Current Trends in Precision Medicine and Next-Generation Sequencing in Head and Neck Cancer.

OPINION STATEMENT: As the field of oncology enters the era of precision medicine and targeted therapies, we have come to realize that there may be no single "magic bullet" for patients with head and neck cancer. While immune check point inhibitors and some targeted therapeutics have shown great promise in improving oncologic outcomes, the current standard of care in most patients with head and neck squamous cell carcinoma (HNSCC) remains a combination of surgery, radiation, and/or cytotoxic chemotherapy. Nevertheless, advances in precision medicine, next-generation sequencing (NGS), and targeted therapies have a potential future in the treatment of HNSCC. These roles include increased patient treatment stratification based on predictive biomarkers or targetable mutations and novel combinatorial regimens with existing HNSCC treatments. There remain challenges to precision medicine and NGS in HNSCC, including intertumor and intratumor heterogeneity, challenging targets, and need for further trials validating the utility of NGS and precision medicine. Additionally, there is a need for evidence-based practice guidelines to assist clinicians on how to appropriately incorporate NGS in care for HNSCC. In this review, we describe the current state of precision medicine and NGS in HNSCC and opportunities for future advances in this challenging but important field.

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.

The Role of Hyperbaric Oxygen in Head and Neck Reconstruction and Facial Cosmetic Surgery.

Hyperbaric oxygen (HBO) is a treatment modality with the primary mechanism of therapy being the delivery of oxygen to hypoxic tissues. A review of HBO applications in the field of head and neck reconstruction and facial cosmetic surgery is provided. HBO can be useful in the management of radiation sequelae and treatment of compromised flaps and grafts. It may also have application in tissue compromise following cosmetic surgery and dermal fillers. We provide evidence from the available literature as well as highlight our experience in using HBO in head and neck reconstruction.

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.

Expanding the Utilization of the Osteocutaneous Radial Forearm Free Flap beyond Mandibular Reconstruction.

Background The osteocutaneous radial forearm free flap (OCRFFF) for mandibular reconstruction has been well described. Despite this flap's utility in the repair of such defects, the indications for the OCRFFF have continued to expand in recent years. The advantages of the OCRFFF allow for a high degree of versatility in the reconstruction of the various anatomical and aesthetic units of the head and neck. In this review, the authors aim to explore the successful utilization of the OCRFFF beyond the reconstruction of composite mandibular defects. Methods A retrospective chart review was performed. All subjects who underwent OCRFFF reconstruction at a tertiary academic center between January 2004 and December 2014 were identified. A total of six patients undergoing this procedure for indications other than composite mandibular defects of the head and neck were included. Results A total of six patients underwent OCRFFF reconstruction for correction of nonmandibular defects. Flap success was experienced in six of six cases (100%). Indications included midface maxillary reconstruction (N = 2), orbit reconstruction (N = 1), frontal sinus and forehead reconstruction (N = 2), and subglottic stenosis reconstruction (N = 1). There were no immediate perioperative complications. On long-term follow-up, one subject developed a nasocutaneous fistula following radiation and eventually required maxillary hardware removal. Conclusion As a result of its growing role and versatility, the OCRFFF should be incorporated as a multipurpose tool in the armamentarium of reconstructive microvascular surgeons in the repair of composite head and neck defects beyond the mandible.

The Use of Chatbots in Head and Neck Mucosal Malignancy Treatment Recommendations.

OBJECTIVE: As cancer patients increasingly use chatbots, it is crucial to recognize ChatGPT's potential in enhancing health literacy while ensuring validation to prevent misinformation. This study aims to assess ChatGPT-3.5's capability to provide appropriate staging and treatment recommendations for head and neck mucosal malignancies for vulnerable populations. STUDY DESIGN AND SETTING: Forty distinct clinical vignettes were introduced into ChatGPT to inquire about staging and treatment recommendations for head and neck mucosal malignancies. METHODS: Prompts were created based on head and neck cancer (HNC) disease descriptions (cancer location, tumor size, lymph node involvement, and symptoms). Staging and treatment recommendations according to the 2021 National Comprehensive Cancer Network (NCCN) guidelines were scored by three fellowship-trained HNC surgeons from two separate tertiary care institutions. HNC surgeons assessed the accuracy of staging and treatment recommendations, such as the completeness of surgery and the appropriateness of treatment modality. RESULTS: Whereas ChatGPT's responses were 95% accurate at recommending the correct first-line treatment based on the 2021 NCCN guidelines, 55% of the responses contained inaccurate staging. Neck dissection was incorrectly omitted from treatment recommendations in 50% of the cases. Moreover, 40% of ChatGPT's treatment recommendations were deemed unnecessary. CONCLUSION: This study emphasizes ChatGPT's potential in HNC patient education, aligning with NCCN guidelines for mucosal malignancies, but highlights the importance of ongoing refinement and scrutiny due to observed inaccuracies in tumor, nodal, metastasis staging, incomplete surgery options, and inappropriate treatment recommendations. Otolaryngologists can use this information to caution patients, families, and trainees regarding the use of ChatGPT for HNC education without expert guidance.

