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.

Reconstruction for Salvage Laryngectomy With Limited Pharyngectomy.

Importance: Closure technique for optimization of postoperative and functional outcomes following salvage laryngectomy remains an area of debate among head and neck surgeons. Objective: To investigate the association of salvage laryngectomy closure technique with early postoperative and functional outcomes. Design, Setting, and Participants: This retrospective cohort study included patients from 17 academic, tertiary care centers who underwent total laryngectomy with no or limited pharyngectomy after completing a course of definitive radiotherapy or chemoradiotherapy with curative intent between January 2011 and December 2016. Patients with defects not amenable to primary closure were excluded. Data were analyzed from February 14, 2021, to January 29, 2024. Exposures: Total laryngectomy with and without limited pharyngectomy, reconstructed by primary mucosal closure (PC), regional closure (RC), or free tissue transfer (FTT). Main Outcomes and Measures: Patients were stratified on the basis of the pharyngeal closure technique. Perioperative and long-term functional outcomes were evaluated with bivariate analyses. A multivariable regression model adjusted for historical risk factors for pharyngocutaneous fistula (PCF) was used to assess risk associated with closure technique. Relative risks (RRs) with 95% CIs were determined. Results: The study included 309 patients (256 [82.8%] male; mean age, 64.7 [range, 58.0-72.0] years). Defects were reconstructed as follows: FTT (161 patients [52.1%]), RC (64 [20.7%]), and PC (84 [27.2%]). A PCF was noted in 36 of 161 patients in the FTT group (22.4%), 25 of 64 in the RC group (39.1%), and 29 of 84 in the PC group (34.5%). On multivariable analysis, patients undergoing PC or RC had a higher risk of PCF compared with those undergoing FTT (PC: RR, 2.2 [95% CI, 1.1-4.4]; RC: RR, 2.5 [95% CI, 1.3-4.8]). Undergoing FTT was associated with a clinically meaningful reduction in risk of PCF (RR, 0.6; 95% CI, 0.4-0.9; number needed to treat, 7). Subgroup analysis comparing inset techniques for the RC group showed a higher risk of PCF associated with PC (RR, 1.8; 95% CI, 1.1-3.0) and predominately pectoralis myofascial flap with onlay technique (RR, 1.9; 95% CI, 1.2-3.2), but there was no association of pectoralis myocutaneous flap with cutaneous paddle interposition with PCF (RR, 1.2; 95% CI, 0.5-2.8) compared with FTT with cutaneous inset. There were no clinically significant differences in functional outcomes between the groups. Conclusion and Relevance: In this study of patients with limited pharyngeal defects, interpositional fasciocutaneous closure technique was associated with reduced risk of PCF in the salvage setting, which is most commonly achieved by FTT in academic practices. Closure technique was not associated with functional outcomes at 1 and 2 years postoperatively.

Insurance Authorization and Access to Proton Therapy for Patients With Head and Neck Cancers.

PURPOSE: We evaluated our institutional experience to assess potential racial inequities in insurance coverage for proton therapy in patients with head and neck (HN) cancer. METHODS AND MATERIALS: We examined the demographics of 1519 patients with HN cancer seen in consultation at our HN multidisciplinary clinic (HN MDC) and 805 patients for whom a proton insurance authorization was sought (PAS) from January 2020 to June 2022. The prospects for proton therapy insurance authorization were prospectively noted based on each patient's ICD-10 (International Classification of Diseases, 10th Revision) diagnosis code and their specific insurance plan. Proton-unfavorable (PU) insurance were those plans whose policy describes proton beam therapy as "experimental" or "not medically necessary" for the given diagnosis. RESULTS: For patients seen in our HN MDC, Black, Indigenous, and people of color (BIPOC) were significantly more likely to have PU insurance than non-Hispanic White (NHW) patients (24.9% vs 18.4%, P = .005). In multivariable analysis including race, average income of residence ZIP code, and Medicare eligibility age, BIPOC patients had an odds ratio of 1.25 for PU insurance (P = .041). In the PAS cohort, while there was no difference in the percentage of patients receiving insurance approval for proton therapy between NHW and BIPOC populations (88% vs 88.2%, P = .80), for patients with PU insurance, the median time to determination was significantly longer (median, 15.5 days), and the median time to start any radiation of any modality was longer (46 vs 35 days, P = .08). Compared with NHW patients, the median time from consultation to start of radiation therapy was longer for BIPOC patients (37 vs 43 days, P = .01). CONCLUSIONS: BIPOC patients were significantly more likely to have insurance plans unfavorable to proton therapy coverage. These PU insurance plans were associated with a longer median time to determination, a lower approval rate for proton therapy, and a longer time to start radiation of any modality.

