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Importance: Late effects of head and neck cancer (HNC) treatment include profound dysphagia, chronic aspiration, and death. Functional laryngectomy (FL) can improve patient survival and quality of life (QoL); however, removing a failing larynx for a noncancer reason is a difficult decision. Data regarding the ability of FL to improve self-perceptions of voice, swallowing, and QOL in survivors of HNC with intractable aspiration are inconclusive., Objective: To investigate the association of FL with changes in self-reported perceptions of voice, swallowing, oral intake, QoL, and mood in survivors of HNC experiencing profound dysphagia and intractable aspiration., Design, Settings, and Participants: This cohort study was conducted at a single academic institution and included survivors of HNC with profound swallowing dysfunction and intractable aspiration who underwent FL from July 2016 through March 2022. Of the initial 22 patients enrolled, 2 patients (15%) died of aspiration pneumonia before receiving FL. Data analyses were performed from July 2016 through March 2023., Main Outcomes and Measures: Self-reported measures of voice using the VHI (30-item Voice Handicap Index), swallowing using the EAT-10 (10-item Eating Assessment Tool), functional oral intake scale using the FOIS (Functional Oral Intake Scale), and quality of life using the FACT-H&N (Functional Assessment of Cancer Therapy-Head & Neck) were assessed before FL and at 1, 3, and 6 months after FL. Mood states were evaluated using the POMS (Profile of Mood States, second edition), before FL and at 6 months after FL., Results: The study analyses included 20 patients (mean [SD] age, 72.4 (7.0) years; 19 [95%] males and 1 [5%] female) who underwent FL and had complete data across all time points. Among these, 12 patients (60%) had received chemoradiation for oropharyngeal, 7 (35%) for laryngeal, or 1 (5%) for nasopharyngeal cancer. The mean (SD) time from completion of oncologic treatment to FL was 15.5 (5.5) years. Mean (SD) score on the EAT-10 improved from 33.2 (7.4) to 23.1 (10.8) at 1 month; 12.1 (9.1) at 3 months; and 8.3 (7.4) at 6 months, with a large effect size (η2 = 0.72; 95% CI, 0.54-0.80). Mean (SD) score on the FOIS improved from 2.0 (1.5) to 2.9 (1.7) at 1 month; 4.8 (2.5) at 3 months; and 5.2 (1.7) at 6 months, with a large effect size (η2 = 0.6; 95% CI, 0.38-0.71). Improvement in oral intake was achieved in 19 patients (95%), and feeding tubes were removed in 10 of 16 patients (63%) who were feeding tube-dependent; 6 patients (27%) continued to require supplemental tube feedings. Mean (SD) score on the VHI improved from 63.6 (34.0) to 86.9 (33.7) at 1 month; 71.3 (36.1) at 3 months; and 39.7 (26.9) at 6 months, with a large effect size (η2 = 0.42; 95% CI, 0.19-0.56). Seventeen patients (85%) were able to use a tracheoesophageal voice prosthesis for alaryngeal communication. Mean (SD) score on the FACT-H&N improved from 86.2 (17.8) to 93.6 (18.4) at 1 month; 109.0 (18.4) at 3 months; and 121.0 (16.8) at 6 months, with a large effect size (η2 = 0.64; 95% CI, 0.42-0.74). Mean (SD) score on the POMS improved from 58.9 (13.2) at baseline to 44.5 (9.9) at 6 months, with a large effect size (Cohen d = 1.04; 95% CI, 0.48-1.57). None of the patients experienced major complications of FL; 1 patient (5%) had a postoperative pharyngocutaneous fistula., Conclusions and Relevance: The findings of this cohort study indicate that FL was associated with marked improvements in self-perception of voice and swallowing, functional oral intake, QoL, and mood state among survivors of HNC. These findings can serve as a framework for FL counseling among HNC survivors experiencing profound dysphagia and intractable aspiration.

Intraoperative identification of head and neck cancer tissue is essential to achieve complete tumor resection and mitigate tumor recurrence. Mesoscopic fluorescence lifetime imaging (FLIm) of intrinsic tissue fluorophores emission has demonstrated the potential to demarcate the extent of the tumor in patients undergoing surgical procedures of the oral cavity and the oropharynx. Here, we report FLIm-based classification methods using standard machine learning models that account for the diverse anatomical and biochemical composition across the head and neck anatomy to improve tumor region identification. Three anatomy-specific binary classification models were developed (i.e., "base of tongue," "palatine tonsil," and "oral tongue"). FLIm data from patients (N = 85) undergoing upper aerodigestive oncologic surgery were used to train and validate the classification models using a leave-one-patient-out cross-validation method. These models were evaluated for two classification tasks: (1) to discriminate between healthy and cancer tissue, and (2) to apply the binary classification model trained on healthy and cancer to discriminate dysplasia through transfer learning. This approach achieved superior classification performance compared to models that are anatomy-agnostic; specifically, a ROC-AUC of 0.94 was for the first task and 0.92 for the second. Furthermore, the model demonstrated detection of dysplasia, highlighting the generalization of the FLIm-based classifier. Current findings demonstrate that a classifier that accounts for tumor location can improve the ability to accurately identify surgical margins and underscore FLIm's potential as a tool for surgical guidance in head and neck cancer patients, including those subjects of robotic surgery.

Purpose: The purpose of this study is to examine the use of the Patient Health Questionnaire-2 (PHQ-2) to screen for depression in patients undergoing treatment for head and neck cancer and to evaluate potential patient-specific risk factors that may contribute to depression., Materials and Methods: This is a retrospective study at a tertiary-level hospital of outpatient adult patients with head and neck cancer who completed the PHQ-2/9 from 2019 to 2020. Patients were given a PHQ-2 during a surveillance visit. A positive PHQ-2 screen (score ≥ 3) prompted further evaluation with a PHQ-9. Patients were stratified into either low risk (PHQ-2 score < 3) or high risk (PHQ-2 score ≥ 3) for depression. Univariate regression was performed on all variables, and a multivariate logistic regression was performed on statistically significant variables (P < 0.05)., Results: In total, 110 patients were included in this study. Fifteen (14 %) patients had a positive PHQ-2 screen with a score ≥ 3 and underwent evaluation with a PHQ-9. The median PHQ-9 score was 15 (6-26). The PHQ-2 ≥ 3 group were significantly younger (59 years vs. 67 years; P = 0.03) and had a greater number of patients with a psychiatric history (33 % vs. 8 %; P < 0.01)., Conclusions: There is a strong association between a PHQ-2 score ≥ 3 and detection of depressive symptoms among patients with head and neck cancer. Younger age and pretreatment mental illness are significant risk factors for developing depression following treatment. Early screening and treatment should be considered for all patients to mitigate the burden of depression and suicide in this patient population. Further research is warranted to investigate utilization of the PHQ-2/9 to detect depression and barriers that exist for timely screening and interventions., Competing Interests: Conflict of interest None., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objectives: Head and neck cancer surgeons frequently interact with dying patients with advanced disease and their families, but little is known about their bereavement practices after a patient's death. The aim of this study is to elucidate the frequency of common bereavement practices, cited barriers to bereavement, and predictive physician factors that lead to an increase in bereavement practices among head and neck cancer surgeons., Methods: A 20-item survey was sent to 827 active surgeons of the American Head and Neck Society. Approval was obtained and the survey was distributed through the American Head and Neck Society. Demographics, frequency of common bereavement practices, empathy, and barriers were assessed. Multiple linear regression was performed to determine physician factors associated with more frequent bereavement follow-up., Results: There were 156 respondents (18.9% response rate). Overall, surgeons were more likely to usually/always call (48.5%) or send a letter (42.4%) compared with other practices such as attending funerals (0%), offering family meetings (18.6%), or referring family members to counseling (7.7%). Many barriers were cited as being at least somewhat important: being unaware about a patient's death (67.3%) was the most cited, whereas 51.3% cited a lack of mentorship/training in this area. Scoring higher on empathy questions (P ≤ .001) was associated with more frequent surgeon bereavement follow-up with the family of deceased patients., Conclusion: There is substantial practice variation among surgeons suggesting a lack of consensus on their roles in bereavement follow-up. Having higher empathy was predictive of higher engagement., Level of Evidence: NA Laryngoscope, 132:1971-1975, 2022., (© 2022 The American Laryngological, Rhinological and Otological Society, Inc.)

