Adverse events associated with anastomotic coupling devices in microvascular reconstruction.

OBJECTIVE: In light of the recent US Food and Drug Administration (FDA) Class 2 safety recall notice for anastomotic coupling devices, it is important to understand related adverse events. The aim of this study was to characterize adverse events in anastomotic coupling devices for microvascular reconstruction. METHODS: A retrospective cross-sectional analysis using the 2011 to 2021 US FDA Manufacturer and User Facility Device Experience (MAUDE) database. All reports of adverse events involving anastomotic coupling devices were retrieved from the MAUDE database. Descriptive statistics were used to analyze categorized events. RESULTS: There were a total of 293 documented adverse events related to anastomotic coupling devices. These adverse events resulted in 91 (31.1 %) patient injuries and 239 (81.6 %) device malfunctions. The most frequent patient problems were thrombosis/hematoma (n = 38; 41.8 %), unspecified injury (n = 31; 34.1 %), and failure to anastomose (n = 13; 14.3 %). Free flap necrosis was reported in 42 % of thrombosis/hematoma cases (n = 16). The most common malfunctions were devices operating differently than expected (n = 74; 31.0 %), connection problems (n = 41; 17.2 %), and twisted/bent material (n = 19; 7.9 %). There was no significant trend in the number of adverse events over the study period (p > 0.05). CONCLUSIONS: Adverse events from anastomotic coupling devices represent an important and modifiable factor in free tissue failure. Adverse events are predominately related to devices operating differently than expected and may result in vascular compromise of the free flap. Reconstructive surgeons should be cognizant of defective anastomotic coupling devices and be prepared to utilize traditional hand-sewn anastomosis.

The "bowtie" reconstruction flap: A unique solution to cervical esophageal discontinuity repair.

OBJECTIVES: Describe a novel technique for repair of cervical esophageal discontinuity. STUDY DESIGN: A 66-year-old female underwent hiatal hernia repair with a Nissen fundoplication. This was complicated by ischemic necrosis of the proximal stomach requiring urgent return to the operative suite for partial gastrectomy, esophageal diversion and subsequent esophagectomy repaired with a colonic interposition graft by Thoracic Surgery. This was further complicated by a cervical esophageal colonic anastomotic leak maturing to a cervical esophageal fistula and necessitating jejunostomy tube placement and consultation to Head and Neck Surgery. METHODS: Case report. RESULTS: In a team approach with Otolaryngology and Thoracic Surgery, she underwent a unique, multilevel repair with a salivary bypass stent bridging the gap between the proximal esophagus and distal colonic conduit. Bilateral local advancement flaps were elevated using the skin lateral to the fistula on each side with a random blood supply pedicled medially. Each flap was rotated medially over the stent and imbricated at midline. Next, a left myogenous pectoralis flap was raised and rotated over the site of imbrication. Lastly, a split thickness skin graft from the thigh was harvested and sutured over the pectoralis flap. Three months postoperatively, the salivary bypass stent was removed and by five months, the fistula was completely closed. With cervical esophageal dilations bimonthly, the patient has graduated to an oral diet without need of her jejunostomy tube for nearly four months. CONCLUSION: This case report describes a novel and efficacious solution to cervical esophageal discontinuity.

Rethinking the 10-pack-year rule for favorable human papillomavirus-associated oropharynx carcinoma: A multi-institution analysis.

