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ABSTRACT: BACKGROUND: Sinonasal undifferentiated carcinoma (SNUC) remains a poorly characterized malignancy at both the clinical and molecular level, and, consequently, the optimal treatment strategy remains undefined. METHODS: We used a mass spectroscopy-based approach (Sequenom) to evaluate 95 hallmark single nucleotide variations (SNVs) within 12 oncogenes or tumor suppressor genes (AKT, BRAF, CDK4, Beta-catenin, epidermal growth factor receptor [EGFR], FBXW7, JAK2, c-KIT, KRAS, PDGFR, PI3K, and vascular endothelial growth factor [VEGF]) in 13 histologically confirmed SNUC cases. RESULTS: None of the samples demonstrated activating mutations in any of the 95 SNVs. CONCLUSION: Select clinically relevant activating genomic mutations were not identified in the 13 patient samples. However, polymorphisms were noted within the promoter region of VEGF. These may merit future studies 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. Head Neck, 2013.
Head & Neck 04/2013; · 2.40 Impact Factor
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ABSTRACT: Esthesioneuroblastoma is a rare malignant neoplasm in the olfactory region of the nasal cavity and anterior skull base. Diagnosis and staging require anatomic imaging and careful pathologic assessment. Standard treatment is anterior craniofacial resection with postoperative irradiation. The role for chemotherapy is not defined, but is generally for the most advanced cases and used in the neoadjuvant setting and/or postoperatively with irradiation. Prognosis is favorable; however, metastasis rates remain relatively high. Regional and distant metastasis portends a poor outcome. Intensity-modulated radiation treatment and endoscopic surgery have reduced morbidity, but outcomes with these techniques must be fully evaluated.
Neurosurgery clinics of North America 01/2013; 24(1):51-65. · 1.73 Impact Factor
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Yoko Takahashi, Michael E Kupferman,
Diana Bell,
Tilajun Jiffar,
June Goo Lee,
Tong Xie,
Ning-Wei Li,
Mei Zhao,
Mitchell J Frederick,
Alexander Gelbard,
Jeffrey N Myers,
Ehab Y Hanna
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ABSTRACT: PURPOSE: Sinonasal undifferentiated carcinoma (SNUC) is a rare and aggressive cancer. Despite the use of multi-modality treatment, the overall prognosis remains poor. To better understand the biological features of SNUC and help develop new therapies for the disease, we established SNUC cell lines and characterized their biological behaviors. Methods: Cell lines were established from a patient with a T4N0M0 SNUC of the right maxillary sinus who was treated with surgical resection at our center. Tumor colonies were harvested and were sequentially replated onto larger plates. Two populations were developed and labeled MDA8788-6 and MDA8788-7. These cell lines were characterized with molecular, biomarker, functional and histologic analyses. RESULTS: Short tandem repeat genotyping revealed that the cell line is isogenic to the parental tumor, and cytogenetic analysis identified 12 chromosomal translocations. The SNUC cell lines do not form colonies in soft agar, but are tumorigenic and non-metastatic in an orthotopic mouse model of sinonasal cancer. Western blot analysis revealed that both MDA8788 cell lines express epithelial markers, but do not express mesenchymal markers or the endocrine marker synaptophysin. CONCLUSIONS: This is the first report of the establishment of stable human-derived SNUC cell lines. The lines were highly tumorigenic and maintain the histologic and molecular features of the original tumor. These cell lines should serve as useful tools for the future study of SNUC biology and the development and testing of novel therapies for this deadly disease.
Clinical Cancer Research 10/2012; · 7.74 Impact Factor
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ABSTRACT: Paragangliomas (PGs) are rare tumors of the head and neck that require a multidisciplinary approach to their management. The
recent elucidation of the genetic and molecular etiology for this disease has led to significant advances in our understanding
of this disease and has had an important clinical impact. Consideration of genetic testing is strongly suggested for selected
patients and their family members. Surgical therapy remains the treatment of choice for most tumors, although a role for stereotactic
radiotherapy is emerging. This review highlights some of the advances made in recent years regarding the diagnosis and treatment
of PG.
Current Oncology Reports 04/2012; 10(2):156-161. · 2.55 Impact Factor
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ABSTRACT: An enlarging tracheoesophageal puncture (TEP) site after total laryngectomy is associated with substantial functional, hygienic, and potentially life-threatening problems. The enlarged TEP is challenging to manage. TEP injection (TEP-I) for control of the enlarged puncture site may be beneficial in avoiding surgery. Our study reviewed the clinical outcomes of patients at a single institution with enlarged TEP treated by office-based TEP-I.
Retrospective study.
