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PurposeThe EGF receptor (EGFR) and COX2 pathways are upregulated in head and neck squamous cell carcinoma (HNSCC). Preclinical models indicate synergistic antitumor activity from dual blockade. We conducted a randomized, double-blind, placebo-controlled window trial of erlotinib, an EGFR inhibitor; erlotinib plus sulindac, a nonselective COX inhibitor; versus placebo.Experimental designPatients with untreated, operable stage II-IVb HNSCC were randomized 5:5:3 to erlotinib, erlotinib-sulindac, or placebo. Tumor specimens were collected before and after seven to 14 days of treatment. The primary endpoint was change in Ki67 proliferation index. We hypothesized an ordering effect in Ki67 reduction: erlotinib-sulindac > erlotinib > placebo. We evaluated tissue microarrays by immunohistochemistry for pharmacodynamic modulation of EGFR and COX2 signaling intermediates.ResultsFrom 2005-2009, 47 patients were randomized for the target 39 evaluable patients. Thirty-four tumor pairs were of sufficient quality to assess biomarker modulation. Ki67 was significantly decreased by erlotinib or erlotinib-sulindac (omnibus comparison, two-sided Kruskal-Wallis, P = 0.04). Wilcoxon pairwise contrasts confirmed greater Ki67 effect in both erlotinib groups (erlotinib-sulindac vs. placebo, P = 0.043; erlotinib vs. placebo, P = 0.027). There was a significant trend in ordering of Ki67 reduction: erlotinib-sulindac > erlotinib > placebo (two-sided exact Jonckheere-Terpstra, P = 0.0185). Low baseline pSrc correlated with greater Ki67 reduction (R(2) = 0.312, P = 0.024).ConclusionsBrief treatment with erlotinib significantly decreased proliferation in HNSCC, with additive effect from sulindac. Efficacy studies of dual EGFR-COX inhibition are justified. pSrc is a potential resistance biomarker for anti-EGFR therapy, and warrants investigation as a molecular target.

This article presents a case study of a 51-year-old Caucasian male with advanced oral cavity cancer who underwent neoadjuvant chemotherapy followed by surgery and radiation therapy. The treatment was successful, resulting in tumor regression and improved pain and eating. The article also discusses the importance of surgical factors and the conflicting results regarding the impact of neoadjuvant therapy on outcomes. Perspectives from plastic surgery, pathology, radiation oncology, speech pathology, and a patient's experience are provided. The document concludes by discussing future directions, including the potential use of immunotherapy. [Extracted from the article]

Objective: Examine outcomes for lateral arm autologous tissue transfer in head and neck reconstruction. Study Design: Retrospective cohort study. Setting: Tertiary cancer center. Methods: All patients who underwent traditional lateral arm, extended lateral arm, and lateral forearm flaps for head and neck reconstruction from 2012 to 2022 were assessed. Disabilities of the arm, shoulder, and hand (DASH) was measured. Factors associated with complications and enteral or mixed diet were evaluated by multivariable regression. Results: Among 160 patients followed for a median of 2.3 ± 2.1 years, defects were 54% oral tongue, 18% external, 9% maxilla, 8% buccal mucosa, 9% floor of mouth, and 3% pharynx. Flap types (and median pedicle lengths) were 41% traditional lateral arm (8 cm), 25% extended lateral arm (11.5 cm), and 34% lateral forearm (14 cm). All donor sites were closed primarily; 19.6% and 0% of patients had increased DASH scores 2 and 12 weeks after reconstruction. Major complications occurred in 18.1% of patients, including 6.3% reoperation, 6.9% readmission, 3.7% fistula, and 1.8% flap loss. Complications were independently associated with peripheral vascular disease (odds ratio [OR]: 5.71, 95% confidence interval [CI]: 1.5‐21.6, P =.01), pharyngeal defects (OR: 11.3, 95% CI: 1.4‐94.5, P =.025), and interposition vein grafts (OR: 3.78, 95% CI: 1.1‐13.3, P =.037). Conclusion: The lateral arm free flap was safe, versatile, and reliable for head and neck reconstruction with low donor‐site morbidity. Complications occurred in a fifth of patients and were associated with peripheral vascular disease, pharyngeal defects, and vein grafts. [ABSTRACT FROM AUTHOR]

ObjectiveTargeting the epidermal growth factor receptor (EGFR) using the tyrosine kinase inhibitor (TKI) erlotinib has demonstrated activity in aerodigestive tract malignancies. Co-targeting of the G-protein-coupled receptor cyclooxygenase (COX) with EGFR inhibitors has shown promise in preclinical models and early phase clinical studies.Materials and methodsWe studied the modulation of serum proteins after neoadjuvant treatment with erlotinib with or without sulindac in head and neck cancer patients. In a prospective, randomized, double-blind clinical trial, paired serum samples were obtained before and after neoadjuvant treatment in three groups of patients (n = 23 total), who were randomized to receive 7-14 consecutive days of erlotinib alone, erlotinib plus sulindac, or placebo. Two separate multiplexed ELISA systems (SearchLight™ or Luminex™) were used to measure serum biomarkers. HGF and IL-6 levels were tested on both systems, and validated using single analyte ELISAs.ResultsSeveral analytes were significantly altered (generally decreased) post-treatment, in patients who received erlotinib (with or without sulindac) as well as in the placebo groups. No single analyte was differentially altered across the three treatment groups using either multiplex platform. Single HGF ELISA suggested a nonspecific decrease in all patients.ConclusionThese results demonstrate the importance of a placebo group when assessing changes in expression of serum biomarkers. While multiplex platforms can provide quantitative information on a large number of serum analytes, results should be cautiously compared across platforms due to their intrinsic features. Furthermore, the dynamic range of expression of a single analyte is constrained in multiplex versus standard ELISA.

Background: Use of postoperative radiation therapy (PORT) in locoregionally advanced medullary thyroid cancer (MTC) remains controversial. The objective was to evaluate the effect of PORT on locoregional control (LRC) and overall survival (OS). Methods: Retrospective cohort study of 346 MTC patients separated into PORT and no‐PORT cohorts. Relative indications for PORT, as well as changes in patterns of treatment, were recorded. Results: 49/346 (14%) received PORT. PORT was associated with worse OS; adjusted HR = 2.0 (95%CI 1.3–3.3). PORT was not associated with improved LRC, even when adjusting for advanced stage (Stage III p = 0.892; Stage IV p = 0.101). PORT and targeted therapy were not associated with improved OS compared to targeted therapy alone; adjusted HR = 1.2 (95%CI 0.3–4.1). Conclusions: Use of PORT in MTC has decreased and its indications have become more selective, coinciding with the advent of effective targeted therapies. Overall, PORT was not associated with improved LRC or OS. [ABSTRACT FROM AUTHOR]