Diagnostic modalities for distant metastasis in head and neck squamous cell carcinoma: Are we changing life expectancy?

Objectives/Hypothesis: To determine if the various imaging modalities for distant metastasis (DM) diagnosis alters life expectancy in head and neck squamous cell carcinoma (HNSCC). Study Design: Retrospective. Methods: One hundred seventy patients (mean age, 59.1 years; male:female, 135:35) with HNSCC who developed DM were reviewed. The main outcome measures were the method of DM diagnosis and time from DM diagnosis to death while controlling for clinical parameters (age, gender, tobacco status, primary tumor site, initial TNM classification, number and site of DM, administration of palliative chemotherapy). Results: Tumor subsites were: 40 oral cavity, 75 oropharynx, 36 larynx, 10 hypopharynx, one nasopharynx, and eight unknown primary. Of the patients, 16.5% (28/170) had distant metastasis at presentation; the remaining 142 patients were diagnosed with DM at a median of 324 days from diagnosis. Although patients diagnosed with DM by positron‐emission tomography (PET) scan were more likely to have multiple DM sites ( P = .0001), there were no differences in life expectancy in patients who were diagnosed with or without PET scan (median, 185 vs. 165 days, P = .833). There were no differences in life expectancy based on age, gender, site of primary tumor, or number/site of DM. The use of palliative chemotherapy resulted in a significantly longer life expectancy (median, 285 vs. 70 days; P = .001). Conclusions: Although a PET scan is more likely to diagnose multiple DM sites, there was no difference in life expectancy based on imaging modality. Patients who are symptomatic from their distant metastasis have a worse life expectancy, and palliative chemotherapy was able to increase life expectancy, even in patients who were symptomatic from the distant metastasis.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/92128/1/23264_ftp.pd

Tetrathiomolybdate inhibits head and neck cancer metastasis by decreasing tumor cell motility, invasiveness and by promoting tumor cell anoikis

<p>Abstract</p> <p>Background</p> <p>The metastatic spread of solid tumors is directly or indirectly responsible for most cancer-related deaths. Tumor metastasis is very complex and this process requires a tumor cell to acquire enhanced motility, invasiveness and anoikis resistance to successfully establish a tumor at a distal site. Metastatic potential of tumor cells is directly correlated with the expression levels of several angiogenic cytokines. Copper is a mandatory cofactor for the function of many of these angiogenic mediators as well as other proteins that play an important role in tumor cell motility and invasiveness. We have previously shown that tetrathiomolybdate (TM) is a potent chelator of copper and it mediates its anti-tumor effects by suppressing tumor angiogenesis. However, very little is known about the effect of TM on tumor cell function and tumor metastasis. In this study, we explored the mechanisms underlying TM-mediated inhibition of tumor metastasis.</p> <p>Results</p> <p>We used two <it>in vivo </it>models to examine the effects of TM on tumor metastasis. Animals treated with TM showed a significant decrease in lung metastasis in both <it>in vivo </it>models as compared to the control group. In addition, tumor cells from the lungs of TM treated animals developed significantly smaller colonies and these colonies had significantly fewer tumor cells. TM treatment significantly decreased tumor cell motility and invasiveness by inhibiting lysyl oxidase (LOX) activity, FAK activation and MMP2 levels. Furthermore, TM treatment significantly enhanced tumor cell anoikis by activating p38 MAPK cell death pathway and by downregulating XIAP survival protein expression.</p> <p>Conclusions</p> <p>Taken together, these results suggest that TM is a potent suppressor of head and neck tumor metastasis by modulating key regulators of tumor cell motility, invasiveness and anoikis resistance.</p

Incidence and management of rhinosinusitis after complex orbitofacial reconstruction.

OBJECTIVE: To examine the sinus-related sequelae of free flap reconstruction for complex orbitofacial defects. STUDY DESIGN: Retrospective chart review METHODS: Demographic, clinical, and radiographic data on a series of 55 patients who had undergone free tissue transfer for orbitofacial reconstruction was retrospectively reviewed. Follow-up of ≥ 3 months was available for 49 patients. Outcome measures studied included clinical or radiographic evidence of sinusitis and the need for sinus surgery. RESULTS: The most commonly involved sinuses were the ethmoid (n=40) and maxillary (n=38) sinuses, and the anterolateral thigh was the most common flap used (n=41). Clinical and/or radiographic sinusitis was evident in 21 patients (43%), and 10 patients (20%) required sinus surgery at some point during follow-up. Involvement of multiple sinuses in the initial orbitofacial surgery was associated with a significantly increased need for subsequent sinus surgery (p=0.009). Adjuvant radiotherapy and adjuvant chemo-radiotherapy were associated with a significantly increased risk for the development of rhinosinusitis (p=0.045 and 0.016 respectively). CONCLUSION: Rhinosinusitis and the need for operative management of sinus obstruction are common in patients having undergone complex orbitofacial reconstruction. Careful management of the paranasal sinuses is an important component of the multidisciplinary treatment of such patients

In vitro cytokine release profile: Predictive value for metastatic potential in head and neck squamous cell carcinomas

