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Figure.  Conditional Probability Plot Showing the Time Point During Years of Follow-up When Competing Causes of Death Surpass Primary Head and Neck Cancer (HNC) as the Leading Cause of Death in the HNC Population
Conditional Probability Plot Showing the Time Point During Years of Follow-up When Competing Causes of Death Surpass Primary Head and Neck Cancer (HNC) as the Leading Cause of Death in the HNC Population

The plots cross at approximately 56 months after diagnosis.

Table.  Characteristics of Patients With Head and Neck Cancer and Logistic Regression for Head and Neck Cancer–Specific vs Competing Causes of Death, Surveillance, Epidemiology, and End Results 18
Characteristics of Patients With Head and Neck Cancer and Logistic Regression for Head and Neck Cancer–Specific vs Competing Causes of Death, Surveillance, Epidemiology, and End Results 18
1.
Cohen  EE, LaMonte  SJ, Erb  NL,  et al.  American Cancer Society head and neck cancer survivorship care guideline.  CA Cancer J Clin. 2016;66(3):203-239.PubMedGoogle ScholarCrossref
2.
Piccirillo  JF.  Importance of comorbidity in head and neck cancer.  Laryngoscope. 2000;110(4):593-602.PubMedGoogle ScholarCrossref
3.
National Cancer Institute. Surveillance, Epidemiology, and End Results Program. Overview of the SEER program. 2016. https://seer.cancer.gov/about/overview.html. Accessed October 9, 2017.
4.
Massa  ST, Osazuwa-Peters  N, Christopher  KM,  et al.  Competing causes of death in the head and neck cancer population.  Oral Oncol. 2017;65:8-15.PubMedGoogle ScholarCrossref
5.
Hashibe  M, Brennan  P, Chuang  SC,  et al.  Interaction between tobacco and alcohol use and the risk of head and neck cancer: pooled analysis in the International Head and Neck Cancer Epidemiology Consortium.  Cancer Epidemiol Biomarkers Prev. 2009;18(2):541-550.PubMedGoogle ScholarCrossref
6.
Kawakita  D, Hosono  S, Ito  H,  et al.  Impact of smoking status on clinical outcome in oral cavity cancer patients.  Oral Oncol. 2012;48(2):186-191.PubMedGoogle ScholarCrossref
Research Letter
February 2018

Primary Cancer vs Competing Causes of Death in Survivors of Head and Neck Cancer

Author Affiliations
  • 1Department of Otolaryngology–Head and Neck Surgery, Saint Louis University School of Medicine, St Louis, Missouri
  • 2Saint Louis University Center for Health Outcomes Research, St Louis, Missouri
  • 3Department of Epidemiology, Saint Louis University College of Public Health and Social Justice, St Louis, Missouri
  • 4Harvard Medical School, Department of Otolaryngology, Massachusetts Eye and Ear Infirmary, Boston
JAMA Oncol. 2018;4(2):257-259. doi:10.1001/jamaoncol.2017.4478

Approximately 436 000 survivors of head and neck cancer (HNC) currently live in the United States, the number increasing because of decreasing smoking rates and increasing human papillomavirus incidence.1 Survivors, however, face several comorbidities that increase their risk of death from competing causes other than primary HNC.2

To our knowledge, no model exists estimating the survival time point when death from competing causes becomes likelier than death from primary HNC. Developing such models may improve clinicians’ long-term surveillance of HNC sequelae.1 We aimed to determine the probability and estimate the time point after diagnosis when death from competing causes becomes more common than that from primary HNC.

Methods

We retrospectively queried the Surveillance, Epidemiology, and End Results (SEER) 18 database3 from 2000 through 2014 for eligible cases of adults with head and neck squamous cell carcinoma (first or only cancer with known cause of death). Because SEER is a publicly available database with deidentified data, this study was exempt from consideration by the Saint Louis University Institutional Review Board. Binomial logistic regression analysis used year of follow-up as predictor, and cause of death (primary HNC and competing causes) as the outcome variables, while controlling for covariates (sex, race, marital status, treatment modality, stage, anatomic site, and county-level median family income). Reported adjusted odds ratios (aORs) were not adjusted using the multiple comparison analysis method.

Conditional probabilities (CP) of failure for both causes of death were plotted by year of follow-up. Statistical analyses were performed using SAS, version 9.4 (SAS Institute). Tests were 2 tailed and conducted at α = .05.

Results

There were 151 155 patients in the cohort. Each increasing year of survival was associated with 26% increased odds of death from competing causes (aOR, 1.26; 95% CI, 1.25-1.27). Male sex (aOR, 1.21; 95% CI, 1.16-1.26), divorced or separated status (aOR, 1.17; 95% CI, 1.11-1.23), and oral cavity cancer (aOR, 1.06; 95% CI, 1.01-1.11) were all associated with greater odds of death from competing causes compared with the variables’ reference groups. Black patients (aOR, 0.93; 95% CI, 0.88-0.98) had lower odds of death from competing causes compared with whites (Table).

