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.

Occult Nodal Metastases in Individuals with Clinically Node-Negative Salivary Gland Malignancies.

OBJECTIVES: Salivary gland malignancies comprise a heterogeneous group of pathologies, for which treatment of the clinically negative neck may vary depending on numerous factors. Herein we present data on occult nodal metastases (ONM) as well as survival and recurrence from a large series of cN0 salivary gland malignancies. METHODS: Retrospective chart review was conducted on 532 patients, with 389 patients with major salivary gland cancers and 143 patients with minor salivary gland cancers. Demographic and treatment data were included and rates of ONM, overall survival, local recurrence, regional recurrence, and distant recurrence were analyzed. RESULTS: We found that the overall rate of ONM for parotid was 27% (63/235), for submandibular/sublingual was 35% (18/52), and for minor was 15% (4/26). Analysis of ONM rate at each nodal level was also performed, finding higher rates of level IV and V ONM than prior studies. Submandibular/sublingual and minor salivary gland malignancies showed a predominance of ONMs at levels I-III. Our survival and recurrence rates were similar to those found in previous studies. CONCLUSION: Our data also demonstrate a predominance of ONM in levels I-III for submandibular/sublingual and minor salivary gland cancers, suggesting elective dissection in these levels. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:1705-1715, 2024.

Head and Neck Surgery-The Call to Joyful Sacrificial Giving.

This Viewpoint explores the role of the servant leader and its implications as a leadership model for head and neck surgeons.

An Unusual Case of a Pharyngeal Fistula to the Cervical Spine Causing Osteomyelitis.

SIGNIFICANCE STATEMENT: Pharyngeal fistulas to the cervical spine resulting in vertebral osteomyelitis are a rare, yet clinically important, complication of total laryngectomy performed in conjunction with chemoradiotherapy or radiation therapy. This complication is likely underdiagnosed and can have a high mortality rate. It is very important that clinicians are aware of this complication as early diagnosis and management may improve patient outcomes.

Prognostic value of computed tomography scan detection of cartilage invasion in advanced laryngeal cancer treated with primary total laryngectomy.

BACKGROUND: We sought to determine whether detection of cartilage invasion (CI) by computed tomography predicts oncologic outcomes after primary total laryngectomy. METHODS: Retrospective cohort study comparing oncologic outcomes between radiologic versus pathologic diagnosis. RESULTS: Assessment of clear CI versus gestalt CI resulted in 84% versus 48% specificity, 90.9% versus 80.3% positive predictive value (PPV), 60.6% versus 80.3% sensitivity, 44.7% versus 48% negative predictive value (NPV), respectively. Disease-free survival (DFS) was similar between cT4a and cT3/cT2 patients (p = 0.87). DFS trended towards superiority among pT3/pT2 versus pT4a patients (p = 0.18). DFS was similar among patients with CI on radiologist gestalt versus no CI (p = 0.94). Histologically confirmed CI was associated with a hazard ratio (HR) of 1.46 (p = 0.27), gestalt CI 1.13 (p = 0.70), and clear CI 1.61 (p = 0.10) for DFS. CONCLUSION: Gestalt determination of CI results in high sensitivity but low specificity, while clear determination of CI results in moderate sensitivity and high specificity.

Poorly Differentiated Thyroid Carcinoma: Single Institution Series of Outcomes.

