PMID- 31476386
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20201001
IS  - 1936-5233 (Print)
IS  - 1936-5233 (Electronic)
IS  - 1936-5233 (Linking)
VI  - 12
IP  - 12
DP  - 2019 Dec
TI  - Next-Generation Sequencing May Discriminate Extreme Long-term versus Short-term 
      Survival in Patients with Metastatic Small Cell Lung Cancer (SCLC).
PG  - 1539-1548
LID - S1936-5233(19)30245-1 [pii]
LID - 10.1016/j.tranon.2019.08.004 [doi]
AB  - BACKGROUND: Molecular underpinnings that may prognosticate survival could 
      increase understanding of small cell lung cancer (SCLC) tumor behavior. Here, we 
      report the clinicopathological characteristics and biomarker profiles of 
      short-term (ST) versus long-term (LT) survival in patients with metastatic SCLC. 
      METHODS: Of the 876 consecutive metastatic SCLC patients receiving standard of 
      care therapy, 44 met the definition of LT and 91 for ST, respectively. Available 
      FFPE tumor tissue blocks were analyzed by next-generation sequencing (NGS). 
      Analysis included gene mutations, copy number variations, mRNA expression, and 
      protein expression by immunohistochemistry, followed by correlation with 
      clinicopathological characteristics. RESULTS: There were no statistically 
      significant and clinically relevant differences in cases with or without FFPE 
      according to major clinicopathological variables in ST and LT. However, according 
      to NGS, five mutually exclusive gene mutations were identified (E1A binding 
      protein P300 [EP300] p.N217S; p.E152K; human epidermal growth factor receptor 4 
      [ERBB4] p.E317K; BRCA1, DNA repair associated [BRCA1] p.E1661N, and epidermal 
      growth factor receptor [EGFR] p.V742A). Comparing LT vs. ST survivals, a twofold 
      increase was found in the average predicted number of drugs per patient off 
      compendium. We found high SSTR2 mRNA expressions in all LT patients (vs. two 
      [20%] ST patients), which may reflect more benign neuroendocrine tumor 
      characteristics. CONCLUSIONS: Consolidation radiation therapy and higher 
      predicted drug sensitivity for off compendium were associated with LT compared to 
      ST patients in SCLC. NGS profiling of extreme survivals may improve 
      classification of SCLC and possibly identify clinically relevant new targets.
CI  - Copyright (c) 2019 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Lohinai, Zoltan
AU  - Lohinai Z
AD  - National Koranyi Institute of Pulmonology, Budapest, Hungary; Department of 
      Thoracic Surgery, Semmelweis University and National Institute of Oncology, 
      Budapest, Hungary; Division of Thoracic Surgery, Department of Surgery, 
      Comprehensive Cancer Center, Medical University of Vienna, Austria. Electronic 
      address: zoltan.lohinai@koranyi.hu.
FAU - Megyesfalvi, Zsolt
AU  - Megyesfalvi Z
AD  - National Koranyi Institute of Pulmonology, Budapest, Hungary; Department of 
      Thoracic Surgery, Semmelweis University and National Institute of Oncology, 
      Budapest, Hungary.
FAU - Dome, Balazs
AU  - Dome B
AD  - National Koranyi Institute of Pulmonology, Budapest, Hungary; Department of 
      Thoracic Surgery, Semmelweis University and National Institute of Oncology, 
      Budapest, Hungary; Division of Thoracic Surgery, Department of Surgery, 
      Comprehensive Cancer Center, Medical University of Vienna, Austria. Electronic 
      address: balazs.dome@meduniwien.ac.at.
FAU - Weiss, Glen J
AU  - Weiss GJ
AD  - MiRanostics Consulting, Oro Valley, AZ, United States.
LA  - eng
PT  - Journal Article
DEP - 20190831
PL  - United States
TA  - Transl Oncol
JT  - Translational oncology
JID - 101472619
PMC - PMC6727016
EDAT- 2019/09/03 06:00
MHDA- 2019/09/03 06:01
PMCR- 2019/08/31
CRDT- 2019/09/03 06:00
PHST- 2019/05/17 00:00 [received]
PHST- 2019/07/31 00:00 [revised]
PHST- 2019/08/02 00:00 [accepted]
PHST- 2019/09/03 06:00 [pubmed]
PHST- 2019/09/03 06:01 [medline]
PHST- 2019/09/03 06:00 [entrez]
PHST- 2019/08/31 00:00 [pmc-release]
AID - S1936-5233(19)30245-1 [pii]
AID - 10.1016/j.tranon.2019.08.004 [doi]
PST - ppublish
SO  - Transl Oncol. 2019 Dec;12(12):1539-1548. doi: 10.1016/j.tranon.2019.08.004. Epub 
      2019 Aug 31.