Innovative Approaches in Precision Radiation Oncology: Advanced Imaging Technologies and Challenges Which Shape the Future of Radiation Therapy

Yue Yan^1,2,3*Daniel A Alexander^1,3Bryan P Bednarz⁴Lawrence Fernando Bronk⁵Huixiao Chen⁶David J Gladstone^1,2,3Bin Han⁷Christopher Iannuzzi⁸Yuting Li⁹Ngoc Nguyen⁶Natasha Mulenga²Natalie N Viscariello¹⁰Yuenan Wang⁸Joseph Weygand^1,3Yana Zlateva⁵Fada Guan⁵

• ¹Dartmouth Hitchcock Medical Center, Lebanon, United States
• ²Dartmouth College Thayer School of Engineering, Hanover, United States
• ³Dartmouth College Geisel School of Medicine, Hanover, United States
• ⁴University of Wisconsin-Madison, Madison, United States
• ⁵The University of Texas MD Anderson Cancer Center Division of Radiation Oncology, Houston, United States
• ⁶Yale University Yale Cancer Center, New Haven, United States
• ⁷Stanford University, Stanford, United States
• ⁸St Vincent's Medical Center, Bridgeport, United States
• ⁹The University of Texas MD Anderson Cancer Center Proton Therapy Center, Houston, United States
• ¹⁰The University of Alabama at Birmingham, Birmingham, United States

Radiation oncology is experiencing a transformative shift toward precision medicine, driven by unprecedented advances in imaging technologies that enable increasingly personalized and adaptive cancer treatment. Traditional anatomical imaging approaches are rapidly being complemented and, in some cases, superseded by sophisticated modalities that integrate functional, molecular, and real-time biological information into treatment planning and delivery. This evolution represents a paradigm shift from static, one-size-fits-all radiation therapy toward dynamic, patient-specific approaches that can adapt to tumor biology, anatomical changes, and treatment response in real-time. The emergence of magnetic resonance-guided radiotherapy (MRgRT) systems has enabled daily soft-tissue visualization and online plan adaptation. Simultaneously, the integration of positron emission tomography (PET) with linear accelerators has introduced biology-guided radiotherapy (BgRT), allowing real-time tracking of metabolically active tumor regions. Advanced cone beam computed tomography (CBCT) systems now support online adaptive workflows through rapid, high-quality imaging and AI-enhanced CT generation. Novel applications including Cherenkov radiation imaging, stereoscopic guidance with surface tracking, and generative AI-based image synthesis are further expanding the precision radiotherapy toolkit. In proton therapy, innovations spanning dual-energy CT, proton CT, and in-vivo range verification are addressing fundamental range uncertainty. This comprehensive review aims to provide a critical, integrated assessment of emerging and advanced imaging technologies that are reshaping precision radiotherapy. Unlike previous reviews that examine individual modalities in isolation, we synthesize the underlying physical principles, current clinical applications, technical challenges, and quality assurance requirements across the complete spectrum of imaging-guided radiation therapy (RT) approaches. This work addresses a critical gap in the literature by providing the first comprehensive, cross-platform analysis of how diverse imaging modalities complement each other within modern precision RT workflows. We emphasize practical implementation challenges—including geometric accuracy requirements, quantitative imaging uncertainties, workflow optimization, and workforce training needs—that are essential for successful clinical translation. Furthermore, we outline a forward-looking framework that integrates multi-omics data with functional and anatomical imaging, supported by trustworthy AI protocols. This integrated perspective is designed to guide clinicians, medical physicists, and researchers in navigating the rapidly evolving landscape of precision radiotherapy while ensuring safe, equitable, and effective implementation of these transformative technologies across diverse patient populations.