Prevalence of comorbidities and effect on survival in survivors of human papillomavirus-related and human papillomavirus-unrelated head and neck cancer in the United States.

BACKGROUND: The increasing incidence of human papillomavirus (HPV)-related head and neck cancer (HNC) has led to the increasing prevalence of survivors, yet to the best of the authors' knowledge the prevalence of comorbidities during the survivorship period and their effects on survival are relatively unknown. METHODS: In this retrospective cross-sectional study, individuals with a first incident primary diagnosis of HNC from 2004 through 2011 from the Surveillance, Epidemiology, and End Results (SEER)-Medicare-linked databases were included in the analysis and classified as patients with HPV-related or HPV-unrelated HNC. The presence of 30 comorbid conditions of interest was identified. Associations between comorbidity and treatment group as well as overall survival were evaluated. RESULTS: The study population consisted of 8025 patients with HPV-unrelated HNC and 2499 patients with HPV-related HNC. Hypertension, congestive heart failure, cerebrovascular disease, and chronic obstructive pulmonary disease all were found to be highly prevalent at the time of the cancer diagnosis and increased over time for both groups. These comorbidities were found at significantly lower rates in the HPV-related HNC population, yet were associated with an increased risk of death in both groups. The probabilities of developing cancer-related comorbidities such as pneumonia, dysphagia, weight loss, malnutrition, and dental issues rose significantly in both groups after treatment but were more likely in patients with HPV-related HNC. In both groups of patients, the presence of each comorbidity either at the time of diagnosis or during survivorship was associated with a significantly increased risk of death. CONCLUSIONS: There is a large burden of comorbidities in both patients with HPV-related and HPV-unrelated HNC, both of which are associated with decreased survival. Oncologic surveillance should not be limited to the evaluation of disease status, but also should include screening for the highly prevalent conditions associated with the risk of death.

Head and neck cancers, Version 2.2014. Clinical practice guidelines in oncology.

This selection from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Head and Neck Cancers focuses on glottic laryngeal cancer, which is the most common type of laryngeal cancer and has an excellent cure rate. The lymphatic drainage of the glottis is sparse, and early stage primaries rarely spread to regional nodes. Because hoarseness is an early symptom, most glottic laryngeal cancer is early stage at diagnosis. Updates to these guidelines for 2014 include revisions to "Principles of Radiation Therapy" for each site and "Principles of Surgery," and the addition of a new section on "Principles of Dental Evaluation and Management."

Prevalence of Comorbidities among Older Head and Neck Cancer Survivors in the United States.

OBJECTIVE: The aim of this study was to evaluate the prevalence of comorbidities among patients with head and neck squamous cell carcinoma (HNSCC) at the time of their cancer diagnosis and during their survivorship trajectory. The second aim was to evaluate the differences in comorbidities developed according to treatment type received. STUDY DESIGN: Retrospective cross-sectional. SETTING: SEER (Surveillance, Epidemiology, and End Results)-Medicare linked database. SUBJECTS AND METHODS: Individuals with a first-incident primary diagnosis of HNSCC from 2004 to 2011 per the SEER-Medicare database were included in analysis. The presence or absence of 30 comorbid conditions of interest was identified during distinct periods and analyzed according to treatment with surgery alone, primary (chemo)radiation, or surgery with (chemo)radiation. RESULTS: The study population consisted of 10,524 individuals diagnosed with HNSCC, with a mean age of 74.8 years. At diagnosis, hypertension, hyperlipidemia, chronic obstructive pulmonary disease, and diabetes were the most prevalent comorbidities, and they increased over time. The probability of developing treatment-related comorbidities such as pneumonia, dysphagia, weight loss, malnutrition, and dental issues rose significantly in the short and long term following treatment ( P < .05). By 5 years from cancer diagnosis, patients were most likely to have newly diagnosed hypertension, dysphagia, anemia, and weight loss. Primary surgery alone was associated with a lower risk of diagnosis with these treatment-related comorbidities, as compared with treatments involving radiation therapy and/or chemotherapy in the primary or adjuvant settings ( P < .05). CONCLUSIONS: There is a large burden of comorbidities among patients following HNSCC treatment, which warrant clinical attention during surveillance.

