title: Cancer-related symptom clusters, eosinophils, and survival in hepatobiliary cancer: an exploratory study.
abstract: BACKGROUND
  The study of symptom clusters is gaining increased attention in the field of oncology in an attempt to improve the quality of life of patients diagnosed with cancer.
  
  
  OBJECTIVE
  The aims of the present study were to 1) determine the prevalence and distribution of pain, fatigue, and symptoms of depression and their covariation as a cluster in people with hepatobiliary carcinoma (HBC), 2) characterize how variation in each individual symptom and/or their covariation as a cluster are associated with changes in immunity, and 3) determine if the symptom clusters, and associated biomarkers, are related to survival in people diagnosed with HBC.
  
  
  METHODS
  Two hundred six participants diagnosed with HBC completed a battery of standardized questionnaires measuring cancer-related symptoms. Peripheral blood leukocytes were measured at diagnosis and at three- and six-month follow-ups. Survival was measured from the date of diagnosis to death.
  
  
  RESULTS
  Cancer-related symptoms were prevalent and two-step hierarchical cluster analyses yielded three symptom clusters. High levels of pain, fatigue, and depression were found to be associated with elevated eosinophil percentages (F[1,78]=3.1, P=0.05) at three- and six-month follow-up using repeated-measures analysis of variance. Using multivariate latent growth curve modeling, pain was the primary symptom associated with elevated eosinophil percentages between diagnosis and six months (z=2.24, P=0.05). Using Cox regression, vascular invasion and age were negatively associated with survival (Chi-square=21.6, P=0.03). While stratifying for vascular invasion, Kaplan-Meier survival analysis was performed, and eosinophil levels above the median for the sample were found to be related to increased survival in patients with and without vascular invasion (Breslow Chi-square=4.9, P=0.03). Symptom clusters did not mediate the relationship between eosinophils and survival.
  