Background: This study evaluated whether fluorescence lifetime imaging (FLIm), coupled with standard diagnostic workups, could enhance primary lesion detection in patients with p16+ head and neck squamous cell carcinoma of the unknown primary (HNSCCUP)., Methods: FLIm was integrated into transoral robotic surgery to acquire optical data on six HNSCCUP patients' oropharyngeal tissues. An additional 55-patient FLIm dataset, comprising conventional primary tumors, trained a machine learning classifier; the output predicted the presence and location of HNSCCUP for the six patients. Validation was performed using histopathology., Results: Among the six HNSCCUP patients, p16+ occult primary was surgically identified in three patients, whereas three patients ultimately had no identifiable primary site in the oropharynx. FLIm correctly detected HNSCCUP in all three patients (ROC-AUC: 0.90 ± 0.06), and correctly predicted benign oropharyngeal tissue for the remaining three patients. The mean sensitivity was 95% ± 3.5%, and specificity 89% ± 12.7%., Conclusions: FLIm may be a useful diagnostic adjunct for detecting HNSCCUP., (© 2022 Wiley Periodicals LLC.)

Objectives/hypothesis: To evaluate the safety and potential efficacy of autologous muscle-derived cells (AMDCs) for the treatment of swallowing impairment following treatment for oropharynx cancer., Study Design: Prospective, phase I, open label, clinical trial., Methods: Oropharynx cancer survivors disease free ≥2 years post chemoradiation were recruited. All patients had swallowing impairment but were not feeding tube dependent (Functional Oral Intake Scale [FOIS] ≥ 5). Muscle tissue (50-250 mg) was harvested from the vastus lateralis and 150 × 10 6 AMDCs were prepared (Cook MyoSite Inc., Pittsburgh, PA). The cells were injected into four sites throughout the intrinsic tongue musculature. Participants were followed for 24 months. The primary outcome measure was safety. Secondary endpoints included objective measures on swallowing fluoroscopy, oral and pharyngeal pressure, and changes in patient-reported outcomes., Results: Ten individuals were enrolled. 100% (10/10) were male. The mean age of the cohort was 65 (±8.87) years. No serious adverse event occurred. Mean tongue pressure increased significantly from 26.3 (±11.1) to 31.8 (±9.5) kPa (P = .017). The mean penetration-aspiration scale did not significantly change from 5.6 (±2.1) to 6.8 (±1.8), and the mean FOIS did not significantly change from 5.4 (±0.5) to 4.6 (±0.7). The incidence of pneumonia was 30% (3/10) and only 10% (1/10) experienced deterioration in swallowing function throughout 2 years of follow-up. The mean eating assessment tool (EAT-10) did not significantly change from 24.1 (±5.57) to 21.3 (±6.3) (P = .12)., Conclusion: Results of this phase I clinical trial demonstrate that injection of 150 × 10 6 AMDCs into the tongue is safe and may improve tongue strength, which is durable at 2 years. A blinded placebo-controlled trial is warranted., Level of Evidence: 3 Laryngoscope, 132:523-527, 2022., (© 2021 The American Laryngological, Rhinological and Otological Society, Inc.)

Background: Immunotherapy agents are used to treat advanced head and neck lesions. We aim to elucidate relationship between immunotherapy and surgical wound complications., Methods: Retrospective multi-institutional case series evaluating patients undergoing ablative and flap reconstructive surgery and immunotherapy treatment., Main Outcome: wound complications., Results: Eight-two (62%) patients received preoperative therapy, 89 (67%) postoperative, and 33 (25%) in both settings. Forty-one (31%) patients had recipient site complications, 12 (9%) had donor site. Nineteen (14%) had major recipient site complications, 22 (17%) had minor. There was no statistically significant difference in complications based on patient or tumor-specific variables. Preoperative therapy alone demonstrated increased major complications (odds ratio [OR] 3.7, p = 0.04), and trend to more donor site complications (OR 7.4, p = 0.06), however treatment in both preoperative and postoperative therapy was not., Conclusions: Preoperative immunotherapy may be associated with increased wound complications. Controlled studies are necessary to delineate this association and potential risks of therapy., (© 2021 Wiley Periodicals LLC.)

We report the case of a myopericytoma of the neck. A 23-year-old female noticed a small, nontender mass in her left supraclavicular fossa. The mass grew over a period of 5 months, prompting the patient to seek evaluation. There were no motor or sensory deficits. Imaging suggested a mass originating from the middle scalene muscle. Computed tomography-guided core needle biopsy demonstrated a spindle cell neoplasm with smooth muscle differentiation. Complete surgical excision was performed. Histopathological and immunohistochemical evaluation of the tissue sample suggested myopericytoma. Myopericytoma is an extremely rare tumor of the head and neck. To our knowledge, this is the first reported case of a myopericytoma originating from a scalene muscle.

Head and neck squamous cell carcinomas (HNSCCs) are malignancies that originate in the mucosal lining of the upper aerodigestive tract. Despite advances in therapeutic interventions, survival rates among HNSCC patients have remained static for years. Cancer stem cells (CSCs) are tumor-initiating cells that are highly resistant to treatment, and are hypothesized to contribute to a significant fraction of tumor recurrences. Consequently, further investigations of how CSCs mediate recurrence may provide insights into novel druggable targets. A key element of recurrence involves the tumor's ability to evade immunosurveillance. Recent published reports suggest that CSCs possess immunosuppressive properties, however, the underlying mechanism have yet to be fully elucidated. To date, most groups have focused on the role of CSC-derived secretory proteins, such as cytokines and growth factors. Here, we review the established immunoregulatory role of exosomes derived from mixed tumor cell populations, and propose further study of CSC-derived exosomes may be warranted. Such studies may yield novel insights into new druggable targets, or lay the foundation for future exosome-based diagnostics.

Objective: Although basal cell carcinoma (BCC) is the most common skin cancer, locally aggressive BCC of the head and neck is rare and not well studied., Study Design: Retrospective review of patients who underwent primary surgical resection of locally aggressive head and neck BCC at a single tertiary academic center., Results: Eighty-seven patients with 98 tumors demonstrated a 5-year Kaplan-Meier estimated recurrence-free survival of 64.5%, overall survival of 83.3%, and disease-specific survival of 98.3%. Intraoperative positive frozen section margin was a strong independent predictor of local recurrence (hazard ratio 6.88, P = 0.038) and was more likely to occur in tumors previously treated with radiation (odds ratio 6.47 = 0.05)., Conclusion: Locally aggressive BCCs of the head and neck have high rates of local recurrence but low disease-specific mortality when treated with primary surgery and selected use of adjuvant therapy. Intraoperative positive frozen section margin is a strong independent predictor of local recurrence and is more likely in tumors that were previously treated with radiation therapy., Level of Evidence: 4 Laryngoscope, 130:115-119, 2020., (© 2019 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives: Compare length of stay, flap failure rate, medical and surgical complications and cost when patients undergoing head and neck free flap reconstruction are monitored in an intensive care unit (ICU) versus a specialty ward unit postoperatively., Materials and Methods: A prospective, non-inferiority, randomized controlled trial was conducted from 7/22/2016 to 9/12/2018 at a single institution. Patients were randomized to the ICU or specialty ward unit. Flap check protocols were identical between the groups. Perioperative and postoperative outcome variables were assessed and compared., Results: 131 patients were enrolled in the study and 118 ultimately underwent head and neck free flap reconstruction. 57 were randomized to the ICU and 61 to the specialty ward unit. There were no significant differences between the ICU and specialty ward unit groups with regard to demographic variables including age, gender, co-morbidities, tobacco or alcohol use, prior chemotherapy or radiation therapy treatment. There were no significant differences in perioperative variables including need for transfusion, tracheostomy, ischemia time, blood loss, fluid administration or post-operative antibiotic use. There was no significant difference in the primary outcome variable, length of stay. There were no significant differences in the number of the medical or surgical complications, flap failure rate, or hospital costs., Conclusion: In this prospective, randomized controlled trial, head and neck free-flap patients cared for on a specialty ward in the immediate post-operative period had equivalent outcomes to those cared for in the ICU., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Physician practice patterns regarding diagnosis and management of malnutrition in the head and neck cancer patient population are not well studied., Methods: A 17-question survey was distributed to 1392 members of the American Head and Neck Society (AHNS). The impact of hospital type, fellowship training, experience, and specialty was assessed., Results: Among AHNS members, there were 124 total respondents (9% response rate), including both otolaryngologists and radiation oncologists. Respondents strongly agreed (90%) that malnutrition negatively impacts patient outcomes. The majority (63%) felt comfortable screening for malnutrition, but 13% reported no routine assessment of malnutrition; 57% were unfamiliar with relevant guidelines. Barriers to screening included lack of familiarity with screening tools/guidelines, lack of time, and lack of access to dietitian., Conclusion: Although there was a strong consensus among respondents that the identification and management of malnutrition among head and neck cancer patients is critical, familiarity with relevant guidelines was poor., (© 2019 Wiley Periodicals, Inc.)

