Patterns of recurrence in head and neck squamous cell carcinoma to inform personalized surveillance protocols.

BACKGROUND: Development of evidence-based post-treatment surveillance guidelines in recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) is limited by comprehensive documentation of patterns of recurrence and metastatic spread. METHODS: A retrospective analysis of patients diagnosed with R/M HNSCC at a National Cancer Institute-designated cancer center between 1998- 2019 was performed (n = 447). Univariate and multivariate analysis identified patterns of recurrence and predictors of survival. RESULTS: Median overall survival (mOS) improved over time (6.7 months in 1998-2007 to 11.8 months in 2008-2019, p = .006). Predictors of worse mOS included human papillomavirus (HPV) negativity (hazard ratio [HR], 1.8; 95% confidence interval [CI], 1.2-2.6), high neutrophil/lymphocyte ratio (HR, 2.1 [1.4-3.0], disease-free interval (DFI) ≤6 months (HR, 1.4 [1.02-2.0]), and poor performance status (Eastern Cooperative Oncology Group, ≥2; HR, 1.91.1-3.4). In this cohort, 50.6% of recurrences occurred within 6 months of treatment completion, 72.5% occurred within 1 year, and 88.6% occurred within 2 years. Metachronous distant metastases were more likely to occur in patients with HPV-positive disease (odds ratio [OR], 2.3 [1.4-4.0]), DFI >6 months (OR, 2.4 [1.5-4.0]), and body mass index ≥30 (OR, 2.3 [1.1-4.8]). Oligometastatic disease treated with local ablative therapy was associated with improved survival over polymetastatic disease (HR, 0.36; 95% CI, 0.24-0.55). CONCLUSION: These data regarding patterns of distant metastasis in HNSCC support the clinical utility of early detection of recurrence. Patterns of recurrence in this population can be used to inform individualized surveillance programs as well as to risk-stratify eligible patients for clinical trials. PLAIN LANGUAGE SUMMARY: After treatment for head and neck cancer (HNC), patients are at risk of recurrence at prior sites of disease or at distant sites in the body. This study includes a large group of patients with recurrent or metastatic HNC and examines factors associated with survival outcomes and recurrence patterns. Patients with human papillomavirus (HPV)-positive HNC have good survival outcomes, but if they recur, this may be in distant regions of the body and may occur later than HPV-negative patients. These data argue for personalized follow-up schedules for patients with HNC, perhaps incorporating imaging studies or novel blood tests.

Stage Migration and Survival Trends in Laryngeal Cancer.

BACKGROUND: During the last two decades, significant advancements in the treatment of laryngeal cancer have occurred. Although survival of head and neck cancer patients has improved over time, the temporal trend of laryngeal cancer survival is an area of controversy. METHODS: From 2004 to 2016, 77,527 patients who had laryngeal cancer treated with curative intent in the United States were identified in the National Cancer Database. Relative and observed survival rates were assessed for temporal trends. Multinomial logistic regression investigated the relationship between American Joint Committee on Cancer (AJCC) stage and increasing calendar year. RESULTS: No significant improvement in 2- or 5-year observed survival (OS) or relative survival (RS) was observed. The 5-year RS ranged from 61.72 to 63.97%, and the 5-year OS ranged from 54.26 to 56.52%. With each increasing year, the proportion of stage 4 disease increased, with risk for stage 4 disease at the time of diagnosis increasing 2.2% annually (adjusted odds ratio [aOR], 1.022; 95% confidence interval [CI], 1.017-1.028; p < 0.001). This increase was driven by a 4.7% yearly increase in N2 disease (aOR, 1.047; 95% CI, 1.041-1.053; p < 0.001), with an annual 1.2% increase in T3 disease (aOR, 1.012; 95% CI, 1.007-1.018; p < 0.001) and a 1.2% increase in T4 disease (aOR, 1.012; 95% CI, 1.005-1.018; p < 0.001). CONCLUSION: Despite advances in the field, laryngeal cancer survival in the United States is not improving over time. This may be due to an increase in the proportion of stage 4 disease, driven primarily by increasing nodal disease. To achieve survival improvement commensurate with scientific and technologic advances, efforts should be made to diagnose and treat laryngeal cancer at earlier stages to prevent further stage migration.