BACKGROUND: De-intensified treatment strategies for early human papillomavirus-positive (HPV+) oropharynx cancer (OPC) rely on selecting patients with an excellent prognosis. The criterion for enrollment in current de-intensification trials is ≤10 pack-years. More nuance to the pack-year criteria may expand enrollment, improve patient outcomes, and prevent overtreatment. It was hypothesized that patients with more than 10 pack-years may experience favorable outcomes if smoking cessation has been achieved. METHODS: From an institutional review board-approved database, patients with HPV+ oropharyngeal squamous carcinoma treated definitively with radiation with or without chemotherapy were retrospectively identified. Patients with a history of smoking who were eligible for national de-intensification trials were included (cT1-2N1-2b or T3N0-2b [American Joint Committee on Cancer, seventh edition]). Cox regression with penalized smoothing splines was used to evaluate nonlinear effects of cessation. Recursive partitioning analysis (RPA) was used to objectively search for relationships between the 2 colinear variables (pack-years and time since cessation). RESULTS: Among 330 patients meeting the inclusion criteria, 130 (40%) were never smokers, 139 (42%) were former smokers, and 61 (18%) were current smokers. With standard therapy, all former smokers achieved a progression-free survival (PFS) rate higher than 91%, regardless of pack-year exposure. Nonlinear Cox regression demonstrated that more recent cessation was associated with significantly worse PFS even among those with ≤20 pack-years. RPA demonstrated that only current smokers experienced a 2-year PFS rate lower than 91%; former smokers, regardless of pack-years, experienced a 2-year PFS rate higher than 91%. CONCLUSIONS: The 10-pack-year rule may not apply to all early HPV+ OPCs, particularly for former smokers. Future randomized de-intensification trials should consider a broader and more nuanced approach until the predictive role of smoking status is established.

Incidence of squamous cell carcinomas of the head and neck following prolonged pegylated liposomal doxorubicin.

Despite numerous case reports, the incidence of a secondary diagnosis of head and neck squamous cell carcinoma (HNC) following pegylated liposomal doxorubicin (PLD) treatment is unknown. Computerized pharmacy records were searched at a large, multi-center healthcare system for patients who received PLD. Electronic medical records were searched to identify the patient's age at treatment initiation of PLD, diagnosis for which they were treated with PLD, number of courses and total cumulative dose of PLD (TCDPLD) and secondary malignancies. Published PLD associated HNC was utilized to determine the lowest and median TCDPLD doses associated with HNC. One thousand two hundred ninety eligible patients who had been treated with PLD were identified. The lowest TCDPLD associated HNC in the literature is 405 mg/m2. In our healthcare system, 275 patients received more than 400 mg/m2 yielding a risk of 0.004%. One hundred fifty-one patients received the lowest TCDPLD associated with HNC cancer in our series which was 640 mg/m2 yielding a risk of 0.007%. Four of 30 patients (13.3%) developed HNC who received the median TCDPLD associated with HNC in the literature of 1440 mg/m2. Five of 20 patients (25%) receiving 1650 mg/m2 developed HNC in our healthcare system. Prolonged therapy with PLD is associated with an increased risk of HNC. This risk appears to be related to the cumulative dose varying from 0.004 to 13.3% at the lowest and median TCDPLD of reported cases in the literature, respectively. Oncologists need to be aware of this risk and to screen patients appropriately.

Does neck dissection affect post-operative outcomes in parotidectomy? A national study.

OBJECTIVE: To characterize post-operative complications in parotidectomy with neck dissection. METHODS: Patients age ≥ 18 receiving a parotidectomy or parotidectomy with neck dissection between 2005 and 2017 were eligible for inclusion. Patients with unknown demographic variables were excluded. Univariate and multivariable logistic regression analyses were performed. RESULTS: A total of 13,609 parotidectomy patients were analyzed, 11,243 (82.6%) without neck dissection and 2366 (17.4%) with neck dissection. Both length of surgery (mean minutes ± standard deviation [SD] = 335.9 ± 189.2 vs. 152.9 ± 99.0, p < 0.001) and length of hospital stay (mean days ± SD = 3.90 ± 4.76 vs. 1.04 ± 2.14, p < 0.001) were greater with dissection. 13.9% of parotidectomies with neck dissection and 3.5% without dissection (p < 0.001) had at least one complication, which remained significant after multivariable adjustment (Odds Ratio[OR] = 1.565 (95%CI = 1.279-1.914), p < 0.001). The increase in post-operative complications was predominately driven by an increased transfusion rate (7.4% vs. 0.5%, p < 0.001). Multivariable analysis also demonstrated no significant difference in rates of returning to the operating room (OR = 1.122 (95%CI 0.843-1.493), p > 0.05) or rates of readmission (OR = 1.007 (95%CI 0.740-1.369), p > 0.05). Parotidectomy with neck dissection was more likely to be inpatient (OR = 4.411 (95%CI 3.887-5.004), p < 0.001) and to be ASA class 3 (OR = 1.367 (95%CI 1.194-1.564), p < 0.001). CONCLUSIONS: Nationwide data demonstrates that parotidectomy with neck dissection is associated with increased rates of post-operative complications; however, neck dissection did not significantly impact readmission or reoperation rates. These findings indicate that neck dissection is a relatively safe addition to parotidectomy and provide novel evidence in the management of parotid malignancies.

