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The prognostic and therapeutic role of genomic subtyping by sequencing tumor or cell-free DNA in pulmonary large-cell neuroendocrine carcinoma.

Abstract

PURPOSE

The optimal systemic treatment for pulmonary large-cell neuroendocrine carcinoma (LCNEC) is still under debate. Previous studies showed that LCNEC with different genomic characteristics might respond differently to different chemotherapy regimens. In this study, we sought to investigate genomic subtyping using cell-free DNA (cfDNA) analysis in advanced LCNEC and assess its potential prognostic and predictive value.

EXPERIMENTAL DESIGN

Tumor DNA and cfDNA from 63 patients with LCNEC were analyzed by target-captured sequencing. Survival and response analyses were applied to 54 patients with advanced-stage incurable disease who received first line chemotherapy.

RESULTS

The mutation landscape of frequently mutated cancer genes in LCNEC from cfDNA closely resembled that from tumor DNA, which led to a 90% concordance in genomic subtyping. The 63 LCNEC patients were classified into small cell lung cancer (SCLC)-like and non-small cell lung cancer (NSCLC)-like LCNEC based on corresponding genomic features derived from tumor DNA and/or cfDNA. Overall, patients with SCLC-like LCNEC had a shorter overall survival (OS) than those with NSCLC-like LCNEC despite higher response rate (RR) to chemotherapy. Furthermore, treatment with etoposide-platinum was associated with superior response and survival in SCLC-like LCNEC compared to pemetrexed-platinum and gemcitabine/taxane-platinum doublets, while treatment with gemcitabine/taxane-platinum led to a shorter survival compared to etoposide-platinum or pemetrexed-platinum in NSCLC-like LCNEC patients.

CONCLUSIONS

Genomic subtyping has potentials in prognostication and therapeutic decision-making for patients with LCNEC and cfDNA analysis may be a reliable alternative for genomic profiling of LCNEC.

Authors+Show Affiliations

Thoracic Medical Oncology, Peking University Cancer Hospital & Institute.Geneplus-Beijing Institute.Thoracic Medical Oncology, Beijing Cancer Hospital.Department of Thoracic and Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center.immunity, Geneplus-Beijing Institute.Department of Pathology, Peking University Cancer Hospital & Institute.Genomic Medicine, University of Texas MD Anderson Cancer Center.Johns Hopkins Hospital.RD, Geneplus-Beijing Institute.Geneplus-Beijing.Department of Thoracic Surgery Ⅱ,, Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute.Department of Thoracic Medical Oncology, Beijing Cancer Hospital & Institute.Geneplus-Beijing, Geneplus-Beijing.Peking University Cancer Hospital & Institute.Thoracic Medical Oncology, Beijing Cancer Hospital.Department of Pathology, School of Basic Medical Sciences, Third Hospital, Peking University Health Science Center.Thoracic Medical Oncology, Beijing Cancer Hospital.Department of Thoracic Medical Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing 100142, China.Department of Thoracic Medical Oncology, Beijing Cancer Hospital & Institute.Thoraxic medical oncology, beijing cancer hospital & institute.Peking University Cancer Hospital & Institute.Computer Science and Technology, Xi'an Jiaotong University.Thoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center.No affiliation info availableThoracic and Head/Neck Medical Oncology, University of Texas MD Anderson Cancer Center.Section of Thoracic Molecular Oncology, Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center.Thoracic and Cardiovascular Surgery, University of Texas MD Anderson Cancer Center.Department of Biostatistics, The University of Texas MD Anderson Cancer Center.Department of Thoracic and Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center.Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center.Department of Pathology, The University of Texas MD Anderson Cancer Center.Geneplus-Beijing Institute.Geneplus-Beijing Institute.Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center.The University of Texas MD Anderson Cancer Center.Genomic Medicine, GenePlus-Beijing Institute.Department of Thoracic and Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center JZhang20@mdanderson.org.Thoracic medical oncology, Beijing cancer hospital & institute.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31694833