Surveillance and Monitoring Techniques for HPV-Related Head and Neck Squamous Cell Carcinoma: Circulating Tumor DNA.

OPINION STATEMENT: Human papilloma virus (HPV) related head and neck cancer is rising in prevalence, preferentially affecting young patients and imparting long term toxicities. Despite this, there are no screening tests or clinical biomarkers for treatment monitoring. HPV circulating tumor DNA (HPV ctDNA) represents a novel circulating biomarker which may provide real-time assessment of tumor response to therapy and recurrence. Early work suggests the promise of this assay as a predictive biomarker in numerous clinical settings, namely risk of recurrence after chemoradiation in locally advanced disease. Advancement of these findings to the clinic will require a collaborative effort in the field, including technical harmonization of assay testing characteristics, understanding of the normal kinetics in patients being treated with standard of care therapies, and appropriately designed phase III trials prior to implementation in the clinic. If successful, HPV ctDNA has the potential to revolutionize clinical trial treatment paradigms and transform patient care.

Predictors of survival in patients undergoing oropharyngeal surgery for cancer recurrence after radiation therapy.

PURPOSE: The incidence of oropharyngeal squamous cell carcinoma continues to rise with the majority of patients receiving definitive or adjunctive radiation. For patients with locoregional recurrence after radiation, optimal treatment involves salvage surgery. The aim of this study is to identify factors that predict survival to ultimately improve patient selection for salvage surgery. METHODS: Retrospective cohort study at an NCI-designated cancer center. We analyzed patients with a history of head and neck radiation who presented with persistent/recurrent or second primary disease requiring salvage oropharyngeal resection from 1998-2017 (n = 120). Patients were stratified into three classes based on time to recurrence and presence of laryngopharyngeal dysfunction. Primary outcomes were 5-year overall survival (OS) and disease specific survival (DSS). RESULTS: Median OS was 27 months (median follow-up 20 months). Five-year OS was 47% for class I (recurrence > 2 years), 26% for class II (recurrence ≤ 2 years), and 0% for class III (recurrence ≤ 2 years and laryngopharyngeal dysfunction), (p < 0.0001). Five-year DSS showed significant differences between classes (p < 0.0001). On multivariate analysis, class remained predictive of OS (p = 0.04- < 0.001) and DSS (p = 0.04-0.001). Adjuvant radiation after salvage surgery with negative margins showed superior OS (71% vs. 28%, p = 0.01) and DSS (83% vs 37%, p = 0.02) compared to surgery alone and was a significant predictor of improved survival on multivariate analysis (HR 0.1, p = 0.04). CONCLUSION: This study identified a subset of patients with oropharyngeal cancer recurrence within two years of initial treatment and with laryngopharyngeal dysfunction who have poor outcomes for salvage surgery.

Targeted Therapy and Traditional Chemotherapy in Melanoma and Cutaneous Squamous Cell Carcinoma.

Cutaneous squamous cell carcinoma (cSCC) and melanoma encompass the majority of all malignant skin cancers. There has been an increase in their incidence globally in recent decades. In cases of high-risk, unresectable, or metastatic disease; or when patient factors or preferences limit the availability of conventional surgery or radiotherapy; or a systemic therapy is often warranted. Our improved understanding of the molecular and immune pathogenesis underlying tumor growth and development has been critical in advancing cancer therapeutics. Over the past several years, several new systemic agents have been approved for both diseases. The role of cytotoxic chemotherapy is gradually waning with the introduction of targeted therapy and immunotherapy. In this article, we review the current and relevant literature and evidence of cytotoxic chemotherapy, targeted therapy, and immune checkpoint inhibitors in the adjuvant and neoadjuvant settings for cSCC and melanoma. Additionally, we describe their role in the unresectable or metastatic disease setting.