Priorities of human papillomavirus-associated oropharyngeal cancer patients at diagnosis and after treatment.

INTRODUCTION: Little is known regarding how human papillomavirus-positive oropharyngeal cancer (HPV-OPC) patient goals change with treatment. This study evaluates whether patient ranking of non-oncologic priorities relative to cure and survival shift after treatment as compared to priorities at diagnosis. MATERIALS AND METHODS: This is a prospective study of HPV-OPC patient survey responses at diagnosis and after treatment. The relative importance of 12 treatment-related priorities was ranked on an ordinal scale (1 as highest). Median rank (MR) was compared using Wilcoxon matched-pairs signed-rank tests. Prevalence of high concern for 11 treatment-related issues was compared using paired t-test. The effect of patient characteristics on change in priority rank and concern was evaluated using linear regression. RESULTS: Among 37 patients, patient priorities were generally unchanged after treatment compared with at diagnosis, with cure and survival persistently ranked top priority. Having a moist mouth uniquely rose in importance after treatment. Patient characteristics largely did not affect change in priority rank. Concerns decreased after treatment, except concern regarding recurrence. DISCUSSION: Treatment-related priorities are largely similar at diagnosis and after treatment regardless of patient characteristics. The treatment experience does not result in a shift of priorities from cure and survival to non-oncologic domains over cure and survival. The rise in importance of moist mouth implies that xerostomia may have been underappreciated as a sequelae of treatment. A decrease in most treatment-related concerns is encouraging, whereas the persistence of specific areas of concern may inform patient counseling.

Oral sampling methods are associated with differences in immune marker concentrations.

OBJECTIVE: To determine whether the concentration and distribution of immune markers in paired oral samples were similar. STUDY TYPE: Clinical research. STUDY DESIGN: Cross-sectional study. METHODS: Paired saliva and oral secretions (OS) samples were collected. The concentration of immune markers was estimated using Luminex multiplex assay (Thermo Fisher Scientific, Waltham, MA). For each sample, the concentration of respective immune markers was normalized to total protein present and log-transformed. Median concentrations of immune markers were compared between both types of samples. Intermarker correlation in each sampling method and across sampling methods was evaluated. RESULTS: There were 90 study participants. Concentrations of immune markers in saliva samples were significantly different from concentrations in OS samples. Oral secretions samples showed higher concentrations of immunoregulatory markers, whereas the saliva samples contained proinflammatory markers in higher concentration. CONCLUSION: The immune marker profile in saliva samples is distinct from the immune marker profile in paired OS samples. LEVEL OF EVIDENCE: 2b. Laryngoscope, 128:E214-E221, 2018.

Assessment of the Predictive Value of the Modified Frailty Index for Clavien-Dindo Grade IV Critical Care Complications in Major Head and Neck Cancer Operations.

