Smoking, age, nodal disease, T stage, p16 status, and risk of distant metastases in patients with squamous cell cancer of the oropharynx

Jonathan J Beitler, Jeffrey M Switchenko, James J Dignam, Mark W McDonald, Nabil F Saba, Dong M Shin, Kelly R Magliocca, Richard J Cassidy, Mark W El-Deiry, Mihir R Patel, Conor E Steuer, Canhua Xiao, Patricia A Hudgins, Ashley H Aiken, Walter J Curran Jr, Quynh-Thu Le, Jonathan J Beitler, Jeffrey M Switchenko, James J Dignam, Mark W McDonald, Nabil F Saba, Dong M Shin, Kelly R Magliocca, Richard J Cassidy, Mark W El-Deiry, Mihir R Patel, Conor E Steuer, Canhua Xiao, Patricia A Hudgins, Ashley H Aiken, Walter J Curran Jr, Quynh-Thu Le

Abstract

Background: With an expectation of excellent locoregional control, ongoing efforts to de-intensify therapy for patients with human papillomavirus-associated squamous cell oropharyngeal cancer necessitate a better understanding of the metastatic risk for patients with this disease. The objective of this study was to determine what factors affect the risk of metastases in patients with squamous cell cancers of the oropharynx.

Methods: Under a shared use agreement, 547 patients from Radiation Therapy Oncology Group 0129 and 0522 with nonmetastatic oropharyngeal squamous cell cancers who had a known p16 status and smoking status were analyzed to assess the association of clinical features with the development of distant metastases. The analyzed factors included the p16 status, sex, T stage, N stage, age, and smoking history.

Results: A multivariate analysis of 547 patients with a median follow-up of 4.8 years revealed that an age ≥ 50 years (hazard ratio [HR], 3.28; P = .003), smoking for more than 0 pack-years (HR, 3.09; P < .001), N3 disease (HR, 2.64; P < .001), T4 disease (HR, 1.63; P = .030), and a negative p16 status (HR, 1.60; P = .044) were all factors associated with an increased risk of distant disease.

Conclusions: Age, smoking, N3 disease, T4 disease, and a negative p16 status were associated with the development of distant metastases in patients with squamous cell cancers of the oropharynx treated definitively with concurrent chemoradiation.

Trial registration: ClinicalTrials.gov NCT00047008 NCT00265941.

Keywords: age; distant metastases; human papillomavirus (HPV); nodal disease; oropharynx; smoking.

© 2018 American Cancer Society.

Figures

Figure 1a.
Figure 1a.
Distant Metastasis-Free Survival by Age, =50 426 78 (18%) 348 (82%) NA (NA, NA) 90.3% (86.9%, 92.8%) 83.6% (79.6%, 87.0%) 82.5% (78.4%, 86.0%) 80.5% (76.1%, 84.2%) 79.6% (75.0%, 83.4%)
Figure 1b.
Figure 1b.
Distant Metastasis-Free Survival by Smoking History, 0 versus >0 Pack Years Smoking history (pack-years) No. of Subject Event Censored Median Survival (95% CI) 1 Yr Survival 2 Yr Survival 3 Yr Survival 4 Yr Survival 5 Yr Survival 0 174 11 (6%) 163 (94%) NA (NA, NA) 98.2% (94.6%, 99.4%) 96.4% (92.1%, 98.3%) 94.5% (89.6%, 97.1%) 93.8% (88.7%, 96.6%) 93.8% (88.7%, 96.6%) >0 373 74 (20%) 299 (80%) NA (NA, NA) 89.1% (85.4%, 92.0%) 81.2% (76.6%, 85.0%) 80.5% (75.9%, 84.4%) 78.5% (73.6%, 82.6%) 77.4% (72.3%, 81.7%)
Figure 1c.
Figure 1c.
Distant Metastasis-Free Survival by AJCC 7th Edition Nodal Staging, N0/N1/N2 versus N3 N stage No. of Subject Event Censored Median Survival (95% CI) 1 Yr Survival 2 Yr Survival 3 Yr Survival 4 Yr Survival 5 Yr Survival N0/N1/N2 497 70 (14%) 427 (86%) NA (NA, NA) 93.4% (90.8%, 95.3%) 87.6% (84.2%, 90.3%) 86.4% (82.9%, 89.2%) 84.9% (81.2%, 88.0%) 84.5% (80.8%, 87.6%) N3 50 15 (30%) 35 (70%) NA (NA, NA) 79.0% (64.4%, 88.1%) 72.0% (56.6%, 82.7%) 72.0% (56.6%, 82.7%) 69.4% (53.6%, 80.7%) 66.5% (50.3%, 78.4%)
Figure 1d.
Figure 1d.
Distant Metastasis-Free Survival by AJCC 7th Edition T Stage, T2/T2 versus T4 T stage No. of Subject Event Censored Median Survival (95% CI) 1 Yr Survival 2 Yr Survival 3 Yr Survival 4 Yr Survival 5 Yr Survival T2/T3 391 53 (14%) 338 (86%) NA (NA, NA) 93.1% (90.0%, 95.2%) 88.2% (84.4%, 91.1%) 87.3% (83.5%, 90.3%) 86.0% (81.9%, 89.2%) 85.1% (80.8%, 88.4%) T4 156 32 (21%) 124 (79%) NA (NA, NA) 89.3% (82.8%, 93.4%) 80.3% (72.4%, 86.2%) 78.6% (70.4%, 84.7%) 76.3% (67.7%, 82.9%) 76.3% (67.7%, 82.9%)
Figure 1e.
Figure 1e.
Distant Metastasis-Free Survival by p16 Status, Negative versus Positive p16 status No. of Subject Event Censored Median Survival (95% CI) 1 Yr Survival 2 Yr Survival 3 Yr Survival 4 Yr Survival 5 Yr Survival Negative 145 31 (21%) 114 (79%) NA (NA, NA) 90.1% (83.5%, 94.1%) 77.8% (69.2%, 84.2%) 75.9% (67.2%, 82.7%) 75.9% (67.2%, 82.7%) 74.0% (64.5%, 81.3%) Positive 402 54 (13%) 348 (87%) NA (NA, NA) 92.8% (89.7%, 94.9%) 88.7% (85.1%, 91.5%) 87.9% (84.2%, 90.8%) 86.0% (82.0%, 89.1%) 85.5% (81.4%, 88.8%)
Figure 2:
Figure 2:
Consort Diagram

Source: PubMed

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