Intensity-Modulated Reirradiation Therapy With Nivolumab in Recurrent or Second Primary Head and Neck Squamous Cell Carcinoma: A Nonrandomized Controlled Trial.

Importance: Intensity-modulated radiation therapy (IMRT) reirradiation of nonmetastatic recurrent or second primary head and neck squamous cell carcinoma (HNSCC) results in poor progression-free survival (PFS) and overall survival (OS). Objective: To investigate the tolerability, PFS, OS, and patient-reported outcomes with nivolumab (approved standard of care for patients with HNSCC) during and after IMRT reirradiation. Design, Setting, and Participants: In this multicenter nonrandomized phase 2 single-arm trial, the treatment outcomes of patients with recurrent or second primary HNSCC who satisfied recursive partitioning analysis class 1 and 2 definitions were evaluated. Between July 11, 2018, and August 12, 2021, 62 patients were consented and screened. Data were evaluated between June and December 2023. Intervention: Sixty- to 66-Gy IMRT in 30 to 33 daily fractions over 6 to 6.5 weeks with nivolumab, 240 mg, intravenously 2 weeks prior and every 2 weeks for 5 cycles during IMRT, then nivolumab, 480 mg, intravenously every 4 weeks for a total nivolumab duration of 52 weeks. Main Outcomes and Measures: The primary end point was PFS. Secondary end points included OS, incidence, and types of toxic effects, including long-term treatment-related toxic effects, patient-reported outcomes, and correlatives of tissue and blood biomarkers. Results: A total of 62 patients were screened, and 51 were evaluable (median [range] age was 62 [56-67] years; 42 [82%] were male; 6 [12%] had p16+ disease; 38 [75%] had salvage surgery; and 36 [71%.] had neck dissection). With a median follow-up of 24.5 months (95% CI, 19.0-25.0), the estimated 1-year PFS was 61.7% (95% CI, 49.2%-77.4%), rejecting the null hypothesis of 1-year PFS rate of less than 43.8% with 1-arm log-rank test P = .002 within a 1-year timeframe. The most common treatment-related grade 3 or higher adverse event (6 [12%]) was lymphopenia with 2 patients (4%) and 1 patient each (2%) exhibiting colitis, diarrhea, myositis, nausea, mucositis, and myasthenia gravis. Functional Assessment of Cancer Therapy-General and Functional Assessment of Cancer Therapy-Head and Neck Questionnaire quality of life scores remained stable and consistent across all time points. A hypothesis-generating trend favoring worsening PFS and OS in patients with an increase in blood PD1+, KI67+, and CD4+ T cells was observed. Conclusions and Relevance: This multicenter nonrandomized phase 2 trial of IMRT reirradiation therapy and nivolumab suggested a promising improvement in PFS over historical controls. The treatment was well tolerated and deserves further evaluation. Trial Registration: ClinicalTrials.gov Identifier: NCT03521570.

Assessing survival outcomes of patients with oral tongue squamous cell carcinoma: Focus on age, sex, and stage.

BACKGROUND: The purpose of this study was to provide further insights into whether age and/or sex are associated with prognosis in oral tongue squamous cell carcinoma. METHODS: This was a retrospective cohort study utilizing hospital registry data from 2006 to 2016 obtained from the National Cancer Database. Identified patients were divided into various cohorts based on age, sex, and staging. A descriptive analysis was performed using chi-square tests and overall survival rates were estimated using Kaplan-Meier method. RESULTS: A total of 17 642 patients were included in the study. The 5-year overall survival rates were 82.0% (95% CI: 79.8%-84.0%) in younger patients versus 67.5% (95% CI: 66.7%-68.3%, p-value <0.0001) older patients. The median overall survival for females was 143.4 months (95% CI: 133.2-NA) versus 129.8 (95% CI: 125.4-138.7, p-value <0.0001) in males. CONCLUSIONS: Our analysis suggests that younger age and female sex are both predictors of improved survival in oral tongue squamous cell carcinoma.

Submental Island Flaps for Lateral Reconstruction: Technical Refinements for Optimal Outcomes and Resource Efficiency.

