Reconstruction After Skin Cancer Resection of the Head and Neck.

Skin cancer defects of the head and neck region can vary greatly in their complexity. Reconstructive surgeons are tasked with maintaining or restoring function as well as providing an excellent aesthetic outcome. This article provides an overview of reconstructive options following skin cancer resection broken down by different aesthetic regions and subunits. Although not meant to serve as an all-encompassing source, it provides common indications for using different sections of the reconstructive ladder based on location of defects, tissues involved, and patient factors.

Functional Outcomes After Transoral Plus Lateral Pharyngotomy Approach for Advanced Oral and Oropharyngeal Tumors.

Objective: The aim of this study was to evaluate our institutional experience with the combined transoral plus lateral pharyngotomy (TO+LP) approach in a subset of patients with advanced or recurrent oral and oropharyngeal malignancy. Study Design: A retrospective study of procedures utilizing TO+LP for cancer resection between January 2007 and July 2019. Setting: Tertiary academic medical center. Methods: Thirty-one patients underwent a TO+LP approach for the resection of oral and oropharyngeal tumors. Functional and oncologic outcomes were analyzed. Results: Eighteen (58.1%) patients were treated with TO+LP for recurrent disease. Twenty-nine required free tissue transfer and 2 (6.5%) had positive margins. The median time to decannulation was 22 days (range 6-100 days). Thirteen (41.9%) patients still required enteral feeding at their most recent follow-up. Patients without a history of prior radiation were decannulated sooner (p = .009) and were less likely to require enteral feeding at the first postoperative follow-up (p = .034) than those who had prior head and neck radiotherapy. Conclusion: A TO+LP approach can be used to achieve good functional and oncologic results for selected patients with advanced or recurrent oral and oropharyngeal cancer when minimally invasive options such as transoral robotic surgery, transoral laser microsurgery, or radiotherapy are not possible.

Interstitial Brachytherapy for Lip Cancer: Technical Aspects to Individualize Treatment Approach and Optimize Outcomes.

Primary radiation therapy using interstitial brachytherapy (IBT) provides excellent local tumor control for early-stage squamous cell carcinoma of the lip. Technical aspects of treatment are important to optimize outcomes. In this report, we discuss patient selection criteria, procedural details, and dosimetric considerations for performing IBT for cancers of the lip. Catheters are inserted across the length of tumor entering and exiting approximately 5 mm beyond the palpable tumor extent. A custom mouthpiece is fabricated to facilitate normal tissue sparing. Patients undergo computed tomography imaging, the gross tumor volume is contoured based on physical examination and computed tomography findings, and an individualized brachytherapy plan is generated with the goals of achieving gross tumor volume D90% ≥ 90% and minimizing V150%. Ten patients with primary (n = 8) or recurrent (n = 2) cancers of the lip who received high-dose-rate lip IBT using 2.0- to 2.5-week treatment regimens are described (median prescription: 47.6 Gy in 14 fractions of 3.4 Gy). Local tumor control was 100%. There were no cases of acute grade ≥4 or late grade ≥2 toxicity, and cosmesis scores were graded as good to excellent in all patients. IBT represents an excellent treatment option for patients with lip squamous cell carcinoma. With careful attention to technical considerations furthered described in the present report, high rates of tumor control, low rates of toxicity, and favorable esthetic and functional outcomes can be achieved with IBT for lip cancer.

Patterns of failure for hypopharynx cancer patients treated with limited high-dose radiotherapy treatment volumes.

