New Approaches in Radiotherapy

Abstract

Radiotherapy (RT) has undergone transformative advancements since its inception over a century ago. This review highlights the most promising and impactful innovations shaping the current and future landscape of RT. Key technological advances include adaptive radiotherapy (ART), which tailors treatment to daily anatomical changes using integrated imaging and artificial intelligence (AI), and advanced image guidance systems, such as MR-LINACs, PET-LINACs, and surface-guided radiotherapy (SGRT), which enhance targeting precision and minimize collateral damage. AI and data science further support RT through automation, improved segmentation, dose prediction, and treatment planning. Emerging biological and targeted therapies, including boron neutron capture therapy (BNCT), radioimmunotherapy, and theranostics, represent the convergence of molecular targeting and radiotherapy, offering personalized treatment strategies. Particle therapies, notably proton and heavy ion RT, exploit the Bragg peak for precise tumor targeting while reducing normal tissue exposure. FLASH RT, delivering ultra-high dose rates, demonstrates promise in sparing normal tissue while maintaining tumor control, though clinical validation is ongoing. Spatially fractionated RT (SFRT), stereotactic techniques and brachytherapy are evolving to treat challenging tumor types with enhanced conformality and efficacy. Innovations such as 3D printing, Auger therapy, and hyperthermia are also contributing to individualized and site-specific solutions. Across these modalities, the integration of imaging, AI, and novel physics and biology-driven approaches is redefining the possibilities of cancer treatment. This review underscores the multidisciplinary and translational nature of modern RT, where physics, engineering, biology, and informatics intersect to improve patient outcomes. While many approaches are in various stages of clinical adoption and investigation, their collective impact promises to redefine the therapeutic boundaries of radiation oncology in the coming decade.

Keywords: adaptive radiotherapy; advanced image guidance; artificial intelligence and data science; boron neutron capture; brachytherapy; flash radiotherapy; heavy ion radiotherapy; proton radiotherapy; radioimmunotherapy; spatially fractionated radiotherapy; stereotactic radiotherapy; theranostics.

Figure 1

New RT approaches for cancer. Abbreviations in the figure: artificial intelligence (AI), boron neutron capture therapy (BNCT), intraoperative RT (IORT), photodynamic therapy (PDT), spatially fractionated RT (SFRT), three-dimensional (3D), total body irradiation (TBI), total marrow irradiation (TMI), volumetric modulated arc therapy (VMAT).

Figure 2

New approaches in brachytherapy. Abbreviations in the figure: dynamic modulated brachytherapy (DMBT), quality assurance (QA), magnetic resonance imaging (MRI), transrectal ultrasound (TRUS).

Figure 3

A schematic comparing conventional RT, offline ART, online ART, and real-time ART. For online and real-time ART, the initial simulation is used to develop a reference (ref) plan.

Figure 4

Immune modulation by radiation therapy. Radiation induces both immunostimulatory and immunosuppressive effects through pathways involving dendritic cell activation, T cell priming, chemokine-driven immune cell infiltration, and the recruitment of immunosuppressive cells within the tumor microenvironment.

Figure 5

Conceptual comparison between the traditional 2D GRID therapy (left) and the 3D LATTICE therapy (right).

Figure 6

A simulated SFRT plan with peak dose 15 Gy per fraction. Solid and dash arrows indicate the peak and valley dose regions, respectively. (Multiplan TPS 5.2.1 for CyberKnife).