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Review
. 2025 Jul 2;26(13):6375.
doi: 10.3390/ijms26136375.

Radiation Therapy Personalization in Cancer Treatment: Strategies and Perspectives

Marco Calvaruso  1 , Gaia Pucci  1 , Cristiana Alberghina  1 , Luigi Minafra  1
Affiliations
Review

Radiation Therapy Personalization in Cancer Treatment: Strategies and Perspectives

Marco Calvaruso et al. Int J Mol Sci. .

Abstract

Modern oncology increasingly relies on personalized strategies that aim to customize medical interventions, using both tumor biology and clinical features to enhance efficacy and minimize adverse effects. In recent years, precision medicine has been implemented as part of systemic therapies; however, its integration into radiation therapy (RT) is still a work in progress. Conventional RT treatment plans are based on the Linear Quadratic (LQ) model and utilize standardized alpha and beta ratios (α/β), which ignore the high variability in terms of treatment response between and within patients. Recent advances in radiobiology, as well as general medical technologies, have also driven a shift toward more tailored approaches, including in RT. This review provides an overview of current knowledge and future perspectives for the personalization of RT, highlighting the role of tumor and patient-specific biomarkers, advanced imaging techniques, and novel therapeutic approaches. As an alternative to conventional RT modalities, hadron therapy and Flash RT are discussed as innovative approaches with the potential to improve tumor targeting while sparing normal tissues. Furthermore, the synergistic combination of RT with immunotherapy is discussed as a potential strategy to support antitumor immune responses and overcome resistance. By integrating biological insights, technological innovation, and clinical expertise, personalized radiation therapy may significantly advance the precision oncology paradigm.

Keywords: personalized medicine; radiobiology; radiotherapy.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Comparison between conventional and personalized RT plans. Although conventional RT follows standardized protocols (external beam RTusing X or γ-rays), its effectiveness varies among patients. Today, the need for personalized therapies is extremely high, and a multidisciplinary strategy is required for more effective, tailored, and biologically driven RT treatments.
Figure 2
Figure 2
Main mechanisms of cancer radioresistance.
Figure 3
Figure 3
A brief history of RT: from the past to future perspectives. A historical timeline describing all the milestones of RT development, from basic to more personalized approaches. (MRI—Magnetic Resonance Imaging; PET—Positron Emission Tomography; TPS—Treatment Planning System; CRT—Conformal Radiation Therapy; SBRT—Stereotactic Body Radiation Therapy; IMRT—Intensity-Modulated Radiation Therapy; VMAT—Volumetric Modulated Arc Therapy; RSI—Radiosensitivity Index; GARD—Genomic-Adjusted Radiation Dose; MBRT—Minibeam Radiation Therapy).
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