Battle of the biopsies: Role of tissue and liquid biopsy in hepatocellular carcinoma.

The diagnosis and management of hepatocellular carcinoma (HCC) have improved significantly in recent years. With the introduction of immunotherapy-based combination therapy, there has been a notable expansion in treatment options for patients with unresectable HCC. Simultaneously, innovative molecular tests for early detection and management of HCC are emerging. This progress prompts a key question: as liquid biopsy techniques rise in prominence, will they replace traditional tissue biopsies, or will both techniques remain relevant? Given the ongoing challenges of early HCC detection, including issues with ultrasound sensitivity, accessibility, and patient adherence to surveillance, the evolution of diagnostic techniques is more relevant than ever. Furthermore, the accurate stratification of HCC is limited by the absence of reliable biomarkers which can predict response to therapies. While the advantages of molecular diagnostics are evident, their potential has not yet been fully harnessed, largely because tissue biopsies are not routinely performed for HCC. Liquid biopsies, analysing components such as circulating tumour cells, DNA, and extracellular vesicles, provide a promising alternative, though they are still associated with challenges related to sensitivity, cost, and accessibility. The early results from multi-analyte liquid biopsy panels are promising and suggest they could play a transformative role in HCC detection and management; however, comprehensive clinical validation is still ongoing. In this review, we explore the challenges and potential of both tissue and liquid biopsy, highlighting that these diagnostic methods, while distinct in their approaches, are set to jointly reshape the future of HCC management.

Characteristics and overall survival in pediatric versus adult pituitary adenoma: a National Cancer Database analysis.

OBJECTIVE: Pituitary adenomas in the pediatric population are extremely rare, resulting in limited information in the literature on these patients. In this study, data from the National Cancer Database (NCDB) to compare pituitary adenoma clinical presentations, treatment management patterns, and overall survival between pediatric and adult patients. METHODS: The NCDB was queried for all cases of histologically confirmed pituitary adenoma treated between 2004 and 2015. Patients were primarily stratified as either pediatric (< 18 years) or adult (≥ 18 years). Patient demographics/socioeconomics and resulting outcomes were then compared. RESULTS: 1893 pediatric and 77,993 adult patients with pituitary adenomas were evaluated. Average tumor size for pediatric and adult patients was 13.6 ± 13.2 mm and 20.1 ± 13.1 mm, respectively (p < 0.001). Pediatric patients were more likely to undergo gross total resection, less likely to receive adjuvant radiation, more likely to receive medical therapy, more likely to undergo active surveillance, and exhibited improved 5-year and 10-year overall survival (OS) (all p < 0.001). Temporal analysis demonstrated a significant increase in endoscopic approach over time (from 48 to 65%) in the pediatric population (R2 = 0.722, p = 0.03). On univariate analysis in the pediatric population, African American race compared to Caucasians (HR: 5.85, 95% CI 1.79-19.2, p < 0.003), patients with government insurance compared to those with private insurance (HR: 5.07, 95% CI 1.31-19.6, p < 0.02) and uninsured patients compared to those with private insurance (HR: 14.4, 95% CI 2.41-86.5, p < 0.003) were associated with decreased OS. Lastly, patients who underwent GTR had improved OS compared to those who underwent subtotal resection (HR: 0.08, 95% CI 0.008-0.93, p < 0.04) in the pediatric population. CONCLUSIONS: Compared to adults, children with pituitary adenomas more commonly underwent GTR, less frequently underwent adjuvant radiotherapy, more frequently underwent medical management and active surveillance, and had improved survival. Temporal analysis demonstrated increasing utilization of the endoscopic approach for surgical treatment of pediatric and adult pituitary adenoma patients. LEVEL OF EVIDENCE: Level III.

Characteristics and overall survival in pediatric versus adult craniopharyngioma: a population-based study.

