What Is the Role of Elective Neck Dissection in the Management of Patients With Buccal Squamous Cell Carcinoma and Clinically Negative Neck?

PURPOSE: Buccal squamous cell carcinoma (BSCC) is rare in the United States. Given its location, few anatomic barriers to spread exist and it has been found to have a high locoregional recurrence rate. The role of elective neck dissection (END) in patients with clinically negative neck (N0) is not clear. This study aims to answer the following research question: Among patients with N0 BSCC, does END improve locoregional control rates, distant metastasis rates, and 2- and 5-year survival rates? MATERIALS AND METHODS: A retrospective cohort study was conducted. The sample included patients who received a diagnosis of BSCC. The primary predictor variable was END status (yes or no). Five institutions participated between June 2001 and June 2011: University of Washington, University of Michigan, University of Tennessee, North Memorial Oral and Maxillofacial Surgery in Minnesota, and Head and Neck Surgical Associates (Portland, OR). The primary outcome variable was locoregional recurrence. Secondary outcome variables were distant metastasis and 2- and 5-year survival rates. Other variables collected were demographic characteristics, initial operation, adjuvant therapy, clinical and pathologic data, and staging. Kaplan-Meier and Cox proportional hazards statistics were computed. RESULTS: The sample was composed of 98 patients with clinical N0 BSCC. The mean age was 66 years (range, 30-88 years), and 54% were men. Of the patients, 74 (76%) underwent END. The locoregional recurrence-free rate was 61% for END versus 38% for no END (P = .042). The distant metastasis rate was 4% for END versus 9% for no END. The 2- and 5-year disease-free survival rates were 91% and 75% (P = .042), respectively, for END and 85% and 63% (P = .019), respectively, for no END. CONCLUSIONS: END had a therapeutic effect, as evidenced by a lower locoregional recurrence rate, lower distant metastasis rate, and improved 2- and 5-year survival rates.

Methods to reduce postoperative surgical site infections after head and neck oncology surgery.

Head and neck cancer surgery is often a complex multi-step procedure that includes major resections, vascularised tissue reconstruction, and extensive neck dissection. The upper aerodigestive tract mucosal lining is often disrupted during surgery, which requires the management of a clean-contaminated field and the need to reconstruct the mucosal lining. With bacterial contamination, surgical site infections (SSI) are a serious complication that can result in delayed wound healing, wound breakdown, fistula formation, and compromised tissue reconstruction. Methods to reduce SSI in patients with head and neck cancer have been intensely researched, yielding evolving and varied practice patterns. In this Review, we outline the data supporting perioperative antibiotic prophylaxis for clean-contaminated surgeries, which suggest that clindamycin is an inadequate prophylactic antibiotic therapy in the reduction of SSI, and that prolonged antibiotic courses have no established benefit. For salvage laryngectomy after radiotherapy with or without chemotherapy, reconstruction with vascularised tissue reduces the frequency and severity of pharyngocutaneous fistula formation. These evidence-based recommendations have been shown to reduce the chance of SSI after head and neck surgery.

Integrative genomics in combination with RNA interference identifies prognostic and functionally relevant gene targets for oral squamous cell carcinoma.

