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1.  Transoral laser microsurgery followed by radiation therapy for oropharyngeal tumors: The Mayo Clinic Arizona Experience 
Head & neck  2013;36(2):220-225.
The purpose of this study was to report the treatment outcomes of patients with advanced oropharyngeal cancer treated with transoral laser microsurgery (TLM) followed by radiation therapy (RT) at Mayo Clinic in Arizona.
A retrospective study of 80 patients treated from January 1, 2000 to November 7, 2011 was performed. All patients had stage III/IV oropharyngeal tumors and underwent TLM with neck dissection. Adjuvant RT was then given. Thirty-seven patients received concurrent adjuvant chemotherapy. The primary outcome was locoregional control.
Median follow-up was 47.3 months (range, 9.7–139.2 months). The 3-year locoregional control, recurrence-free survival, and overall survival rates were 98.6% (95% confidence interval [CI], 91% to 100%), 91.1% (95% CI, 81% to 96%), and 93.7% (95% CI, 84% to 98%), respectively. There were a total of 5 treatment failures, 1 regional and 4 distant. Twenty-six patients underwent neck only RT with exclusion of the primary site.
TLM followed by RT for advanced oropharyngeal cancer results in excellent locoregional control rates.
PMCID: PMC4335799  PMID: 23529906
transoral laser microsurgery; transoral; radiation; head neck cancer; oropharyngeal
2.  [No title available] 
PMCID: PMC4053486  PMID: 24430914
Head & neck  2011;34(6):776-784.
This study examined risk factors for dysphagia, a common and serious condition in patients with head and neck cancer, and the association between severity of dysphagia and survival.
Chart reviews were performed on patients diagnosed with head and neck cancer between January 2001 and April 2003, who had dysphagia diagnoses or swallowing evaluations. Regression analyses determined factors associated with dysphagia and the association between observed survival and severity of dysphagia.
Almost 50% of the 407 patients had dysphagia. Risk factors included advanced stage, older age, female sex, and hypopharyngeal tumors. The most severe dysphagia ([L.] nil per os or “nothing by mouth” status), which was associated with lower survival rates, was the strongest independent predictor of survival.
Swallowing problems should be considered when determining appropriate cancer-directed treatment and posttreatment care. Because of dysphagia’s high incidence rate and association with survival, a speech-language pathologist should be involved to ensure routine diagnostic and therapeutic swallowing interventions.
PMCID: PMC4304637  PMID: 22127835
head and neck cancer; dysphagia; swallowing; swallowing therapy; survival
4.  Clinicopathologic predictors of recurrence and overall survival in adenoid cystic carcinoma of the head and neck: A single institutional experience at a tertiary care center 
Head & neck  2014;36(12):1705-1711.
The purpose of this study was to determine factors that impact recurrence and long-term survival of head and neck adenoid cystic carcinoma (ACC).
We conducted a retrospective review of 87 patients with head and neck ACC who were evaluated between 1992 and 2009. Staining for Ki-67, p53, α-estrogen receptor (αER), and progesterone receptor (PR) was performed.
Forty men (46%) and 47 women (54%) were included in this study. Median follow-up for patients was 98 months. Five-year recurrence-free and overall survival (OS) rates were 56% and 81%, respectively. Ki-67 and p53 expression was observed in 5 (6%) and 2 (2%) patients, respectively. αER and PR were all negative. The most important determinants of disease-free survival (DFS) were perineural invasion (PNI; p = .001) and female sex (p = .027). Disease site (major vs minor salivary gland) was the only predictor of worse OS on multivariate analysis.
Perineural invasion, female sex, and disease site were the most consistent predictors of poor outcome in head and neck ACC.
PMCID: PMC4299584  PMID: 24166847
adenoid cystic carcinomas; head and neck; prognostic factors; disease-free survival; overall survival
5.  Molecular Profiling of Sinonasal Undifferentiated Carcinoma 
Head & neck  2013;36(1):10.1002/hed.23267.
Sinonasal undifferentiated carcinoma remains a poorly characterized malignancy at both the clinical and molecular level, and consequently the optimal treatment strategy remains undefined.