  
  CONCLUSIONS
  Cancer-related symptoms, particularly pain and depression, were associated with increased percentages of eosinophils. The presence of symptoms may reflect tumor cell death and be indicative of response to treatment, or other processes, in patients with HBC.
authors.affiliation: Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA. steeljl@upmc.edu
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Steel
authors.forename: Kevin H
authors.initials: KH
authors.lastname: Kim
authors.forename: Mary Amanda
authors.initials: MA
authors.lastname: Dew
authors.forename: Mark L
authors.initials: ML
authors.lastname: Unruh
authors.forename: Michael H
authors.initials: MH
authors.lastname: Antoni
authors.forename: Marion C
authors.initials: MC
authors.lastname: Olek
authors.forename: David A
authors.initials: DA
authors.lastname: Geller
authors.forename: Brian I
authors.initials: BI
authors.lastname: Carr
authors.forename: Lisa H
authors.initials: LH
authors.lastname: Butterfield
authors.forename: T Clark
authors.initials: TC
authors.lastname: Gamblin
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D001661:Biliary Tract Neoplasms / Q000453:epidemiology* / Q000276:immunology; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology* / Q000276:immunology; D016000:Cluster Analysis; D015897:Comorbidity; D003863:Depression / Q000453:epidemiology; D004804:Eosinophils / Q000276:immunology*; D005221:Fatigue / Q000453:epidemiology; D005260:Female; D006304:Health Status; D006801:Humans; D008113:Liver Neoplasms / Q000453:epidemiology* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010146:Pain / Q000453:epidemiology; D010147:Pain Measurement; D018579:Patient Selection; D015995:Prevalence; D011788:Quality of Life; D012044:Regression Analysis; D012720:Severity of Illness Index; D011795:Surveys and Questionnaires; D015996:Survival Rate
references.citation: Int J Cancer. 1993 Apr 22;54(1):8-15
references.pmid: 8386711
references.citation: Cancer Res. 2004 Sep 15;64(18):6402-9
references.pmid: 15374947
references.citation: Pain. 1996 Oct;67(2-3):267-73
references.pmid: 8951920
references.citation: J Clin Oncol. 2002 May 1;20(9):2229-39
references.pmid: 11980994
references.citation: Proc Natl Acad Sci U S A. 2003 Jun 24;100(13):7830-5
references.pmid: 12808148
references.citation: Biol Psychiatry. 2003 Aug 1;54(3):283-94
references.pmid: 12893104
references.citation: Biochem J. 2000 Oct 1;351(Pt 1):95-105
references.pmid: 10998351
references.citation: J Cell Physiol. 2001 Jun;187(3):374-85
references.pmid: 11319761
references.citation: Semin Hematol. 1997 Jul;34(3 Suppl 2):13-9
references.pmid: 9253779
references.citation: Neurosci Lett. 2004 May 6;361(1-3):184-7
references.pmid: 15135924
references.citation: Psychiatry Res. 2001 Dec 15;105(1-2):45-55
references.pmid: 11740974
references.citation: Science. 1986 Aug 8;233(4764):652-4
references.pmid: 3014662
references.citation: Ann N Y Acad Sci. 1998 May 1;840:269-81
references.pmid: 9629255
references.citation: Brain Behav Immun. 2002 Oct;16(5):596-601
references.pmid: 12401474
references.citation: Mol Psychiatry. 1999 Mar;4(2):182-8
references.pmid: 10208451
references.citation: Cancer. 2003 Jun 1;97(11):2919-25
references.pmid: 12767108
references.citation: Neoplasma. 1984;31(3):323-6
references.pmid: 6738756
references.citation: J Clin Pathol. 1981 Dec;34(12):1343-8
references.pmid: 7035499
references.citation: Psychol Bull. 1990 Mar;107(2):238-46
references.pmid: 2320703
references.citation: Psychosom Med. 2003 May-Jun;65(3):362-8
references.pmid: 12764208
references.citation: Am J Psychiatry. 2001 Aug;158(8):1252-7
references.pmid: 11481159
references.citation: Hepatology. 1998 Jul;28(1):57-67
references.pmid: 9657097
references.citation: Psychosom Med. 2002 Jul-Aug;64(4):604-11
references.pmid: 12140350
references.citation: Cancer. 1998 Jul 1;83(1):58-63
references.pmid: 9655293
references.citation: Sem Hop. 1982 Jan 21;58(3):133-7
references.pmid: 6278618
references.citation: Anticancer Res. 2002 Mar-Apr;22(2A):931-6
references.pmid: 12014674
references.citation: Cancer Immunol Immunother. 2004 Oct;53(10):844-54
references.pmid: 15197495
references.citation: Exp Neurol. 2005 Apr;192(2):444-62
references.pmid: 15755561
references.citation: Biol Psychiatry. 2001 Mar 1;49(5):391-404
references.pmid: 11274650
references.citation: J Pain Symptom Manage. 2006 Jan;31(1):85-95
references.pmid: 16442485
references.citation: Liver. 1991 Apr;11(2):106-13
references.pmid: 1646927
references.citation: J Immunother Emphasis Tumor Immunol. 1996 May;19(3):218-23
references.pmid: 8811496
references.citation: Eur J Biochem. 2001 Aug;268(16):4513-9
references.pmid: 11502212
references.citation: Blood. 1992 Jun 15;79(12):3101-9
references.pmid: 1596561
references.citation: Anticancer Res. 1997 Jan-Feb;17(1A):181-8
references.pmid: 9066649
references.citation: Clin Microbiol Rev. 1996 Oct;9(4):532-62
references.pmid: 8894351
references.citation: Curr Opin Cell Biol. 2005 Apr;17(2):150-7
references.pmid: 15780591
references.citation: Eur J Cancer. 1990;26(9):965-9
references.pmid: 2177616
references.citation: Neurosignals. 2005;14(4):166-74
references.pmid: 16215299
references.citation: Jpn J Clin Oncol. 1987 Dec;17(4):327-32
references.pmid: 2826847
references.citation: Front Neuroendocrinol. 1995 Apr;16(2):151-82
references.pmid: 7621980
references.citation: J Adv Nurs. 2001 Mar;33(5):668-76
references.pmid: 11298204
references.citation: Brain Behav Immun. 2001 Mar;15(1):7-24
references.pmid: 11259077
references.citation: N Engl J Med. 2003 Mar 27;348(13):1199-200
references.pmid: 12660383
references.citation: J Immunother. 2007 Jan;30(1):16-28
references.pmid: 17198080
references.citation: Psychosom Med. 2001 May-Jun;63(3):453-62
references.pmid: 11382273
references.citation: J Immunol. 1989 Mar 15;142(6):2162-7
references.pmid: 2784151
references.citation: Hepatology. 2000 Nov;32(5):962-9
references.pmid: 11050046
references.citation: J Clin Oncol. 1993 Mar;11(3):570-9
references.pmid: 8445433
references.citation: Ann Oncol. 2004 Aug;15(8):1237-42
references.pmid: 15277264
references.citation: Zhonghua Zhong Liu Za Zhi. 1995 May;17(3):167-9
references.pmid: 7656817
references.citation: Cancer. 2001 Sep 15;92(6 Suppl):1684-8
references.pmid: 11598887
references.citation: J Gastroenterol Hepatol. 1990 Sep-Oct;5(5):542-8
references.pmid: 1966592
references.citation: Int J Oncol. 2001 Jan;18(1):41-7
references.pmid: 11115537
references.citation: J Hepatol. 1999 Apr;30(4):653-9
references.pmid: 10207807
references.citation: Adv Exp Med Biol. 1999;461:25-46
references.pmid: 10442165
references.citation: Chin Med J (Engl). 1997 Feb;110(2):114-7
references.pmid: 9594281
references.citation: Neuropsychopharmacology. 2002 May;26(5):643-52
references.pmid: 11927189
references.citation: NIH Consens State Sci Statements. 2002 Jul 15-17;19(4):1-29
references.pmid: 14984106
references.citation: Cancer Immunol Immunother. 1992;35(4):246-50
references.pmid: 1511459
references.citation: Hepatogastroenterology. 1990 Oct;37(5):465-8
references.pmid: 2174825
references.citation: Adv Exp Med Biol. 1999;461:59-73
references.pmid: 10442167
references.citation: J Natl Cancer Inst Monogr. 2004;(32):17-21
references.pmid: 15263036