Citation

Zhuo, Minglei, et al. "The Prognostic and Therapeutic Role of Genomic Subtyping By Sequencing Tumor or Cell-free DNA in Pulmonary Large-cell Neuroendocrine Carcinoma." Clinical Cancer Research : an Official Journal of the American Association for Cancer Research, 2019.
Zhuo M, Guan Y, Yang X, et al. The prognostic and therapeutic role of genomic subtyping by sequencing tumor or cell-free DNA in pulmonary large-cell neuroendocrine carcinoma. Clin Cancer Res. 2019.
Zhuo, M., Guan, Y., Yang, X., Hong, L., Wang, Y., Li, Z., ... Zhao, J. (2019). The prognostic and therapeutic role of genomic subtyping by sequencing tumor or cell-free DNA in pulmonary large-cell neuroendocrine carcinoma. Clinical Cancer Research : an Official Journal of the American Association for Cancer Research, doi:10.1158/1078-0432.CCR-19-0556.
Zhuo M, et al. The Prognostic and Therapeutic Role of Genomic Subtyping By Sequencing Tumor or Cell-free DNA in Pulmonary Large-cell Neuroendocrine Carcinoma. Clin Cancer Res. 2019 Nov 6; PubMed PMID: 31694833.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The prognostic and therapeutic role of genomic subtyping by sequencing tumor or cell-free DNA in pulmonary large-cell neuroendocrine carcinoma. AU - Zhuo,Minglei, AU - Guan,Yanfang, AU - Yang,Xue, AU - Hong,Lingzhi, AU - Wang,Yuqi, AU - Li,Zhongwu, AU - Chen,Runzhe, AU - Abbas,Hussein, AU - Chang,Lianpeng, AU - Gong,Yuhua, AU - Wu,Nan, AU - Zhong,Jia, AU - Chen,Wenting, AU - Chen,Hanxiao, AU - Dong,Zhi, AU - Zhu,Xiang, AU - Li,Jianjie, AU - Wang,Yuyan, AU - An,Tongtong, AU - Wu,Meina, AU - Wang,Ziping, AU - Wang,Jiayin, AU - Roarty,Emily B, AU - Rinsurongkawong,Waree, AU - Lewis,Jeff, AU - Roth,Jack A, AU - Swisher,Stephen G, AU - Lee,J Jack, AU - Heymach,John V, AU - Wistuba,Ignacio I, AU - Kalhor,Neda, AU - Yang,Ling, AU - Yi,Xin, AU - Futreal,P Andrew, AU - Glisson,Bonnie S, AU - Xia,Xuefeng, AU - Zhang,Jianjun, AU - Zhao,Jun, Y1 - 2019/11/06/ PY - 2019/10/28/accepted PY - 2019/02/15/received PY - 2019/06/20/revised PY - 2019/11/8/entrez PY - 2019/11/7/pubmed PY - 2019/11/7/medline JF - Clinical cancer research : an official journal of the American Association for Cancer Research JO - Clin. Cancer Res. N2 - PURPOSE: The optimal systemic treatment for pulmonary large-cell neuroendocrine carcinoma (LCNEC) is still under debate. Previous studies showed that LCNEC with different genomic characteristics might respond differently to different chemotherapy regimens. In this study, we sought to investigate genomic subtyping using cell-free DNA (cfDNA) analysis in advanced LCNEC and assess its potential prognostic and predictive value. EXPERIMENTAL DESIGN: Tumor DNA and cfDNA from 63 patients with LCNEC were analyzed by target-captured sequencing. Survival and response analyses were applied to 54 patients with advanced-stage incurable disease who received first line chemotherapy. RESULTS: The mutation landscape of frequently mutated cancer genes in LCNEC from cfDNA closely resembled that from tumor DNA, which led to a 90% concordance in genomic subtyping. The 63 LCNEC patients were classified into small cell lung cancer (SCLC)-like and non-small cell lung cancer (NSCLC)-like LCNEC based on corresponding genomic features derived from tumor DNA and/or cfDNA. Overall, patients with SCLC-like LCNEC had a shorter overall survival (OS) than those with NSCLC-like LCNEC despite higher response rate (RR) to chemotherapy. Furthermore, treatment with etoposide-platinum was associated with superior response and survival in SCLC-like LCNEC compared to pemetrexed-platinum and gemcitabine/taxane-platinum doublets, while treatment with gemcitabine/taxane-platinum led to a shorter survival compared to etoposide-platinum or pemetrexed-platinum in NSCLC-like LCNEC patients. CONCLUSIONS: Genomic subtyping has potentials in prognostication and therapeutic decision-making for patients with LCNEC and cfDNA analysis may be a reliable alternative for genomic profiling of LCNEC. SN - 1078-0432 UR - https://www.unboundmedicine.com/medline/citation/31694833/The_prognostic_and_therapeutic_role_of_genomic_subtyping_by_sequencing_tumor_or_cell-free_DNA_in_pulmonary_large-cell_neuroendocrine_carcinoma L2 - http://clincancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=31694833 DB - PRIME DP - Unbound Medicine ER -