In oral squamous cell carcinoma (OSCC), metastasis to lymph nodes is associated with a 50% reduction in 5-year survival. To identify a metastatic gene set based on DNA copy number abnormalities (CNAs) of differentially expressed genes, we compared DNA and RNA of OSCC cells laser-microdissected from non-metastatic primary tumors (n = 17) with those from lymph node metastases (n = 20), using Affymetrix 250K Nsp single-nucleotide polymorphism (SNP) arrays and U133 Plus 2.0 arrays, respectively. With a false discovery rate (FDR)<5%, 1988 transcripts were found to be differentially expressed between primary and metastatic OSCC. Of these, 114 were found to have a significant correlation between DNA copy number and gene expression (FDR<0.01). Among these 114 correlated transcripts, the corresponding genomic regions of each of 95 transcripts had CNAs differences between primary and metastatic OSCC (FDR<0.01). Using an independent dataset of 133 patients, multivariable analysis showed that the OSCC-specific and overall mortality hazards ratio (HR) for patients carrying the 95-transcript signature were 4.75 (95% CI: 2.03-11.11) and 3.45 (95% CI: 1.84-6.50), respectively. To determine the degree by which these genes impact cell survival, we compared the growth of five OSCC cell lines before and after knockdown of over-amplified transcripts via a high-throughput siRNA-mediated screen. The expression-knockdown of 18 of the 26 genes tested showed a growth suppression ≥ 30% in at least one cell line (P<0.01). In particular, cell lines derived from late-stage OSCC were more sensitive to the knockdown of G3BP1 than cell lines derived from early-stage OSCC, and the growth suppression was likely caused by increase in apoptosis. Further investigation is warranted to examine the biological role of these genes in OSCC progression and their therapeutic potentials.

How does the close surgical margin impact recurrence and survival when treating oral squamous cell carcinoma?

PURPOSE: The surgical margin is the main prognostic factor over which the surgeon has control during resection of oral squamous cell carcinoma (OSCC). This study examined the association between surgical excision margins of patients with OSCC and outcomes of disease-free and overall survival. MATERIALS AND METHODS: The authors implemented a retrospective cohort study. The sample was composed of patients with OSCC having resection as their initial treatment. The predictor variable was the pathologic surgical margin, defined as clear (>5 mm), close (1 to 5 mm), or involved (<1 mm). The outcome variables were disease-free (absence of locoregional recurrence) and overall survival. Data were analyzed using Kaplan-Meier survival curves and Cox regression hazard model. RESULTS: The sample was composed of 54 patients with a mean age of 60.5 years (range, 19 to 85 yr) and 26% were women. The 2- and 5-year overall survival rates were 59 and 50%, respectively. The clear surgical margin group showed higher disease-free survival rates than patients with close and involved margins (5-yr probability, 0.78 vs 0.43 and 0.29; P = .014) and a trend toward increased overall survival at 2 and 5 years (P = .093). CONCLUSION: The results suggest that the presence of a close surgical margin (1 to 5 mm) is an adverse risk feature comparable to an involved margin and therefore is associated with decreased disease-free and overall survival. Future studies are needed to replicate these findings before they can be used as a basis for clinical recommendations.

The prevalence of lymph node metastases in clinically N0 necks with oral cavity squamous cell carcinoma: is CT good enough for nodal staging?

BACKGROUND: Nodal metastases and extracapsular extension (ECE) are important prognostic indicators. However, the diagnostic accuracy of CT is still limited for patients with clinically N0 neck. PURPOSE: To determine the prevalence of lymph node (LN) metastases and ECE for oral cavity squamous cell carcinoma (SCC) patients with clinical and CT negative preoperative neck. MATERIAL AND METHODS: Thirty-two patients with N0 oral cavity SCC who underwent neck dissection were included in this retrospective analysis. The size of LN was measured on transverse CT images, and radiological size criterion was based upon a minimal axial diameter of 10 mm. Pathology was used as the standard reference. Imaging and histopathological correlation was done for 132 LN levels in the 32 patients. RESULTS: Fourteen of 32 patients (44%) had metastatic nodes and six patients had ECE. Among 132 LN levels, 22 levels (17%) had metastatic LNs (level I 5/37, level II 8/39, level III 7/35, level IV 2/18), and eight of 22 levels with metastases had ECE. Poorly differentiated histology was a predictive factor for LN metastases or ECE (poorly versus well and moderately differentiated SCC: P=0.07 for LN metastases and P=0.08 for ECE, respectively). T-classification was also an important predictor for occult nodal metastases (2 of 10 patients in T1, 12 of 22 patients in T2-4), although it did not reach statistical significance (P=0.11). CONCLUSION: Diagnostic accuracy of CT is limited among N0 oral cavity SCC patients. Neck dissection should be performed, particularly for patients with poorly differentiated SCC or higher T-classification.

