Elevated neutrophil and monocyte counts in peripheral blood are associated with poor survival in patients with metastatic melanoma: a prognostic model

Schmidt, Henrik; Bastholt, Lars; Geertsen, Poul F.; Christensen, Ib Jarle; Larsen, Stine Rosenkilde; Gehl, Julie; Maase, Hans von der

doi:10.1038/sj.bjc.6602702

Cited by 296 publications

(251 citation statements)

References 30 publications

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“…25 In patients with metastatic melanoma, elevated monocyte counts in peripheral blood were associated with poor survival. 26 In our study, we found a statistically significant association between a low L/ M ratio and CCS and DFS in STS patients in univariate as well as multivariate analysis for both data sets. These findings are in line with previously published studies from hematological cancer.…”

Section: Discussionsupporting

confidence: 60%

The lymphocyte/monocyte ratio predicts poor clinical outcome and improves the predictive accuracy in patients with soft tissue sarcomas

et al. 2014

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Increasing evidence indicates the involvement of inflammation and coagulation in cancer progression and metastases. Inflammatory biomarkers hold great promise for improving the predictive ability of existing prognostic tools in cancer patients. In the present study, we investigated several inflammatory indices with regard to their prognostic relevance for predicting clinical outcome in soft tissue sarcoma (STS) patients. Three hundred and forty STS patients were divided into a training set (n 5 170) and a validation set (n 5 170). Besides well-established clinico-pathological prognostic factors, we evaluated the prognostic value of the neutrophil/lymphocyte (N/L) ratio, the lymphocyte/monocyte (L/M) ratio and the platelet/lymphocyte (P/L) ratio using Kaplan-Meier curves and univariate as well as multivariate Cox regression models. Additionally, we developed a nomogram by supplementing the L/M ratio to the well-established Kattan nomogram and evaluated the predictive accuracy of this novel nomogram by applying calibration and Harrell's concordance index (c-index). In multivariate analysis, a low L/M ratio was significantly associated with decreased CSS and DFS (HR 5 0.41, 95% CI 5 0.18-0.97, p 5 0.043; HR 5 0.39, 95% CI 5 0.16-0.91, p 5 0.031, respectively) in the training set. Using the validation set for confirmation, we found also in multivariate analysis an independent value for CSS (HR 5 0.33, 95% CI 5 0.12-0.90, p 5 0.03) and for DFS (HR 5 0.36, 95% CI 5 0.16-0.79, p 5 0.01). The estimated c-index was 0.74 using the original Kattan nomogram and 0.78 when the L/M ratio was added. Our study reports for the first time that the pre-operative L/M ratio represents a novel independent prognostic factor for prediction the clinical outcome in STS patients. This easily determinable biomarker might be helpful in improved individual risk assessment.Soft tissue sarcomas (STS) account for nearly 11,280 cases per year and are responsible for about 3,900 deaths in the United States annually, mainly due to local recurrence or metastatic disease. 1 Therefore, it is crucial to understand the biological mechanisms that contribute to tumor progression and to identify novel prognostic markers to generate individualized treatment and follow-up schedules. In a large retrospective study of 2,136 STS patients, Kattan et al. developed a postoperative prognostic model that predicts sarcomaspecific death, based on traditional prognostic factors such as age at diagnosis, tumor size, histologic grade, histologic subtype, tumor depth and site. 2 This nomogram is useful for general risk assessment and has potential value in determining surgical strategy and adjuvant management. Nevertheless, novel prognostic factors might be helpful in improving its predictive ability. Current approaches in cancer research have focused on the characterization of novel biomarkers, which ideally should be easily accessible, highly reproducible, cheap and most importantly, identify patients at high risk for disease-recurrence and death. Increasing evidence su...

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Section: Discussionsupporting

confidence: 60%

The lymphocyte/monocyte ratio predicts poor clinical outcome and improves the predictive accuracy in patients with soft tissue sarcomas

et al. 2014

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“…The prognostic value of the circulating neutrophil count has been reported previously in numerous malignancies, 21,22,26,41 including primary CRC. 23,39 Whilst it is possible that increasing neutrophil count is simply an epiphenomenon of the inflammatory response in the vicinity of the tumour, the emerging theory of 'immune enhancement' suggests that cells of the myeloid lineage, particularly neutrophils, are recruited from the circulation and play a direct role in promoting aggressive tumour phenotypes.…”

Section: Discussionmentioning

confidence: 66%

“…As reported previously, 20,22,26,41 a simple prognostic score for overall survival was derived from variables maintaining significance on multivariable analysis.…”