Objective: The recommended treatment for cutaneous squamous cell cancer (CuSCC) of the head and neck is Mohs surgical excision or wide local excision. Excision is recommended to a gross surgical margin of 4-6 mm however this is based on limited evidence and specify a goal histologic margin. The objective of this study was therefore to examine the reported histological margin distance following WLE of advanced CuSCC and its association with recurrence and survival., Study Design: Retrospective database review., Setting: All patients included received treatment at UC Davis Department of Otolaryngology-Head and Neck Surgery and/or Radiation Oncology in Sacramento, California., Subjects and Methods: The patients included were treated for advanced CuSCC with primary surgery with or without adjuvant therapy. Kaplan Meier survival curves with log rank analysis were then performed to compare 5-year recurrence free survival, and disease-specific survival for patients with different margin distances., Results: Total number of subjects was 92. The overall 5-year DSS and RFS was 68.8 and 51.0% respectively. When the pathological margin distance was ≥5 mm, 5-year disease specific survival was improved when compared to margin distance less than 5 mm (94.7 vs 60.7 p = 0.034)., Conclusion: The findings of this study suggest that a histologic margin of at least 5 mm may increase survival in advanced head and neck CuSCC patients.

Importance: Cutaneous squamous cell carcinoma (CSCC) is one of the most common malignant tumors worldwide. There is conflicting evidence regarding the indications for and benefits of adjuvant radiation therapy for advanced CSCC tumors of the head and neck., Objective: To assess indications for adjuvant radiation therapy in patients with CSCC., Design, Setting, and Participants: Retrospective analysis of 349 patients with head and neck CSCC treated with primary resection with or without adjuvant radiation therapy at 2 tertiary referral centers from January 1, 2008, to June 30, 2016., Main Outcomes and Measures: Data were compared between treatment groups with a χ2 analysis. Disease-free survival (DFS) and overall survival (OS) were analyzed using a Kaplan-Meier survival analysis with log-rank test and a Cox proportional hazards multivariate regression., Results: A total of 349 patients had tumors that met the inclusion criteria (mean [SD] age, 70 [12] years; age range, 32-94 years; 302 [86.5%] male), and 191 (54.7%) received adjuvant radiation therapy. The 5-year Kaplan-Meier estimates were 59.4% for DFS and 47.4% for OS. Patients with larger, regionally metastatic, poorly differentiated tumors with perineural invasion (PNI) and younger immunosuppressed patients were more likely to receive adjuvant radiation therapy. On Cox proportional hazards multivariate regression, patients with periorbital tumors (hazard ratio [HR], 2.48; 95% CI, 1.00-6.16), PNI (HR, 1.90; 95% CI, 1.12-3.19), or N2 or greater nodal disease (HR, 2.16; 95% CI, 1.13-4.16) had lower DFS. Immunosuppressed patients (HR, 2.17; 95% CI, 1.12-4.17) and those with N2 or greater nodal disease (HR, 2.43; 95% CI, 1.42-4.17) had lower OS. Adjuvant radiation therapy was associated with improved OS for the entire cohort (HR, 0.59; 95% CI, 0.38-0.90). In a subset analysis of tumors with PNI, adjuvant radiation therapy was associated with improved DFS (HR, 0.47; 95% CI, 0.23-0.93) and OS (HR, 0.44; 95% CI, 0.24-0.86). Adjuvant radiation therapy was also associated with improved DFS (HR, 0.36; 95% CI, 0.15-0.84) and OS (HR, 0.30; 95% CI, 0.15-0.61) in patients with regional disease., Conclusions and Relevance: Among patients with advanced CSCC, receipt of adjuvant radiation therapy was associated with improved survival in those with PNI and regional disease.

The incidence of oropharyngeal cancer (OPC) related to infection with human papillomavirus (HPV) is rising, making it now the most common HPV-related malignancy in the United States. These tumors present differently than traditional mucosal head and neck cancers, and those affected often lack classic risk factors such as tobacco and alcohol use. Currently, there are no approved approaches for prevention and early detection of disease, thus leading many patients to present with advanced cancers requiring intense surgical or nonsurgical therapies resulting in significant side effects and cost to the health-care system. In this review, we outline the evolving epidemiology of HPV-related OPC. We also summarize the available evidence corresponding to HPV-related OPC prevention, including efficacy and safety of the HPV vaccine in preventing oral HPV infections. Finally, we describe emerging techniques for identifying and screening those who may be at high risk for developing these tumors.

Recovery after major head and neck cancer surgery is a complex process. In addition to perioperative sequelae such as pain, wound infections, venous thromboembolism (VTE), and pneumonia, these patients frequently suffer from malnutrition. We provide a contemporary evidence-based approach to common aspects of perioperative care to guide the clinician in the optimal management of patients. Particular emphasis is placed on the preoperative education of patients and the identification and management of malnutrition around the time of surgery. This article discusses recommendations for perioperative antibiotics, pain management, and prophylaxis against VTE and pneumonia in this patient population., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective Cutaneous squamous cell carcinoma (CSCC) is one of the most common malignancies worldwide. With advanced CSCC of the head and neck, there is conflicting evidence on what constitutes high-risk disease. Our objective is to evaluate which factors are predictive of recurrence and nodal spread and survival. Study Design Case series with chart review. Setting Tertiary academic institution. Subjects and Methods Patients with advanced head and neck CSCC treated with primary resection identified by chart review. Results A total of 212 patients met inclusion criteria, with a mean age of 70.4 years; 87.3% were men. Mean tumor diameter was 3.65 cm, with an average depth of invasion of 1.38 cm. The mean follow-up time was 35 months (median, 21.5), and over that period 67 recurrences were recorded, 49 of which were local. The 5-year Kaplan-Meier estimate of disease-free survival for the cohort was 53.2%. On Cox multivariate analysis, recurrent disease, perineural invasion (PNI), and poorly differentiated histology were independent predictors of recurrence. On multinomial logistic regression, patients with primary tumors on the ear, cheek, temple, or lip, as well as those with PNI, were more likely to present with nodal metastasis. Conclusion For advanced CSCCs of the head and neck, patients with recurrent disease, PNI, and poorly differentiated tumors are at highest risk for local recurrence. Patients with tumors or the ear, cheek, temple, or lip, as well as those with PNI, are at increased risk of harboring nodal disease.

Importance: Head and neck cancers often require complex, labor-intensive surgeries, especially when free flap reconstruction is required. Enhanced recovery is important in this patient population but evidence-based protocols on perioperative care for this population are lacking., Objective: To provide a consensus-based protocol for optimal perioperative care of patients undergoing head and neck cancer surgery with free flap reconstruction., Evidence Review: Following endorsement by the Enhanced Recovery After Surgery (ERAS) Society to develop this protocol, a systematic review was conducted for each topic. The PubMed and Cochrane databases were initially searched to identify relevant publications on head and neck cancer surgery from 1965 through April 2015. Consistent key words for each topic included "head and neck surgery," "pharyngectomy," "laryngectomy," "laryngopharyngectomy," "neck dissection," "parotid lymphadenectomy," "thyroidectomy," "oral cavity resection," "glossectomy," and "head and neck." The final selection of literature included meta-analyses and systematic reviews as well as randomized controlled trials where available. In the absence of high-level data, case series and nonrandomized studies in head and neck cancer surgery patients or randomized controlled trials and systematic reviews in non-head and neck cancer surgery patients, were considered. An international panel of experts in major head and neck cancer surgery and enhanced recovery after surgery reviewed and assessed the literature for quality and developed recommendations for each topic based on the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system. All recommendations were graded following a consensus discussion among the expert panel., Findings: The literature search, including a hand search of reference lists, identified 215 relevant publications that were considered to be the best evidence for the topic areas. A total of 17 topic areas were identified for inclusion in the protocol for the perioperative care of patients undergoing major head and neck cancer surgery with free flap reconstruction. Best practice includes several elements of perioperative care. Among these elements are the provision of preoperative carbohydrate treatment, pharmacologic thromboprophylaxis, perioperative antibiotics in clean-contaminated procedures, corticosteroid and antiemetic medications, short acting anxiolytics, goal-directed fluid management, opioid-sparing multimodal analgesia, frequent flap monitoring, early mobilization, and the avoidance of preoperative fasting., Conclusions and Relevance: The evidence base for specific perioperative care elements in head and neck cancer surgery is variable and in many cases information from different surgerical procedures form the basis for these recommendations. Clinical evaluation of these recommendations is a logical next step and further research in this patient population is warranted.