Head and neck free flap reconstruction in patients older than 80 years.

BACKGROUND: Free tissue transfer is a reliable method for reconstruction of head and neck defects. With the growing number of octogenarians in the population, it is important to understand how these patients respond to these procedures. METHODS: Through a retrospective chart review of patients who underwent a free-flap reconstruction from 2000 to 2010 at an academic medical center, 48 patients, aged 80 years and older, were compared with a control group consisting of 97 similar patients, aged younger than 80 years. We compared the intensive care unit (ICU) length of stay, overall hospital stay, and the incidence of perioperative complications between the cohorts. RESULTS: The average length of stay in the ICU was significantly longer for the octogenarian group as compared with the younger group (101 vs. 41 hours, p-value = 0.007). The average length of hospital stay was not significantly different between the two groups (difference = 40 hours, p-value = 0.102). The incidence of perioperative complication was 75% in the octogenarian group and 60% in the younger group (p-value = 0.095). There were two flap failures in the younger group, and none in the octogenarian group. There was a significantly higher rate of death within 30 days in the octogenarian group. CONCLUSIONS: Microvascular free tissue transfer is a reliable and safe method of reconstruction of head and neck defects in patients over 80 years of age. Patients should be counseled about the potential risks of increased incidence of medical complications, ICU length of stay, and rate of perioperative death when recommended to undergo free tissue transfer reconstruction.

Prevention and Management of Osteoradionecrosis in Patients With Head and Neck Cancer Treated With Radiation Therapy: ISOO-MASCC-ASCO Guideline.

PURPOSE: To provide evidence-based recommendations for prevention and management of osteoradionecrosis (ORN) of the jaw secondary to head and neck radiation therapy in patients with cancer. METHODS: The International Society of Oral Oncology-Multinational Association for Supportive Care in Cancer (ISOO-MASCC) and ASCO convened a multidisciplinary Expert Panel to evaluate the evidence and formulate recommendations. PubMed, EMBASE, and Cochrane Library databases were searched for randomized controlled trials and observational studies, published between January 1, 2009, and December 1, 2023. The guideline also incorporated systematic reviews conducted by ISOO-MASCC, which included studies published from January 1, 1990, through December 31, 2008. RESULTS: A total of 1,539 publications were initially identified. There were 487 duplicate publications, resulting in 1,052 studies screened by abstract, 104 screened by full text, and 80 included for systematic review evaluation. RECOMMENDATIONS: Due to limitations of available evidence, the guideline relied on informal consensus for some recommendations. Recommendations that were deemed evidence-based with strong evidence by the Expert Panel were those pertaining to best practices in prevention of ORN and surgical management. No recommendation was possible for the utilization of leukocyte- and platelet-rich fibrin or photobiomodulation for prevention of ORN. The use of hyperbaric oxygen in prevention and management of ORN remains largely unjustified, with limited evidence to support its practice.Additional information is available at www.asco.org/head-neck-cancer-guidelines.

Clarification of the margin status by the multidisciplinary tumor board following transoral robotic surgery for p16 positive oropharyngeal squamous cell carcinoma.

Objectives: Margin status interpretation following transoral robotic surgery (TORS) for oropharyngeal squamous cell carcinoma (OPSCC) is challenging. This study aims to assess the discrepancy between status of margins as reported by the pathologist versus as determined by multi-disciplinary team review (MDTB). Methods: A retrospective study of 57 patients with OPSCC who underwent TORS from January 2010 to December 2016 was conducted. Our primary outcome measure was the discrepancy between the surgical specimen margins as described in the pathology report versus final margin status that was determined after the multi-disciplinary team discussion. Fisher's exact test was used. Results: Based on the pathologist-report, 29 subjects (51%) had positive margins, compared to 2 (4%) after multi-disciplinary team discussion. Receipt of chemotherapy correlated with final margin status as determined by MDTB, not with initial main specimen margins (p = .02 and p = .08, respectively). With a median follow up of 28.4 months, two subjects (4%) had loco-regional recurrence. Conclusion: Following TORS, there was a significant discrepancy between status of margins as reported by the pathologist versus as determined by MDTB review. Chemotherapy was avoided in 93.1% of cases that were originally reported as positive margins by the pathologist with an acceptably low recurrence rate. Level of evidence: 4.

