PMID- 34272914
OWN - NLM
STAT- MEDLINE
DCOM- 20211025
LR  - 20240403
IS  - 1549-490X (Electronic)
IS  - 1083-7159 (Print)
IS  - 1083-7159 (Linking)
VI  - 26
IP  - 10
DP  - 2021 Oct
TI  - One-Step Polymerase Chain Reaction-Free Nanowire-Based Plasma Cell-Free DNA Assay 
      to Detect EML4-ALK Fusion and to Monitor Resistance in Lung Cancer.
PG  - e1683-e1692
LID - 10.1002/onco.13902 [doi]
AB  - BACKGROUND: Next-generation sequencing has mostly been used for genotyping 
      cell-free DNA (cfDNA) in plasma. However, this assay has several clinical 
      limitations. We evaluated the clinical utility of a novel polymerase chain 
      reaction-free nanowire (NW)-based plasma cfDNA assay for detecting ALK fusion and 
      mutations. PATIENTS, MATERIALS, AND METHODS: We consecutively enrolled 99 
      patients with advanced non-small cell lung cancer undergoing a fluorescence in 
      situ hybridization (FISH) test for ALK fusion; ALK-positive (n = 36). The 
      NW-based assay was performed using 50-100 muL of plasma collected at pretreatment 
      and every 8 weeks during ALK inhibitor treatment. RESULTS: There was high 
      concordance between the NW-based assay and the FISH test for identification of 
      ALK fusion (94.9% with a kappa coefficient value of 0.892, 95% confidence 
      interval [CI], 0.799-0.984). There was no difference in the response rate to the 
      first anaplastic lymphoma kinase inhibitor between the ALK-positive patients 
      identified by the NW-based assay and by the FISH test (73.5% vs. 72.2%, 
      p = .931). In the ALK variant analysis, variants 1 and 3 subgroups were detected 
      in 27 (75.0%) and 8 (22.2%) patients, respectively. Among 24 patients treated 
      with crizotinib, variant 3 subgroup was associated with worse median overall 
      survival than variant 1 subgroup (36.5 months; 95% CI, 0.09-87.6 vs. 19.8 months; 
      95% CI, 9.9-not reached, p = .004]. A serial assessment identified that ALK 
      L1196M resistance mutation emerged before radiologic progression during 
      crizotinib treatment. CONCLUSION: The newly developed simple NW-based cfDNA assay 
      may be clinically applicable for rapid diagnosis of ALK fusion with its variant 
      forms and early detection of resistance. IMPLICATIONS FOR PRACTICE: The authors 
      developed a novel one-step polymerase chain reaction-free nanowire (NW)-based 
      plasma cell-free DNA (cfDNA) assay. This study evaluated the clinical utility of 
      this novel method for the diagnosis of EML4-ALK fusion in advanced non-small cell 
      lung cancer (NSCLC). The NW-based assay and FISH test showed high concordance 
      rate in 99 patients with advanced NSCLC. Serial cfDNA assessment demonstrated 
      this method provided early detection of resistance before radiologic progression 
      during crizotinib treatment. Taken together, plasma cfDNA genotyping by the 
      NW-based cfDNA assay may be useful for the rapid diagnosis of ALK fusion, 
      classifying variants, and early detection of resistance.
CI  - (c) 2021 The Authors. The Oncologist published by Wiley Periodicals LLC on behalf 
      of AlphaMed Press.
FAU - Lee, Youngjoo
AU  - Lee Y
AUID- ORCID: 0000-0003-0180-189X
AD  - Center for Lung Cancer, National Cancer Center Korea, Goyang, Republic of Korea.
FAU - Cho, Youngnam
AU  - Cho Y
AD  - Translational Research Branch, National Cancer Center Korea, Goyang, Republic of 
      Korea.
AD  - Department of Cancer Biomedical Science, Graduate School of Cancer Science and 
      Policy, Goyang, Republic of Korea.
AD  - Genopsy Inc., Seoul, Republic of Korea.
FAU - Park, Eun Young
AU  - Park EY
AD  - Biostatics Collaboration Team, National Cancer Center Korea, Goyang, Republic of 
      Korea.
FAU - Park, Seong-Yun
AU  - Park SY
AD  - Department of Pathology, National Cancer Center Korea, Goyang, Republic of Korea.
FAU - Hwang, Kum Hui
AU  - Hwang KH
AD  - Center for Lung Cancer, National Cancer Center Korea, Goyang, Republic of Korea.
FAU - Han, Ji-Youn
AU  - Han JY
AD  - Center for Lung Cancer, National Cancer Center Korea, Goyang, Republic of Korea.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210802
PL  - England
TA  - Oncologist
JT  - The oncologist
JID - 9607837
RN  - 0 (Cell-Free Nucleic Acids)
RN  - 0 (EML4-ALK fusion protein, human)
RN  - 0 (Oncogene Proteins, Fusion)
RN  - 0 (Protein Kinase Inhibitors)
RN  - EC 2.7.10.1 (Anaplastic Lymphoma Kinase)
SB  - IM
MH  - Anaplastic Lymphoma Kinase/genetics
MH  - *Carcinoma, Non-Small-Cell Lung/diagnosis/drug therapy/genetics
MH  - *Cell-Free Nucleic Acids/genetics
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - *Lung Neoplasms/diagnosis/drug therapy/genetics
MH  - *Nanowires
MH  - Oncogene Proteins, Fusion/genetics
MH  - Protein Kinase Inhibitors/therapeutic use
PMC - PMC8488792
OTO - NOTNLM
OT  - Circulating tumor DNA
OT  - EML4-ALK
OT  - Lung cancer
OT  - Nanowire
OT  - Plasma
COIS- Disclosures of potential conflicts of interest may be found at the end of this 
      article.
EDAT- 2021/07/18 06:00
MHDA- 2021/10/26 06:00
PMCR- 2021/10/01
CRDT- 2021/07/17 08:38
PHST- 2020/07/29 00:00 [received]
PHST- 2020/12/04 00:00 [accepted]
PHST- 2021/07/18 06:00 [pubmed]
PHST- 2021/10/26 06:00 [medline]
PHST- 2021/07/17 08:38 [entrez]
PHST- 2021/10/01 00:00 [pmc-release]
AID - ONCO13902 [pii]
AID - 10.1002/onco.13902 [doi]
PST - ppublish
SO  - Oncologist. 2021 Oct;26(10):e1683-e1692. doi: 10.1002/onco.13902. Epub 2021 Aug 
      2.