Increased pathologic upstaging with rising time to treatment initiation for head and neck cancer: A mechanism for increased mortality.

BACKGROUND: Time to treatment initiation (TTI) is increasing and is associated with worsening survival. In the current study, the authors sought to identify a mechanism for this relationship by assessing the effect of TTI on clinical-to-pathologic upstaging in patients with head and neck squamous cell carcinoma (HNSCC). METHODS: Using the National Cancer Data Base, the authors analyzed patients receiving definitive surgery for SCC of the oral cavity, oropharynx, larynx, and hypopharynx from 2005 through 2014. The primary outcome was T, N, or stage group upstaging, defined as higher pathologic stage than clinical stage. TTI was defined as the time between diagnosis and surgery. Multivariable logistic and Cox proportional hazards regression modeled upstaging and survival, respectively. RESULTS: Cohorts of 60,194 patients, 51,380 patients, and 52,980 patients, respectively, with complete T, N, and stage group data were included. N upstaging was most common (18.6%), followed by stage group (17.4%) and T (12.1%) upstaging; all types were predicted by TTI. Compared with a TTI of 1 to 6 days, TTIs as short as 7 to 13 days (odds ratio, 1.20; P = .038) or ≥ 70 days (odds ratio, 2.04; P < .001) were found to predict T upstaging, a finding that is consistent for N and stage group upstaging. Using restricted cubic splines, relative odds of T and stage group upstaging escalated to 2.25 and 1.93, respectively, at a TTI of 365 days. In survival analyses, T (hazard ratio [HR], 1.53), N (HR, 1.88), and stage group (HR, 1.69) upstaging all predicted mortality (P < .001), whereas TTI only predicted mortality after 70 days (HR, 1.11; P = .023). CONCLUSIONS: Tumor progression, measured by clinical-to-pathologic upstaging, increases mortality for patients with HNSCC experiencing treatment delays. Cancer 2018;124:1400-14. © 2018 American Cancer Society.

Comprehensive approach to reestablishing form and function after radical parotidectomy.

INTRODUCTION: The reconstructive goals following radical parotidectomy include restoration of symmetry, reanimation of the face, and reestablishment of oral competence. We present our experience utilizing the anterolateral thigh (ALT) free flap, orthodromic temporalis tendon transfer (OTTT), and facial nerve cable grafting to reestablish form and function. MATERIAL AND METHODS: From 2010 to 2016, 17 patients underwent radical parotidectomy followed by immediate reconstruction. An ALT was harvested to accommodate the volume and skin defect. Additional fascia lata and motor nerve to vastus lateralis (MNVL) were obtained. Anastomosis of the ALT to recipient vessels was performed, most commonly using the facial artery and internal jugular vein. OTTT was performed by securing the medial tendon of the temporalis to orbicularis oris through a nasolabial incision. Fascia lata was tunneled through the lower lip, then secured laterally to the temporalis tendon. The MNVL was cable grafted from either the proximal facial nerve or masseteric nerve to the distal facial nerve branches. ALT fascia was suspended to the superficial muscular aponeurotic system. RESULTS: Average follow up was 19 months. Only one patient failed to achieve symmetry attributed to dehiscence of OTTT. All patients achieved oral competence and dynamic smile with OTTT activation. Facial nerve recovery was seen in 8 patients. 5 reached a House Brackman Score of 3. Two donor site seromas and two wound infections occurred. CONCLUSION: Simultaneous ALT, OTTT, and facial nerve cable grafting provides early reestablishment of facial symmetry, facial reanimation, and oral competence with minimal morbidity.

The contemporary utility of intraoperative frozen sections in thyroid surgery.

