PMID- 35838647
OWN - NLM
STAT- MEDLINE
DCOM- 20221004
LR  - 20230223
IS  - 1557-3265 (Electronic)
IS  - 1078-0432 (Linking)
VI  - 28
IP  - 19
DP  - 2022 Oct 3
TI  - Clinical, Pathologic, and Molecular Prognostic Factors in Patients with 
      Early-Stage EGFR-Mutant NSCLC.
PG  - 4312-4321
LID - 10.1158/1078-0432.CCR-22-0879 [doi]
AB  - PURPOSE: In early-stage, EGFR mutation-positive (EGFR-M+) non-small cell lung 
      cancer (NSCLC), surgery remains the primary treatment, without personalized 
      adjuvant treatments. We aimed to identify risk factors for recurrence-free 
      survival (RFS) to suggest personalized adjuvant strategies in resected 
      early-stage EGFR-M+ NSCLC. EXPERIMENTAL DESIGN: From January 2008 to August 2020, 
      a total of 2,340 patients with pathologic stage (pStage) IB-IIIA, non-squamous 
      NSCLC underwent curative surgery. To identify clinicopathologic risk factors, 
      1,181 patients with pStage IB-IIIA, common EGFR-M+ NSCLC who underwent surgical 
      resection were analyzed. To identify molecular risk factors, comprehensive 
      genomic analysis was conducted in 56 patients with matched case-controls (pStage 
      II and IIIA and type of EGFR mutation). RESULTS: Median follow-up duration was 
      38.8 months (0.5-156.2). Among 1,181 patients, pStage IB, II, and IIIA comprised 
      577 (48.9%), 331 (28.0%), and 273 (23.1%) subjects, respectively. Median RFS was 
      73.5 months [95% confidence interval (CI), 62.1-84.9], 48.7 months (95% CI, 
      41.2-56.3), and 22.7 months (95% CI, 19.4-26.0) for pStage IB, II, and IIIA, 
      respectively (P < 0.001). In multivariate analysis of clinicopathologic risk 
      factors, pStage, micropapillary subtype, vascular invasion, and pleural invasion, 
      and pathologic classification by cell of origin (type II pneumocyte-like tumor 
      cell vs. bronchial surface epithelial cell-like tumor cell) were associated with 
      RFS. As molecular risk factors, the non-terminal respiratory unit (non-TRU) of 
      the RNA subtype (HR, 3.49; 95% CI, 1.72-7.09; P < 0.01) and TP53 mutation (HR, 
      2.50; 95% CI, 1.24-5.04; P = 0.01) were associated with poor RFS independent of 
      pStage II or IIIA. Among the patients with recurrence, progression-free survival 
      of EGFR-tyrosine kinase inhibitor (TKI) in those with the Apolipoprotein B mRNA 
      Editing Catalytic Polypeptide-like (APOBEC) mutation signature was inferior 
      compared with that of patients without this signature (8.6 vs. 28.8 months; HR, 
      4.16; 95% CI, 1.28-13.46; P = 0.02). CONCLUSIONS: The low-risk group with TRU 
      subtype and TP53 wild-type without clinicopathologic risk factors might not need 
      adjuvant EGFR-TKIs. In the high-risk group, with non-TRU subtype and/or TP 53 
      mutation, or clinicopathologic risk factors, a novel adjuvant strategy of 
      EGFR-TKI with others, e.g., chemotherapy or antiangiogenic agents needs to be 
      investigated. Given the poor outcome to EGFR-TKIs after recurrence in patients 
      with the APOBEC mutation signature, an alternative adjuvant strategy might be 
      needed.
CI  - (c)2022 American Association for Cancer Research.
FAU - Jung, Hyun Ae
AU  - Jung HA
AUID- ORCID: 0000-0002-1583-4142
AD  - Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, 
      School of Medicine, Sungkyunkwan University, Seoul, Republic of Korea.
FAU - Lim, Jinyeong
AU  - Lim J
AUID- ORCID: 0000-0001-9358-9552
AD  - Department of Health Sciences and Technology, Samsung Advanced Institute for 
      Health Science and Technology, Sungkyunkwan University, Seoul, Republic of Korea.
AD  - Samsung Genome Institute, Samsung Medical Center, Sungkyunkwan University, Seoul, 
      Republic of Korea.
FAU - Choi, Yoon-La
AU  - Choi YL
AUID- ORCID: 0000-0002-5788-5140
AD  - Department of Pathology and Translational Genomics, Samsung Medical Center, 
      School of Medicine, Sungkyunkwan University, Seoul, Republic of Korea.
FAU - Lee, Se-Hoon
AU  - Lee SH
AD  - Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, 
      School of Medicine, Sungkyunkwan University, Seoul, Republic of Korea.
FAU - Joung, Je-Gun
AU  - Joung JG
AUID- ORCID: 0000-0003-2859-1036
AD  - Department of Biomedical Science, College of Life Science, CHA University, 
      Seongnam, Republic of Korea.
