In this study, we first showed that about 80% patients suffer from leucopenia during RT in cervical cancer. Zachariah B et al reported that in spite of significant decline, the white blood cell count (WBC) of all 108 patients was clinically normal during 6-week pelvic RT. 12 Blank RK also demonstrated that few patients experienced drops in their WBCs below critical nadirs during the period of RT in prostate cancer. 13 Thus we speculate that though both belonging to the category of pelvic RT, the hematotoxicity of irradiation for cervical cancer is greater than that for prostate cancer. Yang EF et al also found dramatically decreased leukocyte in various types of cancer, 14 however, the change of white blood cells in cervical cancer during RT has not been separately illustrated. Although previous studies have suggested gynecological malignancies receiving whole pelvis irradiation would be at risk for depression of granulocyte reserves, 15 it is indicated that the irradiation-related myelosuppression effect is greatly underestimated in cervical cancer. Moreover, we found more than 60% patients with leucopenia would develop into moderate level, further confirming the severity of myelosuppression by pelvis irradiation. Patients with leucopenia are at risk to experience fever or infection, which prolongs length of hospital stay, delays RT, and increases economic burden.
Secondly, we showed a lower baseline leukocyte count in patients with leucopenia after pelvis irradiation. Previous study demonstrated a strong correlation between starting complete blood counts and nadirs. 14 However, clinical factors that may affect the blood cell count during RT were not ruled out. By univariate and multivariate logistic regression analysis, excluding the factors for age, BMI, TNM stage, surgery and GTV dose, we indicate that baseline leukocyte count is an important independent predictor of RT-induced leucopenia. Furthermore, it is found that the mean value of baseline leukocyte count here is lower than that in previous study. Dovšak Tadej et al has reported that surgery has an effect on the peripheral blood count in oral cancer, 16 and in our study 73% patients underwent surgery before RT, which may contribute to the lower baseline leukocyte count.
Thirdly, we showed that despite a continuing drop trend, the leukocyte, neutrophil and lymphocyte count had significant decrease during 7–14 days (week 2) irradiation, and the adjusted p value of leukocyte, neutrophil and lymphocyte count at baseline and week 1 was of no significance by Friedman test, which is not consistent with previous studies. Yang EF reported the largest decline in leukocytes was seen during the first week. 14 Trask CWL et al also found T cell loss followed an exponential pattern was statistically significant by the end of the first week of pelvic irradiation. 17 However, only 5 patients were included in the pelvis group, and two were of cervical cancer. Two main reasons may explain for the difference: 1. patients included in this study are all with cervical cancer, and RT-induced hematotoxicity in cervical cancer may different from other types of cancer within pelvic irradiation. 2. The data of blood cell count was of non-normal distribution, and thus Friedman test was used to judge the difference between groups by rank analysis and adjusted p value. Furthermore, we for the first time showed NLR and MLR during RT in cervical cancer, and both NLR and MLR were markedly elevated following the RT period. However, by logistic regression analysis, NLR and MLR are not able to predict the risk of leucopenia. We also analyzed other blood parameters like platelets, red blood cells, hemoglobin, C-reactive protein etc., and the results were in consistent with previous studies with no more explanation here.
It is reported that radiation dose and fractionation schedule, treatment field size and intestinal volume irradiated are the key determinant of intestinal radiation induced toxicity. 18 Michael Pinkawa et al demonstrated that early lymphocyte level elevation was protective against late urinary and bowel toxicity, 19 indicating hematologic changes may be also associated with intestinal toxicity during RT. Thus we analyzed the relationship between blood parameters and intestinal toxicity in cervical cancer. However, no significance was found between the changes of leukocyte count as well as NLR/MLR and intestinal toxicity during 5 week-RT.
Administration of G-CSF drugs is a common method for clinical treatment of leucopenia due to the prompt and high efficacy as well as the low price. However, Pape H et al demonstrate that simultaneous treatment with G-CSF during radiotherapy reduces the mobilization of CD34 + progenitor cells and exhaust the bone marrow capacity while peripheral leukocyte counts remain at baseline levels, 20 which indicates the hazards for repeat use of G-CSF and the importance for prevention of leucopenia.