Main Session
Sep 27
PQA 01 - Gastrointestinal Cancer and Central Nervous System

2095 - Comparative Effectiveness of Intensity-Modulated Proton Therapy (IMPT), Passive-Scattering Proton Therapy (PSPT), and Volumetric-Modulated Arc Therapy (VMAT) on Radiation-Induced Lymphopenia (RIL) in Esophageal Cancer (EC) Chemoradiotherapy

03:00pm - 04:00pm ET
Poster Hall - Exhibit Hall A
Screen: 23
POSTER

Presenter(s)

Zongsheng Hu, PhD Headshot
Zongsheng Hu, PhD - University of Pennsylvania, Philadelphia, PA

Z. Hu1, Y. Li1, C. R. Peeler1, Y. Chen2, B. Gao1, U. Titt1, S. H. Lin3, and R. Mohan1; 1Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, TX, 2Department of Epidemiology and Biostatistics, Texas A&M University, College Station, TX, 3Division of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX

Purpose/Objective(s):

Previously, severe RIL during chemoradiotherapy of EC has been found to produce inferior treatment outcomes. We propose to test the hypothesis that IMPT is associated with improved lymphocyte preservation compared with VMAT and PSPT, and that differences in dose to immune-relevant organs contribute to observed modality effects.

Materials/Methods:

We retrospectively analyzed 191 patients treated with definitive or neoadjuvant chemoradiotherapy for esophageal cancer (VMAT n=92, PSPT n = 53, IMPT n = 46) at one institution. Generalized overlap weighting based on multinomial propensity scores was used to balance baseline covariates including body mass index, planning target volume, age, and baseline absolute lymphocyte count (ALC) across treatment cohorts. Weighted log-linear regression models were fit for during-treatment ALC nadir. Adjusted marginal geometric means and pairwise contrasts were estimated. Attenuation analysis assessed the contribution of immune-relevant organs, including heart, spleen, lung, and body dose, to modality-related differences using Shapley value-based decomposition.

Results: After overlap weighting, baseline covariates were well balanced across treatment modalities. IMPT was associated with a significantly higher ALC nadir compared with VMAT (+74.2%, 95% CI 42.4%-113.1%) and PSPT (+48.7%, 95% CI 20.1%-84.1%). The adjusted geometric mean ALC nadir were 221 (CI 190-256), 262 (CI 222-309), and 387 (CI 340-439) cells/µL for VMAT, PSPT, and IMPT respectively. The incidence of grade 4 RIL (ALC nadir < 200 cells/µL) were 33.7%, 27.7%, and 10.2% for VMAT, PSPT, and IMPT, respectively, demonstrating substantially improved immune preservation with IMPT.

Attenuation analysis showed that reduced dose to immune-relevant organs of IMPT accounted for most of the observed modality-associated improvement, explaining approximately 72% of the IMPT-VMAT difference and 53% of the IMPT-PSPT difference. Shapley value-based decomposition further demonstrated that, among the four immune-relevant organs, reduced body and spleen dose were the principal contributors to the explained improvement for IMPT versus VMAT, accounting for 31.2% and 22.2% of the dose-attributable association, respectively. For IMPT versus PSPT, reduced spleen dose was the dominant contributor, accounting for 58% of the explained improvement.

Conclusion:

In this overlap-weighted comparative effectiveness analysis of esophageal chemoradiotherapy, IMPT was associated with substantially improved lymphocyte preservation compared with VMAT and PSPT. Reduced dose to immune-relevant organs, particularly the spleen and body, accounted for a large proportion of the observed benefit. These findings support immune-organ sparing as a potential planning objective in EC chemoradiotherapy and motivate prospective evaluation of body integral dose and spleen-aware treatment planning strategies.