BACKGROUND AND AIM: Poorly differentiated thyroid cancer (PDTC) is a rare but aggressive subtype of thyroid cancer that portends a poor prognosis. There remains a paucity of literature on PDTC outcomes. The aim of our study was to evaluate outcomes of PDTC in our tertiary care facility. PATIENTS AND METHODS: We identified all histologically confirmed PDTC cases from 1997-2018 treated at our Institution and collected data points in an IRB-approved registry. We then conducted a retrospective study to assess outcomes and identified factors associated with inferior outcomes. RESULTS: Twenty-three patients were identified with a median age at diagnosis of 60 years (range=39-89 years). Nineteen (83%) underwent total thyroidectomy. Eight (42%) patients had lymph node dissections and 2 (11%) underwent adjuvant radiation. Thirteen (68%) patients were treated with radioactive iodine (RAI). Those who underwent total thyroidectomy had a median overall survival (mOS) of 88 months, 5 year-OS of 56%, 5 year-local recurrence-free survival (LRFS) of 45%, and 5 year-distant recurrence-free survival (DRFS) of 36%. T4 disease had worse mOS (14 vs. 87 m, p=0.0082), and 5 year-LRFS rate (12 vs. 74%, p=0.0312) compared to T1-3. N0 disease had an improved mOS (172 vs. 32 m, p=0.0013), 5 year-LRFS rate (63 vs. 17%, p=0.0033), and 5 year-DRFS (57 vs. 0%, p=0.0252). Eight out of 23 patients (35%) were alive at last follow-up, with a median of 68 months (range=20-214). The most common cause of death was distant recurrence (73%). Six patients received systemic therapy with various tyrosine kinase inhibitors with a median duration on treatment of 7 months (range=1-30 months). CONCLUSION: Advanced T and N stage were factors associated with significantly inferior outcomes. While select patients benefited with systemic treatment, it remains unclear if intensified locoregional therapy should be considered in patients with PDTC.

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 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.

Influence of Treatment Package Time on outcomes in High-Risk Oral Cavity Carcinoma in patients receiving Adjuvant Radiation and Concurrent Systemic Therapy: A Multi-Institutional Oral Cavity Collaborative study.

OBJECTIVES: To explore the influence of treatment package time(TPT) in high-risk oral cavity squamous cell carcinoma(OCSCC) receiving adjuvant radiotherapy with concurrent chemotherapy(CRT). MATERIALS AND METHODS: We queried our multi-institutional OCSCC collaborative database for cases diagnosed between 2005 and 2015 who underwent surgery followed by adjuvant CRT. All patients had high-risk features: extranodal extension(ENE) and/or positive surgical margin(PM). TPT was days between surgery to last radiotherapy fraction. Kaplan-Meier curves, log-rank p-values and multivariate analysis(MVA) were used to investigate the impact of TPT on overall(OS), disease-free(DFS), locoregional failure-free(LRFS) and distant metastases-free(DMFS) survival. RESULTS: We identified 187 cases: median age 58 (range, 24-87 years), males 66%, and ever smokers 69%. ENE and PM were detected in 85% and 32%, and oral tongue and floor of the mouth constituted 49% and 18%, respectively. Median radiotherapy and cisplatin doses received were 66 Gy and 200 mg/m2. Overall, median TPT was 98 (range, 63-162 days). OS was worse for TPT > 90-days (n = 134) than TPT ≤ 90 (n = 53) at two-(65% vs. 71%) and five-years (45% vs. 62%); p = 0.05, with similar results for DFS. No influence on LRFS or DMFS was noted. More lymph nodes(LN) dissected(P = 0.039), T3-4 disease(P = 0.017), and unplanned reoperations(P = 0.037) occurred with TPT > 90-days. On MVA, TPT in 10-day increments was independently detrimental for OS (Hazard Ratio: 1.14; 95 %Confidence Interval [1-1.28]; P = 0.043), perineural invasion, age and positive LN (p < 0.05 for all). CONCLUSION: In one of the largest multi-institutional cohorts, TPT > 90-days predicted worse OS for high-risk OCSCC receiving adjuvant CRT. All efforts are needed to optimize perioperative care and baseline conditions for favorable outcomes.

Updated Outcomes of Split Course Radiotherapy in Elderly or Infirm Patients With Advanced Cancers of the Head and Neck.

BACKGROUND/AIM: Head and neck cancers are often treated with extended courses of radiotherapy (RT), which may prove excessively toxic for frail patients. Split course RT (SCRT) delivers two courses of RT separated by 4-6 weeks, personalizing treatment intensity based on response. In this study, we present our updated experience using this technique. PATIENTS AND METHODS: From a single institution database, we identified patients considered for SCRT. For patients undergoing a second course of RT, cumulative incidence of locoregional recurrence (LRR) and overall survival (OS) are reported. RESULTS: A total of 98 patients were included, of whom seventy-five percent underwent a second course of RT. The most common fractionation was 30 Gy in 10 fractions for each course, with a median cumulative dose of 60 Gy. In those undergoing a second course of RT, median OS was 9.7 months and cumulative incidence of LRR at 6, 12, and 24 months was 17.0%, 23.1%, and 29.4%, respectively. CONCLUSION: SCRT offers an attractive treatment paradigm to personalize radiation intensity based on patient tolerance, while maintaining reasonable safety and efficacy in those unfit for standard full course RT.

