Lymphocyte-sparing effect of stereotactic body radiation therapy compared to conventional fractionated radiation therapy in patients with locally advanced pancreatic cancer

BACKGROUND: Conventionally fractionated (CF) radiation therapy (RT) has been associated with lymphopenia, leading to compromised overall survival (OS) in cancer patients. It currently remains unknown if stereotactic body (SB) RT induces lymphopenia to the same degree. The aim of this study is to determine if SBRT with either chemotherapy (CMT) (Fluorouracil (5FU) or capecitabine) or Nelfinavir (NFV) to pancreatic adenocarcinoma induces lymphopenia to the same degree as CFRT with 5FU or capecitabine and how any associated difference affects patient survival outcomes. METHODS: Medical records of pancreatic adenocarcinoma patients treated with induction CMT followed by RT with concurrent CMT or NFV were reviewed. Patients with total lymphocyte counts (TLCs) available both prior to and following initiation of RT were included. Three groups were identified: CFRT/CMT, SBRT/CMT, and SBRT/NFV. Median delivered RT doses for CFRT and SBRT were 50.4 Gy in 1.8 Gy fractions and 35 Gy in 7 Gy fractions, respectively. TLCs from day 0 (the first day of RT) to 40 were recorded and analyzed using the Kruskal-Wallis test with p-values adjusted with Bonferroni’s method. Linear regressions were utilized to estimate the slope of TLCs as it changes with time and survival analysis was performed via Kaplan-Meier plots. RESULTS: One hundred patients were identified (28 CFRT/CMT, 27 SBRT/CMT, 45 SBRT/NFV). Median pre-RT TLCs were not different among groups. Median lowest TLCs were significantly lower (p < 0.0001) and median TLCs reduction over time were significantly greater (p < 0.0001) in the CFRT group than SBRT groups. There was no difference in lowest TLCs or TLCs reduction over time between SBRT groups. Across all groups, the median time to lowest TLCs was similar. Survival analysis revealed no significant difference in median OS between SBRT and CFRT groups. However, in patients with surgery, Median OS for patients with SBRT/CMT was significantly higher than in those with SBRT/NFV (p = 0.03). CONCLUSIONS: Compared to CFRT, SBRT is associated with less lymphopenia. Further study of the effect of radiation technique on immune status is warranted.