Adaptive Radiotherapy for Safe Hypofractionation

Condition(s) studied

Investigational drug(s) / intervention(s)

Adaptive Hypofractionated Radiotherapy: Adaptive Radiotherapy (ART) in this study is a real-time, online daily adaptation approach in which high-resolution on-table imaging (kV-CBCT or real-time MRI) is performed prior to each fraction, with the treatment plan immediately recalculated or re-optimized using reduced PTV margins before delivery if needed, enabling safe hypofractionation through tighter margins.

Standard-of-care Radiotherapy: Planned radiotherapy delivered according to physician discretion, without daily online contour adaptation or plan re-optimization prior to treatment delivery.

Study summary

This phase II, registry-based cohort-multiple randomized controlled trial (cmRCT) evaluates whether daily online adaptive radiotherapy (ART) enables the safe delivery of hypofractionated, iso-biologically equivalent (EQD2) external beam radiotherapy compared with standard-of-care (SOC) fractionation.

Conventional radiotherapy requires generous planning target volume (PTV) margins to account for inter-fraction anatomical variation, which increases radiation exposure to surrounding organs at risk (OARs) and may contribute to toxicity. Modern ART platforms using daily on-table imaging (kV-CBCT or MRI guidance) allow real-time contour adaptation and online plan re-optimization based on same-day anatomy. This approach enables margin reduction while maintaining target coverage and may permit safe hypofractionation.

Eligible patients enrolled in an institutional prospective registry will be randomized (1:1) to receive either SOC radiotherapy or hypofractionated ART across multiple pelvic disease strata (post-prostatectomy prostate cancer, intact prostate cancer, endometrial cancer, cervical cancer, and rectal cancer).

The primary objective is to demonstrate non-inferiority of hypofractionated ART compared with SOC in terms of cumulative incidence of Grade ≥2 toxicity (CTCAE v5). Secondary outcomes include acute and late toxicity, oncologic outcomes (progression-free survival, locoregional failure, distant metastases, overall survival), patient-reported outcomes, treatment efficiency, and dosimetric parameters.

A Bayesian monitoring framework with pre-specified safety and futility stopping rules will be used to ensure patient safety and clinical equipoise throughout the trial.

Eligibility

Primary outcome measure(s)

• Physician-reported Grade 2+ toxicity — 24 months
  The primary endpoint is the cumulative incidence of physician-reported Grade 2+ toxicity (CTCAE v5) occurring within 24 months from the completion of radiotherapy.

Trial sites (1)

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