We utilized a mass spectroscopy-based approach (Sequenom™) to evaluate 95 hallmark single nucleotide variations within 12 oncogenes or tumor suppressor genes (AKT, BRAF, CDK4, Beta-catenin, EGFR, FBXW7, JAK2, c-KIT, KRAS, PDGFR, PI3K, VEGF) in 13 histologically confirmed SNUC cases.
None of the samples demonstrated activating mutations in any of the 95 SNVs.
Select clinically relevant activating genomic mutations were not identified the 13 patient samples. However, polymorphisms were noted within the promoter region of VEGF. These may merit future study as predictive biomarkers for treatment response or overall survival. Additionally, future studies focusing on larger tumor sets and utilizing whole genome or exome sequencing may help define genetic aberrations in SNUC that can be clinically targeted with available or emerging biological agents.
PMCID: PMC3874284  PMID: 23633104
SNUC; Sinonasal Undifferentiated Carcinoma; Paranasal sinus tumors; VEGF; Sequenom
6.  Transoral robotic approach to carcinoma of unknown primary 
Head & neck  2013;36(6):848-852.
The management of carcinoma of unknown primary (CUP) is one of the challenging conditions in head and neck oncologic surgery. Despite various diagnostic tools, the primary tumor site in more than half of cases remains unidentified. The purpose of this study was to assess the feasibility and efficiency of utilizing transoral robotic surgery (TORS) for the diagnosis and treatment of CUP in the head and neck.
In this prospective, single-institutional, clinical TORS trial, 22 of 181 patients were treated for CUP between 2008 and 2012.
Among all those 22 patients, primary tumor site identification and complete tumor removal was achieved in 17 patients (77.3%) with TORS. Tonsil (59.1%) and base of tongue (18.1%) were identified as the most common tumor locations.
Together with panendoscopy, directed biopsies, and positron emission tomography (PET)/CT, TORS is a valuable option in the identification and treatment of primary tumor sites.
PMCID: PMC4266274  PMID: 23720223
carcinoma of unknown primary; transoral robotic surgery; daVinci
7.  A novel DICER1 mutation causes multi-nodular goiter in children 
Head & neck  2013;35(12):10.1002/hed.23250.
To present a rare case of an adolescent with multinodular goiter (MNG) found to have a DICER1 mutation.
Chart review including endocrine hormone tests, thyroid ultrasound, and genetic testing for DICER1.
A 12-year-old female presented with a diffusely enlarged thyroid gland. Family history revealed an older sister with a history of bilateral ovarian Sertoli-Leydig cell tumors and MNG. Thyroid function tests were normal. Serial thyroid ultrasounds showed enlarging multiple bilateral nodules. Fine needle aspiration suggested MNG. Genetic testing revealed a novel heterozygous premature termination mutation (c.1525C>T p.R509X) in the DICER1 gene.
Thyroid nodules are rare in children but carry a higher risk for malignancy. It is essential to inquire about family history and refer for genetic evaluation with a family history of MNG. In patients with DICER1 mutations, tumor surveillance is critical due to the increased risk of multiple tumors, including ovarian tumors and pleuropulmonary blastoma.
PMCID: PMC3762914  PMID: 23728841
DICER1; multi-nodular goiter; ovarian Sertoli-Leydig cell tumors; tumor surveillance; family history
8.  Adherence to Preventive Exercises and Self-Reported Swallowing Outcomes in Post-Radiation Head and Neck Cancer Patients 
Head & neck  2013;35(12):1707-1712.
To reduce the risk of long-term swallowing complications after radiation, swallowing exercises may be helpful. Both the rate of adherence to swallowing exercises and its impact on future swallowing function is unknown.
109 oropharyngeal cancer patients beginning radiation were tracked for two years to determine adherence to swallowing exercises. Participants completed the M.D. Anderson Dysphagia Inventory (MDADI) 1–2 years after treatment to assess self-reported swallowing function. Adherence, demographics, tumor and treatment variables were multivariably regressed onto the MDADI physical subscale score.
Per speech pathologist documentation, 13% of the participants were fully adherent and 32% were partially adherent. Adherence was associated with the Physical MDADI Subscale score in the multivariate model (p=.01).
