Ellie Maghami

Head and Neck Cancers

Recent evidence suggests that dysregulated translation and its control significantly contribute to the etiology and pathogenesis of the head and neck cancers, specifically to that of squamous cell carcinoma (HNSCC). eIF4E is one of the most studied components of the translation machinery implicated in the development and progression of HNSCC. It appears that dysregulation of eIF4E levels and activity, namely by the PI3K/AKT/mTOR pathway, plays an important role in the etiology and pathogenesis of HNSCC and correlates with clinical outcomes. In this chapter, we will discuss the role of eIF4E and some other translation factors as they relate to the biology and treatment of HNSCC.

Oral complications of cancer and cancer therapy: from cancer treatment to survivorship.

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Head and neck cancers, version 1.2015 featured updates to the NCCN guidelines

These NCCN Guidelines Insights focus on nutrition and supportive care for patients with head and neck cancers. This topic was a recent addition to the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Head and Neck Cancers. The NCCN Guidelines Insights focus on major updates to the NCCN Guidelines and discuss the new updates in greater detail. The complete version of the NCCN Guidelines for Head and Neck Cancers is available on the NCCN Web site (NCCN.org).

Squamous Cell Carcinoma Related Oncogene/DCUN1D1 Is Highly Conserved and Activated by Amplification in Squamous Cell Carcinomas

Chromosomal amplification at 3q is common to multiple human cancers, but has a specific predilection for squamous cell carcinomas (SCC) of mucosal origin. We identified and characterized a novel oncogene, SCC-related oncogene (SCCRO), which is amplified along the 3q26.3 region in human SCC. Amplification and overexpression of SCCRO in these tumors correlate with poor clinical outcome. The importance of SCCRO amplification in malignant transformation is established by the apoptotic response to short hairpin RNA against SCCRO, exclusively in cancer cell lines carrying SCCRO amplification. The oncogenic potential of SCCRO is underscored by its ability to transform fibroblasts (NIH-3T3 cells) in vitro and in vivo. We show that SCCRO regulates Gli1--a key regulator of the hedgehog (HH) pathway. Collectively, these data suggest that SCCRO is a novel component of the HH signaling pathway involved in the malignant transformation of squamous cell lineage.

NCCN Guidelines Insights: Head and Neck Cancers, Version 2.2017

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Head and Neck Cancers provide treatment recommendations for cancers of the lip, oral cavity, pharynx, larynx, ethmoid and maxillary sinuses, and salivary glands. Recommendations are also provided for occult primary of the head and neck (H&N), and separate algorithms have been developed by the panel for very advanced H&N cancers. These NCCN Guidelines Insights summarize the panels discussion and most recent recommendations regarding the increase in human papillomavirus-associated oropharyngeal cancer and the availability of immunotherapy agents for treatment of patients with recurrent or metastatic H&N cancer.

Identification of Angiogenesis/Metastases Genes Predicting Chemoradiotherapy Response in Patients With Laryngopharyngeal Carcinoma

PURPOSE To identify genes related to angiogenesis/metastasis that predict locoregional failure in patients with laryngopharyngeal cancer (LPC) undergoing chemoradiotherapy (CRT) treatment. METHODS Tumor tissue was collected and snap-frozen from 35 sequential patients with histologically confirmed LPC being treated with CRT. Gene expression analysis was performed using a novel cDNA array consisting of 277 genes functionally associated with angiogenesis (n = 152) and/or metastasis (n = 125). Locoregional response was correlated to the gene expression profiles to identify genes associated with outcome. These genes were internally validated by real-time reverse transcriptase polymerase chain reaction (RT-PCR) and validated externally by immunohistochemistry analysis on an independent set of patients. RESULTS Locoregional failure occurred in nine of 35 patients. Seventeen genes from the cDNA microarray correlated with locoregional failure (two-sample t test, P < .05). Seven genes were chosen for additional analysis based on the availability of antibodies for immunohistochemistry. Of these seven genes, real-time RT-PCR validated four genes: MDM2, VCAM-1, erbB2, and H-ras (Wilcoxon rank sum test, P = .008, .02, .04, and .04, respectively). External validation by immunohistochemistry confirmed MDM2 and erbB2 as being predictive of locoregional response. Controlling for stage of disease, positivity for MDM2 or erbB2 was an independent negative predictor of locoregional disease-free survival. CONCLUSION Genomic screening by cDNA microarray and validation internally by real-time RT-PCR and externally by immunohistochemistry have identified two genes (MDM2 and erbB2) as predictors of locoregional failure in LPC patients treated with CRT. The role of these genes in treatment selection and the functional basis for their activity in CRT response merit additional consideration.

Cancer of the nasal cavity and paranasal sinuses

Sinonasal malignancies continue to have poor survival rates. Disease-related mortality is usually the result of disease recurrence and progression at the primary site despite aggressive therapy. Complete surgical excision with postoperative radiation therapy remains the standard of care for resectable lesions. Improved reconstructive techniques have increased our ability to aggressively clear locally advanced disease in this anatomically challenging region, while reducing associated functional and cosmetic morbidity. Intensive multimodality treatment regimens coupled with newer medical technology may ultimately improve the long-prevailing poor prognosis of these tumors.

