Austin C. Cao

Objectives: Treatment of patients with head and neck squamous cell carcinoma of unknown primary (CUP) is challenging. Given the relative rarity of this condition and the recent use of primary transoral robotic surgery (TORS) in modern diagnostic and treatment algorithms, long‐term oncologic outcomes are unclear. The objectives were to evaluate oncologic outcomes of patients treated with TORS for management of CUP. Methods: This retrospective case series was conducted at a tertiary care academic medical center from 2010 to 2021. All patients with HPV‐mediated CUP who underwent TORS‐assisted endoscopy were included. CUP was defined as biopsy‐proven squamous cell carcinoma in a cervical lymph node with uncertain primary location following standard‐of‐care clinical and radiologic assessment. Primary outcomes were recurrence‐free survival and overall survival. Secondary outcomes included usage of radiation and chemotherapy. Results: In total, 157 patients were included in the study. Median follow‐up time was 62 months. Primary tumor was identified in 88% of patients. Surgery alone was performed in 21%, although adjuvant therapy was recommended but declined in 13%. Adjuvant radiation was completed in 46% and adjuvant chemoradiation in 33%. Two‐thirds of patients avoided chemoradiation. Overall survival was 94% and recurrence‐free survival was 92% at 5 years. Conclusion: In the largest reported experience to date of TORS‐assisted management of CUP, we demonstrate that this approach facilitates a high rate of identification of occult mucosal malignancies and can eliminate the need for chemotherapy and potentially radiation therapy in select patients without compromising excellent oncologic and functional outcomes. Level of Evidence: 4.

Objectives: To describe swallowing and feeding-tube outcomes in patients with high-risk oropharyngeal cancer treated with trimodality therapy (TMT), including transoral robotic surgery (TORS) and adjuvant chemoradiotherapy. Methods: A chart review was conducted on patients with HPV+ OPSCC receiving TMT with TORS at an academic medical center from March 2010 to March 2021. Data collected included demographics, treatment, feeding tube placement, functional oral intake scale (FOIS) scores, and swallowing-language pathology (SLP) evaluations. Results: A total of 255 patients met selection criteria (mean age 61 years, 88% male). Following intraoperative nasogastric tube (NG) placement, 31% remained NG tube dependent after 3 weeks. A gastrostomy tube was placed in 19% of patients, and at 1 year after end-of-treatment (EOT), 3.5% overall remained tube-dependent. Mean FOIS scores were 6.9 (SD = 0.3) at pre-operative visit, 2.6 (1.8) at first post-operative visit, and 5.5 (1.5) after EOT. In the subset of patients with follow-up longer than 2 years (n = 118), the mean FOIS was 6.1 (SD = 1.3) at most recent visit. Clinical signs of aspiration/penetration were suspected on SLP evaluation in 18% of patients. These patients were subsequently evaluated with fiberoptic endoscopic evaluation of swallowing (FEES) and/or barium swallow study, which confirmed signs of aspiration in 2.7% of patients overall. Delayed NG tube removal after 3 weeks was predictive of (1) gastrostomy tube requirement and (2) clinical signs of aspiration on an SLP visit after EOT. Conclusions: Favorable functional and feeding-tube outcomes are demonstrated in patients with HPV-associated OPSCC undergoing TMT. In this single-institution study, we found low rates of long-term feeding tube dependence and high median FOIS following treatment. Review of routine SLP visits provides a detailed and easily accessible means for assessing swallowing function in this cohort.

6056 Background: The DepMap genome-wide loss of function CRISPR screens offer new insight into gene dependencies in HPV(-) head and neck squamous cell carcinoma (HNSCC) cell lines. We aimed to leverage this data to guide preclinical studies by cataloging targetable dependencies and identifying ones predicted to offer a therapeutic window. We also aimed to identify targets representing potential synthetic lethalities by testing for associations between genetic alterations and dependency profile. Methods: DepMap was queried for gene probability and effect scores in cell lines from 77 tumors, including 62 HPV(-) HNSCCs plus 15 ESCCs, which have comparable etiology, genetic features, and tissue of origin. A probability score of ≥ 0.5 was used as the threshold for essentiality. Essential genes were selected for analysis by 3 criteria: (1) presence in ≥10% cell lines, (2) lack of dependency in CRISPR screens of normal human cell lineages, and (3) designation as druggable by the Drug-Gene Interaction Database. Gene set enrichment analysis was performed using the Hallmark Gene Sets. DepMap gene effect scores were used to prioritize targets likely to have a useful therapeutic window based on median scores greater than for EGFR (0.676), a target with established albeit modest utility for HNSCC. The Open Targets platform was used to identify targets with inhibitors used in trials for other cancers and/or nonmalignant diseases. Associations between dependencies and genetic alterations were defined using two-sample t-tests, with filter conditions of p < 0.05 and effect size ≥1. Results: The 231 genes meeting selection criteria had a median gene effect score of 0.56. The criteria captured targets of standard therapeutic agents including TYMS (5-FU), tubulin genes (paclitaxel), EGFR (cetuximab), plus known oncogenes like PIK3CA. GSEA showed enrichment of known oncogenic signaling pathways including PI3K/AKT and JAK/STAT, as well as hallmark cancer processes like DNA repair and apoptosis. 90% were not known oncogenes cataloged in the OncoKB Database. 45 genes had a median gene effect score between that of EGFR and the median for common essential genes, including 7 without known cancer-promoting roles: OTOP1, DHRSX, UTP11, MBTPS1, SLC25A3, PPIAL4G, and RBM10. 17% had inhibitors that reached a non-HNSCC phase II trial, including 10 targets not previously tested in cancer. Novel associations between dependencies and genetic alterations included DDX3X with NOTCH1mut, ITGB1 with CDKN2Amut, and ATP1A1 with HRASmut. Conclusions: We catalog targetable dependencies in cell line models of HNSCC. While well-studied targets were captured, many genes lacked known roles in malignancy. Targets of inhibitors tested in other diseases provide new tools to guide preclinical studies. Association of some dependencies with known molecular subgroups in HNSCC may enhance use of cell line models to personalize therapy.

Objectives/Hypothesis: Intubation with inappropriately sized endotracheal tubes (ETT) can cause long‐term tracheal and laryngeal injuries often requiring surgical intervention. Although tracheal size has been demonstrated to vary based on height and sex, it is unclear whether these guidelines are regularly implemented in patients undergoing endotracheal intubation. The objective of this study is to determine the rate of appropriate ETT size selection in patients undergoing intubation and assess provider decision making in ETT size selection.Study Design: Retrospective cohort study.Methods: The study population was all patients who underwent endotracheal intubation over a two‐week period at a tertiary academic medical center. Data were collected on patient age, gender, height, BMI, comorbidities, ETT size, duration of intubation, bronchoscopies, and type of practitioner who performed the intubation. A height‐based nomogram for ETT size selection was used to determine the recommended ETT size for each patient.Results: One hundred five patients met the inclusion criteria. 22% of patients were intubated with an inappropriately large tube, defined as 1.0 mm larger than the recommended size. Women were more likely to be intubated with an inappropriately large ETT (OR = 13.58, P = .001), as were patients with height less than 160 cm (OR = 141, P = .001). Other factors related to disease severity, anticipation for bronchoscopy, and BMI were not risk factors for the use of inappropriately large ETT.Conclusions: Although there is compelling evidence that height is a strong predictor of tracheal morphology and appropriate ETT size, height‐based guidelines have yet to be universally adopted for ETT size selection. Laryngoscope, 131:1967–1971, 2021