Modern radiotherapy faces two critical challenges: overcoming biological heterogeneity and enhancing physical precision beyond anatomical constraints. Traditional approaches have primarily focused on refining energy delivery to well-defined targets, treating biological effects as downstream consequences of dose distribution. However, recent advances in both physics and biology suggest a transformative new paradigm: radiotherapy can be actively co-engineered to modulate biological response in real time. The emergence of ultra-precise physical triggers, dynamic biomarkers, and smart theranostic systems creates unprecedented opportunities. By integrating knowledge across scales—from nanoscale energy deposition to systems-level biological insights—it is now feasible to design radiotherapy protocols that are finely tailored to individual patient vulnerabilities and tumor characteristics. This convergence promises not only greater efficacy but also reduced side effects and improved quality of life for patients. Such a shift is essential in the era of personalized medicine, where the goal is to maximize therapeutic benefit while minimizing harm. This Research Topic aims to capture pioneering research at this intersection, driving the evolution toward truly individualized and adaptive radiotherapy systems.

This Research Topic highlights transformative research at this convergence. By emphasizing the interface between physics and biology, it seeks to catalyze the development of solutions that transcend conventional techniques. This involves utilizing ultra-precise physical triggers to manipulate biological processes and making use of biological feedback to adjust physical parameters dynamically. Such a comprehensive, dual-track framework is essential for the transition from passive dose distribution to the active co-engineering of physical delivery and biological response.

While focusing on combining the strengths of physics and biology in radiotherapy to break new ground, we welcome articles addressing, but not limited to, the following themes:
● Engineering ultra-precise physical triggers for targeted radiotherapy
● Decoding and targeting tumor vulnerabilities through biomarker integration
● Designing closed-loop clinical trials informed by physics-biology insights
● Developing smart theranostic systems for integrated treatment and imaging
● Overcoming current challenges in therapy with emerging intelligent platforms

We invite contributions that transcend conventional anatomical targeting, focusing instead on how physics-driven technologies can be designed to actively modulate biological responses, and conversely, on how biological insights can guide the real-time optimization of physics parameters.

Please note: Manuscripts consisting solely of bioinformatics, computational analysis, or predictions of public databases which are not accompanied by validation (independent clinical or patient cohort, or biological validation in vitro or in vivo, which are not based on public databases) are not suitable for publication in this journal.

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Towards Individual Radiotherapy Systems: Integrating Physics and Biology Across Scales

Topic Coordinator