Chart review of eight patients who had an enlarged TEP with leakage around the prosthesis treated with TEP-I after attempted customization of voice prostheses. Patient demographics and treatments were reviewed, and injection efficacy was evaluated by the duration of leakage resolution.
Eight patients underwent 20 TEP-I procedures. The average duration of leak resolution after each injection was 174.5 days. There were no complications. Six patients required custom modifications of the voice prosthesis to control TEP leakage after TEP-I, and all patients resumed their baseline speech and swallowing function. There was a trend toward an increase in number of injections among patients with N+ disease, disease recurrence, a history of irradiation and secondary TEP. No patients required surgical closure of the TEP.
Office-based TEP-I is a safe and effective treatment option for patients with an enlarged TEP site who have failed more conservative measures. A history of irradiation, disease recurrence, secondary TEP, and high-volume neck disease were predictive of multiple injections. Further study is warranted to accurately identify patients who may benefit from TEP-I to control leakage around the TEP.
The Laryngoscope 03/2012; 122(3):590-4. · 1.75 Impact Factor
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ABSTRACT: Minor salivary gland malignancies in children are rare and data on treatment and outcomes are limited.
A retrospective chart review of all pediatric patients with the pathologic diagnosis of minor salivary gland malignancy at a tertiary care cancer hospital was used to conduct this review.
From 1952 to 2006, 35 children with minor salivary gland cancers were treated at The University of Texas MD Anderson Cancer Center. Mean age was 15.2 +/- 2.9 years with a slight female predominance. Recurrence occurred in 4 patients and was significantly associated with positive margins, advanced stage, and high histologic grade. Overall survival (OS) and disease-specific survival (DSS) were 89.3% and 88.4%, respectively, at 5 years. Advanced stage, positive margins, and high grade were associated with adverse survival.
Minor salivary gland malignancies in children are rare. Surgical resection with clear margins yields excellent outcomes in patients with low-intermediate grade and early stage tumors. Patients with high-grade malignancies do poorly despite multimodality therapy. © 2012 Wiley Periodicals, Inc. Head Neck, 2012.
Head & Neck 01/2012; 34(11):1648-51. · 2.40 Impact Factor
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ABSTRACT: Total laryngectomy (TL) can be offered for management of chronic aspiration, radionecrosis, and/or airway compromise after head and neck cancer (HNC) treatment. The objective of this study was to evaluate functional outcomes after TL in disease-free HNC survivors.
Retrospective case series with chart review.
The University of Texas MD Anderson Cancer Center.
Twenty-three disease-free HNC survivors who underwent TL for laryngopharyngeal dysfunction.
TL ± pharyngectomy.
Post-TL swallowing-related (diet, gastrostomy dependence, and pneumonia rates) and communication outcomes.
All patients who underwent TL for dysfunction were previously treated with radiotherapy (12/23, 52%) or chemoradiotherapy (11/23, 48%). Preoperative complications included aspiration (22/23, 96%), pneumonia (16/23, 70%), tracheostomy (9/23, 39%), and stricture (7/23, 30%); 17 patients (74%) required enteral/parenteral nutrition, and 13 of 23 (57%) were nothing per oral (NPO). Rates of pneumonia, NPO status, and feeding tube dependence significantly decreased after TL (P < .001). At last follow-up after TL, all patients tolerated oral intake, but 4 (17%) required supplemental enteral nutrition. Continued smoking after radiotherapy and a preoperative history of recurrent pneumonia were significantly (P < .05) associated with final tube dependence and/or diet level. Sixteen patients (70%) underwent tracheoesophageal (TE) puncture, and 57% (13 of 23) communicated using TE voice after TL.
Salvage TL may improve health status by significantly decreasing the rate of pneumonia and improve quality of life by restoring oral intake in patients with refractory laryngopharyngeal dysfunction after HNC treatment. TE voice restoration may enhance functional outcomes in select patients treated with elective TL for dysfunction.
