title: Does Unintentional Splenic Radiation Predict Outcomes After Pancreatic Cancer Radiation Therapy?
abstract: To determine whether severity of lymphopenia is dependent on radiation dose and fractional volume of spleen irradiated unintentionally during definitive chemoradiation (CRT) in patients with locally advanced pancreatic cancer (LAPC).
  
  
  
  177 patients with LAPC received induction chemotherapy (mainly gemcitabine-based regimens) followed by CRT (median 50.4 Gy with concurrent capecitabine) from January 2006 to December 2012. Absolute lymphocyte count (ALC) was recorded at baseline, before CRT, and 2 to 10 weeks after CRT. Splenic dose-volume histogram (DVH) parameters were reported as mean splenic dose (MSD) and percentage of splenic volume receiving at least 5- (V5), 10- (V10), 15- (V15), and 20-Gy (V20) dose. Overall survival (OS) was analyzed with use of the Cox model, and development of post-CRT severe lymphopenia (ALC <0.5 K/UL) was assessed by multivariate logistic regression with use of baseline and treatment factors.
  
  
  
  The median post-CRT ALC (0.68 K/UL; range, 0.13-2.72) was significantly lower than both baseline ALC (1.42 K/UL; range, 0.34-3.97; P<.0001) and pre-CRT ALC (1.32 K/UL, range 0.36-4.82; P<.0001). Post-CRT ALC <0.5 K/UL was associated with inferior OS on univariate analysis (median, 11.1 vs 15.3 months; P=.01) and multivariate analysis (hazard ratio = 1.66, P=.01). MSD (9.8 vs 6 Gy, P=.03), median V10 (32.6 vs 16%, P=.04), V15 (23.2 vs 9.5%, P=.03), and V20 (15.4 vs 4.6%, P=.02) were significantly higher in patients with severe lymphopenia than in those without. On multivariate analysis, postinduction lymphopenia (P<.001; odds ratio [OR] = 5.25) and MSD (P=.002; OR= 3.42) were independent predictors for the development of severe post-CRT lymphopenia.
  
  
  
  Severe post-CRT lymphopenia is an independent predictor of poor OS in LAPC patients receiving CRT. Higher splenic doses increase the risk for the development of severe post-CRT lymphopenia. When clinically indicated, assessment of splenic DVHs before the acceptance of treatment plans may minimize the risk of severe post-CRT lymphopenia.
authors.affiliation: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Awalpreet S
authors.initials: AS
authors.lastname: Chadha
authors.affiliation: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Guan
authors.initials: G
authors.lastname: Liu
authors.affiliation: Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Hsiang-Chun
authors.initials: HC
authors.lastname: Chen
authors.affiliation: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Prajnan
authors.initials: P
authors.lastname: Das
authors.affiliation: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Minsky
authors.affiliation: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Usama
authors.initials: U
authors.lastname: Mahmood
authors.affiliation: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Marc E
authors.initials: ME
authors.lastname: Delclos
authors.affiliation: Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Yelin
authors.initials: Y
authors.lastname: Suh
authors.affiliation: Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas; Graduate School of Biomedical Sciences, The University of Texas, Houston, Texas.
authors.forename: Gabriel O
authors.initials: GO
authors.lastname: Sawakuchi
authors.affiliation: Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Sam
authors.initials: S
authors.lastname: Beddar
authors.affiliation: Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Matthew H
authors.initials: MH
authors.lastname: Katz
authors.affiliation: Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Jason B
authors.initials: JB
authors.lastname: Fleming
authors.affiliation: Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Milind M
authors.initials: MM
authors.lastname: Javle
authors.affiliation: Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Gauri R
authors.initials: GR
authors.lastname: Varadhachary
authors.affiliation: Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Wolff
authors.affiliation: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Christopher H
authors.initials: CH
authors.lastname: Crane
authors.affiliation: Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Xuemei
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Howard
authors.initials: H
authors.lastname: Thames
authors.affiliation: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas. Electronic address: skrishnan@mdanderson.org.
authors.forename: Sunil
authors.initials: S
authors.lastname: Krishnan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D059248:Chemoradiotherapy / Q000009:adverse effects*; D005260:Female; D006801:Humans; D060828:Induction Chemotherapy; D016015:Logistic Models; D018655:Lymphocyte Count; D008231:Lymphopenia / Q000209:etiology* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D058958:Organs at Risk / Q000528:radiation effects*; D010190:Pancreatic Neoplasms / Q000628:therapy*; D016016:Proportional Hazards Models; D011879:Radiotherapy Dosage; D013154:Spleen / Q000528:radiation effects*; D013997:Time Factors