PURPOSE: This study uses a large-population national database to describe the presenting clinical, sociodemographic, treatment, and clinical outcome differences between pediatric and adult craniopharyngiomas. METHODS: This study utilized the 2004-2015 National Cancer Database and was queried for all cases of craniopharyngioma. Multivariate Cox proportional-hazards analysis was used to determine clinical and sociodemographic factors associated with mortality. Kaplan-Meier log-rank test determined differences in overall survival (OS) time. RESULTS: The cohort consisted of 3638 patients, with 816 (22.4%) pediatric (≤ 18 years) patients. Pediatric patients presented with significantly higher frequency of large tumors (> 3 cm, 54.1 vs. 31.8%, p < 0.001), lower frequency of papillary subtype (0.9 vs. 11.5%, p < 0.001), and were exclusively treated at academic centers (100 vs. 73.4%, p < 0.001). Pediatric patients had significantly higher rates of adjuvant radiation (34.3 vs. 22.3%; p < 0.001), and had significantly lower 90-day mortality (1.6 vs. 4.9%; p < 0.001); however, no significant differences in extent of resection (p = 0.93), length of hospital stay (p = 0.53), and 30-day readmissions (p = 0.06) were observed between pediatric and adult patients. On Kaplan-Meier log-rank test, there were no significant differences in OS in pediatric patients receiving gross total resection (GTR), subtotal resection (STR), or STR + adjuvant radiation (p = 0.68). Lastly, when comparing endoscopic and open surgical approaches in pediatric patients, there were no significant differences in extent of surgical resection (p = 0.81), length of hospital stay (p = 0.54), 30-day readmissions (p = 0.22), and 90-day mortality (p = 0.80). CONCLUSION: Craniopharyngioma has improved OS in pediatric compared to adult patients. Pediatric craniopharyngioma patients are best managed within multidisciplinary teams at academic centers with an individualized approach.

Characteristics and overall survival in pediatric versus adult skull base chordoma: a population-based study.

PURPOSE: Less than 5% of chordomas occur in pediatric patients. While many studies have explored the treatment and outcomes of skull base chordomas, few have focused on the differences between pediatric and adult populations. The aim of this study is to analyze the epidemiological variables and clinical outcomes between pediatric and adult skull base chordomas using a large-sample, population-based cancer database. METHODS: The National Cancer Database was queried between 2004 and 2015 for skull base chordomas. We stratified patients as pediatric (<18 years) and adults (≥18 years). We compared several clinical covariates between the two groups. RESULTS: Our cohort consisted of 658 patients, 61 pediatric (9.3%), and 597 adults (90.7%). Pediatric patients were more likely to have larger tumor size (41.4 ± 15.7 mm versus 34.1 ± 15.8 mm, p < 0.01) and universally treated at academic facilities. There was no significant difference in overall survival. CONCLUSIONS: Pediatric skull base chordomas are rare tumors that are managed with aggressive surgical resection, followed by radiation. While there may be difference between tumor presentation, outcomes between pediatric and adult patients are similar.

Temporal patterns of nasal symptoms in patients with mild severity SARS-CoV-2 infection.

BACKGROUND: No study to date has analyzed the progression of sinonasal symptoms over time in COVID-19 patients. The purpose of this study is to analyze the progression of sinonasal symptoms and risk factors for olfactory dysfunction in the mild severity COVID-19 patient. METHODS: An internet survey was used to assess sinonasal symptoms in patients with COVID-19. Changes in rhinologic domain and symptom-specific Sinonasal Outcome Test (SNOT-22) scores were compared at five time points: two weeks before diagnosis, at diagnosis, two weeks after diagnosis, four weeks after diagnosis, and six months after diagnosis. RESULTS: 521 responses were collected. Rhinologic domain SNOT-22 scores increased significantly (p < 0.001) to 8.94 at the time of diagnosis, remained elevated two weeks post-diagnosis (5.14, p = 0.004), and decreased significantly four weeks post-diagnosis (3.14, p = 0.004). Smell-specific SNOT-22 scores peaked at the time of diagnosis (2.05, p < 0.001), remained elevated two weeks after diagnosis (1.19, p < 0.001), and returned to baseline four weeks post-diagnosis (0.64, p > 0.999). Taste-specific SNOT-22 scores also peaked at diagnosis (2.06, p < 0.001), remained elevated two weeks after diagnosis (1.19, p < 0.001), and returned to baseline four weeks after diagnosis (0.71, p > 0.999). There were no significant differences in sense of smell or taste between 1-month and 6-month timepoints. CONCLUSION: Sinonasal symptoms, particularly loss of smell and taste, may be important presenting symptoms in the mild severity COVID-19 patient. Our findings support incorporating these symptoms into screening protocols. LEVEL OF EVIDENCE: 4.