PURPOSE: Optimal radiotherapy treatment volumes for patients with locally advanced hypopharynx squamous cell carcinoma should ensure maximal tumor coverage with minimal inclusion of normal surrounding structures. Here we evaluated the effectiveness of a direct 3-mm high-dose gross tumor volume to planning target volume expansion on clinical outcomes for hypopharynx cancers. MATERIALS AND METHODS: We performed a retrospective analysis of patients with hypopharynx carcinoma treated between 2004 and 2018 with primary radiotherapy using a direct high-dose gross tumor volume to planning target volume expansion and with or without concurrent systemic therapy. Diagnostic imaging of recurrences was co-registered with the planning CT. Spatial and volumetric analyses of contoured recurrences were compared with planned isodose lines. Failures were initially defined as in field, marginal, elective nodal, and out of field. Each failure was further classified as central high-dose, peripheral high-dose, central intermediate/low-dose, peripheral intermediate/low-dose, and extraneous. Clinical outcomes were analyzed by Kaplan-Meier estimation. RESULTS: Thirty-six patients were identified. At a median follow-up at 52.4 months, estimated 5-year overall survival was 59.3% (95% confidence interval [CI], 36.3%-74.1%), 5-year local and nodal control was 71.7% (95% CI, 47.1%-86.3%) and 69.9% (95% CI, 57.0%-82.6%), respectively. The most common failure was in the high-dose primary target volume. The gastrostomy tube retention rate at 1 year among patients without recurrence was 13.0% (95% CI, 3.2%-29.7%). CONCLUSION: Minimal high-dose target volume expansions for hypopharynx cancers were associated with favorable locoregional control. This approach may enable therapy intensification to improve clinical outcomes.

Prospective Study of PET/MRI Tumor Response During Chemoradiotherapy for Patients With Low-risk and Intermediate-risk p16-positive Oropharynx Cancer.

OBJECTIVE: The objective of this study was to examine tumor response with positron emission tomography (PET)/magnetic resonance imaging (MRI) during chemoradiotherapy as a predictor of outcome in patients with p16-positive oropharynx cancer. MATERIALS AND METHODS: Patients with p16-positive oropharynx cancer were treated with chemoradiotherapy. Low-risk (LR) disease was defined as T1-T3 and N0-2b and ≤10 pack-years and intermediate-risk (IR) disease as T4 or N2c-3 or >10 pack-years. Patients underwent a PET/MRI scan pretreatment and at fraction 10. Change in value of imaging means were analyzed by analysis of variance. K-means clustering with Euclidean distance functions were used for patient clustering. Silhouette width was used to determine the optimal number of clusters. Linear regression was performed on all radiographic metrics using patient and disease characteristics. RESULTS: Twenty-four patients were enrolled with 7 LR and 11 IR patients available for analysis. Pretreatment imaging characteristics between LR and IR patients were similar. Patients with LR disease exhibited a larger reduction in maximum standardized uptake value (SUV) compared with IR patients (P<0.05). Cluster analysis defined 2 cohorts that exhibited a similar intratreatment response. Cluster 1 contained 7 of 7 LR patients and 8 of 11 IR patients. Cluster 2 contained 3 of 11 IR patients. Cluster 2 exhibited significant differences compared with cluster 1 in the change in primary tumor peak SUV and largest lymph node median SUV. CONCLUSIONS: We identified that IR p16-positive oropharynx cancers exhibit heterogeneity in their PET/MRI response to chemoradiotherapy. These data support further study of intratreatment imaging response as a potential mechanism to identify patients with IR oropharynx cancer suitable for treatment deintensification.

The radial forearm snake flap: An underutilized technique for fasciocutaneous and osteocutaneous forearm flaps with primary closure.

BACKGROUND: The radial forearm free flap (RFFF) is associated with troublesome donor site morbidity related to split thickness skin grafting (STSG). The radial forearm snake flap with primary closure of the donor site may reduce donor site complications. METHODS: Single institution, retrospective cohort study comparing rates of delayed donor site wound healing and tendon exposure in 52 patients undergoing radial forearm snake flap and 95 patients undergoing conventional RFFF with STSG closure of the donor site. RESULTS: Tendon exposure occurred in zero (0%) patients undergoing snake flap and four (4.2%) patients undergoing conventional RFFF (0/52 vs. 4/95; p = 0.297). Delayed wound healing occurred in zero (0%) patients undergoing snake flap and 19 (20.0%) patients undergoing conventional RFFF (0/52 vs. 19/95; p < 0.001). CONCLUSIONS: The radial forearm snake flap provides an alternative to conventional RFFF harvest, which enables primary donor site closure with reduced rates of delayed donor site healing.

