Radiotherapy-induced Haematological and Intestinal Toxicity in Cervical Cancer

Radiotherapy-induced Haematological and Intestinal Toxicity in Cervical Cancer | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Radiotherapy-induced Haematological and Intestinal Toxicity in Cervical Cancer Ruishuang Ma, Xiaoxian Ye, Jianliang Zhou, Pengrong Lou, Shenchao Guo, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-265849/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Chemotherapy-induced myelosuppression is common and threatening, however, the effect of radiation on bone marrow activity especially leukocyte count has been underestimated in cervical cancer. Pelvic radiation-related intestinal toxicity is prevalent, and the relationship between leukopenia and intestinal toxicity is not clear. The clinical data of 59 patients who underwent conventional radiation alone for cervical cancer were retrospectively analyzed. The patients had normal leukocyte count on admission, and the blood cell count, GTV dose, intestinal toxicity were evaluated. During radiotherapy (RT), 47 patients (79.7%) developed into leukopenia with 38.3% mild and 61.7% moderate. The mean time for leucopenia was 9 days. Compared with leucopenia-negative patients, leucopenia-positive ones had lower baseline leukocyte count, while the neutrophil/lymphocyte (NLR) and monocyte/lymphocyte (MLR) showed no significance. Logistic regression analysis indicated that excluding the factors for age, BMI, TNM stage, surgery and GTV dose, baseline leukocyte count was an important independent predictor of leucopenia (OR=0.383). During RT, the significant reduction was found in leukocyte, neutrophil and lymphocyte count at week 2 while monocyte count after 2 weeks. Furthermore, NLR and MLR showed significant and sustained upward trend. About 54.2% patients had gastrointestinal symptoms, however, no significant difference was noted between leukocyte count as well as NLR/MLR and intestinal toxicity. Our results suggest a high prevalence of leucopenia in cervical cancer patients receiving RT, and those with low baseline leukocyte count are more likely for leucopenia, for whom early prevention of infection may be needed during RT. Oncology Cancer Biology Cervical cancer Radiotherapy-induced leucopenia Intestinal toxicity Figures Figure 1 Figure 2 Introduction The radical hysterectomy with pelvic lymphadenectomy is acknowledged as the primary therapeutic option for early-stage cervical cancer. 1 – 3 For patients with increased risk for disease relapse (intermediate and high-risk pathological factors) postoperative pelvic radiotherapy (RT, with or without platinum-based chemotherapy) is recommended. 4 – 6 Compared with patients treated only with surgery, postoperative RT reduces risk for local recurrence to 47%. In the group of elderly patients with late stage, surgery as well as chemotherapy can not bring good curative effect, and then RT is indicated as the preferred treatment modality for cervical cancer. Compared with chemical agents, the side effects of limited radiation seems mild, but it can not be ignored. The most common postirradiation toxicities in the pelvic are gastrointestinal, genitourinary as well as haematological. 7 The RT area of cervical cancer covers the whole pelvic cavity, including anterior superior iliac spine and iliac spine, which are important hematopoietic organs. Chemotherapy-induced myelosuppression has been well recognized in solid tumor, 8 – 10 however, less study is focused on the role of irradiation alone in bone marrow activity especially in cervical cancer. Furthermore, the effects of RT on the degree of leukopenia is still controversial and the related factors are not fully evaluated. Pelvic radiation-related intestinal toxicity is also prevalent, 11 and the relationship between leukopenia and intestinal toxicity is not clear. In this study, complete blood parameters before and during RT were collected and the changes of leukocytes, neutrophil/lymphocyte (NLR) and monocyte/lymphocyte (MLR) were assessed. Logistic regression analysis was used to analyze the factors contributing to leucopenia and the correlation between leukocyte cell count and intestinal toxicity. Our study will provide new insight into the irradiation-induced leucopenia and evidence for the prevention of infection complications. Method Patients A total of 59 patients with cervical cancer from Ningbo First Hospital between January 2018 to December 2020 were enrolled. The inclusion conditions were as follows: 1. Patients were diagnosed with cervical cancer by pathology; 2. only received RT without chemotherapy; 3. completed the entire radiation therapy plan; 4. the baseline of leukocyte count before RT was normal (≥3.5×10 9 /L). We excluded those who had inflammation, intestinal or hematological diseases, or who received prior or concurrent chemotherapy, hyperfractionated RT, or RT to multiple sites concurrently. All patients signed informed consent. The study was approved by the Ethics Committee of Ningbo First Hospital. Treatment All patients received RT for at least 5 weeks using Intensity Modulated Radiation Therapy (IMRT) and a three-dimensional treatment planning system (3D-CRT). The median dose for pelvic radiation was 45 Gy, and patients with metastatic pelvic or abdominal lymph nodes had 54-60 Gy. Blood counts Blood samples of patients were collected and leukocyte count at baseline (on admission), weekly during RT, and at the end of RT were analyzed. The normal rang of leukocyte count was 3.5-9.5×10 9 /L. Leucopenia was defined as: mild (3-3.5×10 9 /L), moderate (2-3×10 9 /L) and severe (<2×10 9 /L). Neutrophil to lymphocyte ratio (NLR) and monocyte to lymphocyte ratio (MLR) were also analyzed. Intestinal toxicity Intestinal toxicity was mainly defined by clinical symptoms. Systemic enteritis were excluded and patients had symptoms