Comparison of the efficacy and safety of ultrasound-guided core needle biopsy versus fine-needle aspiration for evaluating thyroid nodules.

OBJECTIVE Ultrasound-guided core needle biopsy (UG-CNB) is a procedure that is often performed either after repeated inadequate or nondiagnostic ultrasound-guided fine-needle aspiration (UG-FNA) or in combination with UG-FNA in the evaluation of thyroid nodules. The purpose of this study was to compare the efficacy and safety of UG-CNB and UG-FNA for evaluating thyroid nodules. METHODS This was a retrospective study of 350 consecutive patients who had thyroid nodules biopsied by UG-CNB or UG-FNA from January 2007 until November 2011 at our institution. Biopsy results were compared to the surgical specimen pathology reports for the 105 patients who subsequently underwent hemi- or total thyroidectomy in order to determine whether UG-CNB has advantages over UG-FNA for diagnosing thyroid malignancy and neoplasia. RESULTS Out of 461 thyroid nodules biopsied from 350 patients, 365 (79%) involved UG-CNB and 96 (21%) involved UG-FNA. The UG-FNA biopsy group had a significantly higher rate of inadequate sampling than the UG-CNB group (P<.0001; Fishers exact test). Out of 365 UG-CNB samples, 6 (2%) were deemed inadequate for histologic diagnosis, whereas 26 (27%) of the 96 UG-FNA samples were considered inadequate for cellularity. Comparison of biopsy results with the surgical specimen pathology reports revealed that the diagnostic accuracy of UG-CNB and UG-FNA for detecting malignancy was similar, at 89 and 94%, respectively (not significant by Fishers exact test). However, the UG-CNB group had a higher detection rate for benign follicular lesions compared to the UG-FNA group (65% versus 48% for UG-FNA; P = .002). Although UG-FNA detected neoplasia with high sensitivity (100%), the specificity was poor (30%). Neither biopsy group had any significant immediate or delayed procedure-related complications. CONCLUSION Our study demonstrated that UG-CNB is safe and is less likely to result in a nondiagnostic biopsy. The accuracy of the UG-CNB technique is similar to that of UG-FNA for detecting thyroid malignancy.

Metastatic Parathyroid Carcinoma to the Liver Treated With Radiofrequency Ablation and Transcatheter Arterial Embolization

A 51-year-old female with history of infiltrating ductal carcinoma of the right breast was diagnosed in late 2001 and treated with mastectomy in February 2002. She was subsequently treated with adjuvant chemotherapy with doxorubicin and cyclophosphamide for four cycles followed by hormonal therapy with letrozole for three years. She was diagnosed with a chest wall recurrence, involving the soft tissues in the right axillary and supra-clavicular areas in early 2006 and underwent six cycles of chemotherapy with albumin-bound nanoparticle-paclitaxel. She subsequently underwent a chest wall resection in September 2006, followed by radiation to the chest wall. She started capecitabine at the dose of 1000 mg twice a day, two weeks on and one week off, in October 2006 (in concurrence with radiation therapy to the chest wall). In December 2006, the dose of capecitabine was increased to 1500 mg AM and 1000 mg PM, also two weeks on and one week off. Bevacizumab was also started in late December 2006 at the dose of 15 mg/kg for 3 weeks for a total of 8 doses, the last one in May 2007. Six weeks following the last dose of bevacizumab, the patient presented with a 2-month history of complaints of lower jaw discomfort and what the she described as protruding bone in the lower jaw. The patient denied any recent history of dental or oral surgery. Examination revealed a small area of bone exposure in the left posterior lingual mandible, measuring approximately 1 1 mm in diameter. The bone appeared necrotic. The surrounding soft tissue appeared normal with no evidence of infection. The rest of the oral and dental examination was unremarkable. The exposed bone was smoothed with a bone file. The patient was prescribed chlorhexidine 0.12% oral rinse. Bevacizumab and capecitabine were discontinued. A few weeks later, the area of exposed bone had resolved. The overlying mucosa appeared normal. However, there was now a new area of 1 1 mm exposed bone in the right posterior lingual mandible (Fig 1A). The bone was mobile and was easily removed. Histological examination of the bony specimen (Fig 1B) showed devitalized, necrotic bone (NB, black arrowhead) demonstrating a scalloped, “moth-eaten” appearance. Bacterial colonies occupied those areas in which there was loss of mineralized bone. Also

Diagnosis and Management of Malignant Salivary Gland Tumors of the Parotid Gland

Malignant parotid tumors are heterogeneous and diverse. Accurate diagnosis requires a pathologist familiar with the various histologic subtypes, immunohistochemistry stains, and common translocations. Clinical course varies according to tumor subtype, ranging from indolent, slow-growing adenoid cystic carcinoma to rapidly progressive, possibly fatal, salivary ductal carcinoma. Histologic grade is important in prognosis and therapy. Surgery remains the mainstay of treatment when negative margins can be achieved. Radiation improves locoregional control of tumors with high-risk features. Chemotherapy for parotid tumors can be disappointing. Studies of new targeted therapies have not offered significant benefits.