Pre-tracheotomy for Potentially Emergent Airway Scenarios: Indications and Outcomes.

OBJECTIVES/HYPOTHESIS: Airway access in the setting of unsuccessful ventilation and intubation typically involves emergent cricothyrotomy or tracheotomy, procedures with associated significant risk. The potential for such emergent scenarios can often be predicted based on patient and disease factors. Planned tracheotomy can be performed in these cases but is not without its own risks. We previously described a technique of pre-tracheotomy or exposing the tracheal framework without entering the trachea, as an alternative to planned tracheostomy in such cases. In this way, a tracheotomy can be easily completed if needed, or the wound can be closed if it is not needed. This procedure has since been used in an array of indications. We describe the clinical situations where pre-tracheotomy was performed as well as subsequent patient outcomes. METHODS: Retrospective series of patients undergoing a pre-tracheotomy from 2015 to 2020. Records were reviewed for patient characteristics, indication, whether the procedure was converted to tracheotomy or closed at the bedside, and any post-procedural complications. RESULTS: Pre-tracheotomy was performed in 18 patients. Indications included failed extubation after head and neck reconstruction, subglottic stenosis, laryngeal masses, laryngeal edema, thyroid masses, and an oropharyngeal bleed requiring operative intervention. Tracheotomy was avoided in 10 patients with wound closed at the bedside; procedure was converted to tracheotomy in the remaining eight. There were no complications. Indications for conversion included failed extubation, intraoperative hemorrhage, significant stridor with dyspnea, and inability to ventilate. CONCLUSION: Pre-tracheotomy offers simplified airway access and provides a valuable option in scenarios where tracheotomy may, but not necessarily, be needed. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:E2802-E2809, 2021.

Clinical outcomes for larynx patients with cancer treated with refinement of high-dose radiation treatment volumes.

BACKGROUND: To evaluate disease control, toxicities, and dose to dysphagia/aspiration risk structures (DARS) using a direct gross tumor volume (GTV70Gy ) to planning target volume expansion (dPTV70Gy ) for patients with squamous cell carcinoma of the larynx (LSCC). METHODS: A retrospective review was performed on patients with LSCC treated between 2003 and 2018. Clinical outcomes, toxicities, and dosimetric data were analyzed. RESULTS: Seventy-three patients were identified. Overall survival at 5-years was 57.8%. Five-year local and regional control was 79.8% and 88.2%, respectively. Distant metastatic-only failure was 2.7%. Eighty percent of failures were 95% contained within the dPTV70Gy . Mean dose and the volume of DARS receiving 70 Gy was significantly lower for dPTV70Gy compared to a consensus-defined PTV70Gy . DISCUSSION: Judicious reduction in high-dose target volumes can preserve high tumor control rates while reducing dose to normal surrounding structures underscoring the potential benefit of this approach in enabling local therapy intensification to improve locoregional control.

Opioid use in patients undergoing treatment for oral cavity cancer.

OBJECTIVE: In the context of the opioid epidemic, there is value in examining the use of opioids in specific cancer patient cohorts. We analyzed opioid use in patients undergoing adjuvant therapy for oral cavity cancer to define the incidence of new persistent use beyond 3 months. STUDY DESIGN: Retrospective. SETTING: Comprehensive academic cancer center. SUBJECTS AND METHODS: We performed a retrospective IRB-approved analysis of opioid use in patients who received adjuvant radiotherapy with or with concurrent systemic therapy for surgically resected oral cavity cancer between 2003 and 2016. Factors associated with opioid use were evaluated by Chi-square test and one-way ANOVA. The Kaplan-Meier method was used to estimate overall survival. RESULTS: Of 77 identified patients, 10 (13%) patients received opioid prescriptions at 3 months or greater following completion of radiotherapy. Patients who were opioid naive prior to surgery required significantly fewer opioid prescriptions than intermittent or chronic opioid users. No specific factors were associated with new persistent opioid use. CONCLUSIONS: Patients undergoing surgery and adjuvant radiotherapy for oral cavity cancer who required opioids for cancer treatment related pain are at minimal risk for new dependency. Judicious pain management should be applied for patients with a history of prior opioid use. Larger patient cohorts will be needed to identify patient, disease, and treatment characteristics associated with new persistent use given its limited incidence.