PURPOSE: To determine the accuracy of intraoperative frozen section analysis on thyroidectomy specimens stratified by the Bethesda classification scheme and its utility for intraoperative decision-making. STUDY DESIGN: Retrospective chart review. METHODS: A retrospective review was performed on all patients who underwent thyroidectomy or thyroid lobectomy with intraoperative frozen sections at a tertiary care academic center from 2009 to 2015. RESULTS: There were 74 total patients who underwent partial or total thyroidectomy with intraoperative frozen section analysis of a thyroid nodule whom had previously undergone a thyroid fine needle aspiration of the nodule. The sensitivity, specificity, positive predictive value, and negative predictive value for a thyroid frozen section with respect to its prediction for malignancy was 81%, 95%, 98%, and 66%, respectively, with a diagnostic accuracy of 85%. For 37 patients with an indeterminate cytologic diagnosis on fine needle aspiration (Bethesda categories III-V), the sensitivity, specificity, positive predictive value, and negative predictive value for a thyroid frozen section was 81%, 91%, 95%, and 67%, respectively, with a diagnostic accuracy of 84%. False positives and false negatives resulted in 1 completion thyroidectomy for benign pathology and 3 reoperations for malignancy not discovered on frozen section. CONCLUSION: While intraoperative frozen sections on thyroid specimens may be helpful if positive, the false negative rate remains high. There appears to be limited value in routine frozen sections to guide clinical management and decision-making in the era of the Bethesda system.

Mandibular Osteoradionecrosis: Defining the Microbial Milieu and Antimicrobial Resistance at the Time of Rescue Flap Surgery.

OBJECTIVE: To report the microorganisms and their antibiotic sensitivity profile from tissue cultures and stains at the time of anterolateral thigh fascia lata (ALTFL) rescue flap for management of mandibular osteoradionecrosis (ORN). METHODS: Retrospective chart review of patients who underwent ALTFL rescue flap for native mandibular ORN between 2011 and 2022. RESULTS: Twenty-six cases comprising 24 patients (mean age 65.4 years, 65.4% male) with mandibular ORN from whom tissue cultures and gram stain were obtained at the time of ALTFL rescue flap. 57.7% grew bacterial species, while 34.6% grew fungal species. Multibacterial speciation was noted in 26.9% of cultures. A combination of bacterial and fungal growth was also seen in 15.4% of cases. All gram-positive cocci (GPC) were pansensitive to antibiotics except for one case of Staphylococcus aureus, which was resistant to levofloxacin. Gram-negative bacilli (GNB) species were isolated in 50.0% of cases. All fungal growth was due to Candida species. No growth was noted in 23.1% of cases. Multidrug resistance was noted in 53.8% of cases when GNB was isolated. CONCLUSION: We report 76.9% of our cases of mandibular ORN had microbial growth from tissue cultures obtained at the time of the ALTFL rescue flap. Fungal growth was noted in a substantial number of cases and should be obtained as a specimen when pursuing culture-driven antibiotic therapy. Most GPCs were pansensitive to antibiotics, while GNBs were often the harbinger of multidrug resistant mandibular ORN. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:166-169, 2024.

Minimally Invasive Approach to Access Vessels for Microvascular Anastomosis in Head and Neck Reconstruction.

OBJECTIVES: To describe our technique, review indications, and evaluate the outcomes of the minimal access approach for recipient vessel identification in microvascular tissue transfer. METHODS: Retrospective chart review of all patients who underwent microvascular reconstruction using the minimal access technique between 2015 and 2021. RESULTS: We report 236 cases, comprising 214 patients with a mean age of 60.2 years (3-88). The most common primary defect sites were the mandible (22.6%), cranium (14%), maxilla (13.2%), skull base (12.8%), and nose/nasal cavity (10.6%). Indications for free flap reconstruction included head and neck cancer extirpation (32.2%), osteoradionecrosis (29.7%), acquired deformity (14.0%), chronic wound (11.9%) and oral motor dysfunction (7.2%). Free flap donor sites used were the anterolateral thigh (84.3%), fibula (7.2%), and radial forearm (6.4%). Vessels utilized include superficial temporal (49.8%), facial (38.3%), angular (11.1%), and transverse cervical (0.4%). The overall complication rate was 14% (n = 33), with surgical complications at the recipient site accounting for 67.6% (n = 25). Flap failure occurred in 3.4% of procedures. Prior head and neck surgery and free flaps were associated with an increased risk of major recipient site complications (n = 20, p = 0.0257 and n = 14, p = 0.0117, respectively). CONCLUSION: Minimal access techniques allow consistent recipient vessel identification for microvascular-free tissue transfer. These approaches may be utilized in reconstructing a broad range of head and neck defects, are low morbidity, and contribute to an overall shorter length of stay. LEVEL OF EVIDENCE: 2 Laryngoscope, 134:2177-2181, 2024.