of acute enteritis after radiation as below: 1. nausea, vomiting, abdominal pain, diarrhea, and tenesmus; 2. diarrhea more than 3 times/day and antidiarrheal agents or antibiotics was needed; 3. symptoms of acute enteritis were improved after a rest of RT. Statistical analysis Clinical variables of the patients were compared with T test for continuous variables, and chi-squared for categorical variables. Logistic regression analysis was used to assess the degree of association among independent variables. SPSS version 23.0 was used for statistical analyses. Statistical significance was defined as p<0.05. Results Leucopenia during RT in cervical cancer Among the 59 patients with cervical cancer receiving RT, 47 patients (79.7%) developed into leucopenia (< 3.5×10 9 /L) and the mean time was 9 days (Table 1 ). Eighteen of them had mild leucopenia (38.3%) and 29 developed into moderate leucopenia (61.7%). Table 1 Clinical characteristics of patients with or without leukopenia Leukopenia- (n = 12) Leukopenia+ (n = 47) P values Age (years) 62.17 ± 13.01 62.43 ± 9.52 0.94 BMI (kg/m 2 ) 23.17 ± 3.54 22.97 ± 4.25 0.88 Surgery 66.67% (8/12) 74.47% (35/47) 0.72 TNM I 7 22 0.79 II 3 18 III 1 2 IV 1 4 WBC (×10 9 /L) 5.99 (4.50, 8.03) 4.78 (4.15, 5.53) 45 5 18 Intestinal toxicity (%) 66.67% (8/12) 51.1% (24/47) 0.33 No significance was found in age, BMI, TNM staging, surgery, radiation dose between the leucopenia-negative and positive groups. Compared with the leucopenia-negative group, the baseline leukocyte count was markedly decreased in leucopenia-positive group. However, the NLR and MLR at baseline showed no significance. Further logistic regression analysis indicated that excluding the factors for age, BMI, TNM stage, surgery and GTV dose, baseline leukocyte count was an important independent predictor of leucopenia (OR = 0.383, 95% CI = 0.193–0.758, p < 0.01). The leukocyte count as well as NLR/MLR at week 1, 2, 4, and 5 after RT were analyzed (Fig. 1 ). The significant reduction was found in leukocyte, neutrophil and lymphocyte count at week 2 [leukocyte week 1 vs week 2: 3.99 (3.25, 5.31) vs 3.46 (2.72, 4.19), adjusted p < 0.01; neutrophil week 1 vs week 2: 2.5 (2.1, 3.2) vs 2.2 (1.6, 2.8), adjusted p < 0.01; lymphocyte baseline vs week 2: 1.5 (1.2, 1.8) vs 0.7 (0.5, 0.9), adjusted p < 0.01]. While monocyte count decreased after 2 weeks [monocyte week 2 vs week 4: 0.3 (0.3, 0.4) vs 0.4 (0.3, 0.5), adjusted p < 0.05]. Furthermore, NLR and MLR showed significant and sustained upward trend. The association between leucopenia and intestinal toxicity As shown in Table 2 , 54.2% patients had intestinal toxicity during RT, and the data of basic characteristics such as age, BMI, surgery, TNM staging, leucopenia and GTV dose didn’t differ between the two groups. Moreover, leukocyte count as well as NLR/MLR before and during RT was compared between patients with or without intestinal toxicity. Mann-Whitney U tests indicated that the changes of leukocyte count as well as NLR/MLR had no significant difference between the two groups (Fig. 2 ). Table 2 Clinical characteristics of patients with or without intestinal toxicity Intestinal toxicity - (n = 27) Intestinal toxicity + (n = 32) P values Age (years) 60.93 ± 9.10 63.59 ± 11.02 0.32 BMI (kg/m 2 ) 23.19 ± 4.38 22.87 ± 3.88 0.77 Surgery 21(21/27) 22(22/32) 0.56 TNM I 13 16 0.63 II 8 12 III 3 1 IV 2 3 WBC (×10 9 /L) 5.00 (4.12, 5.87) 4.89 (4.44, 6.00) 0.36 NLR (%) 1.85 (1.59, 2.79) 1.87 (1.56, 2.34) 0.43 MLR (%) 0.24 (0.19, 0.28) 0.25 (0.18, 0.33) 0.72 GTV dose (Gy) 0.19 ≤ 45 19 17 > 45 8 15 Discussion 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. Conclusion Our results suggest that RT-induced haematological toxicity especially leucopenia in cervical cancer is of high prevalence and severity, which shall be paid more attention to reduce the occurrence of other complications and ensure the completeness of RT safely and smoothly. Abbreviations RT, radiotherapy; NLR, neutrophil to lymphocyte ratio; MLR, monocyte to lymphocyte ratio; IMRT, intensity Modulated Radiation Therapy; 3D-CRT, three-dimensional treatment planning system; WBC, white blood cell count; BMI, body mass index Declarations Ethical Approval and Consent to participate Not applicable Consent for publication Not applicable Availability of supporting data Not applicable Competing interests The authors report no conflicts of interest in this work. Funding This work was supported by the National Natural Science Foundation of China (81903144). Author Contribution Ruishuang Ma designed the research, made the figures and wrote the paper; Xiaoxian Ye, Jianliang Zhou, Shenchao Guo analyzed data; Ruishuang Ma obtained the funding; Pengrong Lou and Jianxin Guo revised the manuscript and provided partial funding support. Acknowledgement We thank Zhongze Lou, Huiling Le Huan Liu and Fan Yang for excellent technical assistance. Ethical Statement This work is original and none of this work has been published before or is under consideration for publication anywhere else. All authors adhere to discipline-specific rules for acquiring, selecting and processing data. References Cohen PA, Jhingran A, Oaknin A, Denny L. Cervical cancer. Lancet. 2019;393(10167):169-182. doi: 10.1016/S0140-6736(18)32470-X. Koh WJ, Abu-Rustum NR, Bean S, Bradley K, Campos SM, Cho KR,et al. Cervical Cancer, Version 3.2019, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2019;17(1):64-84. doi: 10.6004/jnccn.2019.0001. Gupta S, Maheshwari A, Parab P, Mahantshetty U, Hawaldar R, Sastri Chopra S, et al. Neoadjuvant Chemotherapy Followed by Radical Surgery Versus Concomitant Chemotherapy and Radiotherapy in Patients With Stage IB2, IIA, or IIB Squamous Cervical Cancer: A Randomized Controlled Trial. J Clin Oncol. 2018;36(16):1548-1555. doi: 10.1200/JCO.2017.75.9985. Naga Ch P, Gurram L, Chopra S, Mahantshetty U. The management of locally advanced cervical cancer. Curr Opin Oncol. 