PMID- 32866654
OWN - NLM
STAT- MEDLINE
DCOM- 20210201
LR  - 20210201
IS  - 1556-1380 (Electronic)
IS  - 1556-0864 (Linking)
VI  - 15
IP  - 12
DP  - 2020 Dec
TI  - Molecular Characterization and Clinical Outcomes in RET-Rearranged NSCLC.
PG  - 1928-1934
LID - S1556-0864(20)30671-7 [pii]
LID - 10.1016/j.jtho.2020.08.011 [doi]
AB  - INTRODUCTION: RET rearrangements are an emerging targetable oncogenic fusion 
      driver in NSCLC. However, the natural history of disease and activity of 
      different classes of systemic therapy remain to be defined. Furthermore, 
      molecular testing for RET is not yet routine, and the optimal method of testing 
      is unclear. We present a comparative analysis of molecular profiling with 
      fluorescence in situ hybridization (FISH) or next-generation sequencing (NGS) and 
      treatment outcomes. METHODS: This study was a retrospective analysis of patients 
      treated at the National Cancer Centre Singapore. Baseline demographics and 
      treatment outcomes were collected. RESULTS: A total of 64 patients were included, 
      with a median age of 62 years (range: 25-85), 56% were women, 77% were of Chinese 
      ethnicity, 95% had adenocarcinoma, and 69% were never smokers. RET rearrangement 
      was detected by FISH in 30 of 34 patients (88%), NGS in 40 of 43 patients (93%), 
      and with discordant results in seven of 13 patients (54%) tested with both 
      methods. Of 61 patients with stage IIIB/IV or recurrent disease, prevalence of 
      central nervous system metastases was 31% and 92% received palliative systemic 
      therapy. Overall survival was prolonged in patients treated with a selective RET 
      tyrosine kinase inhibitor versus untreated patients (median 49.3 versus 15.3 mo; 
      hazard ratio [HR]: 0.16, 95% confidence interval [CI]: 0.06-0.40, p < 0.001). 
      However, it was not different in patients treated with immunotherapy versus 
      untreated patients (median 37.7 versus 49.3 mo; HR: 1.30, 95% CI: 0.53-3.19, p = 
      0.53). Overall survival was also prolonged in patients with CCDC6-RET fusion 
      versus those with KIF5B-RET fusion (median 113.5 versus 37.7 mo; HR: 0.12, 95% 
      CI: 0.04-0.38, p = 0.009). CONCLUSIONS: In RET-rearranged NSCLC, selective RET 
      tyrosine kinase inhibitor therapy is associated with improved survival outcomes, 
      especially in patients with CCDC6-RET fusion. However, immunotherapy has poor 
      efficacy. NGS and FISH testing methods may also result in substantial 
      discordance.
CI  - Copyright (c) 2020. Published by Elsevier Inc.
FAU - Tan, Aaron C
AU  - Tan AC
AD  - Division of Medical Oncology, National Cancer Centre Singapore, Singapore, 
      Singapore.
FAU - Seet, Amanda O L
AU  - Seet AOL
AD  - Division of Medical Oncology, National Cancer Centre Singapore, Singapore, 
      Singapore.
FAU - Lai, Gillianne G Y
AU  - Lai GGY
AD  - Division of Medical Oncology, National Cancer Centre Singapore, Singapore, 
      Singapore.
FAU - Lim, Tse Hui
AU  - Lim TH
AD  - Division of Pathology, Singapore General Hospital, Singapore, Singapore.
FAU - Lim, Alvin S T
AU  - Lim AST
AD  - Division of Pathology, Singapore General Hospital, Singapore, Singapore; Duke-NUS 
      Medical School, National University of Singapore, Singapore, Singapore.
FAU - Tan, Gek San
AU  - Tan GS
AD  - Division of Pathology, Singapore General Hospital, Singapore, Singapore.
FAU - Takano, Angela
AU  - Takano A
AD  - Division of Pathology, Singapore General Hospital, Singapore, Singapore; Duke-NUS 
      Medical School, National University of Singapore, Singapore, Singapore.
FAU - Tai, David W M
AU  - Tai DWM
AD  - Division of Medical Oncology, National Cancer Centre Singapore, Singapore, 
      Singapore.
FAU - Tan, Tira J Y
AU  - Tan TJY
AD  - Division of Medical Oncology, National Cancer Centre Singapore, Singapore, 
      Singapore.
