title: Prognostic significance of plasma osteopontin in patients with locoregionally advanced head and neck squamous cell carcinoma treated on TROG 02.02 phase III trial.
abstract: OBJECTIVE
  High plasma osteopontin (OPN) levels have been reported to be an adverse prognostic factor in head and neck squamous cell carcinomas (HNSCC), correlate with tumor hypoxia, and be predictive of benefit from hypoxia-targeted therapy. We sought to confirm the prognostic and predictive significance of OPN in patients treated on a large international trial.
  
  
  METHODS
  Patients with stage III/IV HNSCC were randomized to receive definitive radiotherapy concurrently with cisplatin or cisplatin plus the hypoxic cell cytotoxin, tirapazamine (TPZ). Eligibility criteria for this prospective substudy included plasma sample availability for OPN assay by ELISA and absence of major radiation therapy deviations (N = 578). OPN concentrations were analyzed for overall survival (OS) and time to locoregional failure (TTLRF), adjusting for known prognostic factors. Additional analysis was carried out in patients with available tumor p16(INK4A) staining status.
  
  
  RESULTS
  The median OPN level was 544 ng/mL (range: 7-2,640). High OPN levels were not associated with worse OS (relative HR, 1.03 for highest tertile) or TTLRF (relative HR 0.91 for highest tertile). There was no interaction between OPN and treatment arm for OS or TTLRF (P = 0.93 for OS; P = 0.87 for TTLRF). For the highest tertile the 2-year OS was 66% on control arm and 67% on TPZ arm (HR = 1.11, P = 0.67). Similarly for p16(INK4A) negative patients in the highest tertile, the 2-year OS was 61% on control arm and 63% on TPZ arm (HR = 1.05, P = 0.86).
  
  
  CONCLUSIONS
  We found no evidence that high plasma OPN levels were associated with an adverse prognosis in HNSCC, or were predictive of benefit with hypoxia targeting therapy.
authors.affiliation: Department of Medical Oncology, Peter MacCallum Cancer Centre, University of Melbourne, Melbourne, Australia.
authors.forename: Annette M
authors.initials: AM
authors.lastname: Lim
authors.forename: Danny
authors.initials: D
authors.lastname: Rischin
authors.forename: Richard
authors.initials: R
authors.lastname: Fisher
authors.forename: Hongbin
authors.initials: H
authors.lastname: Cao
authors.forename: Kathleen
authors.initials: K
authors.lastname: Kwok
authors.forename: Daniel
authors.initials: D
authors.lastname: Truong
authors.forename: Grant A
authors.initials: GA
authors.lastname: McArthur
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Young
authors.forename: Amato
authors.initials: A
authors.lastname: Giaccia
authors.forename: Lester
authors.initials: L
authors.lastname: Peters
authors.forename: Quynh-Thu
authors.initials: QT
authors.lastname: Le
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood*; D002294:Carcinoma, Squamous Cell / Q000097:blood* / Q000188:drug therapy; D002945:Cisplatin / Q000008:administration & dosage; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D006258:Head and Neck Neoplasms / Q000097:blood* / Q000188:drug therapy; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000097:blood* / Q000188:drug therapy; D009367:Neoplasm Staging; D053495:Osteopontin / Q000097:blood*; D011446:Prospective Studies; D015996:Survival Rate; D000077704:Tirapazamine; D016896:Treatment Outcome; D014227:Triazines / Q000008:administration & dosage
chemical_list: D014408:Biomarkers, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16; D014227:Triazines; D053495:Osteopontin; D000077704:Tirapazamine; D002945:Cisplatin
references.citation: J Clin Oncol. 2010 Sep 20;28(27):4142-8
references.pmid: 20697079
references.citation: Oral Oncol. 2007 Oct;43(9):920-32
references.pmid: 17306612
references.citation: J Am Soc Nephrol. 2008 May;19(5):884-90
references.pmid: 18443355
references.citation: BMC Cancer. 2008 Jan 31;8:38
references.pmid: 18237408
references.citation: Lancet Oncol. 2005 Oct;6(10):757-64
references.pmid: 16198981
references.citation: Clin Cancer Res. 2003 Jan;9(1):59-67
references.pmid: 12538452
references.citation: Radiother Oncol. 2010 Jan;94(1):30-5
references.pmid: 19910068
references.citation: Eur J Clin Invest. 2010 Apr;40(4):288-93
references.pmid: 20192976
references.citation: J Clin Oncol. 2010 Jun 20;28(18):2989-95
references.pmid: 20479425
references.citation: Radiother Oncol. 2005 Oct;77(1):18-24
references.pmid: 16098619
references.citation: J Biol Chem. 2000 Jun 2;275(22):16666-72
references.pmid: 10747989
references.citation: FASEB J. 2004 Apr;18(6):734-6
references.pmid: 14766790
references.citation: Br J Cancer. 2010 Sep 7;103(6):861-9
references.pmid: 20823889
references.citation: Radiother Oncol. 1998 Feb;46(2):135-46
references.pmid: 9510041
references.citation: Clin Cancer Res. 2004 Dec 15;10(24):8501-11
references.pmid: 15623631
references.citation: Nat Rev Cancer. 2008 Mar;8(3):212-26
references.pmid: 18292776
references.citation: Clin Exp Metastasis. 2003;20(1):77-84
references.pmid: 12650610
references.citation: Semin Radiat Oncol. 1996 Jan;6(1):10-21
references.pmid: 10717158
references.citation: Cancer Metastasis Rev. 2010 Jun;29(2):295-307
references.pmid: 20386958
references.citation: J Clin Oncol. 2010 Jun 20;28(18):2996-3001
references.pmid: 20479390
references.citation: J Clin Oncol. 2006 May 1;24(13):2098-104
references.pmid: 16648512
references.citation: Ann N Y Acad Sci. 1995 Apr 21;760:177-89
references.pmid: 7785894
references.citation: Int J Radiat Oncol Biol Phys. 2011 May 1;80(1):249-57
references.pmid: 21300470
references.citation: Atherosclerosis. 2003 Oct;170(2):333-7
references.pmid: 14612215
references.citation: BMC Cancer. 2006 Aug 15;6:207
references.pmid: 16911785