Section: Prognostic Scorementioning

confidence: 99%

Evaluation of the prognostic value of systemic inflammation and socioeconomic deprivation in patients with resectable colorectal liver metastases

Neal¹,

Mann²,

Sutton³

et al. 2009

European Journal of Cancer

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Background: There is increasing evidence that the presence of a preoperative systemic inflammatory response (SIR) independently predicts poor long-term outcome in patients with colorectal cancer (CRC).Socioeconomic deprivation was reported to correlate with the presence of the SIR and to itself independently predict poor outcome following primary CRC resection. The aim of this study was to determine the prognostic value of preoperative systemic inflammatory biomarkers and socioeconomic deprivation in patients undergoing resection of colorectal liver metastases (CLM) and to examine correlations between these variables in this context. Results: On multivariable analysis, poor CRS (3-5), high neutrophil count (>6.0 x10 9 /L) and low serum albumin (<40 g/dL) were the only independent predictors of shortened overall survival following metastasectomy, with neutrophil count representing the greatest relative risk of death. These factors were also the only independent predictors of shortened disease-free survival 3 following hepatectomy. Socioeconomic deprivation was associated with neither systemic inflammation nor long-term outcome in this context. Patients and methods: Conclusions:The presence of a preoperative systemic inflammatory response, but not socioeconomic deprivation, independently predicts shortened survival following resection of CLM.4

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“…Furthermore, we have previously reported an association between pretreatment elevated neutrophil counts in blood and poor prognosis in metastatic renal cell carcinoma and metastatic melanoma. [29][30][31] In the present study, we unfortunately had no full blood count from the patient population. Plasmacytoid dendritic cells (CD123þ) are known to be an important resource of interferons (IFNs) in their activated state.…”

Section: Discussionmentioning

confidence: 87%

Intratumoral neutrophils and plasmacytoid dendritic cells indicate poor prognosis and are associated with pSTAT3 expression in AJCC stage I/II melanoma

Jensen

Schmidt

Møller

et al. 2011

Cancer

231

181

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BACKGROUND: Tumor cell and host immune cell interaction plays a key role in carcinogenesis. Signal transducer and activator of transcription 3 (STAT3) is constitutively activated in cancer and believed to be an important mediator of tumor-induced immunosuppression. This paper aims to describe the prognostic impact of neutrophil and dendritic cell infiltration in primary melanoma and the association of this infiltration with activated STAT3 (pSTAT3) in primary melanoma cells. METHODS: Formalin-fixed, paraffin-embedded primary melanomas from 186 stage-I/II melanoma patients surgically resected from 1997 to 2000. Infiltrating neutrophils (CD66b), dendritic cells (CD123þ and DC-LAMPþ), T-lymphocytes (CD8) and pSTAT3 melanoma cell expression were studied by immunohistochemistry and evaluated as present or absent. DC-LAMPþ cell infiltration was evaluated as absent/few versus dense. Study endpoints: relapse-free survival, melanoma-specific, and overall survival. RESULTS: The median observation time was 12.2 years (range, 10.4-14.2 years). Fifty-one deaths were observed of which 38 (20%) were melanoma-specific. In a multivariate Cox proportional hazards model including ulceration and melanoma thickness, neutrophil and CD123þ dendritic cell infiltration were independently associated with poor prognosis (CD66b: hazard ratio [HR] ¼ 3.13; 95% confidence interval [CI], 1.43-6.83; P ¼ .004; CD123: HR ¼ 2.45; 95% CI, 1.22-4.92; P ¼ .012). The association between melanoma cell pSTAT3 expression and immune infiltration (neutrophils and CD123þ cells) was strong. pSTAT3 expression, CD8 and DC-LAMP infiltration were not independently associated with poor prognosis. CONCLUSIONS: Neutrophil infiltration and CD123þ dendritic cell infiltration in primary melanoma are independently associated with poor prognosis. Melanoma cell expression of pSTAT3 is strongly associated with the surrounding immune infiltrate. Cancer 2012;118:2476-

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Elevated neutrophil and monocyte counts in peripheral blood are associated with poor survival in patients with metastatic melanoma: a prognostic model

Cited by 296 publications

References 30 publications

The lymphocyte/monocyte ratio predicts poor clinical outcome and improves the predictive accuracy in patients with soft tissue sarcomas

The lymphocyte/monocyte ratio predicts poor clinical outcome and improves the predictive accuracy in patients with soft tissue sarcomas

Evaluation of the prognostic value of systemic inflammation and socioeconomic deprivation in patients with resectable colorectal liver metastases

Intratumoral neutrophils and plasmacytoid dendritic cells indicate poor prognosis and are associated with pSTAT3 expression in AJCC stage I/II melanoma

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