The relation between mean platelet volume/platelet count ratio and prognostic factors in patients with advanced non-small cell lung cancer

Mean platelet volume (MPV) is a platelet volume index2. Classically, MPV was recognized gnized as a hallmark of platelet activation. There fore MPV is related to various thromboembolic disorders. Besides, MPV is the most commonly used measure of platelet size and is a potential marker of platelet reactivity. Noteworthy, MPV is typically in the range of 5 -15 femtoliters. Recent studies revealed that MPV/PC ratio can predict long term mortality in patients with ischemic cardiovascular diseases3.


INTRODUCTION
Lung cancer is highly lethal tumor.The 5-year relative survival rate varies markedly, depending on how advanced the disease is at diagnosis 1 , as follows: 49% for local disease, 16% for regional disease, 2% for distant stage disease.
Mean platelet volume (MPV) is a platelet volume index 2 .Classically, MPV was recognized gnized as a hallmark of platelet activation.There fore MPV is related to various thromboembolic disorders.Besides, MPV is the most commonly used measure of platelet size and is a potential marker of platelet reactivity.Noteworthy, MPV is typically in the range of 5 -15 femtoliters.Recent studies revealed that MPV/PC ratio can predict long term mortality in patients with ischemic cardiovascular diseases 3 .These indices were also associated with the pathophysiologic characteristics of various disorders including malignant tumors 4 , the prognostic impact of "platelet count" Approximately one third of patients present with locally advanced non metastatic disease, many of whom are surgically unresectable due to the extent of disease or medically inoperable because of pulmonary and/or other co-morbidities.
Thrombocytosis was recognized as unfavorable predictive factor for overall survival.In a Japanese study, MPV/PC ratio was closely associated with survival in patients with advanced NSCLC with cutoff value of 0.408730 (sensitivity of 62.3%, specificity of 74.6%) 6 .
The aim of this study was to study the relation between MPV/PC ratio and some prognostic factors in advanced NSCLC patients

METHODS
Patients with advanced NSCLC (stage III, stage IV) were included and their files were retrospectively evaluated during the period from January 2010 to the end of 2012.The clinical stage was assigned based on the 7th edition of TNM classification of lung cancer 7 .
We have reviewed all patients' medical records at Clinical Oncology Department, Assuit University Hospital for sex, age, histologic subtype, smoking history, staging and Eastern Cooperative Oncology Group "ECOG" performance status.
The first complete blood pictures of patients before the start of systemic chemotherapy were reviewed for platelet indices; mean platelet volume (MPV) and platelet count, then the ratio was calculated, the cut off value was previously determined to be 0.408730 (sensitivity of 62.3%, specificity of 74.6%) 6 .patients were grouped into two groups above and below the previous cutoff point.The demograghic and clinical characteristics of each group were determined Patients with large cell neuroendocrine carcinoma, previous curative thoracic irradiation were excluded.Also those with previous history of malignancy or elevated C-reactive protein or active infection were excluded.Statistical analysis was performed using the Statistical Package for the Social Sciences, version 14.0 (SPSS Inc, Chicago, Illinois).All statistical tests were two sided and P<0.05 was considered significant.

RESULTS
From January, 2010 to December, 2012, a total 69 patients with advanced NSCLC were enrolled.

The clinical characteristics of patients are shown in Table (1).
The average MPV/PC ratio for the whole group of patients was 0.348327 (±0.1261) and the median was 0.32157 (range: 0.1403 -0.7535).
Lower average MPV/PC ratio was associated with more advanced stage (Figure 1).
Lower average MPV/PC ratio was associated with higher ECOG performance status score (Figure 2).
Older patients had a significantly lower MPV/PC ratio as shown in Figure 3 (Pearson correlation = -0.245,p=0.043).
Using the cutoff value of 0.40873, patients were divided into two groups.The comparison between the two groups is shown in Table 2.
Patients with an MPV/PC ratio <0.40873 were significantly more likely to be older in age, have a worse performance status and higher stage.There was no significant correlation with sex, smoking history or histologic subtype.

