Radiation-Induced Lymphopenia Risks of Photon Versus Proton Therapy for Esophageal Cancer Patients.

Saba Ebrahimi,Amy Liu,Steven H Lin,Clemens Grassberger,Gino Lim,Radhe Mohan,Wenhua Cao,Susannah G Ellsworth

doi:10.14338/ijpt-20-00086

Abstract

PurposeTo assess possible differences in radiation-induced lymphocyte depletion for esophageal cancer patients being treated with the following 3 treatment modalities: intensity-modulated radiation therapy (IMRT), passive scattering proton therapy (PSPT), and intensity-modulated proton therapy (IMPT).Methods and MaterialsWe used 2 prediction models to estimate lymphocyte depletion based on dose distributions. Model I used a piecewise linear relationship between lymphocyte survival and voxel-by-voxel dose. Model II assumes that lymphocytes deplete exponentially as a function of total delivered dose. The models can be fitted using the weekly absolute lymphocyte counts measurements collected throughout treatment. We randomly selected 45 esophageal cancer patients treated with IMRT, PSPT, or IMPT at our institution (15 per modality) to demonstrate the fitness of the 2 models. A different group of 10 esophageal cancer patients who had received PSPT were included in this study of in silico simulations of multiple modalities. One IMRT and one IMPT plan were created, using our standards of practice for each modality, as competing plans to the existing PSPT plan for each patient. We fitted the models by PSPT plans used in treatment and predicted absolute lymphocyte counts for IMRT and IMPT plans.ResultsModel validation on each modality group of patients showed good agreement between measured and predicted absolute lymphocyte counts nadirs with mean squared errors from 0.003 to 0.023 among the modalities and models. In the simulation study of IMRT and IMPT on the 10 PSPT patients, the average predicted absolute lymphocyte count (ALC) nadirs were 0.27, 0.35, and 0.37 K/μL after IMRT, PSPT, and IMPT treatments using Model I, respectively, and 0.14, 0.22, and 0.33 K/μL using Model II.ConclusionsProton plans carried a lower predicted risk of lymphopenia after the treatment course than did photon plans. Moreover, IMPT plans outperformed PSPT in terms of predicted lymphocyte preservation.

Highlights

Radiation-induced lymphopenia (RIL), lymphocyte depletion, is a common toxicity of radiation therapy and is associated with worse outcomes in a number of solid tumors, including esophageal cancer [1,2,3,4]
We modeled and compared expected absolute lymphocyte count (ALC) depletion kinetics in esophageal cancer patients treated with the following 3 different modalities: intensity-modulated radiation therapy (IMRT), passive-scattering proton therapy (PSPT), and intensity-modulated proton therapy (IMPT)
We will describe 2 prediction models for lymphocyte depletion based on radiation doses and report the patient selection for model validation as well as treatment planning of IMRT and IMPT for patients treated with passive scattering proton therapy (PSPT)

Summary

Introduction

Radiation-induced lymphopenia (RIL), lymphocyte depletion, is a common toxicity of radiation therapy and is associated with worse outcomes in a number of solid tumors, including esophageal cancer [1,2,3,4]. In conventional photon radiation therapy, the large low- and medium-dose bath expose substantial fractions of circulating lymphocytes. Clinical data show that dose distribution patterns and fractionation regimens significantly influence lymphocyte depletion [15, 16]. Dose distribution patterns from protons and photons can differ greatly, and the dosimetric advantages of the state-of-theart proton therapy over photon therapy in terms of sparing of organs at risk and normal tissue have been demonstrated extensively [17, 18]. Intensity-modulated proton therapy (IMPT) performs further better than intensity-modulated radiation therapy (IMRT) in terms of normal tissue sparing [19]

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