Radiation therapy for low- and high-risk perineural invasion in head and neck cutaneous squamous cell carcinoma: Clinical outcomes and patterns of failure.

BACKGROUND: Perineural invasion (PNI) in head and neck squamous cell carcinoma (HNSCC) portends poor prognosis. Extent of treatment of nerve pathways with varying degrees of PNI and patterns of failure following elective neural radiotherapy (RT) remain unclear. METHODS: Retrospective review of HNSCC patients with high-risk (clinical/gross, large-nerve, extensive) or low-risk (microscopic/focal) PNI who underwent curative-intent treatment from 2010 to 2021. RESULTS: Forty-four patients (mean follow-up 22 months; 59% high-risk, 41% low-risk PNI) were included. Recurrence following definitive treatment occurred in 31% high-risk and 17% low-risk PNI patients. Among high-risk patients, 69% underwent surgery with post-operative RT and 46% underwent elective neural RT. Local control (83% low-risk vs. 75% high-risk), disease-free, and overall survival did not differ between groups. CONCLUSIONS: High local control rates were achieved in high-risk PNI patients treated with adjuvant or primary RT, including treatment of both involved and uninvolved, communicating cranial nerves, with few failures in electively treated regions.

Oncologic outcomes of salvage surgery and immune checkpoint inhibitor therapy in recurrent head and neck squamous cell carcinoma: A single-institution retrospective study.

BACKGROUND: Survival outcomes in recurrent head and neck squamous cell carcinoma (HNSCC) are poor. This study aimed to compare survival outcomes between salvage surgery and immunotherapy in patients with recurrent advanced HNSCC. METHODS: Patients with advanced stage (stage III or IV) recurrent HNSCC following treatment with platinum-based chemotherapy were included. Survival was estimated using the Kaplan-Meier method, and Cox regression was used for multivariate logistic regression. RESULTS: Two-year overall survival after salvage surgery was 68.6% and after immunotherapy patients was 24.6%. Multivariate logistic regression showed that salvage surgery was associated with improved survival without statistical significance (hazard ratio [HR] 0.12, p = 0.25). Subgroup analysis of patients with oral cavity/oropharyngeal cancer noted improved survival with salvage surgery over immunotherapy (HR 0.006, p = 0.01) and decreased survival with neutrophil-to-lymphocyte ratio (NLR) > 5 (HR 6.4, p = 0.02). CONCLUSION: Our retrospective single-institutional data suggest that resectable advanced stage recurrent HNSCC may have improved survival with salvage surgery in appropriately selected patients, but larger prospective studies are required.

Impact of HPV status on immune responses in head and neck squamous cell carcinoma.