Background: Treatment recommendations for advanced-stage laryngeal squamous cell carcinoma (SCC) have evolved significantly over the last 2 decades., Methods: We retrospectively analyzed patients in the Surveillance, Epidemiology, and End Results (SEER) database with advanced-stage laryngeal SCC treated between 2004 and 2012., Results: A total of 6797 patients were identified in the SEER database who met inclusion criteria, with 2051 patients undergoing primary surgery and 4746 patients undergoing primary radiotherapy (RT) or chemoradiotherapy (CRT). Disease-specific survival (DSS) and overall survival (OS) were significantly better for patients treated with primary surgery when compared using Kaplan-Meier curves and a Cox multivariate regression. When survival analysis was repeated for patients stratified by T classification, N classification, and subsite, OS and DSS benefits from primary surgery were observed for patients with T3 and T4a tumors, N0 neck disease, or supraglottic primaries., Conclusion: Patients with advanced-stage laryngeal SCC with T3 and T4a tumors, N0 neck disease, or supraglottic primaries have the greatest chance of survival when treated with primary surgery. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1380-1386, 2016., (© 2016 Wiley Periodicals, Inc.)

Background: The purpose of this study was to compare outcomes among patients treated by intensity-modulated radiotherapy (IMRT) with daily image-guided radiotherapy (IGRT) for head and neck cancer according to the margins used to expand the clinical target volume (CTV) to create a planning target volume (PTV)., Methods: Three hundred sixty-seven consecutive patients were treated with IMRT for squamous cell carcinoma of the head and neck. The first 103 patients were treated with 5-mm CTV-to-PTV margins. The subsequent 264 patients were treated using reduced (3 mm) margins., Results: The 3-year locoregional control for patients treated using 5-mm and 3-mm CTV-to-PTV margins, respectively, was 78% and 80% (p = .75). The incidence of gastrostomy-tube dependence at 1 year was 10% and 3%, respectively (p = .001). The incidence of posttreatment esophageal stricture was 14% and 7%, respectively (p = .01)., Conclusion: The use of reduced (3 mm) CTV-to-PTV margins was associated with reduced late toxicity while maintaining locoregional control., (© 2014 Wiley Periodicals, Inc.)

The overall objective of this study was to develop an optical imaging approach to simultaneously measure altered cell metabolism and changes in tissue extracellular pH with the progression of cancer using clinically isolated biopsies. In this study, 19 pairs of clinically normal and abnormal biopsies were obtained from consenting patients with head and neck cancer at University of California, Davis Medical Center. Fluorescence intensity of tissue biopsies before and after topical delivery of 2-NBDG (2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-D-glucose) and Alexa 647-pHLIP [pH (low) insertion peptide] was measured noninvasively by widefield imaging, and correlated with pathologic diagnosis. The results of widefield imaging of clinical biopsies demonstrated that 2-NBDG and pHLIP peptide can accurately distinguish the pathologically normal and abnormal biopsies. The results also demonstrated the potential of this approach to detect subepithelial lesions. Topical application of the contrast agents generated a significant increase in fluorescence contrast (3- to 4-fold) in the cancer biopsies as compared with the normal biopsies, irrespective of the patient and location of the biopsy within a head and neck cavity. This unpaired comparison across all the patients with cancer in this study highlights the specificity of the imaging approach. Furthermore, the results of this study indicated that changes in intracellular glucose metabolism and cancer acidosis are initiated in the early stages of cancer, and these changes are correlated with the progression of the disease. In conclusion, this novel optical molecular imaging approach to measure multiple biomarkers in cancer has a significant potential to be a useful tool for improving early detection and prognostic evaluation of oral neoplasia., (©2014 American Association for Cancer Research.)

Objectives/hypothesis: To examine functional and quality-of-life outcomes for patients treated by reirradiation to the head and neck for recurrent or new primary cancers., Study Design: Retrospective review., Methods: The University of Washington Quality of Life Instrument (UW-QOL) scores were reviewed with swallow evaluations for 17 patients with biopsy-proven recurrent or new primary squamous cell carcinoma of the head and neck treated with reirradiation who were clinically without evidence of disease at a minimum follow-up of 1 year. All patients had received their initial radiation therapy to a median dose of 66 Gy (range, 60-72 Gy). The median interval between radiation courses was 30 months (range, 6-132 months). The median reirradiation dose was 60 Gy (range, 54-70 Gy)., Results: At 1 year after reirradiation, the mean UW-QOL composite score was 67.0 (range, 22.1-83.5), which did not differ significantly from baseline (P = .57). The proportion of patients who rated their global quality of life as "very good" or "outstanding" at 1 year after reirradiation was 35%. The percentage of patients who reported their global quality of life as "good/fair" and "poor/very poor" were 59% and 6%, respectively., Conclusions: The majority of survivors in this highly selected series were devoid of new impairment after reirradiation and were satisfied with their functional status. Although nearly all patients had side effects from their prior radiation course prior to reirradiation, no patient reported a decline in global quality of life from before reirradiation to 1 year post-treatment., (© 2013 The American Laryngological, Rhinological and Otological Society, Inc.)

Objective: To demonstrate the feasibility of helical tomotherapy (HT)-based intensity-modulated radiotherapy (IMRT) for the treatment of synchronous primary cancers arising from the head and neck., Methods: 14 consecutive patients with histologically proven squamous cell carcinoma of the head and neck were determined to have a second primary cancer in the upper aerodigestive tract on further evaluation and were treated with HT using simultaneous integrated boost IMRT. Megavoltage CT scans were acquired daily as part of an image-guided registration protocol. Concurrent platinum-based systemic therapy was given to nine patients (64%)., Results: HT resulted in durable local control in 21 of the 28 primary disease sites irradiated, including a complete clinical and radiographic response initially observed at 17 of the 20 sites with gross tumour. The mean displacements to account for interfraction motion were 2.44 ± 1.25, 2.92 ± 1.09 and 2.31 ± 1.70 mm for the medial-lateral (ML), superior-inferior (SI) and anteroposterior (AP) directions, respectively. Table shifts of >3 mm occurred in 19%, 20% and 22% of the ML, SI and AP directions, respectively. The 2-year estimates of overall survival, local-regional control and progression-free survival were 58%, 73% and 60%, respectively., Conclusion: The effectiveness of HT for the treatment of synchronous primary cancers of the head and neck was demonstrated., Advances in Knowledge: HT is a feasible option for synchronous primary cancers of the head and neck and can result in long-term disease control with acceptable toxicity in appropriately selected patients.

Objectives/hypothesis: To analyze outcomes among patients with residual positron-emission tomography (PET)-negative lymphadenopathy after chemoradiotherapy for head and neck cancer based on whether or not they underwent neck dissection., Study Design: Retrospective review., Methods: Fifty-five patients with stage III/IV squamous cell carcinoma of the head and neck were identified with residual PET-negative lymphadenopathy based on standardized uptake value of <3. All patients had been treated with chemoradiotherapy to a median dose of 70 Gy (range, 60-4 Gy)., Results: With a median follow-up of 30 months (range, 6-67 months), the 3-year overall survival (85% vs. 81%, P = .57), progression-free survival (88% vs. 88%, P = .42), and local-regional control (96% vs. 100%, P = .68), did not differ between patients treated by neck dissection or observation., Conclusions: Omission of neck dissection appears to be reasonable for patients with residual lymphadenopathy but negative PET after chemoradiotherapy for head and neck cancer., Level of Evidence: 4., (© 2013 The American Laryngological, Rhinological and Otological Society, Inc.)