FAU - Lam, Justina Y C
AU  - Lam JYC
AD  - Division of Medical Oncology, National Cancer Centre Singapore, Singapore, 
      Singapore.
FAU - Ng, Matthew C H
AU  - Ng MCH
AD  - Division of Medical Oncology, National Cancer Centre Singapore, Singapore, 
      Singapore; Duke-NUS Medical School, National University of Singapore, Singapore, 
      Singapore.
FAU - Tan, Wan Ling
AU  - Tan WL
AD  - Division of Medical Oncology, National Cancer Centre Singapore, Singapore, 
      Singapore.
FAU - Ang, Mei-Kim
AU  - Ang MK
AD  - Division of Medical Oncology, National Cancer Centre Singapore, Singapore, 
      Singapore; Duke-NUS Medical School, National University of Singapore, Singapore, 
      Singapore.
FAU - Kanesvaran, Ravindran
AU  - Kanesvaran R
AD  - Division of Medical Oncology, National Cancer Centre Singapore, Singapore, 
      Singapore; Duke-NUS Medical School, National University of Singapore, Singapore, 
      Singapore.
FAU - Ng, Quan Sing
AU  - Ng QS
AD  - Division of Medical Oncology, National Cancer Centre Singapore, Singapore, 
      Singapore.
FAU - Jain, Amit
AU  - Jain A
AD  - Division of Medical Oncology, National Cancer Centre Singapore, Singapore, 
      Singapore; Duke-NUS Medical School, National University of Singapore, Singapore, 
      Singapore.
FAU - Rajasekaran, Tanujaa
AU  - Rajasekaran T
AD  - Division of Medical Oncology, National Cancer Centre Singapore, Singapore, 
      Singapore; Duke-NUS Medical School, National University of Singapore, Singapore, 
      Singapore.
FAU - Lim, Wan-Teck
AU  - Lim WT
AD  - Division of Medical Oncology, National Cancer Centre Singapore, Singapore, 
      Singapore; Duke-NUS Medical School, National University of Singapore, Singapore, 
      Singapore.
FAU - Tan, Eng-Huat
AU  - Tan EH
AD  - Division of Medical Oncology, National Cancer Centre Singapore, Singapore, 
      Singapore; Duke-NUS Medical School, National University of Singapore, Singapore, 
      Singapore.
FAU - Lim, Tony Kiat Hon
AU  - Lim TKH
AD  - Division of Pathology, Singapore General Hospital, Singapore, Singapore; Duke-NUS 
      Medical School, National University of Singapore, Singapore, Singapore.
FAU - Tan, Daniel S W
AU  - Tan DSW
AD  - Division of Medical Oncology, National Cancer Centre Singapore, Singapore, 
      Singapore; Duke-NUS Medical School, National University of Singapore, Singapore, 
      Singapore. Electronic address: daniel.tan.s.w@singhealth.com.sg.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200828
PL  - United States
TA  - J Thorac Oncol
JT  - Journal of thoracic oncology : official publication of the International 
      Association for the Study of Lung Cancer
JID - 101274235
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-ret)
RN  - EC 2.7.10.1 (RET protein, human)
SB  - IM
CIN - J Thorac Oncol. 2020 Dec;15(12):1803-1805. PMID: 33246592
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Female
MH  - Gene Rearrangement
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - *Lung Neoplasms/genetics/therapy
MH  - Male
MH  - Middle Aged
MH  - Proto-Oncogene Proteins c-ret/genetics
MH  - Retrospective Studies
OTO - NOTNLM
OT  - Fluorescence in situ hybridization (FISH)
OT  - Molecular profiling
OT  - Next-generation sequencing (NGS)
OT  - Non-small cell lung cancer (NSCLC)
OT  - RET fusion
OT  - RET rearrangement
EDAT- 2020/09/01 06:00
MHDA- 2021/02/02 06:00
CRDT- 2020/09/01 06:00
PHST- 2020/06/15 00:00 [received]
PHST- 2020/08/07 00:00 [revised]
PHST- 2020/08/09 00:00 [accepted]
PHST- 2020/09/01 06:00 [pubmed]
PHST- 2021/02/02 06:00 [medline]
PHST- 2020/09/01 06:00 [entrez]
AID - S1556-0864(20)30671-7 [pii]
AID - 10.1016/j.jtho.2020.08.011 [doi]
PST - ppublish
SO  - J Thorac Oncol. 2020 Dec;15(12):1928-1934. doi: 10.1016/j.jtho.2020.08.011. Epub 
      2020 Aug 28.