S1088
Clinical – Upper GI
ESTRO 2026
≥ 60% of their radiotherapy fractions within a 4-hour sliding window (at every point in time ±2 hours), the proportions of those who developed grade 4 lymphopenia are plotted. Conclusion: In neoadjuvant CRT for esophageal cancer, receipt of P.M. radiotherapy is significantly associated with pCR. This effect may be partially mediated through milder lymphopenia incurred by later time-of-day RT. Additional mechanistic and prospective clinical studies of chronotherapy are warranted. References: 1. Qian DC, et al. Lancet Oncol 20212. Wang C, et al. Nature 20223. McMillan MT, et al. Radiother Oncol 20254. Davuluri R, et al. Int J Radiat Oncol Biol Phys 20175. Scheiermann C, et al. Nat Rev Immunol 2013 Keywords: Esophageal Cancer, Circadian Rhythm, Lymphopenia Digital Poster 2836 Temporal heart dose variations during IMPT for esophageal cancer and the impact of an adaptation protocol Richard Canters, Vlad Badiu, Dominique Reijtenbagh, Esther Kneepkens, Gloria Vilches-Freixas, Maaike Berbee Department of Radiation Oncology (Maastro), GROW School for Oncology and Reproduction, Maastricht University Medical Centre+, Maastricht, Netherlands Purpose/Objective: In intensity-modulated proton therapy (IMPT) for esophageal cancer, organ motion is a likely contributor to variations in the delivered dose to both the tumor and surrounding organs of interest (OOIs). Due to the posterior beam arrangement, the heart is particularly vulnerable to dosimetric changes, as the distal edge of the beam often terminates in or near cardiac tissue. This study investigates heart dose variations during treatment and explores correlations with anatomical changes. Material/Methods: We retrospectively analyzed 200 esophageal cancer patients treated with IMPT, using weekly repeat CT scans (reCTs) acquired throughout the treatment course. Patients received either 23 × 1.8 Gy or 28 × 1.8 Gy (RBE). Treatment plans were recalculated on each reCT to extract the mean heart dose (MHD) and heart V40Gy. We assessed trends and systematic changes in these dosimetric parameters, alongside anatomical variables such as diaphragm baseline shift, heart position and volume, heart displacement, intratumoral air, target volume, dorsal fat, and dysphagia scores. Sttistically significant parameters were included in a gradient boosting regression trees machine learning
Results: Following propensity score-matching, 540 patients were included in this study with post-surgery median follow-up of 43 months (IQR 20–107). Patient characteristics were well-balanced. Receipt of ≥ 60% of RT fractions after 12:00 was associated with higher rate of pCR (25% vs. 14%, ORunivar 2.10 [95% CI 1.20– 3.67], P=0.009). This finding remained robust to multivariable adjustment (ORmultivar 2.16 [95% CI 1.20–3.88], P=0.010) for baseline clinicopathologic characteristics and ALC nadir. Grade 4 lymphopenia was less common among patients with RT appointments concentrated in the early evening (Figure 1) and moreover, higher ALC nadir was independently associated with pCR status (ORmultivar 1.21 per 100/ μ l increment [95% CI 1.05–1.41], P=0.011). There were no discernible associations between chemotherapy time-of-day infusions and pCR status.
Figure 1. Lymphopenia occurrence vs. time-of-day radiotherapy. Among all patients who had received
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