The Temporoparietal Fascia Flap is an Effective Strategy for Cochlear Implant Wound Coverage.

OBJECTIVE: To report the rate of major soft tissue complications after cochlear implantation and to describe the use of the temporoparietal fascia (TPF) flap for such complications. STUDY DESIGN: Retrospective case series. SETTING: Tertiary care, University Hospital. SUBJECTS AND METHODS: Chart review of all patients who underwent cochlear device implantation over a 5-year period to identify patients and to determine the rate of soft tissue complications. Five patients with major soft tissue complications underwent TPF flap with device salvage or explantation/reimplantation. RESULTS: The rate of major skin complications was 6 out of 281 (2.1%) over 5 years, with 5 patients undergoing TPF flap. The average follow-up was 25.8 months (range, 5-58 months). TPF flap represented the definitive, successful solution for all 5 patients. One postoperative hematoma occurred after TPF flap, with no long-term sequelae. The average hospital length of stay was 2.2 nights (range, 1-5 nights). One patient required IV antibiotics for 4 weeks; the remaining patients were treated with a postoperative course of oral antibiotics. The original device remained in place for 4 patients, while one case required device explantation and staged re-implantation. Post-TPF flap hearing results were equal to if not superior to their preoperative results. CONCLUSION: Major soft tissue complications following cochlear device implantation are rare. The temporoparietal fascia flap is an excellent option for reconstruction of device site soft tissue dehiscences when local wound care and primary closure are not sufficient, and can potentially prevent explantation of a functional implant.

Multispecialty Microsurgical Course Utilizing the Blue-Blood Chicken Thigh Model Significantly Improves Resident Comfort, Confidence, and Attitudes in Multiple Domains.

BACKGROUND: The high level of technical skill required by microsurgical procedures has prompted the development of in vitro educational models. Current models are cost-ineffective, unrealistic, or carry ethical implications and are utilized as isolated experiences within single surgical specialties. The purpose of this study was to assess the educational and interprofessional effect of a microsurgical training course utilizing the nonliving "Blue-Blood" chicken thigh model (BBCTM) in a multidisciplinary environment. METHODS: A 10-hour course was developed integrating didactic lectures, case presentations, and one-on-one practical sessions utilizing hydrogel microvessels and the BBCTM. Pre- and postcourse surveys were administered assessing participants' self-reported comfort and confidence within fundamental microsurgical domains, assessments of the models utilized, and the effects of a multidisciplinary environment on the experience. RESULTS: A total of 19 residents attended the course on two separate occasions (n = 10 and n = 9, respectively). Respondents varied from postgraduate year-2 (PGY-2) to PGY-6+ and represented plastic and reconstructive surgery (n = 10), urology (n = 6), and otolaryngology (n = 3). On average, each participant performed 4.3 end-to-end, 1.3 end-to-side, and 0.4 coupler-assisted anastomoses. Following the course, participants felt significantly more comfortable operating a microscope and handling microsurgical instruments. They felt significantly more confident handling tissues, manipulating needles, microdissecting, performing end-to-end anastomoses, performing end-to-side anastomoses, using an anastomotic coupler, and declaring anastomoses suitable (all p < 0.05). The majority of participants believed that the use of live animals in the course would have minimally improved their learning. All but two respondents believed the course improved their awareness of the value of microsurgery in other specialties "very much" or "incredibly." CONCLUSION: A microsurgical training course utilizing nonliving models such as the "BBCTM significantly improves resident comfort and confidence in core operative domains and offers an in vivo experience without the use of live animals. Multispecialty training experiences in microsurgery are beneficial, desired, and likely underutilized.