The majority of head and neck cancer patients are nonadherent to swallowing exercise regimens and may benefit from supportive care strategies to optimize their adherence.
PMCID: PMC3943468  PMID: 24142523
Adherence; dysphagia; exercises; oropharyngeal cancer
9.  Circulating CD4-positive lymphocyte levels predict response to induction chemotherapy in patients with advanced laryngeal cancer 
Head & neck  2013;36(1):9-14.
Tumor regression after induction chemotherapy (ICT) identifies laryngeal cancers that are responsive to chemoradiation. Patient immune parameters have recently been associated with response to chemotherapy and may identify responding patients. A retrospective analysis was performed to determine if pretreatment, circulating T lymphocyte levels, predicted ICT response in patients with advanced laryngeal cancer.
Pretreatment, circulating T lymphocyte subpopulations were correlated with response to therapy and survival. Results were compared with similar data from an identical Phase II trial involving patients with oropharyngeal cancer. An increased percentage of CD4+ cells predicted response to ICT and suggested improved survival in patients with laryngeal, but not oropharyngeal, cancer. In the combined group of patients, increased CD4 levels predicted response to ICT.
These findings demonstrate the potential importance of the immune system in chemotherapy response and clinical outcome. Differences in findings between patients with advanced laryngeal and oropharyngeal cancer may reflect different cellular immunity function in the patients with HPV-16+ oropharyngeal cancer.
PMCID: PMC4243470  PMID: 23765859
laryngeal cancer; chemotherapy; T lymphocytes; immunity; oropharyngeal cancer
10.  Head & Neck Squamous Cell Carcinoma of Unknown Primary: Neck Dissection and Radiotherapy or Definitive Radiotherapy 
Head & neck  2013;36(11):1589-1595.
Management of head and neck carcinoma from unknown primary (HNCUP) remains controversial, with neck dissection and radiotherapy (ND+RT) or definitive RT both commonly used. We aimed to characterize HNCUP and retrospectively compare outcomes for patients treated with ND+RT versus definitive RT.
From 1994-2009, 41 HNCUP patients underwent either ND+RT (n=22) or definitive RT+ concurrent chemotherapy (n=19) at our institution. Treatment outcomes were compared using Kaplan-Meier methods and log-rank test.
There were no differences between patients treated with ND+RT and definitive RT in overall survival (OS), progression-free survival (PFS), or locoregional-relapse-free survival, freedom-from-locoregional failure, or freedom-from-distant failure. Among 17 ND+RT patients for whom human papillomavirus (HPV) status could be determined, HPV(+) patients trended towards improved OS (p=0.06)and PFS (p=0.15).
Neck dissection and post-op RT resulted in similar outcome as definitive RT. The prognostic implications of HPV(+) nodes in HNCUP are similar to those in oropharyngeal primary cancers.
PMCID: PMC4241546  PMID: 23996575
Unknown primary; neck dissection; radiation therapy; human papillomavirus
11.  Depth of invasion, tumor budding, and worst pattern of invasion: Prognostic indicators in early-stage oral tongue cancer 
Head & Neck  2013;36(6):811-818.
Oral (mobile) tongue squamous cell carcinoma (SCC) is characterized by a highly variable prognosis in early-stage disease (T1/T2 N0M0). The ability to classify early oral tongue SCCs into low-risk and high-risk categories would represent a major advancement in their management.
Depth of invasion, tumor budding, histologic risk-assessment score (HRS), and cancer-associated fibroblast (CAF) density were studied in 233 cases of T1/T2 N0M0 oral tongue SCC managed in 5 university hospitals in Finland.
Tumor budding (≥5 clusters at the invasive front of the tumor) and depth of invasion (≥4 mm) were associated with poor prognosis in patients with early oral tongue SCC (hazard ratio [HR], 2.04; 95% confidence interval [CI], 1.17–3.55; HR, 2.55; 95% CI, 1.25–5.20, respectively) after multivariate analysis. The HRS and CAF density did not predict survival. However, high-risk worst pattern of invasion (WPOI), a component of HRS, was also an independent prognostic factor (HR, 4.47; 95% CI, 1.59–12.51).
