Severe lymphopenia during neoadjuvant chemoradiation for esophageal cancer: A propensity matched analysis of the relative risk of proton versus photon-based radiation therapy

Circulating lymphocytes are exquisitely sensitive to radiation exposure, even to low scattered doses which can vary drastically between radiation modalities. We compared the relative risk of radiation-induced lymphopenia between intensity modulated radiation therapy (IMRT) or proton beam therapy (PBT) in esophageal cancer (EC) patients undergoing neoadjuvant chemoradiation therapy (nCRT). EC patients treated with IMRT and PBT were propensity matched based on key clinical variables. Treatment-associated lymphopenia was graded using CTCAE v.4.0. Using matched cohorts, univariate and multivariable multiple logistic regression was used to identify factors associated with increased risk of grade 4 lymphopenia as well as characterize their relative contributions. Among the 480 patients treated with nCRT, 136 IMRT patients were propensity score matched with 136 PBT patients. In the matched groups, a greater proportion of the IMRT patients (55/136, 40.4%) developed grade 4 lymphopenia during nCRT compared with the PBT patients (24/136, 17.6%, P