Low-risk human papilloma virus positive oropharyngeal cancer with one positive lymph node: Equivalent outcomes in patients treated with surgery and radiation therapy versus surgery alone.

BACKGROUND: For human papilloma virus positive (HPV+) oropharyngeal squamous cell carcinoma (OPSCC), management recommendations for patients with a single metastatic lymph node <6 cm in diameter remain nebulous, leading to treatment heterogeneity in this common subgroup of patients. METHODS: We utilized the National Cancer Database to perform survival and multivariable analyses of patients with HPV+ OPSCC with one positive lymph node <6 cm and negative surgical margins. RESULTS: We found that 5-year survival is comparable between patients who receive surgery and adjuvant radiation versus surgery alone. In multivariable analyses, we found no significant difference in the hazard ratio of overall survival after adjusting for various potential confounders. CONCLUSIONS: These data suggest that patients with margin-negative HPV+ OPSCC with a single positive lymph node <6 cm have comparable survival with or without adjuvant radiation. Future studies exploring outcomes for this specific group in randomized-controlled trials will be critical for further evaluating these initial observations.

Ultrasound Training for Head and Neck Surgeons in Rural Kenya: A Feasibility Study.

OBJECTIVE: To determine the feasibility of training otolaryngologists to perform head and neck ultrasound in low- and middle-income countries over a short timeframe. DESIGN: Prospective cohort evaluating an ultrasound training course for otolaryngologists in low- and middle-income countries. SETTING: Surgical training camp for otolaryngologists in semirural Kenya. METHODS: Participants were prospectively recruited to participate in an ultrasound training course during a 2-week surgical training camp. They performed baseline ultrasound exams (9-item test, 5-point scale) with no assistance, followed by didactic sessions teaching ultrasound techniques. Participating surgeons then performed head and neck ultrasound exams on patients in clinic or in the operating room with direct supervision. Postcourse ultrasounds were performed, and the results of these tests were compared to baseline exams. RESULTS: Eight surgeons were enrolled out of a total of 13 (62%). Three were attending surgeons (37.5%), 1 enrollee was a head and neck surgery fellow, and 4 were senior residents (50%). Six of 8 surgeons were from Kenya. The mean precourse test score was 25 (range 21-30) compared to a mean postcourse test score of 40 (range 37-45, p < 0.005). All participants significantly improved their scores, with a mean improvement of 16 points (range 10-23). DISCUSSION: Otolaryngologists are uniquely equipped to learn head and neck ultrasound given their familiarity with the anatomy and pathology in this region. Training physicians without prior experience can be done even over short timeframes. Early training should focus on ultrasound, with later stages of training focusing on pathology.

Regulation of heparin-binding EGF-like growth factor by miR-212 and acquired cetuximab-resistance in head and neck squamous cell carcinoma.

BACKGROUND: We hypothesized that chronic inhibition of epidermal growth factor receptor (EGFR) by cetuximab, a monoclonal anti-EGFR antibody, induces up-regulation of its ligands resulting in resistance and that microRNAs (miRs) play an important role in the ligand regulation in head and neck squamous cell carcinoma (HNSCC). METHODOLOGY/PRINCIPAL FINDINGS: Genome-wide changes in gene and miR expression were determined in cetuximab-sensitive cell line, SCC1, and its resistant derivative 1Cc8 using DNA microarrays and RT-PCR. The effects of differentially expressed EGFR ligands and miRs were examined by MTS, colony formation, ELISA, and western blot assays. Heparin-binding EGF-like growth factor (HB-EGF) and its regulator, miR-212, were differentially expressed with statistical significance when SCC1 and 1Cc8 were compared for gene and miR expression. Stimulation with HB-EGF induced cetuximab resistance in sensitive cell lines. Inhibition of HB-EGF and the addition of miR-212 mimic induced cetuximab sensitivity in resistant cell lines. MicroRNA-212 and HB-EGF expression were inversely correlated in an additional 33 HNSCC and keratinocyte cell lines. Six tumors and 46 plasma samples from HNSCC patients were examined for HB-EGF levels. HB-EGF plasma levels were lower in newly diagnosed HNSCC patients when compared to patients with recurrent disease. CONCLUSIONS/SIGNIFICANCE: Increased expression of HB-EGF due to down-regulation of miR-212 is a possible mechanism of cetuximab resistance. The combination of EGFR ligand inhibitors or miR modulators with cetuximab may improve the clinical outcome of cetuximab therapy in HNSCC.