Lymphocyte-sparing effect of stereotactic body radiation therapy in patients with unresectable pancreatic cancer Journal Article


Authors: Wild, A. T.; Herman, J. M.; Dholakia, A. S.; Moningi, S.; Lu, Y.; Rosati, L. M.; Hacker-Prietz, A.; Assadi, R. K.; Saeed, A. M.; Pawlik, T. M.; Jaffee, E. M.; Laheru, D. A.; Tran, P. T.; Weiss, M. J.; Wolfgang, C. L.; Ford, E.; Grossman, S. A.; Ye, X.; Ellsworth, S. G.
Article Title: Lymphocyte-sparing effect of stereotactic body radiation therapy in patients with unresectable pancreatic cancer
Abstract: Purpose Radiation-induced lymphopenia (RIL) is associated with inferior survival in patients with glioblastoma, lung cancer, and pancreatic cancer. We asked whether stereotactic body radiation therapy (SBRT) decreases severity of RIL compared to conventional chemoradiation therapy (CRT) in locally advanced pancreatic cancer (LAPC). Methods and Materials Serial total lymphocyte counts (TLCs) from patients enrolled in a prospective trial of SBRT for LAPC were compared to TLCs from an existing database of LAPC patients undergoing definitive CRT. SBRT patients received 33 Gy (6.6 Gy × 5 fractions). CRT patients received a median dose of 50.4 Gy (1.8 Gy × 28 fractions) with concurrent 5-fluorouracil (77%) or gemcitabine (23%) therapy. Univariate and multivariate analyses (MVA) were used to identify associations between clinical factors and post-treatment TLC and between TLC and survival. Results Thirty-two patients received SBRT and 101 received CRT. Median planning target volume (PTV) was smaller in SBRT (88.7 cm3) than in CRT (344.6 cm3; P<.001); median tumor diameter was larger for SBRT (4.6 cm) than for CRT (3.6 cm; P=.01). SBRT and CRT groups had similar median baseline TLCs. One month after starting radiation, 71.7% of CRT patients had severe lymphopenia (ie, TLC <500 cells/mm3 vs 13.8% of SBRT patients; P<.001). At 2 months, 46.0% of CRT patients remained severely lymphopenic compared with 13.6% of SBRT patients (P=.007). MVA demonstrated that treatment technique and baseline TLCs were significantly associated with post-treatment TLC at 1 but not 2 months after treatment. Higher post-treatment TLC was associated with improved survival regardless of treatment technique (hazard ratio [HR] for death: 2.059; 95% confidence interval: 1.310-3.237; P=.002). Conclusions SBRT is associated with significantly less severe RIL than CRT at 1 month in LAPC, suggesting that radiation technique affects RIL and supporting previous modeling studies. Given the association of severe RIL with survival in LAPC, further study of the effect of radiation technique on immune status is warranted.
Keywords: radiation; radiotherapy; confidence interval; multivariate analysis; patient treatment; stereotactic body radiation therapy; multivariant analysis; lymphocytes; diseases; planning target volumes; treatment techniques; methods and materials; chemoradiation therapies; locally advanced pancreatic cancers
Journal Title: International Journal of Radiation Oncology, Biology, Physics
Volume: 94
Issue: 3
ISSN: 0360-3016
Publisher: Elsevier Inc.  
Date Published: 2016-03-01
Start Page: 571
End Page: 579
Language: English
DOI: 10.1016/j.ijrobp.2015.11.026
PROVIDER: scopus
PUBMED: 26867885
PMCID: PMC4847529
DOI/URL:
Notes: Article -- Export Date: 2 May 2016 -- Source: Scopus
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  1. Aaron Tyler Wild
    19 Wild