S3034
Invited Speaker
ESTRO 2026
Theranostic approaches can guide this treatment in the future. However, clinical trials are necessary to investigate the value of this promising new combined modality treatment. References: Teunissen FR, Oprea-Lager DE, Peters SMB, Smeenk RJ, Heskamp S, Bussink J. Current developments in combining external-beam radiotherapy and 177Lu- labeled PSMA ligands for prostate cancer treatment. J Nucl Med. 2025 Dec 3;66(12):1852-1858. 5422 Combined dosimetry: Challenges and opportunities Johannes Tran-Gia Department of Nuclear Medicine, University Hospital Würzburg, Würzburg, Germany The combination of external beam radiotherapy (EBRT) and targeted radionuclide therapy (TRT) offers the potential to improve tumour control by complementing spatially confined high-dose irradiation with systemic targeting of microscopic disease. However, translating this concept into quantitative and clinically actionable treatment planning remains a major challenge. A key challenge arises from fundamental differences between the modalities. Although both EBRT and TRT are described using absorbed dose (Gy), this shared unit does not imply biological equivalence. EBRT delivers dose at high dose rates with high spatial precision and relative homogeneity at the voxel level, governed primarily by anatomical targeting. In contrast, TRT delivers radiation continuously at low dose rates, with dose distributions driven by patient- specific pharmacokinetics and receptor expression. Importantly, TRT exhibits pronounced intra-voxel heterogeneity, with clinically relevant microdistributions (e.g. kidney cortex versus medulla or bone marrow niches) that are not resolved by imaging. As a result, the dose distribution at the cellular level may differ substantially from the voxel- averaged signal observed in SPECT/CT (spatial resolution ~5–10 mm). Thus, even if voxel-based dose maps are aligned, the underlying biologically relevant dose distributions remain fundamentally different. These differences complicate dose accumulation, requiring accurate image registration, temporal integration of activity distributions, and appropriate biological modelling to account for dose-rate effects. In practice, this process is further limited by the insufficient spatial resolution and quantitative accuracy of current TRT dosimetry, particularly due to partial-volume effects, hindering direct integration with EBRT planning data.
The aim of this presentation is to illustrate how the distinct radiobiological effects of EBRT and RPT could be used to build highly effective combined regimens.
5421 Clinical rationale for combined therapies: The radiation oncologist's point of view. Johan Bussink, Frederik R Teunissen Radiation Oncology, Radbouduniversity Medical Center, Nijmegen, Netherlands Every year, over 15,000 men in the Netherlands are diagnosed with prostate cancer (PCa). External beam radiotherapy (EBRT) is well recognized for its ability to cure localized prostate cancer. However, the efficacy of EBRT in eradicating all tumor cells in scenarios with affected pelvic lymph nodes or macroscopic metastases, is limited by surrounding organs at risk (OARs). Furthermore, microscopic metastases may be located outside the (elective) radiotherapy field. Together, these factors reduce the chance of complete tumor control for high-risk localized and oligometastatic PCa. It is essential to increase the chance of cure for these patients with high-risk localized and oligometastatic PCa. This will prevent second-line treatments, such as long-term androgen deprivation therapy (ADT), and improve overall survival and quality of life. [ ¹⁷⁷ Lu]Lu-PSMA radioligand therapy is approved by the FDA and EMA for the treatment of castration-resistent PCa (CRPC) patients who progress under at least one novel androgen receptor pathway inhibitor and one or two lines of taxanes, or as a way to delay taxane-based chemotherapy. In addition, several recent studies indicate the potential role of [ ¹⁷⁷ Lu]Lu-PSMA ligand therapy at earlier stages of PCa, aiming for cure or delaying ADT. There is increasing evidence that EBRT and [ ¹⁷⁷ Lu]Lu- PSMA ligands can be administered concomitantly in a safe manner, as their toxicities are non-overlapping. This provides an opportunity to explore this combined therapy for treatment with curative intent. The combined treatment will increase the radiation dose to tumors without increasing the dose to OARs. Also, [ ¹⁷⁷ Lu]Lu-PSMA ligand therapy can target micrometastases located outside the EBRT field. Therefore, it may improve (progression-free) survival and prevent long-term ADT, resulting in a better quality of life. Conclusion Combining external beam radiotherapy with [177Lu]Lu-PSMA may improve tumor control without increasing toxicity for high risk prostate cancer patients. To find the optimal treatment scheduling, dosing regimens, the role of dosimetry, and specific clinical indications will require further investigation.
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