ESTRO 2022 - Abstract Book

S761

Abstract book

ESTRO 2022

across cancer-related disciplines and will focus on what one discipline needs to know form other disciplines’ curricula. One of the aims is to secure online education but also to increase mobility. Hopefully, together with other initiatives, we will be able to support mobility – and not just from an economically point of view. The talk will go through some of these possibilities.

Mini-Oral: 21: Radiomics & modelling

MO-0875 Thoracic regions contributing to radiation induced lymphocyte depletion in lung cancer patients

S. Monti 1 , L. Cella 1 , T. Xu 2 , R. Mohan 3 , Z. Liao 2 , G. Palma 1

1 National Research Council, Institute of Biostructures and Bioimaging, Naples, Italy; 2 The University of Texas MD Anderson Cancer Center, Department of Radiation Oncology, Houston, USA; 3 The University of Texas MD Anderson Cancer Center, Department of Radiation Physics, Houston, USA Purpose or Objective The absolute lymphocyte count (ALC) at the end of radiation therapy (RT) or at nadir were traditionally considered as representative of radiation-induce lymphopenia (RIL). These parameters are highly affected by individual patient baseline counts and by the blood test time point. Our aim was to characterize new measures for RIL and identify thoracic regions contributing to RIL in non-small cell lung cancer (NSCLC) patients treated with chemo-radiotherapy (RT). Materials and Methods We identified 164 NSCLC patients with blood tests weekly during RT available (prescribed dose of 66/74 Gy, 2 Gy daily fractionation). The ALC loss curve was investigated assuming the following function [Ellsworth et al 2020]: ALC( t ) = a ⋅ exp(- b ⋅ t ) + c where t is the treatment time from the start of RT, b the ALC depletion rate and c the ALC plateau in later phases of the treatment course. For each patient, the curve parameters were fitted. The estimated dose of radiation to immune cells (EDRIC) was also computed [Ladbury et al 2019]. The relationships between clinical factors, EDRIC and RIL kinetic parameters ( i.e. b and c ) were tested by Spearman’s rank correlation and by Mann-Whitney U test or its extension Kruskal-Wallis H test, when appropriate. A Voxel-Based Analysis (VBA) was performed to assess voxel-wise the relationship between per-fraction-dose and RIL kinetic parameters. Planning CTs and per-fraction dose maps were spatially normalized to a common anatomical reference after masking the GTV. The generalized linear model (GLM) was then designed to include dose maps and each non-dosimetric variables significantly correlated with RIL outcomes [Palma et al 2019] A non-parametric permutation test of the maximum threshold-free cluster-enhanced statistic accounted for multiple comparisons. Maps of model coefficients and their significance maps were generated. The median ALC depletion rate and plateau were 0.10 [0.01—0.55] day -1 and 0.34 [0.00 - 0.96] x10 9 cells/L. None of the clinical factors significantly correlated with RIL measures, hence multivariable VBAs were designed by including only dosimetric variables in the GLM. Mean and standard deviation of per-fraction dose maps are shown in Fig. a-b. The VBA identified regions of significant association between per-fraction dose and ALC plateau in heart, lungs, and lymphoid organs, such as thymus and bone marrow located in vertebrae, ribs, and sternum (Figure, c). Less marked spatial correlations were found for ALC rate, with the most significant association in the heart and in vertebrae (Fig. d). Results

EDRIC (median value 10.3 Gy [1.1-17.4] Gy) was strongly correlated with ALC depletion rate ( p <10 -4 ).

Conclusion The VBA highlighted relevant relationships between the lymphocyte loss curve parameters and local dose in organs considered at risk of lymphopoietic capacity impairment. These findings offer new hints on the radiobiological pathways leading to RIL and support a complex model of lymphopoiesis and of response of the immune system to irradiation injury.