Lymphocyte-Sparing Effect of Stereotactic Body Radiation Therapy in Patients with Unresectable Pancreatic Cancer

Publication date: Available online 1 December 2015
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Aaron T. Wild, Joseph M. Herman, Avani S. Dholakia, Shalini Moningi, Yao Lu, Lauren M. Rosati, Amy Hacker-Prietz, Ryan K. Assadi, Ali M. Saeed, Timothy M. Pawlik, Elizabeth M. Jaffee, Daniel A. Laheru, Phuoc T. Tran, Matthew J. Weiss, Christopher L. Wolfgang, Eric Ford, Stuart A. Grossman, Xiaobu Ye, Susannah G. Ellsworth
PurposeRadiation-induced lymphopenia (RIL) is associated with inferior survival in glioblastoma, lung cancer, and pancreatic cancer. We studied whether stereotactic body radiation therapy (SBRT) decreases severity of RIL compared to conventional chemoradiation (CRT) in locally advanced pancreatic cancer (LAPC).Methods/MaterialsSerial total lymphocyte counts (TLCs) from patients enrolled on 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). CRT patients received median 50.4 Gy (1.8 Gy×28) with concurrent 5-fluorouracil (77%) or gemcitabine (23%). Uni- and multivariate analyses (MVA) were used to identify associations between clinical factors and post-treatment TLC and between TLC and survival.ResultsThirty-two patients received SBRT and 101 CRT. Median planning target volume (PTV) was smaller in SBRT (88.7cc) versus CRT (344.6cc; p<0.001); median tumor diameter was larger for SBRT (4.6cm) versus CRT (3.6cm; p=0.01). SBRT and CRT groups had similar median baseline TLC. One month after starting radiation, 71.7% of CRT patients had severe lymphopenia, i.e., TLC<500 cells/mm³ versus 13.8% of SBRT patients (p<0.001). At 2 months, 46.0% of CRT patients remained severely lymphopenic versus 13.6% of SBRT patients (p=0.007). MVA demonstrated that treatment technique and baseline TLC were significantly associated with post-treatment TLC at one but not two months after treatment. Higher post-treatment TLC was associated with improved survival regardless of treatment technique (HR for death 2.059 (1.310 – 3.237), p = 0.002).ConclusionsSBRT is associated with significantly less severe RIL than CRT at one 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.

Teaser

This study compared post-treatment total lymphocyte counts (TLC) in patients treated with SBRT vs. conventional chemoradiation; multivariate analysis demonstrated that treatment technique and baseline TLC were significantly associated with post-treatment TLC at one but not two months post-treatment, providing preliminary support of a model predicting that fraction number and field size are associated with post-treatment TLC. Additionally, severe radiation-induced lymphopenia was associated with inferior survival regardless of treatment technique.


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