IMPORTANCE: Functional status and physiologic deficits independent of age are being recognized for surgical risk stratification. Frailty is expressed as a combination of decreased physiologic reserve and multisystem impairments distinct from normal aging processes. OBJECTIVE: To assess the predictive value of the Modified Frailty Index (mFI) for Clavien-Dindo grade IV (CDIV) (intensive care unit-level complications) and grade V (mortality) after major head and neck oncologic surgery. DESIGN, SETTING, AND PARTICIPANTS: Retrospective analysis of prospectively collected American College of Surgeons National Surgical Quality Improvement Program data. All major head and neck cancer operations data were obtained from the January 1, 2006, to December 31, 2013, American College of Surgeons National Surgical Quality Improvement Program databases. Fifteen variables composed a previously validated mFI, with higher mFIs identifying more frail patients. Clavien-Dindo grade IV and mortality were defined using a preexisting mapping scheme from the Canadian Study of Health and Aging. Multivariable logistic regression analyses were performed. MAIN OUTCOMES AND MEASURES: The primary outcome measures were Clavien-Dindo Grade IV critical care complications and Grade V complications (mortality). Second outcomes included morbidity, readmission, and reoperation. RESULTS: There were 1193 major head and neck operations in the American College of Surgeons National Surgical Quality Improvement Program databases, with 86 (7.2%) CDIV complications. The mean (SD) age of all patients was 63.4 (12.4) years, and 67.7% (807 of 1193) were male. Clavien-Dindo grade IV significantly increased from 4.6% (22 of 483) to 100% (1 of 1) from nonfrail to the frailest patients (R2 = 0.79, P < .001). Mortality increased with the mFI (but not significantly) from 0.8% (4 of 483) to 3.6% (2 of 55) (R2 = 0.46, P = .42). Overall morbidity was not significantly associated or correlated with the mFI. On cross tabulation, increases in the mFI led to more CDIV complications in patients undergoing glossectomy (P = .03), mandibulectomy (P = .02), or laryngectomy (P = .002). Patients undergoing pharyngectomy or esophagectomy did not have significant increases in CDIV complications by the mFI. The coefficients of determination for each category were R2 = 0.62 for glossectomy, R2 = 0.72 for mandibulectomy, R2 = 0.97 for laryngectomy, R2 = 0.94 for pharyngectomy, and R2 = 1.00 for esophagectomy. On multivariable analysis, the mFI was associated with CDIV complications (odds ratio, 1.65; 95% CI, 1.15-2.37) but not mortality (odds ratio, 0.78; 95% CI, 0.34-1.76). CONCLUSIONS AND RELEVANCE: The mFI is predictive of postoperative critical care support after surgery for head and neck cancer. Specifically, increases in mFIs were strongly associated with CDIV complications for glossectomy, mandibulectomy, and laryngectomy. Classifying patients by their functional status using the mFI may help predict outcomes after head and neck oncologic surgery.

Detection of somatic mutations and HPV in the saliva and plasma of patients with head and neck squamous cell carcinomas.

To explore the potential of tumor-specific DNA as a biomarker for head and neck squamous cell carcinomas (HNSCC), we queried DNA from saliva or plasma of 93 HNSCC patients. We searched for somatic mutations or human papillomavirus genes, collectively referred to as tumor DNA. When both plasma and saliva were tested, tumor DNA was detected in 96% of 47 patients. The fractions of patients with detectable tumor DNA in early- and late-stage disease were 100% (n = 10) and 95% (n = 37), respectively. When segregated by site, tumor DNA was detected in 100% (n = 15), 91% (n = 22), 100% (n = 7), and 100% (n = 3) of patients with tumors of the oral cavity, oropharynx, larynx, and hypopharynx, respectively. In saliva, tumor DNA was found in 100% of patients with oral cavity cancers and in 47 to 70% of patients with cancers of the other sites. In plasma, tumor DNA was found in 80% of patients with oral cavity cancers, and in 86 to 100% of patients with cancers of the other sites. Thus, saliva is preferentially enriched for tumor DNA from the oral cavity, whereas plasma is preferentially enriched for tumor DNA from the other sites. Tumor DNA in saliva was found postsurgically in three patients before clinical diagnosis of recurrence, but in none of the five patients without recurrence. Tumor DNA in the saliva and plasma appears to be a potentially valuable biomarker for detection of HNSCC.

Management of cervical metastases in advanced squamous cell carcinoma of the base of tongue.

