Vitamin D Status and Clinical Outcomes in Locally Advanced Cervical Cancer

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.

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.