Enhancing peripheral nerve regeneration with neurotrophic factors and bioengineered scaffolds: A basic science and clinical perspective.

Despite the peripheral nervous systems (PNS) capacity to regenerate, functional restoration is highly variable following peripheral nerve injury (PNI), oftentimes leading to persistent functional deficits. In the preclinical arena, advances in the therapeutic use of exogenous neurotrophic factors and synthetic neural scaffold technology hold promise in augmenting endogenous PNS regeneration following PNI. Clinical trials utilizing neurotrophic factors for other indications (eg, peripheral neuropathy) may provide insight into their role in PNI. Here we provide an updated review of progress made toward enhancing regeneration after PNI with a focus on neurotrophic factors and bioengineered scaffolds.

The role of frailty in geriatric cranial neurosurgery for primary central nervous system neoplasms.

OBJECTIVE: Frailty is a clinical state of increased vulnerability due to age-associated decline and has been well established as a perioperative risk factor. Geriatric patients have a higher risk of frailty, higher incidence of brain cancer, and increased postoperative complication rates compared to nongeriatric patients. Yet, literature describing the effects of frailty on short- and long-term complications in geriatric patients is limited. In this study, the authors evaluate the effects of frailty in geriatric patients receiving cranial neurosurgery for a primary CNS neoplasm. METHODS: The authors conducted a retrospective cohort study of geriatric patients receiving cranial neurosurgery for a primary CNS neoplasm between 2010 and 2017 by using the Nationwide Readmission Database. Demographics and frailty were queried at primary admission, and readmissions were analyzed at 30-, 90-, and 180-day intervals. Complications of interest included infection, anemia, infarction, kidney injury, CSF leak, urinary tract infection, and mortality. Nearest-neighbor propensity score matching for demographics was implemented to identify nonfrail control patients with similar diagnoses and procedures. The analysis used Welch two-sample t-tests for continuous variables and chi-square test with odds ratios. RESULTS: A total of 6713 frail patients and 6629 nonfrail patients were identified at primary admission. At primary admission, frail geriatric patients undergoing cranial neurosurgery had increased odds of developing acute posthemorrhagic anemia (OR 1.56, 95% CI 1.23-1.98; p = 0.00020); acute infection (OR 3.16, 95% CI 1.70-6.36; p = 0.00022); acute kidney injury (OR 1.32, 95% CI 1.07-1.62; p = 0.0088); urinary tract infection prior to discharge (OR 1.97, 95% CI 1.71-2.29; p < 0.0001); acute postoperative cerebral infarction (OR 1.57, 95% CI 1.17-2.11; p = 0.0026); and mortality (OR 1.64, 95% CI 1.22-2.24; p = 0.0012) compared to nonfrail geriatric patients receiving the same procedure. In addition, frail patients had a significantly increased inpatient length of stay (p < 0.0001) and all-payer hospital cost (p < 0.0001) compared to nonfrail patients at the time of primary admission. However, no significant difference was found between frail and nonfrail patients with regard to rates of infection, thromboembolism, CSF leak, dural tear, cerebral infarction, acute kidney injury, and mortality at all readmission time points. CONCLUSIONS: Frailty may significantly increase the risks of short-term acute complications in geriatric patients receiving cranial neurosurgery for a primary CNS neoplasm. Long-term analysis revealed no significant difference in complications between frail and nonfrail patients. Further research is warranted to understand the effects and timeline of frailty in geriatric patients.