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/100299/1/hed23191.pd

Metallopanstimulin as a marker for head and neck cancer

BACKGROUND: Metallopanstimulin (MPS-1) is a ribosomal protein that is found in elevated amounts in the sera of patients with head and neck squamous cell carcinoma (HNSCC). We used a test, denoted MPS-H, which detects MPS-1 and MPS-1-like proteins, to determine the relationship between MPS-H serum levels and clinical status of patients with, or at risk for, HNSCC. PATIENTS AND METHODS: A total of 125 patients were prospectively enrolled from a university head and neck oncology clinic. Participants included only newly diagnosed HNSCC patients. Two control groups, including 25 non-smokers and 64 smokers, were studied for comparison. A total of 821 serum samples collected over a twenty-four month period were analyzed by the MPS-H radioimmunoassay. RESULTS: HNSCC, non-smokers, and smokers had average MPS-H values of 41.5 ng/mL, 10.2 ng/mL, and 12.8 ng/mL, respectively (p = 0.0001). CONCLUSION: We conclude that MPS-1 and MPS-1-like proteins are elevated in patients with HNSCC, and that MPS-H appears to be a promising marker of presence of disease and response to treatment in HNSCC patients

TriCurin, a novel formulation of curcumin, epicatechin gallate, and resveratrol, inhibits the tumorigenicity of human papillomaviruspositive head and neck squamous cell carcinoma

Head and neck squamous cell carcinoma (HNSCC) is the sixth most prevalent cancer worldwide with about 600,000 new cases diagnosed in the last year. The incidence of human papillomavirus-positive head and neck squamous cell carcinoma (HPV-positive HNSCC) has rapidly increased over the past 30 years prompting the suggestion that an epidemic may be on the horizon. Therefore, there is a clinical need to develop alternate therapeutic strategies to manage the growing number of HPV-positive HNSCC patients. TriCurin is a composition of three food-derived polyphenols in unique stoichiometric proportions consisting of curcumin from the spice turmeric, resveratrol from red grapes, and epicatechin gallate from green tea. Cell viability, clonogenic survival, and tumorsphere formation were inhibited and significant apoptosis was induced by TriCurin in UMSCC47 and UPCI:SCC090 HPV-positive HNSCC cells. Moreover, TriCurin decreased HPV16E6 and HPV16E7 and increased p53 levels. In a pre-clinical animal model of HPV-positive HNSCC, intratumoral injection of TriCurin significantly inhibited tumor growth by 85.5% compared to vehicle group (P \u3c 0.05, n = 7). Our results demonstrate that TriCurin is a potent anti-tumor agent for HPV-positive HNSCC. Further development of TriCurin as a novel anti-cancer therapeutic to manage the HPV-positive HNSCC population is warranted

The prognostic value of the hypoxia markers CA IX and GLUT 1 and the cytokines VEGF and IL 6 in head and neck squamous cell carcinoma treated by radiotherapy ± chemotherapy

BACKGROUND: Several parameters of the tumor microenvironment, such as hypoxia, inflammation and angiogenesis, play a critical role in tumor aggressiveness and treatment response. A major question remains if these markers can be used to stratify patients to certain treatment protocols. The purpose of this study was to investigate the inter-relationship and the prognostic significance of several biological and clinicopathological parameters in patients with head and neck squamous cell carcinoma (HNSCC) treated by radiotherapy ± chemotherapy. METHODS: We used two subgroups of a retrospective series for which CT-determined tumoral perfusion correlated with local control. In the first subgroup (n = 67), immunohistochemistry for carbonic anhydrase IX (CA IX) and glucose transporter-1 (GLUT-1) was performed on the pretreatment tumor biopsy. In the second subgroup (n = 34), enzyme linked immunosorbent assay (ELISA) was used to determine pretreatment levels of the cytokines vascular endothelial growth factor (VEGF) and interleukin-6 (IL-6) in serum. Correlation was investigated between tumoral perfusion and each of these biological markers, as well as between the markers mutually. The prognostic value of these microenvironmental parameters was also evaluated. RESULTS: For CA IX and GLUT-1, the combined assessment of patients with both markers expressed above the median showed an independent correlation with local control (p = 0.02) and disease-free survival (p = 0.04) with a trend for regional control (p = 0.06). In the second subgroup, IL-6 pretreatment serum level above the median was the only independent predictor of local control (p = 0.009), disease-free survival (p = 0.02) and overall survival (p = 0.005). CONCLUSION: To our knowledge, we are the first to report a link in HNSCC between IL-6 pretreatment serum levels and radioresistance in vivo. This link is supported by the strong prognostic association of pretreatment IL-6 with local control, known to be the most important parameter to judge radiotherapy responses. Furthermore, the combined assessment of CA IX and GLUT-1 correlated independently with prognosis. This is a valuable indication that a combined approach is important in the investigation of prognostic markers

Intensive care unit versus non–intensive care unit postoperative management of head and neck free flaps: Comparative effectiveness and cost comparisons

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106719/1/hed23325.pd