Locally Advanced Cervical Cancer, Vitamin D Concentration
Conditions
Keywords
Locally advanced cervical cancer;, vitamin D;, hypovitaminosis D;, serum vitamin D;, cervical lavage;, chemoradiotherapy;, radiotherapy;, cisplatin;, brachytherapy;, treatment response;, radiation toxicity;, RECIST 1.1;, CTCAE;, chemoradiosensitivity;, chemoradioresistency
Brief summary
Background. Definitive chemoradiotherapy represents the standard therapeutic approach for the management of locally advanced cervical cancer. Vitamin D plays an important role in the regulation of cellular growth and differentiation, immune system function, and the modulation of inflammatory processes. Hypovitaminosis D may be associated with the development of cervical cancer, whereas its impact on the effects of oncological treatment remains insufficiently elucidated. The aim of this study is to investigate the predictive significance of vitamin D in patients with locally advanced cervical cancer treated with definitive chemoradiotherapy. Methods. This study is designed as a clinical, observational, prospective cohort study. Patients with locally advanced cervical cancer undergoing definitive chemoradiotherapy at the Clinic for Radiation Oncology, University Clinical Center Kragujevac, will be enrolled. Vitamin D concentrations will be measured before the initiation of treatment in both serum and cervical lavage samples. Baseline vitamin D levels will be analyzed in relation to treatment outcome and the occurrence of acute radiation toxicity. In addition, vitamin D concentrations will be evaluated in the context of clinical and morphological parameters, therapeutic response, and treatment-related toxicity. Expected Results. This study will enable an assessment of the actual significance of pretreatment vitamin D concentrations in serum and cervical lavage as a potential novel biomarker in relation to chemoradiosensitivity and/or chemoradioresistance of cervical cancer, as well as the response of organs at risk, in patients with locally advanced disease.
Detailed description
Definitive concurrent chemoradiotherapy is the standard treatment for locally advanced cervical cancer. Although it achieves high response rates, some patients do not attain a complete therapeutic response, potentially because of chemoradioresistance. Radiotherapy also exerts immunomodulatory effects within the tumor microenvironment, which may be particularly relevant in cervical cancer because of its association with persistent human papillomavirus infection. Identifying biomarkers associated with treatment response and toxicity could therefore support more individualized treatment strategies. Vitamin D regulates cellular proliferation and differentiation, immune responses, and inflammatory processes. Hypovitaminosis D and reduced vitamin D receptor expression have been associated with cervical cancer and other malignancies. However, the predictive value of pretreatment vitamin D status in patients undergoing modern definitive chemoradiotherapy remains insufficiently established. Pretreatment vitamin D concentrations will be measured in serum and cervical lavage fluid. All participants will receive standard definitive treatment comprising external beam radiotherapy, brachytherapy, and concurrent weekly cisplatin-based chemotherapy. Acute treatment-related toxicity will be assessed throughout chemoradiotherapy, and the definitive therapeutic response will be evaluated by pelvic magnetic resonance imaging five months after treatment completion. Pretreatment serum and cervical lavage vitamin D concentrations will be analyzed in relation to therapeutic response, acute treatment-related toxicity, and relevant clinical, morphological, treatment-related, and sociodemographic parameters. The study will also evaluate the correlation between systemic and local vitamin D concentrations and explore potential cut-off values for predicting complete therapeutic response and clinically significant acute toxicity. Participants with low pretreatment vitamin D concentrations will not receive supplementation as part of the study protocol.
Interventions
DIAGNOSTIC_TESTPretreatment Vitamin D Assessment in Serum and Cervical Lavage Fluid
Vitamin D concentrations will be measured before the initiation of definitive chemoradiotherapy in serum and cervical lavage fluid using chemiluminescence, as the standard institutional laboratory method. Baseline vitamin D levels will be analyzed in relation to treatment response, acute radiation toxicity, and selected clinical, morphological, treatment-related, and socio-demographic parameters.
Sponsors
University of Kragujevac
Study design
Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Female patients aged 18 to 80 years. * Histopathologically confirmed cervical cancer. * Locally advanced disease, FIGO 2018 stage IIB to IVA. * Eastern Cooperative Oncology Group performance status 0-1. * Planned treatment with definitive concurrent chemoradiotherapy. * Signed informed consent. * Ability to comply with study procedures and follow-up visits.
Exclusion criteria
* Age under 18 years. * Pregnancy or lactation. * Previous or synchronous diagnosis of another pelvic or abdominal malignancy. * Previous chemotherapy. * Previous radiotherapy. * Previous treatment with immune checkpoint inhibitors. * Current or recent vitamin D supplementation. * Interrupted oncological treatment. * Failure to attend scheduled follow-up visits. * Incomplete medical documentation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Complete therapeutic response after definitive chemoradiotherapy | Five months after the last radiotherapy fraction. | The proportion of patients achieving complete therapeutic response after definitive concurrent chemoradiotherapy. Treatment response will be assessed by pelvic magnetic resonance imaging and clinical examination, according to RECIST 1.1 criteria. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinically significant acute radiation toxicity | First radiotherapy fraction until 90th day (acute toxicity). | The proportion of patients developing clinically significant acute radiation toxicity during definitive chemoradiotherapy. Clinically significant toxicity will be defined as CTCAE v. 6 grade II or higher. |
| Severity of acute radiation toxicity | First radiotherapy fraction until 90th day. | The maximum grade of acute radiation toxicity observed during chemoradiotherapy, assessed according to CTCAE v.6 criteria. |
| Association between pretreatment serum vitamin D concentration and treatment response | Baseline before treatment initiation and five months after the last radiotherapy fraction. | Association between pretreatment serum vitamin D concentration and complete therapeutic response versus absence of complete therapeutic response after definitive chemoradiotherapy. Serum vitamin D concentration will be measured before treatment initiation using chemiluminescence as the standard institutional laboratory method. |
| Association between pretreatment cervical lavage vitamin D concentration and treatment response | Baseline before treatment initiation and five months after the last radiotherapy fraction. | Association between pretreatment vitamin D concentration in cervical lavage fluid and complete therapeutic response versus absence of complete therapeutic response after definitive chemoradiotherapy. Vitamin D concentration in cervical lavage fluid will be measured before treatment initiation using chemiluminescence as the standard institutional laboratory method. |
| Association between pretreatment vitamin D concentration and acute radiation toxicity | Baseline before treatment initiation and 90th day. | Association between pretreatment vitamin D concentrations in serum and cervical lavage fluid and the occurrence of clinically significant acute radiation toxicity, defined as CTCAE v.6 grade II or higher. |
| Correlation Between Serum and Cervical Lavage Vitamin D Concentrations | Baseline before initiation of chemoradiotherapy. | Correlation between pretreatment vitamin D concentrations measured in serum and cervical lavage fluid. |
| Optimal pretreatment vitamin D cut-off value for prediction of treatment response and toxicity | Five months after the last radiotherapy fraction. | Receiver operating characteristic curve analysis will be used to determine the optimal pretreatment vitamin D cut-off value for prediction of complete therapeutic response and clinically significant acute radiation toxicity. |
Countries
Serbia
Contacts
CONTACTMarija Živković Radojević, MD, PhD, Radiation Oncologist
CONTACTNeda Milosavljević, MD, PhD, Radiation Oncologist
PRINCIPAL_INVESTIGATORMarija Živković Radojević, MD, PhD, Radiation Oncologist
Faculty of Medical Sciences, University of Kragujevac, Serbia, University Clinical Centre Kragujevac, Center for radiation oncology
Outcome results
None listed