An Investigation into the Delta Lymphocyte-to-Monocyte Ratio as Prognostic Markers in Head and Neck Cancer Arif
1 Mahmud ,
Andrew
1 Ko ,
Josue
1 Minaya ,
and Tristan
2 Tham
1Donald
and Barbara Zucker School of Medicine at Hofstra/Northwell 2Department of Otolaryngology - Head and Neck Surgery, Zucker School of Medicine at Hofstra/Northwell
Results
Head and neck cancers are some of the most common cancers worldwide, estimated to have more than 880,000 new cases in 2018 alone, resulting in more than 450,000 deaths. [1] Cancers of this variety are considered to occur in the larynx, oral cavity, oropharynx, nasopharynx, nasal cavity, paranasal sinuses, hypopharynx, and salivary glands. Treating head and neck cancers currently include treatment modalities such as surgery, chemotherapy, radiation therapy, or any combination of the three. The treatment is dependent on various characteristics including the TNM (T: Tumor Size, N: number of nearby lymph nodes involved, M: presence of distant metastases) staging of the tumor, the anatomical site of the tumor, the histological type, as well as the associated risk factors. Recently, there has been increasing interest in using various criteria to stratify patients in order to better individualize the prognosis and treatment plan. Some such criteria include easily obtainable blood inflammatory biomarkers which have shown some evidence in being able to predict the prognosis of head and neck cancers. [2,3,4] In this study, we discuss the results of lab values of 89 patients with head and neck squamous cell carcinoma (HNSCC) to determine their pretreatment and posttreatment lymphocyte to monocyte ratio (LMR), platelet to lymphocyte ratio (PLR), and neutrophil to lymphocyte ratio (NLR). The objective of this study is to determine the prognostic value of these pretreatment biomarkers, posttreatment biomarkers, and the change (delta) of these biomarkers.
Future Direction
100-Specificity
Resources
We hypothesized that a change in LMR, PLR, and/or NLR value posttreatment, as compared to pretreatment, would be associated with an increased event free survival.
1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries [published correction appears in CA Cancer J Clin. 2020 Jul;70(4):313]. CA Cancer J Clin. 2018;68(6):394-424. doi:10.3322/caac.21492
Survival Probability (%)
Data for n=86 patients were pulled from the Northwell redcap database. In order to determine if there were statistically significant changes in event free survival for patients with decreased LMR, PLR, and/or NLR, we first developed a receiver operating characteristic (ROC) curve in order to find the optimal cutoff points for the continuous variables NLR, LMR, PLR, and their delta values. To do this, a plot of the sensitivity against 1-specificity, of the detection of the endpoint (EFS – Event free survival), was generated (Area under curve, AUC = 0.667). After the ROC curve is constructed, the discrimination threshold of the continuous variable was identified using the Youden index, which is the level at which the continuous variable maximizes both sensitivity and specificity. Using this method, separate cutoff estimates were obtained for all continuous variables of interest (NLR, LMR, PLR, and their delta values) for EFS. The Kaplan–Meier curve was then used to estimate survival endpoints, and the logrank test was used to find survival differences between curves.
More work needs to be done in elucidating the reasoning behind why this decrease in LMR leads to an increase in event free survival. One possible explanation is that lymphocytes in head and neck cancer provide an inflammatory microenvironment that is beneficial for the tumor growth. Thus a decrease in the ratio of lymphocytes to monocytes may lead to a decrease in the release of inflammatory cytokines that produce a pro-tumor microenvironment.
Figure 1: ROC curve to determine Delta LMR cutoff
Hypothesis Methods
Conclusions Of all the variables collected, the only variable that provided prognostic value in head and neck cancer, was the LMR. The delta LMR (change in LMR between preand post-treatment) cutoff was decided to be 1.48. In other words, patients with a post-treatment LMR value that decreased by 1.48 or more as compared to the pre-treatment LMR value, were shown to have a statistically significant increase in event free survival, as demonstrated by the Kaplan Meier curve, (P<0.05). This result supported our hypothesis that a change in the post-treatment LMR would lead to a significant increase in the event free survival, thus indicating that LMR is indeed a potential prognostic marker in head and neck cancer.
Sensitivity
Background
2. Takenaka Y, Oya R, Kitamiura T, et al. Prognostic role of neutrophil-to-lymphocyte ratio in head and neck cancer: A meta-analysis. Head Neck. 2018;40(3):647-655. doi:10.1002/hed.24986
3. Tham T, Olson C, Khaymovich J, Herman SW, Costantino PD. The lymphocyte-to-monocyte ratio as a prognostic indicator in head and neck cancer: a systematic review and meta-analysis. Eur Arch Otorhinolaryngol. 2018;275(7):1663-1670. doi:10.1007/s00405-018-4972-x 4. Bardash Y, Olson C, Herman W, Khaymovich J, Costantino P, Tham T. Platelet-Lymphocyte Ratio as a Predictor of Prognosis in Head and Neck Cancer: A Systematic Review and Meta-Analysis. Oncol Res Treat. 2019;42(12):665-677. doi:10.1159/000502750
Time
Figure 2: Event Free Survival in Patients Stratified by Delta LMR