Managing Oromandibular Hardware Failure after Free Flap Surgery.

Hardware failure after oromandibular reconstruction using free tissue transfer can delay additional therapies directed at cancer treatment and prevent patients from returning to normal oral function. Understanding and strict adherence to principles of rigid fixation is critical in preventing complications. Early surgical intervention for hardware exposure as well as utilization of locoregional flaps may prevent the need for more extensive revision surgery.

Oropharyngeal reconstruction after transoral robotic surgery.

PURPOSE OF REVIEW: Transoral robotic surgery (TORS) has experienced an evolution in recent years. This technique has proved to be a safe and effective method for extirpation of select oropharyngeal tumors. Advances in technology as well as improved surgeon experience allow for the resection of larger, more complex cancers. Although healing by secondary intention remains the current standard for limited oropharyngeal defects, larger resections demand reconstruction with vascularized tissue to minimize morbidity and optimize functional outcomes. The objective of this review is to evaluate recent literature regarding oropharyngeal reconstruction after TORS. RECENT FINDINGS: A variety of reconstructive options to manage oropharyngeal defects exist. Several reconstructive algorithms have been suggested; however, careful consideration must be used to select the most ideal flap type. Locoregional flaps have shown excellent functional outcomes with limited morbidity. An increase in free flap reconstruction has been demonstrated, particularly among patients with larger TORS defects and following chemoradiation therapy. Despite limited data, robotic-assisted flap inset and microvascular anastomosis has recently shown promise. SUMMARY: Reconstruction and flap selection following TORS should be tailored to the patient and unique oropharyngeal defect. Functional outcomes are promising with low complication rates among these patients.

The Promise of Circulating Tumor DNA in Head and Neck Cancer.

As the seventh most common cancer globally, head and neck cancers (HNC) exert considerable disease burden, with an estimated 277,597 deaths worldwide in 2020 alone. Traditional risk factors for HNC include tobacco, alcohol, and betel nut; more recently, human papillomavirus has emerged as a distinct driver of disease. Currently, limitations of cancer screening and surveillance methods often lead to identifying HNC in more advanced stages, with associated poor outcomes. Liquid biopsies, in particular circulating tumor DNA (ctDNA), offer the potential for enhancing screening, early diagnosis, and surveillance in HNC patients, with potential improvements in HNC patient outcomes. In this review, we examine current methodologies for detecting ctDNA and highlight current research illustrating viral and non-viral ctDNA biomarker utilities in HNC screening, diagnosis, treatment response, and prognosis. We also summarize current challenges and future directions for ctDNA testing in HNC patients.

Predictors of survival following carotid blowout syndrome.

OBJECTIVES: Carotid blowout syndrome (CBS) is a rare, life-threatening complication for patients with head and neck cancer (HNC). The primary objective was to identify factors associated with survival following CBS. MATERIALS AND METHODS: A retrospective analysis of HNC patients treated at a single tertiary care hospital with CBS between 2016 and 2020 was performed. A multivariate Cox proportional-hazards model identified independent predictors of survival. A p value of <0.05 was considered significant. Kaplan-Meier survival analysis was performed. RESULTS: 45 patients were identified. The majority were male (80.0%) with a mean age of 64 years at time of blowout. Oropharynx was the most common primary site (48.9%) and 73.3% of patients had stage IV disease. 35 (77.7%) patients had active tumor at time of CBS. 93.3% of patients previously received RT with a mean total dose of 62.5 ± 14.8 Gy. Threatened/type I, impending/type II, and acute/type III CBS occurred in 6.7%, 62.2%, and 31.1% of cases, respectively. Patients underwent either embolization (80.0%) or endovascular stent placement (20.0%). The 30-day and 1-year OS rates were 70.1% and 32.0%, respectively. Primary oropharyngeal tumors (adjusted hazard ratio [aHR], 4.31 [1.30-15.15 95% confidence interval]), active tumor at time of CBS (aHR 8.21 [2.10-54.95]), ICA or CCA rupture (aHR 5.81 [1.63-21.50]), and acute/type III CBS (aHR 2.98 [1.08-7.98]) were independent predictors of survival. CONCLUSION: Primary oropharyngeal tumors, active tumor at time of CBS, ICA or CCA rupture, and acute/type III hemorrhage were independent predictors of survival. Multidisciplinary management and prompt, protocol-directed intervention may improve outcomes following CBS.