2018;30(5):323-329. doi: 10.1097/CCO.0000000000000471. Kim HJ, Chang JS, Koom WS, Lee KC, Kim GE, Kim YB. Radiotherapy is a safe and effective salvage treatment for recurrent cervical cancer. Gynecol Oncol. 2018;151(2):208-214. doi: 10.1016/j.ygyno.2018.08.029. Matsuo K, Nusbaum DJ, Machida H, Huang Y, Khetan V, Matsuzaki S, et al. Populational trends and outcomes of postoperative radiotherapy for high-risk early-stage cervical cancer with lymph node metastasis: concurrent chemo-radiotherapy versus radiotherapy alone. Am J Obstet Gynecol. 2020;222(5):484.e1-484.e15. doi: 10.1016/j.ajog.2019.10.010. Klopp AH, Yeung AR, Deshmukh S, Gil KM, Wenzel L, Westin SN, et al. Patient-Reported Toxicity During Pelvic Intensity-Modulated Radiation Therapy: NRG Oncology-RTOG 1203. J Clin Oncol. 2018;36(24):2538-2544. doi: 10.1200/JCO.2017.77.4273. Weitzner O, Yagur Y, Kadan Y, Beiner ME, Fishman A, Ben Ezry E, et al. Chemotherapy Toxicity in BRCA Mutation Carriers Undergoing First-Line Platinum-Based Chemotherapy. Oncologist. 2019;24(12):e1471-e1475. doi: 10.1634/theoncologist.2019-0272. Narayan V, Vaughn D. Pharmacokinetic and toxicity considerations in the use of neoadjuvant chemotherapy for bladder cancer. Expert Opin Drug Metab Toxicol. 2015;11(5):731-42. doi: 10.1517/17425255.2015.1005600. Testart-Paillet D, Girard P, You B, Freyer G, Pobel C, Tranchand B. Contribution of modelling chemotherapy-induced hematological toxicity for clinical practice. Crit Rev Oncol Hematol. 2007;63(1):1-11. doi: 10.1016/j.critrevonc.2007.01.005. Hale MF. Radiation enteritis: from diagnosis to management. Curr Opin Gastroenterol. 2020;36(3):208-214. doi: 10.1097/MOG.0000000000000632. Zachariah B, Jacob SS, Gwede C, Cantor A, Patil J, Casey L, Zachariah AB. Effect of fractionated regional external beam radiotherapy on peripheral blood cell count. Int J Radiat Oncol Biol Phys. 2001;50(2):465-72. doi: 10.1016/s0360-3016(00)01587-x. Blank KR, Cascardi MA, Kao GD. The utility of serial complete blood count monitoring in patients receiving radiation therapy for localized prostate cancer. Int J Radiat Oncol Biol Phys. 1999;44(2):317-21. doi: 10.1016/s0360-3016(99)00018-8. Yang FE, Vaida F, Ignacio L, Houghton A, Nauityal J, Halpern H, Sutton H, Vijayakumar S. Analysis of weekly complete blood counts in patients receiving standard fractionated partial body radiation therapy. Int J Radiat Oncol Biol Phys. 1995;33(3):617-17. Hellman S, Fink ME. Granulocytie reserve followingradiation tberapy as studied by tbe response to a bacterial Blood. 1965;25:310-324. Dovšak T, Ihan A, Didanovič V, Kansky A, Verdenik M, Hren NI. Effect of surgery and radiotherapy on complete blood count, lymphocyte subsets and inflammatory response in patients with advanced oral cancer. BMC Cancer. 2018;18(1):235. doi: 10.1186/s12885-018-4136-9. PMID: 29490633 Trask CW, Llewellyn I, Souhami RL. The effect of radiotherapy on blood mononuclear cell numbers and phagocyte migration. Clin Radiol. 1980;31(6):733-8. doi: 10.1016/s0009-9260(80)80032-8. Lu L, Li W, Chen L, Su Q, Wang Y, Guo Z, Lu Y, Liu B, Qin S. Radiation-induced intestinal damage: latest molecular and clinical developments. Future Oncol. 2019;15(35):4105-4118. doi: 10.2217/fon-2019-0416. Verdenik M, Hren NI. Effect of surgery and radiotherapy on complete blood count, lymphocyte subsets and inflammatory response in patients with advanced oral cancer. BMC Cancer. 2018;18(1):235. doi: 10.1186/s12885-018-4136-9. Pape H, Orth K, Heese A, Heyll A, Kobbe G, Schmitt G, Niederbichler AD, Peiper M, Schwarz A, Boelke E. G-CSF during large field radiotherapy reduces bone marrow recovery capacity. Eur J Med Res. 2006;11(8):322-8. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-265849","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research","associatedPublications":[],"authors":[{"id":15370613,"identity":"9a65be07-683c-4163-9ade-ee43874c293b","order_by":0,"name":"Ruishuang Ma","email":"","orcid":"","institution":"Ningbo City First Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Ruishuang","middleName":"","lastName":"Ma","suffix":""},{"id":15370614,"identity":"eccf12bd-88ac-4dc6-b73a-4603426e94e2","order_by":1,"name":"Xiaoxian Ye","email":"","orcid":"","institution":"Ningbo First Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Xiaoxian","middleName":"","lastName":"Ye","suffix":""},{"id":15370615,"identity":"0dfa0b66-825d-485e-bedf-6abe2d0d2829","order_by":2,"name":"Jianliang Zhou","email":"","orcid":"","institution":"Ningbo First Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Jianliang","middleName":"","lastName":"Zhou","suffix":""},{"id":15370616,"identity":"e393ab4d-8216-4071-b0e1-d00c3d8cf909","order_by":3,"name":"Pengrong Lou","email":"","orcid":"","institution":"Ningbo First Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Pengrong","middleName":"","lastName":"Lou","suffix":""},{"id":15370617,"identity":"14941979-eb31-4d07-a558-9d4f13cb6c71","order_by":4,"name":"Shenchao Guo","email":"","orcid":"","institution":"Ningbo First Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Shenchao","middleName":"","lastName":"Guo","suffix":""},{"id":15370618,"identity":"ebeae020-6775-4bd1-80be-f850064f2504","order_by":5,"name":"Jianxin Guo","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAwklEQVRIiWNgGAWjYDACCQYDEMXMwN7Y+PADaVp4DjcbS5CiBchIbxPgIUaHuXTzNmnetlp2g5sP24D67eR0GwhosZxzrAyo5Tiz5OzEtgcFDMnGZgcIaDG4kWMG1HKMmV86sd1AguFA4jaitbBJHmyT4CFBSw0zvwQjsVruHCu2nHPuALNkTyIwkA2I8cvt5o033pTVJRscP/7w4YcKOzmCWoCARYqX7XAy1ATCykGA+eOPP3V2xKkdBaNgFIyCEQkAn7JCUwjJG+MAAAAASUVORK5CYII=","orcid":"","institution":"Ningbo first hospital","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Jianxin","middleName":"","lastName":"Guo","suffix":""}],"badges":[],"createdAt":"2021-02-22 