Pretreatment neutrophil-to-lymphocyte ratio is a predictive biomarker for EGFR TKI-treated patients with advanced EGFR-mutant Non-small cell lung cancer

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Abstract

Background

Neutrophil-lymphocyte ratio (NLR) has been reported as a prognostic biomarker in various cancers, but its prognostic value for advanced epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC) treated with EGFR tyrosine kinase inhibitors (TKIs) remains unclear. To address this issue, we performed a retrospective study to investigate the clinical value of NLR in these patients.

Methods

All data were collected from medical records. Sixty-five cases with stage IIIB-IVB EGFR-mutant NSCLC treated with EGFR-TKIs were enrolled. The pretreatment NLR was analyzed for associations with disease control rate (DCR) and progression-free survival (PFS). The primary outcomes of interest were DCR and PFS. All the data were analyzed using SPSS 23.0. The PFS curves were plotted by Kaplan-Meier analysis and log-rank test. Univariate and multivariate Cox regression analyses were used to determine the factors affecting PFS.

Results

The results indicated that, compared with those with lower NLR (<2.57), the patients with a higher NLR (≥2.57) showed a significantly shorter PFS (8.8 vs. 12.2 months, P<0.01), and decreased DCR by the end of 8, 10 months after TKIs treatment (62.5% vs. 93.3%, P=0.014; 38.5% vs. 77.8%, P=0.037). COX multivariate analysis showed that NLR was an independent prognostic factor for PFS (P<0.001).

Conclusions

Elevated NLR is significantly associated with lower DCR, shorter PFS, and might act as a meaningful biomarker for predicting the efficacy of TKIs treatment and the prognosis of advanced EGFR-mutant NSCLC. High-quality prospective clinical trials with longer follow-up are needed to further confirm the results.

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Most cited references 27

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Cancer statistics, 2019

Rebecca Siegel, Kimberly D Miller, Ahmedin Jemal (2019)

Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths that will occur in the United States and compiles the most recent data on cancer incidence, mortality, and survival. Incidence data, available through 2015, were collected by the Surveillance, Epidemiology, and End Results Program; the National Program of Cancer Registries; and the North American Association of Central Cancer Registries. Mortality data, available through 2016, were collected by the National Center for Health Statistics. In 2019, 1,762,450 new cancer cases and 606,880 cancer deaths are projected to occur in the United States. Over the past decade of data, the cancer incidence rate (2006-2015) was stable in women and declined by approximately 2% per year in men, whereas the cancer death rate (2007-2016) declined annually by 1.4% and 1.8%, respectively. The overall cancer death rate dropped continuously from 1991 to 2016 by a total of 27%, translating into approximately 2,629,200 fewer cancer deaths than would have been expected if death rates had remained at their peak. Although the racial gap in cancer mortality is slowly narrowing, socioeconomic inequalities are widening, with the most notable gaps for the most preventable cancers. For example, compared with the most affluent counties, mortality rates in the poorest counties were 2-fold higher for cervical cancer and 40% higher for male lung and liver cancers during 2012-2016. Some states are home to both the wealthiest and the poorest counties, suggesting the opportunity for more equitable dissemination of effective cancer prevention, early detection, and treatment strategies. A broader application of existing cancer control knowledge with an emphasis on disadvantaged groups would undoubtedly accelerate progress against cancer.

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New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1).

E A Eisenhauer, P Therasse, J. Bogaerts … (2009)

Assessment of the change in tumour burden is an important feature of the clinical evaluation of cancer therapeutics: both tumour shrinkage (objective response) and disease progression are useful endpoints in clinical trials. Since RECIST was published in 2000, many investigators, cooperative groups, industry and government authorities have adopted these criteria in the assessment of treatment outcomes. However, a number of questions and issues have arisen which have led to the development of a revised RECIST guideline (version 1.1). Evidence for changes, summarised in separate papers in this special issue, has come from assessment of a large data warehouse (>6500 patients), simulation studies and literature reviews. HIGHLIGHTS OF REVISED RECIST 1.1: Major changes include: Number of lesions to be assessed: based on evidence from numerous trial databases merged into a data warehouse for analysis purposes, the number of lesions required to assess tumour burden for response determination has been reduced from a maximum of 10 to a maximum of five total (and from five to two per organ, maximum). Assessment of pathological lymph nodes is now incorporated: nodes with a short axis of 15 mm are considered measurable and assessable as target lesions. The short axis measurement should be included in the sum of lesions in calculation of tumour response. Nodes that shrink to <10mm short axis are considered normal. Confirmation of response is required for trials with response primary endpoint but is no longer required in randomised studies since the control arm serves as appropriate means of interpretation of data. Disease progression is clarified in several aspects: in addition to the previous definition of progression in target disease of 20% increase in sum, a 5mm absolute increase is now required as well to guard against over calling PD when the total sum is very small. Furthermore, there is guidance offered on what constitutes 'unequivocal progression' of non-measurable/non-target disease, a source of confusion in the original RECIST guideline. Finally, a section on detection of new lesions, including the interpretation of FDG-PET scan assessment is included. Imaging guidance: the revised RECIST includes a new imaging appendix with updated recommendations on the optimal anatomical assessment of lesions. A key question considered by the RECIST Working Group in developing RECIST 1.1 was whether it was appropriate to move from anatomic unidimensional assessment of tumour burden to either volumetric anatomical assessment or to functional assessment with PET or MRI. It was concluded that, at present, there is not sufficient standardisation or evidence to abandon anatomical assessment of tumour burden. The only exception to this is in the use of FDG-PET imaging as an adjunct to determination of progression. As is detailed in the final paper in this special issue, the use of these promising newer approaches requires appropriate clinical validation studies.

