An Investigation into the Delta Neutrophil-to-Lymphocyte Ratio as Prognostic Markers in Head and Neck Cancer Andrew Ko, BS, Arif Mahmud, BS, Josue Minaya, BS, Tristan Tham, MD Donald and Barbara Zucker School of Medicine at Hofstra/Northwell New York Head & Neck Institute, Northwell Health System
Background
Results
Conclusions
Head and neck cancers (HNC) contribute greatly to the cancer burden worldwide. In fact, much of these cancers have preventable risk factors, such as tobacco and alcohol use.1 There has been increased interest in the use of inflammatory biomarkers as prognostic indicators for HNC.2-4 For example, the neutrophil-tolymphocyte ratio (NLR) can actually be used to predict 5 favorable outcomes in patients with colon cancers. There is currently little research into the use of inflammatory biomarkers as prognostic markers, and more specifically in the use of the delta ratio (pretreatment subtracted from post-treatment). The important ratios to be looked at include the NLR, platelet-to-lymphocyte ratio (PLR), and lymphocyte-to monocyte ratio (LMR).
A receiver operating characteristic (ROC) curve was produced to determine the cutoff point for a Kaplan Meier curve for delta NLR, delta PLR, and delta LMR. Logrank test was performed on the survival curves to determine if there was a statistical difference, of which was present with only delta LMR (p=0.0058). Univariable and multivariable analysis was performed on all analyzed data, resulting in staging of N=3 and delta LMR having a statistically significant effect (p<0.05) on event-free survival.
The data shows that there is an inverse correlation between the delta LMR and event free survival, which is in conjunction with research by Chia-Hsin Lin et al.6 The mechanism of how a decreased LMR contributes to better outcomes is no understood. It is possible that there is a change in the tumor microenvironment as a result of treatment, leading to an increased differentiation of monocytes to become M1 tumorassociated macrophages, which are primarily antitumorigenic.
A retrospective study was performed on a cohort of 281 patients who presented with squamous cell carcinoma in the oral cavity, larynx, or oropharynx, who were treated at the New York Head and Neck Institute from 2009 to 2016. Patients were included if they had a curative treatment recorded and pre- and post-operative labs available. Patients were excluded if they had palliative treatment, metastatic disease at time of presentation, or incomplete data. Analyzed data included age, sex, ethnicity, body mass index (BMI), ACE-27 comorbidity score, tumor location, tumor staging, treatment, history of alcohol use or smoking, ECOG performance score, Karnofsky score, p16 expression, NLR, PLR, and LMR (pre- and posttreatment). A total of 89 patients met all inclusion and exclusion criteria, of which 52 had complete data to be analyzed.
Sensitivity
Figure 1. ROC curve for delta LMR. The cutoff point was determined by maximizing the area under the curve (AUC = 0.667, p = 0.036).
1 - specificity
Survival Probability %
Methods
Future Direction
Figure 7: Independent CRISPR knockout of CDK4 or CDK6 does not cause dropout in most breast cancer cell lines studied.
Time
As there is currently very little research in the prognostic value of HNC, as a preliminary study, this helps to set the stage that there is benefit to inflammatory markers. With an increase in sample size, as well as expanding the reliability by performing a prospective study, future research can help determine more specifically which markers are decent prognostic markers for HNC.
Resources Figure 2: Kaplan Meier Curve of Event Free Survival (EFS) in Patients Stratified by Delta LMR. The probability of survival with no events (death, recurrence, etc.) over time was graphed based on whether the Delta LMR was less than or equal to -1.48 (blue) or greater than 1.48 (green).
1. Jemal A, Bray F, Center MM et al (2011) Global cancer statistics. CA Cancer J Clin 61(2):69–90. 2. Tham, T., Olson, C., Khaymovich, J. et al. The lymphocyte-to-monocyte ratio as a prognostic indicator in head and neck cancer: a systematic review and metaanalysis. Eur Arch Otorhinolaryngol 275, 1663–1670 (2018). 3. Tham T, Bardash Y, Herman SW, Costantino PD. Neutrophil-to-lymphocyte ratio as a prognostic indicator in head and neck cancer: a systematic review and meta-analysis. Head Neck 40(11), 2546–2557 (2018). 4. Zhou, S., Yuan, H., Wang, J., Hu, X., Liu, F., Zhang, Y., … Zhang, W. (2020). Prognostic value of systemic inflammatory marker in patients with head and neck squamous cell carcinoma undergoing surgical resection. Future Oncology.. 5. Li Z, Zhao R, Cui Y, Zhou Y, Wu X. The dynamic change of neutrophil to lymphocyte ratio can predict clinical outcome in stage I-III colon cancer. Sci Rep. 2018;8(1):9453. Published 2018 Jun 21. 6. Lin C-H, Chou W-C, Wu Y-Y, et al. Prognostic significance of dynamic changes in lymphocyte-to-monocyte ratio in patients with head and neck cancer treated with radiotherapy: results from a large cohort study. Radiotherapy and Oncology. 2021;154:76-86.