Fluorescently labeled cetuximab to evaluate head and neck cancer response to treatment.

OBJECTIVE: Combining the therapeutic and diagnostic properties of targeted antibodies may improve clinical assessment of disease with limited added toxicity during treatment. METHODS: Mice (n = 10) were xenografted with SCC-1 tumor cells and then treated with radiation, cisplatin and cetuximab. Brightfield and fluorescent imaging was performed after systemically injecting fluorescently labeled cetuximab prior to treatment and at six or ten weeks after initiation of treatment. The relative fluorescence intensity was determined for each image. RESULTS: The tumor luminosity measured before (week 0), during (week 6) and after treatment (week 10) did not significantly change. Actual tumor measurement corresponded to fluorescent measurements of tumors both before treatment and after treatment. Complete response to therapy occurred in one animal, where resolution of the tumor correlated with loss of fluorescent activity. CONCLUSIONS: This preclinical data suggests combining the diagnostic and therapeutic properties of cetuximab may be clinically useful.

Sensitivity and specificity of fluorescent immunoguided neoplasm detection in head and neck cancer xenografts.

OBJECTIVES: To determine whether fluorescently labeled anti-epidermal growth factor (EGFR) antibody could be used to detect residual disease and to guide surgical resections by comparing the sensitivity and specificity of optical fluorescence imaging with the sensitivity and specificity of histopathologic evaluation. DESIGN: A preclinical model of head and neck squamous cell carcinoma. SUBJECTS: Mice xenografted with SCC-1 tumor cells. INTERVENTIONS: The mice underwent systemic injection with anti-EGFR antibody (cetuximab) conjugated to an optically active fluorophore (Cy5.5). Both a subcutaneous flank model (n = 18) and an orthotopic murine model (n = 15) were used to assess for the presence of residual disease by fluorescent stereomicroscopy after subtotal resections of tumors. Histologic analysis was performed to confirm the presence or absence of disease. RESULTS: In the subcutaneous flank model, a diagnostic dose (50 microg) and therapeutic dose (250 microg) of fluorescent-labeled anti-EGFR were administered. When a diagnostic dose was given, the sensitivity was 86%, which was less than the 91% sensitivity when the higher dose was given. Tumor biopsy specimens in which disease was detected by histologic analysis but not by fluorescence (false-negative result) averaged 166 cells (range, 50-350 cells). The specificity of optical fluorescence to predict the presence of tumor in both groups was 100%. In the floor of the mouth model, we demonstrated a sensitivity of 81% and a specificity of 100%. False-negative results were obtained in a tumor fragment measuring less than 0.5 mm in diameter. CONCLUSION: These data support further investigation of fluorescently labeled anti-EGFR antibody to detect disease in the surgical setting.

Pediatric otolaryngologists' use of genetic testing.

OBJECTIVE: To assess the use of genetic testing by pediatric otolaryngologists in evaluating a child with prelingual sensorineural hearing impairment (SNHI). DESIGN: Questionnaire on the use of genetic testing in the evaluation of prelingual SNHI was made available to pediatric otolaryngologists through the American Society of Pediatric Otolaryngology (ASPO) Web site (http://www.aspo.us). Each ASPO member was invited by e-mail to complete the questionnaire. PARTICIPANTS: Sixty-three ASPO members. RESULTS: Forty-two (69%) of 61 respondents indicated that they use genetic testing of the connexin 26 (Cx26) gene (GJB2) as an initial test in their workup of prelingual SNHI, and 30 (71%) of 42 reported that they provide genetic counseling for their patients and their families. However, 17 (45%) of 38 respondents answered questions regarding recurrence risks incorrectly or stated that they did not know the correct response. In addition, 7 (12%) of 60 respondents reported that they do not use DNA-based testing at any point in their workup. CONCLUSIONS: Many pediatric otolaryngologists use DNA-based testing in their evaluation of prelingual SNHI. However, many pediatric otolaryngologists do not have an adequate knowledge of the implications of genetic testing. Because it will take on an increasingly large role in clinical practice, pediatric otolaryngologists must be familiar with current genetic testing, counseling, and treatment recommendations. As these results demonstrate, such knowledge is still lacking in this physician population.

In vivo detection of head and neck cancer orthotopic xenografts by immunofluorescence.

PURPOSE: To determine whether Cy5.5-labeled antiepidermal growth factor (EGFR) antibody could be used to detect head and neck squamous cell carcinoma (HNSCC) xenografts in vivo. METHODS: AntiEGFR antibody (cetuximab) was labeled with Cy5.5, a fluorophore with emission in the near infrared range. The cetuximab-Cy5.5 conjugate was systemically administered in subtherapeutic doses (50 microg) to mice bearing orthotopically xenografted HNSCC cell lines (SCC1, CAL27, and FaDu). As a control, isotype-matched human immunoglobulin (Ig)G1k antibody labeled with Cy5.5 was systemically injected in parallel experiments. All tumor regions (n = 6) were imaged by fluorescent stereomicroscopy at 0, 6, 24, 48, or 72 hours. Tumor size was measured by high-frequency ultrasonography at 72 hours. Transcervical partial and near-total resections were then performed with stereomicroscopic imaging after each resection. The mandible and associated structures were then resected, paraffin embedded, and then serial sectioned for analysis. RESULTS: Tumors could be clearly visualized by near infrared fluorescent stereomicroscopy at 48 and 72 hours after systemic administration of cetuximab-Cy5.5 but not after administration with the labeled isotype control antibody, IgG1k-Cy5.5. Ultrasound measurement of tumors (n = 5) correlated with fluorescent measurements of tumor (Spearman's coefficient, 0.92, P

Pretreatment, preoperative swallowing exercises may improve dysphagia quality of life.

OBJECTIVES: Dysphagia is commonly associated with head and neck cancer treatment. Traditional dysphagia management strategies focus on post-treatment therapy. This study evaluated the utility of pretreatment swallowing exercises in improving post-treatment swallowing quality of life (QOL). STUDY DESIGN: Prospective cohort study and cross-sectional QOL analysis. METHODS: This study includes 37 patients who underwent primary radiation or combined chemoradiation treatment for newly diagnosed hypopharyngeal, laryngeal, or oropharyngeal primary tumors at the University of Alabama at Birmingham. Of the 37, 25 patients underwent swallowing exercises beginning 2 weeks prior to the start of radiation. The M.D. Anderson Dysphagia Inventory (MDADI) was administered an average of 14 months after treatment to assess the success of the protocol. Analysis of QOL scores related to gender, primary site, stage, and race were obtained. RESULTS: Patients who performed pretreatment swallowing exercises (n = 25) showed improvement in the overall MDADI score (P = .0002) compared to the control population (n = 12) who underwent post-treatment therapy. Furthermore, a separate analysis of individual domains of the MDADI (global, emotional, functional, and physical) demonstrated improved quality of life. CONCLUSIONS: Implementation of pretreatment swallowing education and exercise may improve dysphagia-specific QOL in head and neck cancer patients undergoing radiation and/or chemoradiation therapy.