Elective Paratracheal Lymph Node Dissection in Salvage Laryngectomy.

BACKGROUND: Indications for and efficacy of paratracheal nodal dissection (PTND) in patients undergoing laryngectomy (salvage) for persistent or recurrent laryngeal squamous cell carcinoma are not well-defined. METHODS: A retrospective cohort study was performed for patients undergoing salvage laryngectomy with clinically and radiographically negative neck disease between 1998 and 2015 (n = 210). Univariate and multivariate Cox regression analyses were performed. RESULTS: PTND was performed on 77/210 patients (36%). The PTND cohort had a greater proportion of advanced T classification (rT3/rT4) tumors (78%) than subjects without PTND (55%; p = 0.001). There was a 14% rate of occult nodal metastases in the paratracheal basin; of these, 55% did not have pathologic lateral neck disease. Multivariate analysis controlling for tumor site, tumor stage, and pathologic lateral neck disease demonstrated that PTND was associated with improved overall survival [OS] (p = 0.03; hazard ratio [HR] 0.60, 95% confidence interval [CI] 0.38-0.96), disease-free survival [DFS] (p = 0.03; HR 0.55, 95% CI 0.31-0.96), and distant DFS survival (p = 0.01; HR 0.29, 95% CI 0.11-0.77). The rate of hypocalcemia did not differ between subjects who underwent bilateral PTND, unilateral PTND, or no PTND (p = 0.19 at discharge, p = 0.17 at last follow-up). CONCLUSIONS: PTND at the time of salvage laryngectomy was more common in patients with rT3/rT4 tumors and was associated with improved OS and DFS, with no effect on hypocalcemia. In patients undergoing PTND, the finding of occult paratracheal metastases was often independent of lateral neck metastases.

A prospective study of severe irritability in youths: 2- and 4-year follow-up.

BACKGROUND: Severe, chronic irritability is receiving increased research attention, and is the cardinal symptom of a new diagnostic category, disruptive mood dysregulation disorder (DMDD). Although data from epidemiological community samples suggest that childhood chronic irritability predicts unipolar depression and anxiety in adulthood, whether these symptoms are stable and cause ongoing clinical impairment is unknown. The present study presents 4-year prospective and longitudinal diagnostic and impairment data on a clinical sample of children selected for symptoms of severe irritability (operationalized as severe mood dysregulation [SMD]). METHODS: Youth meeting criteria for SMD (n = 200) were evaluated at baseline using standard diagnostic methods. Two-year (n = 78) and 4-year (n = 46) follow-up diagnostic and clinical impairment ratings collected at 6-month intervals were completed with those youths enrolled in the study for a sufficient time. RESULTS: Although the number of youth meeting strict categorical SMD criteria declined over time (49 and 40% at 2 and 4 years, respectively), many individuals not meeting full criteria continued to display clinically significant irritability symptoms (2 years: 42%; 4 years: 37%). Impairment due to these irritability symptoms remained consistently in the moderate range on the Clinical Global Impressions Scale. CONCLUSIONS: By the 4-year follow-up, only 40% of youths meet strict SMD criteria; however, most continue to display clinically impairing symptoms and significant impairment warranting psychiatric treatment. These findings provide evidence for the course of irritability, with implications for DMDD. Future research with populations meeting DMDD criteria and followed through the ages of high risk for psychiatric diagnoses is necessary.

Association of preoperative thyroid hormone replacement with perioperative complications after major abdominal surgery.