Fetal Bovine Serum-Derived Extracellular Vesicles Persist within Vesicle-Depleted Culture Media.

It is known that culture media (CM) promotes cellular growth, adhesion, and protects explanted primary brain cells from in vitro stresses. The fetal bovine serum (FBS) supplement used in most CM, however, contains significant quantities of extracellular vesicles (EVs) that confound quantitative and qualitative analyses from the EVs produced by the cultured cells. We quantitatively tested the ability of common FBS EV-depletion protocols to remove exogenous EVs from FBS-supplemented CM and evaluated the influence such methods have on primary astrocyte culture growth and viability. We assessed two methodologies utilized for FBS EV removal prior to adding to CM: (1) an 18-h ultracentrifugation (UC); and (2) a commercial EV-depleted FBS (Exo-FBS™). Our analysis demonstrated that Exo-FBS™ CM provided the largest depletion (75%) of total FBS EVs, while still providing 6.92 × 108 ± 1.39 × 108 EVs/mL. In addition, both UC and Exo-FBS™ CM resulted in poor primary astrocyte cell growth and viability in culture. The two common FBS EV-depletion methods investigated, therefore, not only contaminate in vitro primary cell-derived EV analyses, but also provide a suboptimal environment for primary astrocyte cell growth and viability. It appears likely that future CM optimization, using a serum-free alternative, might be required to advance analyses of cell-specific EVs isolated in vitro.

Lipid Nanovesicle Platforms for Hepatocellular Carcinoma Precision Medicine Therapeutics: Progress and Perspectives.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality globally. HCC is highly heterogenous with diverse etiologies leading to different driver mutations potentiating unique tumor immune microenvironments. Current therapeutic options, including immune checkpoint inhibitors and combinations, have achieved limited objective response rates for the majority of patients. Thus, a precision medicine approach is needed to tailor specific treatment options for molecular subsets of HCC patients. Lipid nanovesicle platforms, either liposome- (synthetic) or extracellular vesicle (natural)-derived present are improved drug delivery vehicles which may be modified to contain specific cargos for targeting specific tumor sites, with a natural affinity for liver with limited toxicity. This mini-review provides updates on the applications of novel lipid nanovesicle-based therapeutics for HCC precision medicine and the challenges associated with translating this therapeutic subclass from preclinical models to the clinic.

Mutational landscape and predictors of survival in head and neck mucosal melanoma.

KEY POINTS: Head and neck mucosal melanomas have a diverse mutational landscape with low mutational burden. A molecular subset (∼13%) has ROS1 mutations, which is an actionable driver mutation. ROS1-mutated patients have improved overall survival likely due to high mutational burden.

Lymphatic endothelial-like cells promote glioblastoma stem cell growth through cytokine-driven cholesterol metabolism.

Glioblastoma is the most lethal primary brain tumor with glioblastoma stem cells (GSCs) atop a cellular hierarchy. GSCs often reside in a perivascular niche, where they receive maintenance cues from endothelial cells, but the role of heterogeneous endothelial cell populations remains unresolved. Here, we show that lymphatic endothelial-like cells (LECs), while previously unrecognized in brain parenchyma, are present in glioblastomas and promote growth of CCR7-positive GSCs through CCL21 secretion. Disruption of CCL21-CCR7 paracrine communication between LECs and GSCs inhibited GSC proliferation and growth. LEC-derived CCL21 induced KAT5-mediated acetylation of HMGCS1 on K273 in GSCs to enhance HMGCS1 protein stability. HMGCS1 promoted cholesterol synthesis in GSCs, favorable for tumor growth. Expression of the CCL21-CCR7 axis correlated with KAT5 expression and HMGCS1K273 acetylation in glioblastoma specimens, informing patient outcome. Collectively, glioblastomas contain previously unrecognized LECs that promote the molecular crosstalk between endothelial and tumor cells, offering potentially alternative therapeutic strategies.

