S2984
Invited Speaker
ESTRO 2026
addressing combined EBRT and molecular radiotherapy approaches. Results
2000]. Functional imaging methods, such as positron emission tomography (PET) or functional magnetic resonance imaging (MRI), are used to depict the tumor biology. Even though these methods have been around for many years, the concept of BTV has not been widely adopted. In the presence of MR- integrated linear accelerators and the advent of PET- integrated linear accelerators, the concept of biologically-guided radiotherapy may finally come into clinical action. During the presentation, the current status and pending challenges will be addressed, such as: (1) results from clinical on dose escalation or de- escalation (in HNSCC, NSCLC, prostate); (2) normal tissue tolerance of tumor-surrounding tissues; (3) availability and reproducibility of the imaging method; and (4) regulatory hurdles. 5265 Molecular microdose meets macrodose: Synergy of theranostics and EBRT Lidia Strigari Medical Physics, Lidia Strigari, BOLOGNA, Italy Purpose/Objective The mechanisms of absorbed dose delivery differ fundamentally across radiotherapy modalities in terms of spatial scale, temporal evolution, and radiobiological relevance. In external beam radiotherapy (EBRT), photon irradiation is planned and optimized mainly at the macroscopic level, encompassing target volumes, organs at risk, and voxel-based dose distributions. In molecular radiotherapy and theranostics, absorbed dose is delivered internally via radiopharmaceutical uptake and clearance, resulting in biologically driven, patient- specific spatiotemporal heterogeneity. This perspective supports the view that EBRT and theranostics are not alternative paradigms, but complementary components of a future multi-scale radiation oncology model. Material/Methods A conceptual multi-scale analysis was conducted to compare how absorbed dose is generated, distributed, and biologically interpreted in EBRT, beta-emitter therapy, and alpha-emitter therapy. Particular emphasis was placed on the dosimetric and radiobiological factors that limit the direct translation of models across modalities, including fractionation, dose rate, temporal protraction, spatial non- uniformity, radionuclide range, crossfire effects, and, for alpha emitters, recoil phenomena, microscale stochasticity, and high LET. In parallel, Working Group 5 of the COST Action RATIONALE project [1] identified studies reporting dose–effect correlations for tumor control and organ-at-risk toxicity, including studies
The analysis shows that radiobiological frameworks developed for EBRT cannot be directly extrapolated to theranostics without scale-aware adaptation. EBRT is dominated by conformal macrodose shaping and established dose–volume and fractionation concepts. Theranostics adds molecular targeting, lesion-specific uptake information, patient-specific kinetics, and radiation-type-dependent heterogeneity. Beta-emitter therapies bridge voxel and lesion scales through non- uniform uptake and crossfire. Alpha-emitter therapies shift the relevant modeling domain toward the cellular and subcellular level. Despite these differences, there is a major opportunity for synergy. Theranostics contributes to biologically selective irradiation and quantitative molecular imaging. Together with EBRT, they create the basis for biologically informed combined treatments. This is possible when the absorbed dose is interpreted within a shared multi- scale framework rather than simply summed across
modalities. Conclusion
The real challenge is not only dose accumulation. It is also the reconciliation of how different radiation types deliver energy and how biology interprets that energy across space and time. A Virtual Human Twin offers a promising integrative framework. This approach combines imaging, dosimetry, radiobiology, anatomy, and patient-specific kinetics into a unified predictive model. Such an approach could enable a clinically meaningful bridge between molecular microdose and macrodose. It would support a new generation of combined EBRT-theranostic strategies. References: [1] https://www.rationalenetwork.eu/en 5266 See, adapt, treat: Functional imaging-driven adaptive radiotherapy Iuliana Toma-Dasu Medical Radiation Physics, Stockholm University and Karolinska Institutet, Stockholm, Sweden Functional and molecular imaging have opened new avenues for biologically guided radiotherapy by enabling the characterization of tumour heterogeneity beyond conventional anatomical imaging. Imaging of key tumour features such as hypoxia, proliferation, and metabolism provides the basis for defining biologically relevant target subvolumes and for tailoring treatment to individual patient characteristics. These developments extend earlier concepts of biologically guided dose prescription and biological target volumes, which highlighted both the
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