Analyzing the depth of invasion, tumor budding, and/or WPOI in prognostication and treatment planning of T1/T2 N0M0 oral tongue SCC is recommended.
PMCID: PMC4229066  PMID: 23696499
oral tongue squamous cell carcinoma; tumor budding; depth of invasion; worst pattern of invasion; histologic risk score; cancer-associated fibroblast; disease-specific mortality; prognosis
12.  Weekly Chemotherapy with Radiation versus High-Dose Cisplatin with Radiation as Organ Preservation for Patients with HPV Positive and HPV Negative Locally Advanced Squamous Cell Carcinoma of the Oropharynx (SCCOP) 
Head & neck  2013;36(5):617-623.
Optimal treatment for locally advanced SCCOP is not well defined. Here we retrospectively compare survival and toxicities from two different organ preservation protocols.
The matched dataset consisted of 35 patients from each trial matched for age, stage, smoking, and tumor HPV status. Patients on University of Michigan Cancer Center (UMCC) trial 9921 were treated with induction chemotherapy followed by high-dose cisplatin and radiation in responders, or surgery in non-responders. Patients on UMCC trial 0221 were treated with weekly carboplatin and paclitaxel and radiation.
Survival was comparable for both studies and did not differ significantly across each trial after stratifying by HPV status. Grade 3 and 4 toxicities were more frequent in UMCC 9921. At 6 months post-treatment, G-tube dependence was not statistically different.
These data suggest that survival outcomes in patients with locally advanced SCCOP are not compromised with weekly chemotherapy and RT, and such treatment is generally more tolerable.
PMCID: PMC4205960  PMID: 23596055
chemoradiation; oropharynx; HPV; weekly; toxicity
13.  ALDH1 immunohistochemical expression and its significance in salivary adenoid cystic carcinoma 
Head & neck  2012;35(4):575-578.
Adenoid cystic carcinoma (ACC) cells with a high level of ALDH1, a known cancer stem cell (CSC) marker, had higher tumorigenic, invasive, and metastatic abilities. We examined the immunohistochemical expression of ALDH1 in ACC and its correlation with survival.
Archival paraffin blocks of ACC were analyzed. A tissue microarray was constructed and immunohistochemical expression of ALDH1 was analyzed using anti-ALDH1 monoclonal antibody. Correlations between ALDH1 expression and clinical and histological parameters were assessed by chi-square tests. Survival was assessed by the Kaplan–Meier method and log-rank test.
Most of the tumors (63%) showed stromal staining only, 11% of the tumors showed both epithelial and stromal expression, and 26% of the tumors did not show either epithelial or stromal staining. Statistical analyses did not show any correlation between the pattern of ALDH1 expression and tumor histology, tumor size, or perineural invasion. There were no significant differences in survival among the 3 patterns of ALDH1 expression.
Other factors, besides CSCs, may play important roles in tumorigenesis, cell differentiation, and tumor progression in these tumors.
PMCID: PMC4186659  PMID: 22581680
ALDH1 expression; adenoid cystic carcinoma; tissue microarray; predictive marker
14.  High Symptom Burden Prior to Radiation Therapy for Head and Neck Cancer: A Patient-Reported Outcomes Study 
Head & neck  2012;35(10):1490-1498.
As a first step toward developing effective strategies to control symptoms associated with head and neck cancer (HNC) and its treatment, we sought to describe the pattern of symptoms experienced before radiation therapy.
Subjects completed the MD Anderson Symptom Inventory—Head and Neck Module before beginning radiation therapy.
270 patients participated. Symptom severity and interference varied between treatment-naïve patients and those with prior treatment. Cluster analyses revealed that 33% of patients had high symptom burden. Symptoms most often rated moderate-to-severe were fatigue, sleep disturbance, distress, pain, and problems chewing and swallowing. Poorer performance status, higher T classification, and receipt of previous treatment correlated with higher symptom burden.
A substantial proportion of patients were experiencing high symptom burden. Because few interventions currently exist for several of the most problematic symptoms, research in symptom reduction that targets the pattern of symptoms described here is greatly needed.
