Update of a prognostic survival model in head and neck squamous cell carcinoma patients treated with immune checkpoint inhibitors using an expansion cohort.

BACKGROUND: Immune checkpoint inhibitors (ICI) treatment in recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) offers new therapeutic venues. We have previously developed a predictive survival model in this patient population based on clinical parameters, and the purpose of this study was to expand the study cohort and internally validate the model. METHODS: A single institutional retrospective analysis of R/M HNSCC patients treated with ICI. Clinical parameters collected included p-16 status, hemoglobin (Hb), albumin (Alb), lactate dehydrogenase (LDH), neutrophil, lymphocyte and platelet counts. Cox proportional hazard regression was used to assess the impact of patient characteristics and clinical variables on survival. A nomogram was created using the rms package to generate individualized survival prediction. RESULTS: 201 patients were included, 47 females (23%), 154 males (77%). Median age was 61 years (IQR: 55-68). P-16 negative (66%). Median OS was 12 months (95% CI: 9.4, 14.9). Updated OS model included age, sex, absolute neutrophil count, absolute lymphocyte count, albumin, hemoglobin, LDH, and p-16 status. We stratified patients into three risk groups based on this model at the 0.33 and 0.66 quantiles. Median OS in the optimal risk group reached 23.7 months (CI: 18.5, NR), 13.8 months (CI: 11.1, 20.3) in the average risk group, and 2.3 months (CI: 1.7, 4.4) in the high-risk group. Following internal validation, the discriminatory power of the model reached a c-index of 0.72 and calibration slope of 0.79. CONCLUSIONS: Our updated nomogram could assist in the precise selection of patients for which ICI could be beneficial and cost-effective.

Treatment decision and estimation of growth of head and neck paragangliomas.

PURPOSE: Head and neck paragangliomas are slow growing tumors where observation has become more widely accepted. Tumor growth rate as well as predictors of increased tumor growth were analyzed with the goal to identify factors to better predict disease progression and counsel patients. MATERIALS AND METHODS: Multi-institutional retrospective cohort study from 2011 to 2020. RESULTS: 130 head and neck paragangliomas in 125 patients were analyzed. 38 were observed (30.4%), 16 radiated (12.8%), and 71 underwent surgery (56.8%). Surgical patients were significantly younger (p = 0.038) and with more genetically mediated paragangliomas (p = 0.026). Significantly more patients were asymptomatic in the observation group (p = 0.005). Of the 39 observed tumors, 43.6% (n = 17) grew with a tumor doubling time of 5.67 years. More than half of the observed paragangliomas had no growth. When examining symptoms postoperatively and at follow-up, the surgical cohort had significantly more worsening symptoms (p = 0.007) and new cranial neuropathies (p = 0.031). CONCLUSIONS: Head and neck paragangliomas have slow growth rates if they grow at all. Patients in the surgical cohort had more clinical symptoms at presentation and worsening postoperative symptoms.

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.

Time to Surgery and Survival in Head and Neck Cancer.

BACKGROUND: The COVID-19 pandemic has required triage and delays in surgical care throughout the world. The impact of these surgical delays on survival for patients with head and neck squamous cell carcinoma (HNSCC) remains unknown. METHODS: A retrospective cohort study of 37 730 patients in the National Cancer Database with HNSCC who underwent primary surgical management from 2004 to 2016 was performed. Uni- and multivariate analyses were used to identify predictors of overall survival. Bootstrapping methods were used to identify optimal time-to-surgery (TTS) thresholds at which overall survival differences were greatest. Cox proportional hazard models with or without restricted cubic splines were used to determine the association between TTS and survival. RESULTS: The study identified TTS as an independent predictor of overall survival (OS). Bootstrapping the data to dichotomize the cohort identified the largest rise in hazard ratio (HR) at day 67, which was used as the optimal TTS cut-point in survival analysis. The patients who underwent surgical treatment longer than 67 days after diagnosis had a significantly increased risk of death (HR, 1.189; 95% confidence interval [CI], 1.122-1.261; P < 0.0001). For every 30-day delay in TTS, the hazard of death increased by 4.6%. Subsite analysis showed that the oropharynx subsite was most affected by surgical delays, followed by the oral cavity. CONCLUSIONS: Increasing TTS is an independent predictor of survival for patients with HNSCC and should be performed within 67 days after diagnosis to achieve optimal survival outcomes.

