The standard treatment for locally advanced cervical cancer is well established as a combination of chemotherapy and radiation, typically over 25-28 daily fractions with the addition of a brachytherapy boost to the primary tumor. An important component to treatment efficacy is overall treatment time. Prolongation of overall treatment time has been shown to lead to worse local control and overall survival; thus, strategies to effectively deliver radiation efficiently is required.

This is a pragmatic feasibility study to determine the impact of upfront brachytherapy combined with hypofractionated external beam radiation for patients with locally advanced cervical cancer (FIGO 2018 stage IB3-IVA) on late gastrointestinal and genitourinary toxicity, oncologic outcomes including recurrence free survival, and systemic and local immune response.

Inclusion Criteria:

• Newly diagnosed biopsy proven FIGO (2018) clinical stage IB3-IVA cervical carcinoma.
• Histological diagnosis of squamous cell carcinoma, adenocarcinoma, or adenosquamous cell carcinoma of the cervix
• Candidate for definitive radiation therapy as determined by treating radiation oncologist.
• At least 18 years of age.
• ECOG performance status ≤ 2
• Ability to understand and willingness to sign an IRB approved written informed consent document. Legally authorized representative may sign and give informed consent on behalf of study participants.

Exclusion Criteria:

• Any prior pelvic radiotherapy.
• Any prior gynecologic or other pelvic malignancy.
• Any prior or concurrent malignancy whose natural history has the potential to interfere with the safety or efficacy assessment of the investigational regimen. Patients with prior or concurrent malignancy that does NOT meet that definition are eligible for the trial.
• Evidence of metastatic disease outside of the pelvis or para-aortic nodes.
• Previous hysterectomy or planned hysterectomy as part of initial cervical cancer therapy; this includes patients with a prior history of supracervical hysterectomy.
• Pregnant and/or breastfeeding. Women of childbearing potential must have a negative pregnancy test day of or within 7 days prior to simulation.
• Major surgery ≤ 3 weeks prior to initiating protocol therapy; if a patient has had major surgery prior to 3 weeks, they must have recovered from any surgical effects.
• Serious, uncontrolled medical disorder, nonmalignant systemic disease, or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 90 days) myocardial infarction, uncontrolled chronic obstructive pulmonary disease, uncontrolled major seizure disorder, unstable spinal cord compression, or superior vena cava syndrome.

Within 6 months of publication.

Data will be available for investigators whose proposed use of the data has been approved by an independent review committee.