Matted nodes: High distant-metastasis risk and a potential indication for intensification of systemic therapy in human papillomavirus-related oropharyngeal cancer.
The purpose of this study was to determine whether matted nodes uniquely identify patients with human papillomavirus (HPV)-positive oropharyngeal cancer at disproportionately high distant failure risk who may benefit from intensified systemic therapy.



One hundred seventy-eight patients with stage III/IV HPV-positive oropharyngeal cancer who completed definitive chemoradiotherapy were stratified by risk group (low-risk = T1-3/N0-2c/<10 pack-years; intermediate-risk = T1-3/N0-2c/≥10 pack-years; and high-risk = T4 or N3). Prognostic impact of matted nodes was assessed.



At the 52-month median follow-up, event rates with and without matted nodes were: locoregional failure: 23.3% versus 12.8% (p = .16), distant failure: 50.0% versus 1.4% (p < .01), any failure: 73.3% versus 14.2% (p < .01); cause-specific mortality: 56.7% versus 5.4% (p < .01), and death: 56.7% versus 13.5% (p < .01). In multivariate analyses, including risk group and individual risk factors, matted nodes were the strongest predictor for all endpoints except locoregional failure. Among patients without matted nodes, risk-group discriminated locoregional failure (at 3 years: low-risk = 2.0%; intermediate-risk = 14.4%; and high-risk = 24.2%; p < .01), but not distant failure (low-risk = 0.0%; intermediate-risk = 2.1%; and high-risk = 3.8%; p = .53).



Matted nodes portended dramatically increased distant failure and death risks in HPV-positive oropharyngeal cancer, identifying a candidate population for consideration of chemo-intensification. © 2015 Wiley Periodicals, Inc. Head Neck 38: E805-E814, 2016.
Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan.
Jeffrey M
JM
Vainshtein
Department of Otolaryngology - Head and Neck Surgery, University of Michigan, Ann Arbor, Michigan.
Matthew E
ME
Spector
Department of Radiology, University of Michigan, Ann Arbor, Michigan.
Mohannad
M
Ibrahim
Department of Radiology, University of Michigan, Ann Arbor, Michigan.
Carol R
CR
Bradford
Department of Otolaryngology - Head and Neck Surgery, University of Michigan, Ann Arbor, Michigan.
Gregory T
GT
Wolf
Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan.
Matthew H
MH
Stenmark
Division of Hematology Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan.
Francis P
FP
Worden
Department of Pathology, University of Michigan, Ann Arbor, Michigan.
Jonathan B
JB
McHugh
Department of Otolaryngology - Head and Neck Surgery, University of Michigan, Ann Arbor, Michigan.
Mark E
ME
Prince
Department of Otolaryngology - Head and Neck Surgery, University of Michigan, Ann Arbor, Michigan.
Thomas
T
Carey
Department of Otolaryngology - Head and Neck Surgery, University of Michigan, Ann Arbor, Michigan.
Douglas B
DB
Chepeha
Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan.
Avraham
A
Eisbruch
D000328:Adult; D000368:Aged; D059248:Chemoradiotherapy; D005260:Female; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000175:diagnosis; D009367:Neoplasm Staging; D009959:Oropharyngeal Neoplasms / Q000473:pathology* / Q000628:therapy / Q000821:virology; D027383:Papillomaviridae; D030361:Papillomavirus Infections / Q000150:complications*; D011379:Prognosis; D012189:Retrospective Studies; D012307:Risk Factors
distant metastases; human papillomavirus; matted nodes; oropharyngeal cancer