Aggressive, Multidisciplinary Staged Microsurgical Resection of a Giant Cervicomedullary Junction Chordoma.

Chordomas of the cranial base are locally destructive tumors since they are surrounded by significant complex neurovascular structures. Thus, their surgical removal is challenging, recurrence rates are high, and their therapeutic strategies remain controversial. In this video, we present a 47-year-old man with a recent onset of swallowing difficulties, hoarseness, and weight loss for several weeks. In the neurological examination, he had complete paralysis of the 9th, 10th, 11th, and 12th cranial nerves. Magnetic resonance imaging (MRI) showed a heterogeneously enhancing expansile invasive mass lesion centered within the clivus and involving the C1, the occipitocervical junction, the retropharynx, and the hypoglossal canal. The decision was made to proceed with multiple staged surgeries. In the first surgical stage, we performed a mastoidectomy with the infralabyrinthine approach to perform a test clip ligation of the sigmoid sinus and to resect the tumor component that extended into the infralabyrinthine space. In the second stage, we performed a far-lateral transcondylar approach for tumor resection and occipitocervical fusion. In the third stage, we used a transoral approach with endoscopic assistance to complete the excision of the remaining tumor in the retropharyngeal space and anterior aspect of C1 and C2 bodies that were not accessible in the first two stages. The surgeries and postoperative course were uneventful. Postoperative MRI showed a gross total resection of the tumor. Histopathology indicated a chordoma. The patient subsequently received proton radiotherapy and has continued to do well without recurrence at 14 months' follow-up. The link to the video can be found at: https://youtu.be/uP9OSlKg_rE .

Auriculotemporal Nerve Involvement in Parotid Bed Malignancy.

OBJECTIVE: To identify and evaluate patients with parotid bed malignancy demonstrating radiographic findings of auriculotemporal (AT) nerve involvement. METHODS: A retrospective review of patients with parotid bed malignancy was performed to identify patients with imaging findings of AT nerve involvement and record associated clinical findings, symptoms, and pathology information. Independent, blinded review of radiographic images by a senior neuroradiologist was performed to identify imaging characteristics and categorize patients into highly likely or possible involvement groups. RESULTS: Of 547 patients identified with parotid bed malignancy, 23 patients exhibited radiographic findings suggestive of AT nerve involvement. Thirteen patients met criteria for highly likely involvement, and 10 patients met criteria for possible involvement. Cutaneous malignancy with metastasis to the parotid bed accounted for 11 of 23 patients, and the most common histology was squamous cell carcinoma (9 patients). Primary parotid malignancy accounted for 12 of 23 patients, and the most common histology was salivary ductal carcinoma (3 patients). All 13 highly likely patients reported periauricular pain, and 11 of 13 demonstrated facial weakness. Features suggesting advanced disease included radiographic findings of intracranial involvement (10/23 patients), nonsurgical primary treatment (13/23 patients), and positive margins on pathology report (7/10 patients). CONCLUSION: AT nerve involvement is an uncommon but important phenomenon that often occurs in the setting of advanced disease and is commonly associated with periauricular pain and coexisting facial weakness. Awareness of the associated clinical features and imaging patterns can allow for appropriate identification of this pattern of spread and help to optimize treatment planning.

Impact of HPV Status on the Prognostic Potential of the AJCC Staging System for Larynx Cancer.

