This review highlights the evidence-based data to support current best management practices for patients with recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). Current limitations and areas of emerging therapeutics are also emphasized. The cornerstone of palliation for patients with R/M HNSCC is a platinum-based backbone. Platinum doublets induce higher response rates than single agents but do not demonstrate a survival advantage and are associated with increased toxicity. The only regimen to demonstrate survival superiority is platinum, fluorouracil, and cetuximab, a monoclonal antibody directed against the epidermal growth factor receptor (EGFR). EGFR inhibitors, including monoclonal antibodies and tyrosine kinase inhibitors, have achieved only modest success in R/M HNSCC, illustrating the importance of identifying predictive biomarkers and finding ways to overcome mechanisms of resistance. Although phosphoinositide 3-kinase pathway alterations are present at a high rate in HNSCC, the identification of efficacious agents in patients with activating alterations has yet to be discovered. Immunotherapy represents an attractive treatment strategy for R/M HNSCC, with promising preliminary data from studies involving immune checkpoint blockade and toll-like receptor agonists. Human papillomavirus has a prognostic role in R/M disease; therefore, stratification of patients by human papillomavirus status in clinical trials is indicated. Although under-represented in clinical trials, elderly patients experience similar survival outcomes compared with younger patients, albeit with increased toxicity. Despite therapeutic advances, prognosis nonetheless remains poor for patients with R/M HNSCC. Enrollment of patients onto clinical trials to investigate novel therapeutics and identify predictive biomarkers is necessary to further refine and improve outcomes.

Purpose Tumor mutational burden detected by tissue next generation sequencing (NGS) correlates with checkpoint inhibitor response. However, tissue biopsy may be costly and invasive. We sought to investigate the association between hyper-mutated blood-derived circulating tumor DNA (ctDNA) and checkpoint inhibitor response. Experimental Design We assessed 69 patients with diverse malignancies who received checkpoint inhibitor-based immunotherapy and blood-derived circulating tumor DNA (ctDNA) NGS testing (54–70 genes). Rates of stable disease (SD) ≥6 months, partial and complete response (PR, CR), as well as progression-free survival (PFS) and overall survival (OS) were assessed based on total and VUS alterations. Results Statistically significant improvement in PFS was associated with high versus low alteration number in variants of unknown significance (VUS, >3 alterations versus VUS ≤3 alterations), SD≥6 months/PR/CR 45% versus 15%, respectively; p = 0.014. Similar results were seen with high versus low total alteration number (characterized plus VUS, ≥6 versus <6). Statistically significant OS improvement was also associated with high VUS alteration status. Two-month landmark analysis showed that responders versus non-responders with VUS>3 had a median PFS of 23 versus 2.3 months (p = 0.0004). Conclusion Given the association of alteration number on liquid biopsy and checkpoint inhibitor-based immunotherapy outcomes, further investigation of hyper-mutated ctDNA as a predictive biomarker is warranted.

A positive surgical margin (PSM) following cancer resection oftentimes necessitates adjuvant treatments and carries significant financial and prognostic implications. We sought to compare PSM rates for the ten most common solid cancers in the United States, and to assess trends over time. Over 10 million patients were identified in the National Cancer Data Base from 1998–2012, and 6.5 million had surgical margin data. PSM rates were compared between two time periods, 1998–2002 and 2008–2012. PSM was positively correlated with tumor category and grade. Ovarian and prostate cancers had the highest PSM prevalence in women and men, respectively. The highest PSM rates for cancers affecting both genders were seen for oral cavity tumors. PSM rates for breast cancer and lung and bronchus cancer in both men and women declined over the study period. PSM increases were seen for bladder, colon and rectum, and kidney and renal pelvis cancers. This large-scale analysis appraises the magnitude of PSM in the United States in order to focus future efforts on improving oncologic surgical care with the goal of optimizing value and improving patient outcomes.

IMPORTANCE Opioid misuse and overuse has become an epidemic. Chronic opioid use among oral cavity cancer patients after surgery has not been described. OBJECTIVES To assess the prevalence of chronic opioid use in patients undergoing surgery for oral cavity cancer, and evaluate possible associated clinical factors; and the association between opioid use and survival. DESIGN, SETTING, AND PARTICIPANTS For this retrospective cohort study of patients undergoing surgery for oral cavity cancer a consecutive sample of 99 patients between January 1, 2011, and September 30, 2016, were identified through the institutional cancer registry from a single academic center. EXPOSURES Surgery for oral cavity cancer. MAIN OUTCOMES AND MEASURES Chronic opioid use, defined as more than 90 days from surgery. Factors associated with chronic opioid use were investigated by univariable and multivariable logistic regression. The Kaplan-Meier method and Cox proportional hazards model were used to assess overall survival and disease-free survival. RESULTS The mean (SD) patient age was 62.6 (14.3) years; 60 patients (60%) were male. Chronic opioid use was observed in 41 patients (41%). On multivariable logistic regression, preoperative opioid use (odds ratio [OR], 5.6; 95% CI, 2.2-14.3), tobacco use (OR, 2.8; 95% CI, 1.0-8.0), and development of persistence, recurrence, or a second primary tumor (OR, 2.8; 95% CI, 1.0-7.4) were associated with chronic opioid use. Among preoperative opioid users, estimated overall survival (hazard ratio [HR], 3.2; 95% CI, 1.4-7.1) was decreased, and chronic opioid use was associated with decreased disease-free survival (HR, 2.7; 95% CI, 1.1-6.6). CONCLUSIONS AND RELEVANCE In patients undergoing surgery for oral cavity tumors, the prevalence of chronic opioid use was considerable. Preoperative opioid use, tobacco use, and development of persistence, recurrence, or a second primary tumor were associated with chronic opioid use after surgery, and both preoperative and chronic opioid use were associated with decreased survival.

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