title: Lymphocyte-Sparing Effect of Stereotactic Body Radiation Therapy in Patients With Unresectable Pancreatic Cancer.
abstract: OBJECTIVE
  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
  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 cm(3)) than in CRT (344.6 cm(3); 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/mm(3) 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.
authors: Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York.
authors: Aaron T
authors: AT
authors: Wild
authors: Department of Radiation Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors: Joseph M
authors: JM
authors: Herman
authors: Department of Radiation Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors: Avani S
authors: AS
authors: Dholakia
authors: Department of Radiation Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors: Shalini
authors: S
authors: Moningi
authors: Department of Oncology Biostatistics, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors: Yao
authors: Y
authors: Lu
authors: Department of Radiation Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors: Lauren M
authors: LM
authors: Rosati
authors: Department of Radiation Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors: Amy
authors: A
authors: Hacker-Prietz
authors: Department of Radiation Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors: Ryan K
authors: RK
authors: Assadi
authors: Department of Radiation Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors: Ali M
authors: AM
authors: Saeed
authors: Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors: Timothy M
authors: TM
authors: Pawlik
authors: Department of Medical Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors: Elizabeth M
authors: EM
authors: Jaffee
authors: Department of Medical Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors: Daniel A
authors: DA
authors: Laheru
authors: Department of Radiation Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors: Phuoc T
authors: PT
authors: Tran
authors: Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors: Matthew J
authors: MJ
authors: Weiss
authors: Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors: Christopher L
authors: CL
authors: Wolfgang
authors: Department of Radiation Oncology, University of Washington School of Medicine, Seattle, Washington.
authors: Eric
authors: E
authors: Ford
authors: Department of Medical Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors: Stuart A
authors: SA
authors: Grossman
authors: Department of Oncology Biostatistics, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors: Xiaobu
authors: X
authors: Ye
authors: Department of Radiation Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland. Electronic address: sbatkoy2@jhmi.edu.
authors: Susannah G
authors: SG
authors: Ellsworth
mesh_terms: D000230:Adenocarcinoma / Q000401:mortality / Q000473:pathology / Q000601:surgery*; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D059248:Chemoradiotherapy / Q000009:adverse effects; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D019583:Dose Fractionation, Radiation; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D006801:Humans; D018655:Lymphocyte Count; D008231:Lymphopenia / Q000209:etiology / Q000401:mortality / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000401:mortality / Q000473:pathology / Q000601:surgery*; D011446:Prospective Studies; D016634:Radiosurgery / Q000009:adverse effects / Q000379:methods*; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; D005472:Fluorouracil; D000093542:Gemcitabine