Objective We evaluated the ability of the American Joint Committee on Cancer (AJCC) seventh edition staging system to prognosticate the overall survival of patients with human papillomavirus (HPV)-positive laryngeal squamous cell carcinoma. Study Design Retrospective analysis. Setting National Cancer Database. Subjects and Methods Patients diagnosed with laryngeal squamous cell carcinoma who were treated with curative intent were identified in the National Cancer Database. Multivariate analysis was utilized to determine factors correlated with overall survival in the HPV-negative and HPV-positive cohorts. Unadjusted and propensity score-weighted Kaplan-Meier estimation was used to determine overall survival of HPV-negative and HPV-positive patients across AJCC stage groupings. Results We identified 3238 patients with laryngeal squamous cell carcinoma, of which 2812 were HPV negative and 426 were HPV positive. Overall survival adjusted for age, sex, and comorbidity status confirmed significant differences among all consecutive stage groupings (I vs II, P < .001; II vs III, P < .05; III vs IVA, P < .001; IVA vs IVB, P < .05) in the HPV-negative cohort, whereas only stages IVAs and IVB ( P < .01) exhibited a significant difference in overall survival for HPV-positive patients. Conclusion The current AJCC staging system does not accurately distinguish risk of mortality for patients with HPV-positive disease. These data support the consideration of HPV status in estimating prognosis as well as clinical trial design and clinical decision making for patients with laryngeal squamous cell carcinoma.

Survival Outcomes for Patients With T3N0M0 Squamous Cell Carcinoma of the Glottic Larynx.

Importance: Radiotherapy (RT)-based organ preservation approaches for patients with advanced laryngeal cancer have been established stepwise through prospective randomized clinical trials. However, broad adoption of these approaches has stimulated discussion about long-term results challenging their applicability in a heterogeneous patient population, most recently for patients with T3 disease. Objective: To define outcomes in patients with clinical T3N0M0 glottic laryngeal cancer treated with definitive surgical and RT-based approaches. Design, Setting, and Participants: This retrospective cohort study included patients treated from January 1, 2004, through December 31, 2013, with a median follow-up time of 58 months (range, 0-126.6 months) in the National Cancer Database. Of the 4003 patients with T3N0M0 disease, 2622 received definitive therapy defined by the study protocol. Data were obtained from the clinical oncology database sourced from hospital registry data that are collected from more than 1500 Commission on Cancer-accredited facilities. Data were analyzed from September 14, 2016, through April 24, 2017. Interventions: Radiotherapy, chemoradiotherapy, surgery, surgery and RT, or surgery and chemoradiotherapy. Main Outcomes and Measures: Five-year overall survival (OS). Results: A total of 2622 patients (2251 men [85.9%] and 371 women [14.1%]; median age, 64 years [range, 19-90 years]) were included in the analytic cohort. In the overall patient cohort, the adjusted 5-year survival probability was 53%. No statistical differences were observed between the primary surgery (53%; 95% CI, 48%-57%) and primary RT (54%; 95% CI, 52%-57%) cohorts. In multivariate analysis, patient factors associated with decreased OS included age (hazard ratio [HR], 1.04; 95% CI, 1.03-1.04), insurance status (HR, 1.26; 95% CI, 1.06-1.50), and increasing comorbidity (HR, 1.20; 95% CI, 1.02-1.42). Conclusions and Relevance: Current management of T3N0M0 glottic laryngeal cancer relies largely on RT-based organ preservation approaches. The present study substantiates randomized clinical trial data supporting the use of RT-based organ preservation approaches for patients with T3N0M0 glottic laryngeal cancer without compromising OS.

Prognostic implications of human papillomavirus status for patients with non-oropharyngeal head and neck squamous cell carcinomas.