National treatment trends in human papillomavirus-positive oropharyngeal squamous cell carcinoma.

BACKGROUND: Human papillomavirus (HPV)-mediated oropharyngeal cancer (OPC) is associated with dramatically improved survival in comparison with HPV-negative OPC and can be successfully treated with surgical and nonsurgical approaches. National treatment trends for OPC were investigated with the National Cancer Data Base (NCDB). METHODS: The NCDB was reviewed for primary HPV-mediated OPC in 2010-2014. Multivariable regression was used to identify predictors of both nonsurgical therapy and receipt of adjuvant chemoradiation (CRT). RESULTS: There were 13,363 patients identified with a median age at diagnosis of 58 years. The incidence of triple-modality treatment (surgery with adjuvant chemotherapy) decreased from 23.7% in 2010 to 16.9% in 2014 (R2  = 0.96), whereas the incidence of nonsurgical treatment increased from 63.9% to 68.7% (R2  = 0.89). Hospitals in the top treatment volume quartile (quartile 1 [Q1]; n = 29) had a lower rate of positive margins (16.3%) than bottom-quartile centers (n = 741; rate of positive margins, 36.4%; P < .001); Q1 hospitals used surgical therapy significantly more. Independent predictors of nonsurgical therapy included older age, advanced disease, lower hospital volume, and living closer to the hospital or outside the Pacific United States. In surgically treated patients, younger age, lower hospital volume, nodal disease, positive surgical margins, and extranodal extension (ENE) also predicted more adjuvant CRT use. CONCLUSIONS: The use of upfront surgical treatment decreased from 2010 to 2014. Hospital volume shows a strong, inverse correlation with the rate of positive surgical margins. The upfront treatment strategy is predicted not only by staging but also by patient-, geographic-, and hospital-specific factors. Lower hospital volume remains independently associated with increased triple-modality therapy after adjustments for positive margins, ENE, and pathologic staging.

Custom Presurgical Planning for Midfacial Reconstruction.

Resection and reconstruction of midface involve complex ablative and reconstructive tools in head and oncology and maxillofacial prosthodontics. This region is extraordinarily important for long-term aesthetic and functional performance. From a reconstructive standpoint, this region has always been known to present challenges to a reconstructive surgeon due to the complex three-dimensional anatomy, the variable defects created, combination of the medical and dental functionalities, and the distance from reliable donor vessels for free tissue transfer. Another challenge one faces is the unique features of each individual resection defect as well as individual patient factors making each preoperative planning session and reconstruction unique. Understanding the long-term effects on speech, swallowing, and vision, one should routinely utilize a multidisciplinary approach to resection and reconstruction, including head and neck reconstructive surgeons, prosthodontists, speech language pathologists, oculoplastic surgeons, dentists, and/or craniofacial teams as indicated and with each practice pattern. With this in mind, we present our planning and reconstructive algorithm in midface reconstruction, including a dedicated focus on dental rehabilitation via custom presurgical planning.

Margin Analysis in Head and Neck Cancer: State of the Art and Future Directions.

BACKGROUND: The status of surgical margins is the most important prognosticator for patients undergoing surgical resection of head and neck squamous cell carcinoma (HNSCC). Despite this, analysis of surgical margins is fraught with inconsistencies, including the ways in which margins are sampled and interpreted. Fundamentally, even the definition what constitutes a "clear" (or negative) margin may vary between institutions, surgeons, and pathologists. METHODS: The PubMed database was queried for articles relevant to the topic, and experts in the field were consulted regarding key articles for inclusion. Abstracts were reviewed and the full text was accessed for articles of particular interest. RESULTS: Data regarding various approaches to traditional margin analysis have been published without consensus. Several next-generation technologies have emerged in recent years that hold promise. CONCLUSION: An overview and appraisal of traditional margin analysis techniques are provided. Additionally, we explore novel technologies that may assist in more accurate margin assessment, guide the extent of surgical resections intraoperatively, and inform decisions regarding adjuvant treatment postoperatively.

RNA Nanoparticle-Based Targeted Therapy for Glioblastoma through Inhibition of Oncogenic miR-21.

