S3037
Invited Speaker
ESTRO 2026
References: Sandul V, Al-Hamami SS, Kube š J, Durante M, Friedrich T. Radiation-induced lymphopenia: A data compilation to unveil relevant factors and mitigation strategies. Clinical and Translational Radiation Oncology 56:101071 (2026). doi:10.1016/j.ctro.2025.101071 Sandul V, Al-Hamami SS, Kube š J, Durante M, Friedrich T. Comprehensive analysis of absolute lymphocyte count dynamics and modeling of lymphocyte sparing in ion therapy. International Journal of Particle Therapy 17:100922 (2025). doi: 10.1016/j.ijpt.2025.100922 Durante M. Kaplan lecture 2023: lymphopenia in particle therapy. International Journal of Radiation Biology 100:669 (2024) doi: 10.1080/09553002.2024.2324472 5429 Tools for assessing doses to the blood/lymphocyte pool Clemens Grassberger Radiation Oncology, University of Washington/Fred Hutch, Seattle, USA Radiotherapy can inadvertently impair antitumor immunity by depleting circulating and tissue-resident lymphocytes. Lymphocytes are central effectors of adaptive immune surveillance, enable durable responses to immune checkpoint blockade, and shape the balance between tumor control and normal-tissue inflammation. In cancer patients, baseline lymphopenia is common and lymphocyte turnover, trafficking, and redistribution across blood, lymphoid organs, and tumor microenvironments are frequently altered by disease and prior therapy. These dynamics make it essential to quantify the “dose” delivered to the blood/lymphocyte pool during radiotherapy and combined-modality regimens.
between mouse and human trafficking kinetics further complicate model calibration and validation. We will highlight strategies to bridge these gaps, including mechanistic links between dose and cell- kill/redistribution, hierarchical modeling to separate patient-level susceptibility from treatment effects, and integration of imaging- and biomarker-based priors. Finally, we will outline emerging approaches to minimize lymphocyte depletion, including lymphocyte- sparing planning, hypofractionation, and proton and ultra-high dose rate (FLASH) strategies. Together, these tools enable a shift from retrospective association to prospective design of regimens that preserve immune competence and potentially improve outcomes. References: 1. Nowicka et al. The Challenges Discovering the Mechanisms Underlying Radiation-Induced Lymphopenia From Clinical Data. IJROBP 2026. 2. Grassberger et al. Combining immunotherapy and radiotherapy in hepatocellular carcinoma: the importance of irradiated tumor burden and the possible role of a low dose radiotherapy induction strategy. Transl. Cancer Res. 2023. 3. McCullum et al. Predicting Severity of Radiation Induced Lymphopenia in Individual Proton Therapy Patients for Varying Dose Rate and Fractionation Using Dynamic 4D Blood Flow Simulations. IJROBP 2023 . 4.Grassberger et al. Assessing the interactions between radiotherapy and antitumour immunity. Nature reviews Clinical oncology 2019. 5430 Recent developments in quantitative cone-beam CT Peter Remeijer Radiotherapy, The Netherlands Cancer intitute, Amsterdam, Netherlands Cone-beam CT (CBCT) has been an integral part of the radiotherapy workflow for more than two decades. Throughout most of this period, its role has predominantly been to serve as a tool for patient positioning and image guidance, rather than for quantitative image assessment. However, in recent years there has been a growing demand for quantitative imaging capabilities. This largely has been driven by the adoption of CBCT-based adaptive radiotherapy and proton therapy, where accurate electron density information is important for reliable dose calculation and treatment planning. In this lecture, I will show why conventional CBCT reconstruction methods fall short in delivering quantitative accuracy. Limitations such as scatter contamination, beam hardening, system and patient- specific artifacts lead to inconsistencies in Hounsfield
This talk reviews approaches for estimating lymphocyte irradiation and the biological
interpretation of these metrics. We will summarize current methodologies that couple treatment-planning dose distributions with models of blood flow and lymphocyte recirculation, ranging from simplified compartment and path-length approaches to patient- specific simulations that integrate beam delivery timing, cardiac output, organ perfusion, and lymphoid organ exposure. A key challenge is connecting calculated dose to observed lymphocyte depletion across heterogeneous clinical and preclinical datasets. Lymphocyte nadirs reflect not only direct irradiation but also inflammation-driven “pull” from other compartments, marrow and thymic reserve, steroid exposure, infection, and concurrent systemic therapies. Measurement timing, assay variability, and differences
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