The main objective of our study was to understand the impact of immune cell composition and the tumor-reactivity of tumor infiltrating lymphocytes (TIL) in HPV-positive (HPV+) and HPV-negative (HPV-) head and neck squamous cell carcinoma (HNSCC). TIL cultures were established from primary HNSCC tumors, the T cell subsets were phenotypically characterized using flow cytometry, and Interferon (IFN)-γ ELISA assay was used to determine TIL function. NanoString Immune Profiler was used to determine an immune signature by HPV-status, and multiplex immunohistochemistry (MIHC) was used to quantify immune cell distributions and their spatial relationships. Results showed that HPV+ and HPV- HNSCC had similar capacity to expand IFN-γ reactive TIL populations, and these TIL populations had similar characteristics. NanoString analysis revealed increased differential expression of genes related to B cell functions in HPV+ HNSCC, which were significant at a Benjamini-Yekutieli adjusted p-value of < 0.001. MIHC also displayed increased CD8+ T cell and CD19/CD20+ B cell densities in the tumor region of HPV+ HNSCC as opposed to HPV- HNSCC (p < 0.01). Increases in a combined metric of tumor B cell content and stromal plasma cell content was associated with increased progression-free survival in HPV- HNSCC patients treated with immune checkpoint inhibitor therapy (p = 0.03). In summary, TIL populations expanded from HPV+ and HPV- HNSCC displayed similar IFN-γ reactivity. However, we identified a strong B-cell signature present within HPV+ HNSCC, and higher B and plasma cell content associated with improved PFS in HPV- HNSCC patients treated with immune checkpoint inhibitors.

Trends in Positive Surgical Margins in cT1-T2 Oral Cavity Squamous Cell Carcinoma.

OBJECTIVES/HYPOTHESIS: To evaluate trends in contemporary positive surgical margin incidence in cT1-T2 oral cavity squamous cell carcinoma and to evaluate factors associated with surgical margin status. STUDY DESIGN: Retrospective analysis of large dataset. METHODS: Retrospective analysis of the National Cancer Database. RESULTS: Between 2004 and 2016, 39,818 patients with cT1 or cT2 oral cavity squamous cell carcinoma received primary curative-intent surgery. Positive surgical margins were present in 7.95% of patients, and univariable adjusted probability of positive surgical margins over the study period declined by 1% per year (odds ratio [OR], 0.99; 95% confidence interval [CI], 0.98-1.0; P = .049). Multivariable regression revealed the annual rate of positive surgical margins declined significantly (OR, 0.95 per year; 95% CI, 0.92-0.97; P < .001). Factors associated with increased odds of positive surgical margins included cT2 disease, subsite, understaged disease, lymphovascular invasion, tumor grade, and positive lymph nodes. Race and socioeconomic status were not associated with surgical margin status. Treatment at an academic center was associated with increased time to definitive surgery (median 35 days IQR 22-50 vs. median 27 days IQR 14-42; P < .001) and a 20% reduction in positive surgical margin rate (OR, 0.80; 95% CI, 0.71-0.90; P < .001). Treatment at high-volume centers was less likely to be associated with positive surgical margins (OR, 0.85; 95% CI, 0.74-0.98; P = .02). CONCLUSION: Surgical subsite, clinical T and N category, presence of lymphovascular invasion, and histologic grade were independent predictors of positive surgical margins. Patients are increasingly being treated at high-volume and academic centers. Overall, the rate of positive surgical margins in cT1-T2 oral cavity squamous cell carcinoma is decreasing. LEVEL OF EVIDENCE: 4 Laryngoscope, 132:1962-1970, 2022.

Performance status (PS) as a predictor of poor response to immune checkpoint inhibitors (ICI) in recurrent/metastatic head and neck cancer (RMHNSCC) patients.

BACKGROUND: Anti-PD1 checkpoint inhibitors (ICI) represent an established standard-of-care for patients with recurrent/metastatic head and neck squamous cell carcinoma (RMHNSCC). Landmark studies excluded patients with ECOG performance status (PS) ≥2; the benefit of ICI in this population is therefore unknown. METHODS: We retrospectively reviewed RMHNSCC patients who received 1+ dose of ICI at our institution between 2013 and 2019. Demographic and clinical data were obtained; the latter included objective response (ORR), toxicity, and any unplanned hospitalization (UH). Associations were explored using uni- and multivariate analysis. Overall survival (OS) was estimated using a Cox proportional hazards model; ORR, toxicity, and UH were evaluated with logistic regression. RESULTS: Of the 152 patients, 29 (19%) had an ECOG PS ≥2. Sixty-six (44%) experienced toxicity; 54 (36%) had a UH. A multivariate model for OS containing PS, smoking status, and HPV status demonstrated a strong association between ECOG ≥2 and shorter OS (p < 0.001; HR = 3.30, CI = 2.01-5.41). An association between OS and former (vs. never) smoking was also seen (p < 0.001; HR = 2.17, CI = 1.41-3.35); current smoking did not reach statistical significance. On univariate analysis, poor PS was associated with inferior ORR (p = 0.03; OR = 0.25, CI = 0.06-0.77) and increased UH (p = 0.04; OR = 2.43, CI = 1.05-5.71). There was no significant association between toxicity and any patient characteristic. CONCLUSIONS: We observed inferior OS, ORR, and rates of UH among ICI-treated RMHNSCC patients with ECOG 2/3. Our findings help frame discussion of therapeutic options in this poor-risk population.

