This study is a randomized controlled trial designed to compare hypofractionated whole pelvic radiotherapy with conventional radiotherapy in patients with cervical cancer undergoing concurrent chemoradiotherapy. Hypofractionated radiotherapy delivers a higher dose per treatment over a shorter overall treatment time, which may reduce the number of hospital visits and improve treatment convenience for patients. Conventional radiotherapy requires more treatment sessions over a longer period. The purpose of this study is to evaluate whether hypofractionated radiotherapy is as safe and effective as conventional radiotherapy. The primary outcomes focus on treatment-related toxicity, while secondary outcomes include tumor response, survival outcomes, quality of life, and treatment-related factors. In addition, this study will evaluate a novel planning approach called the indirect excess dose volume ratio (iRex) to optimize brachytherapy planning and potentially reduce radiation-related side effects.
Cervical cancer remains a significant global health burden, particularly in low- and middle-income countries. Standard treatment for locally advanced cervical cancer consists of conventional fractionated radiotherapy combined with concurrent chemotherapy, followed by brachytherapy. However, conventional radiotherapy requires prolonged treatment duration, which may negatively impact patient compliance, healthcare resource utilization, and treatment outcomes. Hypofractionated radiotherapy delivers a higher dose per fraction while maintaining a comparable total biological dose, thereby reducing the overall treatment time. Shortening treatment duration may improve tumor control based on radiobiological principles and reduce patient burden, including travel and treatment-related costs. Previous studies suggest that hypofractionated radiotherapy may provide comparable oncologic outcomes to conventional radiotherapy, with acceptable toxicity profiles. However, high-quality randomized evidence remains limited, particularly using modern radiotherapy techniques such as intensity-modulated radiotherapy (IMRT) and image-guided adaptive brachytherapy (IGABT). This study is a Phase II randomized controlled trial designed to evaluate the safety and feasibility of hypofractionated whole pelvic radiotherapy compared with conventional fractionation. Patients will be randomized to receive either hypofractionated or conventional external beam radiotherapy, both combined with concurrent chemotherapy and followed by brachytherapy. In addition, this study incorporates a novel dosimetric parameter, the indirect excess dose volume ratio (iRex), to optimize brachytherapy planning. The use of iRex in combination with standard dose constraints may improve spatial dose control and reduce radiation-induced toxicity. The primary objective is to assess treatment-related toxicity, while secondary objectives include tumor response, survival outcomes, quality of life, dosimetric parameters, and cost-effectiveness. This study aims to provide evidence supporting a shorter, more efficient radiotherapy regimen without compromising safety or efficacy.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
40
Whole pelvic radiotherapy delivered using hypofractionation (2.2 Gy per fraction over 20 fractions) with IMRT.
Whole pelvic radiotherapy delivered using conventional fractionation (1.8 Gy per fraction over 25 fractions) with IMRT.
Cisplatin-based concurrent chemotherapy administered intravenously at a dose of 40 mg/m² once weekly during external beam radiotherapy for 5 to 6 cycles.
Image-guided adaptive brachytherapy delivered following external beam radiotherapy.
Brachytherapy treatment planning optimized using iReX in addition to standard D2cc constraints.
Conventional brachytherapy treatment planning using standard D2cc constraints without iReX optimization.
Siriraj Hospital
Bangkok, Bangkok, Thailand
Incidence of Acute Treatment-Related Toxicity
Incidence of acute treatment-related toxicity during radiotherapy and at 1- and 3-month follow-up after treatment, assessed using CTCAE version 5.0.
Time frame: During treatment and up to 3 months after completion of radiotherapy
Incidence of Late (Chronic) Treatment-Related Toxicity
Incidence of late (chronic) treatment-related toxicity assessed at 6 and 12 months, and at 3 and 5 years after treatment using CTCAE version 5.0.
Time frame: From 6 months up to 5 years after completion of radiotherapy
Tumor Response Rate
Tumor response rate assessed after external beam radiotherapy and at 3-, 6-, and 12-month follow-up.
Time frame: Up to 12 months after completion of radiotherapy
Quality of Life Assessed by EQ-5D-5L
Patient-reported quality of life assessed using the EuroQol 5-Dimension 5-Level questionnaire (EQ-5D-5L) during treatment and at 1-, 3-, 6-, and 12-month, and 3- and 5-year follow-up. The EQ-5D-5L descriptive system assesses mobility, self-care, usual activities, pain/discomfort, and anxiety/depression across 5 levels of severity. The EQ Visual Analog Scale (EQ-VAS) ranges from 0 to 100, with higher scores indicating better perceived health status.
Time frame: During treatment and up to 5 years after completion of radiotherapy
Local Recurrence-free Survival
Time from completion of radiotherapy to local tumor recurrence.
Time frame: At 3 and 5 years after completion of radiotherapy
Nodal Recurrence-free Survival
Time from completion of radiotherapy to nodal recurrence.
Time frame: At 3 and 5 years after completion of radiotherapy.
Distant Metastasis-free Survival
Time from completion of radiotherapy to distant metastasis.
Time frame: At 3 and 5 years after completion of radiotherapy.
Disease-specific Survival
Time from completion of radiotherapy to death due to cervical cancer.
Time frame: At 3 and 5 years after completion of radiotherapy.
Overall Survival
Time from completion of radiotherapy to death from any cause.
Time frame: At 3 and 5 years after completion of radiotherapy.
Correlation of Dosimetric Parameters With Tumor Control and Toxicity
Exploratory analyses will assess the correlation between dosimetric parameters from brachytherapy treatment planning, including dose-volume histogram (DVH) metrics and iRex optimization values, and clinical outcomes, including local tumor control and incidence of treatment-related gastrointestinal and genitourinary toxicities assessed using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
Time frame: During treatment and follow-up up to 5 years after completion of radiotherapy.
High-risk Clinical Target Volume D90 Comparison Between iRex-oriented and Conventional Brachytherapy Planning
Comparison of high-risk clinical target volume (HR-CTV) D90 dose between iRex-oriented optimization and conventional brachytherapy planning.
Time frame: From treatment initiation through completion of brachytherapy treatment, an average of 4 weeks.
Number of Brachytherapy Fractions Achieving Successful iRex Optimization
Number and percentage of brachytherapy fractions achieving successful iRex-oriented dose optimization according to predefined planning objectives.
Time frame: From treatment initiation through completion of brachytherapy treatment, an average of 4 weeks.
Dose-Response Relationship Between iRex and Toxicity
Evaluation of the relationship between iRex values and treatment-related toxicity.
Time frame: During follow-up up to 5 years
Incremental Cost-effectiveness Ratio per Quality-adjusted Life Year Between Hypofractionated and Conventional Radiotherapy
Cost and utility data will be used to evaluate cost-effectiveness by calculating the incremental cost-effectiveness ratio (ICER) between hypofractionated and conventional radiotherapy. Uncertainty analyses will be performed using oneway sensitivity analysis, probabilistic sensitivity analysis, and threshold analysis.
Time frame: During treatment and follow-up up to 5 years after completion of radiotherapy.
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