OBJECTIVE: To determine the association between preoperative thyroid hormone replacement and complications following major abdominal surgery. METHODS: A retrospective case series was performed of patients enrolled in the Michigan Surgical Quality Collaborative (MSQC) who underwent major abdominal surgery at an academic institution over a 10-year period. The principal explanatory variable was preoperative thyroid hormone replacement. Primary outcomes were morbidity, mortality and length of stay. RESULTS: 2700 patients were identified. On multivariate analysis correcting for established predictors of operative morbidity, patients on preoperative thyroid replacement had a 1.5- fold increased risk of serious morbidity(p â€‹= â€‹0.01), and a 1.7- fold greater risk for serious sepsis(p â€‹= â€‹0.04). Thyroid replacement was associated with longer length of stay(p â€‹< â€‹0.001). While there was a high degree of missing data for surgical approach (31.1 â€‹% missing data), results suggest that patients on thyroid hormone replacement were more likely to undergo an open rather than minimally invasive surgery(p â€‹< â€‹0.01). Open surgery was associated with greater risk of serious morbidity(p â€‹= â€‹0.003) and longer length of stay(p â€‹< â€‹0.001). CONCLUSIONS: Preoperative thyroid hormone replacement independently predicts operative morbidity and length of stay following major abdominal surgery.

The osteocutaneous radial forearm free flap: A pictorial essay.

The osteocutaneous radial forearm free flap (OCRFFF) is a versatile flap with the ability to reconstruct complex defects. We detail the techniques necessary to harvest an OCRFFF, including an outline on making 90-degree osteotomies to maximize bone harvest. In this pictorial essay, we provide illustrations of the anatomy and surgical techniques necessary for OCRFFF harvest. Detailed discussion is provided on how to protect the perforators to the bone and the approach to making osteotomies in a 90-degree fashion. The approach for prophylactic plating of the radius to prevent radius fractures is outlined. A case presentation on the real-life utilization of this flap is included. The OCRFFF is an excellent head and neck reconstructive option. While there are limitations to its use for patients requiring dental rehabilitation or long/anterior mandibular defects, for the right patient and indication it has shown great success in reconstructive efforts.

National Trends in 30-Day Readmission Following Transoral Robotic Surgery for Oropharyngeal Squamous Cell Carcinoma.

Importance: As the incidence of oropharyngeal squamous cell carcinoma (OPSCC) continues to rise in the US, an increasing number of patients are being treated with transoral robotic surgery (TORS). Readmission following surgery can potentially delay initiation of adjuvant treatment and affect survival outcomes. Objective: To identify risk factors for 30-day postoperative readmission in patients undergoing TORS for OPSCC. Design, Setting, and Participants: This retrospective, population-based cohort study used data from the Nationwide Readmissions Database from 2010 to 2017. All patients undergoing TORS for OPSCC were identified using International Classification of Diseases codes and included. Exclusion criteria were age younger than 18 years or incomplete information regarding index admission or readmission. The analysis was performed from April to October 2023. Exposure: TORS for OPSCC. Main Outcomes and Measures: Univariate and multivariate analyses were performed to determine factors associated with 30-day readmission. Covariates included demographics and medical comorbidities, socioeconomic factors, hospital characteristics, and surgical details. Trends in readmission over time, reasons for readmission, and characteristics of the readmission were also examined. Results: A weighted total of 5544 patients (mean [SD] age, 60.7 [0.25] years; 4475 [80.7%] male) underwent TORS for OPSCC. The overall readmission rate was 17.5% (n = 971), and these rates decreased over the study period (50 of 211 patients [23.7%] in 2010 vs 58 of 633 patients [9.1%] in 2017). Risk factors associated with readmission included male sex (adjusted odds ratio [AOR], 1.54; 95% CI, 1.07-2.20) and a diagnosis of congestive heart failure (AOR, 2.42; 95% CI, 1.28-4.58). Factors associated with decreased rate of readmission included undergoing concurrent selective neck dissection (AOR, 0.30; 95% CI, 0.22-0.41). Among the 971 readmissions, the most common readmission diagnoses were bleeding (151 [15.6%]), electrolyte and digestive problems (44 [4.5%]), pneumonia (44 [4.5%]), and sepsis (26 [2.7%]). Conclusions and Relevance: In this cohort study, readmission rates following TORS for oropharynx cancer decreased over time; however, a subset of patients required readmission most commonly related to bleeding, infection, and electrolyte imbalance. Concurrent neck dissection may be protective against readmission. Elucidation of risk factors for readmission after TORS for OPSCC offers opportunities for evidence-based shared decision-making, quality improvement initiatives, and improved patient counseling.