OBJECTIVE: To clarify the role of neck dissection following primary radiotherapy for treatment of squamous cell carcinoma of the base of tongue. DESIGN: Case series. SETTING: Academic, tertiary care medical center. PATIENTS OR OTHER PARTICIPANTS: A consecutive series of 45 patients with biopsy-proven squamous cell carcinoma of the base of tongue and cervical metastases treated with primary radiotherapy at The University of California, San Francisco, was examined. Patients with a prior history of neck irradiation, neck dissection, or head and neck cancer within 5 years were excluded. MAIN OUTCOME MEASURES: Overall survival and regional control. RESULTS: Of the 45 patients treated with definitive radiotherapy, 25 (56%) achieved a complete response, 13 (29%) achieved a partial response, 4 (9%) were nonresponders, and 3 (7%) did not complete radiotherapy. Two thirds of the complete responders had N2 or N3 disease; 3 had recurrences in the neck, 1 of which was an isolated neck recurrence. Of the 13 partial responders, 5 had isolated persistence of disease, with 4 undergoing neck dissections. The only long-term survivors among the partial responders were those 4 who underwent a neck dissection. Overall survival was 50% at 3 years and 32% at 5 years. Regional control for complete responders was 84% at 5 years. CONCLUSIONS: The low rate of isolated regional recurrence in patients with a complete response to radiotherapy supports the practice of surveillance alone in such patients. Patients with less than a complete response appear to benefit from prompt surgical salvage.

Mandibular osteotomies for access to select parapharyngeal space neoplasms.

BACKGROUND: Tumors involving the parapharyngeal space present a challenge of surgical access. METHODS: We reviewed all parapharyngeal space tumors resected at the University of California, San Francisco, between 2003 and 2006 and identified 14 patients who had a mandibular osteotomy to enhance surgical access to the parapharyngeal space. RESULTS: The surgical approach for the 14 patients who had a mandibulotomy was accomplished via either 1 or 2 mandibular osteotomies. A single paramedian osteotomy between the canine and the first premolar was used in 4 cases, whereas a combination of a horizontal osteotomy above the lingula and a paramedian osteotomy between the canine and first premolar was employed in 8 cases. A lingual dental splint and rigid fixation were used to achieve mandibular stabilization and fixation. CONCLUSION: We found that the single and double mandibular osteotomies provided excellent surgical access allowing for total tumor removal with few sequelae.

Intensity-modulated chemoradiation for treatment of stage III and IV oropharyngeal carcinoma: the University of California-San Francisco experience.

BACKGROUND: Treatment outcomes for stage III and IV oropharyngeal carcinoma treated with intensity-modulated radiotherapy (IMRT) and concurrent chemotherapy without prior surgical resection were reviewed. METHODS: Between April 2000 and September 2004, 71 patients underwent IMRT concurrent with chemotherapy without prior surgical resection for stage III and IV oropharyngeal carcinoma. Chemotherapy was platinum based. The gross tumor volume (GTV) received 70 Gy in 2.12 Gy per fraction. The high-risk clinical tumor volume (CTV) received 59.4 Gy in 1.80 Gy per fraction, and the low-risk CTV received 54 Gy in 1.64 Gy per fraction. RESULTS: With a median follow-up of 33 months, the 3-year local, regional, and locoregional progression-free probabilities were 94%, 94%, and 90%, respectively. The 3-year overall survival estimate was 83%. Locoregional failures occurred in the GTV in 7 patients. Acute grade 3 or 4 toxicity developed in 35 patients. A feeding gastrostomy was placed in 25 patients. Late xerostomia was grade 0 in 16 patients, grade 1 in 31 patients, and grade 2 in 24 patients at last follow-up. No patients experienced grade 3 or 4 late toxicity, except for 1 who developed osteoradionecrosis of the mandible. CONCLUSIONS: Excellent local and regional control was achieved with IMRT and concurrent chemotherapy without prior surgical resection in the treatment of stage III and IV oropharyngeal carcinoma. Significant sparing of the parotid glands and other critical normal tissues was possible using IMRT with moderate acute toxicities and minimal severe late effects.