Kinetics and dosimetric predictors of acute radiation-induced lymphopenia in pancreatic cancer.

Abstract

300 Background: Radiation (RT) induced lymphopenia (RIL) is an adverse prognostic factor in pancreatic cancer (PC) and is likely due to the irradiation of lymphocytes in the RT field. The goal of this study was to identify dosimetric predictors for high rates of absolute lymphocyte count (ALC) loss during RT for PC. Methods: This was a retrospective study of 34 PC patients in an institutional database who had received concurrent 5-FU or gemcitabine-based chemoradiation (50-54 Gy) and had ≥ 3 ALCs measured during RT. Baseline ALC was normal (>1000 cells/uL) in 28/34 (82%) and grade 3-4 RIL occurred in 24/34 (71%). ALC was plotted against fraction # and a best-fit line for each patient was created to determine per-fraction loss in ALC (PFLAC). Linear regression was used to correlate PFLAC with dosimetric parameters including mean dose to gut, liver, kidney, spleen, and cisterna chyli, as well as estimated dose to immune cells (EDIC), which calculates dose to immune cells according to the % of body lymphocytes contained in each organ. Results: All patients exhibited exponential loss in ALC during RT. Mean PFLAC was 6.8% (range 1.7-13.4); fraction # was strongly correlated with ALC (mean R2 = 0.89). Patients with >/= grade 3 lymphopenia had a significantly higher PFLAC than those with grade 0 - 2 lymphopenia (mean daily loss 7.8% in Gr 3-4 vs. 4.8% in Gr 0-2, p = 0.001; independent sample T test). Field size was not correlated with PFLAC for high (> 1 Gy) or low (< 0.5 Gy) isodose volumes. Mean whole body (r = 0.59, p < 0.001), bowel (r = 0.39, p = 0.012), liver (r = 0.42, p = 0.007), and cisterna chyli (r = 0.583, p = 0.004) doses were moderately correlated with PFLAC; mean kidney (r = 0.22, p = 0.11) and spleen (r = 0.26, p = 0.06) doses were weakly correlated with PFLAC. EDIC was more strongly correlated with PFLAC than any individual organ mean dose (r = 0.69, p < 0.001). Conclusions: Patients undergoing RT for PC experience a predictable RIL characterized by an exponential loss of lymphocytes per day. PFLAC is a useful method of characterizing RIL and facilitates evaluation of dosimetric predictors of RIL. We identified dose to cisterna chyli as a significant contributor to RIL in PC; however, EDIC has a stronger correlation with RIL severity than any single organ dose.