Patterns of failure after salvage head and neck surgery.

BACKGROUND: Advancements in immunotherapy for recurrent head and neck cancer have necessitated a better understanding of salvage surgical outcomes. This study aimed to determine patterns of failure following salvage head and neck surgery. METHODS: A retrospective cohort study was conducted of 280 patients who underwent salvage surgery for recurrent mucosal squamous cell carcinoma from 1997 to 2018. Cumulative incidence was calculated using the nonparametric Aalen-Johansen estimator. Time to recurrence (TTR) and overall survival (OS) were estimated using the Kaplan-Meier method and multivariable Cox proportional hazard models were used to evaluate associated factors. RESULTS: The 2 and 5-year cumulative incidence rates of second recurrence were 48.3 % (95 % CI 42.4-54.3) and 54.9 % (95 % CI 48.9-60.8), respectively. At 5 years, second locoregional recurrence was twice as common as distant recurrence (41.5 % [95 % CI 35.6-47.4] vs. 21.7 % [95 % CI 16.8-26.6]). The median TTR was 21.1 months (95 % CI 4.4-34.8), which varied by site (38.2 larynx/hypopharynx, 13.9 oral cavity, 8.3 sinonasal, and 7.8 oropharynx, P=.0001). The median OS was 32.1 months (95 % CI 24.1-47.6) and was worse for patients who were Black (hazard ratio [HR] 2.15, 95 % CI 1.19-3.9), current smokers (HR 2.73, 95 % CI 1.53-4.88), former smokers (HR 2.00, 95 % CI 1.19-3.35), ≥ 60 years of age (HR 1.41, 95 % CI 1.01-1.97), or received multimodal primary therapy (HR 1.98, 95 % CI 1.26-3.13). CONCLUSION: Rates of recurrence and mortality after salvage surgery were poor but worse for patients who were Black, older, smoked, had initial multimodal therapy, or had sinonasal or oropharyngeal cancers.

Primary fit tracheoesophageal puncture in primary versus salvage laryngectomy: Short-term and long-term complications and functional outcomes.

BACKGROUND: Primary fit tracheoesophageal puncture (TEP) is widely preferred for individuals who have not undergone prior radiation. However, there is no consensus on the relative utility of primary-fit TEP in the setting of salvage laryngectomy. METHODS: A retrospective, single-center review was conducted of individuals undergoing laryngectomy with primary fit TEP between 2012 and 2018. Multivariable analysis was conducted to compare short-term and long-term complications, as well as speech and swallowing outcomes, of those who underwent primary versus salvage laryngectomy. RESULTS: In this study, 134 patients underwent total laryngectomy with primary fit TEP. Aside from a higher rate of peristomal dehiscence (13.1% vs. 1.4%) found in the salvage group, there was no difference in incidence of all other complications, including pharyngocutaneous fistula formation. The groups had comparable speech and swallow outcomes. CONCLUSION: Primary fit TEP is a safe and effective surgical choice for individuals undergoing salvage laryngectomy who desire a voice prosthesis.

Evaluation of Anterolateral Thigh Fascia Lata Rescue Flap for Mandibular Osteoradionecrosis.

