Mean cardiopulmonary dose and vertebral marrow dose differentially predict lineage-specific leukopenia kinetics during radiotherapy for esophageal cancer

Background and purpose: Lymphopenia is associated with poor outcomes in esophageal cancer (EC) patients undergoing chemoradiotherapy (CRT). We hypothesized that radiation dose to marrow (central) vs. circulating (peripheral) leukocytes (WBCs) may have unique effects on WBC counts and clinical outcomes in EC. Materials and methods: Weekly and 90-day post-CRT blood cell counts were evaluated for 46 patients with stage II-III EC treated with CRT. Thoracic vertebral volume spared (TVS) radiation was extracted from dose volume histograms (DVH). Mean cardiopulmonary dose (mCPD) was calculated as mean dose to the volumetric sum of heart, lungs, and great vessels as a surrogate for circulating blood pool. Linear and logistic regression identified associations between dosimetric variables and hematologic toxicities (HT). Repeated measures ANOVA tested associations between cell count trends and clinical predictors. Results: WBCs and platelets reached nadir at week 6 of CRT. On multivariate analysis, mCPD was associated with lower WBC and neutrophil nadirs (p < 0.05). TVS5-40 Gy were associated with higher lymphocyte nadirs (all p < 0.05). Repeated measures ANOVA revealed an interaction effect of sex on absolute lymphocyte trend as well as age (<67 vs. >67) and diabetes on normalized lymphocyte trend (all p < 0.015). Conclusions: mCPD and volume of thoracic marrow spared radiation differentially predict lineage-specific leukopenias during CRT for EC. mCPD is significantly associated with lower total WBC and neutrophil nadirs. In contrast, greater thoracic marrow spared radiation is associated with mitigation of lymphopenia during CRT. Clinical factors such as sex, age, and diabetes may be associated with a more rapid decline in hematologic counts during treatment.