Lymphocyte-Sparing Effect of Stereotactic Body Radiation Therapy Compared to Conventional Fractionated Radiation Therapy in Patients With Locally Advanced Pancreatic Cancer

Abstract

Conventional fractionated radiation therapy (CFRT)-induced lymphopenia has been reported to be associated with compromised survival in patients with glioblastoma, lung cancer, and pancreatic cancer. However, it is unknown if stereotactic body radiation therapy (SBRT) will induce lymphopenia and its relationship with survival outcomes. Due to smaller fields and a faster dose fall off of SBRT, we hypothesize that SBRT will induce less lymphopenia when compared to CFRT, which may lead to improved survival outcomes on patients with locally advanced pancreatic adenocarcinoma. Medical records of patients with locally advanced pancreatic adenocarcinoma treated at UNMC with neoadjuvant or definitive CFRT or SBRT following induction chemotherapy from 2004-2016 were reviewed. Patients who had baseline and follow-up total lymphocyte counts (TLCs) measured at our institution were included in this study. Patients were stratified into 4 groups: 1) CFRT/5-fluorouracil (5FU), 2) SBRT/5FU, 3) SBRT/Nelfinavir (NVF) and 4) SBRT alone. Median CFRT and SBRT prescription doses were 50.4 Gy (range 8 – 50.4 Gy) at 1.8-2 Gy per fraction and 35 Gy (range 25 - 40 Gy) in 5 fractions, respectively. Serial TLCs from day 0 (the first day of RT) to 40 were recorded. Multiple comparisons were performed using the Kruskal–Wallis test and P values were adjusted with Bonferroni method. Linear regression was used to estimate the slope of TLCs change with time. The Kaplan-Meier plot was used for survival analysis. Among 103 patients identified, 28 were treated with CFRT/5FU, 17 SBRT/5FU, 46 SBRT/NVF and 12 SBRT alone. The median pre-RT baseline TLCs were 1.5 (range 0.5-2.8), 1 (range 0.4-3.3), 1.2 (range 0.3-2.6) and 1.5 (range 0.7-2.3) cells/mm3, respectively. There was no difference in median baseline TLCs among 4 groups (p > 0.05). The median slopes of TLCs changed from day 0 to 40 after starting radiation and were increasing in the following sequence: CFRT/5FU (-0.0239) < SBRT/5FU (-0.0042) < SBRT/NFV (-0.0016) < SBRT alone (0.0024). The median lowest TLCs were 0.2 (range 0-1.6), 0.4 (range 0.1-1.5), 0.7 (range 0-1.6) and 1.1 (range 0.3-1.5) cells/mm3, respectively. CFRT patients had significantly lower lowest TLCs than all SBRT subgroups (P <0.001). The median time to lowest TLCs were 30, 26, 28 and 23 days, respectively. There was no difference in time to lowest TLCs among groups (P >0.05). Survival analysis revealed no significant difference in median overall survival among all groups. SBRT is associated with significant less treatment-induced lymphopenia than CFRT. This did not translate into survival benefit. Further study of the effect of radiation technique on immune status is warranted.