Targeted inhibition of oncogenic miRNA-21 has been proposed to treat glioblastoma by rescuing tumor suppressors, PTEN and PDCD4. However, systemic delivery of anti-miR-21 sequences requires a robust and efficient delivery platform to successfully inhibit this druggable target. Three-way-junction (3WJ)-based RNA nanoparticles (RNP), artificially derived from pRNA of bacteriophage phi29 DNA packaging motor, was recently shown to target glioblastoma. Here, we report that multi-valent folate (FA)-conjugated 3WJ RNP constructed to harbor anti-miR-21 LNA sequences (FA-3WJ-LNA-miR21) specifically targeted and delivered anti-miR-21 LNA and knocked down miR-21 expression in glioblastoma cells in vitro and in vivo with favorable biodistribution. Systemically injected FA-3WJ-LNA-miR21 RNP efficiently rescued PTEN and PDCD4, resulting in glioblastoma cell apoptosis and tumor growth regression. Overall survival rate was also significantly improved by FA-3WJ-LNA-miR21 RNP. These results are indicative of the clinical benefit of FA-3WJ RNP-based gene therapy for the successful targeted therapy of developing and even recurring glioblastoma.

Management of complications and compromised free flaps following major head and neck surgery.

Microvascular free flaps are preferred for most major head and neck reconstruction surgeries because of better functional outcomes, improved esthetics, and generally higher success rates. Numerous studies have investigated measures to prevent flap loss, but few have evaluated the optimal treatment for free flap complications. This study aimed to determine the complication rate after free flap reconstructions and discusses our management strategies. Medical records of 260 consecutive patients who underwent free flap reconstructions for head and neck defects between July 2006 and June 2010 were retrospectively reviewed for patient and surgical characteristics and postoperative complications. The results revealed that microvascular free flaps were extremely reliable, with a 3.5 % incidence of flap failure. There were 78 surgical site complications. The most common complication was neck wound infection, followed by dehiscence, vascular congestion, abscess, flap necrosis, hematoma, osteoradionecrosis, and brisk bleeding. Twenty patients with poor wound healing received hyperbaric oxygen therapy, which was ineffective in three patients who eventually experienced complete flap loss. Eleven patients with vascular congestion underwent medicinal leech therapy, which was effective. Among the 78 patients with complications, 44 required repeat surgery, which was performed for postoperative brisk bleeding in three. Eventually, ten patients experienced partial flap loss and nine experienced complete flap loss, with the latter requiring subsequent pectoralis major flap reconstruction. Microvascular free flap reconstruction represents an essential and reliable technique for head and neck defects and allows surgeons to perform radical resection with satisfactory functional results and acceptable complication rates.

Transoral robotic surgery for carcinoma of unknown primary in the head and neck.

Multiple diagnostic and treatment paradigms exist for the management of carcinoma of unknown primary (CUP) metastatic to cervical lymph nodes. Transoral robotic surgery (TORS) has emerged as a modality for diagnosis and treatment of CUP, optimizing identification and resection of the primary tumor, although also preventing chemotherapy in a subset of patients. This article presents the authors' treatment paradigm and reviews the literature supporting the use of TORS in the management of CUP.

Emerging role of nanog in tumorigenesis and cancer stem cells.

Nanog is a transcription factor that is well-established as a key regulator of embryonic stem cell (ESC) maintenance. Recent evidence demonstrates that Nanog is dysregulated and intimately involved in promoting tumorigenesis in part through regulation of the cancer stem cell (CSC) population. Elevated Nanog is associated with poorer outcome in numerous epithelial malignancies. Nanog is enriched in CSCs and ablation of Nanog is sufficient to reduce the CSC pool. Nanog has also been implicated to promote chemoresistance and epithelial-mesenchymal transition (EMT). Insight into the Nanog signaling cascade, upstream regulators and downstream effectors, is beginning to emerge but remains to be fully elucidated. This review highlights the current literature on the emerging role of Nanog in tumorigenesis and CSCs.

Elevated intrinsic cancer stem cell population in human papillomavirus-associated head and neck squamous cell carcinoma.