07:39:50","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-265849/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-265849/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":6775073,"identity":"db67bf71-4c1e-417d-a8fa-51db647395fb","added_by":"auto","created_at":"2021-03-10 00:12:07","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":97733,"visible":true,"origin":"","legend":"The changes of leukocyte and NLR/MLR during radiotherapy in cervical cancer. *p\u003c0.05, ** p\u003c0.01, data were present with median and quartile.","description":"","filename":"figure1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-265849/v1/8423ac0dd2f0a1e1e9fc094f.jpg"},{"id":6774561,"identity":"227067a5-f6b3-4241-b77f-ad437addd63c","added_by":"auto","created_at":"2021-03-10 00:09:07","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":112791,"visible":true,"origin":"","legend":"The changes of leukocyte and NLR/MLR during radiotherapy in patients with or without intestinal toxicity. No significance were found in leukocyte as well as NLR/MLR between the intestinal toxicity-negative and positive groups at each week. Data were present with median and quartile.","description":"","filename":"figure2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-265849/v1/1647307a69d897a9e0bbf0ff.jpg"},{"id":13676673,"identity":"d8f69985-7938-4883-8ced-66a916e27558","added_by":"auto","created_at":"2021-09-17 11:31:47","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":402950,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-265849/v1/a74e67e7-b4e3-40d7-a5df-21554421fada.pdf"}],"financialInterests":"","formattedTitle":"\u003cp\u003eRadiotherapy-induced Haematological and Intestinal Toxicity in Cervical Cancer\u003c/p\u003e","fulltext":[{"header":"Introduction","content":" \u003cp\u003eThe radical hysterectomy with pelvic lymphadenectomy is acknowledged as the primary therapeutic option for early-stage cervical cancer. \u003csup\u003e\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e For patients with increased risk for disease relapse (intermediate and high-risk pathological factors) postoperative pelvic radiotherapy (RT, with or without platinum-based chemotherapy) is recommended. \u003csup\u003e\u003cspan additionalcitationids=\"CR5\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e Compared with patients treated only with surgery, postoperative RT reduces risk for local recurrence to 47%. In the group of elderly patients with late stage, surgery as well as chemotherapy can not bring good curative effect, and then RT is indicated as the preferred treatment modality for cervical cancer.\u003c/p\u003e \u003cp\u003eCompared with chemical agents, the side effects of limited radiation seems mild, but it can not be ignored. The most common postirradiation toxicities in the pelvic are gastrointestinal, genitourinary as well as haematological. \u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e The RT area of cervical cancer covers the whole pelvic cavity, including anterior superior iliac spine and iliac spine, which are important hematopoietic organs. Chemotherapy-induced myelosuppression has been well recognized in solid tumor, \u003csup\u003e\u003cspan additionalcitationids=\"CR9\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e however, less study is focused on the role of irradiation alone in bone marrow activity especially in cervical cancer. Furthermore, the effects of RT on the degree of leukopenia is still controversial and the related factors are not fully evaluated.\u003c/p\u003e \u003cp\u003ePelvic radiation-related intestinal toxicity is also prevalent, \u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e and the relationship between leukopenia and intestinal toxicity is not clear. In this study, complete blood parameters before and during RT were collected and the changes of leukocytes, neutrophil/lymphocyte (NLR) and monocyte/lymphocyte (MLR) were assessed. Logistic regression analysis was used to analyze the factors contributing to leucopenia and the correlation between leukocyte cell count and intestinal toxicity. Our study will provide new insight into the irradiation-induced leucopenia and evidence for the prevention of infection complications.\u003c/p\u003e "},{"header":"Method","content":"\u003cp\u003e\u003cstrong\u003ePatients\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA total of 59 patients with cervical cancer from Ningbo First Hospital between January 2018 to December 2020 were enrolled. The inclusion conditions were as follows: 1. Patients were diagnosed with cervical cancer by pathology; 2. only received RT without chemotherapy; 3. completed the entire radiation therapy plan; 4. the baseline of leukocyte count before RT was normal (\u0026ge;3.5\u0026times;10\u003csup\u003e9\u003c/sup\u003e/L). We excluded those who had inflammation, intestinal or hematological diseases, or who received prior or concurrent chemotherapy, hyperfractionated RT, or RT to multiple sites concurrently. All patients signed informed consent. The study was approved by the Ethics Committee of Ningbo First Hospital.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTreatment\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll patients received RT for at least 5 weeks using Intensity Modulated Radiation Therapy (IMRT) and a three-dimensional treatment planning system (3D-CRT). The median dose for pelvic radiation was 45 Gy, and patients with metastatic pelvic or abdominal lymph nodes had 54-60 Gy.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eBlood counts\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eBlood samples of patients were collected and leukocyte count at baseline (on admission), weekly during RT, and at the end of RT were analyzed. The normal rang of leukocyte count was 3.5-9.5\u0026times;10\u003csup\u003e9\u003c/sup\u003e/L. Leucopenia was defined as: mild (3-3.5\u0026times;10\u003csup\u003e9\u003c/sup\u003e/L), moderate (2-3\u0026times;10\u003csup\u003e9\u003c/sup\u003e/L) and severe (\u0026lt;2\u0026times;10\u003csup\u003e9\u003c/sup\u003e/L). Neutrophil to lymphocyte ratio (NLR) and monocyte to lymphocyte ratio (MLR) were also analyzed.