Importance: Mandibular osteoradionecrosis (ORN) is a progressive disease that can be difficult to treat. Conservative measures often fail, while conventional definitive management requires a morbid segmental resection with osteocutaneous reconstruction. Evidence of the anterolateral thigh fascia lata (ALTFL) rescue flap technique's safety, effectiveness, and long-term outcomes is needed. Objective: To determine the long-term outcomes of the ALTFL rescue flap procedure for treating patients with mandibular ORN. Design, Settings, and Participants: This was a retrospective medical record review performed at a single tertiary-level academic health care institution with patients who were appropriate candidates for the ALTFL procedure to treat mandibular ORN from March 3, 2011, to December 31, 2022. Data analyses were performed from January 1 to March 26, 2023. Main Outcomes and Measures: Patient characteristics, preoperative radiographic Notani staging, intraoperative defect size, length of stay, complication rates, and clinical and radiographic findings of progression-free intervals. Results: The study population of 43 patients (mean [SD] age, 66.1 [47-80] years; 24 [55.8%] male individuals) included 52 cases of mandibular ORN. The preoperative Notani staging of the study population was known for 46 of the 52 total cases: 11 cases (23.9%) were stage I; 21 (45.7%), stage II; and 14 (30.4%), stage III. The mean defect area was 20.9 cm2. Successful arrest of ORN disease progression was noted in the clinical and radiographic findings of 50 of the 52 (96.2%) cases, with only 2 (3.8%) cases subsequently requiring fibular free flap reconstruction. The major complication rate was 1.9% (1 case). Clinical and radiographic progression-free intervals were assessed, and no statistically significant differences were noted between Notani staging groups (log-rank P = .43 and P = .43, respectively); ie, patients with stage III disease had no significant difference in risk of clinical (HR, 0.866; 95% CI, 0.054-13.853) or radiographic (HR, 0.959; 95% CI, 0.059-15.474) progression vs those with stage I disease. Weibull profiling revealed 96.9%, 94.6%, and 93.1% successful mandibular ORN arrest at 1, 3, and 5 years, respectively. The major complication rate was 1.9%. Mean (SD) length of stay was 2.7 (0.0-7.0) days. Mean (SD) radiographic follow-up was 29.3 (30.7) months. Conclusions and Relevance: The findings of this large retrospective patient case series support the continued success of the ALTFL rescue flap technique, a safe and highly effective long-term treatment for mandibular ORN in carefully selected patients.

Association between hypertension requiring medication and 30-day outcomes in head and neck microvascular surgery.

BACKGROUND: Hypertension has been shown to be both a protective factor and a risk factor for complications in head and neck reconstructive surgery. METHODS: Retrospective analysis of microvascular free tissue transfer patients using the National Surgical Quality Improvement Program database. RESULTS: Hypertensive patients (n = 1598; 46.9%) had a significantly higher rate of complications, including pneumonia (p < 0.001), myocardial infarction (p = 0.003), and intra/post-operative transfusion (p < 0.001). In a multivariable model, hypertension was associated with returning to the operating room (OR = 1.45 [95% CI 1.20, 1.76], p < 0.001), post-operative medical complications (OR = 1.53 [95% CI 1.24, 1.90], p < 0.001), and surgical complications (OR = 1.17 [95% CI 1.00, 1.37], p = 0.047). However, no difference in 30-day readmission was found (p > 0.05). CONCLUSIONS: Hypertension is a modifiable risk factor for post-operative complications in head and neck free tissue transfer, in which prospective studies are required to establish causation. This study may serve as an impetus for proactive recommendations to manage hypertension before undergoing head and neck microvascular surgery.

Outcomes After Oral Cavity and Oropharyngeal Salvage Surgery.

