Vitamin D Status and Clinical Outcomes in Locally Advanced Cervical Cancer

Официальное название

Pretreatment Vitamin D Status and Clinical Outcomes in Patients With Locally Advanced Cervical Cancer Undergoing Definitive Chemoradiotherapy

Обзор

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.

Подробное описание

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.

Вмешательства

• Диагностический тест Pretreatment 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.

Первичные конечные точки

• Complete therapeutic response after definitive chemoradiotherapy [Срок оценки: Five months after the last radiotherapy fraction.]

Вторичные конечные точки (7)

• Clinically significant acute radiation toxicity [Срок оценки: First radiotherapy fraction until 90th day (acute toxicity).]
• Severity of acute radiation toxicity [Срок оценки: First radiotherapy fraction until 90th day.]
• Association between pretreatment serum vitamin D concentration and treatment response [Срок оценки: Baseline before treatment initiation and five months after the last radiotherapy fraction.]
• Association between pretreatment cervical lavage vitamin D concentration and treatment response [Срок оценки: Baseline before treatment initiation and five months after the last radiotherapy fraction.]
• Association between pretreatment vitamin D concentration and acute radiation toxicity [Срок оценки: Baseline before treatment initiation and 90th day.]
• Correlation Between Serum and Cervical Lavage Vitamin D Concentrations [Срок оценки: Baseline before initiation of chemoradiotherapy.]
• Optimal pretreatment vitamin D cut-off value for prediction of treatment response and toxicity [Срок оценки: Five months after the last radiotherapy fraction.]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Модель наблюдения

Случай-контроль

Центры проведения

Сербия · 1 центр

• University Clinical Center Kragujevac — Kragujevac

Идентификаторы

NCT: NCT07743918 · CERVITAL-2025

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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