Predictors of Clinical Hematological Toxicities under Radiotherapy in Patients with Cervical Cancer-A Risk Analysis

Abstract

Background: Cervical cancer ranks third in frequency among female cancers globally and causes high mortality worldwide. Concurrent chemoradiotherapy improves the overall survival in cervical cancer patients by 6% but it can cause significant acute and late toxicities affecting patient quality of life. Whole pelvis radiotherapy doses of 10-20 Gy can lead to myelosuppression and to subsequent hematological toxicities since pelvic bones contain half of bone marrow tissue.

Methods: A total of 69 patients with IB-IVB-staged cervical cancer have been included in this retrospective cohort study. We analyzed clinical adverse events and changes in blood cell counts (hemoglobin, neutrophils, leukocytes, and platelets) during radiation or chemoradiotherapy received at the Oncological Institute of Bucharest from 2018 to 2021.

Results: Decreases in hemoglobin levels of over 2.30 g/dL during treatment were associated with BMI > 23.2 kg/m² (OR = 8.68, 95%CI = [1.01, 75.01]), age over 53 years (OR = 4.60 95%CI = [1.10, 19.22]), with conformational 3D irradiation (OR = 4.78, 95%CI = [1.31, 17.40]) and with total EQD2 of over 66.1 Gy (OR = 3.67, 95%CI = [1.02, 13.14]). The hemoglobin decrease rate of 0.07 g/dL/day was related to 95% isodose volume (OR = 18.00). Neutropenia is associated frequently with gastrointestinal side effects and with the bowel and rectal V45 isodoses (OR = 16.5 and OR = 18.0, respectively). Associations of total external and internal radiation dose with the time durations calculated from the initiation of treatment to the onset of hematological adverse reactions were also obtained. The maximum drop in leukocytes was observed before day 35 from the RT initiation in patients who underwent treatment with 3D conformal radiotherapy (OR = 4.44, 95%CI = [1.25, 15.82]). Neutrophil levels under 2.2 × 10³/μL and thrombocyte levels under 131 × 10³/μL during the follow-up period were associated with a total planned dose of 54 Gy to the pelvic region volume (OR = 6.82 and OR = 6.67, respectively).

Conclusions: This study shows the existence of clinical and blood predictors of hematological adverse reactions in cervical cancer patients. Thus, patients who are in a precarious clinical situation, with low hematological values (but not yet abnormal), should be monitored during days 29-35 after the initiation of RT, especially if they are obese or over 53 years of age.

Keywords: anemia; cervical cancer; chemoradiotherapy; leukocytosis; neutropenia; thrombocytopenia.

Figure 1

Axial planning CT sections of the pelvis with isodose levels depicted in color-wash and the corresponding dose–volume histograms (DVH) of cervical cancer patients treated with radiation therapy at the Oncological Institute of Bucharest. (a) The 3D-CRT treatment plan; (b) VMAT treatment plan; (c) 3D-CRT treatment plan DVH; (d) VMAT treatment plan DVH. Still images obtained from Eclipse™ (Varian Medical Systems Inc., Palo Alto, CA, USA) (a,c) and Monaco™ (Elekta, Stockholm, Sweden) (b,d).

Figure 2

Trends of 4 hematologic variables during intratherapeutic (during radiotherapy) and post-therapeutic monitoring: (a) leukocytes, (b) hemoglobin, (c) neutrophils and (d) platelets in 4 different sets of 10 randomly selected patients from our cohort. The dashed orange lines represent the lower limits of the range of normal reference values of our institution’s laboratory for (a) leukocytes (4 × 10^3/μL), (b) hemoglobin (12 g/dL), (c) neutrophils (2.2 × 10^3/μL) and (d) platelets (150 × 10^3/μL).