PURPOSE: We examined overall survival in a large cohort of patients with human papillomavirus (HPV)-positive and HPV-negative non-oropharyngeal squamous cell carcinoma of the head and neck (non-OPSCC). METHODS: Patients diagnosed with non-OPSCC and known HPV status were identified in the National Cancer Database (NCDB). Multivariate logistic regression was applied to examine factors associated with HPV status. Multivariate analysis was utilized to determine factors correlated with overall survival. Propensity score-weighted Kaplan-Meier estimation was used to adjust for confounders in survival analyses. Multiple imputation method was used for sensitivity analysis. RESULTS: We identified 19,993 non-OPSCC patients with 5070 being positive for HPV in the NCDB. Median follow-up was 23.5 months. HPV-positive patients were more commonly male, white, with a lower comorbidity index score, presenting with T-stage <2, and N-stage ≥1. Unadjusted 3-year overall survival was 62% and 80% for HPV-negative and HPV-positive patients, respectively (p < 0.0001). On multivariate analysis, mortality was reduced for HPV-positive patients with early stage (HR = 0.68) and locally advanced disease (HR = 0.46). Adjusted 3-year overall survival was 65% for HPV-negative and 76% for HPV-positive patients (p < 0.0001). The survival advantage of HPV was maintained in all subsites and robust on sensitivity analysis. CONCLUSIONS: Patients with HPV-positive non-OPSCC exhibit similar characteristics as HPV-positive OPSCC. Overall survival was significantly higher for patients with HPV-positive versus HPV-negative non-OPSCC. These data reveal that HPV-positive non-OPSCC represent a favorable cohort that warrants recognition in the design of future clinical trial investigation.

Clinical outcomes for patients presenting with N3 head and neck squamous cell carcinoma: Analysis of the National Cancer Database.

BACKGROUND: There is a paucity of data regarding head and neck squamous cell carcinomas (HNSCCs) and N3 nodal disease. METHODS: Retrospective analysis of patients with N3 HNSCC identified in the National Cancer Database (NCDB) was performed. RESULTS: We identified 4867 patients with N3 HNSCC treated with primary surgery or chemoradiotherapy (CRT). Propensity-adjusted median survival was 54.2 and 44.8 months for surgery and CRT, respectively (P = .06). Oropharyngeal primary subsite demonstrated a survival advantage with surgery versus CRT with propensity-adjusted median survivals of 86.0 and 61.9 months, respectively (P < .05). CONCLUSION: Management of N3 HNSCC relies largely on CRT. Patients with N3 nodal disease with nonoropharyngeal primary tumors exhibit 5-year overall survival approaching 30% independent of initial treatment modality. Patients with oropharyngeal primaries exhibit improved outcomes with surgery largely influenced by the human papillomavirus (HPV)-negative subset. These data represent the most comprehensive analysis of N3 HNSCC outcomes and serves as a foundation for future research and clinical management.

Radiosensitization of Adenoid Cystic Carcinoma with MDM2 Inhibition.

Purpose: Adenoid cystic carcinoma (ACC) is a rare cancer arising from the major or minor salivary gland tissues of the head and neck. There are currently no approved systemic agents or known radiosensitizers for ACC. Unlike the more common head and neck squamous cell carcinomas that frequently harbor TP53 mutations, ACCs contain TP53 mutations at a rate of <5%, rendering them an attractive target for MDM2 inhibition.Experimental Design: We report the successful establishment and detailed characterization of a TP53-WT ACC patient-derived xenograft (PDX), which retained the histologic features of the original patient tumor. We evaluated this model for response to the MDM2 inhibitor AMG 232 as monotherapy and in combination with radiotherapy.Results: AMG 232 monotherapy induced modest tumor growth inhibition, and radiation monotherapy induced a transient tumor growth delay in a dose-dependent fashion. Strikingly, combination treatment of AMG 232 with radiotherapy (including low-dose radiotherapy of 2 Gy/fraction) induced dramatic tumor response and high local tumor control rates 3 months following treatment. Posttreatment analysis revealed that although both AMG 232 and radiotherapy alone induced TP53 tumor-suppressive activities, combination therapy amplified this response with potent induction of apoptosis after combination treatment.Conclusions: These data identify that MDM2 inhibition can provide potent radiosensitization in TP53-WT ACC. In light of the absence of effective systemic agents for ACC, the powerful response profile observed here suggests that clinical trial evaluation of this drug/radiotherapy combination may be warranted to improve local control in this challenging malignancy. Clin Cancer Res; 23(20); 6044-53. ©2017 AACR.