FAU - Jeon, Yeong Jeong
AU  - Jeon YJ
AUID- ORCID: 0000-0001-6745-6131
AD  - Department of Thoracic and Cardiovascular Surgery, Samsung Medical Center, 
      Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
FAU - Choi, Jae Won
AU  - Choi JW
AD  - Department of Thoracic and Cardiovascular Surgery, Samsung Medical Center, 
      Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
FAU - Shin, Sumin
AU  - Shin S
AD  - Department of Thoracic and Cardiovascular Surgery, Samsung Medical Center, 
      Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
FAU - Cho, Jong Ho
AU  - Cho JH
AD  - Department of Thoracic and Cardiovascular Surgery, Samsung Medical Center, 
      Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
FAU - Kim, Hong Kwan
AU  - Kim HK
AD  - Department of Thoracic and Cardiovascular Surgery, Samsung Medical Center, 
      Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
FAU - Choi, Yong Soo
AU  - Choi YS
AD  - Department of Thoracic and Cardiovascular Surgery, Samsung Medical Center, 
      Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
FAU - Zo, Jae Ill
AU  - Zo JI
AD  - Department of Thoracic and Cardiovascular Surgery, Samsung Medical Center, 
      Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
FAU - Shim, Young Mog
AU  - Shim YM
AD  - Department of Thoracic and Cardiovascular Surgery, Samsung Medical Center, 
      Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
FAU - Park, Sehhoon
AU  - Park S
AD  - Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, 
      School of Medicine, Sungkyunkwan University, Seoul, Republic of Korea.
FAU - Sun, Jong-Mu
AU  - Sun JM
AUID- ORCID: 0000-0001-9683-4111
AD  - Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, 
      School of Medicine, Sungkyunkwan University, Seoul, Republic of Korea.
FAU - Ahn, Jin Seok
AU  - Ahn JS
AD  - Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, 
      School of Medicine, Sungkyunkwan University, Seoul, Republic of Korea.
FAU - Ahn, Myung-Ju
AU  - Ahn MJ
AUID- ORCID: 0000-0002-5740-9654
AD  - Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, 
      School of Medicine, Sungkyunkwan University, Seoul, Republic of Korea.
FAU - Han, Joungho
AU  - Han J
AD  - Department of Pathology and Translational Genomics, Samsung Medical Center, 
      School of Medicine, Sungkyunkwan University, Seoul, Republic of Korea.
FAU - Park, Woong-Yang
AU  - Park WY
AUID- ORCID: 0000-0003-4234-0380
AD  - Department of Health Sciences and Technology, Samsung Advanced Institute for 
      Health Science and Technology, Sungkyunkwan University, Seoul, Republic of Korea.
AD  - Samsung Genome Institute, Samsung Medical Center, Sungkyunkwan University, Seoul, 
      Republic of Korea.
FAU - Kim, Jhingook
AU  - Kim J
AD  - Department of Thoracic and Cardiovascular Surgery, Samsung Medical Center, 
      Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
FAU - Park, Keunchil
AU  - Park K
AUID- ORCID: 0000-0002-4846-7449
AD  - Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, 
      School of Medicine, Sungkyunkwan University, Seoul, Republic of Korea.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Clin Cancer Res
JT  - Clinical cancer research : an official journal of the American Association for 
      Cancer Research
JID - 9502500
RN  - 0 (Angiogenesis Inhibitors)
RN  - 0 (Apolipoproteins)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (RNA, Messenger)
RN  - 63231-63-0 (RNA)
RN  - EC 2.7.10.1 (EGFR protein, human)
RN  - EC 2.7.10.1 (ErbB Receptors)
SB  - IM
CIN - Clin Cancer Res. 2023 Feb 1;29(3):687. PMID: 36722137
CIN - Clin Cancer Res. 2023 Feb 1;29(3):686. PMID: 36722138
MH  - Angiogenesis Inhibitors/therapeutic use
MH  - Apolipoproteins/genetics/therapeutic use
MH  - *Carcinoma, Non-Small-Cell Lung/drug therapy/genetics/pathology
MH  - Chemotherapy, Adjuvant
MH  - ErbB Receptors/genetics
MH  - Humans
MH  - *Lung Neoplasms/drug therapy/genetics/pathology
MH  - Mutation
MH  - Neoplasm Staging
MH  - Prognosis
MH  - Protein Kinase Inhibitors/therapeutic use
MH  - RNA
MH  - RNA, Messenger
MH  - Retrospective Studies
MH  - *Small Cell Lung Carcinoma/pathology
EDAT- 2022/07/16 06:00
MHDA- 2022/10/05 06:00
CRDT- 2022/07/15 11:13
PHST- 2022/03/23 00:00 [received]
PHST- 2022/05/17 00:00 [revised]
PHST- 2022/07/13 00:00 [accepted]
PHST- 2022/07/16 06:00 [pubmed]
PHST- 2022/10/05 06:00 [medline]
PHST- 2022/07/15 11:13 [entrez]
AID - 707035 [pii]
AID - 10.1158/1078-0432.CCR-22-0879 [doi]
PST - ppublish
SO  - Clin Cancer Res. 2022 Oct 3;28(19):4312-4321. doi: 10.1158/1078-0432.CCR-22-0879.