Purpose: Data from a prospective screening protocol administered for patients previously irradiated for head-and-neck cancer was analyzed to identify dosimetric predictors of brachial plexus-associated neuropathy., Methods and Materials: Three hundred fifty-two patients who had previously completed radiation therapy for squamous cell carcinoma of the head and neck were prospectively screened from August 2007 to April 2013 using a standardized self-administered instrument for symptoms of neuropathy thought to be related to brachial plexus injury. All patients were disease-free at the time of screening. The median time from radiation therapy was 40 months (range, 6-111 months). A total of 177 patients (50%) underwent neck dissection. Two hundred twenty-one patients (63%) received concurrent chemotherapy., Results: Fifty-one patients (14%) reported brachial plexus-related neuropathic symptoms with the most common being ipsilateral pain (50%), numbness/tingling (40%), and motor weakness and/or muscle atrophy (25%). The 3- and 5-year estimates of freedom from brachial plexus-associated neuropathy were 86% and 81%, respectively. Clinical/pathological N3 disease (P<.001) and maximum radiation dose to the ipsilateral brachial plexus (P=.01) were significantly associated with neuropathic symptoms. Cox regression analysis revealed significant dose-volume effects for brachial plexus-associated neuropathy. The volume of the ipsilateral brachial plexus receiving >70 Gy (V70) predicted for symptoms, with the incidence increasing with V70 >10% (P<.001). A correlation was also observed for the volume receiving >74 Gy (V74) among patients treated without neck dissection, with a cutoff of 4% predictive of symptoms (P=.038)., Conclusions: Dose-volume guidelines were developed for radiation planning that may limit brachial plexus-related neuropathies., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Purpose: The objective of this study is to determine the prevalence of tobacco consumption (i.e., cigarette use) among survivors of head and neck cancer after treatment with radiation therapy (RT)., Methods and Materials: A longitudinal study was conducted with 230 patients previously treated with RT for squamous cell carcinoma of the head and neck. All patients were clinically without evidence of disease and had a minimum of 1 year follow-up. Patients were summarily asked about the use of tobacco products at each follow-up visit. To explore for associations between potential predictors of post-RT smoking, the Chi-square test and Spearman's correlation coefficient were employed., Results: The percentage of patients who were actively smoking was 21%, 21%, and 20%, at 1, 2, and 3 years post-RT, respectively. When the analysis was limited to patients with a former smoking history (i.e., excluding all never-smokers), these percentages increased to 32%, 27%, and 25%, respectively. The intensity of smoking at follow-up ranged from one cigarette daily to 2.5 packs daily. Forty-two of 76 (55%) patients who were smoking at diagnosis were found to be smoking at 1-year follow-up compared to 7 of 154 patients who were not (p < 0.001). The only factor that significantly predicted for persistent smoking at follow-up was the presence of a preexisting psychiatric condition (most commonly, a mood disorder) at initial cancer diagnosis., Conclusions: A significant proportion of former smokers are actively smoking during follow-up despite having completed intensive RT and having their cancers evidently under control. Innovative interventional approaches to target those at highest risk for continued smoking are warranted., (Copyright © 2013 John Wiley & Sons, Ltd.)

Importance: Radiation therapy to the head and neck has traditionally been associated with adverse effects that can affect oral health and physical functioning. Although intensity-modulated radiotherapy (IMRT) has been widely adopted as a means of decreasing toxic effects, limited clinical data exist on its potential effect on long-term quality of life., Objective: To analyze quality of life among long-term survivors of head and neck cancer treated with IMRT., Design, Setting, and Participants: This cross-sectional analysis studied 50 consecutive long-term survivors of head and neck cancer from a comprehensive cancer center who had previously undergone IMRT that required bilateral neck irradiation for locally advanced disease. All patients were clinically without evidence of recurrent disease and had at least 5 years of follow-up., Main Outcomes and Measures: The University of Washington Quality of Life (UW-QOL) scores were reviewed for all study participants. The UW-QOL questionnaire consists of 12 domains that pertain to the degree of quality of life in the categories of pain, appearance, activity, recreation, swallowing, chewing, speech, shoulder function, taste, saliva, mood, and anxiety., Results: Five years after completion of IMRT, 42 patients (84%) reported that their health-related quality of life was "much better" or "somewhat better" than at the time of cancer diagnosis. With respect to recent health-related quality of life during the preceding 7 days at the time of completing the UW-QOL questionnaire, 40 patients (80%) treated with IMRT reported "outstanding" or "very good" levels of functioning. Five years after completion of treatment, 41 (82%) rated their overall quality of life as "outstanding" or "very good." The lowest domain score on the UW-QOL questionnaire at 5 years pertained to salivary dysfunction. However, 42 patients (84%) reported saliva "of normal consistency" or "less saliva than normal but enough" compared with 8 (16%) reporting "too little saliva." No patient reported having "no saliva.", Conclusions and Relevance: Our findings add to the body of literature that supports the acceptance of IMRT as standard treatment for head and neck cancer. The fact that most 5-year survivors were satisfied with their quality of lives points to the ability of IMRT to preserve long-term functioning.

Objectives: Although concurrent chemoradiation is increasingly used for patients with locally advanced head and neck cancer, many elderly patients receive radiation alone due to toxicity concerns. We evaluate acute and late toxicity among patients age ≥ 65 who received concurrent chemoradiation for head and neck cancer., Design: Retrospective review., Setting: Tertiary care center., Participants: Between 6/2003 and 8/2011, 40 consecutive patients age ≥ 65 underwent combined chemoradiation for head and neck cancer. Ten patients were treated in the postoperative setting and 30 underwent definitive chemoradiation. Twenty-eight patients received concurrent platinum-based chemotherapy and 12 received concurrent weekly paclitaxel. Treatment plans were designed to provide a dose of 66-72 Gy at 2-2.12 Gy/fraction to >95% of the gross tumor volume in the definitive setting or for positive margins and 60-66 Gy at 2 Gy/fraction post-operatively. Median follow-up was 23.2 months (range: 0-94.4 months)., Main Outcomes Measures: Acute skin and mucosal toxicity, unplanned treatment interruptions, and chronic treatment related toxicity including gastrostomy tube dependence as graded by the CTCAE v3.0., Results: Eight patients (20%) required a radiation treatment break of ≥ 3 days. Thirteen (33%) required unplanned hospitalization during or immediately following treatment. No grade 4+ skin or mucosal toxicity was noted. Five patients remained PEG tube dependent at >1 year. One patient developed non-healing mandibular osteoradionecrosis >3 years following chemoradiation. The 2-year Kaplan-Meier estimate of overall survival was 55%., Conclusion: Higher-than-expected rates of in-patient hospitalization with significant acute toxicity were noted in this cohort with a correspondingly high rate of radiation treatment breaks. Late toxicity rates were similar to those observed in historical controls with younger patients. Careful patient selection criteria should be employed for elderly patients considering concurrent chemoradiation for head and neck cancer., (© 2013 Elsevier Inc. All rights reserved.)

Background: To report a single institutional experience with definitive radiation therapy alone for human papillomavirus (HPV)-positive head and neck cancer., Methods: A total of 67 patients were treated by radiation therapy alone to a median dose of 70 Gy (range, 66-72 Gy) for squamous cell carcinoma of the head and neck. Paraffin-embedded, formalin-fixed pretreatment tumor tissues were used to establish HPV-positivity using standardized techniques of immunohistochemistry for p16 and polymerase chain reaction for HPV., Results: In all, 23 patients with HPV-positive cancers were identified. With a median follow-up of 28 months (range, 6-85 months), the 3-year actuarial rates of overall survival, locoregional control, and distant metastasis-free survival were 83%, 90%, and 88%, respectively., Conclusion: These findings attest to the exquisite radiosensitivity of HPV-positive head and neck cancer. The clinical outcomes observed from this selected series compare favorably with historical controls treated by more intensive chemoradiotherapy strategies., (Copyright © 2013 Wiley Periodicals, Inc.)

Importance: The diagnosis and subsequent treatment of head and neck cancer can have a potentially devastating impact on psychosocial functioning. Although the long-term physical adverse effects of radiation therapy (RT) for head and neck cancer have been well described, relatively few studies have evaluated psychosocial functioning after treatment., Objective: To determine the prevalence of self-reported depression among survivors of head and neck cancer returning for follow-up after being treated with RT., Design, Setting, and Participants: Cross-sectional analysis among 211 comprehensive cancer center patients with squamous cell carcinoma of the head and neck, who had been previously treated with RT and were disease-free with at least 1 year of follow-up. Patients with a history of mood disorder, use of mental health services in the past, or previous or current use of antidepressants or anxiolytics, excluding sleep medications, were specifically excluded., Interventions: The University of Washington Quality of Life instrument (UW-QOL), a brief, previously validated, self-administered questionnaire, was used to analyze rates of depression., Main Outcomes and Measures: The UW-QOL assigned scores of 0, 25, 50, 75, and 100 subjective responses of mood being "extremely depressed," "somewhat depressed," "neither in a good mood or depressed," "generally good," and "excellent," respectively., Results: The mean mood score did not differ at 1, 3, and 5 years after treatment, with scores of 52.0, 55.7, and 62.1, respectively. The proportion of patients who reported their mood as "somewhat depressed" or "extremely depressed" was 17%, 15%, and 13% at 1, 3, and 5 years, respectively. Variables that were significantly associated with post-RT depression included the presence of tracheostomy tube or laryngeal stoma (P = .01), gastrostomy tube dependence (P = .01), and continued smoking at the time of follow-up (P < .001). Among the patients reporting their mood as either "somewhat depressed" or "extremely depressed" at 1, 3, and 5 years, the proportion using antidepressants at the time was 6%, 11%, and 0%, respectively. The corresponding proportion of patients actively undergoing or seeking psychotherapy and/or counseling was 3%, 6%, and 0%, respectively., Conclusions and Relevance: Despite a relatively high rate of depression among patients with head and neck cancer in the post-RT setting, mental health services are severely underutilized.