PMCID: PMC3788079  PMID: 23169304
head and neck cancer; patient-reported outcomes; symptom burden; MDASI-HN; symptom research
15.  A Multi-institutional Investigation of the Prognostic Value of Lymph Nodal Yield in Advanced Stage Oral Cavity Squamous Cell Carcinoma (OCSCC) 
Head & neck  2014;36(10):1446-1452.
Although existing literature provides surgical recommendations for treating occult disease (cN0) in early stage oral cavity squamous cell carcinoma, a focus on late stage OCSCC is less pervasive.
The records of 162 late stage OCSCC pN0 individuals that underwent primary neck dissections were reviewed. Lymph node yield (LNY) as a prognosticator was examined.
Despite being staged pN0, patients that had a higher LNY had an improved regional/distant control rates, DFS, DSS, and OS. LNY consistently outperformed all other standard variables as being the single best prognostic factor with a tight risk ratio range (RR = 0.95–0.98) even when correcting for the number of lymph nodes examined.
The results of this study showed that lower regional recurrence rates and improved survival outcomes were seen as lymph node yield increased for advanced T-stage OCSCC pN0. This suggests that increasing lymph node yield with an extended cervical lymphadenectomy may result in lower recurrence rates and improved survival outcomes for this advanced stage group.
PMCID: PMC4136977  PMID: 24038739
16.  Clinicopathologic features are stronger prognostic factors than histology or grade in risk stratification of primary parotid malignancies 
Head & neck  2011;33(2):225-231.
To determine the relative contribution of clinicopathologic risk factors versus low- and high-risk grade histologic groups to assist management of primary parotid cancers.
Study design
Retrospective chart review.
168 primary parotid malignancies were treated surgically at a tertiary care center from 1982 to 2005. Of these, 115 patients with complete follow up information were further analyzed. Pathologic updating and re-classification in 28% of cases enabled comparison of tumor histology or grade with current consensus criteria. Clinical outcomes of high- and low-risk histology and grade were compared with the influence of traditional clinicopathologic risk factors.
Of 115 cases, the male: female ratio was equal and the median age was 63 years (range, 15 to 89 years). Mucoepidermoid carcinoma (n=28) was the most common histology. The median follow-up was 44 months (range, 0 to 278 months). 40% of low-risk histology patients who underwent neck dissection had pN+ disease. The median time to recurrence was not reached for low-risk tumors as compared to 29 months for high-risk tumors (p = .0001). Interestingly, extracapsular spread (ECS) and margin status were independent prognostic factors and conferred significantly greater prognostic value than histologic grade risk group. Disease free survival (DFS) and overall survival (OS) at 5-years for the entire cohort was 51% and 57%, respectively. Risk group was a strong independent predictor of OS but not DFS.
Risk group defined by histology and grade was associated with disease-free survival. ECS and margin status were independent predictors of disease-free survival. Inclusion of ECS and margin status substantially improved the prediction of disease recurrence, supporting elective neck dissection and post-operative radiotherapy for high-grade tumors or low risk histologies with positive margins or ECS.
PMCID: PMC4164959  PMID: 21298822
Malignant parotid tumors; prognostic factors; neck dissection; neck metastasis
17.  Role of parathyroid hormone therapy in reversing radiation-induced nonunion and normalization of radiomorphometrics in a murine mandibular model of distraction osteogenesis 
Head & neck  2013;35(12):1732-1737.
The use of mandibular distraction osteogenesis (MDO) for tissue replacement after oncologic resection or for defects caused by osteoradionecrosis has been described but, in fact, has seen limited clinical utility. Previous laboratory work has shown that radiation (XRT) causes decreased union formation, decreased cellularity, and decreased mineral density in an animal model of MDO. Our global hypothesis is that radiation-induced bone damage is partly driven by the pathologic depletion of both the number and function of osteogenic cells. Parathyroid hormone (PTH) is a U.S. Food and Drug Administration-approved anabolic hormonal therapy that has demonstrated efficacy for increasing bone mineral density for the treatment of osteoporosis. We postulate that intermittent systemic administration of PTH will serve as an anabolic stimulant to cellular function that will act to reverse radiation-induced damage and enhance bone regeneration in a murine mandibular model of DO.