Free Flap Fat Volume is Not Associated With Recurrence or Wound Complications in Oral Cancer.

Objective: Adipose stem cells (ASCs) have been shown in many preclinical studies to be potent suppressors of the immune system. Prior studies suggest that ASCs may promote cancer progression and wound healing. However, clinical studies investigating the effects of native, or fat-grafted adipose tissue on cancer recurrence have generated mixed results. We investigated whether adipose content in reconstructive free flaps for oral squamous cell carcinoma (OSCC) is associated with disease recurrence and/or reduction in wound complications. Study Design: Retrospective chart review. Setting: Academic medical center. Methods: We performed a review of 55 patients undergoing free flap reconstruction for OSCC over a 14-month period. Using texture analysis software, we measured the relative free flap fat volume (FFFV) in postoperative computed tomography scans and compared fat volume with patient survival, recurrence, and wound healing complications. Results: We report no difference in mean FFFV between patients with or without recurrence: 13.47 cm3 in cancer-free survivors and 17.99 cm3 in cases that recurred (p = .56). Two-year recurrence-free survival in patients with high and low FFFV was 61.0% and 59.1%, respectively (p = .917). Although only 9 patients had wound healing complications, we found no trend in the incidence of wound healing complications between patients with high versus low FFFV. Conclusion: FFFV is not associated with recurrence or wound healing in patients undergoing free flap reconstruction for OSCC, suggesting adipose content should not be of concern to the reconstructive surgeon.

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.

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.

To Scan or Not to Scan: The Dilemma of Posttreatment Imaging Surveillance of Head and Neck Cancer.

Locoregional recurrence remains common after treatment of head and neck cancer, warranting careful surveillance in follow-up. Although randomized data support an initial positron emission tomography/computed tomography several months after treatment, evidence supporting subsequent imaging is limited, and most recurrences ultimately manifest clinically. Cooperative group studies and consensus guidelines vary widely in their recommendations regarding surveillance imaging. Patients with indeterminate findings, new symptoms, or areas difficult to examine in clinic may avoid invasive and potentially morbid interventions with judicious use of subsequent imaging. For any patient undergoing posttreatment imaging, standardized reporting criteria provide a framework for risk-stratification that can enhance communication and potentially guide management.

Tipifarnib enhances anti-EGFR activity of cetuximab in non-HRas mutated head and neck squamous cell carcinoma cancer (HNSCC).

OBJECTIVE: To test the potential ability of tipifarnib to impair proliferation and to enhance the activity of the EGFR inhibitor cetuximab in wild-type H-Ras HNSCC, which accounts for the majority of HNSCC. MATERIALS AND METHODS: Cell growth, apoptosis and signaling changes in HNSCC cells following tipifarnib exposure in vitro were assessed by SRB, colony formation assay, annexin V staining and Western blot, respectively. A patient-derived xenograft (PDX) animal model was adopted to evaluate the efficacy of tipifarnib in vivo with and without cetuximab. RESULTS: Treatment of wild-type H-Ras HNSCC cell lines in vitro with tipifarnib reduced cell growth and increased levels of defarnesylated H-Ras in a dose-dependent manner. In a PDX mouse model, treatment with single-agent tipifarnib led to only near-significant growth inhibition. The addition of cetuximab resulted in increased anti-proliferative effect both in culture and in PDX models, which was also mirrored by Western blot and apoptosis assay results. CONCLUSION: Tipifarnib has only a moderate ability to slow tumor growth as a single agent in HNSCC with wild type H-Ras, despite specifically inhibiting the farnesyltransferase upon which the function of H-Ras depends. The combination of cetuximab and tipifarnib appears to enhance the anti-proliferative effect of single-agent tipifarnib and marginally enhance that of single agent cetuximab. These findings deserve further evaluation.

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.

A Protocol for Resection and Immediate Reconstruction of Pediatric Mandibles Using Microvascular Free Fibula Flaps.

PURPOSE: The use of a vascularized free fibula graft (FFF) for the reconstruction of a mandible in a child with a mandibular tumor is infrequent. The purpose of this study is to report our protocol for resection of mandibular jaw tumors and immediate reconstruction using FFF in pediatric patients. METHODS: This was a retrospective case series of children with a mandibular tumor, which was resected and immediately reconstructed with FFF. All patients were treated via the same staged protocol: 1) presurgical digital planning, 2) surgical intervention (resection and immediate reconstruction), 3) postoperative care in the pediatric intensive unit, and 4) prosthodontic dental rehabilitation. Outcomes were complications and recurrence. Medical records were reviewed to document demographic information, tumor details, surgical interventions, postoperative course, and prosthodontic rehabilitation. RESULTS: Fifteen patients (10 males, average age of 13.7 years) met inclusion criteria. Ten patients had mandibular ameloblastoma. All patients were treated by a dedicated pediatric team and followed the same protocol. The average tumor size was 4.87 × 3.22 × 2.03 cm. Most fibulas (n = 12) had one osteotomy to reestablish mandibular continuity and create appropriate contour. The most common microvascular anastomosis was with a facial artery (n = 13) and the external jugular vein (n = 9). At an average follow-up of 15.5 months, there were only 3 minor donor site complications. Eight implants were placed without complications. No tumors recurred. CONCLUSIONS: The results of this study suggest that pediatric mandibular tumors can be successfully treated using a specific protocol involving resection and immediate reconstruction using FFF with minimal complications and without recurrence.