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Inflammation and cancer: back to Virchow?

Fran Balkwill, Alberto Mantovani (2001)

The response of the body to a cancer is not a unique mechanism but has many parallels with inflammation and wound healing. This article reviews the links between cancer and inflammation and discusses the implications of these links for cancer prevention and treatment. We suggest that the inflammatory cells and cytokines found in tumours are more likely to contribute to tumour growth, progression, and immunosuppression than they are to mount an effective host antitumour response. Moreover cancer susceptibility and severity may be associated with functional polymorphisms of inflammatory cytokine genes, and deletion or inhibition of inflammatory cytokines inhibits development of experimental cancer. If genetic damage is the "match that lights the fire" of cancer, some types of inflammation may provide the "fuel that feeds the flames". Over the past ten years information about the cytokine and chemokine network has led to development of a range of cytokine/chemokine antagonists targeted at inflammatory and allergic diseases. The first of these to enter the clinic, tumour necrosis factor antagonists, have shown encouraging efficacy. In this article we have provided a rationale for the use of cytokine and chemokine blockade, and further investigation of non-steroidal anti-inflammatory drugs, in the chemoprevention and treatment of malignant diseases.

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Author and article information

Journal

Journal ID (nlm-ta): Transl Cancer Res

Journal ID (iso-abbrev): Transl Cancer Res

Journal ID (publisher-id): TCR

Title: Translational Cancer Research

Publisher: AME Publishing Company

ISSN (Print): 2218-676X

ISSN (Electronic): 2219-6803

Publication date (Print and electronic): April 2020

Publication date (Print): April 2020

Volume: 9

Issue: 4

Pages: 2875-2883

Affiliations

[1 ]deptState Key Laboratory of Quality Research in Chinese Medicine , Macau University of Science and Technology , Avenida Wai Long, Taipa, Macau 999078, China, ;

[2 ]deptFaculty of Chinese Medicine , Macau University of Science and Technology , Avenida Wai Long, Taipa, Macau 999078, China, ;

[3 ]deptDepartment of Cancer Pharmacology, Holistic Integrative Pharmacy Institutes, College of Medicine , Hangzhou Normal University , Hangzhou 311121, China;

[4 ]deptDepartment of Medical Oncology, Holistic Integrative Oncology Institutes and Holistic Integrative Cancer Center of Traditional Chinese and Western Medicine, the Affiliated Hospital of Hangzhou Normal University, College of Medicine , Hangzhou Normal University , Hangzhou 311121, Zhejiang, China

Author notes

Contributions: (I) Conception and design: Q Wu, EL Leung, X Sui; (II) Administrative support: C Xu, X Yao, T Li; (III) Provision of study materials or patients: C Xu, Q Wu, J Wang; (IV) Collection and assembly of data: C Xu, X Yao, T Li, B An, J Wang; (V) Data analysis and interpretation: C Xu, X Yao; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors.

[#]

These authors contributed equally to this work.

Correspondence to: Xinbing Sui. Department of Medical Oncology, Holistic Integrative Oncology Institutes and Holistic Integrative Cancer Center of Traditional Chinese and Western Medicine, the Affiliated Hospital of Hangzhou Normal University, College of Medicine, Hangzhou Normal University, Hangzhou 311121, China. Email: hzzju@ 123456zju.edu.cn ; Elaine Lai-Han Leung. State Key Laboratory of Quality Research in Chinese Medicines, Macau University of Science and Technology, Avenida Wai Long, Taipa, Macau, China. Email: lhleung@ 123456must.edu.mo ; Qibiao Wu. State Key Laboratory of Quality Research in Chinese Medicines, Macau University of Science and Technology, Avenida Wai Long, Taipa, Macau, China. Email: qbwu@ 123456must.edu.mo .

Article

Publisher ID: tcr-09-04-2875

DOI: 10.21037/tcr.2020.02.28

PMC ID: 8797611

PubMed ID: 35117644

SO-VID: f8024e55-ae66-42aa-a48d-818d52528048

License:

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

History

Date received : 16 September 2019

Date accepted : 03 January 2020

Funding

Funded by: the Science and Technology Development Fund, Macau SAR

Award ID: File No.: 130/2017/A3

Award ID: 0099/2018/A3

Award ID: 0096/2018/A3

Funded by: National Natural Science Foundation of China

Award ID: 81672932

Award ID: 81874380

Award ID: 81730108

Funded by: Zhejiang Provincial Natural Science Foundation of China for Distinguished Young Scholars

Award ID: LR18H160001

Funded by: Zhejiang province medical science and technology project

Award ID: 2017RC007

Funded by: Talent Project of Zhejiang Association for Science and Technology

Award ID: 2017YCGC002

Funded by: Zhejiang province science and technology project of TCM

Award ID: 2019ZZ016

Funded by: Zhejiang Provincial Project for the key discipline of traditional Chinese Medicine

Pretreatment neutrophil-to-lymphocyte ratio is a predictive biomarker for EGFR TKI-treated patients with advanced EGFR-mutant Non-small cell lung cancer

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Abstract

Background

Methods

Results

Conclusions

Related collections

New directions in predictive processing

Most cited references 27

Cancer statistics, 2019

New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1).

Inflammation and cancer: back to Virchow?

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