Purpose: To compare the long-term quality of life among patients treated with and without intensity-modulated radiotherapy (IMRT) for head-and-neck cancer., Methods and Materials: The University of Washington Quality of Life instrument scores were reviewed for 155 patients previously treated with radiation therapy for locally advanced head-and-neck cancer. All patients were disease free and had at least 2 years of follow-up. Eighty-four patients (54%) were treated with IMRT. The remaining 71 patients (46%) were treated with three-dimensional conformal radiotherapy (3D CRT) by use of initial opposed lateral fields matched to a low anterior neck field., Results: The mean global quality of life scores were 67.5 and 80.1 for the IMRT patients at 1 and 2 years, respectively, compared with 55.4 and 57.0 for the 3D CRT patients, respectively (p < 0.001). At 1 year after the completion of radiation therapy, the proportion of patients who rated their global quality of life as "very good" or "outstanding" was 51% and 41% among patients treated by IMRT and 3DCRT, respectively (p = 0.11). At 2 years, the corresponding percentages increased to 73% and 49%, respectively (p < 0.001). On multivariate analysis accounting for sex, age, radiation intent (definitive vs. postoperative), radiation dose, T stage, primary site, use of concurrent chemotherapy, and neck dissection, the use of IMRT was the only variable independently associated with improved quality of life (p = 0.01)., Conclusion: The early quality of life improvements associated with IMRT not only are maintained but apparently become more magnified over time. These data provide powerful evidence attesting to the long-term benefits of IMRT for head-and-neck cancer., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Purpose: To identify clinical and treatment-related predictors of brachial plexus-associated neuropathies after radiation therapy for head-and-neck cancer., Methods and Materials: Three hundred thirty patients who had previously completed radiation therapy for head-and-neck cancer were prospectively screened using a standardized instrument for symptoms of neuropathy thought to be related to brachial plexus injury. All patients were disease-free at the time of screening. The median time from completion of radiation therapy was 56 months (range, 6-135 months). One-hundred fifty-five patients (47%) were treated by definitive radiation therapy, and 175 (53%) were treated postoperatively. Radiation doses ranged from 50 to 74 Gy (median, 66 Gy). Intensity-modulated radiation therapy was used in 62% of cases, and 133 patients (40%) received concurrent chemotherapy., Results: Forty patients (12%) reported neuropathic symptoms, with the most common being ipsilateral pain (50%), numbness/tingling (40%), motor weakness, and/or muscle atrophy (25%). When patients with <5 years of follow-up were excluded, the rate of positive symptoms increased to 22%. On univariate analysis, the following factors were significantly associated with brachial plexus symptoms: prior neck dissection (p = 0.01), concurrent chemotherapy (p = 0.01), and radiation maximum dose (p < 0.001). Cox regression analysis confirmed that both neck dissection (p < 0.001) and radiation maximum dose (p < 0.001) were independently predictive of symptoms., Conclusion: The incidence of brachial plexus-associated neuropathies after radiation therapy for head-and-neck cancer may be underreported. In view of the dose-response relationship identified, limiting radiation dose to the brachial plexus should be considered when possible., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Purpose: To compare patterns of disease failure among patients treated with intensity-modulated radiotherapy (IMRT) in conjunction with daily image-guided radiotherapy (IGRT) for head and neck cancer, according to the margins used to expand the clinical target volume (CTV) to create a planning target volume (PTV)., Methods and Materials: Two-hundred and twenty-five patients were treated with IMRT for squamous cell carcinoma of the head and neck. Daily IGRT scans were acquired using either kilovoltage or megavoltage volumetric imaging prior to each delivered fraction. The first 95 patients were treated with IMRT with 5-mm CTV-to-PTV margins. The subsequent 130 patients were treated using 3-mm PTV expansion margins., Results: Two-year estimates of overall survival, local-regional control, and distant metastasis-free survival were 76%, 78%, and 81%, respectively. There were no differences with respect to any of these endpoints among patients treated with 5-mm and 3-mm PTV expansion margins (p > 0.05, all). The 2-year local-regional control rate for patients treated with IMRT with 5-mm and 3-mm PTV margins was 78% and 78%, respectively (p = 0.96). Spatial evaluation revealed no differences in the incidences of marginal failures among those treated with 5-mm and 3-mm PTV margins., Conclusions: The use of 3-mm PTV expansion margins appears adequate and did not increase local-regional failures among patients treated with IMRT for head and neck cancer. These data demonstrate the safety of PTV reduction of less than 5 mm and support current protocols recommending this approach in the setting of daily IGRT., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Purpose: To determine how the addition of cisplatin-based concurrent chemotherapy to radiation therapy influences outcomes among a cohort of patients treated for head-and-neck cancer of unknown primary origin., Methods and Materials: The medical records of 60 consecutive patients treated by radiation therapy for squamous cell carcinoma of the head and neck presenting as cervical lymph node metastasis of occult primary origin were reviewed. Thirty-two patients (53%) were treated by concurrent chemoradiation, and 28 patients (47%) were treated by radiation therapy alone. Forty-five patients (75%) received radiation therapy after surgical resection, and 15 patients (25%) received primary radiation therapy. Thirty-five patients (58%) were treated by intensity-modulated radiotherapy., Results: The 2-year estimates of overall survival, local-regional control, and progression-free survival were 89%, 89%, and 79%, respectively, among patients treated by chemoradiation, compared to 90%, 92%, and 83%, respectively, among patients treated by radiation therapy alone (p > 0.05, for all). Exploratory analysis failed to identify any subset of patients who benefited from the addition of concurrent chemotherapy to radiation therapy. The use of concurrent chemotherapy was associated with a significantly increased incidence of Grade 3+ acute and late toxicity (p < 0.001, for both)., Conclusions: Concurrent chemoradiation is associated with significant toxicity without a clear advantage to overall survival, local-regional control, and progression-free survival in the treatment of head-and-neck cancer of unknown primary origin. Although selection bias cannot be ignored, prospective data are needed to further address this question., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Purpose: To describe the spatial distribution of local-regional recurrence (LRR) among patients treated postoperatively with intensity-modulated radiotherapy (IMRT) for head and neck cancer., Methods and Materials: The medical records of 90 consecutive patients treated by gross total resection and postoperative IMRT for squamous cell carcinoma of the head and neck from January 2003 to July 2009 were reviewed. Sites of disease were the oral cavity (43 patients), oropharynx (20 patients), larynx (15 patients), and hypopharynx (12 patients). Fifty patients (56%) received concurrent chemotherapy., Results: Seventeen of 90 patients treated with postoperative IMRT experienced LRR, yielding a 2-year estimate of local regional control of 80%. Among the LRR patients, 11 patients were classified as in-field recurrences, occurring within the physician-designated clinical target volume, and 6 patients were categorized as marginal recurrences. There were no out-of-field geographical misses. Sites of marginal LRRs included the contralateral neck adjacent to the spared parotid gland (3 patients), the dermal/subcutaneous surface (2 patients), and the retropharyngeal/retrostyloid lymph node region (1 patient)., Conclusions: Although the incidence of geographical misses was relatively low, the possibility of this phenomenon should be considered in the design of target volumes among patients treated by postoperative IMRT for head and neck cancer., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Purpose: To report a single-institutional experience using intensity-modulated radiotherapy with daily image-guided radiotherapy for the reirradiation of recurrent and second cancers of the head and neck., Methods and Materials: Twenty-one consecutive patients were prospectively treated with intensity-modulated radiotherapy from February 2006 to March 2009 to a median dose of 66 Gy (range, 60-70 Gy). None of these patients received concurrent chemotherapy. Daily helical megavoltage CT scans were obtained before each fraction as part of an image-guided radiotherapy registration protocol for patient alignment., Results: The 1- and 2-year estimates of in-field control were 72% and 65%, respectively. A total of 651 daily megavoltage CT scans were obtained. The mean systematic shift to account for interfraction motion was 1.38 ± 1.25 mm, 1.79 ± 1.45 mm, and 1.98 ± 1.75 mm for the medial-lateral, superior-inferior, and anterior-posterior directions, respectively. Pretreatment shifts of >3 mm occurred in 19% of setups in the medial-lateral, 27% in the superior-inferior, and 33% in the anterior-posterior directions, respectively. There were no treatment-related fatalities or hospitalizations. Complications included skin desquamation, odynophagia, otitis externa, keratitis, naso-lacrimal duct stenosis, and brachial plexopathy., Conclusions: Intensity-modulated radiotherapy with daily image guidance results in effective disease control with relatively low morbidity and should be considered for selected patients with recurrent and second primary cancers of the head and neck., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Purpose: An increasing proportion of patients with head and neck cancer have no history of smoking. The purpose of this analysis was to compare the clinical outcomes between patients without a history of smoking (never-smokers) and those with a previous history of smoking (ever-smokers) treated by radiation therapy., Methods and Materials: Seventy patients with newly diagnosed squamous cell carcinoma of the oropharynx or oral cavity without a previous history of smoking were matched to a control ever-smoker with a positive tobacco history (>10 pack-years) based on age, gender, ethnicity, Karnofsky Performance Status, primary tumor site, disease stage, primary treatment, radiation dose, and start date. Outcome was compared using Kaplan-Meier analysis. Normal tissue effects were graded according to the Radiation Therapy Oncology Group/European Organization for the Treatment of Cancer radiation toxicity criteria., Results: With a median follow-up of 33 months, lifelong never-smokers had an increased 3-year overall survival (86% vs. 69%), disease-free survival (82% vs. 65%), and local-regional control (85% vs. 70%) compared with the ever-smoker control population (P < 0.05, for all). These differences remained statistically significant when patients treated by postoperative or definitive radiation therapy were analyzed separately. The incidence of grade 3+ complications was also significantly lower among never-smokers compared with ever-smokers (10% vs. 29%, P = 0.01)., Conclusions: Prognosis differed significantly between never-smokers and ever-smokers with head and neck cancer treated by radiation therapy. Further studies analyzing the biologic and molecular reasons underlying these differences are planned.