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eIntestinal toxicity\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIntestinal toxicity was mainly defined by clinical symptoms. Systemic enteritis were excluded and patients had symptoms of acute enteritis after radiation as below: 1. nausea, vomiting, abdominal pain, diarrhea, and tenesmus; 2. diarrhea more than 3 times/day and antidiarrheal agents or antibiotics was needed; 3. symptoms of acute enteritis were improved after a rest of RT.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical analysis \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eClinical variables of the patients were compared with T test for continuous variables, and chi-squared for categorical variables. Logistic regression analysis was used to assess the degree of association among independent variables. SPSS version 23.0 was used for statistical analyses. Statistical significance was defined as p\u0026lt;0.05.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003eLeucopenia during RT in cervical cancer\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAmong the 59 patients with cervical cancer receiving RT, 47 patients (79.7%) developed into leucopenia (\u0026lt;\u0026thinsp;3.5\u0026times;10\u003csup\u003e9\u003c/sup\u003e/L) and the mean time was 9 days (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e). Eighteen of them had mild leucopenia (38.3%) and 29 developed into moderate leucopenia (61.7%).\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003ctable id=\"Tab1\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eClinical characteristics of patients with or without leukopenia\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eLeukopenia- (n\u0026thinsp;=\u0026thinsp;12)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eLeukopenia+ (n\u0026thinsp;=\u0026thinsp;47)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eP values\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAge (years)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e62.17\u0026thinsp;\u0026plusmn;\u0026thinsp;13.01\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e62.43\u0026thinsp;\u0026plusmn;\u0026thinsp;9.52\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.94\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eBMI (kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e23.17\u0026thinsp;\u0026plusmn;\u0026thinsp;3.54\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e22.97\u0026thinsp;\u0026plusmn;\u0026thinsp;4.25\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.88\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSurgery\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e66.67% (8/12)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e74.47% (35/47)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.72\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eTNM\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eI\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e7\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e22\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.79\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eII\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e18\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eIII\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eIV\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eWBC (\u0026times;10\u003csup\u003e9\u003c/sup\u003e/L)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e5.99 (4.50, 8.03)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e4.78 (4.15, 5.53)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e\u0026lt;\u0026thinsp;0.05\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNLR (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.81 (1.61, 3.00)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.87 (1.56, 2.44)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.53\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMLR (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.22 (0.19, 0.33)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.24 (0.19, 0.31)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.59\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eTime (days)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNA\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e9 (7, 15)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eGTV dose (Gy)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.83\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026le;\u0026thinsp;45\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e7\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e29\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026gt;\u0026thinsp;45\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e5\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e18\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eIntestinal toxicity (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e66.67% (8/12)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e51.1% (24/47)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.33\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eNo significance was found in age, BMI, TNM staging, surgery, radiation dose between the leucopenia-negative and positive groups. Compared with the leucopenia-negative group, the baseline leukocyte count was markedly decreased in leucopenia-positive group. However, the NLR and MLR at baseline showed no significance. Further logistic regression analysis indicated that excluding the factors for age, BMI, TNM stage, surgery and GTV dose, baseline leukocyte count was an important independent predictor of leucopenia (OR\u0026thinsp;=\u0026thinsp;0.383, 95% CI\u0026thinsp;=\u0026thinsp;0.193\u0026ndash;0.758, p\u0026thinsp;\u0026lt;\u0026thinsp;0.01).