Objective: To describe our modifications to the submental island flap (SMIF) in a case series that demonstrates improved reproducibility, shortened length of stay (LOS), and reduced utilization of hospital resources. Study Design: This retrospective case series with chart review included adult patients who underwent resection of malignant or benign tumors resulting in lateral facial, parotid, or temporal bone defects, which were reconstructed with SMIF. Setting: A tertiary-care academic referral center. Methods: Retrospective case series included all adult patients who underwent SMIF reconstruction between March 2020 and August 2021. Patient demographic and clinical data were collected. Primary outcomes were measures of hospital utilization including duration of surgery, LOS, and postoperative outcomes. Results: Twenty-eight patients were included with a mean age of 71.7 years. Eighty percent were male. All patients underwent parotidectomy, and the mean operative time was 347 minutes. The median LOS was 2.5 days (range 0-16 days). Seventy-five percent of the flaps drained into the internal jugular vein, and 25% drained into the external jugular vein. No patients required reoperation or readmission. All flaps survived. Conclusion: SMIFs are a safe and effective option for reconstruction of lateral facial, parotid, and temporal bone defects. Compared to free flap reconstruction, SMIFs offer reduced length of surgery, decreased use of health care resources, and lower rate of reoperation. As health care resource allocation is increasingly important, the SMIF offers an excellent alternative to free flap reconstruction of lateral defects.

The role of surgery and deescalation for HPV-related oropharyngeal cancer.

Recently published and ongoing trials are helping to define the role of transoral robotic surgery for oropharyngeal cancer. Evidence to date supports the use of surgery as a valuable tool in the multidisciplinary deescalation of low-risk human papillomavirus-related oropharyngeal squamous cell carcinoma.

Oral Cavity Cancer Surgical and Nodal Management: A Review From the American Head and Neck Society.

Importance: Lymph node metastases from oral cavity cancers are seen frequently, and there is still inconsistency, and occasional controversies, regarding the surgical management of the neck in patients with oral cancer. This review is intended to offer a surgically focused discussion of the current recommendations regarding management of the neck, focusing on the indications and extent of dissection required in patients with oral cavity squamous cell carcinoma while balancing surgical risk and oncologic outcome. Observations: The surgical management of the neck for oral cavity cancer has been robustly studied, as evidenced by substantial existing literature surrounding the topic. Prior published investigations have provided a sound foundation on which data-driven treatment algorithms can generally be recommended. Conclusions: Existing literature suggests that patients with oral cavity cancer should be fully staged preoperatively, and most patients should receive a neck dissection even when clinically N0. Quality standards supported by the literature include separation of each level during specimen handling and lymph node yield of 18 or more nodes. Sentinel lymph node biopsy can be considered in select tumors and within a well-trained multidisciplinary team.

Specimen-Based Resection Margins and Local Control during Transoral Robotic Surgery for Oropharyngeal HPV-Mediated Squamous Cell Carcinoma.

OBJECTIVES: The aim of the study was to investigate the association of surgical margin conditions, including positive specimen margins revised to negative relative to local recurrence, disease-free survival, and overall survival (OS) within a cohort of HPV-mediated oropharyngeal squamous cell carcinoma (OPSCC) who underwent en bloc resection via transoral robotic surgery (TORS). MATERIALS AND METHODS: Retrospective cohort of patients with untreated HPV-mediated OPSCC cT1 or T2 undergoing TORS resection between October 2014 and March 2020. The methodologic description of our interdisciplinary institutional approach, number of cut-through margins (CTMs) during intraoperative consultation, percentage of final positive margin cases, and disease-free survival and OS stratified by margin status and margin tumor-free distance is identified. RESULTS: 135 patients with primary cT1/T2 HPV-mediated OPSCC met inclusion criteria. Twenty-eight of 135 (20.7%) specimens revealed CTM and were revised during the same operative setting. Three of 135 (2.2%) surgical cases had positive final margin status. Local control rate was 97%. On univariate analysis, margin distance did not impact OS. CTM and final positive margins had lower OS than initially negative margins (p = 0.044). Pathologic N-stage significantly impacted OS (p < 0.001). CONCLUSIONS: High local control rate and low final positive margin status confound the study of specimen margin-based techniques in HPV-mediated OPSCC resected en bloc with TORS. Pathologic N-stage may impact OS more than margin status. Larger numbers are needed to confirm differences.

Ninety-day mortality following transoral robotic surgery or radiation at Commission on Cancer-accredited facilities.