BACKGROUND: Human papillomavirus 16 (HPV16) is a major risk factor for the development of head and neck squamous cell carcinoma (HNSCC), particularly the development of oropharyngeal squamous cell carcinoma (OPSCC). Cancer stem cells (CSCs) are resistant to conventional therapies, and it is postulated that they are responsible for disease recurrence and/or progression. Because the prognoses of patients with HPV16-positive and HPV-negative HNSCC are distinct, the authors sought to determine whether differences in the number of CSCs could account for this clinical observation. METHODS: CSC populations in HPV16-positive and HPV-negative HNSCC were assessed using a proprietary assay based on expression of the enzyme aldehyde dehydrogenase (ALDH), an in vitro tumorsphere formation assay, and an in vivo limiting cell dilution in nonobese diabetic/severe combined immunodeficiency mice. A high-density tissue microarray was stained with ALDH1, a CSC marker, to determine the association between CSCs and HPV16-positive/HPV-negative OPSCC. RESULTS: HPV16-positive HNSCC had a greater intrinsic CSC pool than HPV-negative HNSCC. Inactivation of p53 has been identified as a major mechanism for the elevated CSC population in HPV16-positive HNSCC. In vivo limiting cell dilution experiments using tumors from patients with HPV16-positive and HPV-negative OPSCC indicated that the CSC frequency was 62.5-fold greater in an HPV16-positive OPSCC tumor than in an HPV-negative OPSCC tumor. Primary tumors from patients with HPV16-positive OPSCC were associated with elevated tumor ALDH1 staining, further extending the association between HPV16 and CSCs. CONCLUSIONS: The current data and the clinical observation that patients with HPV16-positive HNSCC respond more favorably to current treatment paradigms than patients with HPV-negative HNSCC support the suggestion that CSC phenotype is not homogeneous. Therefore, the reliance on the CSC number may be insufficient to accurately assess the potential of a particular tumor for disease recurrence and/or progression.

Efficacy and safety of near-infrared fluorescence identification of the thoracic duct during left lateral neck dissection.

BACKGROUND: Thoracic duct leaks occur in up to 5% of left lateral neck dissections. No one imaging modality is routinely used to identify the thoracic duct intraoperatively. The goal of our study was to evaluate the efficacy and safety of indocyanine green lymphangiography for intraoperative identification of the thoracic duct compared to traditional methods using ambient and evaluate the optimal timing of indocyanine green administration. METHODS: We enrolled all patients who underwent left lateral neck dissection at our institution from 2018 to 2022 in this prospective clinical trial. After indocyanine green injection into the dorsum of the foot, we performed intraoperative imaging was performed with a near-infrared fluorescence camera. We reported the data using descriptive statistics. RESULTS: Of the 42 patients we enrolled, 14 had prior neck surgery, and 3 had prior external beam radiation. We visualized the thoracic duct with ambient light in 48% of patients and with near-infrared fluorescence visualization in 64%. In 17% of patients, we could identify the thoracic duct only using near-infrared fluorescence visualization, which occurred within 3 minutes of injection, and were required to re-dose 5 patients. We visualized the thoracic duct with near-infrared fluorescence in all patients with prior neck radiation and 77% of patients with prior neck surgery. One adverse reaction occurred (hypotension), and 5 intraoperative thoracic duct injuries occurred that were ligated. There with no chylous fistulas postoperatively. CONCLUSION: This trial demonstrates that near-infrared fluorescence identification of the thoracic duct is feasible and safe with indocyanine green lymphangiography, even in patients with prior neck surgery or radiation.

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.

Single-Cell RNA-Seq Analysis of Patient Myeloid-Derived Suppressor Cells and the Response to Inhibition of Bruton's Tyrosine Kinase.

Myeloid-derived suppressor cell (MDSC) levels are elevated in patients with cancer and contribute to reduced efficacy of immune checkpoint therapy. MDSC express Bruton's tyrosine kinase (BTK) and BTK inhibition with ibrutinib, an FDA-approved irreversible inhibitor of BTK, leads to reduced MDSC expansion/function in mice and significantly improves the antitumor activity of anti-PD-1 antibody treatments. Single-cell RNA sequencing (scRNA-seq) was used to characterize the effect of ibrutinib on gene expression of fluorescence-activated cell sorting-enriched MDSC from patients with different cancer types [breast, melanoma, head and neck squamous cell cancer (HNSCC)]. Melanoma patient MDSC were treated in vitro for 4 hours with 5 µmol/L ibrutinib or DMSO, processed for scRNA-seq using the Chromium 10× Genomics platform, and analyzed via the Seurat v4 standard integrative workflow. Baseline gene expression of MDSC from patients with breast, melanoma, and HNSCC cancer revealed similarities among the top expressed genes. In vitro ibrutinib treatment of MDSC from patients with melanoma resulted in significant changes in gene expression. GBP1, IL-1ß, and CXCL8 were among the top downregulated genes whereas RGS2 and ABHD5 were among the top upregulated genes (P < 0.001). Double positive CD14+CD15+ MDSC and PMN-MDSC responded similarly to BTK inhibition and exhibited more pronounced gene changes compared with early MDSC and M-MDSC. Pathway analysis revealed significantly downregulated pathways including TREM1, nitric oxide signaling, and IL-6 signaling (P < 0.004). IMPLICATIONS: scRNA-seq revealed characteristic gene expression patterns for MDSC from different patients with cancer and BTK inhibition led to the downregulation of multiple genes and pathways important to MDSC function and migration.