DISCUSSION
In advanced lung cancer (stage III-IV), there are several options of oncology treatment (including chemotherapy, radiotherapy, targeted therapy) or best supportive care alone 8 .The benefits of any treatment must be balanced with side-effects, which are often considerable.
A fundamental factor influencing treatment decisions in advanced lung cancer is the expected prognosis.there are no good predictors for the benefit of chemotherapy, however, the prognosis is currently being used to select those who receive chemotherapy.In general, good performance status, female sex, age ≤ 70 years, Hb level > 11 g/dL and normal lactate dehydrogenase levels are associated with improved outcomes in patients with advanced NSCLC 9 .Upon the guidelines for lung cancer treatment, the most established factor for assessing prognosis is performance status.Studies have also linked weight loss in lung cancer to reduced survival 10 .
Measures of the systemic inflammatory response are of independent prognostic value in cancer.A combination of the inflammatory markers C-reactive protein and albumin termed the modified Glasgow Prognostic Score (mGPS).The so-called mGPS has been the most extensively studied and validated prognostic scoring tool 11 .
Recently, evaluation of the MPV is attracting a great deal of interest.Several reports have shown that an elevation of MPV is closely associated with the severity and prognosis of cerebro-and cardio-vascular disorders 3 .
In addition to ischemic cardiovascular disorders, the elevation of MPV has also been reported in malignant tumors.Osada et al showed that the MPV was higher in patients with gastric cancer than in control patients 12 .
Cho SY et al demonstrated that MPV and MPV/ PC ratio were elevated in patients with hepatocellular carcinoma 4 .
In this study; we tried to answer why those with high MPV/PC ratio were associated with better OS in comparison to those with low ratio, and found that the former were associated with better other prognostic factors like age, stage, performance status.Platelets play important role in pathophysiology of tumor angiogenesis by transporting vascular endothelial growth factor (VEGF), which is the target for antiangiogenic agents 13 .MPV is a parameter of platelet size and can reflect changes in the rate of platelet production.Previous studies have demonstrated that the MPV was higher in patients with gastric cancer than in control patients.Also, MPV/PC ratio differed significantly between patients with hepatocellular carcinoma and controls 4 .Oge et al. showed that MPV was significantly higher in endometrial cancer patients than in the control group 13 .Our data showed statistically significant lower MPV/PC ratios in NSCLC patients with poor prognostic indicators, which may be explained by the increased inflammation and increased platelet activation in the advanced disease.
In the study conducted by Inagaki et al, low MPV/ PC ratio was associated with significantly shorter overall survival when compared to the other group (10 months vs. 15 months, respectively; p =0.025) in univariate analysis 6 .Multivariate analysis further confirmed that low MPV/PC is an independent predictor of poor overall survival (p=0.0008) 6.
In the current study, low MPV/PC ratio was significantly associated with poor prognostic factors in NSCLC patients; namely poorer performance status, more advanced disease stage and older age.A key consideration in deciding appropriate treatment in an advanced lung cancer patient is prognosis, however, recent work has demonstrated that approximately 10% of metastatic lung cancer patients receive anti-cancer therapy in the last 30 days of life 14 .
Accordingly, accurate assessment of prognosis is needed to inform complex decisions between patients and clinicians.Most important is the urgency for improved survival prediction in metastatic lung cancer.

CONCLUSION
Low MPV/PC ratio was associated significantly with poor prognostic indicators in a group of Egyptian patients with advanced NSCLC.Future studies investigating the correlation between MPV/PC ratio and survival of NSCLC patients with different stages are needed.

Figure 1 :
Figure 1: The average MPV/PC ratio according to the stage in patients with advanced NSCLC (p=0.015).

Figure 2 :
Figure 2: The average MPV/PC ratio according to the ECOG performance status of patients with advanced NSCLC (p=0.004).

Figure 3 :
Figure 3: The relation between MPV/PC ratio and age of patients with advanced NSCLC.

Table 2 :
Comparison between patients with an MPV/PC ratio above and below a cutoff value of 0.40873