| Background and purposeCancer incidence and mortality in China have been increasing year by year,making cancer the leading cause of death since 2010 and a major public health problem in Chinese society.It is estimated that about 281.4 million people died of cancer in 2015,of which the overall incidence of malignant melanoma is low,accounting for about 4%-5%.However,malignant melanoma has a high degree of malignancy and early metastasis,and the incidence rate has been increasing in recent years.For a long time,the classical treatment methods of malignant tumors include surgery,radiotherapy and chemotherapy.However,because malignant tumors are often insidious and easily confused,in addition to the lack of awareness of regular physical examination,they are mostly found in the middle and advanced stages,which brings difficulties to the treatment,resulting in poor prognosis and short survival time for many patients.In recent years,cancer immunotherapy has made continuous breakthroughs,providing new options and hopes for cancer patients.Cancer immunotherapy was ranked as the greatest progress in cancer research in the 2016 American Cancer Research Progress Annual.Clinical studies of immune checkpoint inhibitors are very popular and have achieved promising efficacy in a variety of solid tumors.In 2011,ipilimumab was approved by the US FDA for marketing and was the first drug shown to prolong the survival of patients with advanced melanoma,and in 2014,the anti-PD-1 antibody drugs pembrolizumab and nivolumab were successively approved.Immune checkpoint inhibitors or combination therapy with other methods in patients with advanced disease conferred more survival benefit.However,its overall response rate is still low,there is no response for the non-target population,and some patients will show special response patterns such as false progression and delayed response,which brings difficulties for its efficacy and prognosis evaluation.At present,the commonly used predictive markers for the efficacy of immune checkpoint inhibitors in clinical practice mostly require tumor tissue samples for examination,which is difficult to obtain,has high detection cost,and there is no unified detection reagent,detection method and positive threshold.Studies have shown that there is a close relationship between chronic inflammation and tumors,and a number of studies at home and abroad have demonstrated that inflammation-related indicators are related to the therapeutic efficacy and prognosis of patients;at the same time,studies have shown that peripheral blood fibrinogen(Fbg)is negatively correlated with the prognosis of a variety of tumors.The combined scoring F-NLR scoring system of the two has also been confirmed to be associated with the efficacy and prognosis of patients with malignant tumors in a large number of studies.However,there is no report on F-NLR score in patients with advanced malignant melanoma treated with anti-PD-1 antibody.Based on this,this study aims to retrospectively analyze the peripheral blood inflammatory indicators and coagulation indicators of patients with advanced malignant melanoma treated with anti-PD-1 antibody and explore the correlation between F-NLR score and short-term efficacy,prognosis and clinical characteristics of patients,in order to find a more convenient and accurate predictive biomarker for efficacy and provide clinical evidence for predicting the prognosis.MethodsA total of 34 patients with stage ? malignant melanoma who visited the the Affiliated Cancer Hospital of Zhengzhou University from January 1,2017 to January 1,2019 were retrospectively analyzed.The clinical data of the patients were collected,including gender,age,smoking history,hematological test results of the patients 1 week before receiving anti-PD-1 antibody treatment,including neutrophils,lymphocytes,platelets,fibrinogen,D-dimer and LDH,and NLR and F-NLR scores were calculated.All patients received at least 3 cycles of anti-PD-1 antibody therapy(Nivolumab 3 mg/kg,once every 2 weeks,Pembrolizumab 2 mg/kg,once every 3 weeks),with or without other targeted,interferon and other therapies.Laboratory tests and imaging examinations such as CT,MRI,and bone scan were performed every about 6 weeks to assess the short-term efficacy,and 12 weeks later,they were divided into progressive disease group(PD group)and non-PD group according to the overall tumor response.The cut-off values of neutrophils,lymphocytes,and platelets were determined using receiver operating curves,and the cut-off values of fibrinogen and NLR were defined as 4 with reference to Takaaki et al.Fisher's exact test was used to analyze the correlation between F-NLR and patients' clinical baseline characteristics and short-term efficacy,Kaplan-Meier method was used for survival analysis and log-rank method was used for test,and Cox proportional hazards regression model was used for univariate and multivariate analysis to assess prognostic factors.P<0.05 was considered statistically significant.ResultsAccording to the receiver operating characteristic(ROC)curve and area under the curve(AUC),the optimal cutoff value of neutrophils was 4.66,the optimal cutoff value of lymphocytes was 1.58,and the optimal cutoff value of platelets was 174.According to the F-NLR score,the patients were divided into three groups:0 point(fibrinogen content<4 g/L and NLR<4),1 point(fibrinogen content>4 g/L or NLR? 4),and 2 points(fibrinogen content? 4 g/L and NLR? 4).The results showed that F-NLR score before anti-PD-1 antibody treatment was significantly correlated with baseline neutrophil count,lymphocyte count,fibrinogen content and the tumor response,with P=0.000,0.005,0.001 and 0.002,respectively.F-NLR value in PD group was higher than that in non-PD group.Univariate analysis of PFS revealed that neutrophil count,lymphocyte count,LDH,NLR value and F-NLR value were significantly correlated with PFS,with P=0·001,0.006,0.001,0.037 and<0.001,respectively.Significant variables in univariate analysis were included in multivariate analysis,and neutrophil count and LDH were independent prognostic factors for PFS(P=0.02,0.044).Univariate analysis of OS revealed that neutrophil count,lymphocyte count,NLR value,and F-NLR value had a significant correlation with OS in patients,with P=0.001,0.001,0.001,and<0.001,respectively,and variables significant by univariate analysis were included in multivariate analysis,yielding lymphocyte count as an independent prognostic factor for OS(P=0.001).ConclusionThe F-NLR scoring system can evaluate the short-term efficacy of patients with stage ? malignant melanoma treated with anti-PD-1 antibody.Patients in PD group have higher F-NLR value than patients in non-PD group,and patients with low F-NLR value may benefit from treatment;F-NLR value has a significant correlation with PFS and OS,but cannot be used as an independent prognostic factor. |
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