\u003c/p\u003e\n\u003cp\u003eThe leukocyte count as well as NLR/MLR at week 1, 2, 4, and 5 after RT were analyzed (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e). The significant reduction was found in leukocyte, neutrophil and lymphocyte count at week 2 [leukocyte week 1 vs week 2: 3.99 (3.25, 5.31) vs 3.46 (2.72, 4.19), adjusted p\u0026thinsp;\u0026lt;\u0026thinsp;0.01; neutrophil week 1 vs week 2: 2.5 (2.1, 3.2) vs 2.2 (1.6, 2.8), adjusted p\u0026thinsp;\u0026lt;\u0026thinsp;0.01; lymphocyte baseline vs week 2: 1.5 (1.2, 1.8) vs 0.7 (0.5, 0.9), adjusted p\u0026thinsp;\u0026lt;\u0026thinsp;0.01]. While monocyte count decreased after 2 weeks [monocyte week 2 vs week 4: 0.3 (0.3, 0.4) vs 0.4 (0.3, 0.5), adjusted p\u0026thinsp;\u0026lt;\u0026thinsp;0.05]. Furthermore, NLR and MLR showed significant and sustained upward trend.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eThe association between leucopenia and intestinal toxicity\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAs shown in Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e, 54.2% patients had intestinal toxicity during RT, and the data of basic characteristics such as age, BMI, surgery, TNM staging, leucopenia and GTV dose didn\u0026rsquo;t differ between the two groups. Moreover, leukocyte count as well as NLR/MLR before and during RT was compared between patients with or without intestinal toxicity. Mann-Whitney U tests indicated that the changes of leukocyte count as well as NLR/MLR had no significant difference between the two groups (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003ctable id=\"Tab2\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eClinical characteristics of patients with or without intestinal toxicity\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eIntestinal toxicity - (n\u0026thinsp;=\u0026thinsp;27)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eIntestinal toxicity + (n\u0026thinsp;=\u0026thinsp;32)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eP values\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAge (years)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e60.93\u0026thinsp;\u0026plusmn;\u0026thinsp;9.10\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e63.59\u0026thinsp;\u0026plusmn;\u0026thinsp;11.02\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.32\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eBMI (kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e23.19\u0026thinsp;\u0026plusmn;\u0026thinsp;4.38\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e22.87\u0026thinsp;\u0026plusmn;\u0026thinsp;3.88\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.77\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSurgery\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e21(21/27)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e22(22/32)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.56\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eTNM\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eI\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e13\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e16\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.63\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eII\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e8\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e12\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eIII\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eIV\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eWBC (\u0026times;10\u003csup\u003e9\u003c/sup\u003e/L)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e5.00 (4.12, 5.87)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e4.89 (4.44, 6.00)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.36\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNLR (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.85 (1.59, 2.79)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.87 (1.56, 2.34)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.43\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMLR (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.24 (0.19, 0.28)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.25 (0.18, 0.33)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.72\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eGTV dose (Gy)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.19\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026le;\u0026thinsp;45\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e19\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e17\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026gt;\u0026thinsp;45\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e8\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e15\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn 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. \u003csup\u003e\u003cspan class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e Blank RK also demonstrated that few patients experienced drops in their WBCs below critical nadirs during the period of RT in prostate cancer. \u003csup\u003e\u003cspan class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e 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, \u003csup\u003e\u003cspan class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e 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, \u003csup\u003e\u003cspan class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e 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.