BACKGROUND: Postoperative mortality for oropharynx squamous cell carcinoma (OPSCC) with transoral robotic surgery (TORS) varies from 0.2% to 6.5% on trials; the real-world rate is unknown. METHODS: NCDB study from 2010 to 2017 for patients with cT1-2N0-2M0 OPSCC with Charleson-Deyo score 0-1. Ninety-day mortality assessed from start and end of treatment at Commission on Cancer-accredited facilities. RESULTS: 3639 patients were treated with TORS and 1937 with radiotherapy. TORS cohort had more women and higher income, was younger, more often treated at academic centers, and more likely to have private insurance (all p < 0.05). Ninety-day mortality was 1.3% with TORS and 0.7% or 1.4% from start or end of radiotherapy, respectively. From end of therapy, there was no significant difference on MVA between treatment modality. CONCLUSIONS: There is minimal difference between 90-day mortality in patients treated with TORS or radiotherapy for early-stage OPSCC. While overall rates are low, for patients with expectation of cure, work is needed to identify optimal treatment.

Survival and functional outcomes after total glossectomy with total laryngectomy: Case series from a high-volume tertiary institution.

OBJECTIVES: Total glossectomy with total laryngectomy (TGTL) is indicated for some cases of advanced oral squamous cell carcinoma. However, this procedure is rarely performed, as quality of life outcomes are often considered poor. Consequently, few studies to date have reported survival and functional outcomes in patients undergoing TGTL. Here, we present the largest cases series to date of TGTL patients and provide relevant data on survival and functional outcomes. METHODS: Patients met inclusion criteria if they underwent TGTL (concurrent or staged) indicated for head and neck squamous cell carcinoma. Patient demographics and disease characteristics, survival outcomes, functional oral intake scores, time to oral intake, gastrostomy tube dependence, and communication methods post-surgery were retrospectively extracted from the electronic medical record. RESULTS: Survival in patients undergoing TGTL was poor. Most patients in this study were eventually approved for some oral intake of restricted consistencies but remained gastrostomy tube dependent for most of their nutritional needs. Baseline oral intake was suboptimal in most patients but often re-achieved approximately 12 months following surgery. Communication methods following surgery included writing, text-to-speech, and augmentative and alternative communication devices. CONCLUSION: Our data provide new insights comparing survival and functional outcomes of patients undergoing TGTL. Additional investigation particularly on patient-perceived quality of life following TGTL is needed to better understand the risks and benefits for patients who are candidates for TGTL.

Oncologic Outcomes After Clinically Node-Negative Salvage Laryngectomy.

Importance: Controversy exists regarding management of the clinically node-negative neck in patients with recurrent larynx or hypopharynx cancers who received total laryngectomy after definitive radiation with or without chemotherapy. Objective: To explore clinical and oncologic outcomes after elective neck dissection vs observation in patients who received clinically node-negative salvage total laryngectomy. Design, Setting, and Participants: This cohort study was performed from January 2009 to June 2021 at a single, high-volume tertiary care center. Follow-up was conducted through June 2021 for all patients. Survival outcomes were based on at least 2 years of follow-up. Patients aged 18 years or older with recurrent, clinically node-negative larynx or hypopharynx tumors after definitive nonsurgical treatment who were treated with a salvage total laryngectomy were included. Data were analyzed from October 2021 through September 2022. Exposures: Elective neck dissection. Main Outcomes and Measures: Presence and location of occult nodal metastasis in electively dissected necks, along with differences in fistula rates and overall and disease-free survival between patients receiving elective neck dissection vs observation. Results: Among 107 patients receiving clinically node-negative salvage total laryngectomy (median [IQR] age, 65.0 [57.8-71.3] years; 91 [85.0%] men), 81 patients underwent elective neck dissection (75.7%) and 26 patients underwent observation (24.3%). Among patients with elective neck dissection, 13 patients had occult nodal positivity (16.0%). Recurrent supraglottic (4 of 20 patients [20.0%]) or advanced T classification (ie, T3-T4; 12 of 61 patients [19.7%]) had an occult nodal positivity rate of 20% or more, and positive nodes were most likely to occur in levels II and III (II: 6 of 67 patients [9.0%]; III: 6 of 65 patients [9.2%]; VI: 3 of 44 patients [6.8%]; IV: 3 of 62 patients [4.8%]; V: 0 of 4 patients; I: 0 of 18 patients). There was a large difference in fistula rate between elective neck dissection (12 patients [14.8%]) and observed (8 patients [30.8%]) groups (difference, 16.0 percentage points; 95% CI, -3.4 to 35.3 percentage points), while the difference in fistula rate was negligible between 50 patients undergoing regional or free flap reconstruction (10 patients [20.0%]) vs 57 patients undergoing primary closure (10 patients [17.5%]) (difference, 2.5 percentage points; 95% CI, -12.4 to 17.3 percentage points). Undergoing elective neck dissection was not associated with a clinically meaningful improvement in overall or disease-free survival compared with observation. Recurrent hypopharynx subsite was associated with an increased risk of death (hazard ratio, 4.28; 95% CI, 1.81 to 10.09) and distant recurrence (hazard ratio, 7.94; 95% CI, 2.07 to 30.48) compared with glottic subsite. Conclusions and Relevance: In this cohort study, patients with recurrent supraglottic or advanced T classification tumors had an increased occult nodal positivity rate, elective neck dissection was not associated with survival, and patients with recurrent hypopharynx subsite were more likely to have a distant recurrence and die of their disease. These findings suggest that underlying disease pathology rather than surgical management may be associated with survival outcomes in this population.