Background: Due to concerns of radiation-related toxicity and hindered wound healing, the presence of a fistulous tract from the aerodigestive airway to the skin is commonly considered a contraindication for the initiation of postoperative radiation therapy (RT)., Methods and Materials: Seventeen patients with an orocutaneous (9 patients) or pharyngocutaneous (8 patients) fistula underwent postoperative RT for head and neck cancer to a median dose of 60 Gy (range, 60-70 Gy). The median time period from surgical resection to the first day of RT was 39 days (range, 23-77 days). All patients were irradiated over an open orocutaneous or pharyngocutaneous fistula using intensity-modulated (10 patients) or conventional (7 patients) techniques. The median size of the fistula at the initiation of RT was 2 cm (range, 0.5-5 cm)., Results: All 17 patients completed postoperative RT without any treatment breaks. However, 4 patients developed serious complications within 3 months after completion of treatment (1 osteomyelitis requiring intravenous antibiotics; 1 flap necrosis requiring surgical debridement; 1 oral commissure dihiscence requiring reconstruction; 1 tracheoesophageal fistula) resulting in a 24% rate of grade 3+ acute toxicity. Closure of the fistulous tract eventually occurred either spontaneously (9 patients) or after additional surgical intervention (8 patients). Late complications included 1 case of severe trismus requiring permanent gastrostomy tube and 1 case of osteoradionecrosis., Conclusion: Postoperative RT in the setting of orocutaneous and pharyngocutaneous fistula should be considered after judiciously weighing the potential benefits and risks. Since excessive delays in starting postoperative RT can portend worse oncologic outcomes, however, this treatment approach seems warranted in selected cases.

Purpose: To compare differences in dosimetric, clinical, and quality-of-life endpoints among a cohort of patients treated by intensity-modulated radiotherapy (IMRT) and conventional radiotherapy (CRT) for head-and-neck cancer of unknown primary origin., Methods and Materials: The medical records of 51 patients treated by radiation therapy for squamous cell carcinoma of the head and neck presenting as cervical lymph node metastasis of occult primary origin were reviewed. Twenty-four patients (47%) were treated using CRT, and 27 (53%) were treated using IMRT. The proportions of patients receiving concurrent chemotherapy were 54% and 63%, respectively., Results: The 2-year estimates of overall survival, local-regional control, and disease-specific survival for the entire patient population were 86%, 89%, and 84%, respectively. There were no significant differences in any of these endpoints with respect to radiation therapy technique (p>0.05 for all). Dosimetric analysis revealed that the use of IMRT resulted in significant improvements with respect to mean dose and V30 to the contralateral (spared) parotid gland. In addition, mean doses to the ipsilateral inner and middle ear structures were significantly reduced with IMRT (p<0.05 for all). The incidence of severe xerostomia in the late setting was 58% and 11% among patients treated by CRT and IMRT, respectively (p<0.001). The percentages of patients who were G-tube dependent at 6 months after treatment were 42% and 11%, respectively (p<0.001)., Conclusions: IMRT results in significant improvements in the therapeutic ratio among patients treated by radiation therapy for head-and-neck cancer of unknown primary origin., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Purpose: To evaluate the effect of continued cigarette smoking among patients undergoing radiation therapy for head-and-neck cancer by comparing the clinical outcomes among active smokers and quitters., Methods and Materials: A review of medical records identified 101 patients with newly diagnosed squamous cell carcinoma of the head and neck who continued to smoke during radiation therapy. Each active smoker was matched to a control patient who had quit smoking before initiation of radiation therapy. Matching was based on tobacco history (pack-years), primary site, age, sex, Karnofsky Performance Status, disease stage, radiation dose, chemotherapy use, year of treatment, and whether surgical resection was performed. Outcomes were compared by use of Kaplan-Meier analysis. Normal tissue effects were graded according to the Radiation Therapy Oncology Group/European Organization for the Treatment of Cancer toxicity criteria., Results: With a median follow-up of 49 months, active smokers had significantly inferior 5-year overall survival (23% vs. 55%), locoregional control (58% vs. 69%), and disease-free survival (42% vs. 65%) compared with the former smokers who had quit before radiation therapy (p < 0.05 for all). These differences remained statistically significant when patients treated by postoperative or definitive radiation therapy were analyzed separately. The incidence of Grade 3 or greater late complications was also significantly increased among active smokers compared with former smokers (49% vs. 31%, p = 0.01)., Conclusions: Tobacco smoking during radiation therapy for head-and-neck cancer is associated with unfavorable outcomes. Further studies analyzing the biologic and molecular reasons underlying these differences are planned., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Purpose: To analyze outcomes after radiation therapy for head-and-neck cancer among a cohort of patients with human immunodeficiency virus (HIV)., Methods and Materials: The medical records of 12 patients with serologic evidence of HIV who subsequently underwent radiation therapy to a median dose of 68 Gy (range, 64-72 Gy) for newly diagnosed squamous cell carcinoma of the head and neck were reviewed. Six patients (50%) received concurrent chemotherapy. Intensity-modulated radiotherapy was used in 6 cases (50%). All patients had a Karnofsky performance status of 80 or 90. Nine patients (75%) were receiving antiretroviral therapies at the time of treatment, and the median CD4 count was 460 (range, 266-800). Toxicity was graded according to the Radiation Therapy Oncology Group / European Organization for the Treatment of Cancer toxicity criteria., Results: The 3-year estimates of overall survival and local-regional control were 78% and 92%, respectively. Acute Grade 3+ toxicity occurred in 7 patients (58%), the most common being confluent mucositis (5 patients) and moist skin desquamation (4 patients). Two patients experienced greater than 10% weight loss, and none experienced more than 15% weight loss from baseline. Five patients (42%) experienced treatment breaks in excess of 10 cumulative days, although none required hospitalization. There were no treatment-related fatalities., Conclusions: Radiation therapy for head-and-neck cancer seems to be relatively well tolerated among appropriately selected patients with HIV. The observed rates of toxicity were comparable to historical controls without HIV., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Purpose: To determine the effect of prophylactic gastrostomy tube (GT) placement on acute and long-term outcome for patients treated with definitive chemoradiotherapy for locally advanced head and neck cancer., Methods and Materials: One hundred twenty consecutive patients were treated with chemoradiotherapy for Stage III/IV head and neck cancer to a median dose of 70 Gy (range, 64-74 Gy). The most common primary site was the oropharynx (66 patients). Sixty-seven patients (56%) were treated using intensity-modulated radiotherapy (IMRT). Seventy patients (58%) received prophylactic GT placement at the discretion of the physician before initiation of chemoradiotherapy., Results: Prophylactic GT placement significantly reduced weight loss during radiation therapy from 43 pounds (range, 0 to 76 pounds) to 19 pounds (range, 0 to 51 pounds), which corresponded to a net change of -14% (range, 0% to -30%) and -8% (range, +1% to -22%) from baseline, respectively (p < 0.001). However, the proportion of patients who were GT-dependent at 6- and 12-months after treatment was 41% and 21%, respectively, compared with 8% and 0%, respectively, for those with and without prophylactic GT (p < 0.001). Additionally, prophylactic GT was associated with a significantly higher incidence of late esophageal stricture compared with those who did not have prophylactic GT (30% vs. 6%, p < 0.001)., Conclusions: Although prophylactic GT placement was effective at preventing acute weight loss and the need for intravenous hydration, it was also associated with significantly higher rates of late esophageal toxicity. The benefits of this strategy must be balanced with the risks., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Background: The purpose of this study was to compare the patterns of failure focusing on the distribution of local-regional recurrence among patients treated postoperatively with conventional radiotherapy (RT) and intensity-modulated radiotherapy (IMRT) for head and neck cancer., Methods: The records of 130 patients treated by surgery and postoperative radiation therapy for squamous cell carcinoma of the head and neck were reviewed. Seventy-eight patients (60%) were treated using conventional RT and 52 patients (40%) were treated using IMRT., Results: The 3-year estimates of local-regional control were 70% and 73% among patients treated by conventional RT and IMRT, respectively (p = .33). Among the local-regional recurrences in the IMRT group, 9 were in-field recurrences occurring within the physician-designated clinical target volume (CTV), and 4 were marginal recurrences involving the contralateral neck adjacent to the spared parotid gland (3 patients) and the retropharyngeal/retrostyloid lymph node region (1 patient)., Conclusion: Our study showed that conventional RT and IMRT result in similar rates of local-regional control. The implications for CTV design are discussed herein.