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.

Risk Assessment in Thyroid Lobectomy and Total Thyroidectomy using Over 100 Thousand Cases.

OBJECTIVES: To assess risk factors and non-thyroid specific postoperative complications for thyroid lobectomy compared to total thyroidectomy. METHODS: A retrospective, cross-sectional study of adults undergoing a lobectomy or total thyroidectomy using the National Surgical Quality Improvement Program database between 2005 and 2017. Patients not treated by otolaryngologists or general surgeons and with unknown demographic variables were excluded. RESULTS: A total of 106 915 patients were analyzed, 64 763 total thyroidectomies and 42 152 lobectomies. Multivariable analysis demonstrated that total thyroidectomy patients were half as likely to return to the operating room (OR = 0.491 (95%CI 0.445-0.542), P < .001). Within this cohort, patients at greater risk for reoperation had a history of hypertension (OR = 1.225 (95%CI 1.090-1.376), P < .001), a malignant pathology (OR = 1.921 (95%CI 1.734-2.128), P < .001), and smoked (OR = 1.237 (95%CI 1.087-1.407), P = .001). Conversely, diabetes and body mass index did not impact the rate of reoperation when assessing total thyroidectomy and lobectomy. The most frequent non-thyroid specific complications in total thyroidectomy were unplanned intubation (0.5%), urinary tract infection (0.3%), and superficial surgical site infection (0.3%). In thyroid lobectomy, the most common complications were superficial surgical site infection (0.3%) and urinary tract infection (0.2%). CONCLUSIONS: Our multi-institutional study indicates specific risk factors for returning to the operating room that may warrant closer follow up after surgery for total thyroidectomy or thyroid lobectomy. We also identified the most common post-operative complications. During pre-operative planning, these findings should be considered by thyroid surgeons to help mitigate risk to patients.

Clinical Versus Pathologic Laryngeal Cancer Staging and the Impact of Stage Change on Outcomes.

OBJECTIVES/HYPOTHESIS: Evaluate the impact and accuracy of clinical laryngeal cancer staging. STUDY DESIGN: Retrospective cohort study. METHODS: Two hundred sixty-five consecutive patients with laryngeal squamous cell carcinoma who underwent total laryngectomy from 2001 to 2017 were studied. Clinical versus pathologic tumor (T) and nodal (N) categories were compared. Logistic regression and Cox proportional hazards analyzed the association of stage change with perioperative factors and outcomes. RESULTS: Forty-seven patients (17.7%, accuracy = 0.969 ± 0.010 [standard error]) changed between T1-2 and T3-4. Sixty-four patients (24.1%, accuracy = 0.866 ± 0.020) had inaccurate N category. Salvage patients were less likely to have stage change (downstage: odds ratio [OR] = 0.20, 95% confidence interval [CI]: 0.08-0.50, P < .001; upstage: OR = 0.41, 95% CI: 0.23-0.74, P = .003), but more likely to have inaccurate nodal category (39.8% vs. 11.7%, P < .001). Patients with stage change tended to have greater odds of positive/close margins (upstage: OR = 1.78, 95% CI: 0.91-3.5, P = .092) and chemotherapy (downstage: OR = 2.21, 95% CI: 0.80-6.14, P = .128; upstage: OR = 1.87, 95% CI: 0.85-4.11, P = .119). Stage change was associated with recurrence (P = .047) with downstaged patients less likely to recur (hazard ratio = 0.26, 95% CI: 0.08-0.82, P = .021). Stage change was not associated with positron emission tomography scan, subsite, time to surgery, or mortality. CONCLUSIONS: A third of laryngeal cancer patients were downstaged or upstaged after laryngectomy with 18% and 24% of clinical T and N categories inaccurate, respectively. Stage change was less common for salvage patients and associated with risk of recurrence. LEVEL OF EVIDENCE: 3 Laryngoscope, 131:559-565, 2021.

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.

A National Comparison of Postoperative Outcomes in Completion Thyroidectomy and Total Thyroidectomy.