Feasibility of clinical evaluation of individuals with increased risk for HPV-associated oropharynx cancer.

BACKGROUND: Human papillomavirus-associated oropharynx squamous cell carcinoma (HPV-OPSCC) has no known pre-malignant lesion. While vaccination offers future primary prevention, there is current interest in secondary prevention. The feasibility of clinical evaluation of individuals at increased risk for HPV-OPSCC is unclear. METHODS: Individuals with risk factors for HPV-OPSCC were enrolled in a prospective study (MOUTH). Participants positive for biomarkers associated with HPV-OPSCC were eligible for a clinical evaluation which comprised a head and neck examination and imaging with ultrasound and/or magnetic resonance imaging (MRI). This study was designed to evaluate feasibility of clinical evaluation in a screening study. RESULTS: Three hundred and eighty-four participants were eligible for clinical evaluation. Of the 384, 204 (53%) completed a head and neck examination or imaging. Of these, 66 (32%) completed MRI (n = 51) and/or ultrasound (n = 64) studies. CONCLUSIONS: Clinical evaluations, including head and neck examination and imaging, are feasible in the context of a screening study for HPV-OPSCC.

Team-Based Surgical Scheduling for Improved Patient Access in a High-Volume, Tertiary Head and Neck Cancer Center.

BACKGROUND: Delays in care can lead to inferior survival outcomes in head and neck cancer and other cancers. In the case of malignancies for which surgery is the preferred primary treatment modality, challenges in surgical scheduling can present a major hurdle to initiating definitive therapy in a timely fashion. It is critical to maintain efficient use of operating room resources. Traditionally, surgery is scheduled with the surgeon who initially saw the patient in consultation, and timing of surgery is tightly linked to the availability and operating room block time of the individual surgeon. METHODS: Scheduling of oncologic head and neck surgery was transitioned from a surgeon-specific method to a team-based approach wherein a patient in need of oncologic head and neck surgery is scheduled with the next-available surgeon with appropriate expertise. RESULTS: Despite substantial growth of our practice, transition to a team-based scheduling approach allowed us to maintain high utilization of operating room block time. Patient and surgeon satisfaction remain high with this new system. CONCLUSIONS: A team-based surgical scheduling approach can help optimize operating room utilization and minimize delays in cancer care, potentially leading to improved oncologic outcomes.

Survival, functional, and quality of life outcomes between total glossectomy with and without total laryngectomy: A narrative review.

BACKGROUND: A total glossectomy (TG) may be required for advanced tongue tumors. TG with total laryngectomy (TGL) may be indicated in some cases with tumor extension into the larynx or high risk of aspiration. Total glossectomy with laryngeal preservation (TGLP) may preserve phonation ability relative to TGL, yet TGLP may increase the risk of aspiration. METHODS: For this narrative review, we performed a comprehensive literature search of studies relevant to TG and TGL. Clinical studies investigating survival, functional outcomes, and quality of life in following TGLP or TGL were of particular interest. RESULTS: Few studies in the literature directly compare survival, functional, and quality of life (QOL) outcomes between TGLP and TGL. TGLP is associated with intelligible speech. However, studies investigating gastrostomy tube dependence following TGLP versus TGL have generated conflicting results. CONCLUSION: Further research on functional and QOL outcomes in patients undergoing TGL or TGLP is needed.

