ESTRO 2025 - Abstract Book

S2932

Physics - Dose prediction, optimisation and applications of photon and electron planning

ESTRO 2025

4368

Proffered Paper Dosimetric Parameters in Total Marrow and Lymphoid Irradiation and Risk of Acute Graft-Versus-Host Disease Simonetta Saldi 1 , Christian Paolo Luca Fulcheri 2 , Claudio Zucchetti 2 , Federico Camilli 3 , Antonio Pierini 4 , Gianluca Ingrosso 3 , Alessandra Carotti 5 , Loredana Ruggeri 5 , Rebecca Sembenico 4 , Francesco Zorutti 4 , Vittorio Bini 1 , Maria Paola Martelli 4 , Cynthia Aristei 6 1 Department of Radiation Oncology, Santa Maria della Misericordia Hospital, Perugia, Italy. 2 Medical Physics Section, Santa Maria della Misericordia Hospital, Perugia, Italy. 3 Department of Radiation Oncology, University of Perugia, Perugia, Italy. 4 Department of Haematology, University of Perugia, Perugia, Italy. 5 Department of Haematology, Santa Maria della Misericordia Hospital, Perugia, Italy. 6 Radiation Oncology section, University of Perugia, Perugia, Italy Purpose/Objective: Following allogeneic hematopoietic stem cell transplantation (HSCT), acute graft-versus-host disease (aGvHD) leads to major morbidity and mortality. Total body irradiation (TBI) in conditioning regimens was associated with a higher incidence of aGvHD than chemotherapy alone. TBI doses correlated with aGvHD severity as radiation-related damage to the gastrointestinal (GI) tract triggered and propagated the cytokine storm in aGvHD development. Total Marrow and Lymphoid Irradiation (TMLI), an alternative to TBI, targets radiation to bone marrow and lymphoid tissues, thus sparing organs at risk (OARs). Objective: This study investigated the impact of TMLI dosimetric parameters on aGvHD, with the goal of identifying critical dose thresholds within the GI tract that correlated with a higher risk of aGvHD Material/Methods: TMLI was administered to 90 patients (median age 56 years, range 21–70), with acute myeloid leukemia (76%), acute lymphoblastic leukemia (13%), and myelodysplastic syndrome (11%). TMLI, delivered by means of helical tomotherapy, administered total doses of 13.5 Gy to skeletal bones and 11.5 Gy to lymphoid organs in 9 fractions over 4.5 days. Dosimetric parameters for the whole intestine (gut) and GI segments (duodenum, sigmoid colon, rectum and gut) included doses to specified volumes (e.g., D5cc, D10cc, D30cc, D50cc, D80cc, D120cc) and volume percentages receiving certain doses (e.g., V5Gy, V11Gy). Receiver operating characteristic (ROC) curves determined predictive thresholds for aGvHD. Results: Twenty-eight percent developed grade ≥2 aGvHD, with 88% of these cases involving the GI tract. Median onset time was 40 days post-transplant. ROC analysis showed higher dosimetric parameters and higher risk of aGvHD risk were significantly associated. Predictive of aGVHD were the following parameters: Colon : D120cc threshold over 10.31 Gy (AUC = 0.641, 77.27% sensitivity, 53.45% specificity), V11Gy threshold over 72.13cc (AUC = 0.647, 80% sensitivity, 50.77% specificity). Whole gut : D80cc threshold over 11.75 Gy (AUC = 0.671, 76% sensitivity, 60% specificity); D120cc threshold over 11.41 Gy (AUC = 0.665, 77.27% sensitivity, 60.34% specificity). The Mann-Whitney U test confirmed significant differences between patients with aGvHD and those without (e.g., D120cc of the colon: p=0.0444; V11Gy of the gut: p=0.0064). Conclusion: TMLI dosimetric parameters, particularly doses delivered to the colon and gut, were associated with an increased risk of developing aGvHD. These results underscore the importance of precise dosimetric planning in TMLI and suggest that optimizing radiation doses to the GI tract may improve outcomes in HSCT. Further studies with larger patient cohorts are recommended to validate these thresholds and define TMLI protocols.

Keywords: TMLI , GVHD