval (CI) 0.762-0.890, p<0.001). Similar trends were shown in the histological subtypes of lung cancer: lung adenocarcinoma (OR per 1 SD increase: 0.816, 95%CI 0.708-0.941, p=0.005) and squamous cell lung cancer (OR per 1 SD increase: 0.883, 95%CI 0.787-0.990, p=0.034). Our sensitivity analyses also showed that there was no directional pleiotropy bias and horizontal pleiotropy bias.

      Table 1. Mendelian randomization estimates of associations of genetically predicted circulating IL-18 and lung cancer and its histological subtypes using different analysis methods.

      Variants

      Outcome

      Method

      OR

      95%CI

      P value

      Heterogeneity p

      MR-Egger intercept p

      IL-18

      Lung cancer

      IVW

      0.824

      0.762-0.890

      <0.001*

      0.868

      MR Egger

      0.964

      0.750-1.239

      0.787

      0.976

      0.251

      Weighted median

      0.823

      0.748-0.906

      <0.001*

      Simple mode

      0.826

      0.714-0.955

      0.042*

      Weighted mode

      0.826

      0.727-0.938

      0.026*

      IL-18

      Lung adenocarcinoma

      IVW

      0.816

      0.708-0.941

      0.005*

      0.216

      MR Egger

      1.137

      0.752-1.720

      0.568

      0.372

      0.159

      Weighted median

      0.840

      0.713-0.989

      0.036*

      Simple mode

      0.807

      0.622-1.046

      0.156

      Weighted mode

      0.827

      0.663-1.032

      0.144

      IL-18

      Squamous cell lung cancer

      IVW

      0.883

      0.787-0.990

      0.034*

      0.809

      MR Egger

      0.791

      0.557-1.123

      0.247

      0.765

      0.545

      Weighted median

      0.927

      0.803-1.070

      0.301

      Simple mode

      0.919

      0.736-1.146

      0.480

      Weighted mode

      0.939

      0.765-1.153

      0.572

      *: P value < 0.05; IVW: inverse­variance weighted; OR: odds ratio; CI: confidence interval.

      Conclusion

      Genetically predicted higher IL-18 is causally associated with lower lung cancer risk, indicating that IL-18 might have the potential to be used clinically to protect against lung cancer. Additional work is warranted to confirm the causality and underline the potential mechanisms.

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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): Gang Chen

      • Abstract
      • Slides

      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.

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