Comparison of the Seventh and Eighth Edition of American Joint Committee on Cancer (AJCC) Staging for Selected and Nonselected Oropharyngeal Squamous Cell Carcinomas.

OBJECTIVES: The eighth edition American Joint Committee on Cancer (AJCC) Staging incorporates significant changes to the seventh edition in the staging of oropharyngeal squamous cell carcinomas (OPSCC). An important change was the inclusion of OPSCC associated with the human papilloma virus (HPV). Our goal is to compare the performance of both staging systems for patients with HPV-selected and unselected clinical characteristics for OPSCC. METHODS: Using the Surveillance, Epidemiology, and End Results (SEER) database, 2004-2016, we identified patients with likely HPV-associated OPSCC based on surrogate markers (white males aged <65 years old with squamous cell carcinomas of the tonsil and base of tongue), excluding those who underwent surgery. We re-classified these patients using seventh and eighth edition staging for HPV-selected OPSCC and compared the prediction performance of both staging editions for overall survival (OS) and disease-specific survival (DSS). We performed the same analysis for clinically unselected patients with OPSCC. RESULTS: Our analysis included 9554 patients with a median follow-up of 67 months. Comparing the eighth versus seventh edition for our HPV-selected cohort, clinical staging changed for 92.3% of patients and 10-year OS was 62.2%, 61.2%, 35.3%, and 15.5% for Stage I, II, III, and IV, versus 52.9%, 59.2%, 61.6%, 55.1%, 38.3%, and 15.5% for stage I, II, III, IVA, IVB, and IVC, respectively. A similar pattern was observed for 10-year DSS. The concordance statistics for our HPV-selected cohort were improved for both AJCC 7 (0.6260) and AJCC 8 (0.6846) compared with the unselected cohort, 0.5860 and 0.6457 for AJCC 7 and 8, respectively. CONCLUSION: The overall performance of discrimination improved from AJCC 7 to AJCC 8 for both clinically selected and unselected patients, but more notably for our HPV-selected cohort. Despite the lack of statistically significant differentiation between Stages I and II in AJCC 8 in either groups, markedly improved discrimination was observed between Stages I/II, III, and IV in the HPV-selected cohort.

The omission of intentional primary site radiation following transoral robotic surgery in 59 patients: No local-regional failures.

BACKGROUND: We assessed locoregional control with omission of intentional primary site radiation after transoral robotic surgery (TORS) and quantified nontargeted primary site dose. METHODS: Following Institutional Review Board (IRB) approval, patients treated with primary TORS resection for squamous cell carcinomas of the oropharynx were reviewed. Patients with cT1-2 tumors, >2 mm margins, in whom the surgeon resected the primary without revising specimen-driven margins, qualified for omission of primary site radiation. RESULTS: From 2014 to 2019, 112 patients met criteria. Fifty-nine (52%) patients did not receive radiation targeting the primary site; of whom, 22 received no radiation. In this group, there were no local failures; mean age was 58 years and median follow-up was 25 months. Thirty-seven patients received adjuvant radiation targeting the neck, mean bystander dose to the primary site was 28.8 Gy (range, 13.3-50.6 Gy). CONCLUSION: In a 59 patient population, omission of radiation to the primary site after TORS resulted in no locoregional failures.

Functional HPV-specific PD-1+ stem-like CD8 T cells in head and neck cancer.