Phase II Clinical Trial of Intravenous Levothyroxine to Mitigate Pharyngocutaneous Fistula in Euthyroid Patients Undergoing Salvage Laryngectomy.

PURPOSE: Patients undergoing head and neck cancer surgery after prior radiation or chemoradiation are at high risk for wound complications. Hypothyroidism is a known risk factor for wound complications, especially fistulae after salvage total laryngectomy. The purpose of this phase II clinical trial is to investigate the effect of peri-operative intravenous levothyroxine supplementation on wound complications in patients undergoing salvage total laryngectomy. PATIENTS AND METHODS: Euthyroid patients previously treated with radiation/chemoradiation undergoing total laryngectomy were prospectively recruited (n=72). Post-operatively, intravenous levothyroxine was administered at a weight-based dose (1.3 mcg/kg/day) and transitioned to enteral dosing on day 7. Free T3, T4, and thyroid stimulating hormone (TSH) were collected and dosing was adjusted accordingly. The primary endpoints were rates of fistula and fistula requiring re-operation, compared to matched historical controls. All patients were monitored for adverse effects. RESULTS: The rate of post-operative hypothyroidism was 21% compared to 49% in a matched historic cohort. The rate of fistula was 18.1% while the rate of fistula requiring re-operation was 4.2%, significantly lower than rates in our historic cohort (34.6% and 14.8% respectively, p=0.02 and 0.01). Post-operative hypothyroidism and recurrent clinical stage predicted fistula requiring re-operation in multivariate analysis; other acute phase reactants were not predictive. There were no observed adverse events related to levothyroxine supplementation. CONCLUSIONS: Post-operative intravenous levothyroxine supplementation reduced rates of acute hypothyroidism, fistula, and fistula requiring re-operation in patients undergoing salvage total laryngectomy without adverse effects. Intravenous levothyroxine is a viable strategy to reduce wound complications in this high-risk patient population.

Immunoprofiles and Oncologic Outcomes of 15 Patients with Androgen Receptor-Positive Salivary Duct Carcinoma.

BACKGROUND: Salivary duct carcinomas (SDC) are a rare and aggressive subtype of salivary gland neoplasm. They can present with distinct immunoprofiles, such as androgen receptor (AR) and HER-2/Neu-positivity. To date, no consensus exists on how to best manage this entity. METHODS: All patients diagnosed with nonmetastatic AR+ SDC of the parotid from 2013 to 2019 treated with curative intent were included. Immunologic tumor profiling was conducted using 24 distinct markers. Kaplan-Meier analyses were used to estimate locoregional recurrence (LRR), distant control, and overall survival (OS). RESULTS: Fifteen patients were included. Nine (60%) patients presented with T4 disease and eight (53%) had positive ipsilateral cervical lymphadenopathy. Ten (67%) patients underwent trimodality therapy, including surgery followed by adjuvant radiation and concurrent systemic therapy. The median follow-up was 5.5 years (interquartile range, 4.8-6.1). The estimated 5-year rates of LRR, distant progression, and OS were 6%, 13%, and 87%, respectively. CONCLUSION: Despite only including AR+ SDC of the parotid, immunoprofiles, such as expression of HER-2, were highly variable, highlighting the potential to tailor systemic regimens based on individual histologic profiles in the future. Studies with larger patient numbers using tumor-specific molecular profiling and tumor heterogeneity analyses are justified to better understand the biology of these tumors. Molecularly informed treatment approaches, including the potential use of AR- and HER-2/Neu-directed therapies upfront in the definitive setting, may hold future promise to further improve outcomes for these patients.