Otolaryngology Head and Neck Surgery 01/2012; 146(4):585-90. · 1.72 Impact Factor
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ABSTRACT: Mechanisms of resistance for HNSCC to cisplatin (CDDP), the foundational chemotherapeutic agent in the treatment of this disease, remain poorly understood. We previously demonstrated that cisplatin resistance (CR) can be overcome by targeting Trk receptor. In the current study, we explored the potential mechanistic role of the BDNF-TrkB signaling system in the development of CDDP resistance in HNSCC. Utilizing an in vitro system of acquired CR, we confirmed a substantial up-regulation of both BDNF and TrkB at the protein and mRNA levels in CR cells, suggesting an autocrine pathway dysregulation in this system. Exogenous BDNF stimulation led to an enhanced expression of the drug-resistance and anti-apoptotic proteins MDR1 and XiAP, respectively, in a dose-dependently manner, demonstrating a key role for BDNF-TrkB signaling in modulating the response to cytotoxic agents. In addition, modulation of TrkB expression induced an enhanced sensitivity of cells to CDDP in HNSCC. Moreover, genetic suppression of TrkB resulted in changes in expression of Bim, XiAP, and MDR1 contributing to HNSCC survival. To elucidate intracellular signaling pathways responsible for mechanisms underlying BDNF/TrkB induced CDDP-resistance, we analyzed expression levels of these molecules following inhibition of Akt. Inhibition of Akt eliminated BDNF effect on MDR1 and Bim expression in OSC-19P cells as well as modulated expressions of MDR1, Bim, and XiAP in OSC-19CR cells. These results suggest BDNF/TrkB system plays critical roles in CDDP-resistance development by utilizing Akt-dependent signaling pathways.
PLoS ONE 01/2012; 7(1):e30246. · 4.09 Impact Factor
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ABSTRACT: Mucoepidermoid carcinoma (MEC) is the most common malignancy of the major salivary glands. Prior reports noted histological grade and tumor stage as consistently important prognostic factors. This study reviewed the experience of patients with MEC at the University of Texas MD Anderson Cancer Center to determine the impact of clinical and pathologic findings on disease outcomes.
A retrospective clinical review was performed of patients with salivary gland MEC treated at a tertiary cancer center from 1990 to 2007.
A total of 125 patients were included. The 5-year overall survival and disease-free survival of all patients were 79.3% and 76.5%, respectively. Patients with low- and intermediate-grade disease had significantly better overall survival and disease-free survival than patients with high-grade disease, but no difference in survival rates was found between low- and intermediate-grade disease. Pathologic results of positive lymph nodes, extracapsular lymph node spread, and perineural invasion were all found to be poor prognostic indicators. On multivariate analysis, advanced disease stage and perineural invasion were found to be the most significant prognostic factors.
Patients with either low- or intermediate-grade tumors uniformly have favorable local control and survival. High histological grade, advanced stage, perineural invasion, positive surgical margins, and submandibular location all portend for poor outcomes in MEC. Further advances in therapy are needed to improve outcomes for high-grade and advanced-stage disease.
Cancer 12/2011; 118(16):3928-36. · 4.77 Impact Factor
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ABSTRACT: To describe a novel germline mutation in the succinate dehydrogenase subunit B (SDHB) gene.
Retrospective review.
The medical records of a patient with bilateral carotid body paragangliomas were reviewed.
A 35-year-old woman with a family history of neck masses presented with bilateral carotid body paragangliomas. DNA sequencing revealed a previously unreported conservative substitution (Leu111Val) mutation in the SDHB gene.
The Leu111Val germline mutation of SDHB is likely associated with a phenotype of head and neck paragangliomas, and carriers would benefit from periodic screening for sympathetic paragangliomas.
The Laryngoscope 12/2011; 121(12):2572-5. · 1.75 Impact Factor
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ABSTRACT: Neuroendocrine carcinoma (NEC) of the paranasal sinuses is rare, accounting for 5% of sinonasal malignancies. The purpose of this study was to assess prognostic factors and survival rates for sinonasal NEC.
A retrospective review of patients with NEC treated from 1990 to 2004 was performed. Patient demographics, TNM classification, treatment modality, recurrences, and survival were evaluated.
NEC was identified in 28 patients; the most common primary site was the ethmoid sinuses. Most patients presented with advanced tumors; few had regional or distant metastasis. Local recurrence rate was 21%. Five-year overall survival (OS) and disease-specific survival (DSS) rates were 65% and 78%, respectively. Response to chemotherapy predicted for improved survival, although no differences in outcomes were noted between definitive management strategies.
NEC of the paranasal sinuses is an exceedingly rare malignancy of the paranasal sinuses. Our data suggests definitive management with surgery or radiotherapy offers durable control. The response to chemotherapy may predict for overall outcomes. © 2011 Wiley Periodicals, Inc. Head Neck, 2011.
Head & Neck 11/2011; 34(10):1372-6. · 2.40 Impact Factor
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ABSTRACT: Sinonasal hemangiopericytomas are rare low-grade sarcomas. The role of endoscopic management has not been adequately studied.
This study was conducted through retrospective medical chart review of patients seen with sinonasal hemangiopericytomas at 2 institutions over a 19-year period. Demographic, clinicopathological, and surgical information was analyzed with descriptive statistics.