T cells are important in tumour immunity but a better understanding is needed of the differentiation of antigen-specific T cells in human cancer1,2. Here we studied CD8 T cells in patients with human papillomavirus (HPV)-positive head and neck cancer and identified several epitopes derived from HPV E2, E5 and E6 proteins that allowed us to analyse virus-specific CD8 T cells using major histocompatibility complex (MHC) class I tetramers. HPV-specific CD8 T cells expressed PD-1 and were detectable in the tumour at levels that ranged from 0.1% to 10% of tumour-infiltrating CD8 T lymphocytes (TILs) for a given epitope. Single-cell RNA-sequencing analyses of tetramer-sorted HPV-specific PD-1+ CD8 TILs revealed three transcriptionally distinct subsets. One subset expressed TCF7 and other genes associated with PD-1+ stem-like CD8 T cells that are critical for maintaining T cell responses in conditions of antigen persistence. The second subset expressed more effector molecules, representing a transitory cell population, and the third subset was characterized by a terminally differentiated gene signature. T cell receptor clonotypes were shared between the three subsets and pseudotime analysis suggested a hypothetical differentiation trajectory from stem-like to transitory to terminally differentiated cells. More notably, HPV-specific PD-1+TCF-1+ stem-like TILs proliferated and differentiated into more effector-like cells after in vitro stimulation with the cognate HPV peptide, whereas the more terminally differentiated cells did not proliferate. The presence of functional HPV-specific PD-1+TCF-1+CD45RO+ stem-like CD8 T cells with proliferative capacity shows that the cellular machinery to respond to PD-1 blockade exists in HPV-positive head and neck cancer, supporting the further investigation of PD-1 targeted therapies in this malignancy. Furthermore, HPV therapeutic vaccination efforts have focused on E6 and E7 proteins; our results suggest that E2 and E5 should also be considered for inclusion as vaccine antigens to elicit tumour-reactive CD8 T cell responses of maximal breadth.

Incidence trends of squamous cell carcinoma of the head and neck (SCCHN) in the aging population--A SEER-based analysis from 2000 to 2016.

BACKGROUND: Tobacco and alcohol use are risk factors for Squamous Cell Carcinoma of the Head and Neck (SCCHN); however, there is growing recognition of HPV as a risk factor for SCCHN. HPV-related SCCHN is thought to affect mostly middle-aged individuals but as the US population ages, it is important to evaluate the change in incidence of HPV- and non-HPV-related SCCHN in individuals who are ≥65 years old. METHODS: This was a retrospective study using data from a population-based cancer registry (SEER) to identify individuals ≥65 years old diagnosed with SCCHN between 2000 and 2016 also stratified by sex, race, and birth cohort. The subgroups of HPV-associated and non-HPV associated sites were analyzed independently. The incidence per year was calculated and joinpoint detection was used to identity significant changes in incidence trends and annual percent change (APC). RESULTS: For HPV-associated sites from 2000 to 2016, there was an average annual rate of 10.8 per 100,000 individuals with an APC of 2.92% (p = <0.05). For HPV- and non-HPV-related SCCHN males had a higher annual rate compared to females, 54.5 versus 18.0 in non-HPV-related and 19.1 versus 4.4 in HPV-related sites. For non-HPV-related sites there was a decrease in APC across all stratified groups. For HPV-related sites there was an increase in APC across all stratified groups, especially males (APC 8.82% 2006-2016 p < 0.05) and White individuals (APC 8.19% 2006-2016 p < 0.05). When stratified by birth cohort, HPV-related SCCHN sites had a higher APC in ages 65-69 (8.38% p < 0.05) and 70-74 (8.54% p < 0.05). CONCLUSION: Among the population ≥65 years old from 2000 to 2016, the incidence rate for HPV-related SCCHN sites has increased across all stratified groups, especially in White individuals, males, and age groups 65-74. The incidence rate for non-HPV-related sites has decreased across all stratified groups during this time.

TORS elective lingual tonsillectomy has less acute morbidity than therapeutic base of tongue TORS.

OBJECTIVE: To determine the impact of diagnostic TORS lingual tonsillectomy (DTLT) on objective swallowing measures for carcinoma of unknown primary (CUP). METHODS: Between 10/2016-1/2020, 27 patients with p16+ squamous cell carcinoma (SCC) level 2a nodal disease underwent DTLT and ipsilateral neck dissection for CUP. No patient had a history of cutaneous SCC. Patients participated in Modified Barium Swallow (MBS) three weeks post-TORS, which were then compared to those from a contemporaneous cohort of 40 patients with clinically-identified p16+ base of tongue (BOT) primary tumors. DIGEST scores were retrospectively calculated. Univariate and multivariate analysis performed, stratified by BOT glossectomy (n = 40) versus lingual tonsillectomy for CUP (n = 27). Radiation to the resected primary or potential primary sources was omitted if margins were ≥3 mm or if no primary identified. RESULTS: Twenty-seven consecutive patients with clinical stage cT0N1 HPV-associated OPSCC had a BOT primary pathologically identified in 18/27 (67%). Univariate analysis of functional swallow assessment on MBSImP correlated with improved post-TORS DIGEST scores for CUP. On multivariate analysis (MVA) DIGEST safety scores were improved for CUP than cT1 BOT glossectomy [Odds Ratio (OR) 0.28, p = 0.038]. MVA on matched pT1 CUP (n = 27) vs. pT1 BOT (n = 19), OR of moderate/severe dysphagia for CUP was 0.54 [0.12-2.38, p = 0.417] for DIGEST safety scores and 0.27 [0.06-1.18, p = 0.082] for DIGEST efficiency scores. Moderate/severe dysphagia as determined by DIGEST overall scores for CUP compared to cT1 and pT1 yielded an OR of 0.39 (p = 0.081) and 0.42 (p = 0.195), respectively. Twenty-six total patients received adjuvant RT, and 18 (11 with ≥3 mm margins, 9 with negative specimens) were spared intentional RT to the oropharynx. Median follow-up was 22.6 months with 100% PFS. CONCLUSIONS: Patients undergoing DTLT for CUP demonstrated acute swallow defecits in the post-operative setting. A comparison of long-term functional results between DTLT and elective irradiation of the primary site should be studied. LEVEL OF EVIDENCE: Level III.

