Prognostic significance of hematological profiles in melanoma patients

Abstract

Cancer-related inflammation may play an important role in disease progression and patient outcome, and could be easily monitored through indirect parameters routinely evaluated at diagnosis. Here, we investigated if peripheral blood cells and the ratios of neutrophils to lymphocytes (NLR) and of lymphocytes to monocytes (LMR) as surrogate markers of cancer related inflammation are associated with disease progression and survival of melanoma patients at any stage of the disease. Records of 1,182 melanoma patients included in an Institutional tumor registry in the period 2000-2010, were reviewed. Among them, 584 patients with a cutaneous or unknown primary melanoma and available pre-operative blood tests were analyzed. Survival was estimated with the Kaplan-Meier method, and analyzed using Log-rank test, Cox regression and multivariate Cox proportional hazard models. We found that patients presenting with distant metastases had higher leukocytes, neutrophils and monocytes, and lower lymphocytes compared to Stage I-III patients. Furthermore, at a single-patient level, hematological profiles changed on disease progression from regional to distant metastatic, with significantly increased circulating leukocytes, neutrophils and monocytes, and decreased lymphocytes. Peripheral blood cell counts were not associated with survival of patients with a localized or regionally metastasized melanoma. Instead, in Stage IV patients, leukocytes (p 5 0.001), neutrophils (p 5 0.0002), monocytes (p 5 0.002), NLR (p < 0.0001) and LMR (p 5 0.005) were all significantly associated with survival, independently of other known prognostic factors. These results suggest that cellular components of peripheral blood do count for survival of patients with advanced melanoma.Melanoma is the most aggressive form of skin cancer, characterized by rapid progression as well as late recurrence 1 and treatment refractoriness. 2 The vast majority of melanomas are diagnosed at a localized stage, when they are potentially curable: with adequate surgery, the 5-year survival rate is >98%. However, the clinical behavior of melanoma is not always predictable on the basis of conventional histopathological criteria, 3,4 and life expectancy dramatically declines for patients diagnosed with a regional or a distant metastatic disease, with 5-year survival rates of 62 and 16%, respectively. 3,5

Neutrophil to Lymphocyte Ratio is Associated With Outcome During Ipilimumab Treatment

“…In a general cohort of melanoma patients at any stage of disease, NLR was not associated with OS in patients with stage I–III disease (Gandini et al, 2016). However, NLR ≥ 5 was statistically significantly associated with OS in patients with stage IV disease, with a hazard ratio of 2.87.…”

Baseline neutrophil-to-lymphocyte ratio in patients with advanced melanoma treated with immune checkpoint inhibitors

“…4 In melanoma, absolute neutrophil count is higher and absolute lymphocyte count lower in patients with stage IV disease than stage I-III. 5 Moreover, high NLR was associated with poor overall survival in patients with stage IV disease. 5 Finally, high NLR is a prognostic biomarker of poorer outcome in patients with melanoma treated with ipilimumab, nivolumab and BRAF inhibitors.…”

“…5 Moreover, high NLR was associated with poor overall survival in patients with stage IV disease. 5 Finally, high NLR is a prognostic biomarker of poorer outcome in patients with melanoma treated with ipilimumab, nivolumab and BRAF inhibitors. [1][2][3] Because of the slow action of immunotherapy, it may be necessary to check that lactate dehydrogenase levels, performance status and NLR are within normal ranges, as all of these indicate longer survival, before prescribing immunotherapy.…”

“…NLR has been fully demonstrated to be associated with overall survival in nearly all types of cancer in a meta‐analysis that included more than 40 000 patients . In melanoma, absolute neutrophil count is higher and absolute lymphocyte count lower in patients with stage IV disease than stage I–III . Moreover, high NLR was associated with poor overall survival in patients with stage IV disease …”

“…In melanoma, absolute neutrophil count is higher and absolute lymphocyte count lower in patients with stage IV disease than stage I–III . Moreover, high NLR was associated with poor overall survival in patients with stage IV disease …”