In an effort to find a test to predict the response of normal tissue to radiotherapy, the lymphocyte micronucleus assay was used on blood samples from patients with cervical carcinoma. Peripheral blood samples from 55 patients with advanced-stage (II B-IV B) cervical carcinoma were obtained before radiotherapy. The patients were treated with external-beam radiotherapy followed by high-dose-rate brachytherapy. Acute and late normal tissue reactions were scored and correlated with the micronucleus frequency in lymphocytes after irradiation with 4 Gy in vitro. Great interindividual variability was observed in the radiation-induced lymphocyte micronucleus frequency, especially at 4 Gy. The mean number of micronuclei per 100 binucleated cells in cells irradiated with 4 Gy in vitro was significantly higher in samples from patients who suffered from acute and/or late normal tissue reactions than in those from patients with no reactions (51.0 +/- 17.7 and 29.6 +/- 10.1, respectively). A significant correlation was also found between the micronucleus frequency at 4 Gy and the severity of acute reactions and late reactions. However, the overlap between the micronucleus frequencies of patients with high-grade late normal tissue reactions and low-grade reactions is too great to recommend the micronucleus assay in its present form for routine clinical application.
A high frequency of micronuclei before radiotherapy and a slight increase of micronucleus frequency during radiotherapy measured after 10 fractions of 2 Gy were independent on stage, statistically significant adverse predictors of clinical outcome in cervical carcinoma patients treated with radiotherapy.
Background
Malignant uterine cervical neoplasms continue to be the fourth leading cause of cancer-related mortality among women globally. There is a growing interest in the prognostic value of routinely performed pre-treatment blood test indices such as red cell distribution width (RDW) or systemic immune-inflammation index (SII), the latter combining neutrophils-to-lymphocyte ratio (NLR) and platelets-to-lymphocyte ratio (PLR). These indices were shown to be prognostic for survival in some malignancies. The purpose of the study was to evaluate the association between pre-treatment RDW and SII, and overall survival (OS) in patients treated with radiotherapy for primary localised cervical cancer.
Methods
This retrospective analysis included patients treated with definitive chemoradiation therapy (CRT) between 2011 and 2017 for histopathologically confirmed FIGO 2018 stage IB2-IVA cervical cancer. Statistical analysis was performed using the Kaplan-Meier method, two-sided log-rank tests, and Cox proportional hazards models, with the Akaike Information Criterion (AIC) serving as a prediction error estimator.
Results
The study group included 249 patients with a median age of 57.2 years and a median follow-up of 75.8 months. The majority were diagnosed with squamous cell carcinoma (237, 95.2%) and had FIGO stage III (211, 84.7%). Approximately half of the patients (116; 46.4%) had regional lymph node metastases.
Patients with low RDW (≤13.4%) and low SII (≤986.01) had a significantly longer OS (p=0.001 and p=0.002). The RDW remained as an independent prognostic factor in the multivariable model (high vs low; HR=2.04; 95%CI: 1.32-3.16; p=0.001). Including RDW in the model decreased Akaike Information Criterion from 1028.25 to 1018.15.
Conclusions
RDW is a cheap and widely available index that is simultaneously an independent prognostic factor for survival and could be used to improve pre-treatment prognosis assessment in cervical cancer patients undergoing CRT. Available data encourages assessing RDW as a prognostic factor in prospective trials to aid identification of candidates for treatment escalation.
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