Scalp Irradiation with 3D-Milled Bolus: Initial Dosimetric and Clinical Experience.

BACKGROUND AND PURPOSE: A bolus is required when treating scalp lesions with photon radiation therapy. Traditional bolus materials face several issues, including air gaps and setup difficulty due to irregular, convex scalp geometry. A 3D-milled bolus is custom-formed to match individual patient anatomy, allowing improved dose coverage and homogeneity. Here, we describe the creation process of a 3D-milled bolus and report the outcomes for patients with scalp malignancies treated with Volumetric Modulated Arc Therapy (VMAT) utilizing a 3D-milled bolus. MATERIALS AND METHODS: Twenty-two patients treated from 2016 to 2022 using a 3D-milled bolus and VMAT were included. Histologies included squamous cell carcinoma (n = 14, 64%) and angiosarcoma (n = 8, 36%). A total of 7 (32%) patients were treated in the intact and 15 (68%) in the postoperative setting. The median prescription dose was 66.0 Gy (range: 60.0-69.96). RESULTS: The target included the entire scalp for 8 (36%) patients; in the remaining 14 (64%), the median ratio of planning target volume to scalp volume was 35% (range: 25-90%). The median dose homogeneity index was 1.07 (range: 1.03-1.15). Six (27%) patients experienced acute grade 3 dermatitis and one (5%) patient experienced late grade 3 skin ulceration. With a median follow-up of 21.4 months (range: 4.0-75.4), the 18-month rates of locoregional control and overall survival were 75% and 79%, respectively. CONCLUSIONS: To our knowledge, this is the first study to report the clinical outcomes for patients with scalp malignancies treated with the combination of VMAT and a 3D-milled bolus. This technique resulted in favorable clinical outcomes and an acceptable toxicity profile in comparison with historic controls and warrants further investigation in a larger prospective study.

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.

History, Innovation, Pearls, and Pitfalls in Complex Midface Reconstruction.

Midface reconstruction in head and neck cancer or individuals with extensive trauma to the face has evolved significantly over the past few decades with the introduction of free flap reconstruction and virtual surgical planning enabling surgeons to obtain optimal cosmetic and functional outcomes. Traditional methods such as the use of obturators or local flaps still have a role in select situations, but complex defects have been replaced by the advent of microvascular free tissue transfer and virtual planning, which can commonly provide a single-stage reconstruction of the midface with excellent aesthetic and functional results. This article provides an overview of the history and evolution of midface reconstruction, a discussion of how to integrate virtual surgical planning into a surgical practice, an example of a complex midface reconstruction case, and pearls and pitfalls that have been experienced by an experienced reconstructive team.

Internal jugular vein reconstruction: An algorithm for reconstructive surgeons.

OBJECTIVES: The internal jugular vein (IJV) provides critical drainage from the brain, skull, and deep regions of the face and neck. Compromise to the bilateral IJVs has severe sequelae, but even unilateral IJV sacrifice or thrombosis after treatment can have sequelae. Despite the potential role of IJV reconstruction for head and neck surgeons, information about the indications, technique, and outcomes of the procedure are sparse. PATIENTS AND METHODS: We present a woman who had IJV sacrifice for an oral cavity cancer along with a contralateral selective neck dissection and adjuvant chemoradiation who developed occlusion of the contralateral IJV after her treatment, resulting in unacceptable cervical lymphedema and extensive neck varicosities. An end-to-side bypass from the superior IJV to the ipsilateral external jugular vein was performed. RESULTS: There were no complications from the procedure, which resulted in dissipation of her preoperative symptoms. We describe the literature surrounding IJV reconstruction, considerations for its use, the technique itself, and advice for perioperative management. CONCLUSION: IJV reconstruction is a valuable but underutilized technique for the head and neck microvascular surgeon in cases of bilateral threatened IJV outflow.