Characterizing postoperative physiologic swallow function following transoral robotic surgery for early stage tonsil, base of tongue, and unknown primary human papillomavirus-associated squamous cell carcinoma.

BACKGROUND: Data objectively evaluating acute post-transoral robotic surgery (TORS) swallow function are limited. Our goal was to characterize and identify clinical variables that may impact swallow function components 3 weeks post-TORS. METHODS: Retrospective cohort study. Pre/postoperative use of the Modified Barium Swallow Impairment Profile (MBSImP) and Penetration-Aspiration Scale (PAS) was completed on 125 of 139 TORS patients (2016-2019) with human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma. Dynamic Imaging Grade of Swallowing Toxicity (DIGEST) scores were retrospectively calculated. Uni/multivariate analysis was performed. RESULTS: Dysfunctional pre-TORS DIGEST scores were predictive of post-TORS dysphagia (p = 0.015). Pre-TORS MBSImP deficits in pharyngeal stripping wave, swallow initiation, and clearing pharyngeal residue correlated with airway invasion post-TORS based on PAS scores (p = 0.012, 0.027, 0.048, respectively). Multivariate analysis of DIGEST safety scores declined with older age (p = 0.044). Odds ratios (ORs) for objective swallow function components after TORS were better for unknown primary and tonsil primaries compared to base of tongue (BOT) (OR 0.35-0.91). CONCLUSIONS: Preoperative impairments in specific MBSImP components, older patients, and BOT primaries may predict more extensive recovery in swallow function after TORS.

Socioeconomic Factors Influence the Impact of Tumor HPV Status on Outcome of Patients With Oropharyngeal Squamous Cell Carcinoma.

PURPOSE: Human papilloma virus (HPV) association remains one of the most important predictors of clinical outcome in oropharyngeal squamous cell carcinoma (OPSCC). We aimed to determine whether the relationship between HPV status and overall survival was influenced by socioeconomic factors. MATERIALS AND METHODS: Using the National Cancer Database, we examined the relationship between socioeconomic status and overall survival, controlling for demographics and socioeconomic variables (age at diagnosis, race, sex, clinical stage, facility type, facility location, insurance status, median-income quartiles, percent of no high-school education quartiles, rural-urban dwelling, Charlson-Deyo score, primary site, and treatment type). RESULTS: HPV-positive patients with private insurance have improved overall survival compared with HPV-positive patients who are uninsured (hazard ratio [HR], 0.51, 95% CI, 0.41 to 0.63, P < .001). HPV-negative patients with private insurance have improved overall survival compared with HPV-negative patients who were uninsured (HR, 0.62, 95% CI, 0.53 to 0.73, P < .001). HPV-positive patients living in the south had improved overall survival compared with HPV-positive patients living in the west (HR, 0.83, 95% CI, 0.72 to 0.96, P = .013). As assessed through interaction, relationships between survival and insurance (P = .004), rural-urban status (P = .009), and facility location (P = .021) statistically differed between HPV-positive and HPV-negative patients. CONCLUSION: HPV status impact on overall survival for patients with OPSCC is influenced by socioeconomic factors including insurance status and treatment facility. A deeper understanding of these interactions is needed to improve equity of care for patients with OPSCC.