A total of 20 isogenic male Lewis rats were randomly assigned into 3 groups. Group 1 (XRT-DO, n = 7) and group 2 (XRT-DO-PTH, n = 5) received a human bioequivalent dose of 70 Gy fractionated over 5 days. All groups including group 3 (DO, n = 8) underwent a left unilateral mandibular osteotomy with bilateral external fixator placement. Four days later, mandibular DO was performed at a rate of 0.3 mm every 12 hours to reach a maximum gap of 5.1 mm. Group 2 was injected PTH (60 μg/kg) subcutaneously daily for 3 weeks following the start of MDO. On postoperative day 41, all left hemimandibles were harvested. Micro-CT at 45-μm voxel size was performed and radiomorphometrics parameters of bone mineralization were generated. Union quality was evaluated on a 4-point qualitative grading scale. Radiomorphometric data were analyzed using 1-way ANOVA, and union quality assessment was analyzed via the Mann–Whitney test. Statistical significance was considered at p ≤ .05.
Groups 1 and 2 appropriately demonstrated clinical signs of radiation-induced stress ranging from alopecia to mucositis. Union quality was significantly higher in PTH-treated XRT-DO animals, compared with XRT-DO group animals (p = .02). Mineralization metrics, including bone volume fraction (BVF) and bone mineral density (BMD), also showed statistically significant improvement. The groups that were treated with PTH showed no statistical differences in union or radiomorphometrics when compared with DO in nonradiated animals.
We have successfully demonstrated the therapeutic efficacy of PTH to stimulate and enhance bone regeneration in our irradiated murine mandibular model of DO. Our investigation effectively resulted in statistically significant increases in BMD, BVF, and clinical unions in PTH-treated mandibles. PTH demonstrates immense potential to treat clinical pathologies where remediation of bone regeneration is essential.
PMCID: PMC4160101  PMID: 23335324
parathyroid hormone; distraction osteogenesis; radiation; mandible; mineral density
18.  In vitro cytokines release profile: Predictive value for metastatic potential in head and neck squamous cell carcinomas 
Head & neck  2013;35(11):1542-1550.
Head and neck squamous carcinomas (HNSCC) have devastating morbidity rates with mortality mainly because of metastasis.
Multiplex Enzyme-linked-immunosorbent-assay (ELISA) to assay a variety of cytokine levels secreted by a panel of stage- and anatomic site-specific primary, recurrent and metastatic University of Michigan-HNSCC cell lines over a 72-hour time-course.
Conditioned medium from metastatic or recurrent HNSCC showed significantly higher amounts of interleukin (IL)-6, IL-6 receptor, Tumor Growth Factor-beta (TGF-β) and Vascular Endothelial Growth Factor (VEGF) than nonmetastatic cells or normal oral keratinocytes. Tumor Necrosis Factor was only secreted by the stage IV, metastatic, or recurrence-derived cell lines.
The cytokine profile of cultured HNSCC cells suggests that high levels of IL-6 and IL-6R, TGF-β, and VEGF are significantly related with their metastatogenic potential and provide rationale for determining if serum testing for a combination of these four soluble factors could be of predictive value for the HNSCC tumor progression and clinical outcome.
PMCID: PMC4157347  PMID: 23322448
Head and neck squamous carcinoma (HNSCC); cell lines; cytokines profiling; multiplex analysis; clinical outcome; metastasis
19.  Aspiration pneumonia after chemo–intensity-modulated radiation therapy of oropharyngeal carcinoma and its clinical and dysphagia-related predictors 
Head & neck  2013;36(1):120-125.
The purpose of this study was to assess aspiration pneumonia (AsPn) rates and predictors after chemo-irradiation for head and neck cancer.
The was a prospective study of 72 patients with stage III to IV oropharyngeal cancer treated definitively with intensity-modulated radiotherapy (IMRT) concurrent with weekly carboplatin and paclitaxel. AsPn was recorded prospectively and dysphagia was evaluated longitudinally through 2 years posttherapy by observer-rated (Common Toxicity Criteria version [CTCAE]) scores, patient-reported scores, and videofluoroscopy.