OBJECTIVES: Investigate outcomes following oral cavity and oropharyngeal salvage surgery. METHODS: Adult patients who underwent salvage surgery for recurrent squamous cell carcinoma of the oral cavity and oropharynx from 1996 to 2018 were analyzed using multivariable Cox proportional hazards regression. Disease-free survival (DFS), overall survival (OS), associated factors, and basic quality measures were analyzed. RESULTS: One hundred and eight patients (72% oral cavity, 28% oropharynx) were followed for a median of 17.9 months. Median DFS and OS were 9.9 and 21 months, respectively. Surgery with adjuvant chemoradiotherapy compared to surgery alone (hazard ratio [HR] = 0.15, 95% confidence interval [CI]: 0.03-0.78) and negative margins (HR = 0.36, 95% CI: 0.14-0.90) were associated with better DFS, while lymphovascular space invasion (LVSI) (HR = 2.66, 95% CI: 1.14-6.19) and higher stage (III vs. I-II, HR = 3.94, 95% CI: 1.22-12.71) were associated with worse DFS. Higher stage was associated with worse OS (HR = 3.79, 95% CI: 1.09-13.19). Patients were hospitalized for a median of 8 days with 24% readmitted within 30 days. A total of 72% and 38% of patients, respectively, underwent placement of a feeding tube or tracheostomy. CONCLUSIONS: After oral cavity and oropharyngeal salvage surgery, adjuvant chemoradiotherapy, negative margins, negative LVSI, and lower stage were associated with a lower risk of recurrence. Only lower-stage disease was associated with improved survival. The majority of patients had feeding tubes, half underwent free tissue transfer, a third required tracheostomy, and a quarter was readmitted. LEVEL OF EVIDENCE: 3 Laryngoscope, 132:1984-1992, 2022.

Nasopharyngeal cancer: Incidence and prognosis of human papillomavirus and Epstein-Barr virus association at a single North American institution.

BACKGROUND: The prognostication of Epstein-Barr virus (EBV) and human papillomavirus (HPV) status in nasopharyngeal cancer (NPC) is unclear. METHODS: This retrospective study analyzed NPC from 2000 to 2019. RESULTS: Seventy-eight patients were included: 43 EBV+ , 12 HPV+ , 23 EBV- /HPV- , and 0 EBV+ /HPV+ . All p16+ tumors were also positive for HPV-CISH. Baseline characteristics were not different between groups except age, N-classification, and Karnofsky Performance Scale (KPS) (p < 0.05). For EBV+ , HPV+ , and EBV- /HPV- respectively, 3-year overall survival (OS) was 89.9%, 69.8%, and 52.5% (p = 0.006). EBV- /HPV- status was significantly associated with worse OS but not freedom from progression (FFP) on univariate analysis, and did not remain a significant predictor of OS after adjusting for KPS, age, and group stage. CONCLUSIONS: EBV+ NPC tumors were seen in younger, healthier patients than HPV+ and EBV- tumors, and there were no cases of coinfection. The association of viral status with OS was insignificant after adjusting for KPS and age.

Limited Toxicity of Hypofractionated Intensity Modulated Radiation Therapy for Head and Neck Cancer.

BACKGROUND/AIM: Hypofractionated radiation therapy is not commonly used in head and neck cancers (HNC) due to increased toxicity observed in historical cohorts. This study reviews our institutional experience using hypofractionated intensity modulated radiation therapy (H-IMRT) for HNC. PATIENTS AND METHODS: A retrospective cohort study of 56 patients with HNC treated with H-IMRT with ≥50 Gy in 20 fractions was conducted. The primary outcomes were acute and late toxicity. RESULTS: Two-year locoregional control was 87% and median overall survival was 46 months. There were no acute or late grade 4 or 5 toxicities. Acute grade 2 and 3 toxicity was seen in 79% (N=44) and 25% (N=14), respectively. Late grade 2 toxicity was seen in 9% (N=5). No patients required the placement of a feeding tube or tracheostomy. CONCLUSION: H-IMRT for the definitive or post-operative treatment of HNC using ≥50 Gy in 20 fractions appears safe and well tolerated with modest toxicity.

Outcomes of Post-Operative Treatment with Concurrent Chemoradiotherapy (CRT) in High-Risk Resected Oral Cavity Squamous Cell Carcinoma (OCSCC): A Multi-Institutional Collaboration.