Impact of Treatment Modalities upon Survival Outcomes in Skull Base and Clival Chordoma: An NCDB Analysis.

Objectives Skull base chordomas are locally aggressive malignant tumors derived from the notochord remnant. There are limited large-scale studies examining the role and extent of surgery and radiation therapy. Design Analysis of the National Cancer Database (NCDB) was performed to evaluate the survival outcomes of various treatments, and to assess for predictors of overall survival (OS). Participants This is a retrospective, population-based cohort study of patients diagnosed with a clival/skull base chordoma between 2004 and 2015 in the NCDB. Main Outcome Measures The primary outcome was overall survival (OS). Results In all, 468 cases were identified. Forty-nine percent of patients received surgery and 20.7% had positive margins. Mean age at diagnosis was 48.4 years in the surgical cohort, and 55% were males. Of the surgical cohort, 33.8% had negative margins, 20.7% had positive margins, and 45.5% had unknown margin status. Age ≥ 65 (hazard ratio [HR]: 3.07; 95% confidence interval [CI]: 1.63-5.76; p < 0.001), diagnosis between 2010 and 2015 (HR: 0.49; 95% CI: 0.26-0.90; p = 0.022), tumor size >5 cm (HR: 2.29; 95% CI: 1.26-4.15; p = 0.007), and government insurance (HR: 2.28; 95% CI: 1.24-4.2; p = 0.008) were independent predictors of OS. When comparing surgery with or without adjuvant radiation, no survival differences were found, regardless of margin status ( p = 0.66). Conclusion Surgery remains the mainstay of therapy. Advanced age (>65 years), large tumor size, and government insurance were predictors of worse OS. Whereas negative margins and the use of adjuvant radiation did not appear to impact OS, these may very well reduce local recurrences. A multidisciplinary approach is critical in achieving optimal outcomes in this challenging disease.

Association Between Olfactory Dysfunction and Critical Illness and Mortality in COVID-19: A Meta-analysis.

LEVEL OF EVIDENCE: 4.

Association Between 5-Item Modified Frailty Index and Short-term Outcomes in Complex Head and Neck Surgery.

OBJECTIVES: To evaluate the impact of preoperative frailty on short-term outcomes following complex head and neck surgeries (HNSs). STUDY DESIGN: Cross-sectional database analysis. SETTING: American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database. METHODS: The 2005 to 2017 ACS-NSQIP was queried for patients undergoing complex HNS. Five-item modified frailty index (mFI) was calculated based on functional status and history of diabetes, chronic obstructive pulmonary disease, congestive heart failure, and chronic hypertension. RESULTS: A total of 2786 patients (73.1% male) with a mean age of 62.0 ± 11.6 years were included. Compared to nonfrail patients (41.2%), patients with mFI ≥1 (58.8%) had shorter length of operation (P = .021), longer length of stay (LOS) (P < .001), and higher rates of 30-day reoperation (P = .009), medical complications (P < .001), discharge to nonhome facility (DNHF) (P < .001), and mortality (P = .047). These parameters remained statistically significant when compared across all individual mFI scores (all P < .05). After adjusting for age, sex, race, body mass index, smoking, and American Society of Anesthesiologists score via multivariate logistic regression, patients with mFI ≥1 were significantly more likely to undergo reoperation (odds ratio [OR], 1.39), surgical complications (OR, 1.19), medical complications (OR, 1.55), prolonged LOS (OR, 1.29), and DNHF (OR, 1.56) (all P < .05). Multivariate logistic regression also demonstrated that after adjusting for confounders, compared to patients with mFI = 1, patients with mFI = 2-5 (18.7%) were more likely to undergo shorter operations (OR, 0.74), have medical (OR, 1.46) or any complications (OR, 1.27), and have DNHF (OR, 1.62) (all P < .05). CONCLUSION: The 5-point mFI can independently predict short-term surgical outcomes following complex HNS. This simple and reliable metric can potentially lead to improved preoperative counseling and postoperative planning for complex HNS patients.