Sixteen patients (20%) developed AsPn. Predictive factors included T classification (p = .01), aspiration detected on videofluoroscopy (videofluoroscopy-asp; p = .0007), and patient-reported dysphagia (p = .02–.0003), but not observer-rated dysphagia (p = .4). Combining T classification, patient reported dysphagia, and videofluoroscopy-asp, provided the best predictive model.
AsPn continues to be an under-reported consequence of chemo-irradiation for head and neck cancer. These data support using patient-reported dysphagia to identify high-risk patients requiring videofluoroscopy evaluation for preventive measures. Reducing videofluoroscopy-asp rates, by reducing swallowing structures radiation doses and by trials reducing treatment intensity in patients predicted to do well, are likely to reduce AsPn rates.
PMCID: PMC4144677  PMID: 23729173
oropharyngeal cancer; head and neck cancer; IMRT; aspiration pneumonia; dysphagia
20.  “Prognostic factors in patients with high-risk locally advanced salivary gland cancers treated with surgery and postoperative radiotherapy” 
Head & neck  2011;33(3):318-323.
We sought to study the outcome of patients with locally advanced salivary gland cancers treated with surgery and postoperative radiotherapy.
Patients and methods:
We conducted a retrospective review of patients with salivary gland cancers registered in University of Pittsburgh databases from 1990-2006.
74 patients were analyzed. Histologic types included salivary duct carcinoma, 24%; adenoid cystic carcinoma, 23%; adenocarcinoma, 19%; mucoepidermoid carcinoma, 14%; N2, 39%; N0-1, 58%; major salivary gland origin, 80%. With a median follow-up of 4.1 years, the 5-year recurrence-free survival (RFS) was 49%, and the 5-year overall survival (OS) 55%. The 5-year local RFS was 76% and the 5-year distant RFS 60%. Using Cox-regression analysis, advanced nodal stage (N2) was the only significant predictor of both RFS and OS.
The long-term outcome of patients with high-risk, locally advanced salivary gland cancers is unsatisfactory. Nodal stage is a strong predictor of recurrence and overall survival.
PMCID: PMC4135528  PMID: 21284048
Head & neck  2008;30(10):1273-1283.
Metastases are the primary cause of cancer treatment failure and death, yet metastatic mechanisms remain incompletely understood.
We studied the molecular basis of head and neck cancer metastasis by transcriptionally profiling 70 samples from 27 patients—matching normal adjacent tissue, primary tumor, and cervical lymph node metastases.
We identified tumor-associated expression signatures common to both primary tumors and metastases. Use of matching metastases revealed an additional 46 dysregulated genes associated solely with head and neck cancer metastasis. However, despite being metastasis-specific in our sample set, these 46 genes are concordant with genes previously discovered in primary tumors that metastasized.
Although our data and related studies show that most of the metastatic potential appears to be inherent to the primary tumor, they are also consistent with the notion that a limited number of additional clonal changes are necessary to yield the final metastatic cell(s), albeit in a variable temporal order.
PMCID: PMC4136479  PMID: 18642293
head and neck cancer; expression profiling; metastasis; gene signatures; oncogenomics
22.  Predictors of survival and recurrence after temporal bone resection for cancer 
Head & neck  2011;34(9):1231-1239.
The purpose of this study was to identify factors predictive of outcome in patients undergoing temporal bone resection (TBR) for head and neck cancer.
This was a retrospective study of 72 patients undergoing TBR. Factors associated with survival and recurrence were identified on multivariable regression.
Most tumors were epithelial (81%), commonly (69%) involving critical structures. Cervical metastases were uncommon (6%). Squamous cell carcinoma (SCC) of the external auditory canal carried a high rate of parotid invasion (25%) and parotid nodal metastases (43%). The 5-year rate of overall survival (OS) was 62%; disease-specific survival (DSS), 70%; recurrence-free survival (RFS), 46%. Factors independently associated with outcome on multivariable analysis were margin status and extratemporal spread of disease to the parotid, mandible, or regional nodes. Recurrence was common (72%) in cT3–4 tumors.
Margin status and extratemporal disease spread are the strongest independent predictors of survival and recurrence. In SCC of the external auditory canal, high rates of parotid involvement support adjunctive parotidectomy. Risk of recurrence in T3–T4 tumors may support a role for adjuvant therapy.
