Dosimetric And Clinical Correlates Of Absolute Neutrophil Count And Overall Survival After Concurrent Chemoradiation For Esophageal Cancer

Strong correlations of post-treatment absolute neutrophil counts with overall survival (OS) have been observed in our patients receiving chemoradiation for esophageal cancers. We sought to retrospectively analyze the relationship of normal tissue doses and clinical variables with both OS and absolute neutrophil counts in these patients. All 395 patients treated with concurrent chemoradiation for Stage I-III esophageal cancer from 1/3/2007-1/1/2016 whose dosimetry was available were included in this study (81 squamous cell carcinoma, 314 adenocarcinoma; 258 ≥Stage III). Prescription doses ranged from 41.4-54 (median 50.4) Gy in 1.8 Gy fractions. 218 of these patients underwent surgery after radiotherapy. Lung and heart dose metrics including mean and max doses, V5 and V20Gy, and (in heart only) V30 and V40Gy, were analyzed in addition to PTV size, histology, stage, surgery, pre-existing heart disease, diabetes, age, and smoking status. The subset of these variables correlating univariately with overall survival were then assessed for their correlations with absolute neutrophil counts at 6 month (ANC6m). 268 patients had absolute neutrophil blood count data available at 6 months (ANC6m). Correlations of overall survival (OS) with dosimetric, blood count, and clinical data were assessed with Cox proportional hazards models, those of dosimetric and clinical variables with ANC6m were assessed using linear regression. For the purposes of hypothesis generation and testing, significance was defined as p≤0.05. Median follow-up in all patients was 24.4 months. Univariately, surgery, Lung V20, age, PTV, Stage III, and mean lung dose were significantly correlated with OS (p = 1.5 X 10-5, 1.8 X 10-4, 3.5 X 10-4, 7.4 X 10-4, 0.001, and 0.0072, respectively). In multivariate models of OS, surgery, Stage III, and age plus either Lung V20 or PTV were competitive. Lung V20 and PTV were correlated (p < 10-7). Median follow-up in patients with available 6m blood counts was 24.3 months. In these patients, age, Stage III, LungV20, mean lung dose, PTV, and ANC6m were all significantly correlated univariately with OS, with p = 1.3x10-10for ANC6m. Multivariately, ANC6m, PTV and Stage III+ remained significant (p = 2.4x10-10, 0.0098, and 0.048, respectively). Of variables univariately correlated with OS, ANC6m was linearly correlated with mean lung dose and LungV20 (p=0.014 and 0.0082, respectively). Overall survival in patients receiving concurrent chemoradiation for esophageal cancer is strongly correlated with 6-month post-treatment absolute neutrophil counts. While Lung V20 was univariately correlated with OS, it was not significant in the presence of ANC6m in multivariate analysis. ANC6m was linearly correlated with LungV20, suggesting that the effect of Lung V20 on OS might be related to its possible effects on ANC6m.