High End-of-Life Health Care Utilization in a Contemporary Cohort of Head and Neck Cancer Patients Treated with Immune Checkpoint Inhibitors.

Background/Objective: End-of-life health care utilization (EOLHCU) is largely uncharacterized among patients with recurrent/metastatic head and neck squamous cell carcinomas (RMHNSCC), particularly now that immune checkpoint inhibitors (ICI) have been introduced to the treatment landscape. We examined this in a single-institution, retrospective study. Design/Settings: We utilized a database of deceased, ICI-treated RMHNSCC patients to obtain demographic and EOLHCU data, the latter of which included advanced care plan documentation (ACPD) and systemic therapy or emergency room (ER)/hospital/intensive care unit (ICU) admission within 30 days of death (DOD). This was compared with a cohort of deceased thoracic malignancy (TM) patients in an exploratory analysis. Multivariate analysis was performed to examine for association between patient factors (such as age, Eastern Cooperative Oncology Group (ECOG) performance status, or smoking status) and overall survival (OS); associations between the said patient factors and EOLHCU were also evaluated. This study was conducted at an academic, tertiary center in the United States. Results: The RMHNSCC patients (n = 74) were more likely to have ACPD (p < 0.01), an emergency department visit (p < 0.01), and/or hospital admission (p < 0.01) within 30 DOD relative to the TM group. There was no difference in ICU admissions, ICU deaths, or systemic therapy at end of life (EOL). The OS declined in association with ECOG performance status (PS) and smoking. No association was observed between patient factors and any EOLHCU metric. Conclusions: At our center, patients with ICI-treated RMHNSCC have higher rates of both ACPD and EOLHCU, suggesting high symptom burden and representing opportunities for further study into supportive care augmentation.

Integrative analysis of DNA copy number and gene expression in metastatic oral squamous cell carcinoma identifies genes associated with poor survival.

BACKGROUND: Lymphotropism in oral squamous cell carcinoma (OSCC) is one of the most important prognostic factors of 5-year survival. In an effort to identify genes that may be responsible for the initiation of OSCC lymphotropism, we examined DNA copy number gains and losses and corresponding gene expression changes from tumor cells in metastatic lymph nodes of patients with OSCC. RESULTS: We performed integrative analysis of DNA copy number alterations (CNA) and corresponding mRNA expression from OSCC cells isolated from metastatic lymph nodes of 20 patients using Affymetrix 250 K Nsp I SNP and U133 Plus 2.0 arrays, respectively. Overall, genome CNA accounted for expression changes in 31% of the transcripts studied. Genome region 11q13.2-11q13.3 shows the highest correlation between DNA CNA and expression. With a false discovery rate < 1%, 530 transcripts (461 genes) demonstrated a correlation between CNA and expression. Among these, we found two subsets that were significantly associated with OSCC (n = 122) when compared to controls, and with survival (n = 27), as tested using an independent dataset with genome-wide expression profiles for 148 primary OSCC and 45 normal oral mucosa. We fit Cox models to calculate a principal component analysis-derived risk-score for these two gene sets ('122-' or '27-transcript PC'). The models combining the 122- or 27-transcript PC with stage outperformed the model using stage alone in terms of the Area Under the Curve (AUC = 0.82 or 0.86 vs. 0.72, with p = 0.044 or 0.011, respectively). CONCLUSIONS: Genes exhibiting CNA-correlated expression may have biological impact on carcinogenesis and cancer progression in OSCC. Determination of copy number-associated transcripts associated with clinical outcomes in tumor cells with an aggressive phenotype (i.e., cells metastasized to the lymph nodes) can help prioritize candidate transcripts from high-throughput data for further studies.