\u003c/p\u003e\n\u003cp\u003eSecondly, 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. \u003csup\u003e\u003cspan class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e 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. Dov\u0026scaron;ak Tadej et al has reported that surgery has an effect on the peripheral blood count in oral cancer, \u003csup\u003e\u003cspan class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e and in our study 73% patients underwent surgery before RT, which may contribute to the lower baseline leukocyte count.\u003c/p\u003e\n\u003cp\u003eThirdly, we showed that despite a continuing drop trend, the leukocyte, neutrophil and lymphocyte count had significant decrease during 7\u0026ndash;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. \u003csup\u003e\u003cspan class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e 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. \u003csup\u003e\u003cspan class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e 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.\u003c/p\u003e\n\u003cp\u003eIt is reported that radiation dose and fractionation schedule, treatment field size and intestinal volume irradiated are the key determinant of intestinal radiation induced toxicity. \u003csup\u003e\u003cspan class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e Michael Pinkawa et al demonstrated that early lymphocyte level elevation was protective against late urinary and bowel toxicity, \u003csup\u003e\u003cspan class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e 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.\u003c/p\u003e\n\u003cp\u003eAdministration 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\u0026thinsp;+\u0026thinsp;progenitor cells and exhaust the bone marrow capacity while peripheral leukocyte counts remain at baseline levels, \u003csup\u003e\u003cspan class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e which indicates the hazards for repeat use of G-CSF and the importance for prevention of leucopenia.\u003c/p\u003e"},{"header":"Conclusion","content":" \u003cp\u003eOur results suggest that RT-induced haematological toxicity especially leucopenia in cervical cancer is of high prevalence and severity, which shall be paid more attention to reduce the occurrence of other complications and ensure the completeness of RT safely and smoothly.\u003c/p\u003e"},{"header":"Abbreviations ","content":"\u003cp\u003eRT, radiotherapy; NLR, neutrophil to lymphocyte ratio; MLR, monocyte to lymphocyte ratio; IMRT, intensity Modulated Radiation Therapy; 3D-CRT, three-dimensional treatment planning system; WBC, white blood cell count; BMI, body mass index\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthical Approval and Consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of supporting data\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors report no conflicts of interest in this work.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported by the National Natural Science Foundation of China (81903144).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contribution\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eRuishuang Ma designed the research, made the figures and wrote the paper; Xiaoxian Ye, Jianliang Zhou, Shenchao Guo analyzed data; Ruishuang Ma obtained the funding; Pengrong Lou and Jianxin Guo revised the manuscript and provided partial funding support.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe thank Zhongze Lou, Huiling Le Huan Liu and Fan Yang for excellent technical assistance.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical Statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work is original and none of this work has been published before or is under consideration for publication anywhere else. All authors adhere to discipline-specific rules for acquiring, selecting and processing data.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eCohen PA, Jhingran A, Oaknin A, Denny L. Cervical cancer. Lancet. 2019;393(10167):169-182. doi: 10.1016/S0140-6736(18)32470-X.\u003c/li\u003e\n\u003cli\u003eKoh WJ, Abu-Rustum NR, Bean S, Bradley K, Campos SM, Cho KR,et al. Cervical Cancer, Version 3.2019, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2019;17(1):64-84. doi: 10.6004/jnccn.2019.0001.\u003c/li\u003e\n\u003cli\u003eGupta S, Maheshwari A, Parab P, Mahantshetty U, Hawaldar R, Sastri Chopra S, et al. Neoadjuvant Chemotherapy Followed by Radical Surgery Versus Concomitant Chemotherapy and Radiotherapy in Patients With Stage IB2, IIA, or IIB Squamous Cervical Cancer: A Randomized Controlled Trial. J Clin Oncol. 2018;36(16):1548-1555. doi: 10.1200/JCO.2017.75.9985.\u003c/li\u003e\n\u003cli\u003eNaga Ch P, Gurram L, Chopra S, Mahantshetty U. The management of locally advanced cervical cancer. Curr Opin Oncol. 2018;30(5):323-329. doi: 10.1097/CCO.0000000000000471.\u003c/li\u003e\n\u003cli\u003eKim HJ, Chang JS, Koom WS, Lee KC, Kim GE, Kim YB. Radiotherapy is a safe and effective salvage treatment for recurrent cervical cancer. Gynecol Oncol. 2018;151(2):208-214. doi: 10.1016/j.ygyno.2018.08.029.\u003c/li\u003e\n\u003cli\u003eMatsuo K, Nusbaum DJ, Machida H, Huang Y, Khetan V, Matsuzaki S, et al. Populational trends and outcomes of postoperative radiotherapy for high-risk early-stage cervical cancer with lymph node metastasis: concurrent chemo-radiotherapy versus radiotherapy alone. Am J Obstet Gynecol. 2020;222(5):484.e1-484.e15. doi: 10.1016/j.ajog.2019.10.010.\u003c/li\u003e\n\u003cli\u003eKlopp AH, Yeung AR, Deshmukh S, Gil KM, Wenzel L, Westin SN, et al. Patient-Reported Toxicity During Pelvic Intensity-Modulated Radiation Therapy: NRG Oncology-RTOG 1203. J Clin Oncol. 2018;36(24):2538-2544. doi: 10.1200/JCO.2017.77.4273.\u003c/li\u003e\n\u003cli\u003eWeitzner O, Yagur Y, Kadan Y, Beiner ME, Fishman A, Ben Ezry E, et al. Chemotherapy Toxicity in \u003cem\u003eBRCA\u003c/em\u003e Mutation Carriers Undergoing First-Line Platinum-Based Chemotherapy. Oncologist. 