Adjuvant chemoradiation (CRT), with high-dose cisplatin remains standard treatment for oral cavity squamous cell carcinoma (OCSCC) with high-risk pathologic features. We evaluated outcomes associated with different cisplatin dosing and schedules, concurrent with radiation (RT), and the effect of cumulative dosing of cisplatin. An IRB-approved collaborative database of patients (pts) with primary OCSCC (Stage I-IVB AJCC 7th edition) treated with primary surgical resection between January 2005 and January 2015, with or without adjuvant therapy, was established from six academic institutions. Patients were categorized by cisplatin dose and schedule, and resultant groups compared for demographic data, pathologic features, and outcomes by statistical analysis to determine disease free survival (DFS) and freedom from metastatic disease (DM). From a total sample size of 1282 pts, 196 pts were identified with high-risk features who were treated with adjuvant CRT. Administration schedule of cisplatin was not significantly associated with DFS. On multivariate (MVA), DFS was significantly better in patients without perineural invasion (PNI) and in those receiving ≥200 mg/m2 cisplatin dose (p < 0.001 and 0.007). Median DFS, by cisplatin dose, was 10.5 (<200 mg/m2) vs. 20.8 months (≥200 mg/m2). Our analysis demonstrated cumulative cisplatin dose ≥200 mg/m2 was associated with improved DFS in high-risk resected OCSCC pts.

Evaluating compliance with process-related quality metrics and survival in oral cavity squamous cell carcinoma: Multi-institutional oral cavity collaboration study.

BACKGROUND: Process-related measures have been proposed as quality metrics in head and neck cancer care. A recent single-institution study identified four key metrics associated with increased survival. This study sought to validate the association of these quality metrics with survival in a multi-institutional cohort. METHODS: Multicenter retrospective study of patients with oral cavity squamous cell (1/2005-1/2015). Baseline patient and disease characteristics and compliance with quality metrics was evaluated. Association between compliance with quality metrics with overall survival (OS), disease-free survival (DFS), and disease-specific survival (DSS) was evaluated using Cox proportional hazards models. RESULTS: Failure to comply with two or more of the quality metrics was associated with worse OS, DFS, and DSS. Adherence to all or all but one of the quality metrics was found to be associated with improved survival. CONCLUSIONS: Process-related quality metrics are associated with increased survival in patients with oral cavity squamous cell carcinoma in a multi-institutional cohort.

Tumor Volume Useful Beyond Classic Criteria in Selecting Larynx Cancers For Preservation Therapy.

OBJECTIVE: To investigate the association between tumor volume and locoregional failure (LRF) after concurrent chemoradiation (CCRT) for locally advanced larynx cancer (LC). METHODS: This is a retrospective cohort study from 2009 to 2014 identified from an institutional review board-approved registry. Fifty-nine of 68 patients with locally advanced larynx cancer treated with definitive CCRT who had available imaging for review were identified. The main endpoint to be assessed was the association between gross tumor volumes (GTV; T = total, P = primary, N = nodal) and LRF. Receiver operative characteristic (ROC) curves were used to investigate diagnostic accuracy. RESULTS: Twenty LRFs were observed, resulting in a 2-year LRF rate of 39% (95% CI, 23-52%). On UVA, the GTV-T (P = .01), GTV-P (P = .05), and GTV-N (P = .04) were statistically significant predictors of LRF. Furthermore, age, smoking status, N-stage, larynx subsite, and tracheostomy/feeding tube dependence were potentially associated with LRF (P < .3), whereas T-stage (T3-4 vs. T2) was not (HR 1.05, 95% CI, 0.38-2.91, P = .92). In the multivariable model, GTV-P (HR 1.022, 95% CI, 0.999-1.046, P = .07) and GTV-N (HR 1.053, 95% CI, 1.0004-1.108, P = .05) were the two most impactful covariates on the model's R2 . ROC analysis suggested an optimal cut point of 12 cc in the GTV-T. The 2-year LRF for GTV-T > 12 cc was 64.2% and ≤ 12 cc was 16.4%, P = .006. CONCLUSION: GTV is associated with LRF after definitive CCRT for LC. Patients with bulky primary and/or nodal tumors may be better served with upfront surgical resection regardless of T-stage. Further investigation into the safety of larynx preservation for low-volume T4 tumors can be considered. LEVEL OF EVIDENCE: 4 Laryngoscope, 130:2372-2377, 2020.