Postoperative Radiation Therapy in Oral Cavity Verrucous Carcinoma.

OBJECTIVES/HYPOTHESIS: We investigate the clinicopathologic and treatment factors associated with the use of postoperative radiation therapy (PORT) and its effect on overall survival (OS) for patients with oral cavity verrucous carcinoma (VC). STUDY DESIGN: Retrospective cohort study. METHODS: A retrospective cohort study of the National Cancer Database (NCDB) from 2006 to 2015 was performed. Multivariable logistic regression was used to identify independent predictive factors associated with the use of PORT. Cox Regression survival and propensity score analyses were used to evaluate the effect of PORT on mortality. RESULTS: A total of 356 adult patients with primary oral cavity VC who underwent definitive surgical resection were identified. A total of 10.7% of patients underwent definitive surgical resection followed by PORT. Variables associated with PORT included distance to the hospital per 10 miles (adjusted odds ratio [aOR], 0.81 [95% confidence interval (CI), 0.70-0.95]) and stage III-IV disease (aOR, 12.13 and 23.92, respectively). Multivariable Cox regression survival analysis indicated no evidence of survival benefit in patients undergoing PORT compared to surgery alone (adjusted hazard ratio 1.50 [0.74-3.05], P = .23). Propensity score analysis also showed no OS benefit with the use of PORT (P = .41). CONCLUSIONS: Variables associated with the use of PORT on multivariable analysis included closer distance to hospital and stage III-IV disease. No clear survival benefit with PORT was identified on either multivariable survival analysis or propensity score analysis. These results suggest that surgery alone with negative margins may be the optimal treatment for patients with oral cavity VC. LEVEL OF EVIDENCE: 4 Laryngoscope, 132:1953-1961, 2022.

Respiratory and pulmonary complications in head and neck cancer patients: Evidence-based review for the COVID-19 era.

BACKGROUND: Pulmonary complications and infections frequently affect patients with head and neck squamous cell carcinoma (HNSCC). Common characteristics can predispose these patients to the development of severe respiratory illness, which may be particularly relevant during the 2019 coronavirus disease (COVID-19) pandemic. METHODS: A scoping review was performed to assess the impact of pulmonary comorbidities and adverse respiratory outcomes in HNSCC patients. RESULTS: Advanced age, history of tobacco and alcohol abuse, and cardiopulmonary comorbidities are significant risk factors for the development of adverse respiratory outcomes. Treatment toxicities from radiation or chemoradiation therapy significantly increase these risks. CONCLUSION: Respiratory complications are a frequent cause of morbidity and mortality among HNSCC patients, and the COVID-19 pandemic may disproportionately affect this population. Interventions designed to decrease smoking and alcohol use, improve oral hygiene, and aggressively manage medical comorbidities are important to the long-term management and health of these patients.

Predictors of Postoperative Radiation Following Laser Resection in Early-Stage Glottic Cancer.