Surgical Resection is Justifiable for Oral T4b Squamous Cell Cancers With Masticator Space Invasion.

OBJECTIVES: To examine survival endpoints in patients with tumor (T)4b oral cavity squamous cell carcinoma (OCSCC) with pathologically proven masticator space invasion treated with primary surgery followed by adjuvant therapy. STUDY DESIGN: Retrospective review at an academic cancer center. METHODS: Twenty-five patients with T4b OCSCC with pathologic masticator space invasion were treated with primary surgery from May 2012 to December 2016. Only patients with ≥ 2 years follow-up from date of surgery were included. Sixteen patients received adjuvant chemoradiation. RESULTS: Median follow-up time was 39 months from date of surgery. Overall survival (OS), disease-specific survival (DSS), and recurrence-free survival at 24 months were 44.0%, 63.2%, and 52.6%, respectively. On univariate analyses, adjuvant chemoradiation was associated with improved OS. Advanced age and prolonged length of hospital stay was associated with worse OS. CONCLUSION: For pT4b OCSCCA involving the masticator space, primary surgical resection followed by adjuvant chemoradiation demonstrates 24-month DSS of > 50% and OS of 44%. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:E466-E472, 2021.

Combinatorial approaches targeting the EGFR family and c-Met in SCCHN.

OBJECTIVE: We aimed to develop novel combinations of inhibitors targeting EGFR family members and c-Met for the treatment of recurrent SCCHN. MATERIALS AND METHODS: Three different c-Met inhibitors in combination with a pan-HER inhibitor (crizotinib/afatinib, tivantinib/afatinib and cabozantinib/afatinib) were investigated for their anti-tumor effects on SCCHN cell lines in vitro. In vivo activity of the combinations was tested in SCCHN cell line xenografts and patient-derived xenograft (PDX) animal models generated from patients with recurrent SCCHN. RESULTS: Western blot assay indicated that activation of EGFR, HER2, HER3, and c-Met was blocked by all three combinations and the downstream PI3K/AKT and ERK signaling pathways were inhibited. Sulforhodamine B colorimetric assay revealed SCCHN cell growth was more effectively inhibited by the combinations than by single agents, particularly in cell lines with high c-Met expression. Furthermore, the combinations were more potent in inducing apoptosis than each of the single agents. In the PDX models, the combination treatments exhibited significantly better efficacy in tumor growth inhibition compared to the respective single agents. CONCLUSION: In conclusion, we demonstrated that the simultaneous targeting of EGFR, HER2, and c-Met is more effective than the individual inhibition of these targets in vitro and in SCCHN cell line xenograft and PDX models. Our findings pave the way for further clinical investigation of such combinations in SCCHN.

Signatures of somatic mutations and gene expression from p16INK4A positive head and neck squamous cell carcinomas (HNSCC).

Human papilloma virus (HPV) causes a subset of head and neck squamous cell carcinomas (HNSCC) of the oropharynx. We combined targeted DNA- and genome-wide RNA-sequencing to identify genetic variants and gene expression signatures respectively from patients with HNSCC including oropharyngeal squamous cell carcinomas (OPSCC). DNA and RNA were purified from 35- formalin fixed and paraffin embedded (FFPE) HNSCC tumor samples. Immuno-histochemical evaluation of tumors was performed to determine the expression levels of p16INK4A and classified tumor samples either p16+ or p16-. Using ClearSeq Comprehensive Cancer panel, we examined the distribution of somatic mutations. Somatic single-nucleotide variants (SNV) were called using GATK-Mutect2 ("tumor-only" mode) approach. Using RNA-seq, we identified a catalog of 1,044 and 8 genes as significantly expressed between p16+ and p16-, respectively at FDR 0.05 (5%) and 0.1 (10%). The clinicopathological characteristics of the patients including anatomical site, smoking and survival were analyzed when comparing p16+ and p16- tumors. The majority of tumors (65%) were p16+. Population sequence variant databases, including gnomAD, ExAC, COSMIC and dbSNP, were used to identify the mutational landscape of somatic sequence variants within sequenced genes. Hierarchical clustering of The Cancer Genome Atlas (TCGA) samples based on HPV-status was observed using differentially expressed genes. Using RNA-seq in parallel with targeted DNA-seq, we identified mutational and gene expression signatures characteristic of p16+ and p16- HNSCC. Our gene signatures are consistent with previously published data including TCGA and support the need to further explore the biologic relevance of these alterations in HNSCC.

