Hypofractionated Chemoradiotherapy for Cervical Cancer

The goal of this clinical trial is to evaluate whether hypofractionated whole pelvic or extended-field concurrent chemoradiotherapy can improve treatment access and efficiency while potentially providing superior oncologic efficacy and safety compared to conventional chemoradiotherapy in patients with early-stage node-positive and locally advanced cervical cancer. Building on encouraging safety and efficacy outcomes from our Phase II HYPOCx-iRex trial (TCTR20210812003), this study will provide data for a critical evidence gap regarding the safety, feasibility, and oncologic efficacy of hypofractionated radiotherapy, including extended-field para-aortic treatment, delivered with concurrent chemotherapy. The main questions it aims to answer are: * Does hypofractionated chemoradiotherapy achieve superior nodal control compared to conventional chemoradiotherapy? * Does hypofractionated chemoradiotherapy achieve superior overall survival compared to conventional chemoradiotherapy? Researchers will compare patients receiving hypofractionated external beam radiotherapy to those receiving conventional fractionation to evaluate if the shortened hypofractionated schedule provides comparable disease control, acceptable toxicity, improved quality of life, and cost-effectiveness. Participants will: * Be randomized to receive either hypofractionated external beam radiotherapy or conventional fractionation radiotherapy, both delivered using modern IMRT/VMAT techniques targeting either the whole pelvis or extended fields (including para-aortic lymph nodes). * Receive concurrent platinum-based chemotherapy during external beam radiation. * Complete image-guided adaptive brachytherapy following external beam radiotherapy. * Attend scheduled follow-up visits to evaluate tumor response, disease control, treatment-related toxicities, quality of life, and survival outcomes.

Sex

Female

Minimum age

18 Years

Inclusion Criteria:

1. Cancer of the uterine cervix considered suitable for curative treatment with definitive radio-(chemo)therapy including imaged-guided BT
2. Positive biopsy showing squamous-cell carcinoma, adenocarcinoma, or adeno-squamous cell carcinoma of the uterine cervix
3. Locally advanced staging according to FIGO 2018 and TNM guidelines (Stage IA1-IVA)
4. MRI of the pelvis at diagnosis is performed
5. MRI, CT, or PET-CT of the retroperitoneal space and abdomen at diagnosis is performed
6. MRI with the applicator in place at the time of (first) BT will be performed
7. GFR ≥ 50 mL/min
8. Patient informed consent

Exclusion Criteria:

1. Other primary malignancies except carcinoma in situ of the cervix and basal cell carcinoma of the skin
2. Small cell neuroendocrine cancer, melanoma and other rare cancers in the cervix
3. Metastatic disease beyond intervertebral disc L2/3 level
4. Previous pelvic or abdominal radiotherapy
5. Previous total or subtotal hysterectomy
6. Combination of preoperative radiotherapy with surgery
7. Patients receiving BT only
8. Patients receiving EBRT only
9. Patients receiving neo-adjuvant chemotherapy or other forms of antineoplastic treatment apart from weekly concomitant cisplatin (40 mg/m2).
10. Contra-indications to MRI
11. Contra-indications to BT