Literature DB >> 28645632

Adjuvant Chemotherapy Guided by Molecular Profiling and Improved Outcomes in Early Stage, Non-Small-Cell Lung Cancer.

Gavitt A Woodard1, Sue X Wang1, Johannes R Kratz1, Clara T Zoon-Besselink1, Chun-Yuan Chiang2, Matthew A Gubens3, Thierry M Jahan3, Collin M Blakely3, Kirk D Jones4, Michael J Mann1, David M Jablons5.   

Abstract

INTRODUCTION: Many early stage non-small-cell lung cancer (NSCLC) patients who are not considered candidates for adjuvant treatment according to current guidelines do harbor occult metastasis, and have disease recurrence despite complete resection. Although National Comprehensive Cancer Network (NCCN) guidelines suggest clinicopathologic characteristics to identify high-risk patients for adjuvant intervention, molecular profiling more accurately predicts 5-year survival. Early evidence of clinical benefit from application of this molecular-based management strategy, however, has not been reported. PATIENTS AND METHODS: An internationally validated, prognostic, 14-gene quantitative polymerase chain reaction expression assay was used to stratify risk prospectively in 100 consecutive patients with stage IA, IB, and IIA nonsquamous NSCLC. Kaplan-Meyer estimates, log rank analysis, and Cox regression were used to compare disease-free survival (DFS) between high-risk patients who did or did not elect adjuvant chemotherapy.
RESULTS: Forty-eight patients (48%) were deemed high-risk according to molecular testing and 36 (36%) met NCCN high-risk criteria; risk designations were discordant in 34 (34%) of all patients. Estimated 5-year DFS was 48.9% among molecular high-risk patients who did not undertake adjuvant chemotherapy, 93.8% among untreated molecular low-risk patients, and 91.7% in molecular high-risk patients who did undergo chemotherapy (P = .004). In contrast, DFS was only 75.2% in untreated NCCN low-risk patients, and 61.9% in untreated NCCN high-risk patients (P = .183).
CONCLUSION: This prospective, nonrandomized study provides initial evidence that high-risk designation according to the 14-gene prognostic assay also predicts benefit from adjuvant chemotherapy for very early stage NSCLC, and further supports the superiority of molecular stratification over current NCCN criteria at identifying high-risk patients.
Copyright © 2017 Elsevier Inc. All rights reserved.

Entities:  

Keywords:  Cisplatin-based adjuvant therapy; NCCN guidelines; Prognostic genetic signature; Risk stratification; Tumor genetic profile

Mesh:

Year:  2017        PMID: 28645632     DOI: 10.1016/j.cllc.2017.05.015

Source DB:  PubMed          Journal:  Clin Lung Cancer        ISSN: 1525-7304            Impact factor:   4.785


  16 in total

1.  Improved outcomes and staging in non-small-cell lung cancer guided by a molecular assay.

Authors:  Alexander R Gupta; Gavitt A Woodard; David M Jablons; Michael J Mann; Johannes R Kratz
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Review 2.  Prognostic and predictive biomarkers post curative intent therapy.

Authors:  Rebecca Feldman; Edward S Kim
Journal:  Ann Transl Med       Date:  2017-09

3.  Gene Expression Signatures Predicting Survival and Chemotherapy Benefit in Patients with Resected Non-small-Cell Lung Cancer.

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Journal:  EBioMedicine       Date:  2018-07       Impact factor: 8.143

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Authors:  Chi-Chen Fan; Sheng-Ta Tsai; Chen-Yuan Lin; Ling-Chu Chang; Juan-Cheng Yang; Guan-Yu Chen; Yuh-Pyng Sher; Shao-Chun Wang; Michael Hsiao; Wei-Chao Chang
Journal:  Redox Biol       Date:  2020-05-16       Impact factor: 11.799

5.  Differential effects of adjuvant EGFR tyrosine kinase inhibitors in patients with different stages of non-small-cell lung cancer after radical resection: an updated meta-analysis.

Authors:  Di Lu; Zhizhi Wang; Xiguang Liu; Siyang Feng; Xiaoying Dong; Xiaoshun Shi; He Wang; Hua Wu; Gang Xiong; Haofei Wang; Kaican Cai
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6.  Could tumor spread through air spaces benefit from adjuvant chemotherapy in stage I lung adenocarcinoma? A multi-institutional study.

Authors:  Donglai Chen; Xiaofan Wang; Fuquan Zhang; Ruoshuang Han; Qifeng Ding; Xuejun Xu; Jian Shu; Fei Ye; Li Shi; Yiming Mao; Yongbing Chen; Chang Chen
Journal:  Ther Adv Med Oncol       Date:  2020-12-14       Impact factor: 8.168

7.  Molecular Analysis of ZNF71 KRAB in Non-Small-Cell Lung Cancer.

Authors:  Qing Ye; Rehab Mohamed; Duaa Dakhlallah; Marieta Gencheva; Gangqing Hu; Martin C Pearce; Siva Kumar Kolluri; Clay B Marsh; Timothy D Eubank; Alexey V Ivanov; Nancy Lan Guo
Journal:  Int J Mol Sci       Date:  2021-04-04       Impact factor: 6.208

Review 8.  Bioinformatic Approaches to Validation and Functional Analysis of 3D Lung Cancer Models.

Authors:  P Jonathan Li; Jeroen P Roose; David M Jablons; Johannes R Kratz
Journal:  Cancers (Basel)       Date:  2021-02-09       Impact factor: 6.639

9.  Development of biomarkers for real precision medicine.

Authors:  Masahiro Shibata; Mohammad Obaidul Hoque
Journal:  Transl Lung Cancer Res       Date:  2018-09

10.  A Six-Gene Signature Predicts Survival of Adenocarcinoma Type of Non-Small-Cell Lung Cancer Patients: A Comprehensive Study Based on Integrated Analysis and Weighted Gene Coexpression Network.

Authors:  Hui Xie; Conghua Xie
Journal:  Biomed Res Int       Date:  2019-12-04       Impact factor: 3.411

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