Phase Ib Study of Chemoprevention with Green Tea Polyphenon E and Erlotinib in Patients with Advanced Premalignant Lesions (APL) of the Head and Neck.

PURPOSE: On the basis of synergistic effects between green tea polyphenon E (PPE) and EGFR-tyrosine kinase inhibitor in preclinical studies, we conducted a phase Ib study of the PPE and erlotinib combination in patients with advanced premalignant lesions (APL) of the oral cavity and larynx. PATIENTS AND METHODS: Patients were treated with a fixed dose of PPE (200 mg three times a day) and dose escalation of erlotinib (50, 75, 100 mg daily) for 6 months with tissue biopsy at baseline and 6 months. Primary endpoints were safety and toxicity; secondary endpoints were evaluation of pathologic response, cancer-free survival (CFS), overall survival (OS), and biomarker modulation. RESULTS: Among 21 enrolled patients, 19 began treatment and 17 completed 6 months of treatment with PPE and erlotinib. Main characteristics of treated patients: 15 severe dysplasia or carcinoma in situ and 17 oral cavity. Only skin rash was associated with dose-limiting toxicity and MTD. Recommended doses for phase II studies are PPE 600 mg daily plus erlotinib 100 mg daily for 6 months. Pathologic responses in 17 evaluable patients: pathologic complete response (47%) and pathologic partial response (18%). The 5-year CFS and OS were 66.3% and 93%, respectively. Among tested biomarkers, only phosphorylated ERK was correlated with response to treatment. CONCLUSIONS: Treatment with PPE and erlotinib combination was well tolerated in patients with APLs of the head and neck, and showed a high rate of pathologic response with excellent CFS. This combination deserves further investigation for the chemoprevention and/or prevention of second primary tumors in early-stage head and neck cancer.

Narrowband Imaging for p16+ Unknown Primary Squamous Cell Carcinoma Prior to Transoral Robotic Surgery.

Our purpose was to assess the potential utility of narrowband imaging (NBI) as a tool in diagnosing and treating unknown primary oropharyngeal squamous cell carcinoma (OPSCC) in patients prior to diagnostic resection with transoral robotic surgery (TORS). Between 2016 and March 2019, 29 patients with carcinoma of unknown primary meeting inclusion criteria were identified and treated with TORS. NBI was used preoperatively in 9 of 29 patients. A suspected tumor site was delineated by NBI in 8 of 9 patients (89%). Of the patients imaged with NBI, 8 of 9 (89%) patients had a pathologically confirmed tumor following TORS, corresponding to the same 8 suspected tumor sites identified with NBI. In contrast, a primary tumor was localized following TORS in 15 of 20 (75%) patients not evaluated with NBI. Thus, we see NBI as a potentially useful tool for the diagnosis and management of p16+ carcinoma of unknown primary.Level of Evidence: IIb.

Image-Guided Percutaneous Gastrostomy Tube Placement is Safe in Patients Requiring Aspirin 325 mg.

RATIONALE AND OBJECTIVES: Requests for gastrostomy tube placement in patients on aspirin (ASA) 325 mg are common, particularly in patients following reconstructive surgery for head and neck cancer, but periprocedural guidelines and recommendations regarding management of high dose aspirin are inconsistent. The purpose of this study was to assess the bleeding risk of percutaneous gastrostomy tube placement in patients on ASA 325 mg. MATERIALS AND METHODS: This retrospective study of 213 patients who underwent image-guided "push" percutaneous gastrostomy tube placement compared rates of significant bleeding and other secondary outcomes (including all-cause mortality within 30 days, procedure-related mortality, bowel perforation, abdominal abscess, peritonitis, aspiration pneumonia, intraprocedural airway complications, and tube dislodgement) between patients maintained on ASA 325 mg and patients not on antiplatelet or anticoagulation therapy. RESULTS: No significant bleeding episodes occurred in patients on ASA 325 mg, compared to three episodes in patients not on ASA 325 mg (p = 0.37). A patient in each group had aspiration pneumonia possibly related to tube placement. There were no other notable secondary outcomes, including intraprocedural airway complications in this population with complex head and neck anatomy. CONCLUSION: These findings suggest that holding ASA 325 mg in patients undergoing percutaneous gastrostomy tube placement is not necessary, especially in patients in whom holding ASA would pose considerable risk. Further multi-institutional longitudinal study is warranted to validate these results.