Lymphocyte Nadir and Esophageal Cancer Survival Outcomes After Chemoradiation Therapy

• Published in: International journal of radiation oncology, biology, physics Vol. 99; no. 1; pp. 128 - 135
• Main Authors: Davuluri, Rajayogesh, Jiang, Wen, Fang, Penny, Xu, Cai, Komaki, Ritsuko, Gomez, Daniel R., Welsh, James, Cox, James D., Crane, Christopher H., Hsu, Charles C., Lin, Steven H.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.09.2017
• Subjects: Adenocarcinoma - immunology; Adenocarcinoma - mortality; Adenocarcinoma - pathology; Adenocarcinoma - therapy; Carcinoma, Squamous Cell - immunology; Carcinoma, Squamous Cell - mortality; Carcinoma, Squamous Cell - pathology; Carcinoma, Squamous Cell - therapy; Chemoradiotherapy - adverse effects; Chemoradiotherapy - methods; Esophageal Neoplasms - immunology; Esophageal Neoplasms - mortality; Esophageal Neoplasms - pathology; Esophageal Neoplasms - therapy; Fluorouracil - therapeutic use; Humans; Incidence; Kaplan-Meier Estimate; Lymphocyte Count; Lymphopenia - epidemiology; Lymphopenia - etiology; Lymphopenia - mortality; Middle Aged; Monocytes - drug effects; Monocytes - radiation effects; Neutrophils - drug effects; Neutrophils - radiation effects; Odds Ratio; Platinum Compounds - therapeutic use; Proportional Hazards Models; Proton Therapy; Radiotherapy Dosage; Regression Analysis; Retrospective Studies; T-Lymphocytes - drug effects; T-Lymphocytes - radiation effects; Taxoids - therapeutic use; Treatment Outcome
• ISSN: 0360-3016; 1879-355X; 1879-355X
• DOI: 10.1016/j.ijrobp.2017.05.037

Host immunity may affect the outcome in patients with esophageal cancer. We sought to identify factors that influenced absolute lymphocyte count (ALC) nadir during chemoradiation therapy (CRT) for esophageal cancer (EC) and looked for clinically relevant associations with survival. 504 patients with stage I-III EC (2007-2013) treated with neoadjuvant or definitive CRT with weekly ALC determinations made during treatment were analyzed. Grade of lymphopenia from ALC nadir during CRT was based on Common Terminology Criteria for Adverse Events version 4.0. Associations of ALC nadir with survival were examined using multivariate Cox proportional hazards analysis (MVA) and competing risks regression analysis. The median follow-up time was 36 months. The incidences of grade 1, 2, 3, and 4 ALC nadir during CRT were 2%, 12%, 59%, and 27%, respectively. The impact was lymphocyte-specific because this was not seen for monocyte or neutrophil count. On MVA, grade 4 ALC nadir (G4 nadir) was significantly associated with worse overall and disease-specific survival outcomes. Predictors of G4 nadir included distal tumor location, definitive CRT, taxane/5-fluorouracil chemotherapy, and photon-based radiation type (vs proton-based). Radiation type strongly influenced the mean body dose exposure, which was a strong predictor for G4 nadir (odds ratio 1.22 per Gray, P<.001). G4 nadir during CRT for EC was associated with poor outcomes, suggesting a role of host immunity in disease control. This observation provides a rationale to prospectively test chemotherapeutic and radiation treatment strategies that may have a lower impact on host immunity.