Prognostic Significance of Host-related Biomarkers for Survival in Patients with Advanced Non-Small Cell Lung Cancer

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Abstract

Objective: This study identified host-related prognostic biomarkers for survival in patients with advanced non-small cell lung cancer (NSCLC).

Methods: This study was based on the retrospective review of the medical records of 135 patients with pathologically confirmed advanced NSCLC. The host-related biomarkers assessed in this study that reflected patient condition included hemoglobin (Hb) levels; platelet (PLT), neutrophil, lymphocyte, and monocyte counts; and ferritin concentrations. The overall survival (OS) was calculated by Kaplan-Meier analysis and compared using log-rank tests. Univariate and multivariate analyses of Cox proportional hazards regression were used to evaluate the prognostic impact for survival.

Results: Of the enrolled patients, 91.1% had stage IV NSCLC, 42.2% had ECOG-PS scores of 2, and 57% had undergone multiple rounds of prior systemic therapy. The prognostic factors included low Hb concentration (men: Hb < 13 g/dL, women: Hb < 12 g/dL; p = 0.046), increased neutrophil count (> 7,700 cells/μL; p < 0.001), decreased lymphocyte count (≤ 1500 cells/μL; p = 0.011), increased monocyte count (> 800 cells/μL; p < 0.001), and high ferritin level (men: > 200 ng/mL, women: > 150 ng/mL; p < 0.001), which were associated with poor OS and increased hazard of mortality. The multivariate proportional hazards model revealed that lymphocyte count, monocyte count, and ferritin level were independent host-related prognostic biomarkers for survival. Increased monocyte count (HR, 3.15; 95% CI, 1.64-6.04; p < 0.001) and high ferritin level (HR, 1.81; 95% CI, 1.24-2.64; p = 0.002) were significantly associated with poor survival, whereas increased lymphocyte count (HR, 0.57; 95% CI, 0.40-0.83; p = 0.004) showed prolonged survival.

Conclusion: Immune factors, such as lymphocyte and monocyte counts, as well as serum ferritin levels, are significant host-related prognostic biomarkers for survival with direct relevance to survival time in patients with advanced NSCLC.

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The blockade of immune checkpoints in cancer immunotherapy.

Drew M Pardoll (2012)

Among the most promising approaches to activating therapeutic antitumour immunity is the blockade of immune checkpoints. Immune checkpoints refer to a plethora of inhibitory pathways hardwired into the immune system that are crucial for maintaining self-tolerance and modulating the duration and amplitude of physiological immune responses in peripheral tissues in order to minimize collateral tissue damage. It is now clear that tumours co-opt certain immune-checkpoint pathways as a major mechanism of immune resistance, particularly against T cells that are specific for tumour antigens. Because many of the immune checkpoints are initiated by ligand-receptor interactions, they can be readily blocked by antibodies or modulated by recombinant forms of ligands or receptors. Cytotoxic T-lymphocyte-associated antigen 4 (CTLA4) antibodies were the first of this class of immunotherapeutics to achieve US Food and Drug Administration (FDA) approval. Preliminary clinical findings with blockers of additional immune-checkpoint proteins, such as programmed cell death protein 1 (PD1), indicate broad and diverse opportunities to enhance antitumour immunity with the potential to produce durable clinical responses.

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CANCER IMMUNOLOGY. The "cancer immunogram".

C U Blank, J. Haanen, Á. Ribas … (2016)

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Is Open Access

Impact of Examined Lymph Node Count on Precise Staging and Long-Term Survival of Resected Non–Small-Cell Lung Cancer: A Population Study of the US SEER Database and a Chinese Multi-Institutional Registry

Wenhua Liang, Jiaxi He, Yaxing Shen … (2016)

Purpose We investigated the correlation between the number of examined lymph nodes (ELNs) and correct staging and long-term survival in non–small-cell lung cancer (NSCLC) by using large databases and determined the minimal threshold for the ELN count. Methods Data from a Chinese multi-institutional registry and the US SEER database on stage I to IIIA resected NSCLC (2001 to 2008) were analyzed for the relationship between the ELN count and stage migration and overall survival (OS) by using multivariable models. The series of the mean positive LNs, odds ratios (ORs), and hazard ratios (HRs) were fitted with a LOWESS smoother, and the structural break points were determined by Chow test. The selected cut point was validated with the SEER 2009 cohort. Results Although the distribution of ELN count differed between the Chinese registry (n = 5,706) and the SEER database (n = 38,806; median, 15 versus seven, respectively), both cohorts exhibited significantly proportional increases from N0 to N1 and N2 disease (SEER OR, 1.038; China OR, 1.012; both P < .001) and serial improvements in OS (N0 disease: SEER HR, 0.986; China HR, 0.981; both P < .001; N1 and N2 disease: SEER HR, 0.989; China HR, 0.984; both P < .001) as the ELN count increased after controlling for confounders. Cut point analysis showed a threshold ELN count of 16 in patients with declared node-negative disease, which were examined in the derivation cohorts (SEER 2001 to 2008 HR, 0.830; China HR, 0.738) and validated in the SEER 2009 cohort (HR, 0.837). Conclusion A greater number of ELNs is associated with more-accurate node staging and better long-term survival of resected NSCLC. We recommend 16 ELNs as the cut point for evaluating the quality of LN examination or prognostic stratification postoperatively for patients with declared node-negative disease.

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Author and article information

Journal

Journal ID (nlm-ta): J Cancer

Journal ID (iso-abbrev): J Cancer

Journal ID (publisher-id): jca

Title: Journal of Cancer

Publisher: Ivyspring International Publisher (Sydney )

ISSN (Electronic): 1837-9664

Publication date Collection: 2017

Publication date (Electronic): 25 August 2017

Volume: 8

Issue: 15

Pages: 2974-2983

Affiliations

[1 ]Depart of Clinical Oncology, College of Korean Medicine, Kyung Hee University;

[2 ]Depart of Medical Oncology and Hematology, College of Medicine, Kyung Hee University;

[3 ]Department of Clinical Korean Medicine, Graduate School, Kyung Hee University.

Author notes

✉ Corresponding author: Sookyung Lee, Department of Clinical Oncology, College of Korean Medicine, Kyung Hee University Hospital at Gangdong, 892 Dongnam-ro, Gangdong-gu, Seoul, 05278, Republic of Korea Tel:+82-2-440-6229 Fax:+82-2-440-7267 e-mail: sookyung@ 123456khu.ac.kr

Competing Interests: The authors have declared that no competing interest exists.

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Publisher ID: jcav08p2974

DOI: 10.7150/jca.20866

PMC ID: 5604449

PubMed ID: 28928889

SO-VID: c6f8aab8-9197-4acb-bb11-85dba768819c

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This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license ( https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions.

Prognostic Significance of Host-related Biomarkers for Survival in Patients with Advanced Non-Small Cell Lung Cancer

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Most cited references 43

The blockade of immune checkpoints in cancer immunotherapy.

CANCER IMMUNOLOGY. The "cancer immunogram".

Impact of Examined Lymph Node Count on Precise Staging and Long-Term Survival of Resected Non–Small-Cell Lung Cancer: A Population Study of the US SEER Database and a Chinese Multi-Institutional Registry

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