OBJECTIVE: To characterize and assess the non-thyroid-specific postoperative complications of completion thyroidectomy as compared with total thyroidectomy. STUDY DESIGN: Retrospective analysis: 2005 to 2017. SETTING: National Surgical Quality Improvement Program database. SUBJECTS AND METHODS: Patients aged >18 years receiving a completion or total thyroidectomy were eligible for inclusion. Patients not treated by otolaryngologists or general surgeons and with unknown demographic variables were excluded. RESULTS: A total of 70,638 patients were analyzed, representing 64,763 total thyroidectomies and 5875 completion thyroidectomies. The 30-day mortality rate was 0.1% for both procedures (P > .05). Overall, 1.7% and 1.4% of patients undergoing total and completion thyroidectomies experienced at least 1 complication (P > .05), while 1.2% and 0.9% had a postoperative medical complication (P = .0186), respectively. On multivariable analysis, patients undergoing total thyroidectomies were significantly more likely to return to the operating room (odds ratio [OR], 1.36; 95% CI, 1.04-1.80; P = .027) and to be readmitted (OR, 1.45; 95% CI, 1.16-1.81; P = .001). Adjusted analysis also demonstrated that patients undergoing total thyroidectomies were more likely to be inpatients (OR, 1.17; 95% CI, 1.11-1.24; P < .001), be treated by nonotolaryngologists (OR, 1.36; 95% CI, 1.29-1.45; P < .001), and smoke (OR, 1.22; 95% CI, 1.13-1.33; P < .001). CONCLUSION: National data suggest that total and completion thyroidectomies are relatively safe procedures but that completion thyroidectomies are associated with lower rates of postoperative complications. These findings may play a role in determining treatment plans for patients and optimizing risk reduction.

Characteristics and Outcomes in Head and Neck Sarcomatoid Squamous Cell Carcinoma: The Cleveland Clinic Experience.

OBJECTIVES: To analyze characteristics, treatment outcomes, and prognostic factors of sarcomatoid squamous cell carcinoma of the head and neck. STUDY DESIGN: Retrospective chart review. SETTING: Tertiary care center. SUBJECTS AND METHODS: Fifty-five patients were treated for sarcomatoid squamous cell carcinoma of the head and neck between 1996 and 2018. Data collection included clinical history, tumor characteristics, pathology, treatment modality, and outcomes. Mean follow up was 17.1 months. Cox univariate analysis was used to evaluate for associations with locoregional recurrence, distant metastasis, and overall survival. RESULTS: Most patients were white males with a smoking history and median age 66 years (range 41-92) at diagnosis. Twenty-two percent had prior head and neck radiation. Tumor site was most frequently oral cavity (41.8%), followed by larynx (29.1%), and oropharynx (16.4%). Half presented with early T stage disease (15.5% T0, 12.7% T1, 30.9% T2) and the remainder with late stage disease (16.4% T3, 34.5% T4). Locoregional recurrence rate was 60.0%, metastatic recurrence was rate 21.8%, with median time to recurrence of 4 months and mean overall survival of 20 months. Presence of lymphovascular space invasion was statistically associated with locoregional recurrence (P = .018, HR 3.55 [95% CI 1.24, 10.14]) and poorer overall survival (P = .015, HR 2.92 [95% CI 1.23, 4.80]). Treatment with multimodality therapy was associated with decreased locoregional recurrence (P = .039, HR 0.39 [95% CI 0.16, 0.95]) but did not impact overall survival. CONCLUSION: Sarcomatoid squamous cell carcinoma remains a rare and aggressive disease variant with high recurrence rates and high mortality. High risk features such as lymphovascular space may indicate the need for more aggressive therapy.

Identifying an oligometastatic phenotype in HPV-associated oropharyngeal squamous cell cancer: Implications for clinical trial design.