Thirteen patients with a diagnosis of sinonasal hemangiopericytomas were treated. The most common symptoms were obstruction (69%) and epistaxis (35%). All tumors were localized in the nasal cavity, and half had extension to 1 or more sinuses. Resection was performed endoscopically in 6 patients. Median intraoperative blood loss was 500 mL; median operative time was 165 minutes. Two patients received postoperative radiation. There were no recurrences with a median follow-up of 25 months. Three patients presented with recurrences, 2 local and 1 distant, up to 13 years after primary tumor removal.
Surgery for sinonasal hemangiopericytomas can be challenging; both endoscopic and open approaches may be used to treat these highly vascular tumors. © 2011 Wiley Periodicals, Inc. Head Neck, 2011.
Head & Neck 10/2011; 34(10):1492-6. · 2.40 Impact Factor
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ABSTRACT: Adenoid cystic carcinoma (ACC) is characterized by slow growth, frequent local recurrences, and distant metastasis (DM). However, these findings frequently are reported in patients with advanced-stage tumors, but the outcomes of early-stage tumors are poorly defined. We sought to evaluate the risk factors for the development of DM in early-stage ACC.
We retrospectively reviewed the charts of 60 patients who were diagnosed with clinical early-stage (T1-2/N0) ACC to determine the risk factors for development of DM and survival of these patients.
DM was detected in 12 (20%) of the patients, with a median latency of 31.5 months after diagnosis. Univariate analysis revealed that DM was associated with age ≥45 years, pathologically positive lymph nodes, extracapsular spread (ECS) from lymph nodes, high-grade histology, and solid tumor subtype. Multivariate analysis revealed solid tumor subtype and ECS to be significantly associated with DM. Disease-specific survival rates at 5 and 10 years for patients with DM were 80% and 40%, respectively, and were both 100% for patients without DM.
Although the majority of patients with clinical early-stage ACC of the major salivary glands have favorable prognosis, a significant percentage of patients will develop DM. Solid tumor subtype and nodal ECS were independent predictors of DM in early-stage ACC of major salivary glands. Other clinical and pathological variables may also contribute. These subgroups had poor overall and disease-specific survival. Such patients should be observed closely for the development of DM. Systemic therapy should be considered at the time of diagnosis.
Cancer 10/2011; 118(11):2872-8. · 4.77 Impact Factor
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Gregory M Chronowski,
Adam S Garden,
William H Morrison,
Steven J Frank,
David L Schwartz,
Shalin J Shah,
Beth M Beadle,
G Brandon Gunn, Michael E Kupferman,
Kian K Ang,
David I Rosenthal
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ABSTRACT: To assess, through a retrospective review, clinical outcomes of patients with squamous cell carcinoma of the tonsil treated at the M. D. Anderson Cancer Center with unilateral radiotherapy techniques that irradiate the involved tonsil region and ipsilateral neck only.
Of 901 patients with newly diagnosed squamous cell carcinoma of the tonsil treated with radiotherapy at our institution, we identified 102 that were treated using unilateral radiotherapy techniques. All patients had their primary site of disease restricted to the tonsillar fossa or anterior pillar, with <1 cm involvement of the soft palate. Patients had TX (n = 17 patients), T1 (n = 52), or T2 (n = 33) disease, with Nx (n = 3), N0 (n = 33), N1 (n = 23), N2a (n = 21), or N2b (n = 22) neck disease.
Sixty-one patients (60%) underwent diagnostic tonsillectomy before radiotherapy. Twenty-seven patients (26%) underwent excision of a cervical lymph node or neck dissection before radiotherapy. Median follow-up for surviving patients was 38 months. Locoregional control at the primary site and ipsilateral neck was 100%. Two patients experienced contralateral nodal recurrence (2%). The 5-year overall survival and disease-free survival rates were 95% and 96%, respectively. The 5-year freedom from contralateral nodal recurrence rate was 96%. Nine patients required feeding tubes during therapy. Of the 2 patients with contralateral recurrence, 1 experienced an isolated neck recurrence and was salvaged with contralateral neck dissection only and remains alive and free of disease. The other patient presented with a contralateral base of tongue tumor and involved cervical lymph node, which may have represented a second primary tumor, and died of disease.
Unilateral radiotherapy for patients with TX-T2, N0-N2b primary tonsil carcinoma results in high rates of disease control, with low rates of contralateral nodal failure and a low incidence of acute toxicity requiring gastrostomy.
International journal of radiation oncology, biology, physics 10/2011; 83(1):204-9. · 4.59 Impact Factor
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ABSTRACT: Sinonasal malignancies in children are rare, histologically diverse tumors that present diagnostic and management challenges. The purpose of this study is to review the experience of a single cancer center in the management of pediatric sinonasal malignancies.
