Abstract
Background: Previous studies have reported any prognostic impact of preoperative leukocytosis, anemia and thrombocytosis in non-small cell lung cancer (NSCLC). The significance of the combined use of these 3 abnormal blood cell counts was investigated. Patients and Methods: Two hundred and eighty-nine consecutive NSCLC patients were reviewed retrospectively. Results: The patients with leukocytosis, anemia and thrombocytosis had significantly worse prognosis. The 5-year survival of the patients with all three of these abnormal blood cell counts was 25.0%, which was significantly poorer compared with that of the patients without any of these abnormal cell counts (78.23%). The 5-year survival of the patients with 1 or 2 out of the three abnormal blood cell counts was an intermediate value. Both univariate and multivariate analyses indicated the independent prognostic impact of the use of these three abnormal blood cell counts combined. Conclusion: The use of leukocytosis, anemia and thrombocytosis combined might be useful for predicting the prognosis of NSCLC patients.
Although multiple prognostic factors have been reported in the literature for patients with non-small cell lung cancer (NSCLC), the majority of these factors cannot be obtained preoperatively. Moreover, some of these factors are available only as research tools.
Previous studies have reported that preoperative leukocytosis (1-5), anemia (6-11) and thrombocytosis (5, 12-16) are related to the prognosis of NSCLC patients. The estimation of the preoperative peripheral blood cell count is easy, readily available and economic. We believe that the measurement of such factors is important and should not be neglected. The majority of previous studies which examined the relationship between abnormal blood cell counts and patient survival (1-10, 12-15) focused on patients with an advanced stage of the disease and small cell lung cancer. Few reports have focused on resectable NSCLC patients (11, 16). Moreover, few studies have estimated the prognostic significance of the use of these abnormal blood cell counts combined in NSCLC patients.
In the present study, therefore, the prognostic impact of the use of preoperative leukocytosis, anemia and thrombocytosis combined was retrospectively investigated for resectable NSCLC patients.
Patients and Methods
Two hundred and eighty-nine consecutive NSCLC patients who had undergone surgical resection from 2000 through 2005, including all patients with NSCLC who had a thoracotomy for intended surgical resection, were included in this study. There were 183 men and 106 women, with ages ranging from 26 to 86 years, with an average of 67 years. The overall follow-up periods ranged from 33 to 103 months. The baseline characteristics are summarized in Table I.
The preoperative white blood cell count, hemoglobin level and platelet count were obtained before invasive diagnostic procedures were performed. Leukocytosis was defined as a white blood cell count >1.0×104/mm3, and anemia as a hemoglobin level <13.0 g/dl in men and 12.0 g/dl in women (7), and thrombocytosis as a platelet count >32×104/mm3.
All the patients had undergone thoracotomy, and pathological (p) TNM staging was recorded for all of them. Follow-up information, including cause of death, was ascertained through a review of clinic notes and direct or family contact.
Survival curves were obtained according to the Kaplan-Meier method. Comparison of survival curves was carried out using the log-rank test. Statistical calculations were conducted with JMP (SAS Institute Inc. Cary, NC, USA) and values of p less than 0.05 were accepted as significant.
Results
The frequency of preoperative leukocytosis, anemia and thrombocytosis was 4.15% (12/289), 35.64% (103/289) and 9.34% (27/289), respectively.
As shown in Figure 1A, the 5-year survival of the patients with and without leukocytosis was 25.0% and 69.17%, respectively (p<0.0001). The patients with anemia also had a significantly poorer prognosis compared with the patients without anemia (50.10% vs. 76.84%, p<0.0001, Figure 1B). Similarly, the 5-year survival of the patients with thrombocytosis was significantly poorer compared with that of patients without thrombocytosis (42.55% vs. 69.56%, p<0.0001, Figure 1C).
The baseline clinicopathological factors.
The use of these blood cell counts (leukocytosis, anemia and thrombocytosis) combined was also evaluated. As shown in Figure 2, the 5-year survival of the patients with all three of these abnormal blood cell counts was 25.0%, which was significantly poorer compared with that of the patients without any abnormal counts (78.23%, p<0.0001). The 5-year survival of the patients with one out of the three abnormal blood cell counts was 55.43%, and that of the patients with two out of the three abnormal blood cell counts was 32.81%.
The results of univariate analysis are summarized in Table II. The gender, histology, pT status, pN status, preoperative serum CEA level and the blood cell counts were related to the patients' prognosis. The results of multivariate analysis including all variables for which p<0.05 on univariate analysis are summarized in Table III. Out of the variables that were included in the multivariate analysis, histology, pT status, pN status and the blood cell counts were independent prognostic determinants.
Survival of patients based on their preoperative leukocytosis (A), anemia (B) and thrombocytosis (C).
Discussion
In the present study, the frequency of preoperative leukocytosis, anemia and thrombocytosis was 4.15%, 35.64% and 9.34%, respectively, while higher frequency with leukocytosis 28-60%, anemia 48-80% and thrombocytosis 16-48% was reported in previous studies (1-10, 12-15). The previous studies included patients with advanced stage and small cell lung cancer (1-10, 12-15), but the present study focused on resectable non-small cell lung cancer patients. Therefore, the reason for the difference in the frequencies might be due to differences in stage and histological distribution of the patient population.
Univariate analysis.
Multivariate analysis.
Leukocytosis is occasionally found in patients with NSCLC either at the time of diagnosis or during the course of the disease (1-5). Leukocytosis in patients with malignant disease usually caused by infection, bone marrow metastasis or the administration of corticosteroids. However, patients with NSCLC sometimes reveal leukocytosis without these conditions (1-5). Such patients may be considered to have tumor-related leukocytosis (2), which is caused mainly by the unregulated production of hematopoietic cytokines, such as granulocyte-colony-stimulating factor (2, 17). Similarly, anemia and thrombocytosis in cancer patients might be regarded as a paraneoplastic phenomenon (6-16). Although the mechanism underlying the development of these abnormal blood cell counts in NSCLC patients remains unclear, tumor-associated soluble molecules might be one of the possible mechanisms. These soluble molecules secreted by the tumor cells and the host response to them might cause leukocytosis, anemia and thrombocytosis (1-16). The results of the present and previous studies (1-16) showed the significant association between abnormal blood cell counts and patient survival. Based on these findings, it is most likely that the association of the preoperative abnormal blood cell counts with patient survival is mainly due to a more aggressive tumor behavior.
Survival of patients based on the combined use of abnormal blood cell counts (leukocytosis, anemia and thrombocytosis).
However abnormal blood cell counts in cancer patients is not always a tumor-related phenomenon. Although Kasuga et al. (2) examined tumor-related leukocytosis, it was difficult to clearly distinguish a tumor-related phenomenon from other causes. Although several previous studies examined the association between abnormal blood cell counts and NSCLC patient survival (1-5, 7, 9, 11-16), few of them estimated the prognostic significance of the use of these abnormal blood cell counts combined in NSCLC patients. In the present study, when the patients were subdivided into 4 groups according to the number of abnormal blood cell counts, their survival was clearly distinguished. Based on this result, the use of these combined abnormal blood cell counts might be helpful in distinguishing NSCLC-related from non-tumor-related abnormal blood cell counts.
Currently, blood cell counts are inexpensive and routine determinations. Despite current advanced diagnostic procedures for the preoperative staging, the present results showed a role for the use of preoperative leukocytosis, anemia and thrombocytosis combined as an adjunct to conventional staging for NSCLC patients.
- Received January 30, 2009.
- Revision received April 9, 2009.
- Accepted May 4, 2009.
- Copyright© 2009 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved
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