OBJECTIVES: Patients with human papillomavirus (HPV) associated squamous cell carcinoma of the oropharynx (SCC-OP) have improved overall survival (OS) after distant metastasis (DM) compared to HPV negative patients. These patients may be appropriate candidates for enrollment on clinical trials evaluating the efficacy of metastasis-directed therapy (MDT). This study seeks to identify prognostic factors associated with OS after DM, which could serve as enrollment criteria for such trials. MATERIALS AND METHODS: From an IRB approved multi-institutional database, we retrospectively identified patients with HPV/p16 positive SCC-OP diagnosed between 2001 and 2018. Patterns of distant failure were assessed, including number of lesions at diagnosis and sites of involvement. The primary outcome was OS after DM. Prognostic factors for OS after DM were identified with Cox proportional hazards. Stepwise approach was used for multivariable analysis. RESULTS: We identified 621 patients with HPV-associated SCC-OP, of whom 82 (13.2%) were diagnosed with DM. Median OS after DM was 14.6 months. On multivariable analysis, smoking history and number of lesions were significantly associated with prolonged OS. Median OS after DM by smoking (never vs ever) was 37.6 vs 11.2 months (p = 0.006), and by lesion number (1 vs 2-4 vs 5 or more) was 41.2 vs 17.2 vs 10.8 months (p = 0.007). CONCLUSION: Among patients with newly diagnosed metastatic HPV-associated SCC-OP, lesion number and smoking status were associated with significantly prolonged overall survival. These factors should be incorporated into the design of clinical trials investigating the utility of MDT, with or without systemic therapy, in this population.

Locoregional and distant recurrence for HPV-associated oropharyngeal cancer using AJCC 8 staging.

INTRODUCTION: The objective of this study is to evaluate locoregional and distant failure for human papillomavirus-associated (HPV+) oropharyngeal squamous cell carcinoma (OPSCC) using American Joint Committee on Cancer eighth edition (AJCC 8) staging. MATERIALS AND METHODS: Retrospective cohort study of 457 patients with HPV + OPSCC, treated with platinum-based chemoradiation from 2002 to 2018, followed for a median of 4.3 years. Time to locoregional failure (TTLRF) and distant failure (TTDF) were estimated by Kaplan-Meier method. Log-rank, recursive partitioning analysis (RPA), and multivariable Cox proportional hazards were used to evaluate associated factors and stratify risk. RESULTS: Rates of five-year locoregional control (LRC) and distant control (DC) were 92% (95% CI, 90-95%) and 89% (95% CI, 85-92%), respectively. Smoking, T4, N3, and stage III were associated with significantly worse TTLRF. RPA identified three distinct locoregional failure groups: cT1-3 and <19 pack-years vs. cT1-3 with ≥19 pack-years vs. cT4 (five-year LRC: 97% vs. 90% vs. 82%, P < .0001). The only factor associated with significantly worse TTDF was smoking status, while stage was not correlated. RPA identified two prognostic groups: former or never smokers vs. current smokers (five-year DC: 92% vs. 77%, P = .0003). DISCUSSION: In the largest evaluation of HPV + OPSCC after platinum-based chemoradiation using AJCC 8, risk for locoregional recurrence was stratified by smoking, T category, N category, and overall stage. Risk of distant recurrence was only stratified by smoking status and not related to stage. This has implications for surveillance and clinical trial design.

Detection and Oncologic Outcomes of Head and Neck Squamous Cell Carcinoma of Unknown Primary Origin.

BACKGROUND/AIM: To assess factors that predict detection of tumors and oncologic outcomes in head and neck squamous cell carcinoma of unknown primary (SCCUP). PATIENTS AND METHODS: This was a retrospective cohort study at a single tertiary care institution. RESULTS: The primary site was detected at examination under anesthesia (EUA) in 92 (51.1%) patients. The primary site was detected by directed biopsies in 60 (65%), palatine tonsillectomy in 28 (30.4%), and lingual tonsillectomy in 4 patients (4.3%). Four of eight lingual tonsillectomies were positive (50%). Primary locations included: palatine tonsils (51, 28.3%), base of tongue (37, 20.6%), larynx (4, 2.2%), oral cavity (3, 1.67%) and nasopharynx (1, 0.6%). Human papillomavirus (HPV) positive status (HR=0.26, p=0.004) and treatment with chemoradiation (CRT) (HR=0.38, p=0.004) were associated with better disease free survival (DFS). CONCLUSION: A primary site was located after aggressive investigation in approximately half of the patients. More research is warranted towards the use of lingual tonsillectomy. Predictors of favorable prognosis included HPV positive status and treatment with CRT.