Relationship Between Spleen Dosimetry Parameters and Lymphocyte Loss in Patients with Abdominal Tumors

Abstract

Radiation (RT)-induced lymphopenia (RIL) is associated with worse survival in patients with solid tumors. Here, it was hypothesized that spleen dosimetry parameters would correlate with lymphocyte loss rate during RT and total % lymphocyte loss. This registry-based study included 211 patients who received conventionally fractionated RT for pancreaticobiliary (PB, n = 86) or gastroesophageal (GE, n = 65) tumors and stereotactic body RT (SBRT, n = 56) for hepatic tumors who had spleen dose volume histograms (DVHs) available. Area under each DVH (AUC) was approximated using the trapezoidal rule. Loss rates were determined through a previously described method where the initial 3 weeks of treatment are fit to an exponential decay in the form ALC(x) = ae-bx and the percent per fraction lymphocyte loss (FLL) was calculated as FLL = (1 – e-b)*100. Intergroup comparisons between PB and GE patients were done with the Mann-Whitney U Test. For each treatment site, spleen volumes receiving anywhere from 2 Gy (V2) to 25 Gy (V25), mean spleen dose, and AUC were correlated with FLL and the total % loss in absolute lymphocyte count (ALC) throughout treatment using simple linear regression. Multiple variable regression was then used to control for planning treatment volume (PTV) for each parameter. Median FLL (9.5, 12.5), % ALC loss (80.0, 88.9), mean spleen dose (7.8, 17.1), V15 (45.3, 114.6), and AUC (2448.7, 3913.9) were all lower for PB patients as compared to GE patients (all p < 0.001). PB and SBRT patients had no correlations between any volume from V2–V25, mean spleen dose, and AUC with FLL or % ALC loss. For GE patients, volumes from V3-V25 (highest at V15, R = 0.363, p = 0.008), mean spleen dose (R = 0.353, p = 0.008), and AUC (R = 0.340, p = 0.011) all correlated with FLL. Similar statistically significant correlations were seen for those parameters with % ALC loss. After controlling for PTV, V15 (p = 0.019) held a significant correlation with FLL, though mean spleen dose (p = 0.055) and AUC (p = 0.059) were borderline insignificant. V15 (p = 0.038), mean spleen dose (p = 0.043), and AUC (p = 0.038) were each significantly correlated with % ALC loss after controlling for PTV. PB and SBRT patients showed no relationship between spleen dosimetry parameters and lymphocyte loss rate or % ALC loss through treatment. Given the relatively small dose delivered to the spleen, these results suggest that ALC loss in these patients is driven primarily by other parameters. In contrast, GE patients showed strong correlations of spleen dosimetry parameters with lymphocyte loss rates and % ALC loss.