Use of the fibula osteocutaneous free flap to reconstruct the midface is highly reliable and our flap of choice for lower maxillary defects requiring bony reconstruction. However, when orbitozygomatic support is the primary objective, the utility of this flap is limited. Because of the complexity of this procedure, the choice of midface reconstruction technique should be individualized for each patient.

Purpose: New and more consistent biomarkers of head and neck squamous cell carcinoma (HNSCC) are needed to improve early detection of disease and to monitor successful patient management. The purpose of this study was to determine whether a new proteomic technology could correctly identify protein expression profiles for cancer in patient serum samples.Experimental Design: Surface-enhanced laser desorption/ionization-time of flight-mass spectrometry ProteinChip system was used to screen for differentially expressed proteins in serum from 99 patients with HNSCC and 102 normal controls. Protein peak clustering and classification analyses of the surface-enhanced laser desorption/ionization spectral data were performed using the Biomarker Wizard and Biomarker Patterns software (version 3.0), respectively (Ciphergen Biosystems, Fremont, CA).Results: Several proteins, with masses ranging from 2,778 to 20,800 Da, were differentially expressed between HNSCC and the healthy controls. The serum protein expression profiles were used to develop and train a classification and regression tree algorithm, which reliably achieved a sensitivity of 83.3% and a specificity of 100% in discriminating HNSCC from normal controls.Conclusions: We propose that this technique has potential for the development of a screening test for the detection of HNSCC.

Adjusting for pathologic factors and adjuvant therapy, lymph node ratio was found to be an independent prognostic factor for locoregional recurrence and overall survival (OS). Patients with lymph node ratio ≥20% are at high risk of locoregional recurrence and death, and may be considered for adjuvant chemoradiation.

Background: New and more consistent biomarkers of head and neck squamous cell carcinoma (HNSCC) are needed to improve early detection of disease and to monitor successful patient management.Objective: To determine if a new proteomic technology can correctly identify protein expression profiles for cancer in patient serum samples as well as detect the presence of a known tumor marker.Design: Direct proteomic analysis and comparison. Methods:The surface-enhanced laser desorption/ ionization time of flight mass spectrometry (SELDI-TOF) ProteinChip system was used to screen for differentially expressed proteins in serum samples from 99 patients with HNSCC, 25 "healthy" smokers, and 102 healthy (normal) controls. Protein peak clustering and classification analyses of the SELDI spectral data were performed.Results: Several proteins, with masses ranging from 2778 to 20 800 Da, were differentially expressed Conclusion:We propose that this technique may allow for the development of a reliable screening test for the early detection and diagnosis of HNSCC, as well as the potential identification of tumor biomarkers.

Purpose: Patients with head and neck squamous cell carcinoma (HNSCC) who actively smoke during treatment have worse survival compared with never-smokers and former-smokers. We hypothesize the poor prognosis in tobacco smokers with HNSCC is, at least in part, due to ongoing suppression of immune response. We characterized the tumor immune microenvironment (TIM) of HNSCC in a retrospective cohort of 177 current, former, and never smokers.Experimental Design: Tumor specimens were subjected to analysis of CD3, CD8, FOXP3, PD-1, PD-L1, and pancytokeratin by multiplex immunofluorescence, whole-exome sequencing, and RNA sequencing. Immune markers were measured in tumor core, tumor margin, and stroma.Results: Our data indicate that current smokers have significantly lower numbers of CD8 þ cytotoxic T cells and PD-L1 þ cells in the TIM compared with never-and former-smokers. While tumor mutation burden and mutant allele tumor heterogeneity score do not associate with smoking status, gene-set enrichment analyses reveal significant suppression of IFNa and IFNg response pathways in current smokers. Gene expression of canonical IFN response chemokines, CXCL9, CXCL10, and CXCL11, are lower in current smokers than in former smokers, suggesting a mechanism for the decreased immune cell migration to tumor sites.Conclusions: These results suggest active tobacco use in HNSCC has an immunosuppressive effect through inhibition of tumor infiltration of cytotoxic T cells, likely as a result of suppression of IFN response pathways. Our study highlights the importance of understanding the interaction between smoking and TIM in light of emerging immune modulators for cancer management.

Efatutazone and paclitaxel in combination were safe and tolerated and had biologic activity.

Molecular descriptions of thyroid lines were matched to the originating tumors, setting a new standard for cell line characterization. Furthermore, suppressed RhoB is implicated as a molecular target for therapy against ATC because five classes of drugs up-regulate RhoB and inhibit growth dose-responsively.

Purpose Our previous work suggested that HER3 inhibition sensitizes HNSCC to EGFR inhibition with cetuximab. This study aimed to define the role of HER3 in cetuximab resistance and the anti-tumor mechanisms of EGFR/HER3 dual targeting in HNSCC. Experimental Design We treated cetuximab-resistant HNSCC UMSCC1-C and parental UMSCC1-P cell lines with anti-EGFR antibody cetuximab, anti-HER3 antibody MM-121, and their combination. We assessed activities of HER2, HER3 and downstream signaling pathways by Western blotting, and cell growth by sulforhodamine B (SRB) and colony formation assays. HER3-specific shRNA was used to confirm the role of HER3 in cetuximab response. The combined efficacy and alterations in biomarkers were evaluated in UMSCC1-C xenograft and patient-derived xenograft (PDX) models. Results Cetuximab treatment induced HER3 activation and HER2/HER3 dimerization in HNSCC cell lines. Combined treatment with cetuximab and MM-121 blocked EGFR and HER3 activities and inhibited PI3K/AKT and ERK signaling pathways and HNSCC cell growth more effectively than each antibody alone. HER3 knockdown reduced HER2 activation and re-sensitized cells to cetuximab. Cetuximab-resistant xenografts and PDX models revealed greater efficacy of dual EGFR and HER3 inhibition compared to single antibodies. In PDX tissue samples, cetuximab induced HER3 expression and MM-121 reduced AKT activity. Conclusion Clinically relevant PDX models demonstrate that dual targeting of EGFR and HER3 is superior to EGFR targeting alone in HNSCC. Our study illustrates the upregulation of HER3 by cetuximab as one mechanism underlying resistance to EGFR inhibition in HNSCC, supporting further clinical investigations using multiple targeting strategies in patients who have failed cetuximab-based therapy.