OBJECTIVE: Guideline recommendations for the treatment of early-stage glottic cancer are limited to single-modality therapy with surgery or radiation alone. We sought to investigate the clinicopathologic and treatment factors associated with the use of postoperative radiation therapy (PORT) following laser excision for patients with T1-T2N0 glottic squamous cell carcinoma (SCC). STUDY DESIGN: Retrospective observational study of the National Cancer Database. SETTING: National Cancer Database review from 2004 to 2014. PATIENTS AND METHODS: A total of 1338 patients with primary cT1-T2N0M0 glottic SCC undergoing primary laser excision were included. Hospitals were divided into quartiles based on yearly volume of laryngeal laser cases performed. Multivariate logistic regression was performed to identify independent predictors of PORT. RESULTS: The overall rate of PORT was 30.0%. Predictors of PORT included treatment at lower-volume hospitals (adjusted odds ratio [aOR] for quartiles 2-4, 1.32-4.84), positive margins (aOR, 3.83 [95% CI, 2.54-5.78]), and T2 tumors (aOR, 3.58 [95% CI, 2.24-5.74]). PORT utilization demonstrated a strong inverse correlation with hospital volume. Among top-quartile hospitals, the rate of PORT was 11.2%, while rates of PORT at second-, third-, and fourth-quartile institutions were 19.2%, 32.2%, and 37.4%, respectively. CONCLUSIONS: Predictors of PORT in multivariable analysis included treatment at lower-volume facilities, positive margins, and T2 disease. This study highlights the importance of treating early-stage glottic carcinoma at high-volume institutions. In addition, there is a need to reevaluate the use of PORT and reduce the rate of dual-modality therapy for patients with early-stage glottic SCC.

Myeloid sarcoma presenting as bilateral acute otitis externa in newly diagnosed acute myeloid leukemia.

Myeloid sarcoma (MS) is an extramedullary collection of immature myeloid cells that can commonly occur with acute myeloid leukemia (AML). While head and neck presentations are not unheard of, there have been few published pediatric cases of external auditory canal MS. Here, we report a case of a 14-year-old male who presented with MS masquerading as bilateral acute otitis externa. To the best of our knowledge, this is the first reported case of a bilateral presentation leading to a new diagnosis of AML. A literature review of head and neck presentations of MS is included.

Salvage laryngectomy following organ-preservation therapy - An evidence-based review.

Salvage total laryngectomy is often indicated in patients with recurrent or persistent laryngeal cancer after radiation or chemoradiation treatment. This article reviews and discusses key considerations regarding salvage laryngectomy. Within this article, a review of the salvage laryngectomy incidence in the major organ preservation trials, survival rates, predictors of outcomes, complication rates, and the roles of elective neck dissection and free tissue transfer for reconstruction in patients undergoing salvage laryngectomy is provided.

Revisiting the argument for 1- versus 2-vein outflow in head and neck free tissue transfers: A review of 317 microvascular reconstructions.

BACKGROUND: The purpose of this study was to determine the benefit of 1-vein versus 2-vein outflow in microvascular free tissue transfers. METHODS: A retrospective review reflects the experience of 6 surgeons. Analysis included all patients who underwent reconstruction at a single institution between January 2004 and December 2012. RESULTS: Three hundred nine patients underwent a total of 317 microvascular free flap reconstructions for head and neck defects. Two hundred thirteen of 317 flaps (67.2%) used 1 venous anastomosis and 104 (32.8%) used 2 venous anastomoses. Venous congestion necessitated urgent take back in 37 of 57 patients (64.9%) requiring exploration for perioperative complications. Thirty of 37 flaps (81.1%) with venous congestion had 1 vein anastomosis, whereas 7 (18.9%) had dual vein outflow (p = .03). Overall flap success was 303 of 317 (95.6%), despite an 18.0% (57 of 317) perioperative take back rate. CONCLUSION: Coapting 2 veins was shown to minimize venous congestion. © 2015 Wiley Periodicals, Inc. Head Neck 38: 820-823, 2016.

Evaluation of bone length and number of osteotomies utilizing the osteocutaneous radial forearm free flap for mandible reconstruction: An 8-year review of complications and flap survival.

BACKGROUND: The purpose of this study was to assess the impact of bone harvest length and multiple osteotomies on osteocutaneous radial forearm free flap (RFFF) complication rates. METHODS: A retrospective chart review was conducted for patients undergoing osteocutaneous RFFF reconstruction during an 8-year period. RESULTS: One hundred fifty-five osteocutaneous RFFF procedures were performed. Recipient-site flap complications were 18 of 55 (32.7%) when bone harvest length was less than 7 cm and 40 of 100 (40.0%) when it was ≥7 cm. No osteotomies were performed in 69 of 155 cases with a corresponding complication rate of 30.4% (21 of 69). One osteotomy was utilized in 69 of 155 flaps, whereas 17 of 155 required more than 1 osteotomy; complications were experienced in 42% (29 of 69) and 47% (8 of 17) of these cases, respectively. CONCLUSION: Osteocutaneous RFFF complication rates were only slightly higher when the bone length was ≥7 cm or when multiple osteotomies were required.