Moderately hypofractionated online adaptive radiotherapy (SWIFT-1) in cervical cancer patients: study protocol for a multi-centered, open-label, two-arm, phase III, randomized controlled study.

Background: External beam radiotherapy (EBRT) is an essential component of standard treatment for locally advanced cervical cancer. Moderately hypofractionated radiotherapy (MHRT) offers the potential to reduce treatment burden while compromising efficacy. Although various studies have investigated the safety and efficacy of MHRT, high-quality evidence remains inadequate. The lack of integration of modern radiotherapy techniques in many existing studies may lead to an overestimation of MHRT-associated toxicity.

Methods: This prospective, multi-center, randomized controlled, non-inferiority phase III trial aims to evaluate the non-inferiority of moderately hypofractionated online adaptive radiotherapy (oART) compared to conventional fractionated radiotherapy (CFRT). A total of 440 participants will be enrolled and randomly assigned in a 1:1 ratio to either the MHRT or CFRT group. Both groups will receive concurrent chemoradiotherapy, and a subset of eligible patients will undergo immunotherapy. The prescribed EBRT dose for the MHRT group will be 43.35 Gy in 17 fractions, with a simultaneous integrated boost of 54.4 Gy in 17 fractions to positive lymph nodes. The CFRT group will receive 45 Gy in 25 fractions, with a simultaneous integrated boost of 60 Gy in 25 fractions to positive lymph nodes. The primary endpoint will be 3-year progression-free survival. Secondary endpoints will include the complete response rate, tumor regression following EBRT, overall survival, locoregional progression-free survival, metastasis-free survival, cervical cancer-specific survival, acute and late toxicity, and quality of life.

Discussion: This randomized controlled trial will prospectively investigate whether MHRT is non-inferior to conventional fractionation in terms of efficacy and safety. Furthermore, the trial will evaluate the potential of moderately hypofractionated oART as a clinically viable alternative to CFRT for the treatment of locally advanced cervical cancer.

Trial registration: This trial was registered at ClincalTrials.gov (NCT06641635) on October 12, 2024.