Objective: To determine the prevalence of esophageal pathology following treatment for primary head and neck cancer (HNCA)., Study Design: Case series with planned data collection., Setting: Academic medical practice., Subjects and Methods: Subjects comprised HNCA survivors. Esophagoscopy was prospectively performed on 100 patients at least three months after treatment for HNCA. Patient demographics including cancer stage, cancer treatment, use of reflux medications, symptoms surveys, and esophageal findings were prospectively determined., Results: The mean age of the cohort was 64 (+/- 10) years; 75 percent were male. The mean time between the end of treatment and endoscopy was 40 (+/- 51) months. Eighty-one percent of HNCA was advanced stage (3 or 4). The distribution of site of the primary HNCA was as follows: oropharynx (38%), larynx (33%), oral cavity (17%), unknown primary (10%), hypopharynx (1%), and nasopharynx (1%). Treatment modalities included surgery alone (15%), surgery with radiation (34%), radiation alone (6%), chemoradiation alone (24%), and chemoradiation with surgery (20%). The findings on esophagoscopy included peptic esophagitis (63%), stricture (23%), candidiasis (9%), Barrett metaplasia (8%), gastritis (4%), and carcinoma (4%). Only 13 percent had a normal esophagoscopy., Conclusion: Esophageal pathology is extremely common in patients treated for HNCA. These findings support routine esophageal screening after HNCA treatment., (Copyright 2010 American Academy of Otolaryngology-Head and Neck Surgery Foundation. Published by Mosby, Inc. All rights reserved.)

Objective: The objectives of this study were to 1) determine differences in lifetime fluorescence between normal and malignant tissue of the upper aerodigestive tract, and 2) evaluate the potential of time-resolved laser-induced fluorescence spectroscopy (TR-LIFS) as a diagnostic instrument for head and neck squamous cell carcinoma (HNSCC)., Study Design: Cross-sectional study., Setting: University-based medical center., Subjects and Methods: Nine patients with suspected HNSCC were included. In the operating room, a nitrogen pulse laser (337 nm, 700-picosecond pulse width) was used to induce tissue autofluorescence of normal tissue and suspected malignant lesions. Spectral intensities and time-domain measurements were obtained and compared with the histopathology at each site. A total of 53 sites were measured. The fluorescence parameters that provided the most discrimination were determined., Results: Differences in spectral intensities allowed for discrimination between malignant and normal tissue. The spectral intensity of malignant tissue was lower than that of normal tissue, and a shift of peak intensity to a longer wavelength was observed in the normalized spectrum of malignant tissue in the range of 360 to approximately 660 nm. Multiple time-resolved fluorescence parameters provided the best diagnostic discrimination between normal tissue and carcinoma, including average lifetimes (i.e., at 390 nm: 1.7 +/- 0.06 ns [not significant] for normal and 1.3 +/- 0.06 ns for tumor, P = 0.0025) and the second-order Laguerre expansion coefficient (LEC-2) (i.e., at 460 nm: 0.135 +/- 0.001 for normal and 0.155 +/- 0.007 for tumor, P < 0.05)., Conclusion: These findings highlight some of the differences in lifetime fluorescence between normal and malignant tissue. TR-LIFS has potential as a noninvasive diagnostic technique for HNSCC., (Copyright 2010 American Academy of Otolaryngology-Head and Neck Surgery Foundation. Published by Mosby, Inc. All rights reserved.)

Purpose: To investigate the association between dose to various anatomical structures and dysphagia among patients with head and neck cancer treated by definitive intensity-modulated radiotherapy (IMRT) and concurrent chemotherapy., Methods and Materials: Thirty-nine patients with squamous cancer of the head and neck were treated by definitive concurrent chemotherapy and IMRT to a median dose of 70 Gy (range, 68 to 72). In each patient, a gastrostomy tube (GT) was prophylacticly placed prior to starting treatment. Prolonged GT dependence was defined as exceeding the median GT duration of 192 days. Dysphagia was scored using standardized quality-of-life instruments. Dose-volume histogram (DVH) data incorporating the superior/middle pharyngeal constrictors (SMPC), inferior pharyngeal constrictor (IPC), cricoid pharyngeal inlet (CPI), and cervical esophagus (CE) were analyzed in relation to prolonged GT dependence, dysphagia, and weight loss., Results: At 3 months and 6 months after treatment, 87% and 44% of patients, respectively, were GT dependent. Spearman's rho analysis identified statistical correlations (p < 0.05) between prolonged GT dependence or high grade dysphagia with IPC V65, IPC V60, IPC Dmean, and CPI Dmax. Logistic regression model showed that IPC V65 > 30%, IPC V60 > 60%, IPC Dmean > 60 Gy, and CPI Dmax > 62 Gy predicted for greater than 50% probability of prolonged GT dependence., Conclusion: Our analysis suggests that adhering to the following parameters may decrease the risk of prolonged GT dependence and dysphagia: IPC V65 < 15%, IPC V60 < 40%, IPC Dmean < 55 Gy, and CPI Dmax < 60 Gy.

Background: Patients with significant medical problems requiring major otolaryngology procedures are at high risk for both medical and surgical complications., Objective: To identify risk factors associated with perioperative complications in medically compromised patients undergoing major otolaryngology procedures., Methods: Ninety-three consecutive patients with significant comorbid medical illnesses (eg, diabetes, hypertension) undergoing major head and neck surgical procedures were referred to a medical consultation center for preoperative assessment and medical management. Patient and surgical characteristics as well as perioperative complications were identified and recorded. Univariate and multivariate analyses were performed to determine which characteristics were associated with complications., Results: Thirty-two patients (34%) had postoperative complications. Twenty-six patients (28%) had serious medical complications, and 18 (19%) had surgical complications. No deaths occurred in the study population. On univariate analysis, the factors associated with all complications included history of hepatitis, flap reconstruction, oncologic surgery, preoperative radiation therapy, preoperative gastrostomy placement, intraoperative transfusion, anesthesia time (> or =8 hours), and those with greater intraoperative fluid replacement and estimated blood losses. Only anesthesia time (> or =8 hours) remained independently significant on multivariate analysis. A history of hepatitis and prolonged anesthesia time were the only independent predictors of medical complications. The only independent predictor of surgical complications was the volume of intraoperative fluid administered., Conclusions: Prolonged anesthesia times of 8 hours or more, a history of hepatitis, and large-volume intraoperative fluid resuscitations predicted adverse outcomes. Special care must be taken in counseling these patients preoperatively and in caring for them during their operative and postoperative course.