Retrospective review.
Retrospective chart review.
Forty-four patients were identified. The median age was 12 years (range: 2-17), 54% were female, and the maxillary sinus was the most common primary site. Facial swelling and pain were the most common presenting complaints. Thirty-four patients (76%) in this series had paranasal sinus sarcomas, three patients had esthesioneuroblastomas, and eight patients had carcinomas. The 5-year overall survival, disease-specific survival, and recurrence rate for the entire group was 71%, 81%, and 43%, respectively.
Pediatric sinonasal malignancies are rare, locally aggressive tumors associated with nonspecific signs and symptoms. Multimodality treatment can result in 5-year overall and disease-specific survival rates of over 70%. A multidisciplinary team approach is essential to optimize outcomes and limit the morbidity of treatment.
The Laryngoscope 07/2011; 121(9):2001-3. · 1.75 Impact Factor
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ABSTRACT: The role of robotic surgery in the skull base is evolving and represents the natural progression toward maximizing surgical resections in confined spaces without compromising oncological principles. In this study, we describe the novel application of robotic surgery to the repair of dural defects in the skull base. A transmaxillary-transantral approach to the nasal cavity was performed bilaterally in a cadaveric model. Repair of the skull base defect was undertaken robotically. In this technical report, we demonstrate the feasibility of a suture-based technique for surgical reconstruction of the skull base with robotic assistance in a cadaveric model. In all cases, suture repair of dural defects was successfully performed with robotic-assisted technique. Although preliminary in nature, this study suggests that traditional suture techniques can be implemented in a confined surgical site with the use of robotic technology.
Skull Base 03/2011; 21(2):79-82. · 0.66 Impact Factor
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The Laryngoscope 02/2011; 121(2):310-2. · 1.75 Impact Factor
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ABSTRACT: The transoral approach to the parapharyngeal and retropharyngeal space (PPS/RPS) for the management of well-differentiated thyroid carcinoma (WDTC) has been previously described in other articles. However, limited exposure with this approach can be a challenge.
This is a retrospective review of 6 patients who underwent ultrasound-guided transoral excision of PPS/RPS WDTC metastases from October 2003 to March 2009 in a cancer center setting. Ultrasound-guided methylene blue dye injection of the node was used in 3 patients to facilitate intraoperative identification. The technique, safety, and feasibility of the procedure are described in this study.
Successful resection of the metastases was accomplished in all cases without intraoperative complication. The 1 definite recurrence was further treated with transmandibular excision.
Transoral excision of PPS/RPS WDTC metastases with ultrasound-guided methylene blue dye injection into the metastatic node is safe, feasible, and may further improve intraoperative identification of metastases in poorly accessible locations in the head and neck.
Head & Neck 02/2011; 33(2):166-70. · 2.40 Impact Factor
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ABSTRACT: Epithelial salivary gland neoplasms are rare in children. Malignant tumors account for 30% to 50% of cases in the pediatric age group, with mucoepidermoid carcinoma as the most common histology.
A retrospective medical record review was conducted from 1953 to 2007 to identify patients with mucoepidermoid carcinoma at the age of 18 years or younger at the time of diagnosis. Forty-nine patients were identified. Their medical records were examined for presentation, treatment, pathologic features, and outcomes.
Forty-nine pediatric patients with mucoepidermoid carcinoma were identified. The parotid gland (49%) and oral cavity (35%) were the most common subsites. Nodal metastasis was seen in 24% of patients. All patients underwent surgery, and 11 patients (22%) were treated with radiation therapy. The 5-year overall survival was 98%, the 10-year overall survival was 94%, and 10% of patients developed recurrence.
Mucoepidermoid carcinoma in children carries a favorable prognosis and can be successfully treated with surgery alone in most cases.
Head & Neck 01/2011; 33(12):1769-73. · 2.40 Impact Factor
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ABSTRACT: We report a case of a cervical rheumatoid nodule in close relation to the hyoid bone mimicking a metastatic carcinoma. A 74-year-old female with a 15-year history of rheumatoid arthritis (RA) on treatment with methotrexate presented with tenderness of the right base of tongue. Imaging demonstrated a 1.4 cm cystic lesion at the hyoid bone. Biopsies were unsuccessful and the patient required surgical resection of the mass. A trans-cervical approach was used. Pathology revealed a necrotizing granuloma compatible with rheumatoid etiology. The clinician should be aware that, in a patient with a neck mass, in the presence of active RA, rheumatoid nodules should be part of the differential diagnosis.
Head & Neck Oncology 01/2011; 3:26. · 3.13 Impact Factor
