S2607
Radiobiology - Radiobiological modelling
ESTRO 2026
framework for advancing personalised molecular radiotherapy. The WG5 report represents a crucial step toward establishing harmonised dose constraints and biomarker-driven treatment optimisation. By promoting systematic dosimetry data collection and outcome correlation, RATIONALE aims to enable evidence- based dose prescription and to support the transition of MRT from palliative to potentially curative indications. Preliminary outcomes and perspectives from the first year of activities will be presented. References: Homepage | Rationale Keywords: dose constraints, tumor biomarkers, theragnostic Digital Poster Highlight 4560 Computational evaluation of PDAC-on-chip relevance for radiobiological and chemo-radiation studies Sofia Tartaro 1 , Alessia Beretta 2 , Paolo Zunino 3 , Tiziana Rancati 1 , Sandro Pasquali 2 , Luca Possenti 1 1 Data Science Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. 2 Molecular Pharmacology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. 3 Department of Mathematics, Politecnico di Milano, Milan, Italy Purpose/Objective: Pancreatic ductal adenocarcinoma (PDAC) is frequently associated with a hypoxic, desmoplastic microenvironment, rich in dense fibrotic stroma, which constitutes up to 90% of the tumour mass, exhibiting elevated matrix stiffness values (2–13 kPa) and poor vascularisation [1]. Such a peculiar microenvironment could impair the diffusion of drugs and oxygen, thereby playing a central role in PDAC radioresistance and chemoresistance. A microfluidic chip model was proposed to mimic this peculiar microenvironment in- vitro (PDAC-on-chip, Figure 1a) [2]. Here, we propose a computational evaluation of PDAC-on-chip relevance as a preclinical model for radiobiological and chemo-radiation applications. Material/Methods: The computational framework integrates two complementary scales: (i) a vascularized Multiscale Model (MM) implemented in GetFem++ (Figure 1b-c) [3], and (ii) an avascular agent-based model (ABM), implemented in PhysiCell [4,5] (Figure 2). The ABM describes the growth of tumour spheroids over 20 days, accounting for oxygen diffusion and hypoxia-induced necrosis. The MM extends the system by introducing a vascular domain that reproduces a microvascular network compartment and a tumoral compartment, accounting for drug uptake and consumption. Model parameters were refined through integration of experimental measurements, literature data, and calibration of tumour growth kinetics. Results: ABM simulations reproduced the experimentally observed growth kinetics of tumour spheroids and predicted oxygen gradients leading to the formation of hypoxic and necrotic cores (Figure 2a-b). A 40–50% reduction in oxygen diffusivity, mimicking the presence of dense fibrin hydrogels, enhanced necrosis and reduced growth (Figure 2c). We estimated that such oxygen levels correspond to Oxygen Enhancement Ratio (OER) values ranging between 1.05 (5%) and 1.17 (17%), using the relation from literature [3,6]. The MM introduced therapeutic agent diffusion through a vascular structure toward the tumoral compartment, elucidating the role of dense hydrogels in acting as a diffusion-limiting barrier in the PDAC-on- chip model. To this aim, gemcitabine diffusion kinetics were simulated in three different hydrogel formulations, with diffusion coefficients reduced by 50%, 90%, and 97% relative to free diffusion in water, demonstrating how these reductions can model diffusion- limited conditions by a dense extracellular matrix (ECM, Figure 1b-c).
suitability for subsequent radiobiological investigations on cells exposed to HDR Ir-192 IRT source. References: [1] Rosa, Enrico, et al. "A Gap Analysis Integrating In Vitro-Research in HDR Interventional Radiotherapy (Modern Brachytherapy): Challenges, Limitations, and Future Directions." Applied Radiation and Isotopes (2025): 112284. [2] Nath R et al. Dosimetry of interstitial brachytherapy sources: Recommendations of the AAPM Radiation Therapy Committee Task Group No. 43. Med Phys 1995; 22: 209-234. [3] Beaulieu, L. et al. Report of the Task Group 186 on model-based dose calculation methods in brachytherapy beyond the TG-43 formalism: Current status and recommendations for clinical implementation. Med. Phys. 2012, 39, 6208–6236 Keywords: In vitro setup, brachytherapy, dosimetry
Digital Poster 4461
The RATIONALE Project: Current Status and Focus on Dose Constraints and Biomarkers for Molecular Radiotherapy Lidia Strigari 1 , Glenn Flux 2 , Daniela Oprea-Lager 3 , Ivo Rausch 4 1 Medical physics, IRCCS Azienda Ospedaliero Universitaria, Bologna, Italy. 2 Radioisotope Physics, Royal Marsden Hospital, Sutton, United Kingdom. 3 Department of Radiology and Nuclear Medicine, Radboud UMC, Nijmegen, Netherlands. 4 Medical physics, IRCCS Azienda Ospedaliero Universitaria, Bologna, Austria Purpose/Objective: Molecular radiotherapy (MRT), incorporating theragnostics, is transforming personalised cancer therapy by integrating diagnostic imaging and targeted radiotherapeutics, enabling precise treatment individualisation and optimisation. However, at the European level, challenges remain, including heterogeneous clinical practice, limited dosimetry implementation, lack of harmonised dose constraints, and insufficient data linking absorbed dose to clinical outcomes. Material/Methods: The EU-funded COST Action RATIONALE (CA22159) was launched in November 2023 to address these challenges through six Working Groups (WGs) focused on: (1) cross-field communication and training; (2) harmonisation of procedures; (3) theragnostic imaging; (4) dosimetry; (5) clinical translation strategies for treatment personalisation and optimisation; and (6) ethical and legal aspects. The Action involves 128 members, including 55 young researchers and innovators, across 32 European countries. Results: Within WG5, the multidisciplinary team has prepared a comprehensive report on dose constraint data and associated biomarkers for MRT, providing a foundation for evidence-based treatment personalization. The report consolidates literature data on organs-at-risk (OARs), toxicity profiles, and related biomarkers across the main MRT modalities, including 177Lu-PSMA therapy, radioembolization, 177Lu-DOTATATE for neuroendocrine tumours, 131I therapies for thyroid malignancies and benign diseases, 131I- mIBG for neuroblastoma and several alpha emitters-labelled molecules. Two reports detail dose–toxicity relationships and OARs with associated biomarkers, and a summary of biomarkers of treatment response and target absorbed doses.Given the differences between external beam radiotherapy and MRT in terms of radiation dose distribution, delivery rate and radiobiological effects, direct translation of QUANTEC values is limited. The report highlights key considerations, including the systemic nature of MRT, heterogeneous absorbed dose distributions, and the distinct toxicity profiles of kidneys, liver, and bone marrow. Conclusion: The RATIONALE Action provides a European collaborative
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