Median survival time for the entire cohort was 80 months (range, 0-180 months). The first 56 months after diagnosis, primary HNC accounted for 73.4% of deaths. However, death from competing causes became more common than death from primary HNC after 57 months and later (competing cause CP at 57 months, 0.0023; 95% CI, 0.0020-0.0026; HNC death CP, 0.0027; 95% CI, 0.0025-0.0030) (Figure). Primary HNC accounted for 38.8% of deaths 6 to 10 years after diagnosis. By 11 to 15 years after diagnosis, primary HNC only accounted for 30.6% of deaths. The most common competing causes of death were cardiovascular disease, second primary cancers, and chronic obstructive pulmonary disease.

Discussion

We showed that each increasing year after HNC diagnosis was associated with a 26% increase in the odds of dying from competing causes, and death from competing causes became more common than primary HNC 5 years after diagnosis. This time point could guide the multidisciplinary cancer team to focus on competing risks that could cause death in HNC survivors, independent of primary disease or recurrence.

Eleven years after diagnosis, only 30.6% died from primary HNC. It is critical to develop lifelong surveillance for competing causes of death, which by this time accounted for greater than two-thirds of deaths. Besides preventing deaths from competing causes, surveillance could help mitigate treatment-related quality-of life issues.

The most common competing causes of death in this cohort were cardiovascular disease, chronic obstructive pulmonary disease, and second primary lung cancer, all linked to tobacco use.4 Despite decreasing national smoking rates, up to 80% of patients with HNC are either current or former smokers.5,6 Thus, tobacco cessation should be standard care for patients with HNC from diagnosis and throughout their lifetime.

In conclusion, more patients with HNC die from competing causes than primary cancer 5 years after diagnosis, and less than 1 in 3 die from primary HNC 11 years after diagnosis. Our study reaffirms the need for a multidisciplinary focus on HNC competing causes of death.

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Article Information

Corresponding Author: Nosayaba Osazuwa-Peters, BDS, MPH, CHES, Department of Otolaryngology-Head and Neck Surgery, Saint Louis University School of Medicine, 3635 Vista Ave, Sixth Floor, Desloge Towers, St Louis, MO 63110-2539 (nosazuwa@slu.edu).

Accepted for Publication: October 10, 2017.

Published Online: December 28, 2017. doi:10.1001/jamaoncol.2017.4478

Author Contributions: Mr Simpson and Dr Osazuwa-Peters had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: Simpson, Massa, Varvares, Osazuwa-Peters.

Acquisition, analysis, or interpretation of data: Simpson, Massa, Adjei Boakye, Antisdel, Stamatakis, Osazuwa-Peters.

Drafting of the manuscript: Simpson, Adjei Boakye, Osazuwa-Peters.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Simpson, Massa, Adjei Boakye.

Administrative, technical, or material support: Simpson, Massa, Antisdel, Osazuwa-Peters.

Study supervision: Massa, Antisdel, Varvares, Osazuwa-Peters.

Conflict of Interest Disclosures: None reported.

References
1.
Cohen  EE, LaMonte  SJ, Erb  NL,  et al.  American Cancer Society head and neck cancer survivorship care guideline.  CA Cancer J Clin. 2016;66(3):203-239.PubMedGoogle ScholarCrossref
2.
Piccirillo  JF.  Importance of comorbidity in head and neck cancer.  Laryngoscope. 2000;110(4):593-602.PubMedGoogle ScholarCrossref
3.
National Cancer Institute. Surveillance, Epidemiology, and End Results Program. Overview of the SEER program. 2016. https://seer.cancer.gov/about/overview.html. Accessed October 9, 2017.
4.
Massa  ST, Osazuwa-Peters  N, Christopher  KM,  et al.  Competing causes of death in the head and neck cancer population.  Oral Oncol. 2017;65:8-15.PubMedGoogle ScholarCrossref
5.
Hashibe  M, Brennan  P, Chuang  SC,  et al.  Interaction between tobacco and alcohol use and the risk of head and neck cancer: pooled analysis in the International Head and Neck Cancer Epidemiology Consortium.  Cancer Epidemiol Biomarkers Prev. 2009;18(2):541-550.PubMedGoogle ScholarCrossref
6.
Kawakita  D, Hosono  S, Ito  H,  et al.  Impact of smoking status on clinical outcome in oral cavity cancer patients.  Oral Oncol. 2012;48(2):186-191.PubMedGoogle ScholarCrossref
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