J. T. Cohen1, A. Blakely1, D. Comissiong1, M. Vezeridis1, T. J. Miner1 1Brown University School Of Medicine,Department Of Surgery,Providence, RI, USA
Introduction:
Serum neutrophil-to-lymphocyte ratio (NLR) has recently gained increasing attention as a readily available biomarker, providing prognostic information in various malignancies including melanoma, breast cancer, non-small cell lung cancer, and hepatocellular carcinoma. An elevated NLR has been demonstrated to be a poor prognostic marker in stage I-II melanoma and high-risk non-metastatic melanoma. In metastatic melanoma, high NLR may predict disease responsiveness to anti-PD-1 immunotherapy. Here, we investigate the NLR in thick melanoma (≥4 mm), in an attempt to elucidate the role of NLR as a marker of immunologic privilege.
Methods:
This is a retrospective review of all patients who underwent wide local excision of melanoma between June 2005 and December 2016 at a single tertiary academic medical center. Patients with thick melanoma (≥4 mm) were selected for analysis. NLR was calculated for patients who had a complete blood count with differential following diagnosis of melanoma but prior to excision. Patients were excluded if they had leukocytosis, neutrophilia, or lymphopenia. A high NLR was defined as >3, as has been described in the literature for high-risk non-metastatic melanoma.
Results:
Of 1,714 patients, 103 (6%) were identified as having thick melanoma. Of these, 39 patients had available laboratory data meeting the inclusion criteria. Fourteen of 39 (35.9%) had High NLR (>3), while 25 of 39 (63.1%) had Low NLR (≤3). The mean NLR in the High group was significantly elevated compared to the Low group (4.83 vs. 2.08 p < 0.0001). There was no significant difference in patient gender, age, location of tumor, tumor thickness, mitotic rate, or positivity of SLNB between the two groups. Median follow up time was 503 days, which did not vary significantly between the cohorts. Margins of excision were <2 cm in 3 patients, all of whom were in the High group. There was no significant difference in number of SLNBs performed. In both univariate and multivariate analysis, NLR was not predictive of overall recurrence, recurrence type, wound complications, or lymphovascular invasion. Median time to recurrence was not significantly different (p=0.2) in the Low group compared with the High (260 vs 174 days).
Conclusion:
NLR is an important prognostic marker in a variety of patients with both local and metastatic melanoma. This may represent an environment in which neutrophils enriched with PD-L1 down-regulate cytotoxic lymphocytes, providing an optimal environment for melanoma cell survival and ultimately recurrence or metastasis.
In this scenario, a high NLR serves as a marker for the degree of immunologic privilege afforded to the melanoma cell at the time of excision. Here we demonstrate NLR is not predictive of recurrence in thick melanoma, which is consistent with aggressiveness of the tumor and suggests that thick melanoma may not require the same degree of immunologic privilege to recur.