PMCID: PMC4126564  PMID: 21953902
temporal bone; ear canal; squamous cell carcinoma; head and neck neoplasms
23.  The Prevalence and Predictive Role of p16 and EGFR in Surgically Treated Oropharyngeal and Oral Cavity Cancer 
Head & neck  2012;35(8):1083-1090.
To describe the relationship of p16 and EGFR expression with survival in surgically treated patients who had oropharyngeal and oral cavity squamous cell carcinoma (OPSCC and OCSCC).
Tissue from 36 OPSCC and 49 OCSCC patients treated between 1997 and 2001 was imbedded and immunostained using a tissue microarray.
p16 was positive in 57% and 13% of OPSCC and OCSCC patients, respectively. EGFR was positive in 60% and 63% of OPSCC and OCSCC patients, respectively. In OPSCC patients, p16 expression was associated with improved disease specific survival (DSS), overall survival (OS), and time to recurrence (TTR) (p <0.01, <0.01, <0.01). EGFR expression was associated with poorer DSS, OS, and TTR (p <0.01, =0.01, <0.01). For OPSCC, when examining both p16 and EGFR expression as combined biomarkers, high p16 expression coupled with low EGFR expression was associated with improved disease-specific survival (pp16 = 0.01; pEGFR= 0.01). OCSCC patients showed no association between biomarker and outcome.
For patients with OPSCC, high p16 and low EGFR were associated with improved outcome, suggesting a predictive role in surgically treated patients.
PMCID: PMC4118462  PMID: 22907805
oropharyngeal neoplasm; oral cavity neoplasm; p16(INK4A); EGFR protein; human papilloma virus
24.  Effects of enhanced bolus flavors on oropharyngeal swallow in patients treated for head and neck cancer 
Head & neck  2012;35(8):1124-1131.
Treatment for head and neck cancer can reduce peripheral sensory input and impair oropharyngeal swallow. This study examined the effect of enhanced bolus flavor on liquid swallows in these patients.
Fifty-one patients treated for head and neck cancer with chemoradiation or surgery and 64 healthy adult control subjects served as subjects. All were randomized to receive sour, sweet, or salty bolus flavor. Patients were evaluated at 7–10 days, 1 month, and 3 months after completion of tumor treatment. Control subjects received 1 assessment.
All bolus flavors affected oropharyngeal swallow; sour flavor significantly shortened pharyngeal transit time across all evaluations.
Sour flavor influenced the swallow of patients treated for head and neck cancer, as well as that of control subjects in a manner similar to those with neurologic impairment observed in an earlier study. Sour flavor may improve the speed of pharyngeal transit regardless of whether a patient has suffered peripheral or central sensory damage.
PMCID: PMC4112944  PMID: 22907789
dysphagia; sensory; flavor; videofluorography; head and neck cancer
25.  Dose-dependent effect of mitomycin C on human vocal fold fibroblasts 
Head & neck  2013;36(3):401-410.
The purpose of this study was to evaluate in vitro cytotoxicity and antifibrotic effects of mitomycin C on normal and scarred human vocal fold fibroblasts.
Fibroblasts were subjected to mitomycin C treatment at 0.2, 0.5, or 1 mg/mL, or serum control. Cytotoxicity, immunocytochemistry, and Western blot for collagen I/III were performed at days 0, 1, 3, and 5.
Significant decreases in live cells were measured for mitomycin C-treated cells on days 3 and 5 for all doses. Extracellular staining of collagen I/III was observed in mitomycin C-treated cells across all doses and times. Extracellular staining suggests apoptosis with necrosis, compromising the integrity of cell membranes and release of cytosolic proteins into the extracellular environment. Western blot indicates inhibition of collagen at all doses except 0.2 mg/mL at day 1.
A total of 0.2 mg/mL mitomycin C may provide initial and transient stimulation of collagen for necessary repair to damaged tissue without the long-term risk of fibrosis.
PMCID: PMC4113207  PMID: 23765508
mitomycin C; larynx; vocal folds; fibroblasts; surgical scar

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