Impaired fixation to eyes during facial emotion labelling in children with bipolar disorder or severe mood dysregulation.

BACKGROUND: Children with bipolar disorder (BD) or severe mood dysregulation (SMD) show behavioural and neural deficits during facial emotion processing. In those with other psychiatric disorders, such deficits have been associated with reduced attention to eye regions while looking at faces. METHODS: We examined gaze fixation patterns during a facial emotion labelling task among children with pediatric BD and SMD and among healthy controls. Participants viewed facial expressions with varying emotions (anger, fear, sadness, happiness, neutral) and emotional levels (60%, 80%, 100%) and labelled emotional expressions. RESULTS: Our study included 22 children with BD, 28 with SMD and 22 controls. Across all facial emotions, children with BD and SMD made more labelling errors than controls. Compared with controls, children with BD spent less time looking at eyes and made fewer eye fixations across emotional expressions. Gaze patterns in children with SMD tended to fall between those of children with BD and controls, although they did not differ significantly from either of these groups on most measures. Decreased fixations to eyes correlated with lower labelling accuracy in children with BD, but not in those with SMD or in controls. LIMITATIONS: Most children with BD were medicated, which precluded our ability to evaluate medication effects on gaze patterns. CONCLUSION: Facial emotion labelling deficits in children with BD are associated with impaired attention to eyes. Future research should examine whether impaired attention to eyes is associated with neural dysfunction. Eye gaze deficits in children with BD during facial emotion labelling may also have treatment implications. Finally, children with SMD exhibited decreased attention to eyes to a lesser extent than those with BD, and these equivocal findings are worthy of further study.

Circulating Tumor DNA in Human Papillomavirus-Mediated Oropharynx Cancer: Leveraging Early Data to Inform Future Directions.

ABSTRACT: Circulating tumor DNA (ctDNA) has become an area of intense study in many solid malignancies including head and neck cancer. This is of particular interest for human papillomavirus-mediated oropharyngeal squamous cell carcinoma as this cohort of patients has excellent survival and is undergoing current clinical trials aimed at treatment de-escalation. Recent studies have demonstrated the prognostic implications of pretreatment ctDNA and the utility of monitoring ctDNA during and posttreatment; however, there is a need for a more critical understanding of ctDNA as it is beginning to be incorporated into clinical trials. This review discusses the current state of ctDNA in oropharynx cancer focusing on ctDNA kinetics and minimal residual disease detection and ends with a discussion of future applications.

High surgical volume is associated with improved survival in head and neck cancer.

OBJECTIVES: Examine the relationship between hospital volume and overall mortality in a surgical cohort of head and neck squamous cell carcinoma (HNSCC) patients. MATERIALS & METHODS: A retrospective review of the NCDB was completed for adults with previously untreated HNSCC diagnosed between 2004 and 2016. Mean annual hospital volume was calculated using the number of head and neck cancer cases treated at a given facility divided by the number of years the facility reported to the NCDB. Facilities were separated into three categories based on their volume percentile, informed by inflection points from a natural cubic spline: Hospital Group 1 (<50%); Hospital Group 2 (50-90%); Hospital Group 3 (90%+). Cox proportional hazard models were used to examine the association between volume percentiles (continuous or categorical) with patient overall survival, adjusting for important patient and facility variables known to impact survival. RESULTS: Risk of death decreased by 2.97% for every 10% increase in facility percentile after adjusting for other risk factors. Patients treated at facilities in Hospital Group 1 had a 23.1% increase in risk of mortality (HR 1.231 [95% CI 1.12-1.35]) relative those at facilities in Hospital Group 3. No significant difference in mortality risk was found between Hospital Group 2 versus Hospital Group 3 (HR 1.031 [95% CI 0.97-1.10]). CONCLUSIONS: Survival of HNSCC patients is significantly improved when treated at facilities >50th percentile in annual hospital volume. This may support the regionalization of care to high volume head and neck centers with comprehensive facilities and supportive services to maximize patient outcomes.