Treatment selection towards active surveillance over definitive treatment for pituitary adenomas is influenced by sociodemographic factors.

BACKGROUND: Clinical and sociodemographic predictors of pituitary adenoma (PA) patients undergoing active surveillance (AS) versus definitive treatment (DT) are poorly understood. OBJECTIVE: This population-based analysis aims to identify clinical and sociodemographic predictors of undergoing AS versus DT. METHODS: The National Cancer Database (NCDB) was utilized to query PA patients diagnosed from 2010 to 2015 undergoing AS or DT. Independent-samples t-test and chi-squared test were used to compare differences in patient baseline characteristics and a stepwise binary logistic regression was performed to elucidate factors implicated in undergoing AS. RESULTS: The cohort consisted of 30,233 PA patients, with 5147 (17.0%) patients undergoing AS. On multivariable logistic regression, patients aged ≥ 65 years (OR=1.65; p < 0.001), African American race (OR=1.12; p = 0.035), having government insurance (OR=1.45; p < 0.001) or those uninsured (OR=1.58; p < 0.001) were significantly more likely to undergo AS compared to DT, while patients with larger tumors (OR=0.90; p < 0.001), receiving treatment at academic facilities (OR=0.75; p < 0.001), and living in West regions of the United States (OR=0.59; p < 0.001) were significantly less likely to undergo AS compared to DT. CONCLUSIONS: Significant sociodemographic disparities exist in patient selection for undergoing AS versus DT, which may modify patient clinical outcomes.

Refusal of Surgery in Pituitary Adenoma Patients: A Population-Based Analysis.

We characterized the clinical and sociodemographic factors predictive of surgery refusal in pituitary adenoma (PA) patients. We queried the National Cancer Database (NCDB) to identify adult PA patients treated from 2004−2015 receiving or refusing surgery. Multivariate logistic regression and Cox proportional-hazards analysis identified clinical and/or sociodemographic factors predictive of surgery refusal or mortality, respectively. Of the 34,226 patients identified, 280 (0.8%) refused surgery. On multivariate logistic regression, age > 65 (OR: 2.64; p < 0.001), African American race (OR: 1.70; p < 0.001), Charlson-Deyo Comorbidity (C/D) Index > 2 (OR: 1.52; p = 0.047), and government insurance (OR: 2.03; p < 0.001) or being uninsured (OR: 2.16; p = 0.03) were all significantly associated with surgery refusal. On multivariate cox-proportional hazard analysis, age > 65 (HR: 2.66; p < 0.001), tumor size > 2 cm (HR: 1.30; p < 0.001), C/D index > 1 (HR: 1.53; p < 0.001), having government insurance (HR: 1.66; p < 0.001) or being uninsured (HR: 1.67; p < 0.001), and surgery refusal (HR: 2.28; p < 0.001) were all significant predictors of increased mortality. Macroadenoma patients receiving surgery had a significant increase in overall survival (OS) compared to those who refused surgery (p < 0.001). There are significant sociodemographic factors that influence surgery refusal in PA patients. An individualized approach is warranted that considers functional status, clinical presentations, and patient choice.

Patterns of Opioid Usage and Predictors of Utilization Following Endoscopic Skull Base Surgery.