2019;24(12):e1471-e1475. doi: 10.1634/theoncologist.2019-0272.\u003c/li\u003e\n\u003cli\u003eNarayan V, Vaughn D. Pharmacokinetic and toxicity considerations in the use of neoadjuvant chemotherapy for bladder cancer. Expert Opin Drug Metab Toxicol. 2015;11(5):731-42. doi: 10.1517/17425255.2015.1005600.\u003c/li\u003e\n\u003cli\u003eTestart-Paillet D, Girard P, You B, Freyer G, Pobel C, Tranchand B. Contribution of modelling chemotherapy-induced hematological toxicity for clinical practice. Crit Rev Oncol Hematol. 2007;63(1):1-11. doi: 10.1016/j.critrevonc.2007.01.005.\u003c/li\u003e\n\u003cli\u003eHale MF. Radiation enteritis: from diagnosis to management. Curr Opin Gastroenterol. 2020;36(3):208-214. doi: 10.1097/MOG.0000000000000632.\u003c/li\u003e\n\u003cli\u003eZachariah B, Jacob SS, Gwede C, Cantor A, Patil J, Casey L, Zachariah AB. Effect of fractionated regional external beam radiotherapy on peripheral blood cell count. Int J Radiat Oncol Biol Phys. 2001;50(2):465-72. doi: 10.1016/s0360-3016(00)01587-x.\u003c/li\u003e\n\u003cli\u003eBlank KR, Cascardi MA, Kao GD. The utility of serial complete blood count monitoring in patients receiving radiation therapy for localized prostate cancer. Int J Radiat Oncol Biol Phys. 1999;44(2):317-21. doi: 10.1016/s0360-3016(99)00018-8.\u003c/li\u003e\n\u003cli\u003eYang FE, Vaida F, Ignacio L, Houghton A, Nauityal J, Halpern H, Sutton H, Vijayakumar S. Analysis of weekly complete blood counts in patients receiving standard fractionated partial body radiation therapy. Int J Radiat Oncol Biol Phys. 1995;33(3):617-17.\u003c/li\u003e\n\u003cli\u003eHellman S, Fink ME. Granulocytie reserve followingradiation tberapy as studied by tbe response to a bacterial Blood. 1965;25:310-324.\u003c/li\u003e\n\u003cli\u003eDov\u0026scaron;ak T, Ihan A, Didanovič V, Kansky A, Verdenik M, Hren NI. Effect of surgery and radiotherapy on complete blood count, lymphocyte subsets and inflammatory response in patients with advanced oral cancer. BMC Cancer. 2018;18(1):235. doi: 10.1186/s12885-018-4136-9. PMID: 29490633\u003c/li\u003e\n\u003cli\u003eTrask CW, Llewellyn I, Souhami RL. The effect of radiotherapy on blood mononuclear cell numbers and phagocyte migration. Clin Radiol. 1980;31(6):733-8. doi: 10.1016/s0009-9260(80)80032-8.\u003c/li\u003e\n\u003cli\u003eLu L, Li W, Chen L, Su Q, Wang Y, Guo Z, Lu Y, Liu B, Qin S. Radiation-induced intestinal damage: latest molecular and clinical developments. Future Oncol. 2019;15(35):4105-4118. doi: 10.2217/fon-2019-0416.\u003c/li\u003e\n\u003cli\u003eVerdenik M, Hren NI. Effect of surgery and radiotherapy on complete blood count, lymphocyte subsets and inflammatory response in patients with advanced oral cancer. BMC Cancer. 2018;18(1):235. doi: 10.1186/s12885-018-4136-9.\u003c/li\u003e\n\u003cli\u003ePape H, Orth K, Heese A, Heyll A, Kobbe G, Schmitt G, Niederbichler AD, Peiper M, Schwarz A, Boelke E. G-CSF during large field radiotherapy reduces bone marrow recovery capacity. Eur J Med Res. 2006;11(8):322-8.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Cervical cancer, Radiotherapy-induced leucopenia, Intestinal toxicity","lastPublishedDoi":"10.21203/rs.3.rs-265849/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-265849/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eChemotherapy-induced myelosuppression is common and threatening, however, the effect of radiation on bone marrow activity especially leukocyte count has been underestimated in cervical cancer. Pelvic radiation-related intestinal toxicity is prevalent, and the relationship between leukopenia and intestinal toxicity is not clear. The clinical data of 59 patients who underwent conventional radiation alone for cervical cancer were retrospectively analyzed. The patients had normal leukocyte count on admission, and the blood cell count, GTV dose, intestinal toxicity were evaluated. During radiotherapy (RT), 47 patients (79.7%) developed into leukopenia with 38.3% mild and 61.7% moderate. The mean time for leucopenia was 9 days. Compared with leucopenia-negative patients, leucopenia-positive ones had lower baseline leukocyte count, while the neutrophil/lymphocyte (NLR) and monocyte/lymphocyte (MLR) showed no significance. Logistic regression analysis indicated that excluding the factors for age, BMI, TNM stage, surgery and GTV dose, baseline leukocyte count was an important independent predictor of leucopenia (OR=0.383). During RT, the significant reduction was found in leukocyte, neutrophil and lymphocyte count at week 2 while monocyte count after 2 weeks. Furthermore, NLR and MLR showed significant and sustained upward trend. About 54.2% patients had gastrointestinal symptoms, however, no significant difference was noted between leukocyte count as well as NLR/MLR and intestinal toxicity. Our results suggest a high prevalence of leucopenia in cervical cancer patients receiving RT, and those with low baseline leukocyte count are more likely for leucopenia, for whom early prevention of infection may be needed during RT. \u003c/p\u003e","manuscriptTitle":"Radiotherapy-induced Haematological and Intestinal Toxicity in Cervical Cancer","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2021-03-10 00:09:06","doi":"10.21203/rs.3.rs-265849/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"d6cdb631-494e-4a17-b04b-2b5399c35e52","owner":[],"postedDate":"March 10th, 2021","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":2859372,"name":"Oncology"},{"id":2859373,"name":"Cancer Biology"}],"tags":[],"updatedAt":"2021-03-18T06:37:38+00:00","versionOfRecord":[],"versionCreatedAt":"2021-03-10 00:09:06","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-265849","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-265849","identity":"rs-265849","version":["v1"]},"buildId":"7rjqhiLT3MXkJMwkYKINL","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}