Hypofractionated Radiotherapy in Cervical Cancer: A Non-inferiority Randomized Controlled Trial

This study is a prospective, parallel-group, randomized, interventional, non-inferiority clinical trial evaluating definitive hypofractionated external beam radiotherapy in comparison with conventional fractionated external beam radiotherapy for women with locally advanced carcinoma of the cervix treated with concurrent cisplatin-based chemoradiation and image-guided brachytherapy. The protocol is designed to test whether reduction of external beam treatment duration through a moderate hypofractionated schedule can maintain pelvic loco-regional control within a prespecified non-inferiority margin while potentially improving feasibility, throughput, and patient adherence in a high-burden practice environment.

The background for the study is rooted in the persistent gap between disease burden and radiotherapy access in cervical cancer. In many low-resource and high-volume centers, a standard course of pelvic chemoradiation followed by brachytherapy requires multiple weeks of daily attendance and often imposes logistical, geographic, and financial burdens on patients. Treatment prolongation and interruptions are clinically important because Overall Treatment Time(OTT) has long been recognized as a determinant of disease control in cervical cancer, and delays may adversely affect local control through accelerated tumor repopulation. A shortened external beam component may therefore provide both operational and biologic advantages if tumor dose, normal tissue constraints, and brachytherapy integration are carefully preserved.

Hypofractionation in gynecologic malignancies has historically been approached cautiously because of concerns related to bowel, bladder, rectal, vaginal, and other pelvic normal tissue tolerance. However, advances in treatment planning and delivery, including three-dimensional conformal radiotherapy, intensity-modulated radiotherapy, volumetric planning, image guidance, and standardized brachytherapy contouring, have increased the feasibility of testing moderate hypofractionated schedules with modern organ-at-risk protection. Available early and phase I/II experience suggests that moderately hypofractionated pelvic radiotherapy may be deliverable with acceptable acute toxicity in selected cervical cancer settings, but large randomized datasets remain limited. This trial is designed to address that evidence gap by generating comparative data in a prospective randomized framework.

The study population comprises women with histopathologically confirmed locally advanced cervical cancer considered suitable for definitive chemoradiation. Participants are expected to have disease stages appropriate for radical treatment, adequate hematologic, renal, and hepatic function to receive concurrent cisplatin, and performance status compatible with curative-intent therapy. Patients with advanced metastatic disease, prior pelvic radiotherapy, prior systemic therapy that would confound response assessment, uncontrolled comorbidity, pregnancy, or other protocol-specified exclusions would not be eligible. Final eligibility, staging workup, and protocol-specific inclusion and exclusion criteria are addressed in the corresponding sections of the registry and protocol document.

After confirmation of eligibility and baseline evaluation, participants will be randomized in a 1:1 allocation ratio to standard fractionation or hypofractionation. Randomization is intended to reduce allocation bias and permit an unbiased estimate of comparative treatment effect across efficacy and safety endpoints. Stratification factors may include clinically relevant prognostic variables such as nodal status or other institutional balancing factors, as prespecified in the protocol and statistical analysis plan.