A genetic expression profile associated with oral cancer identifies a group of patients at high risk of poor survival.

PURPOSE: To determine if gene expression signature of invasive oral squamous cell carcinoma (OSCC) can subclassify OSCC based on survival. EXPERIMENTAL DESIGN: We analyzed the expression of 131 genes in 119 OSCC, 35 normal, and 17 dysplastic mucosa to identify cluster-defined subgroups. Multivariate Cox regression was used to estimate the association between gene expression and survival. By stepwise Cox regression, the top predictive models of OSCC-specific survival were determined and compared by receiver operating characteristic analysis. RESULTS: The 3-year overall mean+/-SE survival for a cluster of 45 OSCC patients was 38.7+/-0.09% compared with 69.1+/-0.08% for the remaining patients. Multivariate analysis adjusted for age, sex, and stage showed that the 45 OSCC patient cluster had worse overall and OSCC-specific survival (hazard ratio, 3.31; 95% confidence interval, 1.66-6.58 and hazard ratio, 5.43; 95% confidence interval, 2.32-12.73, respectively). Stepwise Cox regression on the 131 probe sets revealed that a model with a term for LAMC2 (laminin gamma2) gene expression best identified patients with worst OSCC-specific survival. We fit a Cox model with a term for a principal component analysis-derived risk score marker and two other models that combined stage with either LAMC2 or PCA. The area under the curve for models combining stage with either LAMC2 or PCA was 0.80 or 0.82, respectively, compared with 0.70 for stage alone (P=0.013 and 0.008, respectively). CONCLUSIONS: Gene expression and stage combined predict survival of OSCC patients better than stage alone.

The role of elective neck dissection in high-grade parotid malignancy: A hospital-based cohort study.

OBJECTIVES/HYPOTHESIS: The role of elective neck dissection (END) in patients with clinically N0 (cN0), high-grade parotid carcinoma is unclear. The objective of this study was to assess the association between END and survival in patients with cN0, high-grade parotid carcinoma. STUDY DESIGN: Retrospective, multicenter cohort study. METHODS: A review of hospital-based cases from the National Cancer Data Base was performed. Participants included patients diagnosed with cN0, high-grade parotid cancer between January 1, 2004 and December 31, 2013. The primary exposure was receipt of neck dissection. Secondary exposures included receipt of adjuvant radiation and/or chemotherapy. Univariate and multivariate survival analyses were performed. Unadjusted and adjusted survival estimates were determined. RESULTS: Overall, 1,547 patients were included, with a median follow-up time of 48 months. END did not have a statistically significant effect on 3-year survival (3-year: 69.9%, 95% confidence interval [CI]: 67.2 to 72.6). Survival at 3-years among those not receiving END was 66.1% (95% CI: 62.7 to 69.5). Parotidectomy and adjuvant radiotherapy had the strongest effect on mortality. There was no difference in 3-year survival among patients who underwent parotidectomy and adjuvant radiation stratified by receipt of END nor did END have a statistically significant effect on survival in mucoepidermoid carcinoma, adenocarcinoma, high-risk histology, high T stage, or academic center treatment subgroups. CONCLUSIONS: END did not have a statistically significant effect on survival among cN0 patients with high-grade parotid cancer when taking into account receipt of adjuvant therapy and confounding. The role of END on survival and locoregional control remains to be further elucidated in prospective studies. LEVEL OF EVIDENCE: 4 Laryngoscope, 130:1487-1495, 2020.

