Online Radiotherapy: The Paradigm Shift to Real-Time Adaptive Radiotherapy

Adaptive radiotherapy (ART) involves the continuous adaptation of the radiation plan according to patient- and tumorspecific feedback. In online ART, the plan is optimized in real time during the treatment; in offline ART, the plan is recalculated between treatment sessions. Hybrid linear accelerators with integrated CT, MRI, or PET are required to perform online ART.

This review is based on clinically relevant studies on online ART (January 2019 - May 2024) that were retrieved by a selective search in PubMed.

Online ART is a new technique for which no phase 3 trials have been published; in contrast, multiple randomized trials are already available for offline ART. The initial findings of a random - ized phase 2 trial of online ART for head and neck cancer showed lower rates of G2 or higher radiation-induced dermatitis (8% vs. 31%, p = 0.05) and a lower dose to the parotid gland (mean dose: 11.5 Gy vs. 16.0 Gy, p = 0.02) with online ART compared to standard radiochemotherapy. Moreover, observational studies show that online ART is feasible and spares organs at risk in patients with esophageal, pancreatic, rectal, and prostatic cancer. Additionally, online ART can enable simulation-free treatment planning and faster initiation of radiotherapy. It is, however, more demanding of time and resources and more costly than standard radiotherapy, and no studies with long-term clinical endpoints are available to date.

Initial studies confirm the feasibility of online ART and arouse the hope that it will enable more precise radiotherapy with less damage to surrounding structures. Phase 3 trials are needed so that the patient groups who stand to benefit most from online ART can be identified.