Demographic and Academic Productivity Trends Among American Head & Neck Society Fellows Over a 20-Year Period.

Importance: Historical data reveal that, compared with women, men are more likely to pursue a head and neck surgical oncology fellowship, but little is known about possible gender differences in academic productivity. Objective: To assess demographic trends and academic productivity among American Head & Neck Society (AHNS) fellowship graduates. Design, Setting, and Participants: This cross-sectional study used electronically published data from the AHNS on fellowship graduates in the US and Canada from July 1, 1997, to June 30, 2022. Scopus was used to extract h-indices for each graduate. Exposure: Scholarly activity. Main Outcomes and Measures: Main outcomes were changes in demographic characteristics and academic productivity among AHNS graduates over time. Data analysis included effect size, η2, and 95% CIs. Results: A total of 691 AHNS fellowship graduates (525 men [76%] and 166 women [24%]) were included. Over the study period, there was an increase in the number of programs offering a fellowship (η2, 0.84; 95% CI, 0.68-0.89) and an increase in the absolute number of women who completed training (η2, 0.66; 95% CI, 0.38-0.78). Among early-career graduates pursuing an academic career, there was a small difference in the median h-index scores between men and women (median difference, 1.0; 95% CI, -1.1 to 3.1); however, among midcareer and late-career graduates, there was a large difference in the median h-index scores (midcareer graduates: median difference, 4.0; 95% CI, 1.2-6.8; late-career graduates: median difference, 6.0; 95% CI, 1.0-10.9). A higher percentage of women pursued academic positions compared with men (106 of 162 [65.4%] vs 293 of 525 [55.8%]; difference, 9.6%; 95% CI, -5.3% to 12.3%). Conclusions and Relevance: This cross-sectional study suggests that women in head and neck surgery begin their careers with high levels of academic productivity. However, over time, a divergence in academic productivity between men and women begins to develop. These data argue for research to identify possible reasons for this observed divergence in academic productivity and, where possible, develop enhanced early faculty development opportunities for women to promote their academic productivity, promotion, and advancement into leadership positions.

Modifiable risk factors for oral cavity cancer in non-smokers: A systematic review and meta-analysis.

BACKGROUND: Oral cavity cancer (OCC) is traditionally associated with smoking, but there is an increasing prevalence of the disease among non-smokers. This review investigates possible modifiable risk factors in the development of OCC in non-smokers (OCCNS). METHODS: PubMed, EMBASE, Web of Science, and Scopus were searched for publications prior to June 2021. Comparative studies investigating modifiable OCCNS risk factors were identified following PRISMA guidelines. Publication date, population size, and results were indexed. Study quality was assessed using MINORS (Methodological Index for Non-Randomized Studies). Factors examined by multiple studies were analyzed using random-effect meta-analysis framework. RESULTS: Literature search resulted in 1,625 unique publications. 52 records met inclusion criterion, investigating alcohol (n = 22), chewing products (n = 18), diet (n = 7), dental health (n = 11), and medical comorbidities (n = 6). CONCLUSION: This review demonstrates the paucity of large studies investigating OCCNS risk factors. Further investigation is warranted to help clinicians risk-stratify patients without traditional risk factors.

Advantages of the scapular system in mandibular reconstruction.

BACKGROUND: Fibula free flaps (FFF) are often considered the first choice for mandibular reconstruction, but scapular system free flaps (SFF) have increased in popularity due to versatility, donor site advantages, and patient factors. METHODS: Retrospective chart review of patients undergoing mandibulectomy with FFF or SFF reconstruction from 2016 to 2021. RESULTS: Hundred and seventy-six patients (FFF n = 145, SFF n = 31) underwent the aforementioned procedures. Mean FFF operative time was 9.47 h versus 9.88 for SFF (p = 0.40). Two-flap reconstructions required 12.65 h versus 10.09 for SFF with soft tissue (p = 0.002). Donor site complications were identified in 65.6% of FFF with skin grafting. CONCLUSIONS: These findings suggest that SFF requires similar operative time and results in reduced donor site morbidity as compared to FFF. Supine, concurrent harvesting of SFF allows for single-flap harvest with significantly shorter operative time. SFF could be considered a primary option for mandible reconstruction for complex defects and in select patients.