Prediction of survival of HPV16-negative, p16-negative oral cavity cancer patients using a 13-gene signature: A multicenter study using FFPE samples.

OBJECTIVES: To test the performance of an oral cancer prognostic 13-gene signature for the prediction of survival of patients diagnosed with HPV-negative and p16-negative oral cavity cancer. MATERIALS AND METHODS: Diagnostic formalin-fixed paraffin-embedded oral cavity cancer tumor samples were obtained from the Fred Hutchinson Cancer Research Center/University of Washington, University of Calgary, University of Michigan, University of Utah, and seven ARCAGE study centers coordinated by the International Agency of Research on Cancer. RNA from 638 Human Papillomavirus (HPV)-negative and p16-negative samples was analyzed for the 13 genes using a NanoString assay. Ridge-penalized Cox regressions were applied to samples randomly split into discovery and validation sets to build models and evaluate the performance of the 13-gene signature in predicting 2-year oral cavity cancer-specific survival overall and separately for patients with early and late stage disease. RESULTS: Among AJCC stage I/II patients, including the 13-gene signature in the model resulted in substantial improvement in the prediction of 2-year oral cavity cancer-specific survival. For models containing age and sex with and without the 13-gene signature score, the areas under the Receiver Operating Characteristic Curve (AUC) and partial AUC were 0.700 vs. 0.537 (p < 0.001), and 0.046 vs. 0.018 (p < 0.001), respectively. Improvement in predicting prognosis for AJCC stage III/IV disease also was observed, but to a lesser extent. CONCLUSIONS: If confirmed using tumor samples from a larger number of early stage oral cavity cancer patients, the 13-gene signature may inform personalized treatment of early stage HPV-negative and p16-negative oral cavity cancer patients.

Treatment of Tonsillar Carcinoma following Nononcologic Tonsillectomy: Efficacy of Transoral Robotic Revision Tonsillectomy.

OBJECTIVE: To evaluate whether transoral robotic surgery (TORS) is a suitable treatment approach for patients diagnosed with tonsillar carcinoma after a standard palatine tonsillectomy. STUDY DESIGN: Retrospective cohort study. SETTING: Tertiary care medical center. SUBJECTS AND METHODS: Patients who underwent TORS at the University of Washington from 2010 to 2017 (n = 150) were identified. All patients who were diagnosed with tonsillar carcinoma following a nononcologic tonsillectomy and subsequently underwent TORS radical tonsillectomy were included (n = 14). Tumor stage-matched subjects (n = 44) were included who did not undergo standard tonsillectomy prior to TORS. Our primary outcome was final margin status. Secondary outcomes were presence of residual tumor, receipt and dose of postoperative adjuvant therapy, disease-free survival (DFS), and disease-specific survival. Patients with <6 months of follow-up following definitive treatment were excluded from survival analyses. RESULTS: Final margin status was clear in all subjects. Residual tumor was not identified in 13 of 14 (92.9%) prior-tonsillectomy subjects following TORS radical tonsillectomy. Seven of 14 (50%) prior-tonsillectomy subjects and 12 of 44 (27.3%) TORS-matched subjects did not require adjuvant therapy due to favorable pathology. Among subjects who received post-TORS radiation therapy (RT) at our institution, RT dose reduction was achieved in 3 of 4 (75%) prior-tonsillectomy subjects and 21 of 24 (87.5%) TORS-matched subjects. Ten of 14 (71.4%) prior-tonsillectomy subjects and 31 of 44 (70.5%) TORS-matched subjects avoided post-TORS chemotherapy. DFS was not significantly different ( P = .87) between prior-tonsillectomy and TORS-matched groups, and no subjects died of related disease. CONCLUSIONS: Patients diagnosed with tonsillar carcinoma following a prior nononcologic standard palatine tonsillectomy are suitable candidates for revision surgery with TORS radical tonsillectomy.