OBJECTIVE: Pain control is an important topic that has not been extensively studied in patients undergoing endoscopic skull base surgery (ESBS). The purpose of this study is to identify opioid requirements after ESBS and the risk factors predictive of increased use. METHODS: This study was a retrospective review of all patients undergoing ESBS at a tertiary academic skull base surgery program between July 2018 and August 2020. The primary outcome variable was total morphine equivalent dose (MED) requirements after surgery, calculated as the sum of all morphine milligram equivalents over a 24-h period, and summated across the duration of each participant's hospital course. RESULTS: 94 patients were included in this review. Average daily MED requirements were 14.00 ± 6.79 mg. Average total MED requirements were 83.78 ± 92.99 mg during hospitalization. Average length of stay (LOS) was 5.71 ± 4.42 days, with 22 (23.4%) patients not requiring opioid use upon discharge. On multivariate analysis, female sex (ß = 49.62; 95% CI [13.53, 85.71], p = 0.008), nasoseptal flap (NSF) reconstruction (ß = 49.56; 95% CI [13.51, 85.61], p = 0.008) and LOS (ß = 4.02; 95% CI [0.001, 8.04], p = 0.050) were independently associated with higher total MED requirements. CONCLUSIONS: We report average total MED requirements of 83.78 mg after ESBS, with female sex, intraoperative use of an NSF, and increased LOS as predictors of higher MED use. This data indicates a subset of patients who may benefit from more aggressive pain control strategies upfront, including consideration of non-opioid, multimodal pain regimens. LEVEL OF EVIDENCE: 3 Laryngoscope, 132:1939-1945, 2022.

Long-term outcomes in sinonasal squamous cell carcinoma arising from inverted papilloma: Systematic review.

Long-term survival and recurrence patterns of squamous cell carcinoma arising from inverted papilloma (IP-SCC) have not been thoroughly investigated. Four electronic databases were searched and primary studies describing overall survival (OS), recurrence, and mean time to recurrence of patients with IP-SCC were included for review. Our search yielded 662 studies. The 28 studies selected for inclusion identified 663 patients with IP-SCC. In 596 patients with reported T classification, 439 (73.7%) were T3/T4 on presentation. Of the 650 participants with recurrence data (local, regional, and distant), 155 (23.8%) experienced a recurrence, with an aggregate mean time-to-recurrence of 24.3 months. In 565 patients with 5-year OS rates, the aggregate 5-year OS was 62%. Based on the literature to date, IP-SCC is associated with a 5-year OS rate of 62%. 23.8% of patients experienced recurrence at a mean time of 24.3 months, suggesting the need for long-term surveillance.

Adjuvant Therapy and Prognosticators of Survival in Head and Neck Mucosal Melanoma.

OBJECTIVES/HYPOTHESIS: To identify prognosticators and determine the efficacies of surgery with adjuvant radiotherapy (SR) and surgery with immunotherapy (SI) of head and neck mucosal melanoma (HNMM). STUDY DESIGN: Retrospective database study. METHODS: The 2004 to 2017 National Cancer Database was queried for HNMM patients. Cox proportional hazards and Kaplan-Meier analyses evaluated prognosticators of mortality and survival benefits conferred by SR, SI, or surgery with adjuvant radiotherapy and immunotherapy (SRI). Logistic regression identified predictors of adjuvant radiotherapy or immunotherapy use. RESULTS: Overall, 1,910 cases (845 surgery, 802 SR, 51 SI, 101 SRI) were analyzed, with 50.3% females and an average age of 68.6 ± 13.8 years. SI was associated with greater overall survival (OS) than surgery (hazard ratio [HR] 0.672; P = .036). SI (HR 0.425; P = .024) and SRI (HR 0.594; P = .045) were associated with superior OS than SR. Older age (HR 1.607; P < .001), female sex (HR 0.757; P = .006), paranasal sinus localization (HR 1.648; P < .001), T4 classification (HR 1.443; P < .001), N1 classification (HR 2.310; P < .001), M1 classification (HR 3.357; P < .001), and positive surgical margins (HR 1.454; P < .001) were survival prognosticators. Adjuvant radiotherapy use was negatively correlated with older age, oral cavity localization, and M0 or T3 tumors (all P < .05). Adjuvant immunotherapy use was positively correlated with younger age and M1 tumors (all P < .05). CONCLUSIONS: Although SR did not confer survival benefits in HNMM patients, SI and SRI yielded greater OS than surgery alone. SRI was associated with superior survival outcomes than SR. Certain demographic and clinical factors were associated with increased mortality risk. Patient age and certain tumor characteristics were predictors of adjuvant radiotherapy or immunotherapy use. LEVEL OF EVIDENCE: 4 Laryngoscope, 132:584-592, 2022.