Hypothyroidism as an Independent Predictor of 30-day Readmission in Head and Neck Cancer Patients.

OBJECTIVES: To define the role of hypothyroidism and other risk factors for unplanned readmissions after surgery for head and neck cancer. STUDY DESIGN: Retrospective cohort study. METHODS: The Nationwide Readmission Database (NRD) was used to identify patients who underwent surgery for mucosal head and neck cancer (oral cavity, oropharynx, larynx, and hypopharynx) between 2010 and 2017. Univariate and multivariate logistic regression were performed to determine patient, tumor, and hospital related risk factors for 30-day readmission. Readmitted patients were stratified by preoperative diagnosis of hypothyroidism to compare readmission characteristics. RESULTS: For the 131,013 patients who met inclusion criteria, the readmission rate was 15.9%. Overall, 11.91% of patients had a preoperative diagnosis of hypothyroidism. After controlling for other variables, patients with a preoperative diagnosis of hypothyroidism had 12.2% higher odds of readmission compared to those without hypothyroidism (OR: 1.12, 1.03-1.22, p = 0.008). Patients with hypothyroidism had different reasons for readmission, including higher rates of wound dehiscence, fistula, infection, and electrolyte imbalance. Among readmitted patients, the length of stay for index admission (mean 10.5 days vs. 9.2 days, p < 0.001), readmission (mean 7.0 vs. 6.6 days, p = 0.05), and total hospital charge were higher for hypothyroid patients ($137,742 vs. $119,831, p < 0.001). CONCLUSION: Hypothyroidism is an independent risk factor for 30-day readmission following head and neck cancer resection. Furthermore, hypothyroid patients are more likely to be readmitted for wound complications, infection, and electrolyte imbalance. Targeted interventions should be considered for hypothyroid patients to decrease readmission rates and associated patient morbidity, potentially leading to earlier initiation of adjuvant treatment. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:2988-2998, 2023.

Immediate resection of positive margins improves local control in oral tongue cancer.

OBJECTIVES: This study investigates the impact of immediate resection of positive margins on local control of oral tongue cancer. MATERIALS AND METHODS: We analyzed 273 consecutive oral tongue cancers resected from 2013 to 2018. Additional resection was performed in cases during the initial operation based on surgeon inspection of the specimen and/or frozen margins. Positive margins were defined as invasive carcinoma/high-grade dysplasia < 1 mm from the inked edge. Patients were grouped as follows: negative margin (Group 1); positive margin with immediate additional tissue resection (Group 2); and positive margin without additional tissue resection (Group 3). RESULTS: Overall, the rate of local recurrence was 7.7 % (21/273), and the rate of positive main specimen margin was 17.9 %. Of these patients, 38.8 % (19/49) underwent immediate additional resection of the presumed positive margin. Group 3 had higher local recurrence rates than Group 1 after adjustment for T-stage (aHR 2.8 [95 % CI 1.0-7.7], p = 0.04). Group 2 had similar rates of local recurrence (aHR 0.45 [95 % CI 0.06-3.6], p = 0.45). Three year local recurrence free survival for Groups 1, 2, and 3 were 91 %, 92 % and 73 %, respectively. Compared to the main specimen margin, sensitivity of intraoperative frozen tumor bed margins was 17.4 %, and specificity was 95 %. CONCLUSION: In patients with positive main specimen margins, anticipation and detection in real-time with immediate additional tissue resection reduced local recurrence to rates similar to those with negative main specimen margins. These findings support the use of technology to provide real-time intraoperative margin data and guide additional resection for improved local control.