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BACKGROUND. EGFR and Src family kinases are upregulated in head and neck squamous cell carcinoma (HNSCC). EGFR interacts with Src to activate STAT3 signaling, and dual EGFR-Src targeting is synergistic in HNSCC preclinical models. pSrc overexpression predicted resistance to the EGFR inhibitor, erlotinib, in a prior window trial. We conducted a 4-arm window trial to identify biomarkers associated with response to EGFR and/or Src inhibition. METHODS. Patients with operable stage II-IVa HNSCC were randomized to 7-21 days of neoadjuvant erlotinib, the Src inhibitor dasatinib, the combination of both, or placebo. Paired tumor specimens were collected before and after treatment. Pharmacodynamic expression of EGFR and Src pathway components was evaluated by IHC of tissue microarrays and reverse-phase protein array of tissue lysates. Candidate biomarkers were assessed for correlation with change in tumor size. RESULTS. From April 2009 to December 2012, 58 patients were randomized and 55 were treated. There was a significant decrease in tumor size in both erlotinib arms (P = 0.0014); however, no effect was seen with dasatinib alone (P = 0.24). High baseline pMAPK expression was associated with response to erlotinib (P = 0.03). High baseline pSTAT3 was associated with resistance to dasatinib (P = 0.099). CONCLUSIONS. Brief exposure to erlotinib significantly decreased tumor size in operable HNSCC, with no additive effect from dasatinib. Baseline pMAPK expression warrants further study as a response biomarker for anti-EGFR therapy. Basal expression of pSTAT3 may be independent of Src, explain therapeutic resistance, and preclude development of dasatinib in biomarker-unselected cohorts. TRIAL REGISTRATION. NCT00779389. FUNDING. National Cancer Institute, American Cancer Society, Pennsylvania Department of Health, V Foundation for Cancer Research, Bristol-Myers Squibb, and Astellas Pharma.

Objectives/Hypothesis: We have seen several incidences of catastrophic bleeding in patients with advanced oropharyngeal squamous cell carcinoma treated nonoperatively. Aside from advanced disease, these patients have not had traditional risk factors for major hemorrhage. Study Design: Retrospective chart review. Methods: Patients treated nonoperatively for oropharyngeal squamous cell carcinoma were compared to determine characteristics that may predisposed to bleeding. Five patients with bleeding were identified and compared with a cohort of stage‐ and treatment‐matched patients without bleeding. Blinded imaging review was performed to characterize the tumor site and its relationship to vasculature using standardized systems. Results: Comparing the bleeder versus nonbleeder groups pre‐treatment, the bleeder group had larger tumors (15.4 vs. 8.3 cm2), greater rates of parapharyngeal fat effacement (80% vs. 20%), and always involved the facial artery. Post‐treatment, endophytic ulcerated tumor beds occurred in 100% of bleeders versus 0% of nonbleeders. Conclusions: Catastrophic oropharyngeal bleeding may be encountered after cytoreductive therapy. Large deeply invasive tumors seem to set the necessary circumstances. Rapid vascular control with interventional radiology has been largely effective therapy. Level of Evidence: 3 Laryngoscope, 131:1049–1052, 2021 [ABSTRACT FROM AUTHOR]

Neuroendocrine dysfunction includes suspected hyper- and hypofunction of the pituitary gland. Causative lesions may include primary masses of the pituitary such as pituitary microadenomas and macroadenomas, as well as extrinsic masses, typically centered in the suprasellar cistern. Clinical syndromes related to hormonal dysfunction can be caused by excessive hormonal secretion or by inhibited secretion due to mass effect upon elements of the hypothalamic-pituitary axis. Additionally, complications such as hemorrhage may be seen in the setting of an underlying mass and can result in hormonal dysfunction. MRI with high-resolution protocols is the best first-line test to evaluate the sella turcica and parasellar region. CT provides complementary information regarding bony anatomy, and may be appropriate as a first-line test in certain instances, but it provides less detail and lesion characterization when compared to MRI. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment. [ABSTRACT FROM AUTHOR]

Objective To compare positive margin rates between the 2 most common subsites of oropharyngeal transoral robotic surgery (TORS), the base of tongue (BOT) and the tonsil, as well as identify preoperative imaging characteristics that predispose toward positive margins. Study Design Case series with chart review. Setting Tertiary care referral center. Subjects and Methods We compared the final and intraoperative positive margin rate between TORS resections for tonsil and BOT oropharyngeal squamous cell carcinoma (OPSCC), as well as the effect of margins on treatment. A blinded neuroradiologist examined the preoperative imaging of BOT tumors to measure their dimensions and patterns of spread and provided a prediction of final margin results. Results Between January 2010 and May 2016, a total of 254 patients underwent TORS for OPSCC. A total of 140 patients who underwent TORS for T1/T2 OPSCC met inclusion criteria. A final positive margin is significantly more likely for BOT tumors than tonsil tumors (19.6% vs 4.5%, respectively, P = .004) and likewise for intraoperative margins of BOT and tonsil tumors (35.3% vs 12.4%, respectively; P = .002). A positive final margin is 10 times more likely to receive chemoradiation compared to a negative margin, controlling for extracapsular spread and nodal status (odds ratio, 9.6; 95% confidence interval, 1.6-59.6; P = .02). Preoperative imaging characteristics and subjective radiologic examination of BOT tumors did not correlate with final margin status. Conclusion Positive margins are significantly more likely during TORS BOT resections compared to tonsil resections. More research is needed to help surgeons predict which T1/T2 tumors will be difficult to completely extirpate. [ABSTRACT FROM AUTHOR]